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Cardiovascular Disease Resulting From a Diet and Lifestyle at Odds With Our Paleolithic Genome: How to Become a 21st-Century Hunter-Gatherer

      Our genetic make-up, shaped through millions of years of evolution, determines our nutritional and activity needs. Although the human genome has remained primarily unchanged since the agricultural revolution 10,000 years ago, our diet and lifestyle have become progressively more divergent from those of our ancient ancestors. Accumulating evidence suggests that this mismatch between our modern diet and lifestyle and our Paleolithic genome is playing a substantial role in the ongoing epidemics of obesity, hypertension, diabetes, and atherosclerotic cardiovascular disease. Until 500 generations ago, all humans consumed only wild and unprocessed food foraged and hunted from their environment. These circumstances provided a diet high in lean protein, polyunsaturated fats (especially omega-3 [ω-3] fatty acids), monounsaturated fats, fiber, vitamins, minerals, antioxidants, and other beneficial phytochemicals. Historical and anthropological studies show hunter-gatherers generally to be healthy, fit, and largely free of the degenerative cardiovascular diseases common in modern societies. This review outlines the essence of our hunter-gatherer genetic legacy and suggests practical steps to realign our modern milieu with our ancient genome in an effort to improve cardiovascular health.
      Humans evolved during the Paleolithic period, from approximately 2.6 million years ago to 10,000 years ago. Although the human genome has remained largely unchanged (DNA evidence documents relatively little change in the genome during the past 10,000 years),
      • Macaulay V
      • Richards M
      • Hickey E
      • et al.
      The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs.
      our diet and lifestyle have become progressively more divergent from those of our ancient ancestors. These maladaptive changes began approximately 10,000 years ago with the advent of the agricultural revolution and have been accelerating in recent decades. Socially, we are a people of the 21st century, but genetically we remain citizens of the Paleolithic era.
      Today most of us dwell in mechanized urban settings, leading largely sedentary lives and eating a highly processed synthetic diet. As a result, two thirds of Americans are overweight or obese.
      • Flegal KM
      • Carroll MD
      • Ogden CL
      • Johnson CL
      Prevalence and trends in obesity among US adults, 1999-2000.
      The lifetime incidence of hypertension is an astounding 90%,
      • Vasan RS
      • Beiser A
      • Seshadri S
      • et al.
      Residual lifetime risk for developing hypertension in middle-aged women and men: the Framingham Heart Study.
      and the metabolic syndrome is present in up to 40% of middle-aged American adults.
      • Ford ES
      • Giles WH
      • Dietz WH
      Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey.
      Cardiovascular disease remains the number 1 cause of death, accounting for 41% of all fatalities, and the prevalence of heart disease in the United States is projected to double during the next 50 years.
      • Foot DK
      • Lewis RP
      • Pearson TA
      • Beller GA
      Demographics and cardiology, 1950-2050.
      Despite remarkable pharmacological and technological advances, the pandemic of cardiovascular disease continues. At least for today, the genes we are born with are those that we will live and die with. Thus, the most practical solution for reducing the incidence of chronic degenerative diseases such as atherosclerosis is to realign our current maladaptive diet and lifestyle to simulate the milieu for which we are genetically designed.
      Living organisms thrive best in the milieu and on the diet to which they were evolutionarily adapted; this is a fundamental axiom of biology. All of the food consumed daily by our ancient ancestors had to be foraged or hunted from wild plants and animals in their natural world. In many respects, that Paleolithic world is gone forever, but insights gained from a wide array of disciplines are providing a clear picture of the ideal diet and lifestyle for humans. The hunter-gatherer mode of life became extinct in its purely non-westernized form in the 20th century.
      At the beginning of the 21st century, we are the first generation to have the genetic and scientific understanding to allow us to reconstruct the essence of this lifestyle and the means to afford it.
      Historical and archaeological evidence shows huntergatherers generally to be lean, fit, and largely free from signs and symptoms of chronic diseases.
      • Eaton SB
      • Konner M
      • Shostak M
      Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective.
      When huntergatherer societies transitioned to an agricultural grainbased diet, their general health deteriorated.
      • Cohen MN
      The significance of long-term changes in human diet and food economy.
      • Cassidy CM
      Nutrition and health in agriculturalists and hunter-gatherers: a case study of two prehistoric populations.
      Average adult height was substantially shorter for both men and women who consumed cereals and starches compared with their hunter-gatherer ancestors who consumed lean meats, fruits, and vegetables.
      • Cohen MN
      Furthermore, studies of bones and teeth reveal that populations who changed to a grain-based diet had shorter life spans, higher childhood mortality, and a higher incidence of osteoporosis, rickets, and various other mineral- and vitamin-deficiency diseases.
      • Cohen MN
      The significance of long-term changes in human diet and food economy.
      • Cassidy CM
      Nutrition and health in agriculturalists and hunter-gatherers: a case study of two prehistoric populations.
      When former hunter-gatherers adopt Western lifestyles, obesity, type 2 diabetes, atherosclerosis, and other diseases of civilization become commonplace.
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      • Rowley KG
      • McDermott R
      • Mylvaganam A
      • O'Dea K
      Diabetes incidence in an Australian aboriginal population: an 8-year follow-up study.
      • Ebbesson SO
      • Schraer CD
      • Risica PM
      • et al.
      Diabetes and impaired glucose tolerance in three Alaskan Eskimo populations: the Alaska-Siberia Project.
      This review outlines the essence of the hunter-gatherer lifestyle and diet and suggests practical steps to realign our modern milieu with our ancient genome in an effort to improve cardiovascular health, vigor, and longevity.

      THE IDEAL HUMAN DIET

      Perhaps no scientific topic has generated more controversy and confusion in recent times than the question of the ideal human diet. Medical experts espouse divergent views of human nutrition with evangelical zeal, each citing scientific data to validate their respective contradictory conclusions. This confusing dialogue is epitomized by the Atkins
      • Atkins RC
      vs Ornish
      • Ornish D
      debate. The Atkins diet includes high protein, high saturated fat, and avoidance of nearly all carbohydrates. In contrast, the Ornish diet consists of 80% carbohydrates and minimized consumption of all animal protein fats. Proponents of both diets insist theirs is the answer to the American epidemics of obesity and cardiovascular disease; however, the advice for these diets is mutually exclusive and diametrically opposed.
      In truth, the ideal diet is neither of these extremes nor what many medical professionals now promote. In a recently published large review of approximately 150 studies on the link between diet and cardiovascular health,
      • Hu FB
      • Willett WC
      Optimal diets for prevention of coronary heart disease.
      the authors concluded that 3 major dietary approaches have emerged as the most effective in preventing cardiovascular events: (1) replacing saturated and trans-fats with monounsaturated and polyunsaturated fats; (2) increasing consumption of omega-3 (ω-3) fats from either fish or plant sources such as nuts; and (3) eating a diet high in various fruits, vegetables, nuts, and whole grains and avoiding foods with a high glycemic load (a large amount of quickly digestible carbohydrates). Despite common misperceptions, this report found no strong evidence for a link between risk of cardiovascular disease and intake of meat, cholesterol, or total fat.
      These broad characteristics are consistent with the diet that Paleolithic humans evolved eating. This is the diet that our hunter-gatherer ancestors thrived on until the advent of the agricultural revolution. Through the millennia, our genome and physiology became adapted to this diet. Of course, this diet varied by paleontological period, geographic location, season, and culture, but many characteristics remained consistent until recent times (Table 1).
      Table 1Comparison of Diets
      Hunter-gathererLow-carbohydrate (Atkins diet)Traditional low-fat (Ornish diet)Traditional Mediterranean
      Protein (%)High (19-35)Moderate (18-23)Low (<15)Moderate (16-23)
      Carbohydrates (%)Moderate (22-40)Low (4-26)High (80)Moderate (50)
      Total fat (%)Moderate (28-47)High (51-78)Low (<10)Moderate (30)
      Saturated fatModerateHighLowLow
      Monounsaturated fatHighModerateLowHigh
      Polyunsaturated fatModerateModerateLowModerate
      Omega-3 fatHighLowLowHigh
      Total fiberHighLowHighHigh
      Fruits and vegetablesHighLowHighHigh
      Nuts and seedsModerateLowLowModerate
      SaltLowHighLowModerate
      Refined sugarsLowLowLowLow
      Glycemic loadLowLowHighLow

      REAL FOOD, NOT SYNTHETIC FOOD

      Our remote ancestors consumed only natural and unprocessed food foraged and hunted from their environment. This subsistence strategy provided a diet of lean protein that was high in fiber, vitamins, minerals, antioxidants, and other beneficial phytochemicals
      • Eaton SB
      • Eaton III, SB
      • Konner MJ
      Paleolithic nutrition revisited: a twelve-year retrospective on its nature and implications.
      (Table 2). The typical Paleolithic diet compared with the average modern American diet contained 2 to 3 times more fiber, 1.5 to 2.0 times more polyunsaturated and monounsaturated fats, 4 times more ω-3 fats, but 60% to 70% less saturated fat. Protein intake was 2 to 3 times higher, and potassium intake was 3 to 4 times higher; however, sodium intake was 4 to 5 times lower.
      • Cordain L
      The nutritional characteristics of a contemporary diet based upon Paleolithic food groups.
      Finally, the Paleolithic diet contained no refined grains and sugars (except for seasonally available honey). Clearly, the ongoing epidemic of cardiovascular diseases is at least in part due to these striking discrepancies between the diet we are designed to eat and what we eat today.
      Table 2Fundamentals of the Hunter-Gatherer Diet and Lifestyle
      • Eat whole, natural, fresh foods; avoid highly processed and high-glycemic-load foods
      • Consume a diet high in fruits, vegetables, nuts, and berries and low in refined grains and sugars. Nutrient-dense, low-glycemic-load fruits and vegetables such as berries, plums, citrus, apples, cantaloupe, spinach, tomatoes, broccoli, cauliflower, and avocados are best
      • Increase consumption of omega-3 fatty acids from fish, fish oil, and plant sources
      • Avoid trans-fats entirely, and limit intake of saturated fats. This means eliminating fried foods, hard margarine, commercial baked goods, and most packaged and processed snack foods. Substitute monounsaturated and polyunsaturated fats for saturated fats
      • Increase consumption of lean protein, such as skinless poultry, fish, and game meats and lean cuts of red meat. Cuts with the words round or loin in the name usually are lean. Avoid high-fat dairy and fatty, salty processed meats such as bacon, sausage, and deli meats
      • Incorporate olive oil and/or non–trans-fatty acid canola oil into the diet
      • Drink water
      • Participate in daily exercise from various activities (incorporating aerobic and strength training and stretching exercises). Outdoor activities are ideal
      In growing season, abundant fruits, berries, and vegetables were consumed. The one variable on which nearly all nutritional experts can agree is the need for increased intake of fruits and vegetables in our modern diet. We do not fully understand all the health-promoting components of unprocessed whole-plant foods; thus, the only way to ensure the benefits is to consume these foods regularly in their natural and unprocessed state. Most experts recommend an intake of 5 servings of fruits and vegetables per day; studies indicate that only 16% of adults are meeting this goal.
      • DeBoer SW
      • Thomas RJ
      • Brekke MJ
      • et al.
      Dietary intake of fruits, vegetables, and fat in Olmsted County, Minnesota.
      However, approximately 8 or more daily servings of fresh fruits and vegetables (avoiding potatoes and bananas because of their high glycemic loads) are necessary to replicate the dietary composition that we evolved eating
      • Cordain L
      The nutritional characteristics of a contemporary diet based upon Paleolithic food groups.
      and to lower the risk of coronary heart disease.
      • Joshipura KJ
      • Hu FB
      • Mason JE
      • et al.
      The effect of fruit and vegetable intake on risk for coronary heart disease.
      Large randomized controlled trials recently have shown antioxidant supplements to be ineffective in improving cardiovascular outcomes.
      Heart Protection Study Collaborative Group
      MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial.
      • GISSI-Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico)
      Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial [published correction appears in Lancet. 2001;357:642].
      In contrast, many epidemiological studies have shown cardiovascular protection from diets that contain foods naturally high in antioxidants, such as vitamins A, C, and E.
      • Joshipura KJ
      • Hu FB
      • Mason JE
      • et al.
      The effect of fruit and vegetable intake on risk for coronary heart disease.
      • Curtis BM
      • O'Keefe Jr, JH
      Understanding the Mediterranean diet: could this be the new “gold standard” for heart disease prevention?.
      The hunter-gatherer diet is high in beneficial phytochemicals and antioxidants, thus rendering multivitamin and mineral supplements superfluous.
      • Cordain L
      The nutritional characteristics of a contemporary diet based upon Paleolithic food groups.

       Caloric Intake

      Throughout most of human history, food consumption (energy intake) was obligatorily linked to food acquisition (energy output). Accordingly, our ancient ancestors expended more energy finding and obtaining food calories than do typical sedentary, westernized citizens for whom there is virtually no connection between energy intake and energy expenditure.
      Our cravings for calorie-dense foods, such as fats, sweets, and starches, are legacies of our Paleolithic ancestors, who sought these foods because they conferred positive survival value in an environment in which these food types were scarce. These cravings betray us in our modern world, where calorie-dense foods are abundant and inexpensive, and most people die of caloric excess manifested as obesity, the metabolic syndrome, hypertension, and cardiovascular disease. Compounding the issue is the fact that our genome became adapted to an environment in which caloric intake was often sporadic and sometimes inadequate. This promoted efficient energy use and storage, commonly referred to as the thrifty gene hypothesis. Although this genetic adaptation (which results in storage of excess calories as intra-abdominal fat) provides a survival advantage in an environment of scarcity, it becomes a liability in the setting of long-term excessive caloric intake.
      Although the key to weight loss is simply the daily consumption of fewer calories than are expended, it is easier to moderate caloric intake in a diet that has adequate quantities of protein and fat because of superior satiety compared with a high-carbohydrate, low-fat diet.
      • Hu FB
      • Willett WC
      Optimal diets for prevention of coronary heart disease.
      • Willett WC
      • Stampfer MJ
      Rebuilding the food pyramid.
      • Sacks FM
      • Katan M
      Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease.
      This strategy in part accounts for the success of the Atkins diet in inducing weight loss,
      • Brehm BJ
      • Seeley RJ
      • Daniels SR
      • D'Alessio DA
      A randomized trial comparing a very low carbohydrate diet and a calorierestricted low fat diet on body weight and cardiovascular risk factors in healthy women.
      but its high levels of saturated fat, low levels of antioxidants, and net metabolic acidosis, which may promote osteoporosis and atherosclerosis, make this a suboptimal eating style.
      • Bravata DM
      • Sanders L
      • Huang J
      • et al.
      Efficacy and safety of low-carbohydrate diets: a systematic review.
      • Reddy ST
      • Wang CY
      • Sakhaee K
      • Brinkley L
      • Pak CY
      Effect of low-carbohydrate high-protein diets on acid-base balance, stoneforming propensity, and calcium metabolism.
      A growing consensus indicates that a diet containing moderate amounts of beneficial fat and protein in addition to carbohydrates consisting exclusively of low-glycemic-load foods (nonstarchy vegetables and fruits) in conjunction with daily exercise is the most effective way to achieve and maintain ideal body weight and prevent cardiovascular disease.
      • Hu FB
      • Willett WC
      Optimal diets for prevention of coronary heart disease.
      • Willett WC
      • Stampfer MJ
      Rebuilding the food pyramid.
      • Sacks FM
      • Katan M
      Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease.
      • Bravata DM
      • Sanders L
      • Huang J
      • et al.
      Efficacy and safety of low-carbohydrate diets: a systematic review.
      This approach was the eating pattern and lifestyle of prehistoric humans.

       ω-3 Fats

      The polyunsaturated fats are classified as ω-6 (generally proinflammatory) and ω-3 (anti-inflammatory with several other inherent cardioprotective effects). ω-3 Fats were abundant in the diet of our Paleolithic ancestors.
      • Eaton SB
      • Eaton III, SB
      • Sinclair AJ
      • Cordain L
      • Mann NJ
      Dietary intake of long-chain polyunsaturated fatty acids during the paleolithic.
      In the natural world, the broad base of the food chain is composed of ubiquitous algae in the sea and of grasses and leaves on land. The small amount of fat in algae, grasses, and leaves is rich in ω-3 fatty acids, which become more concentrated in larger animals up through both the land and marine food chains, especially in fish and larger grazing animals. Today, meat from domesticated animals is low in ω-3 fats because these animals are generally grain-fed or corn-fed rather than grass-fed.
      • Cordain L
      • Watkins BA
      • Florant GL
      • Kelher M
      • Rogers L
      • Li Y
      Fatty acid analysis of wild ruminant tissues: evolutionary implications for reducing diet-related chronic disease.
      This and other issues have resulted in much lower intake of ω-3 fats today compared with our remote ancestors.
      • Eaton SB
      • Eaton III, SB
      • Sinclair AJ
      • Cordain L
      • Mann NJ
      Dietary intake of long-chain polyunsaturated fatty acids during the paleolithic.
      • Cordain L
      • Watkins BA
      • Florant GL
      • Kelher M
      • Rogers L
      • Li Y
      Fatty acid analysis of wild ruminant tissues: evolutionary implications for reducing diet-related chronic disease.
      The correction of this ω-3 deficiency in the modern diet is a key step to improving the cardiovascular risk in our population.
      • O'Keefe Jr, JH
      • Harris WS
      From Inuit to implementation: omega-3 fatty acids come of age.
      Two randomized trials, the Lyon Diet Heart Study,
      • de Lorgeril M
      • Salen P
      • Martin JL
      • Monjaud I
      • Delaye J
      • Mamelle N
      Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study.
      which involved 600 postinfarction patients, and the Indo-Mediterranean Diet Heart Study
      • Singh RB
      • Dubnov G
      • Niaz MA
      • et al.
      Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomized single-blind trial.
      (Figure 1), which involved 1000 coronary heart disease patients, evaluated a standard low-fat American Heart Association diet vs a traditional Mediterranean diet (similar in composition to our ancestral hunter-gatherer diet; Table 1). The patients on the Mediterranean diet rich in ω-3 and monounsaturated fats, fruits, vegetables, legumes, and nuts experienced 50% to 70% reductions in risk of cardiovascular events during long-term follow-up.
      Figure thumbnail gr1
      Figure 1The Indo-Mediterranean Diet Heart Study
      • Singh RB
      • Dubnov G
      • Niaz MA
      • et al.
      Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomized single-blind trial.
      showed a reduction of cardiac deaths and myocardial infarctions in patients on the intervention diet (a traditional Mediterranean diet high in omega-3 fats, fruits, and vegetables and low in saturated fat) compared with a standard American Heart Association (control) diet.
      The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico Prevenzione study
      • Marchioli R
      • Barzi F
      • Bomba E
      • GISSI-Prevenzione Investigators
      • et al.
      Early protection against sudden dealth by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.
      randomized more than 11,000 myocardial infarction survivors to 1 g/d of an 85% ω-3 supplement or control. The ω-3 group experienced a 45% reduction in sudden cardiac death and a 20% decrease in all-cause mortality during a 3½-year period
      • Marchioli R
      • Barzi F
      • Bomba E
      • GISSI-Prevenzione Investigators
      • et al.
      Early protection against sudden dealth by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.
      (Figure 2). Prospective studies indicate that increased intake of fat in the form of ω-3 fatty acids from either plant sources (α-linolenic) or fish oils (eicosahexanoic acid and docasahexanoic acid) will reduce cardiovascular risk up to 32% to 50%.
      • Cordain L
      • Watkins BA
      • Florant GL
      • Kelher M
      • Rogers L
      • Li Y
      Fatty acid analysis of wild ruminant tissues: evolutionary implications for reducing diet-related chronic disease.
      • O'Keefe Jr, JH
      • Harris WS
      From Inuit to implementation: omega-3 fatty acids come of age.
      • de Lorgeril M
      • Salen P
      • Martin JL
      • Monjaud I
      • Delaye J
      • Mamelle N
      Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study.
      • Singh RB
      • Dubnov G
      • Niaz MA
      • et al.
      Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomized single-blind trial.
      • Marchioli R
      • Barzi F
      • Bomba E
      • GISSI-Prevenzione Investigators
      • et al.
      Early protection against sudden dealth by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.
      • Lemaitre RN
      • King IB
      • Mozaffarian D
      • Kuller LH
      • Tracy RP
      • Siscovick DS
      N-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study.
      Recently, for the first time, the American Heart Association recommended that a nutrient, ω-3 fatty acids, be consumed as a supplement if the diet contained an insufficient amount of this fat.
      • Kris-Etherton PM
      • Harris WS
      • Appel LJ
      • American Heart Association
      • Nutrition Committee
      Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease [published correction appears in Circulation. 2003;107:512].
      Figure thumbnail gr2
      Figure 2The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico Prevenzione study
      • Marchioli R
      • Barzi F
      • Bomba E
      • GISSI-Prevenzione Investigators
      • et al.
      Early protection against sudden dealth by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.
      showed a 45% reduction in sudden cardiac death (SCD) among patients receiving a concentrated fish oil supplement containing approximately 850 mg of omega-3 fats.

       Monounsaturated Fats

      Monounsaturated fats made up approximately half of the total fat in the diets of most hunter-gatherers.
      • Cordain L
      • Eaton SB
      • Miller JB
      • Mann N
      • Hill K
      The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic.
      Monounsaturated fats reduce cardiovascular risk, especially when substituted for easily digestible starches and sugars.
      • Ascherio A
      Epidemiologic studies on dietary fats and coronary heart disease.
      Nuts are a valuable source of monounsaturated fats and have been shown to be cardioprotective in at least 6 epidemiological studies.
      • Hu FB
      • Willett WC
      Optimal diets for prevention of coronary heart disease.
      • Curtis BM
      • O'Keefe Jr, JH
      Understanding the Mediterranean diet: could this be the new “gold standard” for heart disease prevention?.
      • Albert CM
      • Gaziano JM
      • Willett WC
      • Manson JE
      Nut consumption and decreased risk of sudden cardiac death in the Physicians' Health Study.
      Our hunter-gatherer ancestors relied on nuts as an easily accessible source of calorie-dense, highly nutritious food that was often available in nonsummer months. The calories in nuts typically are 80% from fat, but most of this is in the form of healthy monounsaturated and polyunsaturated fatty acids (including some ω-3 fat). Epidemiological studies show that frequent nut consumption (5 or more times per week) is associated with up to a 50% reduction in risk of myocardial infarction compared with the risk of people who rarely or never eat nuts.
      • Albert CM
      • Gaziano JM
      • Willett WC
      • Manson JE
      Nut consumption and decreased risk of sudden cardiac death in the Physicians' Health Study.
      Other studies show that nut consumption reduces the risk of developing type 2 diabetes,
      • Jiang R
      • Manson JE
      • Stampfer MJ
      • Liu S
      • Willett WC
      • Hu FB
      Nut and peanut butter consumption and risk of type 2 diabetes in women.
      lowers the atherogenic low-density lipoprotein (LDL) cholesterol level without lowering the high-density lipoprotein (HDL) level,
      • Lovejoy JC
      • Most MM
      • Lefevre M
      • Greenway FL
      • Rood JC
      Effect of diets enriched in almonds on insulin action and serum lipids in adults with normal glucose tolerance or type 2 diabetes.
      and provides plant-based protein and other potentially cardioprotective nutrients such as vitamin E, folate, magnesium, copper, zinc, and selenium. Because of their high levels of fiber, protein, and fat, nuts also provide better and longer-lasting satiety compared with high-glycemicload snack foods typically consumed today. Oleic acid is the major monounsaturated fat in our diets and is found in meats, nuts, avocados, dark chocolate, and olive oil. Although some of these foods were not part of the ancient ancestral diet, they can improve the cardiovascular risk profile when substituted for sugar, starches, trans-fats, and saturated fats that are prevalent in the modern diet. Studies suggest that replacing saturated fat with monounsaturated fat would result in a 30% reduction in risk, or 3 times the risk reduction achieved by replacing saturated fat with carbohydrates.
      • Ascherio A
      Epidemiologic studies on dietary fats and coronary heart disease.

       Vegetarian vs “Breaditarian”

      All evidence points to the fact that hunter-gatherers were omnivorous.
      • Cordain L
      • Miller JB
      • Eaton SB
      • Mann N
      • Holt SH
      • Speth JD
      Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets.
      Strictly vegetarian diets are difficult to follow and are not necessarily associated with better health. A study of 2 groups of Bantu villagers in Tanzania compared 618 people who lived on a lakeshore and consumed large amounts of fish to 645 people who lived in the nearby hills and were vegetarians.
      • Pauletto P
      • Puato M
      • Caroli MG
      • et al.
      Blood pressure and atherogenic lipoprotein profiles of fish-diet and vegetarian villagers in Tanzania: the Lugalawa study.
      The lifestyles, gene pools, and diets (except for the fish) were similar in the 2 groups. The fish-consuming group had lower blood pressure levels; lower triglyceride, cholesterol, and leptin levels; and higher plasma ω-3 fat levels than the vegetarian group.
      • Pauletto P
      • Puato M
      • Caroli MG
      • et al.
      Blood pressure and atherogenic lipoprotein profiles of fish-diet and vegetarian villagers in Tanzania: the Lugalawa study.
      • Winnick M
      • Somers VK
      • Accurso V
      • et al.
      Fish-rich diet, leptin, and body mass.
      Many current vegetarians would be more appropriately labeled “breaditarians.” Modern vegetarian diets often rely heavily on processed carbohydrates such as white rice, potatoes, and white flour and sugars. The South Asian paradox refers to the relatively high prevalence of coronary heart disease despite low levels of LDL cholesterol and low prevalence of obesity in urban vegetarians from India who consume a diet high in refined carbohydrates.
      • Singh RB
      • Dubnov G
      • Niaz MA
      • et al.
      Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomized single-blind trial.
      In westernized societies, sugar intake has increased substantially during the past 2 centuries (Figure 3
      • Cordain L
      • Eades MR
      • Eades MD
      Hyperinsulinemic diseases of civilization: more than just Syndrome X.
      ). A recent study showed that a high-glycemic-load diet is the most important dietary predictor of HDL level (as an inverse relationship).
      • Ford ES
      • Liu S
      Glycemic index and serum high-density lipoprotein cholesterol concentration among US adults.
      A high-glycemic-load diet predisposes a person to the metabolic syndrome and cardiovascular disease and is one of the most atherogenic features of our modern eating pattern.
      • Ford ES
      • Liu S
      Glycemic index and serum high-density lipoprotein cholesterol concentration among US adults.
      • Leeds AR
      Glycemic index and heart disease.
      • Ludwig DS
      The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease.
      • Liu S
      • Willett WC
      Dietary glycemic load and atherothrombotic risk.
      Figure thumbnail gr3
      Figure 3Average per capita consumption of sugar in England (1815-1970) and in the United States (1970-2000).
      • Cordain L
      • Eades MR
      • Eades MD
      Hyperinsulinemic diseases of civilization: more than just Syndrome X.

       Can Meat Be Cardioprotective?

      Comprehensive studies of diverse hunter-gatherer populations show that these people typically derived 45% to 60% of their calories from animal food.
      • Cordain L
      • Eaton SB
      • Miller JB
      • Mann N
      • Hill K
      The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic.
      • Cordain L
      • Miller JB
      • Eaton SB
      • Mann N
      • Holt SH
      • Speth JD
      Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets.
      Only 14% of hunter-gatherer societies obtained more than 50% of their calories from plant sources.
      • Cordain L
      • Eaton SB
      • Miller JB
      • Mann N
      • Hill K
      The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic.
      • Cordain L
      • Miller JB
      • Eaton SB
      • Mann N
      • Holt SH
      • Speth JD
      Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets.
      Paleolithic humans often lived in temperate climates and were confronted with winters during which most plant-based food was unavailable. Early humans adapted to these conditions by eating meat, organs, marrow, and fat from animals during the winter months. Paradoxically, these meat-based hunter-gatherer diets were nonatherogenic.
      • Cordain L
      • Eaton SB
      • Miller JB
      • Mann N
      • Hill K
      The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic.
      • Cordain L
      • Miller JB
      • Eaton SB
      • Mann N
      • Holt SH
      • Speth JD
      Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets.
      Although increased meat consumption in Western diets has been associated with increased cardiovascular risk, the hunter-gatherer societies were relatively free of the signs and symptoms of cardiovascular disease.
      • Eaton SB
      • Konner M
      • Shostak M
      Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective.
      The flesh of wild game is typically about 2% to 4% fat by weight and contains relatively high levels of monounsaturated and ω-3 fats compared with fatty grain-produced domestic meats, which can contain 20% to 25% fat by weight, much of it in the form of saturated fat.
      • Reddy ST
      • Wang CY
      • Sakhaee K
      • Brinkley L
      • Pak CY
      Effect of low-carbohydrate high-protein diets on acid-base balance, stoneforming propensity, and calcium metabolism.
      Wild game meat is not widely accessible today, and many people do not prefer the “game” taste, which is at least in part conferred by a higher ω-3 content and by aromatic oils from plant foods consumed by the herbivore. The modern-day alternative is to choose animal protein sources that are low in saturated fat, such as skinless poultry, fish, eggs (especially high–ω-3 varieties), and lean cuts of red meat with visible fat trimmed.
      It is not the amount of meat eaten but rather the composition of the meat and cooking methods that determine the health effects of this food. Accumulating scientific evidence indicates that meat consumption is not a risk for cardiovascular disease, but instead, the risk is secondary to high levels of saturated fat typically found in the meat of most modern domesticated animals.
      • Cordain L
      • Eades MR
      • Eades MD
      Hyperinsulinemic diseases of civilization: more than just Syndrome X.
      • O'Dea K
      • Traianedes K
      • Chisholm K
      • Leyden H
      • Sinclair AJ
      Cholesterol-lowering effect of a low-fat diet containing lean beef is reversed by the addition of beef fat.
      Diets high in lean protein can improve lipid profiles and overall health, especially if care is taken to trim any visible fat from the meats and to allow the fat to drain when cooking.
      • Wolfe BM
      • Piche LA
      Replacement of carbohydrate by protein in a conventional-fat diet reduces cholesterol and triglyceride concentrations in healthy normolipidemic subjects.
      • Parker B
      • Noakes M
      • Luscombe N
      • Clifton P
      Effect of a high-protein, high-monounsaturated fat weight loss diet on glycemic control and lipid levels in type 2 diabetes.
      • Wolfe BM
      • Giovannetti PM
      Short-term effects of substituting protein for carbohydrate in the diets of moderately hypercholesterolemic human subjects.
      • Layman DK
      • Boileau RA
      • Erickson DJ
      • et al.
      A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women.
      • O'Dea K
      • Traianedes K
      • Ireland P
      • et al.
      The effects of diet differing in fat, carbohydrate, and fiber on carbohydrate and lipid metabolism in type II diabetes.
      • Torbay N
      • Baba NH
      • Sawaya S
      • et al.
      High protein vs high carbohydrate hypoenergetic diet in treatment of obese normoinsulinemic and hyperinsulinemic subjects.
      Lean animal protein eaten at regular intervals (with each meal) improves satiety levels,
      • Westerterp-Plantenga MS
      • Rolland V
      • Wilson SA
      • Westerterp KR
      Satiety related to 24 h diet-induced thermogenesis during high protein/carbohydrate vs high fat diets measured in a respiration chamber.
      • Stubbs RJ
      Macronutrient effects on appetite.
      • Long SJ
      • Jeffcoat AR
      • Millward DJ
      Effect of habitual dietary-protein intake on appetite and satiety.
      increases dietary thermogenesis,
      • Westerterp-Plantenga MS
      • Rolland V
      • Wilson SA
      • Westerterp KR
      Satiety related to 24 h diet-induced thermogenesis during high protein/carbohydrate vs high fat diets measured in a respiration chamber.
      • Crovetti R
      • Porrini M
      • Santangelo A
      • Testolin G
      The influence of thermic effect of food on satiety.
      • Johnston CS
      • Day CS
      • Swan PD
      Postprandial thermogenesis is increased 100% on a high-protein, low-fat diet versus a high-carbohydrate, low-fat diet in healthy, young women.
      improves insulin sensitivity,
      • Torbay N
      • Baba NH
      • Sawaya S
      • et al.
      High protein vs high carbohydrate hypoenergetic diet in treatment of obese normoinsulinemic and hyperinsulinemic subjects.
      • Piatti PM
      • Monti F
      • Fermo I
      • et al.
      Hypocaloric high-protein diet improves glucose oxidation and spares lean body mass: comparison to hypocaloric high-carbohydrate diet.
      • Layman DK
      • Shiue H
      • Sather C
      • Erickson DJ
      • Baum J
      Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss.
      and thereby facilitates weight loss
      • Parker B
      • Noakes M
      • Luscombe N
      • Clifton P
      Effect of a high-protein, high-monounsaturated fat weight loss diet on glycemic control and lipid levels in type 2 diabetes.
      • Skov AR
      • Toubro S
      • Ronn B
      • Holm L
      • Astrup A
      Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity.
      • Baba NH
      • Sawaya S
      • Torbay N
      • Habbal Z
      • Azar S
      • Hashim SA
      High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects.
      while providing many essential nutrients.
      • Red Meat and Health Expert Advisory Committee
      The Role of Red Meat in Healthy Australian Diets.
      However, cooking red meats at high temperatures produces charring and high levels of heterocyclic amines, which have been implicated in the risk of gastrointestinal and prostate cancers.
      • Rohrmann S
      • Linseisen J
      • Becker N
      • European Prospective Investigation into Cancer and Nutrition (EPIC)
      • et al.
      Cooking of meat and fish in Europe—results from the European Prospective Investigation into Cancer and Nutrition (EPIC).
      Highly salted and preserved meats may also contain carcinogens. Lean, fresh meat cooked appropriately is a healthy and beneficial component of a varied diet, especially in conjunction with a high intake of vegetables and fruits.
      • Red Meat and Health Expert Advisory Committee
      The Role of Red Meat in Healthy Australian Diets.

       Trans-Fatty Acids

      Trans-fatty acids are found in small quantities in the fat tissues of all ruminant animals. However, in recent decades, intake of trans-fatty acids has increased markedly because of their ubiquitous presence in commercially prepared foods. Trans-fatty acids are synthesized when hydrogen is applied to edible oils under high pressure and temperature in the presence of a catalyst. Hydrogenation of the edible oils is typically done in the prepared food industry to prolong shelf-life in commercial baked goods such as cookies, crackers, donuts, croissants, and processed snack foods. Trans-fatty acids are also found in shortenings, most margarines, and deep-fried foods, and recently in many brands of commercially available canola oils.
      • Vermunt SH
      • Beaufrere B
      • Riemersma RA
      • TransLinE Investigators
      • et al.
      Dietary trans α-linolenic acid from deodorised rapeseed oil and plasma lipids and lipoproteins in healthy men: the TransLinE Study.
      Trans-fats lower HDL levels, increase LDL levels, and increase risk of both cardiovascular disease and cancer.
      • Sacks FM
      • Katan M
      Randomized clinical trials on the effects of dietary fat and carbohydrate on plasma lipoproteins and cardiovascular disease.
      • Ascherio A
      Epidemiologic studies on dietary fats and coronary heart disease.
      Studies indicate that replacing trans-fatty acids (typically 2% of total daily calories in the American diet) with the same amount of natural unsaturated fatty acids would result in a large (50%) decrease in risk of coronary heart disease.
      • Ascherio A
      Epidemiologic studies on dietary fats and coronary heart disease.

       Beverages

      Our Paleolithic ancestors drank water almost exclusively. Recent data suggest that generous water intake, 5 or more glasses daily, is associated with a lower risk of coronary heart disease.
      • Chan J
      • Knutsen SF
      • Blix GG
      • Lee JW
      • Fraser GE
      Water, other fluids, and fatal coronary heart disease: the Adventist Health Study.
      This may be simply a function of the fact that water, when consumed frequently, displaces calorie-dense beverages such as sugared sodas from the diet. Or it may be that water provides adequate hydration and reduces blood viscosity better than other commonly ingested drinks. In any event, water is the beverage we are adapted to drink, and evidence suggests that it should remain the principal fluid we drink.
      Sugared sodas are the predominant beverage consumed in America today. These are calorie-dense, nutritionally barren drinks that have contributed to the rise in obesity and insulin resistance. Generally, fruit juices are also high in sugar, and thus it is preferable to eat the whole fruit, which provides fiber and a lower glycemic load.
      • Joshipura KJ
      • Hu FB
      • Mason JE
      • et al.
      The effect of fruit and vegetable intake on risk for coronary heart disease.
      • Ludwig DS
      The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease.
      Tea (Camellia sinensis) has been brewed for thousands of years as a favorite drink in several parts of the world. This beverage has been shown to be high in natural antioxidant phytochemicals (polyphenolic compounds). Drinking tea has been shown to reverse endothelial vasomotor dysfunction in people with coronary artery disease,
      • Duffy SJ
      • Keaney Jr, JF
      • Holbrook M
      • et al.
      Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease.
      which may in part explain the inverse relationship between tea consumption and cardiovascular disease seen in observational studies. In 2 recent epidemiological studies, tea consumption (>2-3 cups per day) was associated with approximately half the risk of myocardial infarction compared with non–tea consumption.
      • Mukamal KJ
      • Maclure M
      • Muller JE
      • Sherwood JB
      • Mittleman MA
      Tea consumption and mortality after acute myocardial infarction.
      • Geleijnse JM
      • Launer LJ
      • Van der Kuip DA
      • Hofman A
      • Witteman JC
      Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study.
      Thus, tea appears to be a natural beverage that may help prevent cardiovascular disease, although more randomized prospective data are needed.

      HUNTER-GATHERER FITNESS

      Our Paleolithic ancestors exerted themselves daily to secure their food, water, and protection.
      • Cordain L
      • Gotshall RW
      • Eaton SB
      • Eaton III, SB
      Physical activity, energy expenditure and fitness: an evolutionary perspective.
      • Cordain L
      • Gotshall RW
      • Eaton SB
      Evolutionary aspects of exercise.
      Although modern technology has made physical exertion optional, it is still important to exercise as though our survival depended on it, and in a different way it still does. We are genetically adapted to live an extremely physically active lifestyle. A sedentary existence predisposes us to obesity, hypertension, the metabolic syndrome, diabetes, and most types of cardiovascular disease, whereas regular exercise decreases the risks of developing all these diseases. Even in times of caloric excess, hunter-gatherers avoided weight gain in part because they were extremely physically active. Studies of obesity consistently show that the best way to maintain weight loss (regardless of the type of diet used) is by daily physical exercise.
      • Wing RR
      Physical activity in the treatment of the adulthood overweight and obesity: current evidence and research issues.
      Our remote ancestors participated in various physical activities daily. They walked and ran 5 to 10 miles daily as they foraged and hunted for their food sources.
      • Cordain L
      • Gotshall RW
      • Eaton SB
      • Eaton III, SB
      Physical activity, energy expenditure and fitness: an evolutionary perspective.
      • Cordain L
      • Gotshall RW
      • Eaton SB
      Evolutionary aspects of exercise.
      They also lifted, carried, climbed, stretched, leaped, and did whatever else was necessary to secure their sustenance and protection. Days of heavy exertion were followed by recovery days. In modern terms, these people cross-trained with aerobic, resistance, and flexibility exercises. According to recent data on physical activity, fitness programs that use various exercises are the most effective in preventing cardiovascular diseases.
      • Tanasescu M
      • Leitzmann MF
      • Rimm EB
      • Willett WC
      • Stampfer MJ
      • Hu FB
      Exercise type and intensity in relation to coronary heart disease in men.

      SUMMARY

      The hunter-gatherer diet and lifestyle are the milieu for which we remain genetically adapted. Although it is neither practical nor even possible to replicate all prehistoric living conditions today, these general characteristics should serve as a template to design and test effective interventions to reduce the incidence of degenerative cardiovascular diseases.

      Acknowledgments

      We acknowledge Connie Smith for her assistance with the preparation of the submitted manuscript.

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