Adoption of the Paleolithic diet assumes that modern humans can reproduce the hunter-gatherer diet. Molecular biologist Marion Nestle argues that "knowledge of the relative proportions of animal and plant foods in the diets of early humans is circumstantial, incomplete, and debatable and that there are insufficient data to identify the composition of a genetically determined optimal diet. The evidence related to Paleolithic diets is best interpreted as supporting the idea that diets based largely on plant foods promote health and longevity, at least under conditions of food abundance and physical activity." Ideas about Paleolithic diet and nutrition are at best hypothetical.
Another 2014 study in the European Journal of Clinical Nutrition compared the effects of the Paleo plan to those of a standard low-fat diet on 70 obese, postmenopausal women. After six months, the Paleo group lost 14 pounds on average, while the other group lost nearly 6 pounds. After a year, the Paleo group had lost 19 pounds on average, and the low-fat dieters had dropped 10 pounds. A year later, both groups had regained some weight: The Paleo group was still down 10 pounds, while the low-fat group had dropped an average of more than 6 pounds.
The WHO trial (so named because the international team of principal investigators contained World Health Organization members) tested the potential of clofibrate, a “pre-statin” cholesterol-lowering agent, to reduce heart attack morbidity and mortality. The investigators ultimately concluded that clofibrate "cannot be recommended as a lipid-lowering drug for community-wide primary prevention of ischaemic heart disease.” Nevertheless, clofibrate remained in use until 2002, when it was pulled for increasing cancer rates. In their review of studies such as the WHO trial, Uffe Ravnskov and David Diamond observe, “Despite the largely disappointing findings from 50 years of cholesterol lower[ing] trials, the indictment and conviction of cholesterol as the causal agent in CVD [cardiovascular disease] has stood the test of time. … [Yet] the grand effort to reduce cholesterol as a strategy to improve health has failed.”