Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin Evolutionary medicine tells us that our genes have been selected in an environment in which we successfully exploited hunting and gathering strategies for survival and procreation (1,2) . Since the agricultural (about 10 000 years ago) and industrial (100 -200 years ago) revolutions, we have, however, drastically changed our conditions of existence and continue to do so with still increasing pace. These changes cause a conflict with our slowly adapting genome that basically still resides in the Paleolithic era (3) . Examples of such changes can be found in our current dietary composition, reduced physical activity, abnormal microbial flora, lack of sleep and environmental pollution (4) . These changes are intimately related and result in a state of homeostatic imbalance that is likely to be based on the pandemic of affluent diseases (3) .Other prominent changes include our current clothing habits and reduced time spent outdoors. The ensuing lack of exposure to direct sunlight negatively affects our vitamin D status, and thereby adds to the current state of homeostatic imbalance. Cutaneous synthesis of vitamin D by exposure to UVB is our principal source of vitamin D, which in reality is a prohormone with both rapid and slow effects and which also controls the expression of about 3 % of our genes (5) . The importance of vitamin D became apparent, for instance, from the loss of skin pigmentation in populations who migrated from Africa to settle at higher latitudes since about 100 000 years ago (6) . Skin depigmentation is likely to be an adaptation that enables vitamin D synthesis at low UVB exposure (7) .The current low vitamin D status of populations living in affluent countries is implicated in many diseases that are related to the calcaemic and non-calcaemic functions of vitamin D, including rickets, osteomalacia, osteoporosis, CHD (hypertension), cancer (colorectal cancer, breast cancer and prostate † These authors contributed equally to this work.

Our genome adapts slowly to changing conditions of existence. Many diseases of civilisation result from mismatches between our Paleolithic genome and the rapidly changing environment, including our diet. The objective of the present study was to reconstruct multiple Paleolithic diets to estimate the ranges of nutrient intakes upon which humanity evolved. A database of, predominantly East African, plant and animal foods (meat/fish) was used to model multiple Paleolithic diets, using two pathophysiological constraints (i.e. protein , 35 energy % (en%) and linoleic acid (LA) . 1·0 en%), at known hunter -gatherer plant/animal food intake ratios (range 70/30 -30/70 en%/en%). We investigated selective and non-selective savannah, savannah/aquatic and aquatic hunter-gatherer/scavenger foraging strategies. We found (range of medians in en%) intakes of moderate-to-high protein (25)(26)(27)(28)(29), moderate-to-high fat (30-39) and moderate carbohydrates (39-40). The fatty acid composition was SFA (11·4 -12·0), MUFA (5·6 -18·5) and PUFA (8·6 -15·2). The latter was high in a-linolenic acid (ALA) (3·7 -4·7 en%), low in LA (2·3 -3·6 en%), and high in long-chain PUFA (LCP; 4·75-25·8 g/d), LCP n-3 (2·26 -17·0 g/d), LCP n-6 (2·54 -8·84 g/d), ALA/LA ratio (1·12 -1·64 g/g) and LCP n-3/LCP n-6 ratio (0·84 -1·92 g/g). Consistent with the wide range of employed variables, nutrient intakes showed wide ranges. We conclude that compared with Western diets, Paleolithic diets contained consistently higher protein and LCP, and lower LA. These are likely to contribute to the known beneficial effects of Paleolithic-like diets, e.g. through increased satiety/satiation. Disparities between Paleolithic, contemporary and recommended intakes might be important factors underlying the aetiology of common Western diseases. Data on Paleolithic diets and lifestyle, rather than the investigation of single nutrients, might be useful for the rational design of clinical trials.Paleolithic diet: Land -water ecosystem: Hunter -gatherers: Evolutionary medicine: Macronutrients: Arachidonic acid: Linoleic acid: a-Linolenic acid: Docosahexaenoic acid: Cholesterol: Long-chain PUFA Our genome is the product of millions of years of evolution in which it slowly adapted to ensure reproductive success under the environmental selective pressures imposed upon our species (1) . Evolutionary medicine predicts that many complex degenerative diseases originate from unfavourable changes in our environment that, in the light of our long generation time, are too rapid to cause appropriate adaptation of our slowly adapting genome (2) . Such genetic adaptations are also unlikely to occur, since these unfavourable changes exert little selection pressure. That is, they do not cause death before reproductive age, but rather reduce years in health at the end of the life cycle (1,3) . Our, nevertheless, increased life expectancy originates mostly from technological achievements (e.g. the introduction of public health sanitation, the prevention of (childhood) infections, famine, homi...

Our ancient 25(OH)D amounted to about 115 nmol/L and sunlight exposure, rather than fish intake, was the principal determinant. The fetoplacental unit was exposed to high 25(OH)D, possibly by maternal vitamin D mobilization from adipose tissue, reduced insulin sensitivity, trapping by vitamin D-binding protein, diminished deactivation, or some combination.

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