Do heart-healthy oils endanger the prostate?

The ebullience associated with n-3 fatty acids has fostered the resurgence of long-chain ingredients and products with EPA and DHA, in a variety of dosage forms, and has vaulted plant-sourced n-3 (alpha-linolenic acid; LNA) ingredients and products into a category unto its own. The benefits associated with n-3 fatty acids are anchored primarily with cardiovascular health and disease modification, reinforced by a substantial evidence base from supplementation trials, primarily with EPA/DHA. However, a large number of epidemiological and observational studies have suggested LNA may increase prostate cancer risk.

The Health Professionals Follow Up Study (HPFUS; a group of more than 50,000 US-based health professionals first enrolled in 1986) and Physicians Health Study (population of almost 15,000 US-based physicians and a subgroup of 120 with and 120 without prostate cancer) were among the first investigations suggesting a risk-increasing relationship between dietary and blood LNA levels and prostate cancer, respectively.1,2 A later study conducted among Norwegian men donating to the Janus serum bank (one of the world?s largest biometric collections, instituted in 1973), and later developing prostate cancer, derived similar results.3 A number of reviews applying varying degrees of rigor have emerged in the recent 18 months. One nonsystematic review4 that claimed to use only Medline to source published studies asserted that the evidence is mixed, citing some large studies reporting no association,5,6 although one of these studies was only a meeting abstract (and did not provide a statistical risk estimate) and is not catalogued on Medline.6

In the same month a more rigorous meta-analysis, but still limited to Medline databases, echoed the findings of clinical trials confirming a cardioprotective effect of high LNA diets, but also reinforced a positive association of high LNA intakes with prostate cancer risk.7

A paper that appeared later last year, as an extension of the HPFUS, presented a quite convincing demonstration of no increased risk of all forms of prostate cancer with LNA intake.8 The dietary intake data from this study, recorded in 1986, 1990 and 1994, did yield a finding of increased risk of advanced prostate cancer among those with the highest LNA intakes.8 In a reply to a letter to the editor,7 the Dutch researchers supplanted the earlier findings of the HPFUS with the more recent data, but still observed a modest increase in risk for total prostate cancer in relation to highest LNA intakes.9 The most recent case-control study included 1,294 Italian men with prostate cancer and 1,451 men without prostate cancer, from the same regions and described an inverse relationship — that is, risk reduction.10

The absence of clinical trials assessing the influence of LNA on prostate cancer tumour markers, let alone cancer incidence, obfuscates this diet-cancer relationship. Additionally, regiospecific/genotypic influences may modify the risk calculations based upon the geographic setting and the dietary sources of LNA (meats vs plant foods).

What may unexpectedly yield some additional light on a lingering question is the ongoing Netherlands-based Alpha-Omega Trial, evaluating the impact of LNA and marine n-3 fatty acid supplements on coronary heart disease mortality in 4,000 myocardial infarction patients: Does cardioprotection outweigh the risk of prostate cancer risk reduction?

Anthony Almada, MSc, is president and chief scientific officer of IMAGINutrition Inc. Respond: [email protected]com

Correction: In the February column on chocolate, reference 2 was inadvertently transposed with reference 3. FF&N regrets the error.

References
1. Giovannucci E, et al. A prospective study of dietary fat and risk of prostate cancer. JNCI 1993; 85:1571-9.
2. Gann PH, et al. Prospective study of plasma fatty acids and risk of prostate cancer. JNCI 1994; 86:281-6.
3. Harvei S, et al. Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk of prostate cancer. Int J Cancer 1997; 71:545-51.
4. Attar-Bashi NM, et al. Alpha-linolenic acid and the risk of prostate cancer. What is the evidence? J Urol 2004; 171:1402-7.
5. Schuurman AG, et al. Association of energy and fat intake with prostate carcinoma risk: results from The Netherlands Cohort Study. Cancer 1999; 86:1019-27.
6. Alberg AJ, et al. Fatty acid levels and the subsequent development of prostate cancer. Proc Am Assoc Cancer Res 1996; 37:96.
7. Brouwer IA, et al. Dietary alpha-linolenic acid is associated with reduced risk of fatal coronary heart disease, but increased prostate cancer risk: a meta-analysis. J Nutr 2004;1 34:919-22.
8. Leitzmann MF, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr 2004; 80:204-16.
9. Brouwer IA, et al. Reply to de Lorgeril and Salen. J Nutr 2004; 134:3386.
10. Bidoli E, et al. Macronutrients, fatty acids, cholesterol and prostate cancer risk. Ann Onc 2005; 16:152-7.

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