For nearly 6 million years, the ability to store dietary energy for later times has served humans well during food scarce periods. In our current world of over‐consumption; overweight and obesity are linked to more deaths worldwide than underweight, with 1.9 billion adults classified as overweight and of these, 600 million obese (World Health Organization, 2014). This puts those individuals at an increased risk for chronic diseases, such as cardiovascular disease, metabolic syndrome, type 2 diabetes (T2D), nonalcoholic fatty liver disease, Alzheimer dementia, and some cancers. This trend has had devastating effects on the loss of health, reductions in quality of life, and health system resources. One approach to slow the pandemic of obesity and chronic disease is to look to our evolutionary past for clues of the changing behaviors contributing to the emergence of ‘diseases of civilization’. One theory is that agricultural and technological advances have introduced pressures (i.e. diet and activity changes) quicker than our genetic ability to respond, causing a mismatch between our systems and the environment. Over the past 10,000 years, we have had profound changes in feeding and activity behavior which have left an imprint on the human genome.PURPOSEThe purpose of this study was to investigate the health effects of diet and exercise patterns that more closely resemble those of our evolutionary past in individuals characterized as having Metabolic Syndrome (MetS).METHODSSubjects (N=4) were instructed to consume a diet consisting of unprocessed lean meat, fish, eggs, leafy and cruciferous vegetables, root vegetables, fruit, and nuts and devoid of cereal grains, dairy, beans, legumes, refined fats, bakery items, soft drinks, beer, extra salt and sugar. Foods such as nuts, dried fruit, potatoes (<1 medium‐sized per day) and wine (<1 glass per day) were recommended in limited amounts. Carbohydrate restriction was set at <50gCHO with emphasis on fat intake for replacement. Subjects also participated in high intensity interval training (HIIT), which included a 3‐min warm‐up, 10 × 60 s cycling intervals interspersed with 60s of active recovery, and a 3‐min cool‐down for 4 total weeks.RESULTSCompared to baseline, the intervention led to improvements in MetS markers; including mean arterial pressure (124+6.2 vs. 82+4.1), waist adiposity (110+8.9 vs. 92.1+9.0), fasting glucose (114.2+6.9 vs. 83.3+5.4), high density lipoprotein (HDL; 34.8+7.4 vs. 54.2+6.9), and triglycerides (TG; 214.8+35.5 vs. 92.9+24.2). Improvements were also observed in peak oxygen uptake (VO2max; 20.5+3.2 vs. 25.1+2.2) and low grade inflammation (hsCRP; 7.2+0.6 vs. 4.4+1.3).CONCLUSIONThe combined intervention of paleolithic diet with exercise elicits favorable metabolic and cardiovascular profiles in those that characterize with MetS. The type 2 diabetes epidemic and associated risk factors may be improved from an evolutionary approach in diet and exercise as a preventable and reversible treatment.