This study showed highly beneficial effects of a Paleolithic diet on risk factors for diseases of affluence when compared to cereal based swine feed. A strength of the study is that the model used is one of the best non-primate models for human disorders, the domestic pig . The present study indicated no difference in glucose disappearance during IVGTT between the groups. During IVGTT plasma insulin increased successively between 30 and 80 min in both groups, possibly due to propofol anesthesia [21, 22], and this precluded the use of the minimal model of glucose disappearance [16, 17]. However, other indices of dynamic insulin sensitivity clearly showed higher insulin sensitivity in the Paleolithic group, which also exhibited a significantly lower insulin response to injected glucose. It is worth noting that the difference in insulin response between groups during IVGTT was observed in the late phase of insulin secretion. Evaluation of multivariate correlation showed that the beneficial effect of Paleolithic diet on insulin sensitivity and insulin response was independent of all other relevant study variables such as body weight, subcutaneous fat thickness and body temperature. A Paleolithic diet thus conferred higher insulin sensitivity, which is central to the prevention of cardiovascular disorders , and consistent with our finding in humans . Furthermore, contrary to our survey in humans , this finding of higher insulin sensitivity was associated with no significant difference between groups in fasting levels of insulin and glucose, indicating that the Paleolithic diet affected insulin action mainly at the level of muscle and adipose tissues rather than the liver .
The Paleolithic group also showed significantly lower levels of C-reactive protein, a physiologic marker of subclinical inflammation, which has been shown to be associated with insulin resistance and cardiovascular disease [23, 25]. Elevated levels of C-reactive protein has been suggested to reflect overproduction by expanded adipose tissue mass . However, evaluation of multivariate correlation showed that the beneficial effect of Paleolithic diet on C-reactive protein was independent of all other relevant study variables including measures of obesity such as body weight and subcutaneous fat thickness. Interestingly, immunohistochemical analysis suggested a diffuse and low-grade pancreatic inflammation in the cereal group, as evidenced by clearly more frequent leukocytes scattered throughout their exocrine pancreatic parenchyma or clustered around pancreatic ducts and blood vessels. This finding offers a novel approach in the research on the association between inflammation and type 2 diabetes . Immunohistochemical analysis also showed that the cereal group could compensate for both pancreatic inflammation and increased need of insulin due to lower insulin sensitivity, without noticeable differences in pancreatic islets between groups.
The shorter length in the Paleolithic group is not unexpected if we consider length in pigs as a correlate of height in humans. Available evidence suggests that hunter-gatherers and similar ethnic groups are shorter than Western populations, and a positive relationship between height and cardiovascular disease has been noted in international comparisons . Insulin resistance and hyperinsulinemia can hypothetically promote growth by way of insulin-like growth factors .
In addition to these significant results, intra-arterial diastolic blood pressure was significantly lower in the Paleolithic group, and this beneficial effect of Paleolithic diet was also independent of all other relevant study variables. The present study thus provides experimental evidence for beneficial effects of a Paleolithic diet on risk factors for diseases of affluence, which might account for their low incidence reported among Non-Western ethnic groups with hunter-gatherer lifestyles and diets [6, 7].
The mechanisms behind these beneficial effects on risk factors are largely unknown. In evaluations of multivariate correlation, diet emerged as a stronger explanatory variable than any other relevant variable for variations in dynamic insulin sensitivity, AUCins0–120, log C-reactive protein and diastolic blood pressure. The observed effects on risk factors thus seem to be primarily caused by diet. However, it is conceivable that this dietary effect on risk factors is a result of differences in other variables induced by dietary assignment. An important finding in this regard is the divergence of the weight curves between the two groups after 3 months of feeding. The Paleolithic group was thus lighter and had a lower energy intake at the end of the study than the Cereal group, despite a threefold larger ration by weight. The diverging weight curves could be interpreted in several ways. They could be interpreted as food restriction in the Paleolithic group, which could explain the observed effects on risk factors . Neither group was fed their respective diet ad libitum but was rather allocated rations on a group basis judged sufficient to achieve healthy animals by an experienced experimental pig farmer. This procedure was chosen due to concerns about the unfamiliar Paleolithic diet as swine feed, and the fact that feeding ad libitum is not the custom in Swedish swine production. The diverging weight curves between the groups could thus possibly be caused by differences in subjectively allocated rations (e.g. difference in energy intake), which could lead to food restriction in the Paleolithic group. However, food restriction typically lowers mean body temperature by 1–2°C , and we found no significant difference in mean body temperature between the two groups, indicating that there was not a substantial food restriction in the Paleolithic group as compared to the Cereal group. In fact, the mean weight in the Paleolithic group is well within the normal range of pigs . The diverging weight curves are thus probably not caused by food restriction in the Paleolithic group but instead could be interpreted as obesity in the Cereal group in analogy with human classification of individual weight based on statistical health effects . The significant difference in subcutaneous fat thickness between groups and the high correlation between weight and subcutaneous fat thickness supports this notion. Obesity in humans is associated with increased insulin resistance, high blood pressure and high levels of C-reactive protein , and could explain the observed effects on risk factors. The difference between the two diets regarding obesity promotion could still be due to differences in subjectively allocated rations, but could alternatively be due to properties of a cereal based swine feed which possibly disturb the regulation of satiation , satiating properties of a Paleolithic diet  and differing effects between the diets on energy metabolism . The satiating properties of a Paleolithic diet could be due to differences in macronutrient diet composition, such as the low protein content of cereals in the Cereal group diet. The Paleolithic group thus ate relatively more protein and less carbohydrates, which through satiating, thermogenic and other properties could account for the results of the study [32, 33], although results from studies on the association between protein intake and diseases of affluence have been contradictory . In future studies of Paleolithic diets it would be valuable to match diets for macronutrient composition. The latter alternative explanations for the diverging weight curves is supported by our epidemiological findings in humans from Kitava, Papua New Guinea, where a non-western lifestyle has been connected to leanness despite food being available ad libitum . The diverging weight curves would then suggest that the beneficial effects on risk factors could be due to differences between diets regarding obesity promotion. Alternatively, obesity could be a marker for other effecting mechanisms, such as leptin resistance, and the diverging weight curves would then suggest that the beneficial effects on risk factors could be due to differences between diets regarding promotion of leptin resistance .