Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis

Eric W Manheimer, Esther J van Zuuren, Zbys Fedorowicz, Hanno Pijl
  • American Journal of Clinical Nutrition, August 2015, Oxford University Press (OUP)
  • DOI: 10.3945/ajcn.115.113613

Paleo systematic review

What is it about?

The paleo diet was the most searched diet-related term on Google in 2014. However, a 2015 US News and World Report ranking of 35 diets with input from a panel of health experts placed the paleo diet dead last, citing a lack of randomized trials that showed clinical benefits. Several randomized trials have been published recently, but these have not, as yet, been systematically reviewed. The paleo diet is modeled on the nutritional patterns of our ancestors from the Paleolithic era (2.6 million to ~10,000 years ago), before the advent of modern (industrial) agriculture. Archeological, anthropological, and genetic evidence suggests that Paleolithic nutrition consisted of meat, fish, eggs, vegetables, fruit, and nuts in variable proportions and did not include dairy, grain products, or legumes. Current pre-industrial hunter-gatherer societies, consuming Paleolithic-like nutrition, are largely free of the degenerative diseases of Western civilization. It has been hypothesized that our physiologic architecture, which came of age over millions of years, cannot adapt rapidly enough to the changes in dietary habits occurring since the agricultural revolution. The ensuing mismatch has been proposed to contribute to the epidemic of chronic disease, which the world faces today. If this hypothesis holds true, one would expect Paleolithic nutrition to ameliorate risk markers of chronic disease, particularly in people who are (genetically) predisposed to develop any of these disorders. Manheimer and coworkers applied Cochrane systematic review methods to evaluate whether current randomized trial evidence supports the postulate that Paleolithic nutrition improves risk factors for chronic disease more than do other dietary interventions in people with one or more components of the metabolic syndrome.

Why is it important?

This systematic review found evidence to suggest that the Paleolithic diet can improve metabolic syndrome components more than currently recommended control diets. These beneficial effects and their longer-term sustainability warrant further evaluation. Moreover, state-of-the-art nutritional science readily explains the metabolic benefits of a (modest) restriction of carbohydrates, a lack of high–glycemic index products, a low ω-6 over ω-3 fatty acid balance, and a reduction of salt intake in patients with insulin resistance and the metabolic syndrome. In contrast, it is less clear whether the avoidance of whole grains and dairy products is a prerequisite for optimal control of metabolism. Additional studies should carefully examine the health significance of avoiding these food groups in the context of Paleolithic nutrition.


Hanno PIjl
Universiteit Leiden

This analysis should be an incentive to further evaluate the clinical benefits of so called paleolithic nutrition in people with the metabolic syndrome and/or type 2 diabetes. The data suggest that food that was presumably consumed prior to the advent of agriculture suits insulin resistant people better than currently recommended diets.

Dr Zbys Fedorowicz
Veritas Health Sciences

Correct nutrition is the key to life whereas incorrect nutrition can have a significant impact on mortality This systematic review set out to assess the effects of clearly articulated and pre-specified nutritional patterns on the risk factors for metabolic syndrome. It would be incorrect to assume that the intention of the review was to consider all nutritional patterns and indeed the/ or a specific 'paleo diet'. There is no single such diet and there is even lack of agreement on what that 'diet' included or excluded. Rather the focus of this review was to evaluate the evidence of effect for relatively closely matched interventions against dietary guidelines and specifically for which the primary research included randomised controlled trials. Thus there was an element of selectivity in deciding which interventions to cover but this is not unique to this systematic review as indeed other reviews are directed by a need to map the evidence for existing interventions. Decisions need to be informed by current best evidence and the process of gathering evidence and mapping gaps in the evidence should follow a set pattern: (1) Systematically review what is already known. (2) Randomise interventions when there is uncertainty in the choice between options. (3) Update reviews of evidence to incorporate the new findings. In that respect this systematic review has taken the first step.

Dr Eric W Manheimer

Everybody is impacted by dietary guidelines. They influence school lunches, nutrition labels, food pyramids hung up in families’ kitchens. But dietary guidelines have often been based on observational studies, which have a high risk of confounding and cannot generate accurate evidence on which to base dietary recommendations for populations. Other healthcare interventions are evaluated by the randomized controlled trial (RCT), considered the highest level of evidence in the evidence-based medicine hierarchy. But nutritional recommendations are not typically held to the same study design hierarchy standard. We used Cochrane systematic review methodology to evaluate RCTs of Paleolithic nutrition compared to control diets for metabolic syndrome. The control diets turned out to be diets recommended around the world in national and international dietary guidelines. They were distinct but broadly similar, and they all advocated increased consumption of cereals and low-fat dairy products, the restriction of saturated fat from 10%-15% of total daily energy, and the allowance of refined vegetable oils and processed foods. The paleo diets were also broadly similar across RCTs and representative of paleo diets in current practice. They comprised only unprocessed meat, fish, eggs, vegetables, fruit, and nuts in variable proportions, and excluded dairy, grains, legumes, and refined and processed foods. Although we identified only 4 RCTs with 159 participants, we found moderate quality evidence of a greater short-term benefit of a Paleolithic nutrition pattern relative to control for each component of the metabolic syndrome. The benefits were similar across the 4 trials and our meta-analysis provides an average estimate of the effects of the paleo diet relative to control. Although our evidence is short-term, isn’t that the question that people want to know? What is the effect of a diet if I stick to it? Everyone knows that a diet works only as long as you stick to it. People on the paleo diet were more likely to maintain it than for 2 of the control diets in our review, one based on national dietary guidelines of Scandinavian countries and the other the Netherlands. A paleo diet could also be difficult to maintain if people eating paleo are hungry all the time. But Jonsson et al found paleo to be more satiating per calorie than either a diabetes guideline diet or a Mediterranean-type diet, the other 2 control diets in our review. Still, additional RCTs with longer term data are necessary to determine whether people can really stick to paleo, and if so, whether the short-term benefits are maintained. For example, our meta-analysis found an average greater weight loss of 2.7 kg (5.9 pounds) in the paleo diet group relative to control. Would this greater weight loss plateau, continue, or slide? Would participants continue to eat paleo-style diets in the long-term, or be tempted back to bread and pasta and cookies? I have had a personal interest in natural nutrition since I read about the work of Weston A. Price (, and how the 'primitive' cultures he studied were largely free of the diseases of civilization. He attributed this to their diet, which included no processed foods, and special foods which the primitive cultures sought out for improved health. Others have continued along this line of research. For example, Staffan Lindeberg studied populations on the Kitava island off the coast of New Guinea, one of the last populations on earth to eat a traditional diet not impacted by Western foods of civilization. Less than 0.2% of the Kitavan caloric intake came from Western food, such as refined sugars and fats, dairy products, cereals, and alcohol, compared with roughly 70% in Western countries. The Kitavan diet was also 69% carbohydrate, consisting largely of root vegetables and fruits, so it was not the meat-based diet that is commonly associated with 'paleo'. But it could still be considered a Paleolithic nutritional pattern. There is no one Paleolithic nutritional pattern and the only requirement is that it approximates as close as possible the foods available to our Paleolithic ancestors. This was the case for the Kitavan islanders ( With their natural diet devoid of processed foods and high glycemic-index foods, yet still high in carbohydrates, the Kitavans were free of cardiovascular disease, stroke, dementia, and other chronic illnesses. Loren Cordain, the world's foremost authority on the evolutionary basis of diet and disease, has made Paleolithic nutrition an accepted topic of debate in the world’s most prestigious nutrition journals. His American Journal of Clinical Nutrition 2005 article 'Origins and evolution of the Western diet: health implications for the 21st century' has 1000+ citations. With his popular book The Paleo Diet, he introduced the health benefits of Stone Age Diets to contemporary people. He also informs the Public through his blog, in which he featured a teaser about our meta-analysis, the same day it was published ( Staffan and Loren were both involved in the preparation of our review. Staffan dug up additional outcomes not published in his RCT that I requested of him for our review, and Loren provided resources and references and oriented me to the ongoing trials. This concept of the evolutionary basis of nutrition is based upon the shoulders of giants. Now our author group is a part of this legacy of scientifically and systematically researching ancestral nutritional patterns, and I had the unique opportunity to combine a personal interest, traditional nutrition, with my professional calling card, systematic review and meta-analysis methodology, to which I’ve devoted my entire career with the Cochrane Collaboration. Most of my previous systematic reviews focused on acupuncture, as listed on my Kudos profile page ( They almost always came to inconclusive findings. This was largely because it's difficult to design a randomized trial that controls for the 'expectation effects' of acupuncture. People want or expect to get acupuncture and if they’re randomized to get acupuncture, they’ll be happy they got the treatment they wanted, and they’ll report feeling less pain on questionnaires regardless of whether their pain really improved. But here, the outcomes are hard outcomes eg, blood pressure, waist circumference, triglycerides, weight loss. For all of these outcomes, the paleo diet did better than the control. This cannot be attributed to placebo or expectation effects. Additionally, unlike acupuncture trials, which are often conducted and reported to low standards, these paleo trials were all well-conducted (adequate randomization, few drop-outs, all outcomes reported), and I contacted all corresponding authors and they each responded to all of my requests for additional unreported methods or outcomes relative to our assessments. The Lancet series Sir Iain Chalmers initiated on value versus waste in research ( has struck a nerve in the research community. It is the focus of the REWARD/EQUATOR Conference 2015 Edinburgh, UK 28-30 September ( I’ve reflected on value versus waste in research when comparing these paleo trials to trials of acupuncture. There have been only 4 paleo trials, but because they were all well-designed and well-conducted, we already have moderate quality evidence that the paleo diet improves risk factors for chronic disease more than control diets. There have been tens of thousands of acupuncture trials, and we still don’t know much more than when we started. Funders and policy-makers should invest in research that matters. That can influence policy-decisions. That can improve the Public’s health. Additional well-designed paleo trials to build upon this existing evidence base can result in the updating of this systematic review. If findings from these initial 4 trials are confirmed, Paleolithic nutrition deserves to be recommended in dietary guidelines the world over as an evidence-based dietary pattern for improving risk factors for chronic disease.

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The following have contributed to this page: Dr Zbys Fedorowicz, Dr Esther J van Zuuren, Hanno PIjl, and Dr Eric W Manheimer