Uric acid, evolution and primitive cultures

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Hypertension is epidemic and currently affects 25% of the world’s population and is a major cause of stroke, congestive heart failure, and end-stage renal disease. Interestingly, there is evidence that the increased frequency of hypertension is a recent event in human history and correlates with dietary changes associated with Westernization. In this article, we review the evidence that links uric acid to the cause and epidemiology of hypertension. Specifically, we review the evidence that the mutation of uricase that occurred in the Miocene that resulted in a higher serum uric acid in humans compared with most other mammals may have occurred as a means to increase blood pressure in early hominoids in response to a low-sodium and low-purine diet. We then review the evidence that the epidemic of hypertension that evolved with Westernization was associated with an increase in the intake of red meat with a marked increase in serum uric acid levels. Indeed, gout and hyperuricemia should be considered a part of the obesity, type 2 diabetes, and hypertension epidemic that is occurring worldwide. Although other mechanisms certainly contribute to the pathogenesis of hypertension, the possibility that serum uric acid level may have a major role is suggested by these studies.

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The uricase mutation in human evolution

Uric acid is a product of purine metabolism that is generated during the enzymatic degradation of xanthine. When the enzyme is xanthine oxidase, both uric acid and superoxide anion are produced, whereas the reaction with xanthine dehydrogenase releases uric acid and the reduced form of nicotinamide-adenine dinucleotide. In most mammals, uric acid is degraded further by the enzyme uricase (also known as urate oxidase) to allantoin. Serum uric acid levels are therefore low (0.5– 2.0 mg/dL) in

The anthropology of blood pressure and uric acid levels

Hypertension in the absence of obvious renal disease (primary or essential hypertension) was first described in the mid-1800s by Frederick Akbar Mahomed from Guy’s Hospital in London.26 It was interesting that hypertension was not uncommon in Victorian England, and similarly gout also was rampant, especially among the wealthy, where it was often the subject for caricatures. Part of the epidemic of gout may have been related to the common drinking of fortified wines, especially port, that were

Other mechanisms modulating blood pressure with Westernization

It is important to recognize that other mechanisms also likely influence the development of hypertension associated with Westernization. There is considerable evidence that the sodium content in the diet influences blood pressure; cultures ingesting a low-sodium diet have a marked lower frequency of hypertension.62, 63 A highly positive correlation between sodium intake with blood pressure was found in an international study of over 10,000 individuals in 52 sites throughout the world.64 Diets

Studies relating uric acid, diet, and hypertension in other species

It is interesting that humans are the only mammalian species that has such a high frequency (25%) of hypertension and arteriolosclerosis. Most studies of primates living in the wild suggest that hypertension and arteriolosclerosis are rare despite the fact that the Great Apes have no functional uricase. This may reflect a diet consisting primarily of fruit and vegetables, and only small amounts of animal protein. As a consequence, serum uric acid levels remain lower in the Great Ape compared

Conclusions

Although many studies suggest that the change in diet may have led to the epidemic of hypertension by increasing serum uric acid levels, there are some caveats. First, studies of the PukaPuka Indians of the Cook Islands have reported that hyperuricemia is common despite minimal evidence of hypertension.76 It is possible that any deleterious action of uric acid to raise blood pressure may be countered by the low salt diet of this population63 or by other components in the diet that may have

References (77)

  • F.W. Lowenstein

    Blood-pressure in relation to age and sex in the tropics and subtropics

    Lancet

    (1961)
  • G.M. Saunders et al.

    Blood pressure studies on negro and white men and women living in the Virgin Islands of the United States

    Am Heart J

    (1942)
  • B.S. Rose

    Gout in the Maoris

    Semin Arthritis Rheum

    (1975)
  • A. Kagan et al.

    Epidemiologic studies on coronary heart disease and stroke in Japanese men living in Japan, Hawaii, and CaliforniaDemographic, physical, dietary and biochemical characteristics

    J Chron Dis

    (1974)
  • I.A.M. Prior et al.

    Hyperuricemia, gout, and diabetic abnormality in Polynesian people

    Lancet

    (1966)
  • American Heart Association: Cardiovascular disease statistics. Available at: www.americanheart.org,...
  • T. Forrester et al.

    Emergence of Western diseases in the tropical worldThe experience with chronic cardiovascular diseases

    Br Med Bull

    (1998)
  • R.B. Singh et al.

    Hypertension and stroke in AsiaPrevalence, control and strategies in developing countries for prevention

    J Hum Hypertens

    (2000)
  • Y.K. Seedat

    Hypertension in developing nations in sub-Saharan Africa

    J Hum Hypertens

    (2000)
  • R.S. Danzinger

    Hypertension in an anthropological and evolutionary paradigm

    Hypertension

    (2001)
  • M. Oda et al.

    Loss of urate oxidase activity in hominoids and its evolutionary implications

    Mol Biol Evol

    (2002)
  • A. Bradley et al.

    Hyperuricemia and urate nephropathy in urate oxidase deficient mice

    Proc Natl Acad Sci U S A

    (1994)
  • E. Orowan

    The origin of man

    Nature

    (1955)
  • B.N. Ames et al.

    Uric acid provides an antioxidant defense in humans against oxidant- and radical-causing aging and cancerA hypothesis

    Proc Natl Acad Sci U S A

    (1981)
  • L. Pauling

    Evolution and the need for ascorbic acid

    Proc Natl Acad Sci U S A

    (1970)
  • R.J. Johnson et al.

    Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease?

    Hypertension

    (2003)
  • S. Watanabe et al.

    Uric acid, hominoid evolution and the pathogenesis of salt-sensitivity

    Hypertension

    (2002)
  • M. Mazzali et al.

    Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism

    Hypertension

    (2001)
  • M. Mazzali et al.

    Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism

    Am J Physiol

    (2002)
  • J. Kanellis et al.

    Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2

    Hypertension

    (2003)
  • D.I. Feig et al.

    Hyperuricemia in childhood essential hypertension

    Hypertension

    (2003)
  • R.J. Johnson et al.

    Uric acid and dietInsights into the epidemic of cardiovascular disease

    N Engl J Med

    (2004)
  • H.K. Choi et al.

    Purine-rich foods, dairy intake, and protein intake, and risk of gout in men

    N Engl J Med

    (2004)
  • J.O. Nriagu

    Saturnine gout among Roman aristocrats. Did lead poisoning contribute to the fall of the Empire

    N Engl J Med

    (1983)
  • A. Haig

    On uric acid and arterial tension

    Br Med J

    (1889)
  • H. Huchard

    ArteriolosclerosisIncluding its cardiac form

    JAMA

    (1909)
  • H. Huchard

    Allgemeine Betrachtungen űber die Arteriosklerose

    Klin Med Berlin

    (1909)
  • A.W. Williams

    Blood pressure of Africans

    East Afr Med J

    (1941)

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    Supported by National Institutes of Health grants HL-68607 and DK-52121.

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