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It is increasingly recognized that certain fundamental changes in diet and lifestyle that occurred after the Neolithic Revolution, and especially after the Industrial Revolution and the Modern Age, are too recent, on an evolutionary time scale, for the human genome to have completely adapted. This mismatch between our ancient physiology and the western diet and lifestyle underlies many so-called diseases of civilization, including coronary heart disease, obesity, hypertension, type 2 diabetes, epithelial cell cancers, autoimmune disease, and osteopo-rosis, which are rare or virtually absent in hunter–gatherers and other non-westernized popula-tions. It is therefore proposed that the adoption of diet and lifestyle that mimic the beneficial characteristics of the preagricultural environment is an effective strategy to reduce the risk of chronic degenerative diseases.
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DOI: 10.2147/RRCC.S16919
The western diet and lifestyle and diseases
of civilization
Pedro Carrera-Bastos1
Maelan Fontes-Villalba1
James H O’Keefe2
Staffan Lindeberg1
Loren Cordain3
1Center for Primary Health Care
Research, Faculty of Medicine at
Lund University, Malmö, Sweden;
2Mid America Heart and Vascul ar
Institute/University of Missouri-
Kansas City, Kansas City, Missouri,
USA; 3Department of Health and
Exercise Science, Colorado State
University, Fort Collins, Colorado,
Correspondence: Pedro Carrera-Bastos
R. Gorgel do Amaral, No. 5, 1 E;
Lisbon 1250-119, Portugal
Tel 351 967 088 799
Abstract: It is increasingly recognized that certain fundamental changes in diet and lifestyle
that occurred after the Neolithic Revolution, and especially after the Industrial Revolution and
the Modern Age, are too recent, on an evolutionary time scale, for the human genome to have
completely adapted. This mismatch between our ancient physiology and the western diet and
lifestyle underlies many so-called diseases of civilization, including coronary heart disease,
obesity, hypertension, type 2 diabetes, epithelial cell cancers, autoimmune disease, and osteopo-
rosis, which are rare or virtually absent in hunter–gatherers and other non-westernized popula-
tions. It is therefore proposed that the adoption of diet and lifestyle that mimic the beneficial
characteristics of the preagricultural environment is an effective strategy to reduce the risk of
chronic degenerative diseases.
Keywords: Paleolithic, hunter–gatherers, Agricultural Revolution, modern diet, western
lifestyle and diseases
The physical activity, sleep, sun exposure, and dietary needs of every living organism
(including humans) are genetically determined. This is why it is being increasingly recog-
nized in the scientific literature, especially after Eaton and Konner’s1 seminal publication
in 1985, that the profound changes in diet and lifestyle that occurred after the Neolithic
Revolution (and more so after the Industrial Revolution and the Modern Age) are too
recent on an evolutionary time scale for the human genome to have fully adapted.1–27
In fact, despite various alleles being targets of selection since the Agricultural
Revolution,28–42 most of the human genome comprises genes selected during the
Paleolithic Era43 in Africa,43–59 a period that lasted from about 2.5 million years ago to
11,000 years ago.14 Indeed, anthropological and genetic studies suggest that all human
beings living in Europe, Asia, Oceania, and the Americas share a common African
Homo sapiens ancestor.47–57 This concept is corroborated by data showing that there
is less genetic diversity throughout the world’s non-African population than there is
within Africa itself.44–46,53,57,58
Moreover, many of the selective pressures underlying these postagriculture alleles
were not induced by changes in sleep, exercise, and diet but rather by pathogens, fatal
diseases, and harsh environments,28–31,37–39 with a few key exceptions.41,42 One of those
exceptions pertains to alleles of the LCT gene (which codes for the enzyme lactase-
phlorizin hydrolase [LPH]) that give rise to the phenotype of adult lactase persistence
(ALP).60 These LPH-encoding alleles were initially selected in populations with a long
history of milk and dairying, such as north-western Europeans and some sub-Saharan
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African and Bedouin pastoralists. Today, ALP occurs in about
35% of the world’s population.60
The impetus for these genetic changes was not to
increase longevity and resistance to chronic degenerative
diseases but rather to increase the probability of survival
and reproductive success.27,61,62 Occasionally, muta-
tions that had positive survival and reproductive value
sometimes also caused adverse health effects in the
postreproductive years.4,27,61,62 Furthermore, single gene
mutations, although relevant for physicians when treat-
ing an individual patient, are imperfect models to prevent
chronic degenerative diseases whose clinical symptoms
normally affect the postreproductive years and involve
numerous genes.61
Importantly, 11,000 years represent approximately
366 human generations,63 which comprise only 0.5% of
the history of the genus Homo (Table 1).14,63–65 Indeed, the
Industrial Revolution and the Modern Age, which mark the
beginning of the western lifestyle, represent only seven and
four human generations, respectively (Table 1),14,63–65 and
were marked by rapid, radical, and still ongoing changes in
lifestyle and diet,14,65 coupled with improved public health
measures that greatly reduced mortality in the prereproduc-
tive years (and hence largely eliminated impaired reproduc-
tive fitness as a selection pressure).62,66 As such, it is highly
unlikely that genetic adaptations that allow us to thrive on a
western diet and lifestyle have occurred.
Health status of preagriculture
traditional populations
The idea that modern Homo sapiens are still adapted to an
ancestral environment is reinforced by data showing that
hunter–gatherers, and other populations minimally affected
by modern habits, exhibit superior health markers, body
composition, and physical fitness compared with industrial-
ized populations, including:
1. Low blood pressure in hunter–gatherers and horticultural-
ists (Table 2)26,67–69 when compared with current optimal
values defined by health institutions (120 mm Hg
and 80 mm Hg for systolic blood pressure and diastolic
blood pressure, respectively)70
2. Lack of association between blood pressure and age in
hunter–gatherers ( Table 3)69 and horticulturalists68 com-
pared with in North Americans and Swedes26,68,70
3. Persisting excellent insulin sensitivity among middle-
aged and older individuals in non-westernized tra-
ditional populations that maintain their ancestral
4. Lower fasting plasma insulin concentrations and higher
insulin sensitivity (measured by the Homeostatic Model
Assessment [HOMA] index) in the horticulturalists of
Kitava (Papua New Guinea) compared with in healthy
Swedes (Figures 1 and 2, respectively)74
5. Lower fasting plasma leptin in the horticulturalists of Kitava
and the Ache hunter–gatherer Indians of Paraguay compared
with in healthy Swedes82 (Figure 3) and North American
male distance runners83 (Figure 4), respectively
6. Lower body mass index (BMI) in hunter–gatherers, tradi-
tional pastoralists, and horticulturalists26 compared with in
westerners.26,84 Fo r in stan ce, as ob ser ved b y Li nde berg ,26 in
Kitava, 87% of men and 93% of women aged 40–60 years
had a BMI below 22 kg/m2 and not a single individual in
this age group was overweight or obese26
7. Lower waist (cm)/height (m) ratio in the horticul-
turalists of Kitava compared with in healthy Swedes
(Figure 5)82
8. Lower tricipital skinfold (mm) in hunter–gatherers com-
pared with in healthy Americans67 (Figure 6)
Table 1 Historical milestones in human generations14,63–65
Historical milestones Generations % total
Homo habilis 76,667 100.0
Homo erectus 60,000 78.2
Modern Homo sapiens 6666 8.7
Neolithic Revolution 366 0.48
Industrial Revolution 7 0.009
Food industry (junk food) and
physical inactivity (Modern Age)
4 0.005
Table 2 Systolic blood pressure (SBP) and diastolic blood
pressure (DBP) at age 40–60 years in hunter–gatherers and
horticulturalists (mm Hg)26,67–69
Population Men Women
Bushmen 108 63 118 71
Yonomamo 104 65 102 63
Xingu 107 68 102 66
Kitava 113 71 121 71
Table 3 Systolic blood pressure and diastolic blood pressure in
Yanomamo Indians (mm Hg)69
Age (years) Men Women
0–9 93/59 96/62
10–19 108/67 105/65
20–29 108/69 100/63
30–39 106/69 100/63
40–49 107/67 98/62
50100/64 106/64
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The Western diet and lifestyle
9. Greater maximum oxygen consumption (VO2 max) in
hunter–gatherers and traditional pastoralists compared
with in average Americans67 (Figure 7)
10. Better visual acuity in hunter–gatherers and other tradi-
tional populations minimally affected by western habits
compared with in industrialized populations85
11. Better bone health markers in hunter–gatherers com-
pared with in western populations and even traditional
12. Lower fracture rates in non-westernized populations
compared with in western populations.26,96–99
Another line of evidence supporting the superior health
markers of hunter–gatherers and other traditional populations
comes from the historical records of explorers, adventurers,
and frontiersmen, which invariably described the populations
they encountered as being healthy, lean, fit, and free of the
signs of chronic degenerative diseases.26 But perhaps even
more important than these observations are the medical and
anthropological reports showing a low incidence of chronic
degenerative diseases such as metabolic syndrome and type 2
diabetes,26,67,73,74,100 ca rdiovasc ular dis ease (CV D),26,65,67,68,100–112
cancer,26,67,113–118 ac ne ,119 a nd eve n m yo pi a85 i n h un te r– gatherers,
traditional pastoralists, and horticulturalists compared with in
western populations26,65,67,85,100,108,109,113,114,119,120 and even ancient
Egyptians67,114,121–123 and medieval Europeans.114
It has been argued that traditional populations may have been
genetically protected against the chronic degenerative diseases
that occur in industrialized countries, yet when non-westernized
individuals adopt a more contemporary lifestyle, their risk for
chronic degenerative diseases is similar or even increased com-
pared with modern populations.26,67,78–80,108,109,124–144 Further, when
they return to their original traditional lifestyle, many disease
markers or symptoms return to normal.81,145 These data
demonstrate that the superior health markers, body composition,
and physical fitness of hunter–gatherers and other populations
minimally affected by modern habits are not due primarily to
genetics but first and foremost to the environment. These studies
also indicate that few or no genetic adaptations have occurred
to protect any population from chronic diseases that are elicited
by modern diet and lifestyles.
Indeed, two different individuals when exposed to the
same modern environment (eg, western diet, physical
inactivity, insufficient and inadequate sleep, chronic psy-
chological stress, insufficient or excessive sun exposure,
use of recreational drugs, smoking, pollution) will prob-
ably express a suboptimal phenotype.27,65,146,147 This may or
may not be considered pathological, depending on genetic
variants (eg, haplotypes, single nucleotide polymorphisms,
microsatellites, simple sequence repeats, insertion/deletion,
copy number variations) and differences in gene expression
regulation (such as epigenetic variations).27,62,146,148
Another common counterargument is the short average
life expectancy at birth of hunter–gatherers. The problem with
this marker is that it is influenced by fatal events (eg, acci-
dents, warfare, infections, exposure to the elements) and
childhood mortality. Today, average life expectancy is higher
not because of a healthier diet and lifestyle but owing to bet-
ter sanitation, vaccination, antibiotics, quarantine policies,
medical care, political and social stability, and less physical
trauma.66 M ore over, G urve n an d Ka plan ,149 in a re cent ass ess -
ment of the mortality profiles of extant hunter–gatherers for
which sufficient high-quality demographic data exist, con-
cluded that “modal adult life span is 68–78 years, and that it
was not uncommon for individuals to reach these ages”.
Of more importance, these individuals reached age
60 years or beyond without the signs and symptoms of chronic
degenerative diseases that afflict the majority of the elderly in
industrialized countries.66 Furthermore, in western countries,
various illnesses and conditions, such as obesity, type 2 dia-
betes, gout, hypertension, coronary heart disease (CHD), and
epithelial cell cancers, which are rare or virtually absent in
hunter–gatherers, horticulturalists, and traditional pastoralists,
are now increasing in younger age groups.26,64–66 Finally, the
fossil record suggests that when hunter–gatherer populations
made the transition to an agricultural pattern of subsistence,
their health status and lifespan decreased.26,109,150
The ancestral environment
With the help of anatomical, biomechanical, and isotopic
analyses of various hominin skeletons, the archaeological
25–39 40–59 60–74 25–39 40–59 60–74
Fasting insulin
Men Women
Figure 1 Fasting plasma insulin (lU/mL) in Kitava horticulturalists versus in healthy
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Carrera-Bastos et al
and geological evaluation of their habitats, and ethnographic
studies of various hunter–gatherer societies (whose diet and
lifestyle resembled the Palaeolithic diet and lifestyle), it was
concluded38,61,64,65,108,151–157 that, despite the existence of dif-
ferent diets and lifestyles, which varied due to differences
in geography, ecological niche, season, and glaciations, they
all had the following characteristics:
uRegular sun exposure38,151 (except for the Inuit, whose
very high intake of vitamin D3 from fish and marine
mammals158,159 may have rendered the lack of ultraviolet-
stimulated cutaneous vitamin D synthesis less relevant)
uSleep patterns in synch with the daily variation in light
uAcute as opposed to chronic stress160
uRegular physical activity, as this was required to obtain
food and water, to escape from predators, for social
interaction, and to build shelters146,147,153
uLack of exposure to man-made environmental
uUniversal fresh (generally unprocessed) food sources as
depicted in Table 4.14,64,65,154,155,157
The Neolithic and industrial
revolutions and their consequences
The Agricultural Revolution began about 11,000 years
ago in the Middle East, later spread to other regions of the
Kitava Sweden
Kitava Sweden
4Males Females
Figure 2 Homeostatic Model Assessment Index in Kitava horticulturalists versus in healthy Swedes.74
<40 40–59 60+ <40 40–59 60+
Fasting leptin
Figure 3 Fasting plasma leptin (ng/mL) in Kitava horticulturalists versus in healthy
1.5 2 2.5
Figure 4 Fasting plasma leptin (ng/mL) in Ache Indians versus in American marathon
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The Western diet and lifestyle
globe,14,65,154 and drastically altered the diet and lifestyle that
had shaped the human genome for the preceding 2 million
plus years. Some of the more significant dietary changes
were the use of cereal grains as staple foods, the introduction
of nonhuman milk, domesticated meats, legumes and other
cultivated plant foods, and later widespread use of sucrose
and alcoholic beverages.14,65
Nevertheless it was the Industrial Revolution (with
the widespread use of ref ined vegetable oils, refined
cereal grains, and refined sugars)14,65 and the Modern Age
(with the advent of the “junk food” industry, generalized
physical inactivity, introduction of various pollutants,
avoidance of sun exposure, and reduction in sleep time
and quality coupled with increased chronic psychological
stress)14,38,65,146,152,153,160 that brought about the most disrup-
tive and maladaptive changes, which may have serious
pathophysiological consequences. For instance, chronic
psychological stress, environmental pollution, and smoking
are associated with low-grade chronic inflammation,161–165
which is one of the main causes of insulin resistance.161,164,165
Moreover, low-grade chronic inflammation is involved in
all stages of the atherosclerotic process166 and is being
increasingly recognized as a universal mechanism in
various chronic degenerative diseases, such as autoimmune
diseases, certain cancers, neuropsychatric diseases, and
osteoporosis.27,65,160,167 Furthermore, some environmental
pollutants, including pesticides and various industrial
chemicals, may act as endocrine disruptors, hence being
suspected of playing a causal role in hormone-dependent
cancers (such as breast and prostate cancer),168 insulin
resistance169 and type 2 diabetes,
169,170 obesity,
171 and
Insufficient sleep (fewer than 6 hours per 24-hour day)
is also associated with low-grade chronic inflammation
and worsening insulin resistance,165,173 as well as increased
risks for obesity, type 2 diabetes, and CVD.165,174,175 This
information is relevant in light of a recent cross-sectional
Men Women
Figure 5 Waist circumference (cm)/height (m) in Kitava horticulturalists versus in
healthy Swedes.82
Modern Americans
African pygmies
Figure 6 Tricipital skinfold (mm) in several populations.67
Figure 7 Maximum oxygen consumption in various populations (mL/kg/min).67
Table 4 Foods consumed during the Paleolithic Era14,64,65,154,155,157
Foods available Foods not available
marine animals, reptiles, birds,
wild terrestrial mammals and eggs
Dairy (except for human milk
during weaning)
Plant leaves, seaweed, sea
grasses and algae
Cereal grains (with the exception
of occasional intake in the upper
Roots Legumes (except certain varieties
that were consumed seasonally)
Tubers Isolated sugar
Berries and wild fruits Isolated oils
Nuts and seeds Alcohol
Honey (occasional intake) 5HÀQHGVDOWHYHQVHDVDOWZRXOG
be available only for shore-based
populations who may have dipped
their food in sea water)
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Carrera-Bastos et al
may progressively reduce plasma 25[OH]D3 concentrations
in humans.
Reduced plasma 25[OH]D concentrations may have
serious health consequences. Indeed, there is an impressive
body of evidence associating low vitamin D status (measured
by plasma 25[OH]D) with an increased incidence of vari-
ous types of cancer (including breast, prostate, and colon),
autoimmune diseases, infectious diseases, muscle weakness,
osteoporosis, hypertension, insulin resistance, cardiovascular,
and all-cause mortality.151,177–179
It should be mentioned that, except for fatty ocean
fish, there is very little vitamin D in commonly consumed
natural (ie, not artificially fortified) foods.177 As such,
sensible sun exposure (adjusted to skin type, climate, time
of year, and geographic region) and/or supplementation
with vitamin D may often be pertinent in order to maintain
serum 25[OH]D above 30 ng/mL177 (or preferably above
45 ng/mL).179
Another important lifestyle change is physical inactivity,
which Booth et al146 call “an ancient enemy”. They make a
compelling case for its possible causal role in insulin resis-
tance, dyslipidemia, obesity, hypertension, type 2 diabetes,
coronary artery disease, angina, myocardial infarction,
congestive heart failure, stroke, intermittent claudication,
gallstones, various types of cancer, age-related cognitive
dysfunction, sarcopenia, and osteopenia, among other
Regarding dietary changes, it should be mentioned
that, in the US, dairy products, cereal grains (especially the
refined form), refined sugars, refined vegetable oils, and
alcohol make up to 70% of the total daily energy consumed.65
As pointed out by Cordain et al,65 these types of foods would
have contributed little or none of the energy in the typical
preagricultural hominin diet. These modern foods introduced
during the Neolithic, Industrial, and Modern eras have
adversely affected the following nutritional characteristics.
Micronutrient density
Calorie per calorie, fish, shellfish, meat, vegetables, and
fruit present a higher micronutrient density than does milk
(with the exception of calcium) and whole cereal grains (and
several orders of magnitude higher than refined grains).65
Moreover, vegetable oils and refined sugars represent more
than 36% of the energy in a typical US diet and are essen-
tially devoid of micronutrients (except for vitamin E in some
vegetable oils).65
Therefore, current food choices,65,154,180,181 together
with soil depletion182–186 and modern food transport and
population-based study showing that 28% of US adults
sleep 6 or less hours per 24-hour period.175 Moreover,
social and work pressures, as well as exposure to artificial
light at atypical biologic times (a very recent phenomenon
in human evolutionary history), induce a disruption of the
normal circadian rhythm, which is believed to play a key role
in various diseases.176 As Vgontzas et al173 point out: “the
idea that sleep or parts of it are optional should be regarded
with caution”.
Perhaps even more important is the chronic vitamin
D deficiency brought about by novel cultural and geo-
graphical changes in human behavior. As Homo sapi-
ens left equatorial Africa and begun to occupy higher
latitude regions, where the proportion of ultraviolet B
wavelengths is decreased and of ultraviolet A vitamin
D-destructive wavelengths is increased, previtamin D3
production became compromised (especially in the winter
time).38 This may have increased the incidence of rick-
ets, muscle weakness, and bacterial and viral infections,
which impaired reproductive fitness and increased early
mortality.38 Thus, it has been hypothesized that these were
the main selective pressures for lighter skin pigmenta-
tion, which is a recent adaptation in human evolution-
ary history.38 Although natural selection for lighter skin
pigmentation may have reduced the prevalence of rickets,
muscle weakness, and bacterial and viral infections, it may
not have assured an optimal vitamin D status, given the
many functions now attributed to 1,25-dihydroxyvitamin
D (1,25[OH]2D), the existence of vitamin D receptors,
and the occurrence of 1,25[OH]2D synthesis in various
Today, vitamin D status is further compromised by
migrations of people with dark skin (adapted to equatorial
and tropical regions) to higher latitudes, and by air pollu-
tion, ozone, clothing, indoor living and working habits, and
sun protection.38,177 Other factors contributing to a lower
vitamin D status in humans include certain medications,
diseases, and conditions (such as obesity, liver and kidney dis-
ease, and conditions that affect fat absorption),177 and perhaps
also modern dietary habits, such as a high intake of cereal
grains. Epidemiological studies of populations consuming
high levels of unleavened whole grain breads show rickets
and vitamin D deficiency to be widespread, and high cereal
diets can induce vitamin D deficiency in animals, including
primates.154 Mo reove r, as p oin ted o ut by Co rda in, 154 a study of
radiolabelled 25-hydroxyvitamin D3 (25[OH]D3) in humans
consuming 60 g of wheat bran on a daily basis for 30 days
showed an increased fecal elimination of 25(OH)D3, which
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The Western diet and lifestyle
stocking,187–189 are perhaps the main reasons why a significant
percentage of the North American population does not reach
the recommended daily allowance (RDA) of various vitamins
and minerals.190,191 This problem is exacerbated by culinary
methods,192–197 smoking (which causes vitamin C depletion198),
and the use of certain foods as staples. For instance, using
cereal grains as staple foods may compromise the status
of various nutrients, such as vitamin B6 (because of low
bioavailability154), biotin (perhaps because of antinutrients
eliciting a depression of biotin metabolism154), magnesium,
calcium, iron, and zinc (because their phytate content reduces
intestinal absorption of these minerals154,180).
Even moderate micronutrient deficiency leads to a wide
spectrum of pathophysiological events, and it is an important
risk factor for several chronic degenerative diseases.65,199–206
For instance, data from the National Health and Nutrition
Examination Survey 2001–2002 show that magnesium intake
for more than 50% of US adults was below the estimated
average requirement.190 Multiple epidemiologic studies
associate magnesium deficiency with an increased risk of
metabolic syndrome201,202 and CVD,
203–205 and this causal
relationship is supported by intervention studies.206–209
Other nutrients whose status is compromised in a typical
western diet are zinc, folate, and vitamins C, E, and K,190,199,200
the latter (especially the K2 form) gaining widespread accep-
tance as a possible player in CVD. Epidemiological studies
associate higher vitamin K2 intake with a reduced CHD and
coronary calcification incidence.210–212
Folic acid deficiency (which would not constitute a
problem in hunter–gatherer diets that included green leafy
vegetables and organ meats65) is also a case for concern in
terms of CVD prevention, as it leads to an increase in plasma
homocysteine, which, although no consensus has been
reached, appears to be a CVD risk factor because it induces
damage of the endothelial cell wall and abnormal arterial lipid
deposition, reduces vasorelaxation, and impairs fibrinolytic
action.213 Perhaps more important, folate, along with vitamin
B6 and B12, choline, betaine, and methionine deficiency in
utero, may result in an altered epigenetic programming,62
which ultimately leads to endothelial dysfunction,214 among
other pathophysiological consequences.62,213
Sodium/potassium ratio
The average potassium content (2620 mg/d) of the typi-
cal US diet is substantially lower than its sodium content
(3271 mg/d), which is due to the use of table salt, a high
intake of processed foods (with added salt), and the displace-
ment of potassium-rich foods (eg, fruit and vegetables) by
potassium-poor foods, such as vegetable oils, refined sugars,
whole grains, and dairy products.65
This inversion of potassium and sodium concentrations
is a recent event in human evolutionary history.63–65,215 It is
believed to contribute to hypertension, stroke, kidney stones,
osteoporosis, gastrointestinal tract cancers, asthma, exercise-
induced asthma, insomnia, air sickness, high-altitude sick-
ness, and Meniere’s syndrome.65
Net acid load
After digestion, absorption, and metabolism, nearly all foods
release either acid or base into the systemic circulation.
Dairy products (especially hard cheeses), cereal grains, salt
(because of the chloride ion), meats, fish, shellfish, and eggs
are net acid yielding, whereas fresh fruit, vegetables, tubers,
roots, and nuts are net base yielding.65,215
It was recently estimated that the diet of East African Homo
sapiens during the Paleolithic era was predominantly net base
producing,216 as opposed to the typical western diet, which is
net acid yielding65,215 and hence leads to a chronic, low-grade
metabolic acidosis, which elicits loss of calcium ions caused by
mobilization of alkaline salts from bone to titrate some of the
retained hydrogen ions.215 Th i s c a l c i u m i s l o st i n t h e u r i n e w i t h -
out a compensatory increase in gastrointestinal absorption.215
Chronic, low-grade metabolic acidosis also induces the release
of amino acids, including glutamine and amino acids that the
liver can convert to glutamine.215 Glutamine is the major nitro-
gen source used by the kidney for synthesis of ammonia, thereby
increasing the excretion of acid (as ammonium ion) in the urine
and mitigating the severity of the acidosis.215 Accordingly, in
the long term, a net acid-yielding diet may increase the risk for
osteoporosis and sarcopenia.65,215
Furthermore, a net acid-yielding diet increases not only
calcium excretion217 but a lso mag nesi um e xcr eti on. 218 Finally,
there is evidence that chloride (a key determinant of the
diet’s net acid load219) may be a major cause of salt-induced
On a final note, this chronic, low-grade metabolic acidosis
is exacerbated in elderly people who experience a decline
in glomerular filtration rate and hence have a decreased
renal acid excretion capacity,65 which is why correcting
diet-induced chronic metabolic acidosis in this age group
is even more important. Hence, we propose as a solution
to this chronic, low-grade metabolic acidosis a decreased
intake of sodium chloride and an increased consumption of
unprocessed fruit and vegetables, at the expense of refined
vegetable oils, refined sugars, cereal grains, hard cheeses,
and processed foods.
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Carrera-Bastos et al
Alterations in gut microbiotica220 and increased intestinal
permeability221 are possible causes of low-grade chronic
inflammation. Indeed, when the intestinal barrier is dis-
rupted, it allows increased passage of gut luminal antigens
derived from food, bacteria, and viruses221 into periph-
eral circulation (endotoxemia222). One particular antigen,
lipopolysaccharide (LPS), from Gram-negative bacteria, is
routinely used in animal experiments to induce acute immune
stimulation.223 When LPS binds Toll-like receptor (TLR)4,
it triggers the release of nuclear factor kappa-B (NF-kb)
dimers that translocate into the cell nucleus, where they
bind to DNA target sites, thereby inducing the expression of
genes that code for various inflammatory enzymes, cytokines
and chemokines, cell adhesion molecules, antiapoptotic and
angiogenesis proteins, inducible nitric oxide synthase, and
matrix-degrading enzymes224 that are involved in the athero-
sclerosis process.19,166,222,224 Moreover, these proinflammatory
cytokines may disrupt insulin signaling, promoting insulin
resistance.164 So a chronic low-grade endotoxemia may lead
to low-grade chronic inflammation,222 which is at the root of
various disorders.160,165–167,222,224,225
In this regard, recent evidence shows that certain western
foods (dairy cream, butter, egg muffins, sausage muffins,
hash browns, and sugar) allow increased passage of luminal
antigens into peripheral circulation, leading to TLR2 and
TLR4 activation.222,226–228 Interestingly, one study found that
these events were prevented by a high intake of orange juice
(perhaps because it contains flavonoids with reactive oxygen
species [ROS] and inflammation-suppressive activities, such
as naringenin and hesperidin),228 which opens the possibility
that other fruit and vegetables may elicit similar effects.
Some factors contributing to increased intestinal per-
meability include nonsteroidal anti-inflammatory drugs,221
antacids,221 ch ang es i n gut mic rob iot a,221 al coh ol, 229 lec tins ,221
saponins,230–235 and gliadin.236
It was recently found that gliadin, a prolamine in wheat
(which is a novel food in the human diet in evolutionary
terms65), increases gut permeability by means of zonulin
production in the gut enterocytes.236 Zonulin causes dis-
ruption of the tight junction proteins that maintain the gut
barrier function and leads to increased gut permeability.237
In addition, gliadin (which is resistant to heat and digestive
enzymes154) is able to interact with gut-associated lymphoid
tissue, stimulating the innate immune system in celiac and
nonceliac individuals (whereas the adaptive immune response
is exclusive of celiac patients).238,239 Gliadin may increase
intestinal permeability and hence induce the production of
proinflammatory cytokines, independent of one’s genetic
predisposition to celiac disease (although, as expected, these
effects are more marked in celiac disease).236,238–240 As such,
we can deduce that chronic consumption of wheat, as hap-
pens in western countries, may lead to low-grade chronic
inflammation. Of relevance, wheat gluten has been implicated
in multiple sclerosis,154,241,242 t ype 1 di abe tes, 154,243 pso ria sis, 244
immunoglobulin (Ig)A nephropathy,154 and rheumatoid
arthritis (RA).154,221 Moreover, rectal mucosal inflammatory
response after gluten challenge has been observed in patients
with Sjögren’s syndrome.245 Furthermore, a gluten-free vegan
diet over 1 year significantly reduced disease activity and
oxidized low-density lipoprotein colesterol (LDL-C) in RA
patients while raising natural atheroprotective antibodies
against phosphorylcholine (anti-PC IgM).246 This may be
relevant, as anti-PC IgM is negatively associated with ath-
erosclerosis development in hypertensive individuals,247 and
low levels of anti-PC IgM independently predict development
of CVD.247 Interestingly, compared with in healthy Swedes,
anti-PC IgM has been found to be significantly higher in the
horticulturalists of Kitava,248 who, at the time of measure-
ment, followed a diet composed of fish, coconut, fruit, and
tubers (and hence devoid of cereal grains, dairy products,
separated fats, and sugars)248 and were virtually free of auto-
immune diseases, osteoporosis, obesity, insulin resistance
and type 2 diabetes, CVD, and acne.26,74,82,112,119
Similar to gliadin, many plant lectins are also a recent
introduction to the human diet.154 Lectins are omnipresent
proteins found in the plant kingdom and likely evolved as
toxic defensive mechanisms to ward off predators.100 Most of
these glycoproteins are believed to be benign and nontoxic to
humans, but the ones that can bind gut tissue may be prob-
lematic, such as those found in cereal grains, legumes, and
certain solanaceous plants (tomatoes and potatoes).154,221,249
Most plant lectins are relatively resistant to heat154 (unless
cooked by pressure cooking250) and digestive enzymes154,221
and have been found intact in the gastrointestinal tracts of
both animals and humans.154,221 Fu rthe rmor e, i n an ima l mo d-
els, lectins from legumes and cereal grains disrupt intestinal
barrier and immunological function when they bind surface
glycans on gut epithelial cells, causing cellular disruption
and increasing gut permeability.221 They may also facilitate
the growth of Gram-negative bacteria strains,221 which could,
in theory, contribute to endotoxemia221 and hence low-grade
inflammation through TLR4 activation by LPS.222 Perhaps
even more importantly, wheat germ agglutinin (WGA)
(a lectin in wheat) and phytohemagglutinin (PHA) (a lectin
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The Western diet and lifestyle
found in beans) are rapidly transported across the gut wall
into systemic circulation of animals,221 and tomato and peanut
lectins have been found in systemic circulation in humans
following consumption of tomato juice and roasted peanuts,
These findings might be important, as virtually every
cell in the body and every extracellular substance can be
bound by lectins because of their ability to bind glycosy-
lated structures.154 Of note, in vitro data have shown that
WGA can bind insulin and leptin receptors,154,252 which
could theoretically elicit insulin and leptin resistance.26,100,154
Moreover, lectins from lentils, kidney beans, peas, and
wheat potently increase the production of inflammatory
cytokines (interleukin [IL]-12, IL-2, and interferon G) in
cell cultures,253 and WGA also stimulates production of
tumor necrosis factor (TNF)-A and IL-1B in vitro.254 Fur-
thermore, WGA and PHA induce the production of metallo-
proteinases (MMPs) in leukocytes,255,256 and WGA directly
causes the activation of platelets and potently increases
their aggregation.257 This may be relevant because rupture
of the fibrous cap and formation of the blood clot, which
is mediated by MMPs and platelets, is a crucial mecha-
nism involved in thrombus production. In this regard and
although these chain of events have not to our knowledge
been examined in vivo, it should be mentioned that peanut
oil has unexpectedly been shown to be highly atherogenic
in rats, rabbits, and primates,258 and reduction of its lectin
content decreases its atherogenicity.258 Interestingly, one of
the very few human-controlled dietary intervention trials
with hard endpoints, DART (Diet And Reinfarction Trial),
found a tendency toward increased cardiovascular mortal-
ity in the group advised to eat more fiber, the majority of
which was derived from cereal grains.259 Of relevance is that
this nonsignificant effect became statistically significant
after adjustment for possible confounding factors (such as
medication and health state).260
Another class of antinutrients that may increase intestinal
permeability in humans and hence endotoxemia are saponins,
which are present in some cereal grains, legumes, quillaja,
alfalfa sprouts, and solanaceous plants such as potatoes and
green tomatoes.230–235 These steroid glycosides or triterpe-
noids are formed by a sugar compound (glucuronic acid, glu-
cose, or galactose, among others) and an aglycone (nonsugar
molecule) portion.230,231 By binding the cholesterol molecule
on gut cell membranes, the aglycone portion disrupts the gut
barrier and increases intestinal permeability.231
Unfortunately, the effects of lectins and saponins on
intestinal permeability, endotoxemia, and inflammation have
been poorly studied in humans to allow us to draw significant
Novel food processing procedures, such as extreme
heating, irradiation, ionization, pasteurization, and steriliza-
tion, may also promote low-grade chronic inflammation by
leading to the nonenzymatic glycation and oxidation of pro-
teins and lipids in common consumed foods.261 This complex
and heterogeneous group of compounds, called advanced
glycation end products (AGEs) and advanced lipid oxida-
tion end products (ALEs), once partially absorbed into the
systemic circulation may have deleterious health effects261
by direct modification of proteins and lipids262,263 (such as
LDL glycation and oxidation, for instance) and perhaps
also indirectly via the receptor for AGEs (RAGE).261,262 Of
relevance to chronic degenerative diseases is the possible
interaction of AGEs and ALEs with RAGE, which may acti-
vate several intracellular signal transduction pathways that
lead to various downstream events, such as the activation
of NF-kb and activator protein-1 transcription factors,261,262
which increases the expression of endothelin-1, angiotensin
II, adhesion molecules, inflammatory cytokines, and plasmin
activator inhibitor-1.261,262
Indeed, in diabetic patients, a high AGE intake was
associated with higher levels of C-reactive protein (CRP),
TNF-A, and vascular cell adhesion molecule (VCAM-1).261
In contrast, low-AGE diets reduce serum AGE levels, as
well as markers of inflammation and vascular dysfunction
(CRP, TNF-A, and VCAM-1) in diabetic and renal failure
patients.261,262 T h e e ff e c t s o f d i e t a r y AG E s a n d AL E s a r e o b v i -
ously more pronounced in diabetics (who present an enhanced
formation of endogenous AGEs due to hyperglycemia)261 and
kidney failure patients (who have an impairment of AGE
renal excretion).261 Nevertheless, in a cross-sectional study
of healthy subjects of different ages, dietary AGE intake was
an independent determinant of high-sensitivity CRP and
of circulating AGEs, which, in turn, were associated with
endogenous lipid peroxidation and HOMA index.263
AGE and ALE content in food is greatly influenced by
processing and cooking conditions, including temperature,
time, and moisture.264 Consequently, the avoidance of pro-
cessed foods and the use of steaming, poaching, boiling,
and stewing as the main cooking methods, instead of frying,
broiling, and grilling, may be a sensible way to decrease the
formation of these compounds.261,264 Of interest, tobacco, by
being processed in the presence of reducing sugars, represents
another source of exogenous AGEs.262 Indeed, circulating
AGE levels have been found to be significantly higher in
smokers than in nonsmokers.265
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Carrera-Bastos et al
During the Paleolithic period, most of the carbohydrate
(CHO) sources were wild fruit, berries, vegetables (typically
presenting low glycemic index [GI]26), and sometimes tubers,
with cereal and honey intake being scarce.14,26,65
Today, most CHO come from processed foods such as
refined sugars and refined cereal grains.65 Even whole grains
possess a higher glycemic load (GL) than does most unpro-
cessed fruit and vegetables.65 The GL takes into account
both the GI and the amount of CHO in a given serving of
a food. It is estimated that the GL of Paleolithic diets was
significantly lower than the GL of western diets.65
This observation is relevant because chronic adop-
tion of a high-GL diet may lead to hyperglycemia and
hyperinsulinemia,266 which may contribute to dyslipidemia
(elevated serum triglycerides, small-dense LDL-C, and
reduced high-density lipoprotein [HDL]-C),266 hy perte ns ion ,267
elevated plasma uric acid,267 and insulin resistance,266 the pri-
mary metabolic defect in metabolic syndrome.266 Moreover, by
eliciting postprandial hyperglycemia, it may increase oxida-
tive stress, proinflammatory cytokines, protein glycation, and
procoagulant activity, thereby adversely affecting endothelial
function, among other pathophysiological effects.266,268–270
Indeed, a recent meta-analysis of 37 prospective cohort stud-
ies suggests that diets with a high GI, high GL, or both may
increase the risk of type 2 diabetes, heart disease, and gallblad-
der disease.270 Furthermore, intervention studies show that a
low GL diet may be an effective strategy for overweight and
obesity271,272 and confer better glucose, insulin, lipoprotein,
and inflammatory cytokine profiles in overweight and type
2 diabetes patients.268 Finally, the chronic adoption of a high
GL diet may lead to a number of hormonal changes (such
as elevated insulin-like growth factor-1 [IGF-1]/insulin-like
growth factor binding protein-3 [IGFBP-3] ratio and increased
ovarian and testicular androgen synthesis, coupled with
decreased sex hormone-binding globulin hepatic synthesis)
that ultimately may result in polycystic ovary syndrome,
epithelial cell cancers, acne, and juvenile myopia, among
other diseases.85,119,266,273
Another nutritional change is fiber intake. Most Paleo-
lithic diets had more fiber (30 g/d), generally from fruit and
vegetables,65 than did the typical western diet, where most of
the fiber derives from cereal grains.65 Fruit and vegetables
have, on a calorie per calorie basis, two and eight times more
fiber than do whole grains.65 In addition, fruit and vegetables
typically contain soluble fiber, whereas much fiber in cereal
grains is of the insoluble type.26
This may all be relevant because dietary fiber, in particu-
lar soluble fiber, increases satiety,274,275 reduces postprandial
free fatty acids,275 and contributes to better glycemic con-
trol (perhaps through a glucagon-like peptide-1 effect).275
Furthermore, dietary fiber appears to play an important
role in intestinal health, as suggested by Higginson and
Oettlé276 in the 1960s. They observed that in Africa, where
“a large amount of roughage is consumed”, colon cancer
and constipation were rare, whereas they were common
diseases in western countries. This was also observed by
Calder et al,277 who reported that a shift from rural to urban
living and at the same time from a traditional to a westerndiet
(containing a low amount of fiber) and lifestyle in Kenya
was associated with diverticulitis and colon carcinoma.
Today, there is an increasing recognition and understanding
of the complex role that fiber plays in maintaining intestinal
health that goes beyond the “traditional” increased bulk and
stool frequency effect. For instance, dietary fiber fermenta-
tion in human intestine produces short-chain fatty acids,
mainly acetic acid, propionic acid, and butyric acid,278 which
exert several beneficial effects on the intestinal tract. For
instance, butyrate and propionate, by inhibition of histone
deacetylase, are able to block the generation of dendritic
cells (DCs) from bone marrow stem cells, thereby inhibit-
ing the inflammatory response mediated by DCs.279 Also,
butyrate controls the assembly of epithelial cell tight junc-
tions, leading to decreased intestinal permeability,280 which
may be central to many inflammatory diseases, as explained
previously. Even more relevant, butyrate reduces bacterial
translocation into peripheral circulation independently of
intestinal permeability,281 most likely through decreased
NF-kB activation.281
Although whole grains are increasingly being recom-
mended, in part to increase fiber intake, given its potential
adverse effects already discussed, it would perhaps be
prudent that most of the dietary fiber came from fruit and
Perhaps even more important, the introduction of refined
sugars and, more recently, of high fructose corn syrup
(HFCS), has increased fructose intake to unprecedented high
levels.65,135 Mounting evidence suggests that this dietary shift
may be an important player in obesity, insulin resistance, dys-
lipidemia, gout, hypertension, kidney disease, and nonalco-
holic fatty liver disease.65,135,266,282,283 Although fruit is a natural
source of fructose, it also contains vitamin C, which offsets
some of the adverse effects of fructose,135 and various other
nutrients, as well as fiber. As such, consuming unprocessed
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The Western diet and lifestyle
fruit is not equivalent to consuming pure fructose, sucrose,
or HFCS.
The simple fact that fructose presents a low GI,266 but yet
because of its unique metabolism135,266 may have numerous
adverse effects, combined with the fact that cereal grains and
isolated sugars are the primary high-GL foods in the western
diet,65 suggests that the historical focus on the GI and GL
is incomplete and has to account for fructose and, perhaps
more important, the food source of CHO.
Another food group that was not part of Paleolithic diets
but is considered a staple today is dairy.65 Milk, yoghurt,
and some lactose-containing cheeses, despite having a low
GL, elicit a very high insulin response.284–288 The implica-
tions of these findings are not entirely known, because
the epidemiological evidence is conflicting regarding
the association of milk and dairy, insulin resistance, and
metabolic syndrome,289–294 but a small dietary intervention
study in young boys observed an increase of 103% and
75% in fasting plasma insulin concentrations and relative
insulin resistance, respectively, after 7 days on a high-
milk diet.288 Furthermore, epidemiologic and intervention
studies in children and adults demonstrate that cow’s milk
significantly increases plasma levels of IGF-1 and, perhaps
more important, the IGF-1/IGFBP-3 ratio.295 Moreover,
milk contains various hormones and growth factors296–300
that may have relevant implications for chronic degenera-
tive diseases. Indeed, epidemiologic evidence suggests that
milk may be implicated in acne273,300 and epithelial cell
cancers,295 particularly prostate cancer.300 Most of these
adverse effects are more likely to manifest in the postrepro-
ductive years and, as such, would not negatively affect the
selection of ALP-associated alleles. Indeed, as indicated
previously, genes that are important for early reproductive
success can be selected despite potentially detrimental
effects subsequent to their continued expression in later
life,301 which is why ALP should not be viewed as genetic
protection against potential adverse effects derived from
long-term dairy intake.
It should be mentioned that reactive monosaccharides
such as glucose and especially galactose (from dairy)302 and
fructose303 (which are muc h mo re r eac tive t han glu cos e)302,303
lead to AGE production and accumulate intra- and
extracellularly.303 Mo reove r, chr oni c hype rglyc emia is a well-
known accelerator of endogenous AGE production.261 In this
regard, the chronic consumption of a high intake of sucrose,
fructose, and galactose and/or the adoption of a high GL diet
may significantly contribute to the formation of AGEs.
It can therefore be concluded that an increase in diet’s GL
and insulinotropic potential, coupled with a higher fructose
(and possibly galactose) intake and a reduction in vitamin C
and dietary fiber consumption, may be another cause of the
high incidence and prevalence in industrialized countries of
epithelial cell cancers, obesity, metabolic syndrome, gout,
CHD, acne, myopia, and various gastrointestinal problems,
including constipation, irritable bowel syndrome, and
Macronutrient distribution
The percentage of total food energy (en%) derived from
macronutrients in Paleolithic diets would typically be
different from current official dietary guidelines (protein 15
en%; CHO 55–60 en%, and dietary fat 30 en%).65
Cordain et al155 estimated that the diets of historically
studied hunter–gatherer populations were higher in protein
(19–35 en%), lower in CHO (22–40 en%), and equivalent or
even higher in dietary fat (28–58 en%).
Even though the RDA for daily protein is 0.8 g/kg of
bodyweight,304 there is evidence that athletes need higher
amounts (in sports medicine, protein intake of 1.4–2 g/kg/d is
increasingly being recommended305). The elderly also need a
higher protein intake to prevent or attenuate sarcopenia306 and
osteopenia,307–309 because dietary protein increases calcium
absorption307,308 and has a n an abol ic e ffe ct o n mus cle 305,306 and
bone cells309,310 (es peci all y in the cont ext of a n et ba se- yielding
diet310). Moreover, high-protein diets (20% of caloric
intake65) have been shown to improve dyslipidemia65,108,109
and insulin sensitivity65,81,108 and are potential effective strat-
egies for improving obesity,65,271,311 metabolic syndrome,
and hypertension.65,312 Furthermore, a long-term high-protein
intake does not appear to adversely affect renal function
in individuals without pre-existing kidney disease.313–316
Nevertheless, there is a hepatic urea synthesis limit, which
lies between 2.6 g/kg/d and 3.6 g/kg/d.155
Regarding the lower CHO content of preagricultural diets,
it should be mentioned that mounting evidence suggests
that a reduced-CHO diet may be superior to a western-type
low-fat, high-CHO diet, especially in metabolic syndrome
patients, because it may lead to better improvement in insu-
lin resistance, postprandial lipemia, serum triglycerides,
HDL-C, total cholesterol/HDL-C (TC/HDL-C) ratio, LDL
particle distribution, apolipoprotein (apo)B/apo A-1 ratio,
postprandial vascular function, and certain inflammatory
biomarkers (such as TNF-A, IL-6, IL-8, MCP-1, E-selectin,
ICAM, and PAI-1).317,318 Nevertheless, because a low-CHO
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Carrera-Bastos et al
diet is obviously lower in sugars (such as sucrose and
fructose) and cereal grains and is often higher in protein,
it is unlikely that all of its positive effects can be attributed
solely to CHO restriction.
The concern that adopting a preagriculture-type diet may
encourage a higher intake of dietary fat with a consequent
increase in CVD risk is not justifiable, because the absolute
amount of dietary fat consumed is probably much less impor-
tant than is the type of fat consumed.24,108,319 For instance, the
traditional diet of Crete, which served as a guiding template
for the “Mediterranean Diet” used in clinical trials, had 35–40
en% from fat (especially cis mon oun sat urat ed f att y ac ids [ cis
MUFA] from olive oil and cis po lyu nsa tur ate d fat ty ac ids [cis
PUFA] of the omega-3 family, supplied by fish, egg yolk, and
wild plants such as purslane).319 The death rates from cancer
and heart disease in this region of Greece were one-third the
corresponding death rates in the US.319
Indeed, Mediterranean populations consuming diets rich
in cis MUFA from virgin olive oil have lower CHD rates,319
and in a recent reconstructed East African Paleolithic diet,157
MUFA represented 6–19 en%. Furthermore, various observa-
tional studies have reported an inverse association between
cis MUFA and CHD risk.24 Moreover, cis MUFA intake is
associated with improved lipoprotein parameters, reduced
LDL oxidation, improved insulin sensitivity, and reduced
thrombogenesis,24 and when it replaces CHO it decreases
triglycerides and total cholesterol/HDL-C ratio.320
A possible and widely available food source of cis MUFA
(which in evolutionary terms is a novel but yet apparently
beneficial food) is virgin olive oil321,322 that also contains
vitamin E (especially A-, B-, and G-tocopherol) and phenolic
compounds, which may reduce LDL and DNA oxidation and
increase plasma antioxidant capacity, resulting in less vascu-
lar damage by ROS.321,322 Furthermore, it may decrease the
activation of NF-kB, inhibit endothelial adhesion molecule
expression and platelet aggregation, and increase nitric oxide
In the reconstructed East African Paleolithic diet157 men-
tioned previously, the intake of saturated fatty acids (SAFA)
was estimated at 11–12 en%, and Cordain156 approximated that
in historically studied hunter–gatherer populations around the
globe, SAFA comprised 10–15 en%. Although this is higher
than the recommended intake (10%),65 it should be men-
tioned that even a 10 en% increase in SAFA intake replacing
complex CHO is estimated to raise total and LDL-C by only
20 mg/dL and 15 mg/dL (0.005 mmol/L and 0.004 mmol/L),
respectively.323 In addition, replacement of SAFA by refined
CHO and sugars increases triglyceride levels and small LDL
particles and reduces HDL-C.320,324 Moreover, not all SAFA
behave in the same manner. For instance, lauric acid has a
more favourable effect on TC/HDL-C than does CHO and
any other fatty acid, either saturated or unsaturated,320 whereas
myristic and palmitic acids appear to have little effect on this
CHD risk factor.320 Furthermore, a recent meta-analysis does
not support the notion that SAFA increase the risk of CHD,
stroke, or CVD,325 and replacement of SAFA with high GI
CHO has actually been found to significantly increase the
risk of myocardial infarction in a recent prospective cohort
study including 53,664 women and men.326 Also, there are
populations, such as the horticulturalists of Kitava and the
natives of Tokelau (Pacific Island), with very high SAFA
intake from coconut (up to 45% of total energy in the case
of Tokelau327) and apparently low CHD rates.68,112,327
Finally, SAFA, when consumed in the context of a higher-
protein, reduced-CHO diet, are not metabolically equivalent
to SAFA in the context of the typical western diet or even
in the context of a prudent low-fat, high-CHO diet. Indeed,
a recent trial observed that a reduced-CHO diet led to a
significant decrease in circulating SAFA in triacylglycerols
and cholesteryl ester, compared to a low-fat, high-CHO diet
containing 3 times less dietary SAFA.328
In light of that information, we propose increasing the
intake of protein (in the form of fish, shellfish, meat from
grass-fed and game animals, and eggs from free-range hens)
and cis MUFA (through virgin olive oil, avocados, and nuts),
decreasing CHO consumption (especially separated sugars
and cereal grains), and maintaining a moderate intake of
SAFA. We also support an elimination of industrial trans
fatty acids (TFA), which have no precedent in human his-
tory and are a recognized CHD risk factor,24,65 and perhaps
replacing myristic and palmitic acids with lauric acid. This
can be achieved through avoidance of fatty domesticated
meats and dairy products and moderate consumption of virgin
coconut oil, which presents antimicrobial properties,157 may
promote a more pronounced reduction in abdominal obesity
in the context of a hypocaloric diet,329 and may also decrease
TC/HDL-C,320 LDL oxidation,330 and lipoprotein(a).331
Omega-6/omega-3 ratio
Kuipers et al157 est ima ted a to tal cis PUFA intake between 8.6
en% and 15.2 en% in East African Paleolithic diets. But more
important is the balance between omega-6 and omega-3 cis
PUFA. In this regard, the ancestral dietary intake of alpha-
linolenic acid (ALA) and linoleic acid (LA) constituted
3.7–4.7 en% and 2.3–3.6 en%, respectively,157 whereas, in
the US,24 ALA represents only 0.6 en% and LA 6–7 en%,
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The Western diet and lifestyle
with similar intake having been reported in various western
countries, leading to an unprecedent increase in the LA/
ALA ratio of the western diet13,65 to 10/1, mainly due to
widespread use of LA-rich vegetable oils.14,24,26,65,157
This practice may have important implications, because
a high LA/ALA ratio is found in countries with a high
CHD incidence,332,333 and a high LA intake reduces the
omega-3 index334 (defined as the percentage of eicosapen-
taenoic acid [EPA] docosahexaenoic acid [DHA] in red
blood cell membranes, relative to all other fatty acids), which
has been proposed as a new CHD risk factor.335 Moreover, as
reviewed by Calder,336 in vitro data from human endothelial
cell studies demonstrate that LA activates NF-kB, leading to
a subsequent production of proinflammatory cytokines such
as IL-6 and TNF-A.
More important, the long-held notion that replacing
SAFA with LA will reduce CHD risk has recently been
challenged.337 As reviewed by Ramsden et al,337 only when
SAFA and TFA were replaced by a combination of omega-6
and omega-3 cis PUFA was there a reduced risk of CHD in
randomized controlled trials. In fact, LA-specific diets actu-
ally produced nonsignificant trends toward increased risks of
all CHD endpoints in randomized controlled trials, with the
increased risk of death from any cause approaching statistical
significance.337 This data, coupled with a long-term multiple
intervention trial with a diet of reduced omega-6 fatty acids
and increased omega-3 fatty acids, which showed a 70%
reduction in CHD events and mortality,338 strongly suggest
that a high LA intake is not necessary to decrease CHD risk
and may possibly increase it.
As for long-chain PUFA, Kuipers et al157 estimated that
the intake of omega-3 fatty acids (EPA DHA) and omega-6
arachidonic acid (AA) in East African Paleolithic diets was
1.7–14.2 g/d and 1.81–5.46 g/d, respectively. This figure con-
trasts with an EPA DHA and AA mean intake of 0.11 g/d
and 0.2 g/d, respectively, in the western diet.24,157
If the omega-3 index becomes accepted as a CHD
risk factor, then a reduced intake of omega-3 fatty acids
(EPA DHA) in the western diet is cause for serious concern.
This observation is further supported by data showing that
increased consumption of omega-3 fatty acids reduces the
risk of cardiovascular mortality in both epidemiological
and intervention studies.24,65 Many of these effects may
derive from the fact that these fatty acids reduce ventricu-
lar arrhythmias24 and are naturally ligands for peroxisome
proliferator-activated receptors (PPAR), sterol regulatory
element-binding proteins (SREBP), and carbohydrate respon-
sive element-binding protein (ChREBP).339 Hence, these fatty
acids modulate gene expression involved in lipid metabolism,
lipogenesis, fatty acid oxidation, cholesterol metabolism,
adipokine secretion, glucose metabolism, insulin sensitivity,
and inflammation.339 Furthermore, they directly downregulate
the transcription factor NF-kB, which has a major role in the
induction of proinflammatory genes.339
On a final note, it should be mentioned that although a
Paleolithic-type diet would lead to a higher intake of AA
and AA-derived eicosanoids, which initiate inflammation,
AA also produces lipoxins that, together with resolvins from
EPA and DHA and protectins and maresins from DHA,
are involved in the resolution phase of inflammation.339,340
Accordingly, increasing the consumption of omega-3
fatty acids (EPA DHA) from fatty fish and/or omega-3
supplements, choosing eggs and meats from grass-fed ani-
mals (which have a lower omega-6/omega-3 ratio than do
grain-fed animal meat and eggs108,319), and decreasing the
consumption of LA-rich vegetable oils may be an effective
strategy to reduce the risk of various chronic inflammatory
The adoption of diet and lifestyle that are very different from
what shaped the human genome for more than 2 million years
is a major factor in the widespread prevalence of chronic
degenerative diseases that are epidemic in western countries.
This conclusion strongly suggests that focusing on isolated
dietary or lifestyle variables is not an appropriate preventive
medicine strategy.
Indeed, the evolutionary template predicts that optimal
gene expression, and ultimately an increase in health span
(the number of years in good health), even if it would not
affect average life expectancy, will not be achieved by any
single dietary or lifestyle change but rather through the
combination of several measures, such as regular physical
exercise; stress management; sun exposure according to
latitude and skin color (in order to maintain plasma 25[OH]
D above 45 ng/mL and at the same time avoiding the adverse
effects of excessive sun exposure); adequate sleep; avoidance
of tobacco smoke; reduced exposure to pollutants, dietary
AGEs, ALES, and other Maillard reaction compounds; and
the adoption of a diet similar to that followed by Paleolithic
hunter–gatherers. Giving support to this notion, four recent
human intervention trials18,23,341,342 an d on e an imal tri al343 have
demonstrated that a diet composed of meat, fish, shellfish,
eggs, fresh fruit and vegetables, roots, tubers, nuts, and
seeds may be superior to so-called healthy diets such as the
Mediterranean diet.341
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Carrera-Bastos et al
We thank Mr Ricardo Reis Carvalho and Drs Christopher
Ramsden and Stephan Guyenet for their critical contributions
to this manuscript. We also express our gratitude to Professor
Frits Muskiet for his enlightening comments regarding evo-
lutionary medicine and the biochemistry of fatty acids.
The authors report no conflicts of interest in this work.
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... The gene pool of contemporary species is the result of their ancestors' adaptation to the environment they lived in. Current research suggests that the agricultural revolution, with the beginning of farming and animal husbandry (approximately, 10 000 years ago), and later on the industrial revolution (approximately, 200 years ago) are too recent in History for the human genome to fully adapt, especially in western societies [1]. ...
... The increase in food accessibility and industrial processing led to higher consumption of simple carbohydrates and saturated fats, whereas decreasing the ingestion of complex carbohydrates, such as fiber [1,4]. Most of the diseases of civilization are correlated with inflammation and an association with the so-called "western diet" has been demonstrated [5,6,3,7]. ...
... Even though most literature agrees that the energy obtained on a Western diet is roughly derived from 49% carbohydrates, 35% fats and 16% protein (resembling the United States of America lifestyle), both macro-and micronutrient compositions of western diets used in animal and human nutritional studies vary and might not be representative of all the western societies [1,[4][5][6][7]. In this way, we acknowledge that the problem is way more ample, and accordingly our main goal with this paper was to raise awareness so that more people get engaged in this discussion and we can, as a collective of experts from different fields, reach consensus in time. ...
Conference Paper
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The industrial revolution was the main driver for the “westernization” of human lifestyle, increasing the intake of highly industrially processed foods, rich in simple sugars and saturated fats. This new dietary pattern is often referred to as the “western diet”. The issue of using this term is that it lacks a standardized definition. Moreover, the dietary pattern that characterizes this diet is not entirely restricted to the West anymore. In this way, we propose a new definition of the diet that is heavily rooted on the process of food choice management, which is influenced by several documented socio-economic factors, such as geography, income and education. Moreover, we suggest that “Globalized diet” should be preferred as a label for the underlying concept of the “Western diet” since developed countries share more dietary traits among themselves than with developing countries, where the industrial revolution was less impactful, and where the globalized lifestyle has yet to be established. We are currently reaching out to as many researchers in the food nutrition field to achieve consensus in our proposed definition as we recognize the importance of standardizing terms for the generation of new knowledge through meta-analysis on broad multi-center nutritional studies.
... Intraluminal digestion, micelle formation, transmembrane transport and enterocyte processing within the endoplasmic reticulum (ER) have been extensively studied and reviewed over the past 5 decades [9][10][11][12][13]. Current understanding reveals that TGs are quantitatively the most abundant component of daily human dietary fat, with the remainder comprising PL, cholesterol esters and FFA [14,15]. When functioning normally, the gastrointestinal system digests and absorbs the majority of naturally structured TGs, with a fecal fat loss of approximately 5% or more indicative of malabsorption [16,17]. ...
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Background Fish oil is routinely concentrated into unmodified triglycerides, or trans-esterified into an ethyl ester form. Re-esterification of the ethyl ester form yields re-esterified triglycerides (rTG), which are reportedly more bioavailable than ethyl ester forms. However, the fidelity of the re-esterification process may yield variable triglyceride forms, with only 55–60% being rTG. Objective To determine whether the blood lipidomic response to supplementation with two rTG supplements, varying by degree of re-esterification, would differ between treatments. Design This was a double-blind, parallel-design, single-center, 128-day study with sixty young, healthy subjects randomized into two groups. One group received a >95% rTG (Ultimate Omega®), as 1,000 mg capsules containing 325 mg eicosapentaenoic acid (EPA) and 225 mg docosahexaenoic acid (DHA), and the other received a <70% rTG (MEG-3) as 1,000 mg capsules containing 300 mg EPA and 200 mg DHA. Total intake was 2,750 and 2,500 mg EPA+DHA for the Ultimate Omega® and MEG-3 groups, respectively, with blood drawn at 4, 16 and 24 weeks and analyzed for serum and erythrocyte phospholipid fatty acid (PLFA) content. Results For erythrocyte PLFA profiles, EPA, docosapentaenoic acid (DPA) and DHA percentage of total erythrocyte PLFA were significantly greater for the Ultimate Omega® group than for the MEG-3 group, at week 16 ( P < 0.05), as were the EPA:arachidonic acid (AA) ratio, DHA:AA ratio and EPA+DHA:AA ratio. For serum PLFA profiles, increases in EPA:AA ratio and EPA+DHA:AA ratio were significantly greater at week 4 in the Ultimate Omega® group compared to the MEG-3 group ( P < 0.05). Conclusions These data suggest that the percentage of rTG in rTG fish oil preparations may evolve as a new chemoprofile/quality control marker that can influence its lipidomic pharmacodynamics. Additional investigations to assess the physiologic/vascular and metabolic/inflammasome responses to concentrated fish oil preparations differing in the percentage of rTG are warranted.
... Given the latter, a related term, lifestyle diseases, is also emerging in this context [14]. This category of diseases includes, among others: obesity, diabetes, hypertension, heart disease, cancer, allergies, but also depression [14][15][16]. Civilization diseases are estimated to be responsible for more than 80% of deaths worldwide [13]. Undoubtedly, these are diseases of particular social importance, as they affect large groups and cause high social costs [17]. ...
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The importance of studying civilization diseases manifests itself in the impact of changing lifestyles, on the number of deaths and causes of death. Technology transfer plays an important role in the prevention and treatment of these diseases. Through this, it is possible to transfer new treatments and diagnostics to clinics and hospitals more quickly and effectively, which leads to better healthcare for patients. Technology transfer can also aid in the development of new drugs and therapies that can be effective in the treatment of civilization diseases. The paper aims to evaluate the technology transfer process in the field of civilization diseases, using COVID-19 as an example of a pandemic that requires quick development and transfer of technology. To achieve the assumed goal, we propose a multivariate synthetic ratio in the field of civilization diseases (SMTT—Synthetic Measure of Technology Transfer) to analyze data from the Global Data database. We used sub-measures like SMTT_value (Synthetic Measure of Technology Transfer_value) and SMTT_quantity (Synthetic Measure of Technology Transfer_quantity) to measure technology transfer and put the data into a graph. Our analysis focuses on 14 diseases over a period of 10 years (2012–2021) and includes nine forms of technology transfer, allowing us to create a tool for analysing the process in multiple dimensions. Our results show that COVID-19 is similar in terms of technology transfer to diseases such as diabetes, cardiovascular diseases, neurodegenerative diseases, and breast cancer, even though data for COVID-19 is available for only 2 years.
... acteristics of an environment closer to nature as an effective strategy to reduce the risk of chronic degenerative diseases (Carrera-Bastos et al. 2011), despite the fact that this would also help to save our planet from excessive land and water consumption for meat production (Arneth et al. 2020). ...
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This book gives positive examples how humans and rivers have been, and are still in some places, living in harmony. It analyses how this knowledge can be transferred into modern river management schemes and thereby it attempts to mitigate the deplorable trend of the decline of biological and cultural heritages and diversities in and along rivers. A harmonious way to live with the river includes i.a. respecting its natural features and ecosystem services. This means that human land use forms and cultures, including fishing, agriculture, navigation and river works respect the natural hydrological patterns (Flood Pulse, Environmental Flows). It also includes the physical-psychological-spiritual linkage of the people to the river (e.g. worshipping, well-being, detention, and in-spiration), and how these linkages serve as a motivation to take action in favor of the river’s nature. Twenty-nine case studies from Africa, Asia, the Americas and Europe, and 7 papers on overarching themes of sustainable river management are presented. Without claiming its completeness, we understand this book as a first attempt to highlight the interactions between the biological-evolutive populations of non-human biota and the biological-evolutive-cultural populations of human beings, using the dynamic riverscape as the physical background. The target audience of this book includes interdisciplinary scientists from the fields of ecology, geosciences, social and political sciences, as well as urban planners and managers of river ecosystems and riverine heritage sites worldwide.
... One potential consequence of food industrialization is that human populations have been deprived of diverse microbial exposures (Marco et al. 2020). In turn, food industrialization has also coincided with low gut microbiome diversity, generating questions about how this loss has contributed to the higher incidence of metabolic and inflammatory diseases observed in the industrialized western world, compared with populations that still rely on traditionaldiets for subsistence (Carrera-Bastos et al., 2011;Pontzer et al., 2012). To address this public health issue, diets targeting the gut microbiome to introduce or enhance certain taxa or specific functionalities have been proposed in precision nutrition and medicine (Wastyk et al., 2021). ...
The industrialization of Western food systems has greatly reduced the regular consumption of lacto-fermented vegetables (LFV). Consuming LFV may exert health benefits through the alteration of the gut microbiome, but the events and mechanisms involved remain unclear. To start understanding the possible benefits of LFV, we compared fecal microbial diversity and composition, as well as dietary habits between individuals who regularly consume LFV (n=23) and those who do not (n=24). We utilized microbial DNA amplicon sequencing (16s rRNA and ITS2) and untargeted metabolomics (LC-MS) to analyze stool samples. Study participants also provided three consecutive days of dietary data. Results show only minor effects on microbiome composition; with the enrichment of a few microorganisms potentially associated with vegetable ferments, such as _Leuconostoc mesenteroides and Rhodotorula mucilaginosa (P<0.05)_, in LFV consumers. However, LFV consumption had greater effects on the fecal metabolome, with higher abundances of butyrate, acetate, and valerate (P<0.05) and significantly greater metabolome diversity (_P<0.001_). Overall, the observations of minor changes in the fecal microbiome and greater effects on the fecal metabolome from LFV consumption warrant further investigations on the health significance of LFV as regular components of the daily diet in humans.
... Traditional food, one part of the cultural heritage, is currently experiencing challenges. The phenomenon of traditional foods gradually vanishes occurs in various ethnic groups worldwide [5,6]. This is very concerning because future generations have the potential to no longer recognize traditional foods that should be preserved or maintained as cultural heritage. ...
... These three nutrition models (DASH, Nordic and Mediterranean diet) are rich in nutrients beneficial for health [33][34][35]. The Western diet contains many harmful elements which may increase the risk of non-communicable diseases [36]. The United Nations Educational, Scientific and Cultural Organization (UNESCO) has listed the Mediterranean diet as an Intangible Cultural Heritage [37]. ...
Full-text available
Metabolic syndrome, also as known as Syndrome X or Insulin Resistance Syndrome, is a complex health problem featuring visceral obesity (the main diagnostic criterion), insulin resistance, dyslipidemia and high blood pressure. Currently, this health condition has gained a momentum globally while raising concerns among health-related communities. The World Health Organization, American Heart Association and International Diabetes Federation have formulated diagnostic criteria for metabolic syndrome. Diet and nutrition can influence this syndrome: for example, the Western diet is associated with increased risk of metabolic syndrome, whereas the Nordic and Mediterranean diets and the Dietary Approach to Stop Hypertension are potentially beneficial. The Mediterranean diet can affect the components of metabolic syndrome due to its high dietary fiber, omega 3 and 9 fatty acids, complex carbohydrates, antioxidants, minerals, vitamins and bioactive substances, such as polyphenols. These nutrients and bioactive substances can combat obesity, dyslipidemia, hypertension and diabetes mellitus. The mechanisms by which they do so are generally related to oxidative stress, inflammation (the most common risk factors for metabolic syndrome) and gastrointestinal function. The literature also shows examples of positive effects of the Mediterranean diet on the metabolic syndrome. In this review of the literature, we shed light on the effects, mechanisms and dynamic relationship between the Mediterranean diet and metabolic syndrome.
... However, increased longevity is associated with a growth in non-communicable and disabling diseases of old age such as neurodegenerative diseases, cardiovascular disease, and cancer. Furthermore, the western diet and lifestyle, characterized by unhealthy diet and sedentariness, has engendered many, so-called diseases of civilization, including obesity-associated metabolic syndrome, coronary heart disease, hypertension, stroke, type 2 diabetes, chronic liver disease, autoimmune disease, epithelial cell cancers, and osteoporosis, which are scarce or non-existent in hunter-gatherers and other non-westernized populations (2). As a consequence of civilization, life expectancy is expected, for the first time, to fall (3,4). ...
Full-text available
Religious fasting is practiced by people of all faiths, including Christianity, Islam, Buddhism, Jainism, as well as Hinduism, Judaism, and Taoism. Individual/clinical, public, global, and planetary health has traditionally been studied as separate entities. Nevertheless, religious fasting, in conjunction with other religious health assets, can provide several opportunities, ranging from the individual to the population, environmental, and planetary levels, by facilitating and supporting societal transformations and changes, such as the adoption of healthier, more equitable, and sustainable lifestyles, therein preserving the Earth's systems and addressing major interconnected, cascading, and compound challenges. In this review, we will summarize the most recent evidence on the effects of religious fasting, particularly Orthodox and Ramadan Islamic fasting, on human and public health. Further, we will explore the potential effects of religious fasting on tackling current environmental issues, with a special focus on nutrition/food restriction and planetary health. Finally, specific recommendations, particularly around dietary intake during the fasting rituals, will be provided to ensure a sustainable healthy planet.
... Consumers prefer the foods that are refined for maximum satiety, because of a desire to feel full at a faster rate while enjoying the sweetness of the food item. Unfortunately, the processing of foods for maximum satiety creates a meal that is low in minerals, vitamins, fibres and plant phytochemicals (bitters), thereby converting the sugar/starch and fat fraction from a potential nutritional package to a serving of mere calories [19]. ...
Full-text available
The rising burden of cardiovascular disease in South Africa gives impetus to managerial changes, particularly to the available foods in the market. Since there are many economically disadvantaged groups in urban societies who are at the forefront of the CVD burden, initiatives to make healthier foods available should focus on affordability in conjunction with improved phytochemical diversity to incentivize change. The modern obesogenic diet is deficient in phytochemicals that are protective against the metabolic products of sugar metabolism, i.e., inflammation, reactive oxygen species and mitochondrial fatigue, whereas traditional southern African food species have high phytochemical diversity and are also higher in soluble dietary fibres that modulate the release of sugars from starches, nurture the microbiome and produce digestive artefacts that are prophylactic against cardiovascular disease. The examples of indigenous southern African food species with high horticultural potential that can be harvested sustainably to feed a large market of consumers include: Aloe marlothii, Acanthosicyos horridus, Adansonia digitata, Aloe ferox, Amaranthus hybridus, Annesorhiza nuda, Aponogeton distachyos, Bulbine frutescens, Carpobrotus edulis, Citrullus lanatus, Dioscorea bulbifera, Dovyalis caffra, Eleusine coracana, Lagenaria siceraria, Mentha longifolia, Momordica balsamina, Pelargonium crispum, Pelargonium sidoides, Pennisetum glaucum, Plectranthus esculentus, Schinziophyton rautanenii, Sclerocarya birrea, Solenostemon rotundifolius, Talinum caffrum, Tylosema esculentum, Vigna unguiculata and Vigna subterranea. The current review explains the importance of phytochemical diversity in the human diet, it gives a lucid explanation of phytochemical groups and links the phytochemical profiles of these indigenous southern African foods to their protective effects against cardiovascular disease.
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Ischemic heart disease is very uncommon in Greenland Eskimos (Harvald, 1974). In his extensive nosography of Greenland, Berthelsen (1940) does not even mention this disease, although he gives some information on atherosclerosis in Greenlanders. Other thrombotic diseases, in both the arterial and the venous systems, are mentioned either very infrequently by him or not at all. In the annual report on the state of health in Greenland (Bøggild et al., 1978) covering the years 1973–1976, death from ischemic heart diseases constitutes an average of 3.5% of all causes of death. In this and in other official medical statistics, no distinction is made between true Greenlanders and Danish workers who spend various amounts of time in Greenland, but who almost invariably carry their Western way of life with them. However, this fraction of the total population of nearly 50,000 inhabitants on this huge island of 2,175,000 km2 is small. Life expectancy rapidly increased in the more than 60 years since tuberculosis was successfully defeated. The most common cause of death is still accidents, amounting to about one-third of all deaths. The same statistical source reports an annual average of 9 1/2 cases of myocardial infarction among hospitalized patients in Greenland. The majority of these, as well as of the deaths reportedly caused by ischemic heart diseases, is from the southern and most “Westernized” part of Greenland, whereas from 1968 to 1978, not a single death from ischemic heart disease or case of myocardial infarction was reported from the UmanaK district (population of about 2600) where the present investigations were carried out.
The aim of this study was to systematically compare postprandial insulin responses to isoenergetic 1000-kJ (240-kcal) portions of several common foods. Correlations with nutrient content were determined. Thirty-eight foods separated into six food categories (fruit, bakery products, snacks, carbohydrate-rich foods, protein-rich foods, and breakfast cereals) were fed to groups of 11-13 healthy subjects. Finger-prick blood samples were obtained every 15 min over 120 min. An insulin score was calculated from the area under the insulin response curve for each food with use of white bread as the reference food (score = 100%). Significant differences in insulin score were found both within and among the food categories and also among foods containing a similar amount of carbohydrate. Overall, glucose and insulin scores were highly correlated (r = 0.70, P < 0.001, n = 38). However, protein-rich foods and bakery products (rich in fat and refined carbohydrate) elicited insulin responses that were disproportionately higher than their glycemic responses. Total carbohydrate (r = 0.39, P < 0.05, n = 36) and sugar (r = 0.36, P < 0.05, n = 36) contents were positively related to the mean insulin scores, whereas fat (r = -0.27, NS, n = 36) and protein (r = -0.24, NS, n = 38) contents were negatively related. Consideration of insulin scores may be relevant to the dietary management and pathogenesis of non-insulin-dependent diabetes mellitus and hyperlipidemia and may help increase the accuracy of estimating preprandial insulin requirements.
We have built a world that no longer fits our bodies. Our genes - selected through our evolution - and the many processes by which our development is tuned within the womb, limit our capacity to adapt to the modern urban lifestyle. There is a mismatch. We are seeing the impact of this mismatch in the explosion of diabetes, heart disease and obesity. But it also has consequences in earlier puberty and old age. Bringing together the latest scientific research in evolutionary biology, development, medicine, anthropology and ecology, Peter Gluckman and Mark Hanson, argue that many of our problems as modern-day humans can be understood in terms of this fundamental and growing mismatch. It is an insight that we ignore at our peril.
'Typically Western' diseases derive from cultural trends that have changed our environment and by which we have pushed our conditions of existence beyond our evolutionary-established flexibility to adapt. Biochemical mechanisms by which our phenotype remains adapted to the environment include adjustment of DNA sequence and adjustments via epigenetics and endogenous sensors. Adjustment of DNA base sequence is a slow process by which a species remains adapted to its (changing) environment and from which eventually new species occur. Famine and microorganisms are among the principal environmental factors that have shaped and still shape our DNA base sequence. An example is the sickle cell gene that confers heterozygote survival advantage against malaria infection in countries like Kenya and Nigeria. There are several other mutations indicating that humans still evolve. Medium and short term adaptations occur by epigenetics, which is the study of changes in gene expression that are not accompanied by alterations of DNA sequence. The epigenome derives from DNA methylation and histone modification. Epigenetic marks are inherently labile and constitute the basis of cell differentiation and parent-of-origin specific effects via 'imprinting'. The epigenome also confers environmental instructions to the genome. These marks constitute a 'memory' by which information on the environment can potentially be transmitted to the next generation(s). Folate is one of many environmental factors that modulate phenotype by epigenetic mechanisms. Uniparental disomy and mutations in the epigenetic machinery are classical examples of epigenetic derangement. Some rare diseases derive from mutations, epigenetic derangements, or combination of these, affecting a single locus. A recent study linked epigenetic mechanisms to the hypothesis of the 'developmental origins of disease'. Mismatch between expected and actual environments may explain occurrence of typically Western diseases. Much progress has been made in the epigenetics of cancer. Tumorigenesis models with mutually-amplifying epigenetic disregulation and mutation have e.g. been postulated. Short term adaptation to the environment occurs by endogenous 'sensors'. For instance, peroxisome-proliferator activated receptors (PPARs) are nuclear transcription factors that function as lipid sensors. Upon activation by dietary fatty acids, they induce the coordinated expression and repression of proteins involved in intermediary metabolism, growth and differentiation, and inflammatory responses. Harmony between our millions of years old genome and environment may increase our numbers of years in health. For clinical chemistry, achievement of this state of 'optimal homeostasis' requires rethinking of the use of reference values and the use of algorithms for 'risk assessment' that enable early intervention. Also Homo sapiens needs to adapt to the conditions of existence on which its genome has been shaped during evolution.
Nutrition science is a highly fractionated, contentious field with rapidly changing viewpoints on both minor and major issues impacting on public health. With an evolutionary perspective as its basis, this exciting book provides a framework by which the discipline can finally be coherently explored. By looking at what we know of human evolution and disease in relation to the diets that humans enjoy now and prehistorically, the book allows the reader to begin to truly understand the link between diet and disease in the Western world and move towards a greater knowledge of what can be defined as the optimal human diet. Written by a leading expert Covers all major diseases, including cancer, heart disease, obesity, stroke and dementia Details the benefits and risks associated with the Palaeolithic diet Draws conclusions on key topics including sustainable nutrition and the question of healthy eating This important book provides an exciting and useful insight into this fascinating subject area and will be of great interest to nutritionists, dietitians and other members of the health professions. Evolutionary biologists and anthropologists will also find much of interest within the book. All university and research establishments where nutritional sciences, medicine, food science and biological sciences are studied and taught should have copies of this title.