The Paleolithic diet (PaleoDiet) is an allegedly healthy dietary pattern inspired by the consumption of wild foods and animals assumed to be consumed in the Paleolithic era. Despite gaining popularity in the media, different operational definitions of this Paleolithic nutritional intake have been used in research. Our hypothesis is that specific components used to define the PaleoDiet may modulate the association of this diet with several health outcomes. We comprehensively reviewed currently applied PaleoDiet scores and suggested a new score based on the food composition of current PaleoDiet definitions and the theoretical food content of a staple dietary pattern in the Paleolithic age. In a PubMed search up to December 2019, fourteen different PaleoDiet definitions were found. We observed some common components of the PaleoDiet among these definitions although we also found high heterogeneity in the list of specific foods that should be encouraged or banned within the PaleoDiet. Most studies suggest that the PaleoDiet may have beneficial effects in the prevention of cardiometabolic diseases (type 2 diabetes, overweight/obesity, CVD and hyperlipidaemias) but the level of evidence is still weak because of the limited number of studies with a large sample size, hard outcomes instead of surrogate outcomes and long-term follow-up. Finally, we propose a new PaleoDiet score composed of eleven food items, based on a high consumption of fruits, nuts, vegetables, fish, eggs and unprocessed meats (lean meats); and a minimum content of dairy products, grains and cereals, and legumes and practical absence of processed (or ultra-processed) foods or culinary ingredients.

CVD are the main cause of death especially in high-income countries. Previously, research focused on single nutrients including saturated and MUFA, sodium and dietary fibre, or specific foods such as fish, fruit and vegetables, and olive oil, in the aetiology of CVD. In recent years, however, the effects of complete dietary patterns on the prevention of CVD have gained interest, to account for diet heterogeneity and food–nutrient interactions. Several dietary patterns have been investigated, such as the Paleolithic diet, the vegetarian and vegan diets, the Diet Approaches to Stop Hypertension (DASH), the Nordic and Mediterranean diets, with many contradictions remaining. The aim of this review is to give an overview of the effects of these dietary patterns on CVD risk, to discuss their overall nutrient adequacy and briefly discuss their environmental impact.

Various individual diet and lifestyle factors are associated with mortality. Investigating these factors collectively may help clarify whether dietary and lifestyle patterns contribute to life expectancy. We investigated the association of previously described evolutionary-concordance and Mediterranean diet pattern scores and a novel evolutionary-concordance lifestyle pattern score with all-cause and cause-specific mortality in the prospective Iowa Women’s Health Study (1986–2012). We created the diet pattern scores from Willett FFQ responses, and the lifestyle pattern score from self-reported physical activity, BMI and smoking status, and assessed their associations with mortality, using multivariable Cox proportional hazards regression. Of the 35 221 55- to 69-year-old cancer-free women at baseline, 18 687 died during follow-up. The adjusted hazard ratios (HR) and 95 % CI for all-cause, all CVD, and all-cancer mortality among participants in the highest relative to the lowest quintile of the evolutionary-concordance lifestyle score were, respectively, 0·52 (95 % CI 0·50, 0·55), 0·53 (95 % CI 0·49, 0·57) and 0·51 (95 % CI 0·46, 0·57). The corresponding findings for the Mediterranean diet score were HR 0·85 (95 % CI 0·82, 0·90), 0·83 (95 % CI 0·76, 0·90) and 0·93 (95 % CI 0·84, 1·03), and for the evolutionary-concordance diet score they were close to null and not statistically significant. The lowest estimated risk was among those in the highest joint quintile of the lifestyle score and either diet score (both Pinteraction <0·01). Our findings suggest that (1) a more Mediterranean-like diet pattern and (2) a more evolutionary-concordant lifestyle pattern, alone and in interaction with a more evolutionary-concordant or Mediterranean diet pattern, may be inversely associated with mortality.

The Paleolithic diet excludes two major sources of fibre, grains and legumes. However, it is not known whether this results in changes to resistant starch (RS) consumption. Serum trimethylamine-N-oxide (TMAO) is produced mainly from colonic fermentation and hepatic conversion of animal protein and is implicated in CVD, but changes in RS intake may alter concentrations. We aimed to determine whether intake of RS and serum concentrations of TMAO varied in response to either the Paleolithic or the Australian Guide to Healthy Eating (AGHE) diets and whether this was related to changes in food group consumption. A total of thirty-nine women (mean age 47 (sd 13) years, BMI 27 (sd 4) kg/m2) were randomised to AGHE (n 17) or Paleolithic diets (n 22) for 4 weeks. Serum TMAO concentrations were measured using liquid chromatography–MS; food groups, fibre and RS intake were estimated from weighed food records. The change in TMAO concentrations between groups (Paleolithic 3·39 μmv. AGHE 1·19 μm, P = 0·654) did not reach significance despite greater red meat and egg consumption in the Paleolithic group (0·65 serves/d; 95 % CI 0·2, 1·1; P <0·01, and 0·22 serves/d; 95 % CI 0·1, 0·4, P <0·05, respectively). RS intake was significantly lower on the Paleolithic diet (P <0·01) and was not associated with TMAO concentrations. However, the limited data for RS and the small sample size may have influenced these findings. While there were no significant changes in TMAO concentrations, increased meat consumption and reduced RS intake warrant further research to examine the markers of gastrointestinal health of Paleolithic diet followers and to update Australian food databases to include additional fibre components.

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 (25–29), 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 α-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.