Case control and prospective studies of dietary alpha linolenic acid intake and prostate cancer risk a meta analysis

Alpha linolenic acid (ALA) is considered to be a cardioprotective nutrient; however, some epidemiological studies have suggested that dietary ALA intake increases the risk of prostate cancer. The main objective was to conduct a systematic review and meta-analysis of case control and prospective studies investigating the association between dietary ALA intake and prostate cancer risk. Design: A systematic review and meta-analysis were conducted by searching MEDLINE and EMBASE for relevant prospective and case control studies. Included studies: We included all prospective cohort, case control, nested case-cohort and nested case  control studies that investigated the effect of dietary ALA intake on the incidence (or diagnosis) of prostate cancer and provided relative risk (RR), HR or OR estimates. Primary outcome measure: Data were pooled using the generic inverse variance method with a random effects model from studies that compared the highest ALA quantile with the lowest ALA quantile. Risk estimates were expressed as RR with 95 per cent CIs. Heterogeneity was assessed by χ2 and quantified by I2. Results: Data from five prospective and seven case control studies were pooled. The overall RR estimate showed ALA intake to be positively but non- significantly associated with prostate cancer risk  but the interpretation was complicated by evidence of heterogeneity not explained by study design. A weak, non-significant protective effect of ALA intake on prostate cancer risk in the prospective studies became significant without evidence of heterogeneity on removal of one study during sensitivity analyses. Conclusions: This analysis failed to confirm an association between dietary ALA intake and prostate cancer risk. Larger and longer observational and interventional studies are needed to define the role of ALA and prostate cancer. (Authors abstract)

Epidemiological and clinical studies  have shown that ALA is associated with a reduction in coronary heart disease (CHD) incidence and heart disease mortality. However, since ALA has also been associated with an increased risk of prostate cancer. While previous meta-analyses  have been conducted to determine whether a relationship exists, there has been no meta-analysis since 2010 that has examined the specific effect of dietary ALA on prostate cancer risk and none since 2009 that included both prospective cohort and case-control studies. The present meta analysis of 12 observational studies (7 case control and 5 prospective) comparing the highest with the lowest categories of dietary ALA intake demonstrated non significant heterogeneous effects of ALA on prostate cancer risk. Overall, there was no significant association between ALA intake and risk of prostate cancer. The subgroup analysis of case–control studies alone showed a positive non significant association, but with substantial heterogeneity. When examining the prospective studies alone, the association between ALA intake and prostate cancer risk was non significantly protective and became weakly but significantly protective with no heterogeneity. The study additionally investigated the association between dietary ALA intake and prostate cancer risk among case control studies and reached the conclusion of non significantly increased risk with high heterogeneity, particularly because of the inclusion of two studies with very high ORs. The study determined whether these heterogeneous results can be explained by a number of factors, such as the variation in ALA consumption, sources or population dietary patterns. However, this heterogeneity among the case control studies may serve to highlight the less reliable nature of case control study design as it inherently involves recall bias since dietary information is collected after disease development. Confounding factors in studies of ALA include heterogeneity and the effect of ALA between studies; Variation in ALA consumption and sources, and population dietary patterns; Variation in ALA exposure levels; Variation in FFQs and food databases; and Variation in adjustment factors. Another issue to consider is confounding from other PUFAs such as n  6 or other n  3 fatty acids (eicosapentaenoic and docosahexaenoic fatty acids) that might affect ALA metabolism and consequently may introduce bias.

In conclusion, these findings provide no clear evidence of an association between dietary ALA intake and prostate cancer risk. Further, since these observational studies can only show association between ALA intake and prostate cancer, possible causation would be difficult to establish. Therefore, additional research from epidemiological, clinical and in vitro studies is required to elucidate whether ALA has a promotional, inhibitory or no effect on prostate cancer risk and development. At present, no significant association has been found and where any support of a positive effect was seen, red meat sources have been strongly implicated. The source of ALA appears to be of importance, particularly identifying whether it is from animal or vegetable sources, as
ALA may be a marker for higher meat and fat intake in some countries, both of which have been associated with increased prostate cancer risk.  Determination of the sources of fatty acids is probably of greater importance since ALA is associated in the North American diet with meat cell membranes and creamy salad dressings, which themselves may be markers of a suboptimal dietary pattern and lifestyle. (Editors comments)