Discussion
Our results suggest that more Paleolithic- and Mediterranean-like dietary patterns may be similarly inversely associated with risk of colorectal adenoma, perhaps especially for men and persons who are overweight or obese, as well as for multiple adenomas or adenomas with a villous component.
The Paleolithic and Mediterranean diet patterns both have several components that could plausibly reduce adenoma risk. Both dietary patterns are high in fruits and vegetables, which may help improve oxidative balance, increase dietary fiber intake, and reduce total energy intake, all of which are thought to reduce colorectal adenoma and cancer risk. They are also both low in red, processed, and fatty meats, which are thought to increase CRC risk via several mechanisms. The 2 diet patterns may also reduce systemic inflammation, which is associated with lower risk of CRC. Given that overweight and obese individuals tend to have higher levels of systemic inflammation, our findings of stronger inverse associations of the diets with adenoma among those who are overweight or obese provide some indirect support for the hypothesis that inflammation is a key pathway by which these diet patterns act. However, women generally have a higher level of systemic inflammation than do men, yet the associations of the diet patterns with adenoma were stronger among men. Stronger associations between dietary patterns and colorectal adenoma or CRC in men have frequently been reported, and it is unclear whether this may be related to true biological differences in diet effects, differences in diet patterns, or differential diet measurement. The stronger associations for multiple adenomas and adenomas with a villous component may be related to inflammation, though the exact mechanism is unclear.
The Paleolithic diet pattern was examined in 3 small pilot dietary intervention studies, 1 uncontrolled (in a healthy, nonobese population) and 2 with comparison groups on conventional healthy diets (in populations of type 2 diabetes or ischemic heart disease patients); the results from these 12-week trials suggested that the Paleolithic diet pattern may improve blood pressure, serum cholesterol level, glycemic control, and C-reactive protein level independent of any decrease in weight. A longer trial of postmenopausal obese women directed to follow a Paleolithic diet or a Nordic Nutrition Recommendations (low-fat, high-fiber) diet found greater fat loss (−6.5 vs. −2.6 kg; P < 0.001) and lower levels of triglycerides at 6 months in the Paleolithic diet group, though much of the fat loss was attenuated after 2 years (−4.6 vs. −2.9 kg; P = 0.095).
While to our knowledge there have been no previous epidemiologic reports on the relationship between a Paleolithic diet score and colorectal neoplasms, 6 prospective cohort studies have examined the Mediterranean diet score (1 in relation to incident adenomas, 1 in relation to adenoma recurrence, and 4 in relation to incident carcinomas), generally finding inverse associations. Among Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial participants, a higher Mediterranean diet score was inversely associated with adenoma (for the highest quintile relative to the lowest, odds ratio = 0.79 (95% confidence interval (CI): 0.68, 0.92); Ptrend < 0.001). A principal-components analysis conducted in the European Cancer Prevention Intervention Study identified a Mediterranean-like dietary pattern that was associated with significantly lower 3-year adenoma recurrence among women only (for the highest tertile relative to the lowest, odds ratio = 0.30 (95% CI: 0.09, 0.98); Ptrend = 0.04). In the 4 studies of incident CRC, the findings for the highest quantiles of the score relative to the lowest were as follows: 1) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, the hazard ratio was 0.89 (95% CI: 0.80, 0.99; Ptrend = 0.02); 2) in the Italian component of EPIC, the hazard ratio was 0.50 (95% CI: 0.35, 0.71; Ptrend =0.04); 3) in the National Institutes of Health-AARP Diet and Health Study, risk ratios were 0.72 (95% CI: 0.63, 0.83) and 0.89 (95% CI: 0.72, 1.11) among men and women, respectively; and 4) in the Nurses' Health Study and Health Professionals Follow-up Study cohorts, risk ratios were 0.88 (95% CI: 0.71, 1.09; Ptrend = 0.25) and 0.89 (95% CI: 0.77, 1.01; Ptrend = 0.06) in men and women, respectively.
This study had several strengths and limitations. Strengths included standardized pathological verification of adenomas, thereby reducing outcome misclassification; the use of 2 control groups, each with its own strengths and limitations; assessment of exposure information prior to endoscopy, reducing opportunity for recall bias; and the collection of detailed information on potentially confounding variables. Whereas there was minimal outcome misclassification among the endoscopy controls, they may have been more similar to the cases in various respects, and whereas the community controls may have been more representative of the general population, some may have been undiagnosed cases; thus, for different reasons, the estimated associations with both control groups were probably attenuated. Although age and sex are known risk factors for colorectal neoplasms and were controlled for in the analyses, the degree to which the endoscopy controls were, on average, younger and more likely to be female raises the possibility of some selection bias. While the inverse associations between each diet and colorectal adenoma frequency were similar to each other, the point estimates for the associations with the fifth quintiles relative to the first quintiles were not statistically significant, underscoring the importance of investigating these diets in larger, preferably prospective, studies. An important limitation of our study was that, for the most part, the actual diets of the participants could not be considered to be strongly consistent with the Paleolithic or Mediterranean diet pattern. This suggests that our findings may substantially underestimate the potential of these diet patterns for reducing risk of colorectal adenoma. Finally, while our Paleolithic diet score was data-derived for the quintile cutoffs, and thus study-specific (see Reedy et al. for a review of diet scores), the schema can be applied to other study populations.
In conclusion, our findings, taken in context with those from previous studies, suggest that a Paleolithic or Mediterranean diet pattern may be inversely associated with risk of incident, sporadic colorectal adenomas.