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A multidisciplinary reconstruction of Palaeolithic nutrition that holds promise for the prevention and treatment of diseases of civilisation

Published online by Cambridge University Press:  02 July 2012

Remko S. Kuipers
Affiliation:
Laboratory Medicine, University Medical Center Groningen (UMCG), Groningen, The Netherlands
Josephine C. A. Joordens
Affiliation:
Human Origins Group, Faculty of Archaeology, Leiden University, Leiden, The Netherlands
Frits A. J. Muskiet*
Affiliation:
Laboratory Medicine, University Medical Center Groningen (UMCG), Groningen, The Netherlands
*
*Corresponding author: Dr Frits A. J. Muskiet, fax +31 50 361 2290, email f.a.j.muskiet@umcg.nl
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Abstract

Evolutionary medicine acknowledges that many chronic degenerative diseases result from conflicts between our rapidly changing environment, our dietary habits included, and our genome, which has remained virtually unchanged since the Palaeolithic era. Reconstruction of the diet before the Agricultural and Industrial Revolutions is therefore indicated, but hampered by the ongoing debate on our ancestors' ecological niche. Arguments and their counterarguments regarding evolutionary medicine are updated and the evidence for the long-reigning hypothesis of human evolution on the arid savanna is weighed against the hypothesis that man evolved in the proximity of water. Evidence from various disciplines is discussed, including the study of palaeo-environments, comparative anatomy, biogeochemistry, archaeology, anthropology, (patho)physiology and epidemiology. Although our ancestors had much lower life expectancies, the current evidence does neither support the misconception that during the Palaeolithic there were no elderly nor that they had poor health. Rather than rejecting the possibility of ‘healthy ageing’, the default assumption should be that healthy ageing posed an evolutionary advantage for human survival. There is ample evidence that our ancestors lived in a land–water ecosystem and extracted a substantial part of their diets from both terrestrial and aquatic resources. Rather than rejecting this possibility by lack of evidence, the default assumption should be that hominins, living in coastal ecosystems with catchable aquatic resources, consumed these resources. Finally, the composition and merits of so-called ‘Palaeolithic diets’, based on different hominin niche-reconstructions, are evaluated. The benefits of these diets illustrate that it is time to incorporate this knowledge into dietary recommendations.

Type
Review Article
Copyright
Copyright © The Authors 2012

Introduction

In the Origin of Species (Reference Darwin1), Darwin recognised that there are two forces of evolution, i.e. natural selection and the conditions of existence, where the latter was considered the most powerful(Reference Crawford, Cunnane and Stewart2). For example, important steps in evolution are the origin of eukaryotic life approximately 1·6–2·7 billion years ago(Reference Knoll, Javaux and Hewitt3, Reference Brocks, Logan and Buick4) and the appearance of photosynthetic cyanobacteria that began to oxygenate the atmosphere about 2400 million years ago (Mya)(Reference Buick5). However, there was relatively little alteration in the design of life forms before the Cambrian explosion about 600 Mya. Only when the oxygen tension in the atmosphere rose above the Pasteur point did aerobic metabolism become thermodynamically possible(Reference Holland6), resulting in an explosion from simple prokaryotics to a diversity of eukaryotic life forms(Reference Crawford and Marsh7).

During the past millions of years of evolution, with relatively little alteration in life forms and environmental circumstances, the human genome has become optimally adapted to its local environment(Reference Eaton and Konner8Reference Eaton and Cordain11). In other words, our genome may have reached a state of homeostasis, defined as the ‘optimal interaction between environment and genome’ or ‘nature in balance with nurture’, to support optimal survival for reproductive success. The aetiologies of many typically Western diseases, also known as diseases of affluence or civilisation, have been attributed to the disturbance of this delicate balance, secondary to the rapid changes in the conditions of existence, while our genome has remained basically unchanged since the beginning of the Palaeolithic era. The former include changes in physical activity, stress, sleep duration, environmental pollution and others(Reference Egger and Dixon12, Reference Egger and Dixon13), but one of the most rapidly changing conditions of existence has been the human diet.

Since the onset of the Agricultural Revolution, some 10 thousand years ago (Kya), and notably in the last 200 years following the start of the Industrial Revolution, humans have markedly changed their dietary habits. Consequently, it has been advocated that the current pandemic of diseases of civilisation results in part from the mismatch between the current diet and our Palaeolithic genome. In other words, ‘we are what we eat, but we should be what we ate’(Reference Wood and Brooks14, Reference Muskiet15). The ensuing poorly adapted phenotype may find its origin as early as in the fetal period(Reference Barker16, Reference Godfrey and Barker17) and possibly as far back as in the maternal grandmother's womb(Reference Drake and Walker18). This phenotype might be laid down in, inherently labile, epigenetic marks that are meant for the short- and intermediate-term adaptation of a phenotype to the conditions of existence. With clear evolutionary advantages they may become transmitted to the next generations as a memory of the environmental conditions that can be expected after birth(Reference Gluckman, Hanson and Morton19). They thereby give rise to a seemingly high contribution of genetics in some of the associated ‘typically Western’ degenerative diseases, which are in fact complex diseases that by definition do not inherit by Mendel's law, illustrating that epigenetic marks can also become erased.

From a pathophysiological point of view, the poorly adapted phenotype in Western countries, ensuing from the conflict between the changing lifestyle and our Palaeolithic genome, centres on chronic low-grade inflammation and the metabolic syndrome (also named the insulin resistance syndrome), which are risk factors for many of the diseases and conditions typical for affluent countries, such as CVD, type 2 diabetes mellitus, osteoporosis, certain types of cancer (notably colon, breast, prostate), fertility problems (polycystic ovary syndrome), pregnancy complications (gestational diabetes, pre-eclampsia), some psychiatric diseases (major and postpartum depression, schizophrenia, autism) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease)(Reference Cordain, Eades and Eades20Reference Pasinetti and Eberstein22). The genetically determined flexibility to adapt to a changing environment appears to have been exceeded and the genetically most vulnerable have become sick first, but ultimately all individuals will become sick with increasing dose and exposure time.

Environment, nutrients and their interaction with the genome

Adjustment of the DNA base sequence is a slow process that in an individual cannot support adaptation to environmental changes occurring at intermediate or rapid pace. Flexibility for rapid adaptation is provided by genetically encoded mechanisms that allow adjustment of phenotype by epigenetics and by the interaction of the environment with sensors, such as those of the sensory organs, but also by the many that remain unnoticed(Reference Muskiet and Kemperman23Reference Muskiet, Kuipers, Cunnane and Stewart25). The role of nutrients in (epi)genetics and their direct interaction with the genome have become increasingly acknowledged(Reference Feige, Gelman and Michalik26). Examples of such nutrients are iodine, Se, vitamins A and D, and n-3-fatty acids, which are direct or indirect ligands of the thyroid hormone receptor (TR), retinoid X receptor (RXR), retinoic acid receptor (RAR), vitamin D receptor (VDR) and PPAR. Homodimerisation and heterodimerisation of these receptors facilitate gene transcription and thereby keep our phenotype optimally adapted to the reigning conditions of existence. The roles of these nutrients, their respective receptors and the interaction between their receptors are indicative of the importance of their dietary presence and of a certain balance between their dietary intakes to arrive at optimal interaction with the genome. Lessons for this optimal interaction, and hence for the development of randomised controlled trials aiming at the study of diet or lifestyle, rather than single nutrients, might derive from knowledge on human evolution and the conditions of existence to which our ancestors have been exposed. These lessons might provide us with valuable information on what we should genuinely define as a ‘healthy diet’.

Evolutionary medicine

The concept that a thorough understanding of evolution is important in the prevention and treatment of (human) diseases has long been recognised. For example, in the early 1960s it was stated that ‘nothing in biology makes sense except in the light of evolution’(Reference Dobzhansky27), while in ethology, a distinction was made between proximate and ultimate (also named evolutionary) causes(Reference Tinbergen28). Proximate explanations provide a direct mechanism for certain behaviour in an individual organism. They explain how biomolecules induce certain behaviour or, for example, an allergic reaction. Proximate explanations, however, provide insufficient information to answer the question why this behaviour or this allergic reaction occurred. Ultimate explanations provide answers explaining why things happen from an evolutionary point of view. Many, if not all, diseases can become explained by both proximate and ultimate explanations. The science searching for the latter explanations has become known as ‘evolutionary medicine’. Unfortunately, modern medicine deals mostly with proximate explanations(Reference Harris and Malyango29, Reference Purushotham and Sullivan30), while ultimate explanations seem more prudent targets for long-time disease prevention(Reference Harris and Malyango29).

The term ‘evolutionary medicine’ (also named Darwinian medicine) was launched by Randolph M. Nesse and George C. Williams(Reference Williams and Nesse31, Reference Nesse and Williams32). They provided evolutionary answers for the understanding of human diseases. Many diseases do not result from a single biological, anatomical or physiological abnormality, but rather from a complex web of interactions. They often reflect the collateral damage of the survival and reproduction strategies of our genes and the genes of other organisms in our environment. The resulting disease manifestations include the outcomes of human defence mechanisms to clear foreign pathogens and the collateral damage of conflicts and trade-offs between humans and foreign invaders. Examples often overlooked are coincidence, in which diseases may result from imperfections of human evolution, and exaptation, in which a feature is not acquired in the context of any function to which it might eventually be put(Reference Gould and Vrba33). For example, the equilibrium between the not yet full-grown, but yet relatively large, brain of a newborn and the small birth canal in its turn is constrained by an upright posture and provides an example of a trade-off in human evolution. The location of the birth canal in its turn provides an example of an evolutionary coincidence that urges to deal with an, in retrospect, imperfect evolutionary design. These examples illustrate that evolution builds on the past: it is not possible to start a completely new design from scratch, which argues against ‘intelligent design’. The most important example of an evolutionary explanation for human disease, however, comes from the mismatch between our slowly adapting genome and the rapidly changing environment, notably our diet.

Evolutionary medicine argues that the chronic degenerative diseases causing most morbidity and mortality in affluent countries occur because of the current mismatch between the rapidly changing conditions of existence and our Palaeolithic genome(Reference Eaton, Eaton and Sinclair34). These mismatches will persist, notably in the light of our long generation time. The genetic adjustments needed to adapt to the new environment are also unlikely to occur, since the mismatch exerts little selection pressure. That is, they do not cause death before reproductive age, but rather reduce the numbers of years in health at the end of the life cycle(Reference Eaton, Cordain and Lindeberg35). Consequently, evolutionary medicine acknowledges a return to the lifestyle before the onset of the Agricultural Revolution as translated to the culture of the 21th century and as popularised by the expression: ‘how to become a 21th century hunter–gatherer’(Reference O'Keefe and Cordain36). Skeptics of evolutionary medicine often raise the intuitive criticism that the human ancestor had a very short life expectancy compared with contemporary individuals(Reference Eaton, Cordain and Lindeberg35). Consequently, they argue, there was no selection pressure on longevity or ‘healthy ageing’, since there were virtually no old people, while the few individuals reaching old (for example, postmenopausal) age provided no evolutionary benefit to younger individuals who were still able to reproduce. The counterargument is multilevelled.

Arguments and counterarguments in evolutionary health promotion

It needs to be emphasised that evolutionary medicine predicts no further increase in life expectancy, but rather a decrease in the numbers in deteriorating health at the end of the life cycle. It has been estimated that the complete elimination of nine leading risk factors in chronic degenerative diseases would increase life expectancy at birth by only 4 years, since these diseases only affect late-life mortality(Reference Hahn, Teutsch and Rothenberg37). Second, the increased life expectancy at present originates mostly from the greatly diminished influence of some unfavourable conditions of existence, including (childhood) infections, famine, homicide and tribal wars(Reference Eaton, Eaton and Sinclair34, Reference Hill, Hurtado and Walker38) secondary to the high levels of medical sciences and continuing civilisation. Thus, to achieve the average life expectancy of 40 years in a present-day hunter–gatherer society, for every child that does not survive beyond 1 year of age, another should reach the age of 80 years. In fact, about 20 % of modern hunter–gatherers reach at least the age of 60 years(Reference Howell39Reference Marlowe41). In other words, the popular argument that very few individuals in these societies live past 50 years(Reference Eaton, Cordain and Lindeberg35) is unsupported by ethnographic data. The third, often raised, argument is that due to the higher life expectancy in present-day humans, it is invalid to compare the mortality figures for cancer and degenerative disease of present-day hunter–gatherers (with low life expectancies) with those of Western populations (with a life expectancy of 80 years). However, early biomarkers of degenerative diseases such as obesity, high blood pressure, atherosclerosis and insulin resistance are also less common in younger, age-matched, members of present hunter–gatherer compared with members of affluent societies(Reference Eaton, Konner and Shostak9, Reference Eaton, Eaton and Stearns42), while measurements indicative for ‘good health’ such as muscular strength and aerobic power are more favourable in the former(Reference Shephard and Roy43). Moreover, even the oldest individuals in hunter–gatherer societies appear virtually free from chronic degenerative diseases(Reference Lindeberg and Lundh44Reference Trowell and Burkitt46). A fourth counterargument against the assumption that our human ancestors before the Agricultural Revolution died at a young age derives from archaeological records. After the transition from hunting and gathering to farming about 10 Kya, life expectancy dropped from about 40 years (as it is in recently studied hunter–gatherers, but also was among students of the Harvard College Class born in 1880(Reference Blacklow47)) to about 20 years(Reference Angel, Cohen and Armelagos48Reference Larsen50). This seemingly evolutionary disadvantage, secondary to a decrease in nutritional quality, is substantiated by a decrease in general health that has become noticeable from a decrease in final height, while skeletal markers of infection and nutritional stress became more common in archaeological finds(Reference Larsen49Reference Cohen, Cohen and Armelagos52). These setbacks were eliminated by a net increase in population growth, secondary to an increased productivity per land area that resulted in more energy intake per capita. Life expectancy remained stable throughout the Neolithic until the late 18th century, seldom exceeding 25 years in ‘civilised’ nations(Reference Eaton, Cordain and Lindeberg35). From this time, improvements in hygiene, food production and manufacturing, energy generation, per capita income, shelter, transportation, clothing and energy intakes substantiated an increase to and beyond the life expectancy that prevailed before the onset of the Agricultural Revolution. Greater energy availability enhanced, for example, the energy requirements of the immune system and for reproduction, both improving longevity(Reference Eaton, Cordain and Lindeberg35, Reference McKeown, Brown and Record53). Importantly, it was concluded that medical treatments had little impact on mortality reduction, while public health achievements (sanitation, food and water hygiene, quarantine and immunisations) have critically improved life expectancy. The fifth counterargument is that old people do provide an evolutionary benefit to the younger generations. Male fertility remains largely intact and male provisioning might help in the problem of high female reproductive costs, although the latter is contested(Reference Blurton-Jones, Marlowe, Hawkes, Cronk, Chagnon and Irons54, Reference Hawkes, O'Connell and Blurton-Jones55). The benefits of older females have been put forward in the grandmother hypothesis. This hypothesis, in which the presence of older females within a certain group benefits the reproductive success of their offspring, is supported by studies in human hunter–gatherer(Reference Hawkes, O'Connell and Jones56Reference Kachel, Premo and Hublin62) and primate societies(Reference Hawkes, O'Connell and Jones56, Reference Hawkes60, Reference Strier, Chaves and Mendes63). Interestingly, the fitness benefits of grandmothering proved insufficient to fully explain the evolution of increased longevity(Reference Kachel, Premo and Hublin62), suggesting that other evolutionary benefits, such as grandfathering, might also be involved in the long reproductive and non-reproductive lifespan of Homo sapiens. A recent analysis supports such benefits for both older males and females, since the presence of post-reproductive women increased the numbers of newborns by 2·7 %, while 18·4 % of the infants in a polygamous society in rural Africa were sired by males aged 50 years and above(Reference van Bodegom64). In support of the statement that ‘nothing in biology makes sense except in the light of evolution’ we therefore conclude that, unless proven otherwise, the presence of a substantial proportion of older males and postmenopausal females in hunter–gatherer, in contrast to primate societies, should be considered as proof for the evolutionary benefit that these individuals are to their progeny. Finally, we propose that this assumption would only be convincible if these individuals were reasonably fit, thereby supporting the concept of healthy ageing. Hence, healthy ageing seems both supported by ethnographic data and its benefit to hunter–gatherer societies. Other commonly raised arguments against the genome–environment mismatch hypothesis are the potential genetic changes since the Agricultural Revolution, the heterogeneity of ancestral environments and innate human adaptabilty(Reference Eaton, Cordain and Lindeberg35). Counterarguments to these critics have been discussed in great detail elsewhere(Reference Eaton, Cordain and Lindeberg35).

In the present review, a multidisciplinary approach is used, including palaeo-environmental reconstruction, comparative anatomy, biogeochemistry, archaeology, anthropology, (patho)physiology and epidemiology, to assess the characteristics of the ecosystem that supported human evolution. Based on this assessment, an approximation is made of the dietary composition that derives from this ecosystem. Finally, the potential benefit of a return to this ‘Palaeolithic diet’ is discussed and an update is provided for the evidence for the positive health effects of these diets.

Human evolution

Hominins are defined as members of the taxon Hominini, which comprises modern Homo sapiens and its extinct relatives over the past about 7 million years. The oldest-known hominins (Fig. 1) are Sahelanthropus tchadensis from Chad (about 7 Mya(Reference Brunet, Guy and Pilbeam65)) and Orrorin tugenensis from Kenya (about 6–5·7 Mya(Reference Senut, Pickford and Gommery66)). The next oldest are Ardipithecus kadabba (Ethiopia, about 5·8 Mya(Reference Haile-Selassie, Suwa and White67)) and A. ramidus (Ethiopia, about 4·4 Mya(Reference White, Asfaw and Beyene68)), Australopithecus anamensis (Kenya, about 4·1–3·9 Mya(Reference Leakey, Feibel and McDougall69)), Au. afarensis (Ethiopia, Tanzania and maybe Kenya, 3·6–3·0 Mya(Reference Kimbel and Delezene70, Reference Harrison and Harrison71)), Au. bahrelghazali (Chad, about 3·5 Mya(Reference Brunet, Beauvilain and Coppens72)), Kenyanthropus platyops (Kenya, about 3·5 Mya(Reference Leakey, Spoor and Brown73)), Au. garhi (Ethiopia, about 2·5 Mya(Reference Asfaw, White and Lovejoy74)) and Au. africanus (South Africa, about 2·9–2·0 Mya(Reference Herries, Hopley and Adams75)). From these earliest hominins evolved the genera Paranthropus (three known subspecies) and Homo. The earliest species that have been designated Homo are Homo rudolfensis, Homo habilis and Homo erectus sensu lato –including H. ergaster (Eastern Africa, about 2–1.8 Mya): these in turn are the presumed ancestors of Asian H. erectus, H. heidelbergensis (Africa, Eurasia 0·6–0·3 Mya), H. neanderthalensis (Eurasia, 0·4–0·03 Mya) and H. sapiens (from about 0·2 Mya onwards)(Reference Tattersall, Cunnane and Stewart76Reference White, Asfaw and DeGusta78). The recently discovered H. floresiensis (0·095–0·013 Mya(Reference Brown, Sutikna and Morwood79)) and the previously unknown hominins from Denisova Cave (about 0·05–0·03 Mya(Reference Reich, Patterson and Kircher80)) show that in the recent past several different hominin lines co-existed with modern humans.

Fig. 1 Scheme of the possible phylogenetic relationships within the family Hominidae. Note that at many time points of evolution, several different hominin species coexisted. Mya, million years ago; H., Homo; Au., Australopithecus; K., Kenyanthropus; P., Paranthropus; Ar., Ardipithecus; O., Orrorin; S., Sahelanthropus. © Ian Tattersall, with permission(Reference Tattersall, Cunnane and Stewart76).

Africa is now generally accepted as the ancestral homeland of Homo sapiens (Reference Stringer77, Reference Stringer81, Reference Templeton82). In several subsequent out-of-Africa waves(Reference Oppenheimer83), hominins of the genus Homo colonised Asia, Australia, Europe and finally the Americas (Fig. 2). Archaic Homo species reached as far as the island of Flores in South-East Asia, East China and Southern Europe (Spain). Homo heidelbergensis remains were found in Africa, Europe and Eastern Asia, while Homo neanderthalensis was restricted to Europe, Western Asia and the Levant. At last, in the later out-of-Africa diaspora starting about 100 Kya, Homo sapiens finally reached Australia and the Americas, while probably replacing earlier hominins in Africa, Europe and Asia that had left during the earlier out-of-Africa waves. However, there remains some debate(Reference Templeton82, Reference Templeton84Reference Templeton86) whether or not the gene pool of archaic hominins contributed to that of modern humans. In the replacement theory, archaic hominins make no contribution to the gene pool of modern man, whereas in the hybridisation theories (either through assimilation or gene flow), newly arriving hominins from the later out-of-Africa wave mixed with archaic predecessors. Current evidence from DNA analyses supports the concept that the gene pool of archaic hominins, notably Neanderthals(Reference Green, Krause and Ptak87), but also Denisovans(Reference Reich, Patterson and Kircher80) contributed to the gene pool of Homo sapiens.

Fig. 2 Coasting out of Africa: following the water in the third out-of-Africa diaspora. Assumed dispersal routes of archaic and anatomically modern man out of Africa and the supportive fossil evidence for hominin presence: (♦), Australopithecus sp.; (●), Homo habilis, erectus, ergaster or antecessor; (■), H. heidelbergensis; (★), H. neanderthalensis; (⊙), H. sapiens. ya, Years ago. Source: National Geographic Society 1988, 1997; adapted from www.handprint.com/LS/ANC/disp.html and Oppenheimer(Reference Oppenheimer83).

The African cradle of humankind is supported by micro-satellite studies(Reference Zhivotovsky, Rosenberg and Feldman88) that reveal that within populations the genetic variation decreases in the following order: sub-Saharan Africa>Eurasia>East Asia>Oceania>America, with the hunter–gatherer Hadzabe of Tanzania separated from the Ju|'hoansi (previously called !Kung) from Botswana by a genetic distance greater than between any other pair of populations(Reference Knight, Underhill and Mortensen89), which indicates the chronology of continent inhabitation and points to South or East Africa as the cradle of humankind(Reference Knight, Underhill and Mortensen89, Reference Henn, Gignoux and Jobin90). Human evolution was characterised by several large-scale decimations, and it has been estimated that the current world population derives from only 1000 surviving individuals at a certain time point(Reference Behar, Villems and Soodyall91). Such bottlenecks(Reference Ambrose92), characterised by strong population decrease, or where groups of hominids were separated due to global climate changes, volcanic winters or geographic boundaries as mountain ridges or seas, caused gene flow and genetic drift. As a result, different phenotypic races emerged in different geographic regions(Reference Zhivotovsky, Rosenberg and Feldman88, Reference Ambrose92). However, differences among these populations contribute only 3–5 % to genetic diversity, while within-population differences among individuals account for 93–95 % of genetic variation(Reference Rosenberg, Pritchard and Weber93). In other words, genetically we belong to one species that originally evolved in Africa and that for the great majority genetically still resides in the Palaeolithic era. Most of the current inter-individual genetic differences were already existent when Homo sapiens emerged, some 200 Kya(Reference White, Asfaw and DeGusta78). Bipedalism, hairlessness, speech and the ability to store fat differentiate humans from the closest relatives, the primates, but it is the uniquely large brain, which allowed for symbolic consciousness and pose ‘what-if’ questions, that finally made humanity(Reference Tattersall, Cunnane and Stewart76).

Changing habitat and increasing brain size

It is assumed that during the early stages of human evolution early hominins introduced more animal food into their diets, at the expense of plant foods(Reference Washburn, Lancaster, Lee and DeVore94, Reference Sailer, Gaulin and Voster95). Subsequent hominins further increased the amount of animal food and consequently the energy density and (micro)nutrient content of their diet, i.e. the dietary quality. While increasing their dietary intake from animal food, early hominins grew taller and increased their brain mass relative to body mass (encephalisation quotient; EQ). Brain mass in primates relates to the number of neurons(Reference Herculano-Houzel96) and global cognition(Reference Deaner, Isler and Burkart97), while the human cortex also has more cycles of cell division compared with other primates(Reference Hill and Walsh98). During hominin evolution the first significant increase in EQ occurred about 2 Mya (Table 1). From about 2 Mya to 200 Kya the human ancestors tripled their brain size from Australopithecus species with an EQ of 1·23–1·92 to an EQ of 1·41–4·26 for the genus Homo (Reference Broadhurst, Cunnane and Crawford99, Reference Cunnane, Cunnane and Stewart100). The increase in brain size and the number of neurons differentiate Homo from their closest primate relatives. However, a large brain requires an adaptation or an exaptation to accommodate it, and notably sufficient intake of so-called ‘brain-selective nutrients’(Reference Cunnane, Cunnane and Stewart100, Reference Cunnane101) to build and conserve it.

Table 1 The development of brain weight relative to body dimensions*

EQ, encephalisation quotient.

* Adapted from Templeton(Reference Templeton85).

Relative to modern Homo sapiens.

Buiding a big brain

Compared with other primates, humans have an extraordinarily large brain(Reference Navarrete, van Schaik and Isler102, Reference Potts103). To understand the expansion of the human brain during evolution, it is important to comprehend its composition and its biochemistry. Brain tissue has a unique profile of long-chain PUFA (LCP)(Reference Broadhurst, Cunnane and Crawford99). Comparison of the brain ethanolamine phosphoglycerols of forty-two studied animal species shows an almost identical LCP pattern, independent of the grade of encephalisation, containing approximately equal proportions of arachidonic acid (AA) and DHA. Consequently, for normal neuronal function, mammalian brain tissue appears to have an invariant structural requirement for both AA and DHA. This shows that both these fatty acids are important building blocks for building a big brain and for encephalisation. The weight of a newborn human brain is about 340 g(Reference Blinkov and Glezer104) and it contains about 9 g lipid(Reference White, Widdowson and Woodard105); the brain of a 10-month-old infant is 850 g and contains 52 g lipid. At 3 years, the brain is 1100 g and contains 130 g lipid. Thus, the major part of the human brain spurt occurs postnatally(Reference Dobbing and Sands106), implying that especially the newborn infant has high demands for AA and DHA.

Toothed whales (brain weight 9000 g) and African elephants (4200 g) have brains much larger than humans, but they have lower cognitive abilities and a lower EQ(Reference Roth and Dicke107). These observations substantiate an EQ-centred approach to explain variation in cognition between species. Recent analyses, however, have shown remarkable differences between primate and non-primate brains; a primate brain contains many more neurons than a non-primate brain of similar size(Reference Herculano-Houzel96, Reference Herculano-Houzel108, Reference Herculano-Houzel109) and the absolute number of neurons, rather than body relative to brain ratio (EQ), best predicts cognitive ability(Reference Deaner, Isler and Burkart97), although it still needs to be determined whether humans have the largest number of brain neurons among all mammals. From this new neuron-centred view, there seems to be nothing special about the human compared with the primate brain, except for its size(Reference Herculano-Houzel96), which basically determines both the number of neurons and non-neurons(Reference Azevedo, Carvalho and Grinberg110, Reference Herculano-Houzel111). Detailed comparisons of human and primate brains have revealed other differences, such as different levels of gene expression(Reference King and Wilson112Reference Caceres, Lachuer and Zapala114), secondary to chromosomal rearrangements(Reference Marques-Bonet, Caceres and Bertranpetit115), differences in the relative extent of the neocortical areas(Reference Herculano-Houzel96, Reference Finlay and Darlington116), the distribution of cell types(Reference Stimpson, Tetreault and Allman117) and the decrease of brain structure volumes with increasing age in man in contrast to chimpanzees(Reference Sherwood, Subiaul and Zawidzki118, Reference Sherwood, Gordon and Allen119). The best predictor of cognitive ability in humans compared with non-primates, however, still needs to be established, but rather than EQ or brain size, the absolute number of neurons seems a prudent candidate(Reference Deaner, Isler and Burkart97, Reference Herculano-Houzel108), since there is no clear relationship between neuron number and the absolute brain size among the different animal species(Reference Herculano-Houzel96, Reference Herculano-Houzel108, Reference Herculano-Houzel109).

In contrast to intuitive belief, growing a large brain and a large skull to accommodate it is less difficult to achieve than it seems at first glance. It was recently shown that different levels of expression of a single gene might have resulted in the markedly different beak shapes and lengths of Darwin's finches. Experimental overexpression of the calmodulin gene in chicken embryos resulted in a significant increase in the length of their beaks(Reference Abzhanov, Kuo and Hartmann120, Reference Patel121). These experiments suggest that small and seemingly insignificant changes can have profound implications for the evolution of anatomical size and shape and thereby provide great potential for explaining the origins of phenotypic variation(Reference Schneider122), including increases in brain and skull size. Analogously, many mutations in humans are associated with either microcephaly(Reference Kaindl, Passemard and Kumar123) or macrocephaly(Reference Williams, Dagli and Battaglia124), while the growth of the skull in hydrocephaly shows that the increased skull size is secondary to the increase of its contents, suggesting that brain rather than skull size is the limiting factor here. The evolution of certain genetic variants associated with brain size has accelerated significantly since the divergence from the chimpanzee some 5–6 Mya. A recent variation that occurred 37 Kya has spread more rapidly through the human population than could be explained by genetic drift(Reference Evans, Anderson and Vallender125Reference Evans, Vallender and Lahn128), suggesting that it conferred evolutionary advantage.

The anatomical and metabolic changes encoded in the genome (see ‘Comparative anatomy’) might have provided hominins with the anatomical and energetic opportunity to, over a period of several million years, steadily increase their brain size, but these mutations per se did not fulfil the nutrient requirements for brain expansion(Reference Cunnane101, Reference Speth129Reference Gibbons131). The underlying small number of mutations should rather have been accompanied, and most probably have been preceded, by increased availability of ‘brain-specific nutrients’ such as LCP for their ultimate conservation through the process of mutation and selection, which basically underlines both Darwin's concept of the crucial importance of ‘the conditions of existence’ and the secondary role of mutation. An example may come from current knowledge on the sources of AA and DHA. In humans, both AA and DHA can be synthesised from their precursor essential fatty acids α-linolenic acid (ALA) and linoleic acid (LA) (Fig. 3), respectively. ALA and LA are present in various natural food resources. ALA is predominantly found in plant foods, while LA is mainly found in vegetable oils such as sunflower-seed oil. Both AA and DHA may derive from their synthesis from abundantly consumed precursor fatty acids ALA and LA, but in humans and especially neonates, these synthetic activities are insufficient to cope with metabolic demands(Reference Crawford132). Consequently both these LCP, but especially those of the n-3 series, need to be present in sufficient quantities in our diet. It is still under debate what dietary resource(s) provided the LCP that enabled us to grow a large brain(Reference Cunnane101, Reference Cordain, Eaton and Sebastian133Reference Langdon137).

Fig. 3 Metabolism of the parent essential fatty acids and endogenously synthesised fatty acids. Δ9, Δ9-Desaturase; CE, chain elongation; Δ6, Δ6-desaturase; Δ5, Δ5-desaturase; CS, chain shortening through peroxisomal β-oxidation. 18 : 3n-3, α-linolenic acid; 18 : 2n-6, linoleic acid; 18 : 1n-9, oleic acid; 20 : 5n-3, EPA; 20 : 4n-6, arachidonic acid; 20 : 3n-9, mead acid; 22 : 6n-3, DHA.

The probability of hunting on the savanna

It has been a longstanding paradigm in palaeoanthopology that early human evolution occurred in a dry and open savanna environment(Reference Dart138Reference Tobias, Cunnane and Stewart140). Recent studies from the Afar basin(Reference White, Asfaw and Beyene68, Reference White, Ambrose and Suwa141), although recently contested(Reference Cerling, Levin and Quade142Reference Cerling, Wynn and Andanje144), indicated that the habitat of Ardipithecus ramidus at about 4·4 Mya was characterised not by savanna but by woodland to grassy woodland conditions. Human characteristics, such as poor water-drinking capacity, excessive urination and transpiration and poor water retention support the argument that we would be poorly adapted savanna dwellers(Reference Tobias, Cunnane and Stewart140).

A second long-reigning paradigm was ‘man the hunter’, which was the standard version of human origins advocated for many years. Washburn & Lancaster(Reference Washburn, Lancaster, Lee and DeVore94) referred at most to our most recent antecessors, Homo sapiens and possibly H. neanderthalensis, when they claimed that our intellect, interests, emotions and basic social life are evolutionary products of the hunting adaptation. The strongest argument against this hunting paradigm comes from combined studies of past and present-day hunter–gatherer societies indicating that the role of hunting is exaggerated, notably (around the campfire) in hunter–gatherer societies, since the majority of the dietary protein is in reality obtained by women gathering nuts, tubers and small animals(Reference Woodburn, Lee and DeVore145Reference Stanford147). Cordain et al. (Reference Cordain, Miller and Eaton148) showed that only 25–35 % of energy (en%) of subsistence in worldwide hunter–gatherer communities is derived from hunting, while the remainder is derived from both plant and fished food. Thus, while meat from large game may have been the most valued food, it is highly unlikely that it was the most valuable (nutritionally important) food resource from a dietary perspective(Reference Marlowe41, Reference Stanford149). At present, the niche of early hominins and thus the environment of human evolution, and, most importantly for the present review, the nutritional composition of the early human diet are still heavily debated(Reference Ungar and Sponheimer150).

Reconstruction of our ancient diet

In the next sections we will discuss various views on (changes in) the hominin ecological niche that over time shaped the human genome to what it currently is.

Palaeo-environments

Sahelanthropus, Orrorin and Ardipithecus

In the late Miocene (up to 5·3 Mya), the African continent became more arid, which resulted in fragmentation of the (sub)tropical forests and the appearance of more open environments(Reference Bernor151). The widespread dispersal of some of the earliest hominins such as Sahelanthropus (Reference Brunet, Guy and Pilbeam65, Reference Lebatard, Bourles and Duringer152), and Australopithecus bahrelghazali from Chad, might be explained by the presence of the relatively low-lying humid East–West corridor constituted by the remnants of the Cretaceous Central African and Sudan Rifts between Western and Eastern Africa(Reference Bosworth and Morley153, Reference Joordens154). The reconstructed environment of Sahelanthropus (about 7 Mya) suggests a mosaic of gallery forest at the edge of a deep, well-oxygenated lake, swampy and vegetated areas, and extensive grasslands(Reference Vignaud, Duringer and Mackaye155). Since there is no indication of carnivore modification or fluvial transport of its bones, Sahelanthropus chadensis probably lived in this area(Reference Stewart, Cunnane and Stewart156). The palaeo-environment of Orrorin (about 6 Mya) was probably characterised by open woodland, with dense stands of trees in the vicinity and possibly fringing the lake margin and/or streams that drained into the lake(Reference Pickford and Senut157). Ardipithecus kadabba (5·6 Mya) remains are associated with wet and closed, grassy woodland and forest habitats around lake or river margins(Reference WoldeGabriel, Haile-Selassie and Renne158). Ardipithicus ramidus (4·4 Mya) lived in or near a groundwater-supported grassy woodland to forest(Reference WoldeGabriel, Ambrose and Barboni159). Additionally, the abundance of fossilised shallow-water aquatic species such as catfish, barbus, cichlidae and crocodiles additionally suggests an episodically present flood-plain environment(Reference WoldeGabriel, Ambrose and Barboni159).

Early Australopithecus species

Australopithecus anamensis appeared at about 4·2 Mya and its environment was characterised by a mix of wetlands and terrestrial environments, such as lacustrine and fluvial floodplains, woodland and gallery forest(Reference Stewart, Cunnane and Stewart156, Reference Feibel, Harris, Brown and Harris160Reference Schoeninger, Reeser and Hallin163). The later Australopithecus afarensis survived in a variety of habitats(Reference Reed164), but apparently thrived better in the more wooded and humid conditions in the Afar basin than in the relatively dry Laetoli area(Reference Su and Harrison165). Stewart(Reference Stewart, Cunnane and Stewart156) pointed out that in Africa the only environmental constant in hominin sites throughout the period from 3·4 to 2·9 Mya was a wetlands habitat, characterised by aquatic herbaceous vegetations around lakes and rivers, with large populations of wetland fauna such as reduncines and hippopotami. Hence, these wetlands could have been refuge for early hominins throughout an extensive period of human evolution.

Paranthropus, late Australopithecus and Homo species

About 2·9–2·5 Mya tectonic and global climatic changes made Africa cooler and drier(Reference Veldkamp, Buis and Wijbrands166Reference Bartoli, Sarnthein and Weinelt169). The great wet forests of middle Africa retreated and made place for more savanna grasslands. It is around this time, from about 2·6 Mya onwards, that the first traces of the new hominin genus Homo appeared in the archaeological record(Reference Tobias, Cunnane and Stewart140). It has been suggested that alternating wet and dry periods after 2·7 Mya could have isolated hominin populations around sources of potable water, while forcing them to the extremes of their conditions of existence(Reference Stewart, Cunnane and Stewart156) and thus facilitating specialisation(Reference Potts170), either by adaptation or exaptation. Compared with Australopithecus, Paranthropus existed in slightly more open habitats, including wetlands and grasslands, but also in woodland and bushland areas. The habitats of Homo species seem similar to those utilised by Paranthropus species(Reference Reed161), but Homo remains at Olduvai Gorge and Koobi Fora are associated with well-vegetated swamps, lakes and river margins, and (semi-) aquatic fauna(Reference Pobiner, Rogers and Monahan171, Reference Ashley, Tactikos and Owen172). Only the later Homo species are also found in assemblages that indicate extremely arid and open landscapes such as savanna(Reference Reed161). Also, it has been suggested that hominins and other (aquatic) species dispersed throughout Africa along water systems, while even the last out-of-Africa migration might have occurred via the ‘green Sahara’ that existed during the last interglacial (125 Kya)(Reference Stewart, Cunnane and Stewart156, Reference Drake, Blench and Armitage173).

In conclusion, the palaeo-environmental evidence suggests that early hominins lived in the proximity of water. However, it is frequently argued that bones are preferentially preserved in lake, river or fluvial sediments, making their recovery in any other than an aquatic setting unlikely(Reference Sikes174). Alternatively, hominin remains may have been relocated to the water by carnivores(Reference Ward, Leakey and Walker162), including crocodiles. Nevertheless, the combined evidence strongly suggests that early hominins frequented the land–water ecosystem and thus lived there. Joordens et al. (Reference Joordens154) proposed, based on comparison with other terrestrial omnivores, that the default assumption should be that hominins living in freshwater or marine coastal ecosystems with catchable aquatic resources could have consumed these aquatic resources(Reference Joordens154, Reference Joordens, Wesselingh and de Vos175).

Comparative anatomy

The diet of our closest relatives

Field studies on our closest relatives, the extant apes, show that their preferred food items are primarily fruits and/or leaves and stems from terrestrial forests. Lowland gorillas, for example, derive 57 % of their metabolisable energy (en%) from SCFA derived from colonic fermentation of fibre, 2·5 en% from fat, 24 en% from protein and 16 en% from carbohydrate(Reference Popovich, Jenkins and Kendall176). ‘Fallback foods’ are consumed when preferred foods are unavailable(Reference Marshall and Wrangham177) and are generally composed of herbaceous plants and high-fibre fruits from aquatic and terrestrial environments(Reference Stewart, Cunnane and Stewart156). Like our closest relatives(Reference Stewart, Cunnane and Stewart156, Reference Nishida178Reference Wrangham, Cheney and Seyfarth181), hominins might have used foods from the aquatic environment as fallback foods, while, although speculative, this niche might eventually have proven favourable with regard to subsequent encephalisation.

Teeth morphology and dental microwear

Comparative anatomy (Fig. 4) of the hominins might confer some information about these fallback and preferred foods of our ancestors. Dental studies of Sahelanthropus (Fig. 1) describe that the teeth had thick enamel(Reference Brunet, Guy and Pilbeam65), similar to orangutans, suggesting that it could eat hard and tough foods(Reference Vogel, van Woerden and Lucas182), such as available from the lakeshore vegetation(Reference Stewart, Cunnane and Stewart156). Ardipithecus ramidus, however, had thin molar enamel and smaller teeth compared with later hominins. This dental morphology is consistent with a partially terrestrial, omnivorous/frugivorous niche(Reference Suwa, Kono and Simpson183). Studies on cranio-dental changes such as tooth size, tooth shape, enamel structure and jaw biomechanics indicate that Australopithecus and Paranthropus had prominent jaws, relatively flat molar teeth, small incisors and thick enamel, suitable for breaking and crushing small hard, brittle foods such as fruits, nuts and underground storage organs(Reference Ungar and Sponheimer150), but unsuitable for breaking down tough plant foods or tearing meat. Together, this would allow early hominins to eat both hard and soft, abrasive and non-abrasive foods, which suits well for life in a variety of habitats(Reference Teaford and Ungar184).

Fig. 4 Lower jaw of a chimpanzee (Pan troglodytes), Australopithecus africanus and Homo sapiens. Note the somewhat human-like shape of the teeth, but ape-like axis in the jaw of Australopithecus. © Australian Museum.

In addition to studies on teeth morphology, microwear studies are essential. Dental microwear studies analyse tooth-wear, showing evidence for where teeth were actually used for and thus what an animal in reality ate(Reference Walker, Hoeck and Perez185). While adaptive morphology will give important clues about what a species was capable of eating, microwear studies reflect what an animal ate during some point in its lifetime. In these studies, ‘complexity’ is used as an indicator for hard and brittle items, while ‘anisotrophy’ is an indicator for tough foods(Reference Ungar, Grine and Teaford186).

Most primates show either low complexity combined with high anisotrophy, indicative of consumption of tough foods such as leaves, stems and meat, or high complexity with low anisotrophy associated with hard-brittle foods, such as nuts and seeds(Reference Ungar and Sponheimer150, Reference Ungar, Scott and Grine187). Ardipithecus ramidus's preference for an omnivorous/frugivorous diet was confirmed by microwear studies (Reference Suwa, Kono and Simpson183), suggesting a diet of fleshy fruits and soft young leaves(Reference Ungar and Sponheimer150). Conversely, microwear textures of Australopithicus afarensis and anamensis show striations rather than pits (low complexity and low anisotrophy), i.e. patterns similar to those of grass-eating and folivorous monkeys instead of the predicted diets predominated by hard and brittle foods(Reference Ungar, Scott and Grine187, Reference Grine, Ungar and Teaford188). Australopithecus africanus showed microwear patterns that were more anisotropic, suggestive for consumption of tough leaves, grasses and stems(Reference Scott, Ungar and Bergstrom189). Paranthropus robustus, also know as the ‘Nutcracker Man’, has enormous, flat, thickly enamelled teeth that are combined with a robust cranium, mandible and powerful chewing muscles, suggestive of breaking hard and brittle foods(Reference Ungar, Grine and Teaford186). After microwear analysis of its teeth, however, Ungar et al. (Reference Ungar and Sponheimer150, Reference Ungar, Grine and Teaford186) showed that P. robustus had low complexity and anisotrophy; thus Paranthropus might only have consumed mechanically challenging items as fallback foods when preferred foods were unavailable. Similarly, microwear studies support the notion that the diet of P. boisei contained large quantities of low-quality vegetation, rather than hard objects(Reference Cerling, Mbua and Kirera190).

Generally, microwear studies confirm earlier dental topography studies(Reference Ungar191), which revealed the incorporation of more fracture-resistant foods, i.e. tougher foods as leaves, woody plants, underground storage organs and animal tissues, in the diet of Australopithecus africanus compared with Australopithecus afarensis and for P. robustus compared with Australopithecus africanus (Reference Ungar, Scott and Grine187). Dental topographic analysis suggested that successive Homo species emphasised more on tougher and elastic foods, perhaps including meat(Reference Ungar191). The latter suggestion is in line with the optimal foraging theory, which states that humans prefer foods with high energy density over those with low energy density(Reference Ulijaszek192, Reference Goldstone, de Hernandez and Beaver193).

Microwear studies confirmed that early Homo, such as H. erectus and H. habilis, did not prefer fracture-resistant foods, although some H. erectus specimens showed more small pits than H. habilis members, suggesting that none of the early Homo specialised on very hard-brittle or tough foods, but rather could consume a varied diet(Reference Ungar, Grine and Teaford194). This does not imply that early Homo had very broad diets, but rather that early Homo was adapted to subsist in a range of different environments, providing evolutionary advantage in the climatic fluctuations and the mosaic of habitats in Africa during the late Pliocene(Reference Ungar, Grine and Teaford195). A study on dental microwear of 300 000-year-old H. heidelbergensis teeth from Sima de los Huesos in Spain showed striation patterns that indicated a highly abrasive diet, with substantial dependence on poorly processed plant foods such as roots, stems and seeds(Reference Perez-Perez, De Castro and Arsuaga196). Lalueza et al. (Reference Lalueza, PerezPerez and Turbon197) compared teeth of very recent hunter–gatherers (Inuit, Fueguians, Bushmen, Aborigines, Andamanese, Indians, Veddahs, Tasmanians, Laps and Hindus) with Middle and Upper Pleistocene fossils. Their results indicate that some Neanderthals resemble carnivorous groups, while archaic H. sapiens show a more abrasive diet, partly dependent on vegetable materials.

Overall, remarkably few studies have related microwear patterns to hominin diet for the period between 1·5 Mya and 50 Kya (PS Ungar, personal communication). Studies in more recent hominins, such as from an Upper Palaeolithic site in the Levant (22 500–23 500 before present; BP) showed a high frequency of long narrow scratches and few small pits, suggesting a tough abrasive diet of aquatic foods rather than a diet with hard foods that needed compressive force(Reference Mahoney198, Reference Mahoney199). A study of subsequent local hunter–gatherer (12 500–10 250 BP) and farmers (10 250–7500 BP) living in the Levant showed larger dental pits and wider scratches among the farmers compared with the hunter–gatherers, suggesting that the implementation of agriculture led to a more fracture-resistant diet(Reference Mahoney199).

Gut morphology, energy expenditure and muscularity

Gut morphology studies(Reference Milton200, Reference Milton201) support the introduction of animal foods, at the expense of vegetable foods, in the diet of early Homo. The dominance of the colon (>45 %) in apes indicates adaptation to a diet rich in bulky plant material, such as plant fibre and woody seeds. In contrast, the proportion of the human gut dominated by the small intestine (>56 %) suggests adaptation to a diet that is highly digestible, indicating a closer structural analogy with carnivores than to folivorous or frugivorous mammals. Importantly, the shorter gut in Homo, as compared with primates, might have had some other advantage. During the evolution from Ardipithecus and Australopithecines to early Homo, the improvement of dietary quality coincided with an increase in height, the size of our brain and its metabolic activity. However, an increase in body size coincides with increased daily energy demands, notably during gestation(Reference Gittleman and Thompson202) and lactation(Reference Oftedal203). It was, for example, calculated that daily energy expenditure for a Homo erectus female is about 66 % higher compared with an Australopithicine female, while being almost 100 % higher in a lactating Homo erectus female compared with a non-lactating, non-pregnant Australopithicine (Reference Aiello and Key204). These high energy demands might have been met by increased female fat reserves(Reference Aiello and Wells205, Reference Cunnane and Crawford206), such as demonstrated by the presence of female steatopygia in some traditional human populations, such as the Khoisan of southern Africa.

Apart from the extra energy need for reproduction and increasing height, the human brain of a modern adult uses 20–25 en% of the total RMR, while this value is 8–9 en% for a primate(Reference Leonard, Robertson and Snodgrass207). It has been postulated that the extra energy needs did not derive from a general increase in RMR, but partly from a concomitant reduction of the gastrointestinal tract(Reference Aiello and Wheeler208) and a reduction in muscularity(Reference Leonard, Robertson and Snodgrass207). These features are combined in the ‘expensive tissue hypothesis’ of Aiello & Wheeler(Reference Aiello and Wheeler208) that points at the observation that the mass of the human gastrointestinal tract is only 60 % of that expected for a similar-sized primate and that humans are relatively under-muscled compared with other primates(Reference Leonard, Robertson and Snodgrass207). Interestingly, the negative relationship between gut and brain size across anthropoid primates(Reference Aiello and Roebroeks209) was confirmed in a study with highly encephalised fish(Reference Kaufman, Hladik and Pasquet210), whereas it became falsified in mammals(Reference Navarrete, van Schaik and Isler102). Unfortunately, however, the latter study did not include marine mammals(Reference Navarrete, van Schaik and Isler102), while it is questionable whether with respect to brain development humans adhere to general mammalian rules(Reference Potts103). Other adaptations might have saved energy expenditure as well. The short human inter-birth interval(Reference Aiello and Key204), compared with inter-birth intervals of 4–8 years in the gorilla, chimpanzee and orangutang(Reference Galdikas and Wood211), reduces the most expensive part of reproduction, i.e. lactation(Reference Isler and van Schaik212, Reference Isler213), while the shift from quadrupedal to bipedal locomotion also reduced daily energy expenditure(Reference Pontzer, Raichlen and Sockol214). Together, all of these adaptations allow for an increased daily energy expenditure, including the reallocation of energy to the metabolically active brain, but were only possible after Homo included more energy-dense foods into its diet. Brain mass in primates is positively related to dietary quality and inversely to body weight(Reference Leonard, Robertson and Snodgrass207). Generally, a shift towards more energy-dense foods includes a shift from primarily carbohydrate-rich vegetables to fat- and protein-rich animal foods. However, it has also been suggested that a shift from the complex carbohydrates in leafy vegetables towards underground storage organs, such as tubers, might have provided easy-to-digest carbohydrates(Reference Milton200, Reference Wrangham, Jones and Laden215) to support a larger hominin body mass.

A phenotypic specialisation on non-preferred resources, without compromising the ability to use preferred resources, is also known as Liem's paradox(Reference Robinson and Wilson216). This paradox is important to keep in mind during attempts to reconstruct the preferred diet from the available evidence. Interestingly, Stewart(Reference Stewart, Cunnane and Stewart156) recently noted that in the case of Paranthropus's phenotype with regard to its fallback food, there is just as much evidence to talk about a ‘Nutcracker Man’ as there is to talk about a ‘Shellcracker Man’. Thus, a phenotypic characterisation needs support from other studies to confirm adaptation to preferred rather than fallback foods. In other words, it should be noted that not all physical characteristics might be taken as unambiguous proof for the preferred diet of early hominins (Liem's paradox). The increasing absolute body size and brain size and the reduction in gut size, however, do indicate a shift from low- to high-dietary-quality foods for more recent hominins.

Biogeochemistry

Evidence from the strontium:calcium ratio

Based upon the principle ‘you are what you eat’(Reference Harris217) several techniques have been developed to study early hominin diets(Reference Sponheimer, Dufour, Hublin and Richards218). Trace element studies first started with Sr:Ca ratios, which decrease as an animal moves up the food chain, secondary to the biological discrimination against strontium(Reference Sillen and Kavanagh219). A first study(Reference Sillen220) suggested that Paranthropus robustus (Fig. 1) had lower Sr:Ca ratios compared with contemporaneous Papio (baboon) and Procavia (hyrax), suggesting that Paranthropus was not an exclusive herbivore. However, a subsequent study showed that two Homo specimens had a higher Sr:Ca ratio than Paranthropus (Reference Sillen, Hall and Armstrong221). Since Homo had been assumed to consume more animal foods than Paranthropus and thus have a lower Sr:Ca ratio, these higher Sr:Ca ratios needed explanation. For example, consumption of specific foods with a high Sr:Ca ratio might have increased the ratio in Homo compared with Paranthropus. Foods in the area of research with elevated Sr:Ca ratios were mainly geophytes. These are notably perennial plants with underground food storage organs, such as roots, bulbs, tubers, corms and rhizomes. Consequently, this discrepancy has been attributed to the consumption of underground storage organs by early Homo (Reference Wrangham, Jones and Laden215, Reference Sillen, Hall and Armstrong221). The use of these underground storage organs may have become necessary from the start of a first period of aridity about 2·8 Mya, when forest was replaced by drier woodlands, forcing hominins to search for available resources around water margins(Reference Conklin-Brittain, Wrangham and Hunt222).

Although promising at first, the use of Sr:Ca ratios was found to suffer from several limitations. For example, a problem is that hominin Sr:Ca ratios in fossilised bones alter with time(Reference Lee-Thorp and Sponheimer223), a process that is known as diagenesis. This problem can be circumvented by the use of tooth enamel, which is less susceptible to diagenesis than bone(Reference Lee-Thorp and Sponheimer223). Subsequent studies showed that Australopithecus africanus had a higher Sr:Ca ratio in its enamel compared with Paranthropus and contemporaneous browsers, grazers, baboons and carnivores(Reference Sponheimer, de Ruiter and Lee-Thorp224Reference Balter and Simon226). The interpretation of these findings, however, remains a subject of debate. For example, a group of brown seaweeds and some aquatic plants discriminate against Ca, resulting in an increase in the Sr:Ca ratio, and likewise in the Sr:Ca ratio of the fish feeding on them(Reference Balter and Simon226, Reference Ophel and Fraser227). Similarly, leaves from trees have lower Sr:Ca ratios compared with grasses, which becomes subsequently reflected in the Sr:Ca ratios of browsers and grazers, respectively(Reference Ambrose and Deniro228). Thus, it might be argued that the relatively high Sr:Ca ratios in Australopithicines and Homo reflect their consumption of aquatic resources or of animals such as insects or other small animals feeding on grasses. For now, the exploration of especially Sr:Ca ratios as a dietary proxy method has largely been stalled(Reference Lee-Thorp, Sponheimer and Passey229).

Evidence from the barium:calcium ratio

Another trace element ratio that might provide information on the composition of the early hominin diet is the Ba:Ca ratio, particularly when used in a multiple-element analysis with Sr:Ca and Sr:Ba ratios(Reference Sponheimer, de Ruiter and Lee-Thorp224, Reference Sponheimer and Lee-Thorp230). Combined Ba:Ca and Sr:Ba ratios clearly differentiate grazers from browsers and carnivores in both modern and fossil mammals(Reference Sponheimer and Lee-Thorp230). Hominins have a lower Ba:Ca and higher Sr:Ba ratio compared with grazers and browsers. Paranthropus shows considerable similarity for both ratios with both carnivores and Papionins (baboons), while Australopithecus shows an even higher Sr:Ba ratio. The unusual combination of a high Sr:Ca and low Ba:Ca ratio in hominins (and baboons) has been further observed for some animals such as warthogs and mole rats that make extensive use of underground resources(Reference Sponheimer, Lee-Thorp and de Ruiter231). Finally, the high Sr:Ba ratio, as observed in Australopithecus, might derive from the consumption of grass seeds, which have Sr:Ba ratios three to four times higher than grass straw, while consumption of these grasses is also consistent with stable-isotope evidence (see below) showing that Australopithecus derived a substantial part of its diet from C4 resources. Although not included in any study so far, Sr:Ba ratios in aquatic foods might add to the understanding of the unusual combination of low Ba:Ca and high Sr:Ba ratios.

Evidence from the 13C:12C ratio

Fractionation studies of carbon isotopes differentiate between different routes of photosynthesis. While most tropical African woody plants from forests (like fruits, leaves, trees, roots, bushes, shrubs and forbs) use the C3 photosynthetic pathway, some South African(Reference Vogel232) and East African(Reference Cerling, Harris and MacFadden233) grasses and sedges use the C4 photosynthetic pathway. C4 plants such as sedges (for example, Cyperus papyrus) typically occur in a mosaic of extensive seasonal and perennial shallow freshwater wetlands that can also be found in savanna and ‘bushvelds’ receiving summer rainfall(Reference Peters and Vogel234). The real impact of C4 plants occurred with their spread into Eastern and Southern Africa during the Pliocene(Reference Segalen, Lee-Thorp and Cerling235). Tissues of plants that utilise the C4 pathway have a relatively high content of the stable carbon isotope 13C (about 1·1 % of carbon), since C3 plants discriminate more strongly against 13CO2 during photosynthesis. As a result C3 and C4 plants have quite different 13C:12C ratios in their tissues, as have the herbivorous animals that feed on these plants(Reference Ambrose and Deniro228, Reference Vogel232) and the carnivores that prey on these herbivores(Reference Goldstone, de Hernandez and Beaver193, Reference Cunnane and Crawford206). Differences are expressed as δ13C values (δ13C =  ((13C:12C)sample − (13C:12C)standard) × 1000/(13C:12C)standard) in parts per thousand (‰) relative to the 13C:12C ratio in the reference standard (named Pee Dee Belemnite; PDB), i.e. the carbonate obtained from the fossil of a marine Cretaceous cephalopod (Belemnitella americana) which is highly enriched in 13C (13C:12C ratio = 0·0112372). Consequently, most animals have negative δ13C values (Fig. 5). The δ13C ranges from − 35 to − 21 ‰ (mean − 26 ‰) in C3 plants and from − 14 to − 10 ‰ (mean − 12 ‰) in C4 plants(Reference Lee-Thorp and Sponheimer225). Studies that attempted to reconstruct mammalian food webs indicated that carbon is slightly enriched (1–2 ‰) with each trophic step(Reference Goldstone, de Hernandez and Beaver193, Reference Cunnane and Crawford206). To facilitate comparison of current and historical animals, δ13C analyses are predominantly performed in hard tissues, such as bone collagen and enamel (notably apatite), since these constitute the majority of the fossil record. It was shown that enamel mineral is enriched by about 13 ‰ compared with dietary δ13C(Reference Sponheimer, Lee-Thorp, de Ruiter and Ungar238), while collagen is enriched by about 5 ‰ compared with dietary δ13C(Reference Lee-Thorp and Sponheimer225). Collagen from terrestrial mammal C3 herbivores shows a value of − 21 ‰ (range − 22 to − 14 ‰), while in collagen of C4 herbivores this value is − 7 ‰ ( − 12 to − 6 ‰). Their respective carnivores show collagen values of − 19 ‰ ( − 21 to − 14 ‰) and − 5 ‰ ( − 8 to − 2 ‰), respectively(Reference Lee-Thorp and Sponheimer225). Marine phytoplankton, which uses the C3 pathway, shows an average value of − 22 ‰(Reference Kelly239). Collagen of marine fish shows a range from − 15 ‰ to − 10 ‰, while the values in collagen of reef fish range from − 8 to − 4 ‰(Reference Schoeninger and Deniro240). Marine carnivores have, similar to terrestrial carnivores, intermediate values of − 14 ‰, ranging from − 10 ‰ in collagen of sea otters to − 15 ‰ in collagen of the common dolphin(Reference Kelly239, Reference Schoeninger and Deniro240). Thus, also the δ13C values of marine carnivores compare well with those of their prey. Finally, δ13C values for the muscle of freshwater fish species range from − 24 to − 13 ‰, but considerable variation may exist between different lakes(Reference Mbabazi, Makanga and Orach-Meza241). Unfortunately, no δ13C data are available for terrestrial piscivorous carnivores, but the consistency of the other data suggests that these might be between − 24 and − 13 ‰, i.e. comparable with their prey (Fig. 5).

Fig. 5 Normalised collagen δ13C values (mean and range; in per thousand (‰)) in plankton, crustaceans, sea grasses, C3 and C4 plants; of marine crustaceans, fish and freshwater fish and their respective carnivores; of terrestrial C3 and C4 herbivores and their carnivores; and of human groups in historic and prehistoric times. * Corrected(Reference Lee-Thorp, Sponheimer and Passey229) for collagen ( − 5 ‰). † Corrected(Reference Sponheimer, Lee-Thorp, de Ruiter and Ungar238) for enamel ( − 13 ‰). ‡ Arbitrary range of ±  1 ‰ due to a lack of data. § As predicted from other predator–prey relationships and after correction(Reference Kelly239) for tropic level (+1 ‰). Adapted from Ambrose & Deniro(Reference Ambrose and Deniro228), Sponheimer et al. (Reference Sponheimer, Lee-Thorp and de Ruiter231, Reference Sponheimer, Loudon and Codron247), Peters & Vogel(Reference Peters and Vogel234), Lee-Thorp et al. (Reference Lee-Thorp, Thackeray and van der Merwe237, Reference Lee-Thorp, Sponheimer and Luyt244), Kelly(Reference Kelly239), Schoeninger & Deniro(Reference Schoeninger and Deniro240), Mbabazi et al. (Reference Mbabazi, Makanga and Orach-Meza241), Schoeninger et al. (Reference Schoeninger, Deniro and Tauber242, Reference Schoeninger, Moore and Sept246), Sponheimer & Lee-Thorp(Reference Sponheimer and Lee-Thorp243, Reference Sponheimer and Lee-Thorp248, Reference Sponheimer and Lee-Thorp249) and van der Merwe et al. (Reference van der Merwe, Masao and Bamford245).

Consistent with the data above, Schoeninger et al. (Reference Schoeninger, Deniro and Tauber242) showed that European agriculturalists consuming C3 grasses had much lower δ13C values in bone collagen ( − 21 to − 19 ‰) compared with Mesoamerican agriculturalist consuming C4 maize ( − 7 to − 5 ‰), while North American and European fisher–gatherers had intermediate values ( − 15 to − 11 ‰). However, bone collagen proved less reliable to study early hominin diets. For that purpose the 13C:12C ratio is preferably measured in tooth enamel. To compare collagen δ13C values with enamel δ13C values, an additional (8 ‰) correction has to be made. Similar to the clear distinctions between bone collagen of modern grazers, browsers and their carnivores, tooth enamel data from fossilised fauna from South Africa showed similar differences for Plio-Pleistocene C3 feeders ( − 11·5 ‰) and C4 feeders ( − 0·5 ‰), with Australopithecus, Paranthropus and Homo taking intermediate positions ( − 10 to − 4 ‰)(Reference Sponheimer, Lee-Thorp and de Ruiter231, Reference Peters and Vogel234, Reference Lee-Thorp, Thackeray and van der Merwe237, Reference Sponheimer and Lee-Thorp243), which compared well with the values for contemporaneous felids ( − 10 to − 0·5 ‰)(Reference Sponheimer, Lee-Thorp and de Ruiter231, Reference Lee-Thorp, Thackeray and van der Merwe237, Reference Lee-Thorp, Sponheimer and Luyt244) (Fig. 5). These results clearly demonstrated that a significant proportion of the diets of the early hominins from Swartkrans, Makapansgat and Sterkfontein derived from C4 resources. Using these data it was calculated that South African Paranthropus derived 14–47 % of its diet from C4 sources, compared with 5–64 % in Australopithecus and 20–35 % in Homo (Reference van der Merwe, Masao and Bamford245).

A second study in Olduvai showed that the Tanzanian Paranthropus boisei derived 77–81 % and Homo 23–49 % from its diet from C4 resources(Reference van der Merwe, Masao and Bamford245). The low nutritional value of grasses, and microwear studies (see above) render it unlikely that humans were directly eating grass(Reference Sponheimer, Lee-Thorp and de Ruiter231, Reference Sponheimer and Lee-Thorp243). Analogously, the sizeable carnivory of C4-consuming mammals (such as cane rats, hyraxes or juvenile bovis) was argued to be practically impossible and thus unable to leave a strong C4 signature(Reference Sponheimer and Lee-Thorp243). However, at about 1·8 Mya, there were extensive wetlands in the Olduvai area, where a river from the Ngorongoro mountains entered the area, while at 1·5 Mya the Peninj river produced wetlands near Lake Natron(Reference Stewart, Cunnane and Stewart156). Some researchers investigated the edible plants in a present-day wetland (Okavango Delta) and found that the rhizomes and culms of three species of C4 sedges were edible, the most common one of which is Cyperus papyrus (Reference van der Merwe, Masao and Bamford245). However, it seems unlikely that the C4 signature in all early hominins derived from the consumption of papyrus. It was recently suggested that P. robustus and especially P. boisei had a diet of primarily C4 resources, most probably grasses or sedges, from savanna or wetland environments, respectively(Reference Cerling, Mbua and Kirera190). Theoretically, a good source of C4 foods would be a seasonal freshwater wetland with floodplains and perennial marshlands, with an abundance of easy accessible aquatic foods, large aggregations of nesting birds and calving ungulates(Reference Peters and Vogel234). Consumption of termites could have contributed to the high C4 signature observed in hominin fossils (Fig. 5), but it seems unlikely that termites could explain values as high as 50 % of the diet from C4(Reference Sponheimer and Lee-Thorp243). Finally, an enamel C4 signature of − 10 to − 4 ‰ in hominins, which translates into a soft tissue signature of − 23 to − 17 ‰ and a collagen signature of − 18 to − 12 ‰ (see above), might also derive from the consumption of small freshwater aquatic animals or fish, since they compare well with the δ13C values of − 24 to − 13 ‰ for freshwater fish(Reference Mbabazi, Makanga and Orach-Meza241) and − 18 to − 9 ‰ in collagen of crustaceans and anthropods(Reference Schoeninger and Deniro240), respectively. Moreover, δ13C values for hominins are similar to those reported for marine mammal hunters, freshwater fish, crustaceans, fisher–gatherers, marine and freshwater carnivores and marine fish (Fig. 5).

In agreement with the variability selection hypothesis of Potts(Reference Potts170), which states that large disparities in environmental conditions were responsible for important episodes of adaptive evolution, the wide range in δ13C values in particularly Australopithecus suggests that early hominins utilised a wide range of dietary sources, including C4 resources. This contrasts with chimpanzees, which, even in the most arid and open areas of their range, are known to consume negligible amounts of C4 resources, despite their local abundancy. Consequently, chimpanzees show very little variability in their δ13C carbon signature(Reference Schoeninger, Moore and Sept246, Reference Sponheimer, Loudon and Codron247). This underscores that even if contemporaneous chimpanzees and early hominins inhabited similar habitats, hominins had broadened their dietary range sufficiently to survive in habitats uninhabitable by chimpanzees. The latter assumption provides an interesting perspective on the recent data, which suggest that C4 foods were absent in the diet of Ardipithecus ramidus at 4·4 Mya. Consequently, it has been proposed that the origins of the introduction of C4 foods into the hominin diet lie in the period between 3 and 4 Mya(Reference Lee-Thorp, Sponheimer and Passey229).

Limited evidence from the 15N:14N ratio

Another stable-isotope ratio that has received considerable attention is the N isotope (15N:14N) ratio. A number of food web studies have shown that each step in the food chain is accompanied by 3–4 ‰ enrichment in δ15N(Reference Ambrose and Deniro228, Reference Kelly239) and that δ15N can therefore be useful as a trophic level indicator. Additionally, animals feeding in marine ecosystems have higher values compared with animals feeding on terrestrial resources(Reference Schoeninger, Deniro and Tauber242). For example, North American and European fisher–gatherers and North American marine mammal hunters and salmon fishers had much higher δ15N values (+13 to +20 ‰) compared with agriculturalists (+6 to +12 ‰). Analyses of phyto- and zooplankton suggest that freshwater organisms have δ15N values intermediate to terrestrial and marine organisms(Reference Schoeninger, Deniro and Tauber242). δ15N values are routinely measured in bone collagen, but it has been shown that good-quality collagen (preserving the original δ15N value) can, and only under favourable conditions, survive up to a maximum of 200 000 years(Reference Lee-Thorp and Sponheimer225). This limits δ15N isotopic studies to Late Pleistocene hominins (see below), but with improved technology, future studies using collagen extracted from tooth enamel may expand their application to early hominins(Reference Sponheimer, Lee-Thorp, de Ruiter and Ungar238).

Limited evidence from the 18O:16O ratio

A final isotope that might provide information about an animal's diet and thermophysiological adaptations is the oxygen isotope ratio (18O:16O). More energy is needed to vaporise H218O than H216O. When ocean water evaporates and during evapotranspiration, i.e. the sum of evaporation and plant transpiration from the earth's land surface to the atmosphere, more of the lighter isotope evaporates as H216O. The ensuing 18O enrichment of transpiring leaves results in 18O enrichment in typical browsers such as kudu and giraffe who rely less on free drinking water and derive most of their water from the consumption of the 18O-enriched plant water. As the 16O-enriched water vapour in clouds moves inland, some of it condenses as rain, during which more of the heavier isotope (as H218O) rains out, making the δ18O of coastal rain only slightly less enriched than the original vaporated ocean water, while the δ18O of the remaining water vapour that eventually comes down is highly negative (i.e. more 18O depleted). Consequently, river water from rain and melting ice is more δ18O negative than seawater. Roots derive their water from meteoric or underground water that is thus relatively depleted from 18O and so become animals that are consuming these roots(Reference Sponheimer and Lee-Thorp248, Reference Sponheimer and Lee-Thorp249). Browsers of leaves undergoing evapotranspiration and consumers of roots may thus be expected to have high and low δ18O values, respectively.

Australopiths showed lower δ18O values compared with Paranthropus, but the meaning of this difference remains uncertain. However, one might argue that Australopithecus preferred less arid conditions compared with Paranthropus or was more dependent on seasonal drinking water(Reference Sponheimer, Lee-Thorp and de Ruiter231). Low δ18O was additionally found in primates and suids, which might be linked to frugivory, although this is not supported by the higher 18O values found in Ardipithecus ramidus compared with Australopithicines (Reference White, Asfaw and Beyene68, Reference Lee-Thorp, Sponheimer and Passey229). Taken together, the use of δ18O for exploration of ancient human diets is still in its infancy, but might, especially in combination with other isotope ratios, become more appreciated in the future.

Isotopic data for more recent hominins

It would be of high interest to explore the hominin diet during the last spurt of encephalisation between 1·9 Mya to 100 Kya, when brain size tripled in size to volumes between 1200 and 1490 cm3 for Homo erectus, H. heidelbergensis, H. neanderthalensis and modern H. sapiens (Reference Cunnane, Cunnane and Stewart100). Isotopic data for this period are, however, absent. Due to the limited preservation of collagen beyond 200 000 years, and the near absence of C4 plants in Europe, these answers will have to come from further studies with tooth enamel in Africa and Asia. So far, there is no isotope evidence for the diet of Homo between 1·5 Mya up to 50 Kya (MP Richards, personal communication).

Dietary information from more recent humans comes from data on δ13C, supplemented with data on δ15N and the 13C:15N ratio. The 15N-isotope values of bone collagen(Reference Schoeninger, Deniro and Tauber242) for differentiation between aquatic and agricultural diets were additionally verified by the study of the sulfur isotope ratios (34S:32S), since high intakes of marine organisms also result in higher δ34S values(Reference Hu, Shang and Tong250). Combined isotope studies reveal high intakes of animal protein, with substantial proportions derived from freshwater fish by Upper and Middle Palaeolithic (40–12 Kya) humans in Eurasia, indicating that in some populations about 30 % of dietary protein came from marine sources(Reference Hu, Shang and Tong250Reference Richards and Trinkaus256). In contrast, isotopic evidence indicates that Neanderthals were top-level carnivores that obtained most of their dietary protein from large terrestrial herbivores, although even Neanderthals certainly exploited shellfish such as clams, oysters, mussels and fish on occasion(Reference Hu, Shang and Tong250Reference Richards, Pettitt and Stiner252). At the onset of the Neolithic period (5200 years ago), there was a rapid and complete change from aquatic- to terrestrial-derived proteins among both coastal and inland Britons compared with Mesolithic (9000–5200 years ago) British humans(Reference Richards, Schulting and Hedges254), which coincides precisely with the local onset of the Agricultural Revolution in Europe.

Conclusions from isotope studies

The isotope systems that have been studied thus far in hominin bone and teeth provide evidence that early hominins were opportunistic feeders(Reference van der Merwe, Thackeray and Lee-Thorp257). The spread of C4 foods in East Africa, and subsequently in the hominin food chain between 3 and 4 Mya, is in agreement with a niche of early hominins that locates close to the water. This conception is in agreement with the palaeo-environmental evidence. However, many questions still remain unanswered. With regard to the possible niche in the water–land interface, it seems interesting to include aquatic as well as terrestrial piscivorous animals into future studies. The data of combined studies of early hominins and the more recent hominins suggest a gradual increase in dietary animal protein, a part of which may derive from aquatic resources. In the more recent human ancestors, a substantial part of the dietary protein was irrefutably derived from marine resources, and this habit was only abandoned in some cases after the introduction of agriculture at the onset of the Neolithic(Reference Richards, Schulting and Hedges254).

Archeology

The oldest stone tools found so far are dated to 2·6 Mya(Reference Semaw, Rogers and Quade258, Reference McPherron, Alemseged and Marean259) and it has been suggested that these were used for flesh removal and percussion on long bones for marrow access. From this time onward stone tools were apparently used for defleshing and butchering of large animals. However, again there is a pitfall in putting too much emphasis on the association between stone tools and hunting and butchering of large animals as the sole food source of the human ancestors, especially with regard to brain foods such as LCP. As stated by Liem's paradox; the apparently overwhelming evidence for the consumption of bone marrow, or even brain from cracked skulls, by the findings of cut marks on animal bone may not be evidence for the primary food resources of human ancestors, but only for its fallback food. Bones, especially long bones, are also better preserved than vegetable material. Moreover, cut marks on bone are easier ascribed to human utilisation than any nearby found fossilised fish bones or molluscan shells that only seldomly bear cut marks(Reference Willis, Eren and Rick260, Reference Braun, Harris and Levin261) and are often not even examined. Hence, while human remains are nearly always found in the vicinity of water and the fossil record of nearby found fish is extensive(Reference Asfaw, White and Lovejoy74, Reference de Heinzelin, Clark and White262), the exploitation of aquatic resources is difficult to relate to early man(Reference Leonard, Robertson, Snodgrass and Roebroeks263).

The present review is about the diet that allowed early humans to increase their brain size and thereby become intelligent enough to develop, for example, symbolic thinking and the controlled use of fire. Hunting and/or scavenging is often invoked as an important source of LCP, but, as pointed out by Crawford(Reference Crawford, Cunnane and Stewart2), even in the more recent certainly ‘hunting’ ancestors ‘a [scavenged] small brain was not going to go far among the ladies [and children] even if it was still in an edible condition when they [the male hunters] got it back [from the savanna]’(Reference Crawford, Cunnane and Stewart2), not even in the scenario(Reference Simpson, Quade and Levin264) that we were specialised, as suggested(Reference Bramble and Lieberman265), in endurance running. Apart from organ tissue (liver and brain) and bone marrow (whether scavenged or hunted), fish, shellfish and other aquatic foods are also mentioned as rich sources of the nutrients involved in brain expansion(Reference Broadhurst, Cunnane and Crawford99, Reference Crawford, Bloom and Broadhurst130, Reference Broadhurst, Wang and Crawford266). Therefore, the question arises whether the archeological evidence for human habitation in the land–water ecosystem only represents facilitated fossilisation or indicates the true ecological niche. The following section will focus on comparable evidence for the concurrent exploitation of aquatic resources.

Living in the water–land ecosystem

Because sea levels have risen up to 150 m in the past 17 000 years, a substantial part of the evidence for the exploitation of aquatic resources is hidden below sea level, if not permanently destroyed by the water(Reference Erlandson267, Reference Marean, Bicho, Haws and Davis268). However, in Kenya, a site in East Turkana provides solid evidence that at about 1·95 Mya hominins enjoyed carcasses of both terrestrial and aquatic animals including turtles, crocodiles and fish, which were associated with Oldowan artifacts(Reference Braun, Harris and Levin261). More ambiguous evidence for the exploitation of freshwater fish, crocodiles, turtles, amphibians and molluscs by Homo habilis in the Olduvai Gorge in Tanzania goes back as far as 1·8–1·1 Mya(Reference Erlandson267, Reference Stewart269). Subsequent tentative evidence from the Olduvai Gorge dates the use of similar aquatic resources by Homo erectus to 1·1–0·8 Mya(Reference Erlandson267, Reference Stewart269). Also the out-of-Africa diaspora probably took place largely via the coastlines(Reference Stringer81), even after the crossing of the Bering Strait into North America(Reference Wang, Lewis and Jakobsson270) (Fig. 2). In Koa Pah Nam, Thailand, 700 000-year-old piles of freshwater oyster shells were associated with Homo erectus (Reference Pope271, Reference Fagan272). In Holon, Israel, freshwater turtles, shells and hippopotamus bones were associated with Homo erectus and dated to 500–400 Kya(Reference Bar-Yosef273). Homo erectus fossils associated with seal remains in Mas del Caves (Lunel-Viel, France) were dated to 400 Kya(Reference Cleyet-Merle, Madelaine and Fischer274).

The archeological evidence for aquatic resource use increases with the appearance of archaic Homo sapiens (Reference Erlandson267). Although dominated by land mammal bones, 400 000–200 000-year-old remains from penguin and cormorants in Duinefontein, South Africa were associated with early Homo (Reference Klein, Avery and Cruz-Uribe275). Shellfish and possibly fish remains, dated 300–230 Kya, were associated with the French coastal campsite at Terra Amata(Reference de Lumley276, Reference Villa277), while marine shellfish and associated early human remains, dated 186–127 Kya, were found in Lazaret, France(Reference Cleyet-Merle, Madelaine and Fischer274). Marean et al. (Reference Marean, Bar-Matthews and Bernatchez278) found evidence for the inclusion of marine resources, at 164 Kya, in the diet of anatomically modern humans from the Pinnacle Point Caves (South Africa). At the Eritrea Red Sea coast, Middle Stone Age artifacts on a fossil reef support the view that early humans exploited near-shore marine food resources by at least 125 Kya(Reference Walter, Buffler and Bruggemann279). In several North African sites, dated to 40–150 Kya(Reference Erlandson267), human remains were associated with shell middens and aquatic resources such as aquatic snails, monk seals, mussels and crabs. Several European sites, dated to 30–125 Kya, are comparable with archeological sites that reveal evidence ranging from thick layers of mussels and large heaps of marine shells in Gibraltar(Reference Erlandson267) to diverse marine shells in Italy(Reference Stiner280), and to a casual description of the presence of marine shells of unknown density in Gruta da Figueira in Portugal(Reference Erlandson267). Further evidence for the use of shellfish, sea mammals and flightless birds comes from: Klasies River Mouth (South Africa) dated between 130 and 55 Kya(Reference Erlandson267, Reference von den Driesch281, Reference Erlandson, Cunnane and Stewart282); from Boegoeberg, where 130 000–40 000-year-old shell middens and cormorant bones were associated with Homo sapiens (Reference Erlandson267, Reference Klein, Cruz-Uribe and Halkett283); from Herolds Bay Cave, where 120 000–80 000-year-old shell middens, shellfish, mussels and otter remains were associated with human hearths(Reference Erlandson267); from Die Kelders (75–55 Kya), where abundant remains of sea mammals, birds and shellfish were found in cave deposits(Reference Erlandson267, Reference Marean, Goldberg and Avery284); and from Hoedjies Punt (70–60 Kya), Sea Harvest (70–60 Kya) and Blombos Cave (60–50 Kya) for the use of shellfish, sea mammals and fish(Reference Erlandson267, Reference Henshilwood and Sealy285). From this period onwards, human settlements are strongly associated with the exploitation of aquatic resources(Reference Erlandson267, Reference Marean, Bicho, Haws and Davis268, Reference Erlandson, Cunnane and Stewart282, Reference Klein, Avery and Cruz-Uribe286Reference Henshilwood, d'Errico and Vanhaeren288). Evidence for more sophisticated fishing by use of barbed bone harpoon points dates back to 90–75 Kya in Katanda, Semlike River, Zaire(Reference Harris, Williamson, Morris and Boaz289, Reference Meylan and Boaz290) and to 70 Kya in South Africa(Reference Henshilwood, Sealy and Yates291). Finally, indications for seafaring are dated to 42–15 Kya(Reference Wickler and Spriggs292Reference O'Connor, Ono and Clarkson294). Possibly, seafaring dates as far back as 800 Kya, as indicated by the finding of Homo erectus stone tools at the Indonesian island of Flores, which is located on the other side of a deep sea strait(Reference Brown, Sutikna and Morwood79, Reference Morwood, O'Sullivan and Aziz295Reference Brumm, Jensen and van den Bergh299). In general, many archeological sites are found along channels, lake- and seashores(Reference Broadhurst, Cunnane and Crawford99, Reference Broadhurst, Wang and Crawford266, Reference Erlandson267, Reference Erlandson, Cunnane and Stewart282) and reveal aquatic fauna, such as catfish, crocodile and hippopotamus(Reference Sept300), but its proves difficult to relate their possible utilisation to our early ancestors.

Several events within the time span of the past about 2 million years have been attributed to the increase in brain size and intelligence. The introduction of meat in the hominin diet, which resulted in a higher dietary quality, has been discussed above. Claims for controlled fire in the Olduvai Gorge (Tanzania) and Koobi Fora (Kenya) go as far back as 1·5 Mya(Reference Wrangham, Jones and Laden215, Reference Gibbons301, Reference Wobber, Hare and Wrangham302). Evidence for cooking is as old as 250 Kya(Reference Gibbons301), but possibly dates back to 800 Kya(Reference Goren-Inbar, Alperson and Kislev303), when indications of controlled fire were found to be present. However, recently it has been concluded that solid evidence for systematic use of fire is only found from 400 to 300 Kya onwards(Reference Roebroeks and Villa304). Evidence that cooking provided increased dietary quality was recently provided by Wrangham et al. (Reference Wrangham, Jones and Laden215). According to archeological evidence, this could only have played an important role since the appearance of Homo sapiens (Reference Wrangham, Jones and Laden215, Reference Gibbons301) and Neanderthals(Reference Henry, Brooks and Piperno305). Also, the inclusion of aquatic resources as an attributor to human brain evolution has been suggested(Reference Crawford, Cunnane and Stewart2, Reference Broadhurst, Cunnane and Crawford99Reference Cunnane101, Reference Crawford, Bloom and Broadhurst130, Reference Broadhurst, Wang and Crawford266, Reference Crawford, Bloom and Cunnane306Reference Parkington, Roggenpoel, Halkett and Conard308), but remains a matter of debate(Reference Carlson and Kingston134, Reference Joordens, Kuipers and Muskiet135, Reference Marean, Bicho, Haws and Davis268, Reference Cordain, Eaton and Sebastian309).

From hunting–gathering to agriculture

The hunter–gatherer lifestyle continued worldwide for several millions of years and ended quite abruptly with the introduction of agriculture. The first indications for the abandonment of the hunter–gatherer lifestyle towards settlement come from a 23 000 year-old fisher–hunter–gatherer's camp at the shore of the Sea of Galilee(Reference Nadel, Weiss and Simchoni310, Reference Weiss, Wetterstrom and Nadel311). The associated return from diets containing substantial amounts of protein (from hunting and gathering) back to substantial amounts of carbohydrates is supported by indications for the ground collecting of wild cereals(Reference Kislev, Weiss, Hartmann and Hartmann312). This was slowly followed by the large-scale utilisation of cereals starting with the onset of the Agricultural Revolution some 10 Kya.

As indicated above (see ‘Biogeochemistry’), there is much controversy about the diet of the earliest humans and until now it is often stated that fishing was only introduced until more recently. From an anthropological perspective this might be true, since certain types (for example, deepwater) of fishing require advanced techniques(Reference O'Connor, Ono and Clarkson294). However, from a nutritional point of view, ‘fishing’ might include anything from collecting sessile shellfish to the seasonal hand capture or clubbing of migrating or spawning fish in very shallow water. Since fresh drinking water is the single most important aquatic resource for humans, hominins probably observed predators and scavengers feeding on aquatic animals. This makes it unlikely that they would not have participated in opportunistic harvesting of the shallow-water flora and fauna, such as molluscs, crabs, sea urchins, barnacles, shrimp, fish, fish roe or spawn, amphibians, reptiles, small mammals, birds or weeds(Reference Joordens, Wesselingh and de Vos175, Reference Erlandson267). There are many indications suggesting that the evolution of early Homo and its development to Homo sapiens did not take place in the ‘classical’ hot, arid and waterless savanna, but occurred in African ecosystems that were notably located in places where the land meets the water (with the land ecosystem possibly consisting of – depending on rainfall – wooded grasslands). Compared with terrestrial hunting and/or scavenging in the savanna, food from this land–water ecosystem is relatively easy to obtain and is rich in the aforementioned combination of haem-Fe, iodine, Se, vitamins A and D, and long-chain n-3-fatty acids(Reference Cunnane, Cunnane and Stewart100, Reference Cunnane101, Reference Broadhurst, Wang and Crawford266).

In conclusion, there is ample archeological evidence for a shift from the consumption of plant towards animal foods. Second, although there is an extensive archeological record for aquatic fossils (representing possible food) in the vicinity of human remains, their co-occurence is usually attributed to the preferential conservation of human remains in the vicinity of water. The present review provides support for the notion that the exploitation of these aquatic resources by hominins in coastal areas should be the default assumption, unless proven otherwise(Reference Joordens154). For a long time period in hominin evolution, hominins derived large amounts of energy from (terrestrial and aquatic) animal fat and protein. This habit became reversed only by the onset of the Neolithic Revolution in the Middle East starting about 10 Kya.

Anthropology

The hunter–gatherer diet

The Homo genus has been on earth for at least 2·4 million years(Reference Kimbel, Walter and Johanson313) and for over 99 % of this period has lived as hunter–gatherers(Reference Lee, Lee and DeVore314). Surprisingly, very little information is available on the macro- and micronutrient compositions of their diet in this extended and important period of human evolution(Reference Eaton, Eaton and Sinclair34, Reference Cordain, Miller and Eaton148). Since the onset of agriculture, about 10 Kya, agriculturalists and nomadic pastoralists have been expanding at the expense of hunter–gatherers(Reference Lee, Lee and DeVore314), with agricultural densities increasing by a factor of 10–1000 compared with the highest hunter densities. For this reason, present-day hunter–gatherers are often found in marginal environments, unattractive for crop cultivation or animal husbandry.

In order to study the original hunter–gatherer way of life, it is appropriate to aim at the few hunter–gatherer communities living in the richer environments that bear closer resemblance to those in which the evolution of the genus Homo probably took place. Most studies on hunter–gatherers and their diets are, however, performed by anthropologists(Reference Murdock315), whose primary interests are different from those of nutritionists. Anthropologists would, for example, conclude that ‘fishing was so unimportant as to be a type of food collection’(Reference Stewart, Lee and DeVore316), or consider collecting both small land fauna and shellfish(Reference Lee, Lee and DeVore314) as part of ‘gathering’, whereas from a nutritional point of view considerable differences exist in energy density, macro- and micronutrient composition between plants, terrestrial and aquatic animal foods.

Hunting v. gathering

Studies on food procurement of present-day hunter–gatherer societies show, in terms of energy gain v. expenditure, the advantage of hunting compared with plant foraging(Reference Ulijaszek192). Nevertheless, three distinct studies(Reference Marlowe41, Reference Cordain, Miller and Eaton148, Reference Lee, Lee and DeVore314) showed that hunting makes up only about 35 % of the subsistence base for worldwide hunter–gatherers, independent of latitude or environment. However, collection of small land fauna and shellfish was included as gathering in these studies. While gathering evidently played an important role over the whole of human evolution, hunting, although introduced later, coincided with ‘a major leap for mankind’ and has ever since played the most dominating cultural role. While hunting may have overtaken gathering in cultural importance, gathering continued to play a very important nutritional role, because: (i) gathering still contributes about 65 % to the subsistence base; (ii) many micronutrients derive only from plant sources; (iii) gathering of, for example, shellfish provides a substantial amount of LCP and other nutrients essential for brain development; and (iv) gathering plays an important cultural role since women, children and grandparents can participate(Reference Hawkes, O'Connell and Jones56, Reference O'Connell, Hawkes and Blurton Jones57, Reference Meehan317).

Contrary to common belief, hunting in present-day hunter–gatherers is still not very successful: the probability for a kill in !Kung bushmen is only 23 %(Reference Lee, Lee and DeVore314) and the subsistence of Hadza, as described by Marlowe(Reference Marlowe41) and Woodburn(Reference Woodburn, Lee and DeVore145), is composed of 75–80 % of plant foods. Conversely, studies of North American hunting–gathering societies describe the dietary role of shellfish as similar to ‘bread and butter’, being the staple food(Reference Moss318) in these societies. The anthropological remark(Reference Lee, Lee and DeVore314) that for many studied hunter–gatherer tribes ‘fishing was only a type of food collection’ also adds to the notion that the collection of aquatic foods might have preceded scavenging and hunting. Collecting aquatic foods is still daily practice in Eastern Africa and picking up, clubbing or spearing stranded aquatic animals seems much easier and safer than either scavenging or hunting game on the Serengeti plains.

We conclude that gathering plays, and most likely always played, the major role in food procurement of humans. Although hunting doubtlessly leaves the most prominent signature in the archaeological record, gathering of vegetables and the collection of animal, notably aquatic, resources (regardless of whether their collection is considered as either hunting or gathering), seems much easier compared with hunting on the hot and arid savanna. We suggest that it seems fair to consider these types of foods as an important part of the human diet, unless proven otherwise(Reference Joordens154). Conversely, while hunting might have played a much more important role at higher latitudes, dietary resources in these ecosystems are rich in n-3-fatty acids (for example, fatty fish and large aquatic mammals), while the hominin invasion of these biomes occurred only after the development of more developed hunting skills.

(Patho)physiology

Brain-selective nutrients

Nutrients and other environmental factors are increasingly recognised to influence epigenetic marks(Reference Godfrey, Lillycrop and Burdge319Reference Godfrey, Sheppard and Gluckman323), either directly or indirectly via many bodily sensors. Food from the diverse East African aquatic ecosystems is rich in haem-Fe, iodine, Se, vitamins A and D, and n-3 fatty acids from both vegetable origin and fish(Reference Cunnane101). All of these nutrients seem to act at the crossroad of metabolism and inflammation(Reference Muskiet, Montmayeur and Coutre24). For example, PPAR(Reference Bensinger and Tontonoz324, Reference Castrillo and Tontonoz325) are lipid-driven nuclear receptors with key cellular functions in metabolism and inflammation(Reference Feige, Gelman and Michalik26). TR(Reference Song, Yao and Ying326), VDR(Reference Bouillon, Bischoff-Ferrari and Willett327), RXR and RAR(Reference McGrane328) are other examples of nuclear transcription factors that serve functions as ligand-driven sensors. The iodine- and Se-dependent hormone triiodothyronine (T3)(Reference Venturi, Donati and Venturi329Reference Gilbert, McLanahan and Hedge331) is a ligand of TR(Reference Song, Yao and Ying326), many fatty acids and their derivatives are ligands of PPAR(Reference Desvergne and Wahli332), the vitamin D-derived 1,25-dihydroxyvitamin D hormone is a ligand of the VDR(Reference Norman and Bouillon333), 9-cis-retinoic acid and the fish oil fatty acid DHA are ligands of RXR(Reference McGrane328), while RAR interacts with vitamin A (retinol) and many of its derivatives such as all-trans-retinoic acid, retinal and retinyl acetate(Reference McGrane328). The ligated nuclear transcription factors usually do not support transcription by themselves, but need to homodimerise or heterodimerise notably with RXR to facilitate gene transcription. Examples of the latter are TR/RXR, PPAR/RXR, VDR/RXR and RAR/RXR. It has become clear that their modes of action illustrate the need of balance between, for example, iodine, Se, fish oil fatty acids and vitamins A and D, a balance that is notably found in the land–water ecosystem.

Deficiencies of the above ‘brain-selective nutrients’ are among the most widely encountered in the current world population(Reference Cunnane101, Reference Holick and Chen334). While iodide is added to table salt in many countries, margarines and milk have become popular food products for fortification with vitamins A and D. After discussing some general health differences between traditionally living individuals and those living in Westernised countries, we focus on the importance of LCP and notably those of the n-3-series, as examples of the above-mentioned nutrients that are especially abundant in the land–water ecosystem.

Hunter–gatherer v. ‘Western’ physiology

There are many differences in health indicators between traditionally living individuals and those living in Western societies. For instance, primary and secondary intervention trials with statins indicate lowest CHD risk at an LDL-cholesterol of 500–700 mg/l (1·3–1·8 mmol/l), which is consistent with levels encountered in primates in the wild and hunter–gatherer populations with few deaths from CVD(Reference Mann, Roels and Price335Reference O'Keefe, Cordain and Harris339). Another example of the healthy lifestyle of present-day hunter–gatherers comes from the observed ‘insulinopenia’ or ‘impaired insulin secretion’ following an oral glucose tolerance test (Fig. 6) in Central African Pygmies and Kalahri Bushmen(Reference Joffe, Jackson and Thomas340, Reference Merimee, Rimoin and Cavalli-Sforza341), respectively. As opposed to the ‘impairments’ noted by these authors, it may also be argued that these researchers were actually witnessing an insulin sensitivity that has become sporadic in Western countries as a consequence of the decrease in physical activity and fitness, increase in fat mass and as a result of the quantity and quality of the foods consumed(Reference O'Keefe and Cordain36, Reference Cordain, Eaton and Sebastian133, Reference Ramsden, Faurot and Carrera-Bastos342). The current consensus is that ‘fat is bad’ and especially saturated fats have become associated with CVD(Reference Keys343Reference Kuipers, de Graaf and Luxwolda345). However, traditional Maasai consumed diets high in protein and fat (milk and meat) and low in carbohydrates(Reference Ho, Biss and Mikkelson346, Reference Biss, Ho and Mikkelson347). They had high intakes of saturated fat and cholesterol, showed extensive atherosclerosis with lipid infiltration and fibrous changes, but had very few complicated lesions, and were virtually devoid of CVD(Reference Mann, Spoerry and Gray348). The average total and LDL-cholesterol in these societies was low and did not increase with age(Reference Mann, Spoerry and Gray348). Finally, the physical fitness of individuals in such traditional societies, such as the Maasai, is often remarkable(Reference Mann, Shaffer and Rich337).

Fig. 6 ‘Abnormal’ insulin response but normal glucose response after oral glucose tolerance test in African Bushmen and Pygmies, compared with Western controls. (a) Plasma glucose response after an oral glucose load of 50 g (Bushmen (♦) and white controls (○)) or 100 g (Pygmy (■), Pygmy with 2 weeks' daily supplementation of 150 g carbohydrates before testing (▲), Bantu (X) and American controls ()). Of note is that Bushmen and Pygmies have significantly lower body weights as compared with Bantu and white and American controls (average weight Bushmen/Pygmy males 46 kg, females 38 kg; controls 65 kg), while each group received the same unadjusted loading dose of 50 g or 100 g glucose. (b) The so-called ‘abnormal’ insulin response or ‘impaired’ insulin secretion as observed by the authors in both Bushmen and Pygmies(Reference Joffe, Jackson and Thomas340, Reference Merimee, Rimoin and Cavalli-Sforza341).

In Kalahari Desert Bushmen and Central African Pygmies, observers could not find any case of high blood pressure and blood pressure did not increase with age(Reference Mann, Roels and Price335, Reference Kaminer and Lutz349). Dental surveys of Kalahari Bushmen(Reference Clement, Fosdick and Plotkin350) and other hunter–gatherers(Reference Larsen49) showed a remarkable absence of caries. The absence was explained by the repetitive annual abstinence of fermentable sugars in their diet, with a consequent inability to build a cariogenic oral Lactobacillus flora(Reference Clement, Fosdick and Plotkin350). Inhabitants of Kitava (Trobriand Islands, Papua New Guinea) have high intakes (70 en%) of carbohydrates from yams, high intakes of SFA from coconuts, and a high fish intake(Reference Lindeberg and Lundh44, Reference Lindeberg, Nilsson-Ehle and Terent45, Reference Lindeberg, Berntorp and Nilsson-Ehle351). Although both high intakes of carbohydrates and saturated fat have been related to the metabolic syndrome and CVD, these traditional Kitavians do not show symptoms of either the metabolic syndrome and are virtually free from the Western diseases that ensue from it.

Evidence-based medicine as applied to long-chain PUFA in CVD and depression

Despite some compelling examples of the healthy lifestyles of traditional populations, current dietary recommendations derive preferably from randomised clinical trials with single nutrients and preferably hard endpoints(Reference Sackett, Rosenberg and Gray352). This approach clearly oversimplifies the effects of dietary nutrients(Reference Blumberg, Heaney and Huncharek353), since neither macronutrients, nor micronutrients, are consumed in isolation and their effects may be the result of a complex web of interactions between all the nutrients present in the biological systems that we consume, such as a banana or a fish.

The current recommendations from many nutritional boards for a daily intake of 450 mg EPA + DHA in adults derive from epidemiological data that demonstrated a negative association of fish consumption with CHD(Reference Dyerberg, Bang and Hjorne354Reference Mozaffarian and Rimm357) that has subsequently become supported by landmark trials with ALA(Reference de Lorgeril, Salen and Martin358) and fish oil(359Reference Yokoyama, Origasa and Matsuzaki361) in CVD. However, not all trials in CVD have been positive(Reference Kromhout, Giltay and Geleijnse362). In addition, a negative association was observed for fish consumption and depression(Reference Hibbeln363Reference Hibbeln365) and for homicide mortality(Reference Hibbeln366). The causality of these relationships was supported by some, but not all, trials with fish oil in depression(Reference Lin and Su367Reference Freeman, Hibbeln and Wisner371), while a recent meta-analysis demonstrated the beneficial effect of EPA supplements with ≥  60 % EPA of total EPA + DHA in a dose range of 200–2200 mg/d of EPA in excess of DHA(Reference Sublette, Ellis and Geant372).

The influence of polymorphisms in the genome is increasingly recognised, but seldom interpreted in an evolutionary context. As argued above, most polymorphisms were already amongst us when Homo sapiens emerged, some 200 Kya, while that also holds true for most, if not all, currently identified ‘disease susceptibility genes’ that are usually abundant but confer low risk(373). A loss-of-function mutation in a specific biosynthetic pathway might be an evolutionary advantage if the specific endproduct has been a consistent part of the diet, such as is probably applicable to all vitamins, for example, vitamin C(Reference Challem374, Reference Nishikimi, Fukuyama and Minoshima375). Applied to our LCP status, it is nowadays well established that all humans synthesise DHA with difficulty(Reference Burdge and Wootton376, Reference Burdge377). Analogously, the recently discovered polymorphisms of fatty acid desaturases 1 (FADS1; also named Δ-5 desaturase) and FADS2 (Δ-6 desaturase) with lower activities in their conversion of the parent essential fatty acid to LCP suggest that from at least the time of their appearance, the dietary intakes of AA, EPA and DHA have been of sufficient magnitude to balance the LCP n-3:LCP n-6 ratio(Reference Kuipers, Luxwolda and Janneke Dijck-Brouwer378, Reference Luxwolda, Kuipers and Smit379) to maintain good health.

Long-chain PUFA benefits in pregnancy and early life

Another indication for the importance of LCP comes from the higher LCP contents in the fetal circulation compared with the maternal circulation, a process named biomagnification(Reference Crawford, Hassam and Williams380Reference Crawford, Hassam and Rivers382), which occurs at the expense of the maternal LCP status(Reference Hornstra383, Reference Hornstra384). The decreasing maternal n-3 LCP status during pregnancy in Western countries is associated with postpartum depression(Reference Hibbeln363, Reference Hibbeln364), although intervention studies with LCP in postpartum depression have been negative so far(Reference Freeman370, Reference Freeman, Hibbeln and Wisner371, Reference Makrides, Gibson and McPhee385, Reference Doornbos, van Goor and Dijck-Brouwer386). However, a positive effect was seen for n-3 LCP supplementation on depression during pregnancy(Reference Su, Huang and Chiu387) and it has been advocated to start supplementation earlier in pregnancy and with higher dosages(Reference Wojcicki and Heyman388).

Maternal LCP intakes have also been related to infant health. AA and DHA in premature and low-birth-weight infants correlated positively with anthropometrics, AA to increased birth weight(Reference Koletzko and Braun389) and DHA to prolonged gestation(Reference Szajewska, Horvath and Koletzko390Reference Olsen, Osterdal and Salvig392). Studies with supplementation of DHA during pregnancy yielded, for example, evidence for: (i) the maturation of the brain, visual system and retina of the newborn at 2·5 and 4 months, but not at 6 months(Reference Malcolm, McCulloch and Montgomery393Reference Smithers, Gibson and McPhee397); (ii) increased problem solving at 9 months but no difference in memory(Reference Judge, Harel and Lammi-Keefe398); and (iii) superior eye–hand coordination at 2·5 years(Reference Dunstan, Simmer and Dixon399) and higher intelligence quotient at 4 years(Reference Helland, Smith and Saarem400) but not at 7 years of age(Reference Helland, Smith and Blomen401). In contrast to the inconclusive human studies, animal studies and combined human and animal studies showed abnormal behaviour together with disturbed cognition at lower brain DHA levels(Reference McCann and Ames402). The importance of dietary AA during pregnancy seems less pronounced, but a positive association between umbilical AA and neonatal neurological development(Reference Koletzko and Braun389) and a lower venous AA for those with slightly abnormal neurological development(Reference Dijck-Brouwer, Hadders-Algra and Bouwstra403) has been shown. A reduced DHA status in the brain is associated with a mildly increased AA status(Reference Moriguchi, Loewke and Garrison404), which is in its turn associated with low-grade inflammation(Reference Rao, Ertley and DeMar405).

Infant health starts with maternal health; thus dietary recommendations issued for pregnant women indirectly also apply to their infants. The recommendation for adults to consume 450 mg DHA + EPA per d translates into a DHA composition in breast milk of about 0·79 %(Reference van Goor, Smit and Schaafsma406). However, current recommendations for the composition of infant formulae derive mainly from the range of human milk fatty acid compositions as observed in Western countries, which in their turn derive from women with recorded intakes below the 450 mg recommended daily intake of EPA + DHA(Reference Brenna, Varamini and Jensen407, Reference Koletzko, Lien and Agostoni408).

The same paradox holds for other fatty acids in breast milk. For instance, there are few recommendations for the medium-chain SFA (MCSFA) content of human milk. High MCSFA contents in some traditional societies derive from their high intakes of 12 : 0 and 14 : 0 from coconuts(Reference Kuipers, Smit and van der Meulen409). Conversely, the high MCSFA contents in Western populations are primarily influenced by maternal carbohydrate intakes(Reference Hachey, Silber and Wong410), since the mammary gland has the unique ability to convert glucose into MCSFA (6 : 0–14 : 0), mainly lauric (12 : 0) and myristic (14 : 0) acids. However, women with regular consumption of coconuts have a much higher 12 : 0:14 : 0 ratio compared with women with high carbohydrate intakes. Both MCSFA are readily absorbed in the gastrointestinal tract, while antiviral as well as antibacterial properties have been attributed to some MCSFA, but mainly to 12 : 0(Reference Kabara411, Reference Bergsson, Steingrimsson and Thormar412).

The PUFA content of Western milk has increased over the last decades(Reference Widdowson, Dauncey and Gairdner413, Reference Ailhaud, Massiera and Weill414). While the human milk LA content in the USA increased by at least 250 %, its DHA content decreased by almost 50 %(Reference Ailhaud, Massiera and Weill414). The (from an evolutionary point of view) abnormally high LA intake is, despite a lack of evidence(Reference Ramsden, Hibbeln and Majchrzak415), advocated for cardiovascular health(Reference Harris, Mozaffarian and Rimm416). The resulting high LA status is likely to interfere with both the incorporation of AA and DHA into phospholipids and also inhibits their synthesis from their parent essential fatty acid(Reference Gibson, Muhlhausler and Makrides417). Major differences are noted in the comparison of the human milk fatty acid compositions of Western mothers compared with some traditional African women(Reference Kuipers, Smit and van der Meulen409, Reference Koletzko, Thiel and Abiodun418), with unknown consequences for infant health or the occurrence of disease at adult age (i.e. the ‘Barker hypothesis’)(Reference Barker16, Reference Godfrey, Robinson and Barker419). It has been proposed that the high concentrations of EPA, DHA as well as AA in human milk, such as described for many fish-consuming societies(Reference Kuipers, Smit and van der Meulen409, Reference Innis and Kuhnlein420, Reference Ruan, Liu and Man421), might be a more appropriate reflection of the Palaeolithic breast milk composition and may therefore constitute a better reference for infant formulae than do Western human milks(Reference Muskiet, Kuipers and Smit422).

The influence of environment

It is estimated that 70 % of all cases of stroke and colon cancer, 80 % of all CVD and 90 % of all cases of type 2 diabetes mellitus have been caused by lifestyle and could have been prevented by paying more attention to modifiable behaviour factors, including specific aspects of diet, overweight, inactivity and smoking(Reference Willett423). The mismatch between the human diet and the Palaeolithic genome might therefore be responsible for many typically Western diseases. In addition to the evidence from many other disciplines, evidence from (patho)physiology and epidemiology adds to the notion that a great deal of information on healthy diets might derive from the study of the diets of the early human ancestors. The metabolic syndrome, characterised by impaired insulin sensitivity, is at the centre of many diseases of civilisation. High intakes of refined carbohydrates as well as low intakes of LCP have been implicated in the development of insulin resistance. As such, low carbohydrate intakes(Reference Yudkin424, Reference Yudkin425) and high LCP(Reference Eaton and Konner8, Reference Eaton, Eaton and Sinclair34, Reference Eaton426, Reference Cordain, Watkins and Mann427) intakes by the early human ancestor might explain in part the low incidence of diseases of civilisation in current hunter–gatherer societies. The available evidence from pathophysiology and epidemiology supports the hypothesis that the land–water ecosystem contributed important and indispensable nutrients to evolving hominins.

Dietary reconstruction of the nutrients available in Eastern Africa

The debate on the ecological niche of human ancestors is unlikely to reach a consensus shortly. The millions of years of human evolution concurred with marked and abrupt climatic changes, which renders a single ecological niche of human ancestry unlikely. However, it is at the same time clear that in a short period of time humans have made tremendous changes in their lifestyle, their diet included, that lie at the basis of the diseases of Western civilisation. This prompted various investigators to reconstruct the possible compositions of diets that could have been consumed by our Palaeolithic ancestors. Their studies are, for example, based on the plausibility that before the Agricultural Revolution, when humans lived as hunter–gatherers, cereals were no appreciable part of the diet and that wild animals living in the Eastern African savanna and in Eastern African aquatic ecosystems have different fatty acid compositions compared with the domesticated animals that have now become staple foods. For example, the lean savanna animals that inhabit the Eastern African plains have much lower fat contents, and the available fat is much more enriched in PUFA(Reference Crawford428). Similarly, high-latitude (fatty) fish have much higher EPA and DHA contents, but lower AA contents compared with low-latitude (lean) fish from tropical waters(Reference O'Dea and Sinclair429Reference Naughton, O'Dea and Sinclair432).

Eaton & Konner(Reference Eaton and Konner8) where the first to use this approach in reconstructing a Palaeolithic diet; their pioneer study was published in the New England Journal of Medicine in 1985. The authors estimated that late Palaeolithic humans consumed diets containing 35 % meat and 65 % vegetable foods, containing 34 en% from protein, 45 en% from carbohydrate and 21 en% from fat, while the ratio between polyunsaturated and saturated fat equalled 1·41 and their fibre intake amounted to 46 g/d(Reference Eaton and Konner8). These outcomes contrasted with the average American diet at the time, that consisted of 12 en% protein, 46 en% carbohydrate and 42 en% fat, with a polyunsaturated:saturated fat ratio of 0·44 and a fibre intake of 20 g/d. After 25 years of additional study, Konner & Eaton confirmed their previous findings by estimating that the Palaeolithic diet provided 25–30 en% protein, 35–40 en% carbohydrate and 20–35 en% fat(Reference Konner and Eaton433), while the polyunsaturated:saturated fat ratio was 1·40(Reference Eaton, Eaton and Konner434). Moreover, they concluded that ‘it has become clear since our initial publications that marine, lacustrine, and riverine species were important sources of animal flesh during the evolution of modern Homo sapiens, and may have played a role in the evolution of brain ontogeny’(Reference Konner and Eaton433). In addition to the earlier studies, they also estimated the vitamin and mineral composition of a Palaeolithic diet, showing higher contents of folate, riboflavin, thiamin, vitamins A and E, Ca, Mg, P, Zn, and notably ascorbate, vitamin D (sunlight), Cu, Fe, Mn and K, while the Palaeolithic diet contained much lower Na compared with contemporary US intakes and recommendations(Reference Konner and Eaton433Reference Eaton and Eaton435). In a subsequent study they estimated that in different ancient hunting and gathering populations, fatty acid intakes would have ranged from 5·19 to 20·6 g LA/d, 0·26 to 4·8 g AA/d, 3·45 to 25·2 g ALA/d and 0·03 to 1·52 g DHA/d, which contrasted with the much higher LA (22·5 g/d) and lower ALA (1·2 g/d), AA (0·6 g/d) and DHA (0·08 g/d) intakes as observed in current Western populations(Reference Eaton, Eaton and Sinclair34).

In a meticulous analysis of worldwide hunter–gatherer diets, Cordain et al. (Reference Cordain, Miller and Eaton148, Reference Cordain, Miller and Eaton436) estimated that the most plausible percentages of total energy from dietary macronutrients would be 19–35 en% from protein, 22–40 en% from carbohydrate and 28–58 en% from fat, which reflects a markedly higher contribution of dietary fat, a similar amount of protein, but a lower contribution of carbohydrates, compared with earlier estimates from Eaton & Konner(Reference Eaton and Konner8, Reference Eaton, Eaton and Konner434). The main differences were explained by the assumption that, wherever it was ecologically possible, hunter–gatherers would have consumed 45–65 % of total energy from animal foods(Reference Cordain, Miller and Eaton148), while in the earlier estimations(Reference Eaton and Konner8, Reference Eaton, Eaton and Konner434) only 35 % derived from animal foods. These higher animal food intakes were explained by their inclusion of both worldwide hunting and fishing hunting–gathering societies into their new calculation models(Reference Cordain, Miller and Eaton148), also including mounted and arctic hunters. Those latter possibilities, however, seem insignificant with regard to early human evolution, which explains why they seem to overestimate the amount of the diet that is derived from animal foods. For example, Marlowe(Reference Marlowe41) estimated that in a warm-climate sample about 53 % of the diet derives from gathering, 26 % from hunting and 21 % from fishing (i.e. about 47 % from hunting).

To subsequently investigate the nutrient compositions of such diets, fish consumption was incorporated as a separate variable to plant and meat consumption in the earlier models, since aquatic and terrestrial animals have markedly different fatty acid compositions. In this most recent analysis(Reference Kuipers, Luxwolda and Dijck-Brouwer437), 12 500 kJ (3000 kcal) Palaeolithic diets were investigated with plant:animal food intake ratios ranging from 70:30 to 30:70 en%/en% under the conditions of four different foraging strategies in which the animal part ranged from exclusive meat consumption including the selective consumption of energy- and LCP-rich fat from bone marrow and brain, respectively(Reference Cordain, Watkins and Mann427), to the consumption of an entirely aquatic diet in an Eastern African water–land ecosystem(Reference Morgan438, Reference Horrobin439). It was found that that the energy intakes from the macronutrients were: 25–29 en% (range 8–35) from protein, 39–40 en% (range Reference Gluckman, Hanson and Morton19Reference Angel, Cohen and Armelagos48) from carbohydrate and 30–39 en% (range 20–72) from fat. Dietary LA ranged from 1·7 to 6·2 en%/d, AA from 1·15 to 10·7 g/d, ALA from 2·1 to 5·8 en%/d and EPA + DHA intakes from 0·87 to 28·3 g/d(Reference Kuipers, Luxwolda and Dijck-Brouwer437). From these data, despite their wide range in outcomes, it can again be concluded that there are substantial differences with respect to the average composition of the current Western diet, notably because of its higher proportions of carbohydrates and LA, and its much lower protein and ALA and LCP contents. It became also conceivable that ancestors living in the East African water–land ecosystem had daily intakes of gram amounts of EPA + DHA. As such, these n-3 LCP intakes were comparable with those of the traditionally living Eskimos in Greenland, who because of their low CVD risk(Reference Dyerberg, Bang and Hjorne354, Reference Bang, Dyerberg and Sinclair355) initiated the current interest in the role of n-3 LCP in both primary and secondary prevention of CVD. In addition to these n-3 fatty acids, the water–land ecosystem is also a rich source of haem-Fe, iodine, Se and the vitamins A and D(Reference Cunnane101), which have important functions and interactions in gene transcription and metabolism(Reference Muskiet, Montmayeur and Coutre24, Reference Feige, Gelman and Michalik26, Reference Hotamisligil and Erbay440).

Dietary changes since the Agricultural Revolution

Whatever the specific composition and wide range of early hunter–gatherer diets, the current consensus is that our diet has changed markedly from the time of large-scale utilisation of cereals and animal domestication (i.e. the Agricultural Revolution) starting some 10 Kya. Contrary to earlier belief, the advent of agriculture coincided with an overall decline in nutrition and general health, but at the same time provided an evolutionary advantage since it increased birth rates and thereby promoted net population growth(Reference Larsen49, Reference Larsen50).

While the decline of nutritional quality and general health started with the onset of the Agricultural Revolution, these processes became even more pronounced with the advent of the Industrial Revolution some 100–200 years ago(Reference Eaton, Konner and Shostak9, Reference Eaton and Cordain11, Reference Cordain, Eaton and Sebastian133). Among the many dietary and lifestyle changes (Fig. 7) are: a grossly decreased n-3:n-6 fatty acid ratio, the combined high intakes of SFA and carbohydrates(Reference Forsythe, Phinney and Fernandez441Reference Forsythe, Phinney and Feinman443), the introduction of industrially produced trans-fatty acids, reduced intakes of n-3 and n-6 LCP, reduced exposure to sunlight, low intakes of vitamins D and K, disbalanced antioxidant status and high intakes of carbohydrates with high glycaemic indices and loads, such as sucrose and industrially produced high-fructose maize syrup(Reference O'Keefe and Cordain36, Reference Cordain, Eaton and Sebastian133, Reference Simopoulos444, Reference Simopoulos445). Many of these changes act in concert, which points at the serious limitations of conclusions from contemporary investigations that study the many nutrients in isolation and form the basis of modern nutritional guidelines. An example is the interaction of dietary carbohydrates with SFA(Reference Forsythe, Phinney and Fernandez441Reference Forsythe, Phinney and Feinman443, Reference Feinman and Volek446).

Fig. 7 The seven dietary characteristics that have been changed since the Agricultural and Industrial Revolutions. Adapted from Muskiet(Reference Muskiet, Montmayeur and Coutre24).

Potential benefits of a Palaeolithic diet

Evidence for the beneficial effects of Palaeolithic diets may derive from their influence on weight reduction and classical coronary artery disease risk factors. In an uncontrolled study with healthy adults, Osterdahl et al. (Reference Osterdahl, Kocturk and Koochek447) showed a decrease in weight, BMI and waist circumference after 3 weeks ad libitum consumption of a Palaeolithic-like diet (i.e. 6627 kJ/d (1584 kcal/d); carbohydrate 40, protein 24, fat 36 en%), compared with their baseline usual diet (10 368 kJ/d (2478 kcal/d); carbohydrate 54, protein 14, fat 30 en%). Additionally, they showed favourable effects on systolic blood pressure and plasminogen activator inhibitor-1. Jönsson et al. (Reference Jönsson, Granfeldt and Ahrén448) performed a cross-over study of 2 ×  3 months in type 2 diabetic patients receiving a Palaeolithic diet (6615 kJ/d (1581 kcal/d), carbohydrate 32, protein 24, fat 39 en%) or a diabetes diet (7858 kJ/d (1878 kcal/d), carbohydrate 42, protein 20, fat 34 en%). They showed a reduction of body weight, BMI and waist circumference and lower HbA1c, TAG and diastolic blood pressure, and higher HDL-cholesterol after consumption of the Palaeolithic diet.

In a randomised trial in patients with IHD plus glucose intolerance or type 2 diabetes, Lindeberg et al. (Reference Lindeberg, Jonsson and Granfeldt449) showed a reduced energy intake after ad libitum consumption of a Palaeolithic diet (5623 kJ/d (1344 kcal/d); carbohydrate 40, protein 28, fat 27 en%) as compared with an ad libitum Mediterranean-like Consensus diet (7510 kJ/d (1795 kcal/d); carbohydrate 52, protein 21, fat 25 en%). They also observed a larger improvement in glucose tolerance in the Palaeolithic diet group, independent of decreased waist circumference. The most convincing evidence so far derives from an uncontrolled trial(Reference Frassetto, Schloetter and Mietus-Synder450) showing that 10 d consumption of an isoenergetic Palaeolithic diet (11 301 kJ/d (2701 kcal/d); carbohydrate 38, protein 30, fat 32 en%) improved blood pressure, arterial distensibility, insulin sensitivity and total, HDL- and LDL-cholesterol in healthy sedentary human subjects, when compared with their baseline usual diet (9924 kJ/d (2372 kcal/d), carbohydrate 44, protein 18, fat 38 en%). Importantly, there were no changes in energy intakes, activity levels and body weight, which indicates that the improved coronary artery disease risk profile was unrelated to weight reduction or other well-known determinants.

Conclusions

The optimal nutrient combination to support good health can be expected to reflect a certain balance. This balance is present in the foods that were consumed by Palaeolithic and possibly by pre-Palaeolithic ancestors, because it is this balance on which the human genome has evolved. This genome has been shaped by millions of years of evolution, during which it adapted to the conditions of existence, including the diet. There are ample indications from many disciplines that the human ancestors evolved in a water–land interface that provided food from both terrestrial and aquatic resources. For instance, the availability of both n-3 and n-6 LCP from the aquatic food chain was one of the many factors that provided early humans with the unique combination of brain-selective nutrients for brain growth(Reference Crawford, Cunnane and Stewart2). The recent deviation from this Palaeolithic diet and lifestyle in general might be at the basis of many, if not all, current diseases of civilisation. Detailed studies with respect to the health effects of the diets of these earlier ancestors are therefore warranted.

Acknowledgements

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

R. S. K. wrote the initial manuscript. After finishing a first outline, all authors contributed to their specific fields of knowledge, i.e. R. S. K. and F. A. J. M. refined the sections ‘Environment, nutrients and their interaction with the genome’, ‘Evolutionary medicine’, ‘Arguments and counter arguments in evolutionary health promotion‘, ‘Human evolution’, ‘Dietary changes since the Agricultural Revolution’ and ‘Potential benefits of a Palaeolithic diet’ and the sub-sections ‘Comparative anatomy’, ‘Biogeochemistry’, ‘Anthropology’, ‘(Patho)physiology’ and ‘Dietary reconstruction of the nutrients available in Eastern Africa’; J. C. A. J. refined the section ‘The probability of hunting on the savanna’ and the sub-sections ‘Palaeo-environments’ and ‘Archeology’.

The authors thank Matt Sponheimer, Mike Richards and Peter Ungar for their willingness to answer their questions.

There are no conflicts of interest.

References

1Darwin, C (1979) The Illustrated Origin of Species. Ede: Zomer & Keuning Boeken B.V.Google Scholar
2Crawford, MA (2010) Long-chain polyunsaturated fatty acids in human brain evolution. In Human Brain Evolution. The Influence of Freshwater and Marine Food Resources, pp. 1331 [Cunnane, SC and Stewart, KM, editors]. Hoboken, NJ: Wiley-Blackwell.Google Scholar
3Knoll, AH, Javaux, EJ, Hewitt, D, et al. . (2006) Eukaryotic organisms in Proterozoic oceans. Phil Trans R Soc Lond B Biol Sci 361, 10231038.Google Scholar
4Brocks, JJ, Logan, GA, Buick, R, et al. . (1999) Archean molecular fossils and the early rise of eukaryotes. Science 285, 10331036.Google Scholar
5Buick, R (2008) When did oxygenic photosynthesis evolve? Phil Trans R Soc Lond B Biol Sci 363, 27312743.Google Scholar
6Holland, HD (2006) The oxygenation of the atmosphere and oceans. Phil Trans R Soc B Biol Sci 361, 903915.Google Scholar
7Crawford, MA & Marsh, DE (1995) Nutrition and Evolution: Food in Evolution and the Future. New Canaan, CT: Keats.Google Scholar
8Eaton, SB & Konner, M (1985) Paleolithic nutrition. A consideration of its nature and current implications. N Engl J Med 312, 283289.Google Scholar
9Eaton, SB, Konner, M & Shostak, M (1988) Stone Agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am J Med 84, 739749.Google Scholar
10Eaton, SB, Eaton, SB III, Konner, MJ, et al. . (1996) An evolutionary perspective enhances understanding of human nutritional requirements. J Nutr 126, 17321740.Google Scholar
11Eaton, SB & Cordain, L (1997) Evolutionary aspects of diet: old genes, new fuels. Nutritional changes since agriculture. World Rev Nutr Diet 81, 2637.Google Scholar
12Egger, G & Dixon, J (2009) Should obesity be the main game? Or do we need an environmental makeover to combat the inflammatory and chronic disease epidemics? Obes Rev 10, 237249.Google Scholar
13Egger, G & Dixon, J (2010) Inflammatory effects of nutritional stimuli: further support for the need for a big picture approach to tackling obesity and chronic disease. Obes Rev 11, 137149.Google Scholar
14Wood, B & Brooks, A (1999) Human evolution. We are what we ate. Nature 400, 219220.Google Scholar
15Muskiet, FAJ (2005) Evolutionaire geneeskunde. U bent wat u eet, maar u moet weer worden wat u at (Evolutionary medicine. You are what you eat, but you must again be what you ate). Ned Tijdsch Klin Chem Labgeneesk 30, 163184.Google Scholar
16Barker, DJ (1990) The fetal and infant origins of adult disease. BMJ 301, 1111.Google Scholar
17Godfrey, KM & Barker, DJ (2000) Fetal nutrition and adult disease. Am J Clin Nutr 71, 1344S1352S.Google Scholar
18Drake, AJ & Walker, BR (2004) The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk. J Endocrinol 180, 116.Google Scholar
19Gluckman, PD, Hanson, MA, Morton, SM, et al. . (2005) Life-long echoes – a critical analysis of the developmental origins of adult disease model. Biol Neonate 87, 127139.Google Scholar
20Cordain, L, Eades, MR & Eades, MD (2003) Hyperinsulinemic diseases of civilization: more than just syndrome X. Comp Biochem Physiol A Mol Integr Physiol 136, 95112.Google Scholar
21Reaven, GM (2005) The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 25, 391406.Google Scholar
22Pasinetti, GM & Eberstein, JA (2008) Metabolic syndrome and the role of dietary lifestyles in Alzheimer's disease. J Neurochem 106, 15031514.Google Scholar
23Muskiet, FA & Kemperman, RF (2006) Folate and long-chain polyunsaturated fatty acids in psychiatric disease. J Nutr Biochem 17, 717727.Google Scholar
24Muskiet, FA (2010) Pathophysiology and evolutionary aspects of dietary fats and long chain polyunsaturated fatty acids across the life cycle. In Fat Detection. Taste, Texture, and Post Ingestive Effects, pp. 1979 [Montmayeur, JP and Coutre, J le, editors]. Boca Raton, FL: CRC Press Taylor & Francis Group.Google Scholar
25Muskiet, FAJ & Kuipers, RS (2010) Lessons from shore-based hunter–gatherer diets in East Africa. In In Human Brain Evolution. The Influence of Freshwater and Marine Food Resources, pp. 77103 [Cunnane, SC and Stewart, KM, editors]. Hoboken, NJ: Wiley-Blackwell.Google Scholar
26Feige, JN, Gelman, L, Michalik, L, et al. . (2006) From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog Lipid Res 45, 120159.Google Scholar
27Dobzhansky, T (1964) Biology, molecular and organismic. Am Zool 4, 443452.Google Scholar
28Tinbergen, N (1963) On the aims and methods of ethology. Zeit Tierpsy 20, 410463.Google Scholar
29Harris, EE & Malyango, AA (2005) Evolutionary explanations in medical and health profession courses: are you answering your students' ‘why’ questions? BMC Med Educ 5, 16.Google Scholar
30Purushotham, AD & Sullivan, R (2010) Darwin, medicine and cancer. Ann Oncol 21, 199203.Google Scholar
31Williams, GC & Nesse, RM (1991) The dawn of Darwinian medicine. Q Rev Biol 66, 122.Google Scholar
32Nesse, RM & Williams, GC (1994) Why We Get Sick. The New Science of Darwinian Medicine. New York: Times Books, Random House, Inc.Google Scholar
33Gould, SJ & Vrba, ES (1982) Exaptation – a missing term in the science of form. Paleobiology 8, 415.Google Scholar
34Eaton, SB, Eaton, SB III, Sinclair, AJ, et al. . (1998) Dietary intake of long-chain polyunsaturated fatty acids during the Paleolithic. World Rev Nutr Diet 83, 1223.Google Scholar
35Eaton, SB, Cordain, L & Lindeberg, S (2002) Evolutionary health promotion: a consideration of common counterarguments. Prev Med 34, 119123.Google Scholar
36O'Keefe, JH Jr & Cordain, L (2004) Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter–gatherer. Mayo Clin Proc 79, 101108.Google Scholar
37Hahn, RA, Teutsch, SM, Rothenberg, RB, et al. . (1990) Excess deaths from nine chronic diseases in the United States, 1986. JAMA 264, 26542659.Google Scholar
38Hill, K, Hurtado, AM & Walker, RS (2007) High adult mortality among Hiwi hunter–gatherers: implications for human evolution. J Hum Evol 52, 443454.Google Scholar
39Howell, N (2001) Demography of the Dobe !Kung, 2nd ed.Piscataway: Aldine Transaction.Google Scholar
40Hill, K & Hurtado, A (1995) Ache Life History: the Ecology and Demography of a Foraging People. Piscataway: Aldine Transaction.Google Scholar
41Marlowe, FM (2010) The Hadza Hunter–Gatherers of Tanzania. Los Angeles: The University of California Press.Google Scholar
42Eaton, SB & Eaton, SBI (1999) The evolutionary context of chronic degenerative diseases. In Evolution in Health and Disease, pp. 251259 [Stearns, SC, editor]. Oxford: Oxford University Press.Google Scholar
43Shephard, RJ & Roy, J (1996) The Health Consequences of Modernization: Evidence from Circumpolar Peoples. Cambridge: Cambridge University Press.Google Scholar
44Lindeberg, S & Lundh, B (1993) Apparent absence of stroke and ischaemic heart disease in a traditional Melanesian island: a clinical study in Kitava. J Intern Med 233, 269275.Google Scholar
45Lindeberg, S, Nilsson-Ehle, P, Terent, A, et al. . (1994) Cardiovascular risk factors in a Melanesian population apparently free from stroke and ischaemic heart disease: the Kitava study. J Intern Med 236, 331340.Google Scholar
46Trowell, HC & Burkitt, DP (1981) Western Diseases: Their Emergence and Prevention. Cambridge, MA: Harvard University Press.Google Scholar
47Blacklow, RS (2007) Actuarially speaking: an overview of life expectancy. What can we anticipate? Am J Clin Nutr 86, 1560S1562S.Google Scholar
48Angel, JL (1984) Health as a factor in the changes from hunting to developed farming in the eastern Mediterranean. In Paleopathology at the Origins of Agriculture, pp. 5173 [Cohen, MN and Armelagos, GJ, editors]. New York: Academic Press.Google Scholar
49Larsen, CS (1995) Biological changes in human populations with agriculture. Annu Rev Anthropol 24, 185213.Google Scholar
50Larsen, CS (2003) Animal source foods and human health during evolution. J Nutr 133, 3893S3897S.Google Scholar
51Larsen, CS (2000) Dietary reconstruction and nutritional assessement of past peoples: the bioanthropological record. In The Cambridge World History of Food, pp. 1334 [Kiple, KF and Ornelas, KC, editors]. Cambridge: Cambridge University Press.Google Scholar
52Cohen, MN (1984) Editors summation. In Paleopathology at the Origins of Ariculture, pp. 585601 [Cohen, MN and Armelagos, GJ, editors]. New York: Academic Press.Google Scholar
53McKeown, T, Brown, RG & Record, RG (1972) An interpretation of the modern rise of population in Europe. Popul Stud (Camb) 26, 345382.Google Scholar
54Blurton-Jones, NG, Marlowe, FW, Hawkes, K, et al. (2000) Paternal investment and hunter–gatherer divorce. In Adaptation and Human Behavior: An Anthropological Perspective, pp. 6190 [Cronk, L, Chagnon, N and Irons, W, editors]. New York: Aldine de Gruyter.Google Scholar
55Hawkes, K, O'Connell, JF & Blurton-Jones, NG (2001) Hunting and nuclear families: some lessons from the Hadza about men's work. Curr Anthropol 42, 681709.Google Scholar
56Hawkes, K, O'Connell, JF, Jones, NG, et al. . (1998) Grandmothering, menopause, and the evolution of human life histories. Proc Natl Acad Sci U S A 95, 13361339.Google Scholar
57O'Connell, JF, Hawkes, K & Blurton Jones, NG (1999) Grandmothering and the evolution of Homo erectus. J Hum Evol 36, 461485.Google Scholar
58Sear, R, Mace, R & McGregor, IA (2000) Maternal grandmothers improve nutritional status and survival of children in rural Gambia. Proc Biol Sci 267, 16411647.Google Scholar
59Bogin, B (2009) Childhood, adolescence, and longevity: a multilevel model of the evolution of reserve capacity in human life history. Am J Hum Biol 21, 567577.Google Scholar
60Hawkes, K (2010) Colloquium paper: how grandmother effects plus individual variation in frailty shape fertility and mortality: guidance from human–chimpanzee comparisons. Proc Natl Acad Sci U S A 107, Suppl. 2, 89778984.Google Scholar
61van Bodegom, D, Rozing, M, May, L, et al. . (2010) When grandmothers matter. Gerontology 56, 214216.Google Scholar
62Kachel, AF, Premo, LS & Hublin, JJ (2011) Grandmothering and natural selection. Proc Biol Sci 278, 384391.Google Scholar
63Strier, KB, Chaves, PB, Mendes, SL, et al. . (2011) Low paternity skew and the influence of maternal kin in an egalitarian, patrilocal primate. Proc Natl Acad Sci U S A 108, 1891518919.Google Scholar
64van Bodegom, D (2011) Selection for longevity in a polygamous society in rural Africa. In Post-Reproductive Survival in a Polygamous Society in Rural Africa, chapter 7, pp. 125140. Doctoral Thesis, Leiden University.Google Scholar
65Brunet, M, Guy, F, Pilbeam, D, et al. . (2002) A new hominid from the Upper Miocene of Chad, Central Africa. Nature 418, 145151.Google Scholar
66Senut, B, Pickford, M, Gommery, D, et al. . (2001) First hominid from the Miocene (Lukeino Formation, Kenya). C R Acad Sci IIA 332, 137144.Google Scholar
67Haile-Selassie, Y, Suwa, G & White, TD (2004) Late Miocene teeth from Middle Awash, Ethiopia, and early hominid dental evolution. Science 303, 15031505.Google Scholar
68White, TD, Asfaw, B, Beyene, Y, et al. . (2009) Ardipithecus ramidus and the paleobiology of early hominids. Science 326, 7586.Google Scholar
69Leakey, MG, Feibel, CS, McDougall, I, et al. . (1998) New specimens and confirmation of an early age for Australopithecus anamensis. Nature 393, 6266.Google Scholar
70Kimbel, WH & Delezene, LK (2009) “Lucy” redux: a review of research on Australopithecus afarensis. Am J Phys Anthropol 140, Suppl. 49, 248.Google Scholar
71Harrison, T (2011) Hominins from the Upper Laetolil and Upper Ndolanya beds, Laetoli. In Paleontology and Geology of Laetoli: Human Evolution in Context: Volume 2: Fossil Hominins and the Associated Fauna, pp. 141188 [Harrison, T, editor]. Dordrecht: Springer.Google Scholar
72Brunet, M, Beauvilain, A, Coppens, Y, et al. . (1995) The first australopithecine 2,500 kilometres west of the Rift Valley (Chad). Nature 378, 273275.Google Scholar
73Leakey, MG, Spoor, F, Brown, FH, et al. . (2001) New hominin genus from eastern Africa shows diverse middle Pliocene lineages. Nature 410, 433440.Google Scholar
74Asfaw, B, White, T, Lovejoy, O, et al. . (1999) Australopithecus garhi: a new species of early hominid from Ethiopia. Science 284, 629635.Google Scholar
75Herries, AI, Hopley, PJ, Adams, JW, et al. . (2010) Letter to the Editor: Geochronology and palaeoenvironments of Southern African hominin-bearing localities – a reply to Wrangham et al., 2009. “Shallow-water habitats as sources of fallback foods for hominins”. Am J Phys Anthropol 143, 640646.Google Scholar
76Tattersall, I (2010) Macroevolutionary patterns, exaptation, and emergence in the evolution of the human brain and cognition. In Human Brain Evolution. The Influence of Freshwater and Marine Food Resources, pp. 111 [Cunnane, SC and Stewart, KM, editors]. Hoboken, NJ: Wiley-Blackwell.Google Scholar
77Stringer, C (2003) Human evolution: out of Ethiopia. Nature 423, 692693, 695.Google Scholar
78White, TD, Asfaw, B, DeGusta, D, et al. . (2003) Pleistocene Homo sapiens from Middle Awash, Ethiopia. Nature 423, 742747.Google Scholar
79Brown, P, Sutikna, T, Morwood, MJ, et al. . (2004) A new small-bodied hominin from the Late Pleistocene of Flores, Indonesia. Nature 431, 10551061.Google Scholar
80Reich, D, Patterson, N, Kircher, M, et al. . (2011) Denisova admixture and the first modern human dispersals into Southeast Asia and Oceania. Am J Hum Genet 89, 516528.Google Scholar
81Stringer, C (2000) Palaeoanthropology. Coasting out of Africa. Nature 405, 2425, 27.Google Scholar
82Templeton, A (2002) Out of Africa again and again. Nature 416, 4551.Google Scholar
83Oppenheimer, S (2009) The great arc of dispersal of modern humans: Africa to Australia. Quat Int 202, 213.Google Scholar
84Templeton, AR (2005) Haplotype trees and modern human origins. Am J Phys Anthropol 128, Suppl. 41, 3359.Google Scholar
85Templeton, AR (2007) Genetics and recent human evolution. Evolution 61, 15071519.Google Scholar
86Templeton, AR (2010) Coherent and incoherent inference in phylogeography and human evolution. Proc Natl Acad Sci U S A 107, 63766381.Google Scholar
87Green, RE, Krause, J, Ptak, SE, et al. . (2006) Analysis of one million base pairs of Neanderthal DNA. Nature 444, 330336.Google Scholar
88Zhivotovsky, LA, Rosenberg, NA & Feldman, MW (2003) Features of evolution and expansion of modern humans, inferred from genomewide microsatellite markers. Am J Hum Genet 72, 11711186.Google Scholar
89Knight, A, Underhill, PA, Mortensen, HM, et al. . (2003) African Y chromosome and mtDNA divergence provides insight into the history of click languages. Curr Biol 13, 464473.Google Scholar
90Henn, BM, Gignoux, CR, Jobin, M, et al. . (2011) Hunter–gatherer genomic diversity suggests a southern African origin for modern humans. Proc Natl Acad Sci U S A 108, 51545162.Google Scholar
91Behar, DM, Villems, R, Soodyall, H, et al. . (2008) The dawn of human matrilineal diversity. Am J Hum Genet 82, 11301140.Google Scholar
92Ambrose, SH (1998) Late Pleistocene human population bottlenecks, volcanic winter, and differentiation of modern humans. J Hum Evol 34, 623651.Google Scholar
93Rosenberg, NA, Pritchard, JK, Weber, JL, et al. . (2002) Genetic structure of human populations. Science 298, 23812385.Google Scholar
94Washburn, SL & Lancaster, CS (1968) The evolution of hunting. In Man the Hunter, pp. 293303 [Lee, RB and DeVore, I, editors]. New York: Aldine Publishing Company.Google Scholar
95Sailer, LD, Gaulin, SC, Voster, JS, et al. . (1985) Measuring the relationship between dietary quality and body size in primates. Primates 26, 1427.Google Scholar
96Herculano-Houzel, S (2009) The human brain in numbers: a linearly scaled-up primate brain. Front Hum Neurosci 3, 31.Google Scholar
97Deaner, RO, Isler, K, Burkart, J, et al. . (2007) Overall brain size, and not encephalization quotient, best predicts cognitive ability across non-human primates. Brain Behav Evol 70, 115124.Google Scholar
98Hill, RS & Walsh, CA (2005) Molecular insights into human brain evolution. Nature 437, 6467.Google Scholar
99Broadhurst, CL, Cunnane, SC & Crawford, MA (1998) Rift Valley lake fish and shellfish provided brain-specific nutrition for early Homo. Br J Nutr 79, 321.Google Scholar
100Cunnane, SC (2010) Human brain evolution: a question of solving key nutritional and metabolic constraints on mammalian brain development. In Human Brain Evolution. The Influence of Freshwater and Marine Food Resources, pp. 3376 [Cunnane, SC and Stewart, KM, editors]. Hoboken, NJ: Wiley-Blackwell.Google Scholar
101Cunnane, SC (2005) Origins and evolution of the Western diet: implications of iodine and seafood intakes for the human brain. Am J Clin Nutr 82, 483484.Google Scholar
102Navarrete, A, van Schaik, CP & Isler, K (2011) Energetics and the evolution of human brain size. Nature 480, 9193.Google Scholar
103Potts, R (2011) Evolution: big brains explained. Nature 480, 4344.Google Scholar
104Blinkov, SM & Glezer, II (1968) The Human Brain in Figures and Tables. New York: Basic Books, Inc.Google Scholar
105White, DR, Widdowson, EM, Woodard, HQ, et al. . (1991) The composition of body tissues (II). Fetus to young adult. Br J Radiol 64, 149159.Google Scholar
106Dobbing, J & Sands, J (1973) Quantitative growth and development of human brain. Arch Dis Child 48, 757767.Google Scholar
107Roth, G & Dicke, U (2005) Evolution of the brain and intelligence. Trends Cogn Sci 9, 250257.Google Scholar
108Herculano-Houzel, S (2011) Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution. PLoS One 6, e17514.Google Scholar
109Herculano-Houzel, S (2011) Not all brains are made the same: new views on brain scaling in evolution. Brain Behav Evol 78, 2236.Google Scholar
110Azevedo, FA, Carvalho, LR, Grinberg, LT, et al. . (2009) Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol 513, 532541.Google Scholar
111Herculano-Houzel, S (2010) Coordinated scaling of cortical and cerebellar numbers of neurons. Front Neuroanat 4, 12.Google Scholar
112King, MC & Wilson, AC (1975) Evolution at two levels in humans and chimpanzees. Science 188, 107116.Google Scholar
113Gu, J & Gu, X (2003) Induced gene expression in human brain after the split from chimpanzee. Trends Genet 19, 6365.Google Scholar
114Caceres, M, Lachuer, J, Zapala, MA, et al. . (2003) Elevated gene expression levels distinguish human from non-human primate brains. Proc Natl Acad Sci U S A 100, 1303013035.Google Scholar
115Marques-Bonet, T, Caceres, M, Bertranpetit, J, et al. . (2004) Chromosomal rearrangements and the genomic distribution of gene-expression divergence in humans and chimpanzees. Trends Genet 20, 524529.Google Scholar
116Finlay, BL & Darlington, RB (1995) Linked regularities in the development and evolution of mammalian brains. Science 268, 15781584.Google Scholar
117Stimpson, CD, Tetreault, NA, Allman, JM, et al. . (2011) Biochemical specificity of von economo neurons in hominoids. Am J Hum Biol 23, 2228.Google Scholar
118Sherwood, CC, Subiaul, F & Zawidzki, TW (2008) A natural history of the human mind: tracing evolutionary changes in brain and cognition. J Anat 212, 426454.Google Scholar
119Sherwood, CC, Gordon, AD, Allen, JS, et al. . (2011) Aging of the cerebral cortex differs between humans and chimpanzees. Proc Natl Acad Sci U S A 108, 1302913034.Google Scholar
120Abzhanov, A, Kuo, WP, Hartmann, C, et al. . (2006) The calmodulin pathway and evolution of elongated beak morphology in Darwin's finches. Nature 442, 563567.Google Scholar
121Patel, NH (2006) Evolutionary biology: how to build a longer beak. Nature 442, 515516.Google Scholar
122Schneider, RA (2007) How to tweak a beak: molecular techniques for studying the evolution of size and shape in Darwin's finches and other birds. Bioessays 29, 16.Google Scholar
123Kaindl, AM, Passemard, S, Kumar, P, et al. . (2010) Many roads lead to primary autosomal recessive microcephaly. Prog Neurobiol 90, 363383.Google Scholar
124Williams, CA, Dagli, A & Battaglia, A (2008) Genetic disorders associated with macrocephaly. Am J Med Genet A 146A, 20232037.Google Scholar
125Evans, PD, Anderson, JR, Vallender, EJ, et al. . (2004) Adaptive evolution of ASPM, a major determinant of cerebral cortical size in humans. Hum Mol Genet 13, 489494.Google Scholar
126Evans, PD, Anderson, JR, Vallender, EJ, et al. . (2004) Reconstructing the evolutionary history of microcephalin, a gene controlling human brain size. Hum Mol Genet 13, 11391145.Google Scholar
127Evans, PD, Gilbert, SL, Mekel-Bobrov, N, et al. . (2005) Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science 309, 17171720.Google Scholar
128Evans, PD, Vallender, EJ & Lahn, BT (2006) Molecular evolution of the brain size regulator genes CDK5RAP2 and CENP. J Gene 375, 7579.Google Scholar
129Speth, JD (1989) Early hominid hunting and scavenging – the role of meat as an energy-source. J Hum Evol 18, 329343.Google Scholar
130Crawford, MA, Bloom, M, Broadhurst, CL, et al. . (1999) Evidence for the unique function of docosahexaenoic acid during the evolution of the modern hominid brain. Lipids 34, Suppl., S39S47.Google Scholar
131Gibbons, A (2002) American Association of Physical Anthropologists meeting. Humans' head start: new views of brain evolution. Science 296, 835837.Google Scholar
132Crawford, MA (2002) Cerebral evolution. Nutr Health 16, 2934.Google Scholar
133Cordain, L, Eaton, SB, Sebastian, A, et al. . (2005) Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 81, 341354.Google Scholar
134Carlson, BA & Kingston, JD (2007) Docosahexaenoic acid, the aquatic diet, and hominin encephalization: difficulties in establishing evolutionary links. Am J Hum Biol 19, 132141.Google Scholar
135Joordens, JC, Kuipers, RS & Muskiet, FA (2007) Preformed dietary DHA: the answer to a scientific question may in practice become translated to its opposite. Am J Hum Biol 19, 582584.Google Scholar
136Joordens, CA, Kuipers, RS & Muskiet, FAJ (2005) On breast milk, diet, and large human brains. Curr Anthropol 46, 122124.Google Scholar
137Langdon, JH (2006) Has an aquatic diet been necessary for hominin brain evolution and functional development? Br J Nutr 96, 717.Google Scholar
138Dart, RA (1925) Australopithecus africanus: the man-ape of South Africa. Nature 115, 195199.Google Scholar
139Tobias, PV (1998) Water and human evolution. Out There 35, 3844.Google Scholar
140Tobias, PV (2010) Foreword: evolution, encephalization, environment. In Human Brain Evolution. The Influence of Freshwater and Marine Food Resources, pp. viixii [Cunnane, SC and Stewart, KM, editors]. Hoboken, NJ: Wiley-Blackwell.Google Scholar
141White, TD, Ambrose, SH, Suwa, G, et al. . (2009) Macrovertebrate paleontology and the Pliocene habitat of Ardipithecus ramidus. Science 326, 8793.Google Scholar
142Cerling, TE, Levin, NE, Quade, J, et al. . (2010) Comment on the paleoenvironment of Ardipithecus ramidus. Science 328, 1105.Google Scholar
143Feibel, CS (2011) Anthropology: shades of the savannah. Nature 476, 3940.Google Scholar
144Cerling, TE, Wynn, JG, Andanje, SA, et al. . (2011) Woody cover and hominin environments in the past 6 million years. Nature 476, 5156.Google Scholar
145Woodburn, J (1968) An introduction to Hadza ecology. In Man the Hunter, [Lee, RB and DeVore, I, editors]. New York: Aldine Publishing Company.Google Scholar
146Tanner, NM & Zihlmann, AL (1976) Women in evolution, part 1: innovation and selection in human origins. Signs 1, 585608.Google Scholar
147Stanford, CB (1999) The hunting people. In The Hunting Apes: Meat Eating and the Origins of Human Behaviour, chapter 5, pp. 136162. Princeton: Princeton University Press.Google Scholar
148Cordain, L, Miller, JB, Eaton, SB, et al. . (2000) Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter–gatherer diets. Am J Clin Nutr 71, 682692.Google Scholar
149Stanford, CB (1999) Man the hunter and other stories. In The Hunting Apes: Meat Eating and the Origins of Human Behaviour, chapter 2, pp. 1551. Princeton: Princeton University Press.Google Scholar
150Ungar, PS & Sponheimer, M (2011) The diets of early hominins. Science 334, 190193.Google Scholar
151Bernor, RL (2007) New apes fill the gap. Proc Natl Acad Sci U S A 104, 1966119662.Google Scholar
152Lebatard, AE, Bourles, DL, Duringer, P, et al. . (2008) Cosmogenic nuclide dating of Sahelanthropus tchadensis and Australopithecus bahrelghazali: Mio-Pliocene hominids from Chad. Proc Natl Acad Sci U S A 105, 32263231.Google Scholar
153Bosworth, W & Morley, CK (1994) Structural and stratigraphic evolution of the Anza rift, Kenya. Tectonophysics 236, 93115.Google Scholar
154Joordens, JC (2011) The Power of Place: Climate Changes as Driver of Hominin Evolution and Dispersal over the Past Five Million Years. Amsterdam: Vrije Universiteit.Google Scholar
155Vignaud, P, Duringer, P, Mackaye, HT, et al. . (2002) Geology and palaeontology of the Upper Miocene Toros-Menalla hominid locality, Chad. Nature 418, 152155.Google Scholar
156Stewart, KM (2010) The case for exploitation of wetlands environments and foods by pre-sapiens hominins. In Human Brain Evolution. The Influence of Freshwater and Marine Food Resources, pp. 137171 [Cunnane, SC and Stewart, KM, editors]. Hoboken, NJ: Wiley-Blackwell.Google Scholar
157Pickford, M & Senut, B (2001) The geological and faunal context of Late Miocene hominid remains from Lukeino, Kenya. C R Acad Sci IIA 332, 145152.Google Scholar
158WoldeGabriel, G, Haile-Selassie, Y, Renne, PR, et al. . (2001) Geology and palaeontology of the Late Miocene Middle Awash valley, Afar rift, Ethiopia. Nature 412, 175178.Google Scholar
159WoldeGabriel, G, Ambrose, SH, Barboni, D, et al. . (2009) The geological, isotopic, botanical, invertebrate, and lower vertebrate surroundings of Ardipithecus ramidus. Science 326, 65e165e5.Google Scholar
160Feibel, CS, Harris, JM & Brown, FH (1991) Paleoenvironmental context for the late Neogene of the Turkana basin. In Koobi Fora Research Project, pp. 321346 [Harris, JM, editor]. Oxford: Clarendon Press.Google Scholar
161Reed, KE (1997) Early hominid evolution and ecological change through the African Plio-Pleistocene. J Hum Evol 32, 289322.Google Scholar
162Ward, C, Leakey, M & Walker, A (1999) The new hominid species Australopithecus anamensis. Evol Anthropol 7, 197205.Google Scholar
163Schoeninger, MJ, Reeser, H & Hallin, K (2003) Paleoenvironment of Australopithecus anamensis at Allia Bay, East Turkana, Kenya: evidence from mammalian herbivore enamel stable isotopes. J Anthropol Archaeol 22, 200207.Google Scholar
164Reed, KE (2008) Paleoecological patterns at the Hadar hominin site, Afar Regional State, Ethiopia. J Hum Evol 54, 743768.Google Scholar
165Su, DF & Harrison, T (2008) Ecological implications of the relative rarity of fossil hominins at Laetoli. J Hum Evol 55, 672681.Google Scholar
166Veldkamp, A, Buis, E, Wijbrands, JR, et al. . (2007) Late Cenozoic fluvial dynamics of the River Tana, Kenya, an uplift dominated record. Quat Sci Rev 26, 28972912.Google Scholar
167Sepulchre, P, Ramstein, G, Fluteau, F, et al. . (2006) Tectonic uplift and Eastern Africa aridification. Science 313, 14191423.Google Scholar
168Trauth, MH, Maslin, MA, Deino, AL, et al. . (2007) High- and low-latitude forcing of Plio-Pleistocene East African climate and human evolution. J Hum Evol 53, 475486.Google Scholar
169Bartoli, G, Sarnthein, M, Weinelt, M, et al. . (2005) Final closure of the Panama and the onset of northern hemisphere glaciation. Earth Planetary Sci Lett 237, 3344.Google Scholar
170Potts, R (1998) Environmental hypotheses of hominin evolution. Yearb Phys Anthropol 41, 93136.Google Scholar
171Pobiner, BL, Rogers, MJ, Monahan, CM, et al. . (2008) New evidence for hominin carcass processing strategies at 1.5 Ma, Koobi Fora, Kenya. J Hum Evol 55, 103130.Google Scholar
172Ashley, GM, Tactikos, JC & Owen, RB (2009) Hominin use of springs and wetlands: paleoclimate and archaeological records from Olduvai Gorge (~ 1.79–1.74 Ma). Palaeogeogr Palaeoclimatol Palaeoecol 272, 116.Google Scholar
173Drake, NA, Blench, RM, Armitage, SJ, et al. . (2011) Ancient watercourses and biogeography of the Sahara explain the peopling of the desert. Proc Natl Acad Sci U S A 108, 458462.Google Scholar
174Sikes, NE (1994) Early hominid habitat preferences in East-Africa – paleosol carbon isotopic evidence. J Hum Evol 27, 2545.Google Scholar
175Joordens, JC, Wesselingh, FP, de Vos, J, et al. . (2009) Relevance of aquatic environments for hominins: a case study from Trinil (Java, Indonesia). J Hum Evol 57, 656671.Google Scholar
176Popovich, DG, Jenkins, DJ, Kendall, CW, et al. . (1997) The western lowland gorilla diet has implications for the health of humans and other hominoids. J Nutr 127, 20002005.Google Scholar
177Marshall, AJ & Wrangham, RW (2007) Evolutionary consequences of fallback foods. Int J Primatol 28, 12181235.Google Scholar
178Nishida, T (1980) Local differences in responses to water among wild chimpanzees. Folia Primatol 33, 189209.Google Scholar
179Sakamaki, T (1998) First record of algae-feeding by a female chimpanzee at Mahale. Pan Afr News 5, 13.Google Scholar
180Kempf, E (2009) Patterns of water use in primates. Folia Primatol (Basel) 80, 275294.Google Scholar
181Wrangham, R, Cheney, D, Seyfarth, R, et al. . (2009) Shallow-water habitats as sources of fallback foods for hominins. Am J Phys Anthropol 140, 630642.Google Scholar
182Vogel, ER, van Woerden, JT, Lucas, PW, et al. . (2008) Functional ecology and evolution of hominoid molar enamel thickness: Pan troglodytes schweinfurthii and Pongo pygmaeus wurmbii. J Hum Evol 55, 6074.Google Scholar
183Suwa, G, Kono, RT, Simpson, SW, et al. . (2009) Paleobiological implications of the Ardipithecus ramidus dentition. Science 326, 9499.Google Scholar
184Teaford, MF & Ungar, PS (2000) Diet and the evolution of the earliest human ancestors. Proc Natl Acad Sci U S A 97, 1350613511.Google Scholar
185Walker, A, Hoeck, HN & Perez, L (1978) Mecrowear of mammalian teeth as an indicator of diet. Science 201, 908910.Google Scholar
186Ungar, PS, Grine, FE & Teaford, MF (2008) Dental microwear and diet of the Plio-Pleistocene hominin Paranthropus boisei. Plos One 3, e2044.Google Scholar
187Ungar, PS, Scott, RS, Grine, FE, et al. . (2010) Molar microwear textures and the diets of Australopithecus anamensis and Australopithecus afarensis. Philos Trans R Soc B Biol Sci 365, 33453354.Google Scholar
188Grine, FE, Ungar, PS, Teaford, MF, et al. . (2006) Molar microwear in Praeanthropus afarensis: evidence for dietary stasis through time and under diverse paleoecological conditions. J Hum Evol 51, 297319.Google Scholar
189Scott, RS, Ungar, PS, Bergstrom, TS, et al. . (2005) Dental microwear texture analysis shows within-species diet variability in fossil hominins. Nature 436, 693695.Google Scholar
190Cerling, TE, Mbua, E, Kirera, FM, et al. . (2011) Diet of Paranthropus boisei in the early Pleistocene of East Africa. Proc Natl Acad Sci U S A 108, 93379341.Google Scholar
191Ungar, P (2004) Dental topography and diets of Australopithecus afarensis and early Homo. J Hum Evol 46, 605622.Google Scholar
192Ulijaszek, SJ (2002) Human eating behaviour in an evolutionary ecological context. Proc Nutr Soc 61, 517526.Google Scholar
193Goldstone, AP, de Hernandez, CG, Beaver, JD, et al. . (2009) Fasting biases brain reward systems towards high-calorie foods. Eur J Neurosci 30, 16251635.Google Scholar
194Ungar, PS, Grine, FE, Teaford, MF, et al. . (2006) Dental microwear and diets of African early Homo. J Hum Evol 50, 7895.Google Scholar
195Ungar, PS, Grine, FE & Teaford, MF (2006) Diet in early Homo: a review of the evidence and a new model of adaptive versatility. Annu Rev Anthropol 35, 209228.Google Scholar
196Perez-Perez, A, De Castro, JMB & Arsuaga, JL (1999) Nonocclusal dental microwear analysis of 300 000-year-old Homo heilderbergensis teeth from Sima de los Huesos (Sierra de Atapuerca, Spain). Am J Phys Anthropol 108, 433457.Google Scholar
197Lalueza, C, PerezPerez, A & Turbon, D (1996) Dietary inferences through buccal microwear analysis of middle and upper pleistocene human fossils. Am J Phys Anthropol 100, 367387.Google Scholar
198Mahoney, P (2007) Human dental microwear from Ohalo II (22 500–23 500 cal BP), Southern Levant. Am J Phys Anthropol 132, 489500.Google Scholar
199Mahoney, P (2006) Dental microwear from Natufian hunter–gatherers and early neolithic farmers: comparisons within and between samples. Am J Phys Anthropol 130, 308319.Google Scholar
200Milton, K (1999) Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us? Nutrition 15, 488498.Google Scholar
201Milton, K (2003) The critical role played by animal source foods in human (Homo) evolution. J Nutr 133, 3886S3892S.Google Scholar
202Gittleman, JL & Thompson, SD (1988) Energy allocation in mammalian reproduction. Am Zool 28, 863875.Google Scholar
203Oftedal, TO (1984) Milk composition, milk yield and energy output a peak lactation: a comparative review. Symp Zool Soc Lond 51, 3385.Google Scholar
204Aiello, LC & Key, C (2002) Energetic consequences of being a Homo erectus female. Am J Hum Biol 14, 551565.Google Scholar
205Aiello, LC & Wells, JCK (2002) Energetics and the evolution of the genus Homo. Annu Rev Anthropol 31, 323338.Google Scholar
206Cunnane, SC & Crawford, MA (2003) Survival of the fattest: fat babies were the key to evolution of the large human brain. Comp Biochem Physiol A Mol Integr Physiol 136, 1726.Google Scholar
207Leonard, WR, Robertson, ML, Snodgrass, JJ, et al. . (2003) Metabolic correlates of hominid brain evolution. Comp Biochem Physiol A Mol Integr Physiol 136, 515.Google Scholar
208Aiello, LC & Wheeler, P (1995) The expensive-tissue hypothesis – the brain and the digestive system in human and primate evolution. Curr Anthropol 36, 199221.Google Scholar
209Aiello, LC (2007) Notes on the implications of the expensive tissue hypothesis for human biological and social evolution. In Guts and Brains. An Integrative Approach to the Hominin Record, pp. 1728 [Roebroeks, W, editor]. Leiden: Leiden University Press.Google Scholar
210Kaufman, JA, Hladik, CM & Pasquet, P (2003) On the expensive-tissue hypothesis: independent support from highly encephalized fish. Curr Anthropol 44, 705707.Google Scholar
211Galdikas, BM & Wood, JW (1990) Birth spacing patterns in humans and apes. Am J Phys Anthropol 83, 185191.Google Scholar
212Isler, K & van Schaik, CP (2009) The expensive brain: a framework for explaining evolutionary changes in brain size. J Hum Evol 57, 392400.Google Scholar
213Isler, K (2011) Energetic trade-offs between brain size and offspring production: marsupials confirm a general mammalian pattern. Bioessays 33, 173179.Google Scholar
214Pontzer, H, Raichlen, DA & Sockol, MD (2009) The metabolic cost of walking in humans, chimpanzees, and early hominins. J Hum Evol 56, 4354.Google Scholar
215Wrangham, RW, Jones, JH, Laden, G, et al. . (1999) The raw and the stolen. Cooking and the ecology of human origins. Curr Anthropol 40, 567594.Google Scholar
216Robinson, BW & Wilson, DS (1998) Optimal foraging, specialization, and a solution to Liem's paradox. Am Nat 151, 223235.Google Scholar
217Harris, WS (2008) You are what you eat applies to fish, too. J Am Diet Assoc 108, 11311133.Google Scholar
218Sponheimer, M & Dufour, DL (2009) Increased dietary breadth in early hominin evolution: revisiting arguments and evidence with a focus on biogeochemical contributions. In The Evolution of Hominin Diets: Integrating Approaches to the Study of Palaeolithic Subsistence, chapter 18, pp. 229240 [Hublin, J-J and Richards, MP, editors]. Dordrecht: Springer.Google Scholar
219Sillen, A & Kavanagh, M (1982) Strontium and paleodietary research: a review. Am J Phys Anthropol 25, 6790.Google Scholar
220Sillen, A (1992) Strontium calcium ratios (Sr/Ca) of Australopithecus robustus and associated fauna from Swartkrans. J Hum Evol 23, 495516.Google Scholar
221Sillen, A, Hall, G & Armstrong, R (1995) Strontium calcium ratios (Sr/Ca) and strontium isotopic-ratios (87Sr/86Sr) of Australopithecus robustus and Homo sp. from Swartkrans. J Hum Evol 28, 277285.Google Scholar
222Conklin-Brittain, NL, Wrangham, RW & Hunt, KD (1998) Dietary response of chimpanzees and cercopithecines to seasonal variation in fruit abundance. II. Macronutrients. Int J Primatol 19, 971998.Google Scholar
223Lee-Thorp, J & Sponheimer, M (2003) Three case studies used to reassess the reliability of fossil bone and enamel isotope signals for paleodietary studies. J Anthropol Archaeol 22, 208216.Google Scholar
224Sponheimer, M, de Ruiter, D, Lee-Thorp, J, et al. . (2005) Sr/Ca and early hommin diets revisited: new data from modern and fossil tooth enamel. J Hum Evol 48, 147156.Google Scholar
225Lee-Thorp, J & Sponheimer, M (2006) Contributions of biogeochemistry to understanding hominin dietary ecology. Yearb Phys Anthropol 49, 131148.Google Scholar
226Balter, V & Simon, L (2006) Diet and behavior of the Saint-Cesaire Neanderthal inferred from biogeochemical data inversion. J Hum Evol 51, 329338.Google Scholar
227Ophel, IL & Fraser, CD (1970) Calcium and strontium discrimination by aquatic plants. Ecology 51, 324327.Google Scholar
228Ambrose, SH & Deniro, MJ (1986) The isotopic ecology of East-African mammals. Oecologia 69, 395406.Google Scholar
229Lee-Thorp, JA, Sponheimer, M, Passey, BH, et al. . (2010) Stable isotopes in fossil hominin tooth enamel suggest a fundamental dietary shift in the Pliocene. Phil Trans R Soc Lond B Biol Sci 365, 33893396.Google Scholar
230Sponheimer, M & Lee-Thorp, JA (2006) Enamel diagenesis at South African Australopith sites: implications for paleoecological reconstruction with trace elements. Geochim Cosmochim Acta 70, 16441654.Google Scholar
231Sponheimer, M, Lee-Thorp, J, de Ruiter, D, et al. . (2005) Hominins, sedges, and termites: new carbon isotope data from the Sterkfontein valley and Kruger National Park. J Hum Evol 48, 301312.Google Scholar
232Vogel, JC (1978) Isotopic assessment of dietary habits of ungulates. S Afr J Sci 74, 298301.Google Scholar
233Cerling, TE, Harris, JM, MacFadden, BJ, et al. . (1997) Global vegetation change through the Miocene/Pliocene boundary. Nature 389, 153158.Google Scholar
234Peters, CR & Vogel, JC (2005) Africa's wild C-4 plant foods and possible early hominid diets. J Hum Evol 48, 219236.Google Scholar
235Segalen, L, Lee-Thorp, JA & Cerling, T (2007) Timing of C-4 grass expansion across sub-Saharan Africa. J Hum Evol 53, 549559.Google Scholar
236Sponheimer, M, Reed, KE & Lee-Thorp, JA (1999) Combining isotopic and ecomorphological data to refine bovid paleodietary reconstruction: a case study from the Makapansgat Limeworks hominin locality. J Hum Evol 36, 705718.Google Scholar
237Lee-Thorp, J, Thackeray, JF & van der Merwe, N (2000) The hunters and the hunted revisited. J Hum Evol 39, 565576.Google Scholar
238Sponheimer, M, Lee-Thorp, JA & de Ruiter, DJ (2007) Icarus, Isotopes, and Australopith Diets. In Evolution of the Human Diet: The Known, the Unknown, and the Unknowable, pp. 132149 [Ungar, P, editor]. Oxford: Oxford University Press.Google Scholar
239Kelly, JF (2000) Stable isotopes of carbon and nitrogen in the study of avian and mammalian trophic ecology. Can J Zool 78, 127.Google Scholar
240Schoeninger, MJ & Deniro, MJ (1984) Nitrogen and carbon isotopic composition of bone-collagen from marine and terrestrial animals. Geochim Cosmochim Acta 48, 625639.Google Scholar
241Mbabazi, D, Makanga, B, Orach-Meza, F, et al. . (2010) Intra-lake stable isotope ratio variation in selected fish species and their possible carbon sources in Lake Kyoga (Uganda): implications for aquatic food web studies. Afr J Ecol 48, 667675.Google Scholar
242Schoeninger, MJ, Deniro, MJ & Tauber, H (1983) Stable nitrogen isotope ratios of bone-collagen reflect marine and terrestrial components of prehistoric human diet. Science 220, 13811383.Google Scholar
243Sponheimer, M & Lee-Thorp, JA (2003) Differential resource utilization by extant great apes and australopithecines: towards solving the C-4 conundrum. Comp Biochem Physiol A Mol Integr Physiol 136, 2734.Google Scholar
244Lee-Thorp, JA, Sponheimer, M & Luyt, J (2007) Tracking changing environments using stable carbon isotopes in fossil tooth enamel: an example from the South African hominin sites. J Hum Evol 53, 595601.Google Scholar
245van der Merwe, NJ, Masao, FT & Bamford, MK (2008) Isotopic evidence for contrasting diets of early hominins Homo habilis and Australopithecus boisei of Tanzania. S Afr J Sci 104, 153155.Google Scholar
246Schoeninger, MJ, Moore, J & Sept, JM (1999) Subsistence strategies of two ‘savanna’ chimpanzee populations: the stable isotope evidence. Am J Primatol 49, 297314.Google Scholar
247Sponheimer, M, Loudon, JE, Codron, D, et al. . (2006) Do “savanna” chimpanzees consume C-4 resources? J Hum Evol 51, 128133.Google Scholar
248Sponheimer, M & Lee-Thorp, JA (1999) Oxygen isotopes in enamel carbonate and their ecological significance. J Archaeol Sci 26, 723728.Google Scholar
249Sponheimer, M & Lee-Thorp, JA (2001) The oxygen isotope composition of mammalian enamel carbonate from Morea Estate, South Africa. Oecologia 126, 153157.Google Scholar
250Hu, Y, Shang, H, Tong, H, et al. . (2009) Stable isotope dietary analysis of the Tianyuan 1 early modern human. Proc Natl Acad Sci U S A 106, 1097110974.Google Scholar
251Richards, MP, Pettitt, PB, Trinkaus, E, et al. . (2000) Neanderthal diet at Vindija and Neanderthal predation: the evidence from stable isotopes. Proc Natl Acad Sci U S A 97, 76637666.Google Scholar
252Richards, MP, Pettitt, PB, Stiner, MC, et al. . (2001) Stable isotope evidence for increasing dietary breadth in the European mid-Upper Paleolithic. Proc Natl Acad Sci U S A 98, 65286532.Google Scholar
253Richards, MP (2002) A brief review of the archaeological evidence for Palaeolithic and Neolithic subsistence. Eur J Clin Nutr 56, 12701278.Google Scholar
254Richards, MP, Schulting, RJ & Hedges, RE (2003) Archaeology: sharp shift in diet at onset of Neolithic. Nature 425, 366.Google Scholar
255Richards, MP, Jacobi, R, Cook, J, et al. . (2005) Isotope evidence for the intensive use of marine foods by Late Upper Palaeolithic humans. J Hum Evol 49, 390394.Google Scholar
256Richards, MP & Trinkaus, E (2009) Isotopic evidence for the diets of European Neanderthals and early modern humans. Proc Natl Acad Sci U S A 106, 1603416039.Google Scholar
257van der Merwe, NJ, Thackeray, JF, Lee-Thorp, JA, et al. . (2003) The carbon isotope ecology and diet of Australopithecus africanus at Sterkfontein, South Africa. J Hum Evol 44, 581597.Google Scholar
258Semaw, S, Rogers, MJ, Quade, J, et al. . (2003) 2.6-Million-year-old stone tools and associated bones from OGS-6 and OGS-7, Gona, Afar, Ethiopia. J Hum Evol 45, 169177.Google Scholar
259McPherron, SP, Alemseged, Z, Marean, CW, et al. . (2010) Evidence for stone-tool-assisted consumption of animal tissues before 3.39 million years ago at Dikika, Ethiopia. Nature 466, 857860.Google Scholar
260Willis, LA, Eren, MI & Rick, TC (2008) Does butchering fish leave cut marks? J Archaeol Sci 35, 14381444.Google Scholar
261Braun, DR, Harris, JW, Levin, NE, et al. . (2010) Early hominin diet included diverse terrestrial and aquatic animals 1·95 Ma in East Turkana, Kenya. Proc Natl Acad Sci U S A 107, 1000210007.Google Scholar
262de Heinzelin, J, Clark, JD, White, T, et al. . (1999) Environment and behavior of 2.5-million-year-old Bouri hominids. Science 284, 625629.Google Scholar
263Leonard, WR, Robertson, ML & Snodgrass, JJ (2007) Energetics and the evolution of brain size in early Homo. In Guts and Brains. An Integrative Approach to the Hominin Record, pp. 2946 [Roebroeks, W, editor]. Leiden: Leiden University Press.Google Scholar
264Simpson, SW, Quade, J, Levin, NE, et al. . (2008) A female Homo erectus pelvis from Gona, Ethiopia. Science 322, 10891092.Google Scholar
265Bramble, DM & Lieberman, DE (2004) Endurance running and the evolution of Homo. Nature 432, 345352.Google Scholar
266Broadhurst, CL, Wang, Y, Crawford, MA, et al. . (2002) Brain-specific lipids from marine, lacustrine, or terrestrial food resources: potential impact on early African Homo sapiens. Comp Biochem Physiol B Biochem Mol Biol 131, 653673.Google Scholar
267Erlandson, JM (2001) The archaeology of aquatic adaptations: paradigms for a new millennium. J Archaeol Res 9, 287350.Google Scholar
268Marean, CW (2010) Coastal South Africa and the co-evolution of the modern human lineage and the coastal adaptation. In Trekking the Shore: Changing Coastlines and the Antiquity of Coastal Settlement, pp. 421440 [Bicho, N, Haws, JA and Davis, LG, editors]. New York: Springer.Google Scholar
269Stewart, KM (1994) Early hominid utilization of fish resources and implications for seasonality and behavior. J Hum Evol 27, 229245.Google Scholar
270Wang, S, Lewis, CM, Jakobsson, M, et al. . (2007) Genetic variation and population structure in native Americans. PLoS Genet 3, e185.Google Scholar
271Pope, GG (1989) Bamboo and human-evolution. In Natural History, pp. 4857, October 1989.Google Scholar
272Fagan, BM (1990) The Journey from Eden: The Peopling of Our World. London: Thames and Hudson.Google Scholar
273Bar-Yosef, O (1994) The lower Paleolithic of the Near East. J World Prehist 8, 211265.Google Scholar
274Cleyet-Merle, J & Madelaine, S (1995) Inland evidence of human sea coast exploitation in Palaeolithic France. In Man and Sea in the Mesolithic, pp. 303308 [Fischer, A, editor]. Oxford: Oxbow Books.Google Scholar
275Klein, RG, Avery, G, Cruz-Uribe, K, et al. . (1999) Duinefontein 2, an Acheulean Site in the Western Cape Province of South Africa. J Hum Evol 37, 153190.Google Scholar
276de Lumley, H (1969) A Paleolithic camp at Nice. In Scientific American, vol. 220, pp. 4250.Google Scholar
277Villa, P (1983) Terra Amata and the Middle Pleistocene Archaeological Record of Southern France (University of California Publications in Anthropology). Berkeley: University of California Press.Google Scholar
278Marean, CW, Bar-Matthews, M, Bernatchez, J, et al. . (2007) Early human use of marine resources and pigment in South Africa during the Middle Pleistocene. Nature 449, 905908.Google Scholar
279Walter, RC, Buffler, RT, Bruggemann, JH, et al. . (2000) Early human occupation of the Red Sea coast of Eritrea during the last interglacial. Nature 405, 6569.Google Scholar
280Stiner, MC (1993) Honor Among Thieves: A Zooarchaeological Study of Neandertal Ecology. Princeton, NJ: Princeton University Press.Google Scholar
281von den Driesch, A (2004) The Middle Stone Age fish fauna from the Klassies River main site, South Africa. Anthropozoologica 39, 3359.Google Scholar
282Erlandson, JM (2010) Food for thought: the role of coastlines and aquatic resources in human evolution. In Human Brain Evolution: The Influence of Freshwater and Marine Food Resources, pp. 125136 [Cunnane, SC and Stewart, KM, editors]. Hoboken, New Jersey: Wiley-Blackwell.Google Scholar
283Klein, RG, Cruz-Uribe, K, Halkett, D, et al. . (1999) Paleoenvironmental and human behavioral implications of the Boegoeberg 1 late pleistocene hyena den, Northern Cape Province, South Africa. Quatern Res 52, 393403.Google Scholar
284Marean, CW, Goldberg, P, Avery, G, et al. . (2000) Middle Stone Age stratigraphy and excavations at Die Kelders Cave 1 (Western Cape Province, South Africa): the 1992, 1993, and 1995 field seasons. J Hum Evol 38, 742.Google Scholar
285Henshilwood, C & Sealy, J (1997) Bone artifacts from the Middle Stone Age at Blombos Cave, southern cape, South Africa. Curr Anthropol 38, 890895.Google Scholar
286Klein, RG, Avery, G, Cruz-Uribe, K, et al. . (2004) The Ysterfontein 1 Middle Stone Age site, South Africa, and early human exploitation of coastal resources. Proc Natl Acad Sci U S A 101, 57085715.Google Scholar
287Avery, G, Halkett, D, Orton, J, et al. . (2008) The Ysterfontein 1 Middle Stone Age rock shelter and the evolution of coastal foraging. S Afr Archaeol Soc Goodwin Ser 10, 6689.Google Scholar
288Henshilwood, C, d'Errico, F, Vanhaeren, M, et al. . (2004) Middle Stone Age shell beads from South Africa. Science 304, 404.Google Scholar
289Harris, JW, Williamson, PG, Morris, PJ, et al. (1990) Archaeology of the Lusso beds. In Evolution of Environments and Hominidae in the African Western Rift Valley, pp. 237272 [Boaz, NT, editor]. Martinsville: Virginia Museum of Natural History.Google Scholar
290Meylan, P (1990) Fossil turtles from the upper Semliki, Zaire. In Evolution of Environments and Hominidae in the African Western Rift Valley, pp. 163170 [Boaz, NT, editor]. Martinsville: Virginia Museum of Natural History.Google Scholar
291Henshilwood, CS, Sealy, JC, Yates, R, et al. . (2001) Blombos Cave, Southern Cape, South Africa: preliminary report on the 1992–1999 excavations of the Middle Stone Age levels. J Archaeol Sci 28, 421448.Google Scholar
292Wickler, S & Spriggs, M (1988) Pleistocene human occupation of the Solomon-Islands, Melanesia. Antiquity 62, 703706.Google Scholar
293Allen, J, Gosden, C, Jones, R, et al. . (1988) Pleistocene dates for the human occupation of New Ireland, northern Melanesia. Nature 331, 707709.Google Scholar
294O'Connor, S, Ono, R & Clarkson, C (2011) Pelagic fishing at 42 000 years before the present and the maritime skills of modern humans. Science 334, 11171121.Google Scholar
295Morwood, MJ, O'Sullivan, PB, Aziz, F, et al. . (1998) Fission-track ages of stone tools and fossils on the east Indonesian island of Flores. Nature 392, 173176.Google Scholar
296Morwood, MJ, Aziz, F, O'Sullivan, P, et al. . (1999) Archaeological and palaeontological research in central Flores, east Indonesia: results of fieldwork 1997–98. Antiquity 73, 273286.Google Scholar
297Morwood, MJ, Brown, P, Jatmiko, , et al. . (2005) Further evidence for small-bodied hominins from the Late Pleistocene of Flores, Indonesia. Nature 437, 10121017.Google Scholar
298Westaway, KE, Morwood, MJ, Roberts, RG, et al. . (2007) Establishing the time of initial human occupation of Liang Bua, western Flores, Indonesia. Quat Geochronol 2, 337343.Google Scholar
299Brumm, A, Jensen, GM, van den Bergh, GD, et al. . (2010) Hominins on Flores, Indonesia, by one million years ago. Nature 464, 748752.Google Scholar
300Sept, JM (1986) Plant foods and early hominids at Site Fxjj 50, Koobi-Fora, Kenya. J Hum Evol 15, 751770.Google Scholar
301Gibbons, A (2007) Paleoanthropology. Food for thought. Science 316, 15581560.Google Scholar
302Wobber, V, Hare, B & Wrangham, R (2008) Great apes prefer cooked food. J Hum Evol 55, 340348.Google Scholar
303Goren-Inbar, N, Alperson, N, Kislev, ME, et al. . (2004) Evidence of hominin control of fire at Gesher Benot Ya'aqov, Israel. Science 304, 725727.Google Scholar
304Roebroeks, W & Villa, P (2011) On the earliest evidence for habitual use of fire in Europe. Proc Natl Acad Sci U S A 108, 52095214.Google Scholar
305Henry, AG, Brooks, AS & Piperno, DR (2011) Microfossils in calculus demonstrate consumption of plants and cooked foods in Neanderthal diets (Shanidar III, Iraq; Spy I and II, Belgium). Proc Natl Acad Sci U S A 108, 486491.Google Scholar
306Crawford, MA, Bloom, M, Cunnane, S, et al. . (2001) Docosahexaenoic acid and cerebral evolution. World Rev Nutr Diet 88, 617.Google Scholar
307Parkington, J (2003) Middens and moderns: shellfishing and the Middle Stone Age of the Western Cape, South Africa. S Afr J Sci 99, 243247.Google Scholar
308Parkington, J, Roggenpoel, C, Halkett, D, et al. (2009) Initial observations on the Middle Stone Age coastal settlement in the Western Cape, South Africa. In Settlement Dynamics of the Middle Paleolithic and Middle Stone Age, pp. 522 [Conard, NJ, editor]. Tubingen: Tubingen Publications in Prehistory.Google Scholar
309Cordain, L, Eaton, SB, Sebastian, A, et al. . (2005) Origins and evolution of the Western diet: implications of iodine and seafood intakes for the human brain – reply. Am J Clin Nutr 82, 483484.Google Scholar
310Nadel, D, Weiss, E, Simchoni, O, et al. . (2004) Stone Age hut in Israel yields world's oldest evidence of bedding. Proc Natl Acad Sci U S A 101, 68216826.Google Scholar
311Weiss, E, Wetterstrom, W, Nadel, D, et al. . (2004) The broad spectrum revisited: evidence from plant remains. Proc Natl Acad Sci U S A 101, 95519555.Google Scholar
312Kislev, ME, Weiss, E, Hartmann, A & Hartmann, A (2004) Impetus for sowing and the beginning of agriculture: ground collecting of wild cereals. Proc Natl Acad Sci U S A 101, 26922695.Google Scholar
313Kimbel, WH, Walter, RC, Johanson, DC, et al. . (1996) Late Pliocene Homo and Oldowan tools from the Hadar formation (Kada Hadar Member), Ethiopia. J Hum Evol 31, 549561.Google Scholar
314Lee, RB (1968) What hunters do for a living, or, how to make out on scarce resources. In Man the Hunter, pp. 3048 [Lee, RB and DeVore, I, editors]. New York: Aldine Publishing Company.Google Scholar
315Murdock, GV (1967) Ethnographic Atlas. Pittsburgh: University of Pittsburgh Press.Google Scholar
316Stewart, JH (1968) Causal factors and processes in the evolution of pre-farming societies. In Man the Hunter, pp. 321334 [Lee, RB and DeVore, I, editors]. New York: Aldine Publishing Company.Google Scholar
317Meehan, B (1982) Shell Bed to Shell Midden. Canberra: Humanity Press.Google Scholar
318Moss, ML (1993) Shellfish, gender, and status on the Northwest Coast – reconciling archaeological, ethnographic, and ethnohistorical records of the Tlingit. Am Anthropol 95, 631652.Google Scholar
319Godfrey, KM, Lillycrop, KA, Burdge, GC, et al. . (2007) Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease. Pediatr Res 61, 5R10R.Google Scholar
320Burdge, GC, Hanson, MA, Slater-Jefferies, JL, et al. . (2007) Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life? Br J Nutr 97, 10361046.Google Scholar
321Waterland, RA & Jirtle, RL (2004) Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition 20, 6368.Google Scholar
322Lillycrop, KA & Burdge, GC (2010) Epigenetic changes in early life and future risk of obesity. Int J Obes (Lond) 35, 7283.Google Scholar
323Godfrey, KM, Sheppard, A, Gluckman, PD, et al. . (2011) Epigenetic gene promoter methylation at birth is associated with child's later adiposity. Diabetes 60, 15281534.Google Scholar
324Bensinger, SJ & Tontonoz, P (2008) Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 454, 470477.Google Scholar
325Castrillo, A & Tontonoz, P (2004) PPARs in atherosclerosis: the clot thickens. J Clin Invest 114, 15381540.Google Scholar
326Song, Y, Yao, X & Ying, H (2011) Thyroid hormone action in metabolic regulation. Protein Cell 2, 358368.Google Scholar
327Bouillon, R, Bischoff-Ferrari, H & Willett, W (2008) Vitamin D and health: perspectives from mice and man. J Bone Miner Res 23, 974979.Google Scholar
328McGrane, MM (2007) Vitamin A regulation of gene expression: molecular mechanism of a prototype gene. J Nutr Biochem 18, 497508.Google Scholar
329Venturi, S, Donati, FM, Venturi, A, et al. . (2000) Role of iodine in evolution and carcinogenesis of thyroid, breast and stomach. Adv Clin Path 4, 1117.Google Scholar
330Kohrle, J & Gartner, R (2009) Selenium and thyroid. Best Pract Res Clin Endocrinol Metab 23, 815827.Google Scholar
331Gilbert, ME, McLanahan, ED, Hedge, J, et al. . (2011) Marginal iodide deficiency and thyroid function: dose–response analysis for quantitative pharmacokinetic modeling. Toxicology 283, 4148.Google Scholar
332Desvergne, B & Wahli, W (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20, 649688.Google Scholar
333Norman, AW & Bouillon, R (2010) Vitamin D nutritional policy needs a vision for the future. Exp Biol Med (Maywood) 235, 10341045.Google Scholar
334Holick, MF & Chen, TC (2008) Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87, 1080S1086S.Google Scholar
335Mann, GV, Roels, OA, Price, DL, et al. . (1962) Cardiovascular disease in African Pygmies. A survey of the health status, serum lipids and diet of Pygmies in Congo. J Chron Dis 15, 341371.Google Scholar
336Mann, GV, Shaffer, RD, Anderson, RS, et al. . (1964) Cardiovascular disease in the Masai. J Atheroscler Res 4, 289312.Google Scholar
337Mann, GV, Shaffer, RD & Rich, A (1965) Physical fitness and immunity to heart disease in Masai. Lancet ii, 13081310.Google Scholar
338Shaper, AG, Leonard, PJ, Jones, KW, et al. . (1969) Environmental effects on the body build, blood pressure and blood chemistry of nomadic warriors serving in the army in Kenya. East Afr Med J 46, 282289.Google Scholar
339O'Keefe, JH Jr, Cordain, L, Harris, WH, et al. . (2004) Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol 43, 21422146.Google Scholar
340Joffe, BI, Jackson, WP, Thomas, ME, et al. . (1971) Metabolic responses to oral glucose in the Kalahari Bushmen. Br Med J 4, 206208.Google Scholar
341Merimee, TJ, Rimoin, DL & Cavalli-Sforza, LL (1972) Metabolic studies in the African pygmy. J Clin Invest 51, 395401.Google Scholar
342Ramsden, CE, Faurot, KR, Carrera-Bastos, P, et al. . (2009) Dietary fat quality and coronary heart disease prevention: a unified theory based on evolutionary, historical, global, and modern perspectives. Curr Treat Options Cardiovasc Med 11, 289301.Google Scholar
343Keys, AB (1980) Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease. Cambridge, MA: Harvard University Press.Google Scholar
344Clarke, R, Frost, C, Collins, R, et al. . (1997) Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ 314, 112117.Google Scholar
345Kuipers, RS, de Graaf, DJ, Luxwolda, MF, et al. . (2011) Saturated fat, carbohydrates and CVD. Neth J Med 69, 2228.Google Scholar
346Ho, KJ, Biss, K, Mikkelson, B, et al. . (1971) The Masai of East Africa: some unique biological characteristics. Arch Pathol 91, 387410.Google Scholar
347Biss, K, Ho, KJ, Mikkelson, B, et al. . (1971) Some unique biologic characteristics of the Masai of East Africa. N Engl J Med 284, 694699.Google Scholar
348Mann, GV, Spoerry, A, Gray, M, et al. . (1972) Atherosclerosis in the Masai. Am J Epidemiol 95, 2637.Google Scholar
349Kaminer, B & Lutz, WPW (1960) Blood pressure in Bushmen of the Kalahari Desert. Circulation 22, 289295.Google Scholar
350Clement, AJ, Fosdick, LL & Plotkin, R (1956) The formation of lactic acid in dental plaques. II. Oral conditions of primitive Bushmen of the Western Kalahari Desert. J Dent Res 35, 786791.Google Scholar
351Lindeberg, S, Berntorp, E, Nilsson-Ehle, P, et al. . (1997) Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study. Am J Clin Nutr 66, 845852.Google Scholar
352Sackett, DL, Rosenberg, WM, Gray, JA, et al. . (1996) Evidence based medicine: what it is and what it isn't. BMJ 312, 7172.Google Scholar
353Blumberg, J, Heaney, RP, Huncharek, M, et al. . (2010) Evidence-based criteria in the nutritional context. Nutr Rev 68, 478484.Google Scholar
354Dyerberg, J, Bang, HO & Hjorne, N (1975) Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr 28, 958966.Google Scholar
355Bang, HO, Dyerberg, J & Sinclair, HM (1980) The composition of the Eskimo food in north western Greenland. Am J Clin Nutr 33, 26572661.Google Scholar
356Burr, ML, Fehily, AM, Gilbert, JF, et al. . (1989) Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet ii, 757761.Google Scholar
357Mozaffarian, D & Rimm, EB (2006) Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 296, 18851899.Google Scholar
358de Lorgeril, M, Salen, P, Martin, JL, et al. . (1999) Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 99, 779785.Google Scholar
359Anonymous (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 354, 447455.Google Scholar
360Marchioli, R, Barzi, F, Bomba, E, et al. . (2002) Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 105, 18971903.Google Scholar
361Yokoyama, M, Origasa, H, Matsuzaki, M, et al. . (2007) Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 369, 10901098.Google Scholar
362Kromhout, D, Giltay, EJ, Geleijnse, JM, et al. . (2010) n-3 Fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 363, 20152026.Google Scholar
363Hibbeln, JR (1998) Fish consumption and major depression. Lancet 351, 1213.Google Scholar
364Hibbeln, JR (2002) Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord 69, 1529.Google Scholar
365Hibbeln, JR (2009) Depression, suicide and deficiencies of omega-3 essential fatty acids in modern diets. World Rev Nutr Diet 99, 1730.Google Scholar
366Hibbeln, JR (2001) Seafood consumption and homicide mortality. A cross-national ecological analysis. World Rev Nutr Diet 88, 4146.Google Scholar
367Lin, PY & Su, KP (2007) A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry 68, 10561061.Google Scholar
368Ross, BM, Seguin, J & Sieswerda, LE (2007) Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids Health Dis 6, 21.Google Scholar
369Sinclair, AJ, Begg, D, Mathai, M, et al. . (2007) Omega 3 fatty acids and the brain: review of studies in depression. Asia Pac J Clin Nutr 16, Suppl. 1, 391397.Google Scholar
370Freeman, MP (2000) Omega-3 fatty acids in psychiatry: a review. Ann Clin Psychiatry 12, 159165.Google Scholar
371Freeman, MP, Hibbeln, JR, Wisner, KL, et al. . (2006) Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry 67, 19541967.Google Scholar
372Sublette, ME, Ellis, SP, Geant, AL, et al. . (2011) Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry 72, 15771584.Google Scholar
373Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14 000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661678.Google Scholar
374Challem, JJ (1997) Did the loss of endogenous ascorbate propel the evolution of Anthropoidea and Homo sapiens? Med Hypotheses 48, 387392.Google Scholar
375Nishikimi, M, Fukuyama, R, Minoshima, S, et al. . (1994) Cloning and chromosomal mapping of the human nonfunctional gene for l-gulono-γ-lactone oxidase, the enzyme for l-ascorbic acid biosynthesis missing in man. J Biol Chem 269, 1368513688.Google Scholar
376Burdge, GC & Wootton, SA (2002) Conversion of α-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr 88, 411420.Google Scholar
377Burdge, GC (2006) Metabolism of α-linolenic acid in humans. Prostaglandins Leukot Essent Fatty Acids 75, 161168.Google Scholar
378Kuipers, RS, Luxwolda, MF, Janneke Dijck-Brouwer, DA, et al. . (2011) Intrauterine, postpartum and adult relationships between arachidonic acid (AA) and docosahexaenoic acid (DHA). Prostaglandins Leukot Essent Fatty Acids 85, 245252.Google Scholar
379Luxwolda, MF, Kuipers, RS, Smit, EN, et al. . (2011) The relation between the omega-3 index and arachidonic acid is bell shaped: synergistic at low EPA+DHA status and antagonistic at high EPA+DHA status. Prostaglandins Leukot Essent Fatty Acids 85, 171178.Google Scholar
380Crawford, MA, Hassam, AG, Williams, G, et al. . (1976) Essential fatty acids and fetal brain growth. Lancet i, 452453.Google Scholar
381Kuhn, DC & Crawford, M (1986) Placental essential fatty acid transport and prostaglandin synthesis. Prog Lipid Res 25, 345353.Google Scholar
382Crawford, MA, Hassam, AG & Rivers, JP (1978) Essential fatty acid requirements in infancy. Am J Clin Nutr 31, 21812185.Google Scholar
383Hornstra, G (2000) Essential fatty acids in mothers and their neonates. Am J Clin Nutr 71, 1262S1269S.Google Scholar
384Hornstra, G (2005) Essential fatty acids during pregnancy. Impact on mother and child. Nestle Nutr Workshop Ser Pediatr Program 55, 8396.Google Scholar
385Makrides, M, Gibson, RA, McPhee, AJ, et al. . (2010) Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA 304, 16751683.Google Scholar
386Doornbos, B, van Goor, SA, Dijck-Brouwer, DA, et al. . (2009) Supplementation of a low dose of DHA or DHA+AA does not prevent peripartum depressive symptoms in a small population based sample. Prog Neuropsychopharmacol Biol Psychiatry 33, 4952.Google Scholar
387Su, KP, Huang, SY, Chiu, TH, et al. . (2008) Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 69, 644651.Google Scholar
388Wojcicki, JM & Heyman, MB (2011) Maternal omega-3 fatty acid supplementation and risk for perinatal maternal depression. J Matern Fetal Neonatal Med 24, 680686.Google Scholar
389Koletzko, B & Braun, M (1991) Arachidonic acid and early human growth: is there a relation? Ann Nutr Metab 35, 128131.Google Scholar
390Szajewska, H, Horvath, A & Koletzko, B (2006) Effect of n-3 long-chain polyunsaturated fatty acid supplementation of women with low-risk pregnancies on pregnancy outcomes and growth measures at birth: a meta-analysis of randomized controlled trials. Am J Clin Nutr 83, 13371344.Google Scholar
391Olsen, SF, Osterdal, ML, Salvig, JD, et al. . (2006) Duration of pregnancy in relation to seafood intake during early and mid pregnancy: prospective cohort. Eur J Epidemiol 21, 749758.Google Scholar
392Olsen, SF, Osterdal, ML, Salvig, JD, et al. . (2007) Duration of pregnancy in relation to fish oil supplementation and habitual fish intake: a randomised clinical trial with fish oil. Eur J Clin Nutr 61, 976985.Google Scholar
393Malcolm, CA, McCulloch, DL, Montgomery, C, et al. . (2003) Maternal docosahexaenoic acid supplementation during pregnancy and visual evoked potential development in term infants: a double blind, prospective, randomised trial. Arch Dis Child Fetal Neonatal Ed 88, F383F390.Google Scholar
394Malcolm, CA, Hamilton, R, McCulloch, DL, et al. . (2003) Scotopic electroretinogram in term infants born of mothers supplemented with docosahexaenoic acid during pregnancy. Invest Ophthalmol Vis Sci 44, 36853691.Google Scholar
395Judge, MP, Harel, O & Lammi-Keefe, CJ (2007) A docosahexaenoic acid-functional food during pregnancy benefits infant visual acuity at four but not six months of age. Lipids 42, 117122.Google Scholar
396Birch, EE, Carlson, SE, Hoffman, DR, et al. . (2010) The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr 91, 848859.Google Scholar
397Smithers, LG, Gibson, RA, McPhee, A, et al. . (2008) Higher dose of docosahexaenoic acid in the neonatal period improves visual acuity of preterm infants: results of a randomized controlled trial. Am J Clin Nutr 88, 10491056.Google Scholar
398Judge, MP, Harel, O & Lammi-Keefe, CJ (2007) Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy: benefit for infant performance on problem-solving but not on recognition memory tasks at age 9 mo. Am J Clin Nutr 85, 15721577.Google Scholar
399Dunstan, JA, Simmer, K, Dixon, G, et al. . (2008) Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 93, F45F50.Google Scholar
400Helland, IB, Smith, L, Saarem, K, et al. . (2003) Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics 111, e39e44.Google Scholar
401Helland, IB, Smith, L, Blomen, B, et al. . (2008) Effect of supplementing pregnant and lactating mothers with n-3 very-long-chain fatty acids on children's IQ and body mass index at 7 years of age. Pediatrics 122, e472e479.Google Scholar
402McCann, JC & Ames, BN (2005) Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. Am J Clin Nutr 82, 281295.Google Scholar
403Dijck-Brouwer, DA, Hadders-Algra, M, Bouwstra, H, et al. . (2005) Lower fetal status of docosahexaenoic acid, arachidonic acid and essential fatty acids is associated with less favorable neonatal neurological condition. Prostaglandins Leukot Essent Fatty Acids 72, 2128.Google Scholar
404Moriguchi, T, Loewke, J, Garrison, M, et al. . (2001) Reversal of docosahexaenoic acid deficiency in the rat brain, retina, liver, and serum. J Lipid Res 42, 419427.Google Scholar
405Rao, JS, Ertley, RN, DeMar, JC Jr, et al. . (2007) Dietary n-3 PUFA deprivation alters expression of enzymes of the arachidonic and docosahexaenoic acid cascades in rat frontal cortex. Mol Psychiatry 12, 151157.Google Scholar
406van Goor, SA, Smit, EN, Schaafsma, A, et al. . (2008) Milk of women with lifetime consumption of the recommended daily intake of fish fatty acids should constitute the basis for the DHA contents of infant formula. J Perinat Med 36, 548549.Google Scholar
407Brenna, JT, Varamini, B, Jensen, RG, et al. . (2007) Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr 85, 14571464.Google Scholar
408Koletzko, B, Lien, E, Agostoni, C, et al. . (2008) The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med 36, 514.Google Scholar
409Kuipers, RS, Smit, EN, van der Meulen, J, et al. . (2007) Milk in the island of Chole [Tanzania] is high in lauric, myristic, arachidonic and docosahexaenoic acids, and low in linoleic acid reconstructed diet of infants born to our ancestors living in tropical coastal regions. Prostaglandins Leukot Essent Fatty Acids 76, 221233.Google Scholar
410Hachey, DL, Silber, GH, Wong, WW, et al. . (1989) Human lactation. II: Endogenous fatty acid synthesis by the mammary gland. Pediatr Res 25, 6368.Google Scholar
411Kabara, JJ (1980) Lipids as host-resistance factors of human milk. Nutr Rev 38, 6573.Google Scholar
412Bergsson, G, Steingrimsson, O & Thormar, H (2002) Bactericidal effects of fatty acids and monoglycerides on Helicobacter pylori. Int J Antimicrob Agents 20, 258262.Google Scholar
413Widdowson, EM, Dauncey, MJ, Gairdner, DM, et al. . (1975) Body fat of British and Dutch infants. Br Med J 1, 653655.Google Scholar
414Ailhaud, G, Massiera, F, Weill, P, et al. . (2006) Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity. Prog Lipid Res 45, 203236.Google Scholar
415Ramsden, CE, Hibbeln, JR, Majchrzak, SF, et al. . (2010) n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials. Br J Nutr 104, 15861600.Google Scholar
416Harris, WS, Mozaffarian, D, Rimm, E, et al. . (2009) Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition. Circulation 119, 902907.Google Scholar
417Gibson, RA, Muhlhausler, B & Makrides, M (2011) Conversion of linoleic acid and α-linolenic acid to long-chain polyunsaturated fatty acids (LCPUFAs), with a focus on pregnancy, lactation and the first 2 years of life. Matern Child Nutr 7, Suppl. 2, 1726.Google Scholar
418Koletzko, B, Thiel, I & Abiodun, PO (1992) The fatty acid composition of human milk in Europe and Africa. J Pediatr 120, S62S70.Google Scholar
419Godfrey, K, Robinson, S, Barker, DJ, et al. . (1996) Maternal nutrition in early and late pregnancy in relation to placental and fetal growth. BMJ 312, 410414.Google Scholar
420Innis, SM & Kuhnlein, HV (1988) Long-chain n-3 fatty acids in breast milk of Inuit women consuming traditional foods. Early Hum Dev 18, 185189.Google Scholar
421Ruan, C, Liu, X, Man, H, et al. . (1995) Milk composition in women from five different regions of China: the great diversity of milk fatty acids. J Nutr 125, 29932998.Google Scholar
422Muskiet, FA, Kuipers, RS, Smit, EN, et al. . (2007) The basis of recommendations for docosahexaenoic and arachidonic acids in infant formula: absolute or relative standards? Am J Clin Nutr 86, 18021803.Google Scholar
423Willett, WC (2002) Balancing life-style and genomics research for disease prevention. Science 296, 695698.Google Scholar
424Yudkin, J (1963) Dietary carbohydrate and ischemic heart disease. Am Heart J 66, 835836.Google Scholar
425Yudkin, J (1967) Evolutionary and historical changes in dietary carbohydrates. Am J Clin Nutr 20, 108115.Google Scholar
426Eaton, SB (1992) Humans, lipids and evolution. Lipids 27, 814820.Google Scholar
427Cordain, L, Watkins, BA & Mann, NJ (2001) Fatty acid composition and energy density of foods available to African hominids. Evolutionary implications for human brain development. World Rev Nutr Diet 90, 144161.Google Scholar
428Crawford, MA (1968) Fatty-acid ratios in free-living and domestic animals. Possible implications for atheroma. Lancet i, 13291333.Google Scholar
429O'Dea, K & Sinclair, AJ (1982) Increased proportion of arachidonic acid in plasma lipids after 2 weeks on a diet of tropical seafood. Am J Clin Nutr 36, 868872.Google Scholar
430Sinclair, AJ, O'Dea, K & Naughton, JM (1983) Elevated levels of arachidonic acid in fish from northern Australian coastal waters. Lipids 18, 877881.Google Scholar
431Gibson, RA, Kneebone, R & Kneebone, GM (1984) Comparative levels of arachidonic acid and eicosapentaenoic acid in Malaysian fish. Comp Biochem Physiol C 78, 325328.Google Scholar
432Naughton, JM, O'Dea, K & Sinclair, AJ (1986) Animal foods in traditional Australian aboriginal diets: polyunsaturated and low in fat. Lipids 21, 684690.Google Scholar
433Konner, M & Eaton, SB (2010) Paleolithic nutrition: twenty-five years later. Nutr Clin Pract 25, 594602.Google Scholar
434Eaton, SB, Eaton, SB III & Konner, MJ (1997) Paleolithic nutrition revisited: a twelve-year retrospective on its nature and implications. Eur J Clin Nutr 51, 207216.Google Scholar
435Eaton, SB & Eaton, SB III (2000) Paleolithic vs. modern diets – selected pathophysiological implications. Eur J Nutr 39, 6770.Google Scholar
436Cordain, L, Miller, JB, Eaton, SB, et al. . (2000) Macronutrient estimations in hunter–gatherer diets. Am J Clin Nutr 72, 15891592.Google Scholar
437Kuipers, RS, Luxwolda, MF, Dijck-Brouwer, DA, et al. . (2010) Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet. Br J Nutr 104, 16661687.Google Scholar
438Morgan, E (1997) The Aquatic Ape Hypothesis. London: Souvenir Press.Google Scholar
439Horrobin, DF (2001) The Madness of Adam and Eve. How Schizophrenia Shaped Humanity. Reading: Cox & Wyman Ltd.Google Scholar
440Hotamisligil, GS & Erbay, E (2008) Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 8, 923934.Google Scholar
441Forsythe, CE, Phinney, SD, Fernandez, ML, et al. . (2008) Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation. Lipids 43, 6577.Google Scholar
442Volek, JS, Phinney, SD, Forsythe, CE, et al. . (2009) Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 44, 297309.Google Scholar
443Forsythe, CE, Phinney, SD, Feinman, RD, et al. . (2010) Limited effect of dietary saturated fat on plasma saturated fat in the context of a low carbohydrate diet. Lipids 45, 947962.Google Scholar
444Simopoulos, AP (1999) Essential fatty acids in health and chronic disease. Am J Clin Nutr 70, 560S569S.Google Scholar
445Simopoulos, AP (2001) Evolutionary aspects of diet and essential fatty acids. World Rev Nutr Diet 88, 1827.Google Scholar
446Feinman, RD & Volek, JS (2006) Low carbohydrate diets improve atherogenic dyslipidemia even in the absence of weight loss. Nutr Metab (Lond) 3, 24.Google Scholar
447Osterdahl, M, Kocturk, T, Koochek, A, et al. . (2008) Effects of a short-term intervention with a Paleolithic diet in healthy volunteers. Eur J Clin Nutr 62, 682685.Google Scholar
448Jönsson, T, Granfeldt, Y, Ahrén, B, et al. . (2009) Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovasc Diabetol 8, 35.Google Scholar
449Lindeberg, S, Jonsson, T, Granfeldt, Y, et al. . (2007) A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease. Diabetologia 50, 17951807.Google Scholar
450Frassetto, LA, Schloetter, M, Mietus-Synder, M, et al. . (2009) Metabolic and physiologic improvements from consuming a Paleolithic, hunter–gatherer type diet. Eur J Clin Nutr 63, 947955.Google Scholar
Figure 0

Fig. 1 Scheme of the possible phylogenetic relationships within the family Hominidae. Note that at many time points of evolution, several different hominin species coexisted. Mya, million years ago; H., Homo; Au., Australopithecus; K., Kenyanthropus; P., Paranthropus; Ar., Ardipithecus; O., Orrorin; S., Sahelanthropus. © Ian Tattersall, with permission(76).

Figure 1

Fig. 2 Coasting out of Africa: following the water in the third out-of-Africa diaspora. Assumed dispersal routes of archaic and anatomically modern man out of Africa and the supportive fossil evidence for hominin presence: (♦), Australopithecus sp.; (●), Homo habilis, erectus, ergaster or antecessor; (■), H. heidelbergensis; (★), H. neanderthalensis; (⊙), H. sapiens. ya, Years ago. Source: National Geographic Society 1988, 1997; adapted from www.handprint.com/LS/ANC/disp.html and Oppenheimer(83).

Figure 2

Table 1 The development of brain weight relative to body dimensions*

Figure 3

Fig. 3 Metabolism of the parent essential fatty acids and endogenously synthesised fatty acids. Δ9, Δ9-Desaturase; CE, chain elongation; Δ6, Δ6-desaturase; Δ5, Δ5-desaturase; CS, chain shortening through peroxisomal β-oxidation. 18 : 3n-3, α-linolenic acid; 18 : 2n-6, linoleic acid; 18 : 1n-9, oleic acid; 20 : 5n-3, EPA; 20 : 4n-6, arachidonic acid; 20 : 3n-9, mead acid; 22 : 6n-3, DHA.

Figure 4

Fig. 4 Lower jaw of a chimpanzee (Pan troglodytes), Australopithecus africanus and Homo sapiens. Note the somewhat human-like shape of the teeth, but ape-like axis in the jaw of Australopithecus. © Australian Museum.

Figure 5

Fig. 5 Normalised collagen δ13C values (mean and range; in per thousand (‰)) in plankton, crustaceans, sea grasses, C3 and C4 plants; of marine crustaceans, fish and freshwater fish and their respective carnivores; of terrestrial C3 and C4 herbivores and their carnivores; and of human groups in historic and prehistoric times. * Corrected(229) for collagen ( − 5 ‰). † Corrected(238) for enamel ( − 13 ‰). ‡ Arbitrary range of ±  1 ‰ due to a lack of data. § As predicted from other predator–prey relationships and after correction(239) for tropic level (+1 ‰). Adapted from Ambrose & Deniro(228), Sponheimer et al.(231,247), Peters & Vogel(234), Lee-Thorp et al.(237,244), Kelly(239), Schoeninger & Deniro(240), Mbabazi et al.(241), Schoeninger et al.(242,246), Sponheimer & Lee-Thorp(243,248,249) and van der Merwe et al.(245).

Figure 6

Fig. 6 ‘Abnormal’ insulin response but normal glucose response after oral glucose tolerance test in African Bushmen and Pygmies, compared with Western controls. (a) Plasma glucose response after an oral glucose load of 50 g (Bushmen (♦) and white controls (○)) or 100 g (Pygmy (■), Pygmy with 2 weeks' daily supplementation of 150 g carbohydrates before testing (▲), Bantu (X) and American controls ()). Of note is that Bushmen and Pygmies have significantly lower body weights as compared with Bantu and white and American controls (average weight Bushmen/Pygmy males 46 kg, females 38 kg; controls 65 kg), while each group received the same unadjusted loading dose of 50 g or 100 g glucose. (b) The so-called ‘abnormal’ insulin response or ‘impaired’ insulin secretion as observed by the authors in both Bushmen and Pygmies(340,341).

Figure 7

Fig. 7 The seven dietary characteristics that have been changed since the Agricultural and Industrial Revolutions. Adapted from Muskiet(24).