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 [?-3] fatty acids), monounsaturated fats, fiber, vitamins, minerals, antioxidants, and other beneficial phytochemicals. Historical and anthropological studies show huntergatherers generally to be healthy, fit, and largely free of the degenerative cardiovascular diseases common in modern societies. This review outlines the essence of our huntergatherer genetic legacy and suggests practical steps to realign our modern milieu with our ancient genome in an effort to improve cardiovascular health. Mayo Clin Proc. 2004;79:101-108HDL = high-density lipoprotein; LDL = low-density lipoprote inHumans 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),1 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.2 The lifetime incidence of hypertension is an astounding 90%,3 and the metabolic syndrome is present in up to 40% of middle-aged American adults.4 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.5 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.6 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.7 When huntergatherer societies transitioned to an agricultural grainbased diet, their general health deteriorated.8,9 Average adult height was substantially shorter for both men and women who consumed cereals and starches compared with
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