Evolutionary Health Promotion

Abstract

Health promotion's promise is enormous, but its potential is, as yet, unmatched by accomplishment. Life expectancy increases track more closely with economic prosperity and sanitary engineering than with strictly medical advances. Notable achievements in the past century--the decreased incidences of epidemic infections, dental caries, and stomach cancer--are owed to virologists, dentists, and (probably) refrigeration more than to physicians. Prevention speaks against tobacco abuse with a single voice, but in many other areas contradictory research findings have generated skepticism and even indifference among the general public for whom recommendations are targeted. Health promotion's shortcomings may reflect lack of an overall conceptual framework, a deficiency that might be corrected by adopting evolutionary premises: (1) The human genome was selected in past environments far different from those of the present. (2) Cultural evolution now proceeds too rapidly for genetic accommodation--resulting in dissociation between our genes and our lives. (3) This mismatch between biology and lifestyle fosters development of degenerative diseases. These principles could inform a research agenda and, ultimately, public policy: (1) Better characterize differences between ancient and modern life patterns. (2) Identify which of these affect the development of disease. (3) Integrate epidemiological, mechanistic, and genetic data with evolutionary principles to create an overarching formulation upon which to base persuasive, consistent, and effective recommendations.

Full text

Preventive Medicine 34, 109–118 (2002)
doi:10.1006/pmed.2001.0876, available online at http://www.idealibrary.com on
REVIEW
Evolutionary Health Promotion
S. Boyd Eaton, M.D.,*
,1
Beverly I. Strassman, Ph.D.,† Randolph M. Nesse, M.D.,‡
James V. Neel, M.D., Ph.D.,§
,2
Paul W. Ewald, Ph.D.,¶ George C. Williams, Ph.D.,얍Alan B. Weder, M.D.,**
Stanley B. Eaton III, M.A.,†† Staffan Lindeberg, M.D., Ph.D.,‡‡ Melvin J. Konner, M.D., Ph.D.,§§
Iver Mysterud, M.Sc.,
¶¶
and Loren Cordain, Ph.D.앚앚
*Department of Anthropology and Department of Radiology, Emory University, 2887 Howell Mill Road NW, Atlanta, Georgia 30327;
†Department of Anthropology, University of Michigan, 1020 LSA Building, Ann Arbor, Michigan 48109-0618;
‡5057 Institute for Social Research, University of Michigan, P.O. Box 1248, Ann Arbor, Michigan 48106; §Department of Human
Genetics, University of Michigan Medical School, Medical Science II M4708, Ann Arbor, Michigan 48109-0618; ¶Department of Biology,
Amherst College, Amherst, Massachusetts 01002-5000; 얍Division of Biological Sciences, Department of Ecology and Evolution, State
University of New York, Stony Brook, New York 11794-5245; **Division of Hypertension, Department of Internal Medicine,
University of Michigan Medical Center, Ann Arbor, Michigan 48109-0356; ††Science Department, Charlotte Lockhart Academy,
Kennesaw, Georgia 30144; ‡‡Primary Health Care Center, P.O. Box 144, S-275 23 Sjobo, Sweden; §§Department of Anthropology
and Department of Neurology, Emory University, 1064 Clifton Road NE, Atlanta, Georgia 30307;
¶¶
Division of Zoology, Department
of Biology, University of Oslo, P.O. Box 1050 Blindern, N-0316 Oslo, Norway; and 앚앚Department of Exercise and Sports Science,
Colorado State University, Fort Collins, Colorado 80323
Published online December 20, 2001
a research agenda and, ultimately, public policy: (1)
Health promotion’s promise is enormous, but its Better characterize differences between ancient and
potentialis, asyet, unmatchedby accomplishment.Life modern life patterns. (2) Identify which of these affect
expectancy increases track more closely with eco- the development of disease. (3) Integrate epidemiologi-
nomic prosperity and sanitary engineering than with cal, mechanistic, and genetic data with evolutionary
strictlymedicaladvances. Notableachievementsin the principles to create an overarching formulation upon
past century—the decreased incidences of epidemic which to base persuasive, consistent, and effective rec-
infections, dental caries, and stomach cancer—are ommendations.
䉷2001 American Health Foundation and Elsevier
owed to virologists, dentists, and (probably) refrigera-
Science (USA)
tion more than to physicians. Prevention speaks Key Words: evolutionary medicine; Darwinian medi-
against tobacco abuse with a single voice, but in many cine; health promotion; disease prevention; human
other areas contradictory research findings have gen- evolution.
erated skepticism and even indifference among the
general public for whom recommendations are tar-
INTRODUCTION
geted. Health promotion’s shortcomings may reflect
lack of an overall conceptual framework, a deficiency
In1930gastriccarcinomawas the most lethal Ameri-
that might be corrected by adopting evolutionary
can neoplasm, while lung cancer ranked seventh. Sub-
premises: (1) The human genome was selected in past
sequently their rankings exchanged places: mortality
environments far different from those of the present.
from bronchogenic neoplasms increased 10-fold as
(2) Cultural evolution now proceeds too rapidly for
deaths from stomach malignancies fell to 20% of their
genetic accomodation—resulting in dissociation
previous rate [1]—contrasting trajectories that reflect
between our genes and our lives. (3) This mismatch
altered tobacco use and food preservation practices
between biology and lifestyle fosters development of
more than medical interventions [2]. Similarly, increas-
degenerative diseases. These principles could inform
ing prevalence of type 2 diabetes (nominally up 3-fold
since 1935) [3] and the 20th century’s rise in coronary
1
To whom reprint requests should be addressed. Fax: (404) 352-
heart disease rates [4–6] have resulted mainly from
2529. E-mail: daphne@mindspring.com.
2
Deceased.
changesinhow people livetheirdaily lives. Preventable
109
0091-7435/01 $35.00
䉷2001 American Health Foundation and Elsevier Science (USA)
All rights reserved.

110
EATON ET AL.
disorders make upapproximately 70% of theAmerican of longer life spans. More important is dissonance be-
tween “Stone Age” genes and “Space Age” circum-illnessburdenanditsassociatedcosts [7]; in some stud-
ies individuals with high-risk health habits have had stances [14–16], with resulting disruption of ancient,
complex homeostatic systems [17].annual medical claims eight times those of individuals
with low-risk behavior [8]. Logically such considera- Evidence for this contention comes from studies of
hunter–gatherers andother peopleswhocontinuecriti-tions should generate palpable enthusiasm for preven-
tive medicine among both health professionals and the cal aspects of Paleolithic life experience. While they
undergoage-relatedbodilydeterioration asdoWestern-general public. Instead, our view of prevention is jaun-
diced: Health conscious Americans ers—albeit, in some respects (vision [18], hearing [19]),
more slowly—their overall health pattern is quite dif-
. . . increasingly find themselves beset with contradictory advice.
ferent. With the exception of osteoarthritis, they rarely
No sooner do they learn the results of one research study than
develop “chronic degenerative diseases” [20–22]. Bio-
they hear of one with the opposite message. N Engl J Med
markers of incipient illness such as rising blood pres-
1994;331:189–90
sure [23], increasing adiposity [24], deficient lean body
The news about health risks comes thick and fast these days
and it seems almost constitutionally contradictory. Science
mass [25], hypercholesterolemia [15,26], nonocclusive
1995;269:164–9
atheromata [27], and insulin resistance [28–32] are
Advice to the public about what to eat . .. and basically how
quite infrequent among foragers and other traditional
to live, seems to do an about-face every time a new study is
peoplescomparedwiththeirprevalenceinsimilar-aged
published in a medical journal. New York Times 1998 Mar
22:WK 4
Western populations. These observations suggest that
many chronic degenerative disorders are not unavoid-
Respected opinion-shapers are not alone in recogniz- able concomitants of aging, but conditions that develop
inghealthpromotiondisarray;ordinarymoviegoers ap- frequently when behavioral and environmental circum-
plaud with ironic appreciation when Woody Allen stances differ from those under which our ancestors
awakes, in Sleeper, to find that beefsteak has become evolved.
a health food. Part of the problem with prevention is Cardinal goals of evolution-based prevention, then,
media-fostered misunderstanding of the epidemiologi- are to (1) characterize differences between patterns of
cal research process, but much results, we suggest, be- life in ancient and modern environments, (2) identify
cause there is no overall conceptual framework for this which of these are involved in the initiation and pro-
field. Here we consider whether evolutionary, or Dar- gression of specific diseases, (3) use this information to
winian, medicine [9,10] may provide a solid foundation design innovativestudiesof the“proximate”pathophys-
for health promotion research and eventually for public iology, and (4) integrate epidemiological, mechanistic,
recommendations. The central premises are straight- and genetic data with evolutionary principles to create
forward: (1) Our gene pool was shaped by natural selec- an overarching “ultimate” [33] formulation upon which
tion for optimal function in past environments far dif- to base persuasive, consistent, and effective public rec-
ferent from the ones in which we now live [11,12]. (2) ommendations.
There have been some genetic changes since the begin-
nings of agriculture, but natural selection is slow so
THE HUMAN EVOLUTIONARY PAST
most of our genome remains adapted for ancestral con-
ditions.(3)The resultingmismatchbetween ourancient Our genome is a temporal collage. Most of its compo-
bodies and the circumstances of modern life in affluent nents are far older than our genus, while some have
Western nations fosters development of chronic degen- changed recently, even since the latest Ice Age [11,12].
erative diseases. If correct, these theses should provide However, many of the characteristics that make us
a parsimonious, plausible basis for health promotion. unique among primates (brain size, maturation sched-
ule, daily foraging range, limb proportions, relative gut
segmentlength,speech,etc.) reflectgeneticchangedur-
EVOLUTIONARY FOUNDATIONS FOR PREVENTION
ing the 2 million years since emergence of the first
Homo species [34,35]. Evolution can be “rapid” [36,37],
especially for traits affecting survival in early life, butSince 1800, life expectancyhas doubled in industrial-
ized nations,partly fromimprovements in medicalcare, overall rates of change are constrained by the complex-
ity of the systems involved [38,39]. Disorders deter-but more from public health measures and general eco-
nomic prosperity [13]. Over this period, the nature of mined by single-gene mutations (e.g., hemoglobinopa-
thies protective against malaria) are often used todisease has changed. As prime causes of mortality, in-
fectious illnesses have been superseded by the degener- illustrate the potential rapidity of natural selection,
but they are imperfect models for chronic degenerativeative diseases now endemic in Western societies. While
longevityplaysarole,aDarwinianperspectivesuggests diseases, whose clinical manifestations chiefly affect
older individuals (i.e., at ages heretofore uncommonlythat such conditions are not the inevitable consequence

EVOLUNTIONARY HEALTH PROMOTION
111
attained) and whose pathophysiology involves tens to Physical Exertion
hundreds of genes [40]. Through nearly all human evolution physical exer-
Some human genetic alteration since the appearance tion and food procurement have been inextricably
of agriculture reflects the effects of pathogens. To the linked. Hierarchical social stratification uncoupled this
extent that microorganisms influence chronic disease relationship for elites; industrialization and mechani-
etiology, such changes may have altered the natural zation have completed the dissociation for practically
history of disorders until recently considered “noninfec- everyone. Prior to the industrial era humans are esti-
tious” (see below). Otherwise, however, evolution since mated to have expended a total of about 3000 kcal (12
the last Ice Age is unlikely to have systematically af- MJ) daily [57]; for current affluent populations compa-
fected the gene pool in ways that could alter genetic rable estimates are 2000 kcal (8 MJ) or less [58]. This
susceptibility to cancer, atherosclerosis, osteoporosis, changehasresultedfrom decreasedenergyexpenditure
and like illnesses. As it relates to such conditions, our through physical exertion: about 20 kcal/kg/day (84 kJ)
genome remains largely adapted for Paleolithic exis- for hunter–gatherers versus ⬍5 kcal/kg/day (21 kJ) for
tence [41,42]. While there was no one specific past envi- sedentary Westerners—a fourfold differential [59].
ronment that can be considered uniquely “natural” for Exercise has important effects on aerobic power [22],
humankind [12], an appreciation of what late Stone muscularstrength[22], andskeletalrobusticity[60,61],
Agelifegenerallyentailed should nonetheless behighly all of which were substantially greater for ancestral
useful in our attempts to explicate environmental fac- populations.Exerciselikelyaffectsthe incidence of age-
torsinfluencingchronic degenerativediseaseincidence. related fractures [62], some cancers [63], and athero-
Nutrition sclerosis [63]. Obligatory exertion promoted greater
lean body mass while attenuating adipose tissue,
There is surprisingly little overlap between current thereby reducing type 2 diabetes risk for our ances-
foods and those of the Paleolithic [43]. We get most of tors [64].
our calories from grains, domesticated livestock, dairy
products, and refined sugars, but preagricultural hu-
mans ate naturally occurring plant foods and wild Reproduction
game. They used almost no cereal grains and had no
dairy foods, no separated oils, no commercial proc- Studies of women in foraging [65] and other tradi-
tional settings [66] suggest substantial differences be-essing, and no sources of “empty calories.” People in
the Stone Age consumed more animal protein than do tween patterns of ancestral and modern reproduction
[65–67]. For preindustrial women menarche was latercurrent Westerners [43]. The proportion of total fat in
Paleolithic diets varied considerably, chiefly with lati- (16 vs 12.5 years) and first birth earlier (⬃19 years) so
that the nubility (menarche to first birth) interval wastude; however, intake of serum-cholesterol-raising fat
was nearly always far less than at present, and there only 3 years, versus about 12 years for average Ameri-
cans and Europeans. Foragers who lived through theirwas more dietary long-chain (C20 and above) polyun-
saturated fatty acid (LCPUFA) [44,45].The preagricul- full reproductive span had high parity: typically 6 live
births vs 1.8 for Americans. Nursing was obligatory,tural essential fatty acid ratio (
␻
-6:
␻
-3) approached
unity [44]; for average Americans it approximates 15:1 intensive (on demand, not on schedule), and commonly
lasted 3 years. Only about 50% of American babies are[45A]. Dietary cholesterol content roughly equaled cur-
rent U.S. levels [45]. Carbohydrate consumption also nursed at all and mean nursing duration is barely 3
months [64]. Age at menopause ishard to ascertain forvaried with latitude, but in all cases came chiefly from
fruits and vegetables, not from cereals, refined sugars, forager women, but menses apparently ceased some-
what earlier than in affluent societies.and dairy products [43]. Compared with the typical
American pattern, Paleolithic diets generally provided New reproductive patterns and the associated ovula-
tory differential (three times as many ovulations forless sodium but more potassium, fiber (soluble and in-
soluble), micronutrients, and, probably, phytochemi- Westerners not using oral contraceptives) [65,66] are
associated with increased risk for cancers of the breastcals [43].
These differences are pertinent to several areas of [68], endometrium, and ovary [65]. For example, imma-
ture breast lobules form at puberty; their rapidly divid-current nutrition-related research, e.g., ␻-3 fatty acids
and depression [46–48];
␻
-6:
␻
-3 ratios and coronary ing cells are relatively susceptible to natural mutation,
genotoxic carcinogens, and clonal promotion (but seeheart disease [49,50]; fruits, vegetables, and phyto-
chemicals as cancer preventive agents [51,52]; optimal [69]). At firstfull-termpregnancymostlobules differen-
tiate into mature forms whose cells divide more slowlyvs minimalrequirements ofvitamins andminerals[53];
dietary sodium, hypertension, and overall mortality and are hence more resistant. Prolonged nubility thus
extends a period of high susceptibility to carcinogene-[54,55]; and the appropriate contribution of fats to di-
etary energy [56]. sis [65,70,71].

112
EATON ET AL.
Infection marginal environments, but average height for Paleo-
lithichumansappearsto haveequaledoreven exceeded
Relationships between humans and microbes were that at present [85,86]. Nevertheless, maturation may
altered by the rise of agriculture. Higher population have been slower, as it is for athletic young women
density, frequent long-distance contacts, settled living, in Western nations [87,88]. Traditional North African
and interactions with domesticated animals vastly in- pastoralists—who have sufficient dietary protein, lim-
creasedpathogentransmission[72]. As aresult,certain ited fat intake, little access to empty calories, and high
infectionsassumedgreater importance,becomingselec- levelsof physical exertion—may simulate the ancestral
tive forces that have subsequently affected the human standard. They experience later puberty and slower
genome (e.g., malaria [73], typhoid fever [74]). More growth in height than do Westerners, attaining full
recently, improved sanitation has reduced transmis- stature only in their early 20s; still, their average adult
sion, a pivotal contribution to the past 2 centuries’ in- height equals that of Europeans [89,90].
creaseinaveragelife expectancy [13]. Discoveryofanti- Rapid growth is usually interpreted asa sign of soci-
biotics had dramatic impact, but intensive usage, etal health, but maximal is not necessarily optimal.
including incorporation into animal feeds, has led to The current experience of puberty 3 years earlier than
emergence of resistant organisms. Consequently, “pre- the hunter–gatherer average may resultindissociation
ventive” anti-infective chemotherapy must now aim at betweenpsychologicaland sexualmaturation,thus con-
minimizing resistance as well as attaining clinical effi- tributing to unwanted teenage pregnancies [91]. Both
cacy. Tothisend, mathematicalmodelsintegratingclas- early menarche [92] and youthful attainment of adult
sic pharmacological approaches with the principles of stature [93]areassociatedwithincreasedbreast cancer
evolutionary biology may help optimize treatment pro- risk.Rapidbodilygrowth may alsoaffectblood pressure
tocols given inherent conflict between the “within host” regulation if renal development is unable to keep pace
and overall epidemiological contexts [75]. Attempts to allometrically, thus requiringcompensatory blood pres-
reduce pathogen virulence may also benefit from Dar- sure elevation to maintain homeostasis and possibly
winian considerations. For example, vaccines directed establishing a pathophysiological trajectory toward
against virulence-enhancing microbial antigens might subsequent hypertension [17]. And, in laboratory ani-
disproportionately affect dangerous strains and pro- mals at least, slower growth during adolescence and
mote their displacement by milder variants [76,77]. early adulthood is associated with increased longev-
While adequate food, public health measures, and ity—apparently independent of any effect on chronic
medical interventions have lowered infectious disease disease susceptibility [94].
mortality during the past century, the megapolitan Psychosocial Factors
crowding and unparalleled mobility in current affluent
nations have probably increased transmission of cer- Genes affecting human behavior are ancient and
tain organisms, especially those spread by sexual and probably coevolved with our life history characteristics.
respiratory contact. This phenomenon could affect For example, prolongation of childhood during hominid
chronic disease prevalence: there are well-established evolution may have facilitated learning and correlated
relationships between viral infections and certain can- with brain expansion occurring over the same period
cers [78,79] as well as intriguing hints of a causal link [95,96]. But, like current sedentism and diet, the social
between microbes and atherosclerosis [80–82]. Epide- circumstances of contemporary existence are novel
miological correlation between infectious exposure [64,97]. Many factors believed to exert important influ-
ratesandincidence ofchronic“noninfectious” degenera- ence on psychological development and interpersonal
tive diseases might ultimately open new avenues for relations are profoundly different from what they are
preventive intervention via evolution-based antibiotic thought to have been during our evolutionary past. Av-
prophylaxis and/or vaccine development. erage birth spacing is now closer, while nursing and
physical contact between infants and adults is much
reduced. In most affluent societies, babies do not sleep
Growth and Development with their mothers—a break from general primate ex-
periencedatingback manymillionsof years[98].Ances-In Western nations, less frequent and severe child-
hood infection, sharply reduced exercise requirements, tral childhood and adolescence were almost certainly
characterized by multiage play groups, less restrictiveand unprecedented caloric availability result in rapid
bodily growth and early sexual maturation. Average supervision, and intense small group interpersonal dy-
namics quite different from the age-segregated, moreadult height is asymptotically approaching amaximum
[83] while age at menarche has fallen to about 12.5 structured routines of contemporary schools and little
leagues. Based on what we know about hunter–years [84], probably near the population’s genetic limit.
Most recent hunter–gatherers have been short-stat- gatherers, Paleolithic teenagers had relativelyclearso-
cietalexpectations,nottheexciting-but-dauntingarrayured, reflecting the nutritional stress of foraging in

EVOLUNTIONARY HEALTH PROMOTION
113
of life choices that confronts young people today. For which cultural changescausespecificdiseases:thegen-
eral hypothesis that our genes and lifestyles have be-adults, a global society has advantages, but it differs
radically from the more human-scale experience of our come discordant can lead to “euphenic” [17,101] health
recommendations only after detailed scientific evalua-ancestors who lived, found their roles, and developed
self-esteem in bands of 15–50 people, most of whom tion. To this end, evolutionary insight must generate
falsifiable predictions amenable to well-designed mech-were relatives [98A]. We have little concrete evidence,
but it seems likely that these differences and others— anistic and epidemiological investigation.
frequentcontactwithstrangers,conflictingsocialroles,
wage labor, working in bureaucracies, reduced support Pregnancy and Birth Weight
from kin, and education that questions social beliefs There is persuasive [102,103], albeit not universally
and ideologies—may contribute to syndromes such as accepted [104], evidence linking low birth weight with
attention deficit/hyperactivity, depression, anxiety dis- adult susceptibility to Syndrome X conditions (insulin
orders, and substance abuse [99,100]. resistance, type 2 diabetes, obesity, hypertension, coro-
nary heart disease, etc.). The responsible mechanisms
HUMAN PREFERENCES AND PREVENTION
could be complex and may involve trade-offs, but an
evolutionary perspective suggests that optimal gesta-
As every physician knows, providing accurate health tional circumstances will resemble those of our ances-
advice is less than half the battle; at least as important tors. Limited maternal intake of simple carbohydrate
is achieving patient compliance. Providing an explana- in the first trimester and substantial third-trimester
tion for health promotion based on a coherent theory animalproteinmay bebeneficial[105], asmaygenerous
of how disease arises from the mismatch between our intake of folate [106], zinc [107], and LCPUFA, espe-
original design and our current circumstances should cially docosahexaenoic acid [DHA (C22:6, ␻-3)] [43,
help. Perhaps equally valuable, however, will be under- 108–110]. Such prenatal nutrition is consistent with
standing why we so often prefer what is harmful to our the typical pregnancy experience of women in ancestral
health. Much public resentment about health promo- conditions [43,44].
tion comes because physicians’ recommendations are
perceived as moralistic prohibitions, which deny people Breast Cancer
basic pleasures. Unfortunately, there is a grain of truth
in this—health advice often counters “natural” inclina- Mathematical modeling suggests that if American
tions. Humans like foods high in fat, salt, and sugar women’s reproductive experiences could somehow be
and they regularly avoid exercise. The explanations for made to resemble those of women prior to the demo-
these tendencies also lie in our evolutionary heritage. graphictransition,breast cancerincidencecould below-
Polyunsaturated fatty acids and sodium are required ered—perhaps by an order of magnitude [65,71,111].
nutrients, but on the African savanna they were some- Societal and demographic constraints preclude reinsti-
times in short supply, so taste preferences for them tution of the actual preindustrial pattern, but interven-
were advantageous; there was active selection against tional endocrinology [65,112–114] (viz. menarcheal de-
wasting calories on unproductive exercise. These and lay, early pseudopregnancy, and oral contraception that
similar insights are not magic bullets, but at least they reduces average serum estrogen levels) could simulate
explain why we have innate propensities which, in to- the ancestral hormonal milieu. This approach may
day’s circumstances, tend to promote disease and why seem intrusively artificial, as did oral contraception in
health practices that forestall chronic illness are actu- 1960, but primate testing and eventual clinical trials
ally in accord with ancestral experience. could expand currently limited preventive options for
high-risk individuals.
A RESEARCH AGENDA
Neurological Development
In order to provide an evolutionary foundation for
preventive recommendations, the most pressing re- Bottle feeding infants, a manifestly unnatural inno-
vation, may adversely affect intelligence. Nursing issearch need is to identify, contact, interview, and exam-
ine remaining hunter–gatherers and other traditional associated with higher cognitive scores and improved
scholasticperformanceamongchildren[115]. This rela-peoples throughout the world. Few such groups still
live in their original settings, but the information they tionship probably reflects multiple factors, but nutri-
tional input is a likely contributor [108,109,115,116].can provide about relevant living patterns is an irre-
placeable and rapidly vanishing resource. This compar- In evolutionary perspective, breast milk composition
represents a compromise between infant needs for nu-atively inexpensive undertaking might return dispro-
portionately valuable health benefits. Of similar trition and maternal needs to conserve resources for
future reproduction [117]. This competition becomesimportance is the need to discover mechanisms by

114
EATON ET AL.
less critical when essential constituents are relatively Also, several studies have shownaninverseassociation
between hemorrhagic stroke and TC [122]. Notwith-abundant in the maternal diet [118]. Over 90% of all
LCPUFA in mammalian brain gray matter is composed standing, an evolutionary perspective suggests that op-
timal human TC is below 150 mg/dl, a value exceedingof arachidonic acid [AA (C20:4,
␻
-6)], docosatetraenoic
acid [DTA (C22:4,
␻
-6)], and DHA—nutrients found the mean for free-living nonhumanprimates[109mg/dl
(2.8 mmol/L)],hunter–gatherers [123 mg/dl (3.2mmol/exclusively in foods of animal origin and not in plants.
From a largely vegetarian primate baseline, dietary L)], and other traditional peoples [134 mg/dl (3.5 mmol/
L)] [15,45]. However, the dietsof modernWestern indi-intake of these nutrients increased fivefold as hunting
and/or scavenging assumed prominence during human viduals whose TC falls below 150 mg/dl are different
from those of hunter–gatherers with comparable val-evolution—coincidentwitha threefoldexpansionofcra-
nial capacity [44]. Brain enlargement in the hominid ues—paleolithic humans almost certainly consumed
more animal protein, more dietary cholesterol, andline was probably driven by social complexity [119];
however, increasing availability of AA, DTA, and DHA more LCPUFA (with a more balanced ␻-6:␻-3 fatty acid
ratio). Furthermore, hypertension is almost nonexis-may have been a contributing factor. While humans
can synthesize these three LCPUFAs from 18 carbon tent among hunter–gatherers, whereas the linkage be-
tween “low” TC and hemorrhagic stroke is largely re-precursors available in plant foods, the process appears
too slow to supply amounts needed for optimal brain stricted to hypertensive individuals [122]. The
relationship of these factors to the putative adversegrowth during fetal development and infancy [44,109].
For now, the evidence justifies studying possible bene- effects of “low” TC in affluent nations bears investiga-
tion.fits of AA and DHA supplementation in maternal diets
and infant formulas.
DARWIN’S RAZOR
Type 2 Diabetes Evolutionary insights provide an independent per-
The relationship between obesity and insulin resist- spective when conventional biomedical investigations
anceiswellrecognized, but evolutionaryconsiderations yield inconclusive or contradictory results. For exam-
suggest that relative skeletal muscle deficiency may ple, dietary sodium has been a major focus of hyperten-
also be important. Contemporary Westerners are dis- sion research, but epidemiological studies regarding
tinguished from ancestral humans by sarcopenia [25]salt intake, blood pressure, and overall mortality have
anddecreasedphysical fitness[15,25,59]aswell ashyp- aroused fierce disagreement [123]. Theodosius Dobz-
eradiposity. Thesealteredfactorsdistort the physiologi- hanskycontendedthat“Nothing inbiologymakessense
cal milieu for insulin action compared with circum- except in thelightofevolution”[124].Can an evolution-
stances existing when the relevant genetic selection ary perspective shed light on this dispute?
occurred. An evolution-based prediction is that func- Contemporary humans are the only free-living pri-
tional insulin resistance, in its earliest stages, is di- mates who habitually consume more sodium than po-
rectly proportional to fat mass, but inversely propor- tassium, the only ones to obtain sodium over and above
tional to the mass and metabolic activity of skeletal that intrinsic to naturally occurring foods, and also the
muscle. This relationship might reflect competition be- only ones to commonly develop hypertension [55].Daily
tween the insulin receptors of myocytes and those of sodium intake for ancestral humans is estimated to
adipocytes for available insulin molecules. The initial have been less than 1000 mg/day (17 mEq) [43] and
effect would be repetitive episodes of transient hyper- data from the Intersalt Study [125] suggest a threshold
glycemia and hyperinsulinemia. In genetically suscep- blood pressureeffectjustabovethislevel [126]. Ecologi-
tible individuals further metabolic deterioration could cal surveyshaveidentified numerous normotensivetra-
resultfromsecondarydown-regulationofinsulinrecep- ditional populations who, like Paleolithic humans,
tors, glucose transporters, and intracellular enzymatic lacked access to commercial salt [15,23]. However, such
sequences, leading ultimately to glucose intolerance groups differed from Westerners in many ways so that
and type 2 diabetes [64]. variables in addition to salt may have affected blood
pressure differences. Observations of acculturating so-
Serum Cholesterol cieties [127–130] (and chimpanzees [131]) with graded
salt availability suggest that sodium is a necessary, butAccording to The National Cholesterol Education
Project, serum cholesterol levels (TC) below 200 mg/ not sufficient, factor in hypertension pathophysiology.
Epidemiological analyses of sodium–blood pressure re-dl (5.2 mmol/L) are “desirable,” yet many myocardial
infarctions occur in persons with TC between 150 (3.9 lationships may be frustrated because almost all con-
temporary humans consume far more sodium thanmmol/L) and 200 mg/dl. When TC is below 150 mg/dl
clinical coronary artery disease is rare, but aggressive their ancestors, well above the hypertension threshold
indicated by Intersalt data. In this range sodium maybehavior and depression are more common [120,121].

EVOLUNTIONARY HEALTH PROMOTION
115
exhibit a permissive rather than a direct relationship illnesses, but chronic degenerative disease incidence
has been little affected [134]. For example, mammogra-to hypertension so even themost amibitious meta-anal-
ysis has difficulty distinguishing the evolutionary phy, chemotherapy, radiation therapy, and breast-con-
serving surgery have improved breast cancer survivor-theme amid other epidemiological factors. These addi-
tional influences—obesity, insulin resistance, poor ship, but increasing incidence leaves age-adjusted
mortality from this malignancy near its 1930 level [1].physical fitness, over-rapid growth, alcohol, and defi-
ciencies of potassium, calcium, fruits, and vegetables— We can hope that future tertiary prevention, such as
gene therapy, will be more efficacious, but dauntingall reflect environmental and behavioral differences
that have appeared or intensified since the rise of agri- ethical, economic, and technical obstacles may be diffi-
cult to overcome [135–137].culture.
[15,22,28–32,,13]
An evolution-based prediction, consistent with prior Prevention research based on attempts to isolate and
identify individual causal factors has contributed muchinvestigative findings, is that individuals who habitu-
ally consume a nutritionally adequate diet providing to our knowledge, but reductionism encounters prob-
lems when addressing multifactorial degenerative ill-less than 1000 mg sodium per day will be free from
essential hypertension. Above this intake level the nesses, the salt–hypertension controversy being a case
inpoint.Furthermore,epidemiological studies ofAmer-prevalence of high blood pressure will be more closely
related to the other influences noted above than to so- ican nurses, traditional Mediterraneans, and the East
Asians of 1960 may be limited because such groupsdium intake per se. lack optimal controls: the lifestyles of nearly all their
members differ dramatically from those of our ances-
GENES AND VARIATION
tors. Valuable data can be derived from investigating
Future research will gradually sort out the contribu- health differences within and between contemporary
tions of inheritance, environment, and behavior in populations, but we suggest that some of the most po-
chronic disease pathophysiology, but evolutionary con- tentially rewarding research involves contrasts be-
siderations argue against blanket categorization of the tween present and previous humans. Evidence arising
genes involved as “defective.” Alleles, which may have from analyzing the biomedical implications of these dif-
been neutral or beneficial in ancestral environments, ferences should allow physicians to offer increasingly
can now promote disease because they interact with validpreventiveadviceand also tocommunicaterecom-
novel modern conditions. Recent foragers—the best mendations more coherently and consistently because
available, if inexact, surrogates for preagricultural hu- of their solid theoretical foundation. “Evolution is now
mans—havebeenlargelyfree fromatherosclerosis,dia- widely recognized as the organizing principle at all lev-
betes, and hypertension, implying that the underlying els of life” [138]. The authors maintain that evolution-
genetic factors probably had little adverse effect during ary principles can provide health promotion with a con-
thePaleolithic.Thishighlightsthefundamentalprinci- sistent, persuasive logic, which may, in turn, advance
ple, still widely misunderstood, that all phenotypes are realization of its full potential.
formed by the interactions of a genotype with the envi-
REFERENCES
ronment and likewise, that degenerative diseases arise
from one degree or another of genetic predisposition
1. Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics,
interacting with operative circumstances. Through
1998. CA Cancer J Clin 1998;48:6–29.
nearly all human evolution genetic adaptation was
2. Bailar JC, Gornik HL. Cancer undefeated. N Engl J Med
1997;336:1569–74.
closely coupled with environmental alterations. Now,
3. American Diabetes Association. Diabetes 1996 vital statistics.
however, cultural change comes too rapidly for genetic
Alexandria (VA): Am Diabetes Assoc 1996:14–5.
accommodation to keep pace [132,133]. We still carry
4. Levy RL, Bruenn HG, Kurtz D. Facts on disease of the coronary
genes that were selected for their utility in the past,
arteries based on a survey of the clinical and pathological re-
but that in the novel circumstances of contemporary
cords of 762 cases. Am J Med Sci 1934;187:376–90.
life confer increased susceptibility to chronic illnesses.
5. White PD. The historical background of angina pectoris. Med
Labeling such alleles “defects” implies an underlying
Concepts Cardiovasc Dis 1974; 43:109–12.
misinterpretation of the body as a designed machine,
6. Hunink MGM, Goldman L, Tosteson ANA, et al. The recent
instead of an organism assembled by whatever genes
decline in mortality from coronary heart disease, 1980–1990.
The effect of secular trends in risk factors and treatment.
best get copies of themselves into future generations.
JAMA 1997;277:535–42.
7. Fries JF, Koop CE, Beadle CE, et al. Reducing health care costs
CONCLUSION by reducing the need and demand for medical services. N Engl
J Med 1993;329:321–5.
The 20th century’s extraordinary medical advances
8. Yen LT, Edington DW, Witting P. Associations between health
eliminated previous scourges such as polio and small-
risk appraisal scores and employee medical claims costs in a
manufacturing company. Am J Health Promot 1991;6:46–54.
pox and have ameliorated the effects of many other

116
EATON ET AL.
9. Stearns SC, editor. Evolution in health and disease. Oxford: 32. Lindeberg S, Eliasson M, Lindahl B, Ahren B. Low serum insu-
lin in traditional Pacific Islanders—the Kitava study. Metabo-Oxford Univ. Press, 1999. lism 1999; 48:1216–9.
10. Trevathan WR, Smith EO, McKenna JJ, editors. Evolutionary 33. Mayr E. Cause and effect in biology. Science 1961;134:1501–6.
medicine. Oxford: Oxford Univ. Press, 1999. 34. RuffCB, Trinkhaus E,Holliday TW.Body massandencephaliza-
11. Strassmann BI,DunbarR. Stoneage legaciesand modernmedi- tion in Pleistocene Homo. Nature 1997;387:173–6.
cine. In: Stearns SC, editor. Evolution in health and disease.
Oxford: Oxford Univ. Press, 1999:91–101. 35. Wood B, Collaid M. The human genus. Science 1999;284:65–71.
12. Irons W. Adaptively relevant environments versus the environ- 36. Carroll RL. Rates of evolution. In: Carroll RL. Patterns and
ment of evolutionary adaptedness. Evol Anthropol 1998;6: processes of vertebrate evolution. Cambridge (UK): Cambridge
194–204. Univ. Press, 1997:72–80.
37. WilliamsGC.Natural selection:domains,levels,and challenges.
13. McKeown T. A basis for health strategies. A classification of New York: Oxford Univ. Press, 1992:127–36.
disease. Br Med J 1983;287:594–6. 38. Waxman D, Peck JR. Pleiotropyand the preservation of perfec-
14. Neel JV. Medicine’s genetic horizons. Ann Intern Med 1958; tion. Science 1998;279:1210–3.
49:472–6. 39. Wagner G. Complexity matters. Science 1998;279:1158–9.
15. Eaton SB, Konner M, Shostak M. Stone agers in the fast lane:
chronic degenerative diseases in evolutionary perspective. Am 40. Sing CF, Haviland MB, Reilly SL. Genetic architecture of com-
J Med 1988;84:739–49. monmultifactorial diseases.In: ChadwickD, CardewG, editors.
Variation in the human genome (Ciba Foundation Symposium
16. Williams GC, Nesse RM. The dawn of Darwinian medicine. Q 197). Chichester: Wiley, 1996:211–32.
Rev Biol 1991;66:1–21. 41. Tattersall I. Becoming human. Evolution and human unique-
17. Neel JV, Weder AB, Julius S. Type II diabetes, essential hyper- ness. New York: Harcourt Brace, 1998:239.
tension, and obesity as “syndromes of impaired genetic homeo- 42. Johanson D. Reading the minds of fossils. Sci Am 1998;278:
stasis”: the “thrifty genotype” hypothesis enters the 21st cen- 102–3.
tury. Perspect Biol Med 1998;42:44–74. 43. Eaton SB, Eaton SB III, Konner MJ. Paleolithic nutrition revis-
18. Salanzo FM, Neel JV. New data on the vision of South American ited: a twelve-year retrospective on its nature and implications.
Indians. Bull Pan Am Health Organ 1976;10:1–8. Eur J Clin Nutr 1997;51:207–16.
19. Rosen S, Bergman M, Plester D, El-Mofty A, Satti MH. Presby- 44. Eaton SB, Eaton SB III, Sinclair AJ, Cordain L, Mann NJ.
cusis study of a relatively noise-free population in the Sudan. Dietary intake of long-chain polyunsaturated fatty acids during
Ann Otol 1962;71:727–43. the Paleolithic. World Rev Nutr Diet 1998;83:12–23.
20. Trowell HC, Burkett DP, editors. Western diseases: their emer- 45. Eaton SB. Humans, lipids and evolution. Lipids 1992;27:
gence and prevention. Cambridge (MA): Harvard Univ. Press, 814–21.
1981:xiii–xvi. 45A. SimopoulosAP.Evolutionaryaspects ofdiet andessentialfatty
21. Lindeberg S, Lundh B. Apparent absence of stroke and ischae- acids. World Rev Nutr Diet 2001;88:18–27.
mic heart disease in a traditional Melanesian population: a 46. Adams PB, Lawson S, Sanigorski A, Sinclair AJ. Arachidonic
clinical study in Kitava. J Intern Med 1993;233:269–75. to eicosapentaenoic acid ratio in blood correlates positively with
22. Shephard RJ, Rode A. The health consequences of moderniza- clinical symptoms of depression. Lipids 1996;31:S167–76.
tion:evidencefrom circumpolarpeoples. Cambridge(UK): Cam- 47. Hibbeln JR, Umhau JC, George DT, Salem N Jr. Do plasma
bridge Univ. Press, 1996:101–8. polyunsaturates predict hostility and depression? World Rev
23. Blackburn H, Poineas R. Diet and hypertension: anthropology, Nutr Diet 1997;82:175–86.
epidemiology, and public health implications. Prog Biochem 48. StollAL, SeverusWE, FreemanMP,et al.Omega 3fatty acidsin
Pharmacol 1983;19:31–79. bipolar disorder. A preliminary double-blind, placebo-controlled
24. Glanville EV, Geerdink RA. Skinfold thickness, body measure- trial. Arch Gen Psychol 1999;56:407–12.
ments and age changes in Trio and Wajana Indians of Surinam. 49. Lands WE, Libelt B, Morris A, et al. Maintenance of lower
Am J Physiol Anthropol 1970;32:455–62. proportion of (n-6) eicosanoid precursors in phospholipids of
25. Rode A, Shephard RJ. The physiological consequences of accul- human plasma in response to added dietary (n-3) fatty acids.
turation: a 20-year study in an Inuit community. Eur J Appl Biochem Biophys Acta 1992;1180:147–62.
Physiol 1994;69:16–24. 50. Kang JX, Leaf A. Antiarrhythmic effects of polyunsaturated
26. Lindeberg S, Nilsson-Ehle P, Tere
´nt A, Vessby B, Schersten B. fatty acids. Circulation 1996;94:1774–80.
Cardiovascular risk factors in a Melanesian population appar- 51. Block G, Patterson B, Subar A. Fruit, vegetables, and cancer
ently free from stroke and ischaemic heart disease: the Kitava prevention: a review of the epidemiological evidence. Cancer
study. J Intern Med 1994;236:331–40. 1992;18:1–29.
27. Vint FW. Post-mortem findings in the natives of Kenya. East 52. World Cancer Research Fund, American Institute for Cancer
African Med J 1937;13:332–40. Research. Food, nutrition, and the prevention of cancer: a global
28. JoffeBI, JacksonWPU, ThomasME,etal.Metabolicresponseto perspective. Washington: Am. Inst. Cancer Res., 1997:506–7.
oral glucose in the Kalahari bushmen. Br Med J 1971;4:206–8. 53. Levine M, Dhariwal KD, Welch RW, Wang Y, Park JB. Determi-
29. Merimee TJ, Rimoin DL, Cavalli-Sforza LL. Metabolic studies nation of optimal vitamin C requirements in humans. Am J
in the African pygmy. J Clin Invest 1972;51:395–401. Clin Nutr 1995;62(Suppl):1347S–56S.
30. Kuroshima A, Itoh S, Azuma T, Agishi Y. Glucose tolerance test 54. Alderman MH, Cohen H, Madhavan S. Dietary sodium intake
in the Ainu. Int J Biometerol 1972;16:193–7. and mortality: the national health and nutrition examination
survey (NHANES1). Lancet 1998;351:781–5.
31. Spielmann RS, Fajans SS, Neel JV, Pek S, Floyd JC, Oliver WJ.
Glucose tolerance in two unacculturated Indian tribes of Brazil. 55. McCarron DA. Diet and blood pressure—the paradigm shift.
Science 1998;281:933–4.Diabetology 1982;23:90–3.

EVOLUNTIONARY HEALTH PROMOTION
117
56. Conner WE, Conner SL, Katan MB, Grundy SM, Willett WC. 78. Zur Hausen H. Viruses in human cancers. Science 1991;
254:1167–73.Should a low-fat, high-carbohydrate diet be recommended for
everyone? N Engl J Med 1997;337:562–7. 79. Parsonnet J, editor. Microbes and malignancy. Infection as a
cause of human cancers. New York: Oxford Univ. Press, 1999.
57. A
˚strand P-O. Whole body metabolism. In: Horton ES, Terjung
RL, editors. Exercise, nutrition and energy metabolism. New 80. LibbyP,EganD,Skarlatos S.Role ofinfectious agentsin athero-
York: Macmillan, 1988:1–8. sclerosis and restenosis. An assessment of the evidence and
need for future research. Circulation 1997;96:4095–103.
58. National Research Council. Diet and health. Implications for
reducing chronic disease risk. Washington: National Academy 81. Danesh J, Collins R, Peto R. Chronic infections and coronary
Press, 1989:140, 142. heart disease: is there a link? Lancet 1997;350:430–6.
59. Cordain L, Gotshall RW, Eaton SB, Eaton SB III. Physical activ- 82. Meier CR, Derby LE, Jick SS, Vasilakis C, Jick H. Antibiotics
ity, energyexpenditure andfitness:anevolutionaryperspective. and risk of subsequent first-time acute myocardial infarction.
Int J Sports Med 1998;19:1–8. JAMA 1999;281:427–31.
60. Ruff CB, Trinkaus E, Walker A, Larsen CS. Postcranial robusti- 83. Van Wieringen JC. Secular growth changes. In: Falkner F, Tan-
city in Homo. I. Temporal trends and mechanical interpreta- ner JM, editors. Human growth. A comprehensive treatise. Vol.
tions. Am J Phys Anthropol 1993;91:21–53. 3. Methodology. Ecological, genetic, and nutritional effects on
growth. 2nd ed. New York: Plenum, 1986:307–31.
61. Larsen CS. Bioarchaeology. Interpreting behavior from the hu-
man skeleton. Cambridge (UK): Cambridge Univ. Press, 84. Dann TC, Roberts DF. End of a trend? A 12-year study of age
1997:225. at menarche. Br Med J 1973;2:265–7.
62. Cooper C, Barker DJP. Risk factors for hip fracture. N Engl J 85. Angel JL. Health as a crucial factor in changes from hunting
Med 1995;332:814–5. to developed farming in the Eastern Mediterranean. In: Cohen
MN, Armelagos GJ, editors. Paleopathology at the origins of
63. U.S.Department ofHealth andHuman Services.Physical activ- agriculture. New York: Academic Press, 1984:51–74.
ity and health: a report of the Surgeon General. Atlanta (GA):
U.S. Department of Health and Human Services, Centers Dis- 86. Walker A. Perspectives on the Nariokotome discovery. In:
ease Control and Prevention, 1996:85–172. Walker A, Leakey R, editors. The Nariokotome Homo erectus
skeleton. Cambridge (MA): Harvard Univ. Press, 1993:411–30.
64. Eaton SB, Eaton SB III. The evolutionary context of chronic
degenerative diseases. In: Stearns SC, editor. Evolution in 87. Merzenich H, Boening H, Wahrendorf J. Dietaryfat and sports
health and disease. Oxford: Oxford Univ. Press, 1999:251–9. activity as determinants for age at menarche. Am J Epide-
miol 1993;138:217–24.
65. Eaton SB, Pike MC, Short RV, et al. Women’s reproductive can-
cers in evolutionary context. Q Rev Biol 1994;69:353–67. 88. CummingsDC, WheelerGD,Harber VJ.Physical activity,nutri-
tion, and reproduction. Ann N Y Acad Sci 1994;709:55–70.
66. Strassman BI. The biology of menstruation in Homo sapiens:
total lifetime menses, fecundity, and nonsynchrony in a natural 89. Little MA. Human biology of African pastoralists. Yearbook
fertility population. Curr Anthropol 1997;38:123–9. Phys Anthropol 1989;32:215–47.
67. Short RV. The evolution of human reproduction. Proc R Soc 90. Galvin KA. Nutritional ecology of pastoralists in dry tropical
London B 1976;195:3–24. Africa. Am J Hum Biol 1992;4:209–21.
68. Coe K, Steadman LB. The human breast and the ancestral 91. Konner MJ, Shostak MJ. Adolescent pregnancy and childbear-
reproductive cycle. Hum Nat 1995;6:197–220. ing: an anthropological perspective. In: Lancaster JB, Hamburg
BA, editors. School-age pregnancy and childbearing: biosocial
69. Farber E. Cell proliferation as a major risk factor for cancer: a dimensions. New York: Aldine, 1986:325–46.
concept of doubtful validity. Cancer Res 1995;55:3759–62. 92. Brinton LA, Schairer C, Hoover RN, Fraumeni JF. Menstrual
70. Russo J, Tay LK, Russo IM. Differentiation of the mammary factors and breast cancer. Cancer Invest 1988;6:245–54.
gland and susceptibility to carcinogenesis. Breast Cancer Res
Treat 1982;2:5–73. 93. Li CI, Malone KE, White E, Daling JR. Age when maximum
height is reached as a risk factor for breast cancer among young
71. Colditz GA, Frazier AL. Models of breast cancer show that risk U.S. women. Epidemiology 1997;8:559–65.
is set by events of early life: prevention efforts must shift focus.
Cancer Epidemiol Biomarkers Prev 1995;4:567–71. 94. Turturro A, Blank K,Murasko D, Hart R. Mechanisms of caloric
restriction affecting aging and disease. AnnNYAcadSci
72. Cohen MN. Health and the rise of civilization. New Haven (CT): 1994;719:159–70.
Yale Univ. Press, 1989:32–54. 95. Bogin B. Patterns of human growth. 2nd ed. Cambridge (UK):
73. Weatherall DJ. The genetics of common diseases: the implica- Cambridge Univ. Press, 1999:188–9.
tions of population variability. In: Chadwick D, Cardew G, edi-
tors. Variationin the human genome (CIBA Foundation Sympo- 96. Leigh SR, Park PB. Evolution of human growth prolongation.
sium 197). Chichester: Wiley, 1996:300–11. Am J Phys Anthropol 1998;107:331–50.
74. Pier GB, Grout M, Zaidi T, et al. Salmonella typhi uses CFTR 97. Hewlett BS. Demography and childcare in preindustrial socie-
to enter intestinal epithelial cells. Nature 1998:393:79–82. ties. J Anthropol Res 1991;47:1–37.
75. LevinBR, AndersonRM.The populationbiologyofanti-infective 98. McKenna J, Mosko S, Richard C. Breast feeding and mother–
chemotherapy and the evolution of drug resistance. In: Stearns infant cosleeping in relation to SIDS prevention. In: Trevathan
SC,editor.Evolution inhealth anddisease.Oxford:OxfordUniv. WR, Smith EO, McKenna JJ, editors. Evolutionary medicine.
Press, 1998:125–137. Oxford: Oxford Univ. Press, 1999:53–74.
76. Ewald PW. Evolution of infectious disease. Oxford: Oxford Univ. 98A. Konner MJ. The natural child. In: Eaton SB, Shostak M,
Press, 1994:207–12. Konner MJ, editors. The paleolithic prescription. New York:
Harper & Row, 1988:200–28.
77. Ewald PW. Using evolution as a tool for controlling infectious
diseases. In: Trevathan WR, Smith EO, McKenna JJ, editors. 99. Nesse RM. Testing evolutionary hypotheses about mental disor-
ders. In: Stearns SC, editor. Evolution in health and disease.Evolutionary medicine. New York: Oxford Univ. Press,
1999:245–69. Oxford: Oxford Univ. Press, 1999:260–6.

118
EATON ET AL.
100. Nesse R. What Darwinian medicine offers psychiatry. In: Treva- 119. Dunbar RIM. The social brain hypothesis. Evol Anthropol
1998;6:178–90.than WR, Smith EO, McKenna JJ, editors. Evolutionary medi-
cine. Oxford: Oxford Univ. Press, 1999:351–73. 120. Erickson MT. Lowered serum cholesterol, famine and aggres-
sion: a Darwinian hypothesis. Soc Sci Inform 1997;36:211–22.
101. Lederberg J. Molecular biology, eugenics, and euphenics. Na-
ture 1963;198:428–9. 121. Kaplan, JR, Klein KP, Manuck SB. Cholesterol meets Darwin:
public health and evolutionary implications of the cholesterol–
102. BarkerDJP.Fetal growthandadult disease.Br JObstet Gynae- serotonin hypothesis. Evol Anthropol 1997;6:28–37.
col 1992;99:275–6. 122. Iso H, Jacobs DR, Wentworth D, Neaton JD, Cohen J. Serum
103. Waterland RA, Garza C. Potential mechanisms of metabolic cholesterol levels and six-year mortality from stroke in 350,977
imprinting that lead to chronic disease. Am J Clin Nutr men screened for the multiple risk factor intervention trial. N
1999;69:179–97. Engl J Med 1989;320:904–10.
104. Joseph KS, Kramer MS. Review of the evidence on fetal and 123. Taubes G. The (political) science of salt. Science 1998;
early childhood antecedents of adult chronic disease. Epidemiol 281:898–907.
Rev 1996;18:158–74. 124. Dobzhansky T. Nothing in biology makes sense except in the
105. GodfreyK, RobinsonS,BarkerDJP,OsmondC,CoxV.Maternal light of evolution. Am Biol Teacher 1973;35:125–9.
nutrition in early and late pregnancy in relation to placental 125. Intersalt Cooperative Research Group. Intersalt: an interna-
and fetal growth. Br Med J 1996;312:410–3. tional study of electrolyte excretion and blood pressure. Results
106. MRC Vitamin Study Research Group. Prevention of neural tube for 24 hour urinary sodium and potassium excretion. Br Med
defects: results from the Medical Research Council Vitamin J 1988;297:319–28.
Study. Lancet 1991;338:131–7. 126. Carvallo JJM, Baruzzi RG, Howard PF, et al. Blood pressure
107. Goldenberg RL, Tamura T, Neggers Y, et al. The effect of zinc in four remote populations in the Intersalt Study. Hyperten-
supplementation on pregnancy outcome. JAMA 1995;274: sion 1989;14:238–46.
463–8. 127. Page LB, Vandevert DE, Nader K, Lubin NK, Page JR. Blood
108. Farquharson J, Cockburn F, Ainslie-Patrick W, Jamieson EC, pressure of Qash’qai pastoral nomads in Iran in relation to
LoganRW.Infantcerebral cortexphospholipid fatty-acidcompo- culture, diet, and body form. Am J Clin Nutr 1981;34:527–38.
sition and diet. Lancet 1992;340:810–3. 128. Kasteloot H, Ndam N, Sasaki S, Kowo M, Seghers V.A survey
109. WoodsJ, Ward G,Salem NJr.Is docosahexaenoicacid necessary of blood pressure distribution in Pygmy and Bantu populations
in infant formula? Evaluation of high linolinate diets in the in Cameroon. Hypertension 1996;27:108–13
neonatal rat. Pediatr Res 1996;40:687–94. 129. Hallenberg NK, Martinez G, McCullough M, et al. Aging, accul-
110. Birch EE, Hoffman DR, Uauy R, Birch DG, Prestidge C. Visual turation, salt intake and hypertension in the Kuna of Panama.
acuity and the essentiality of docosahexaenoic acid and arachi- Hypertension 1997;29:171–6.
donicacid inthe dietofterminfants.Pediatr Res1998;44:201–9. 130. Page LB, Danion A, Moellering RD. Antecedents of cardiovascu-
111. Strassman BI. Menstrual cycling and breast cancer: an evolu- lar disease in six Solomon Islands societies. Circulation
tionary perspective. J Women Health 1999;8:193–201. 1974;49:1132–46.
112. Russo IH, Korszalka M, Russo J. Comparative study of the 131. Denton D, Weisinger R, Mundy NI, et al. The effect of increased
influence of pregnancy and hormonal treatment on mammary salt intake on blood pressure of chimpanzees. Nat Med
carcinogenesis. Br J Cancer 1991;64:481–4. 1995;1:1009–16.
113. Henderson M. Current approaches to breastcancer prevention. 132. Klein RG. The human career. Human biological and cultural
Science 1993;259:630–1. origins. Chicago: Univ. Chicago Press, 1999:494, 514, 590.
114. Spicer DV, Krecker EA, Pike MC. The endocrine prevention of 133. Wilson EO. Consilience. The unity of science. New York: Knopf,
breast cancer. Cancer Invest 1995;13:495–504. 1998:171, 182.
115. Horwood LJ, Fergusson DM. Breastfeeding and later cognitive 134. Burkitt DP. The Bower science lecture. Philadelphia: Franklin
and academic outcomes. Pediatrics 1998;101:e9. Inst., 1993 Jan 15.
135. Williams GC. Pleiotropy, natural selection, and the evolution
116. Willatts P, Forsyth JS, DiModugno MK, Varma S, Colvin M. of senescence. Evolution 1957;11:398–411.
Effect of long-chain polyunsaturated fatty acids in infant for-
mula on problem solving at 10 months of age. Lancet 1998; 136. Mysterud I. Gener, atferd og sykdom: En skeptikers syn pa
˚
352:688–91. genkartlegging og genterapi. [Genes, behavior and disease: A
skeptics view of gene mapping and gene therapy]. J Norwegian
117. Haig D. Genetic conflicts of pregnancy and childhood. In: Med Assoc 1995;115:2114–9.
Stearns SC, editor. Evolution in health and disease. Oxford:
Oxford Univ. Press, 1998:77–90. 137. Neel JV. Looking ahead: some genetic issues of the future. Per-
spect Biol Med 1997;40:328–47.
118. Francois CA, Connor SL, Wander RC, Conner WE. Acute effects
of dietary fatty acids on the fatty acids of human milk. Am J 138. Bull J, Wichman H. A revolution in evolution. Science 1998;
281:1959.Clin Nutr 1998;67:301–8.