Study: Effects of diet and supplements on prostate cancer risk

reference

Kristal AR, Arnold KB, Neuhouser ML, Goodman P, Platz EA, Albanes D, Thompson IM. Diet, supplement intake and prostate cancer risk: results of the prostate cancer prevention study.Am J Epidemiol.2010;172(5):566-5770.

background

The prostate cancer prevention study was a randomized, placebo-controlled trial that tested whether finasteride, a 5-alpha-reductase inhibitor, could reduce the 7-year prevalence of prostate cancer. Beginning in 1993, 18,880 men aged ≥55 years in the United States and Canada with normal digital rectal examination (DRE) results were examined; Prostate-specific antigen (PSA) levels of 3 ng/mL or less; and without a history of prostate cancer, severe lower urinary tract symptoms, or clinically significant comorbidities were randomized to receive either finasteride (5 mg/day) or placebo. During PCPT, men underwent DRE and PSA testing annually, and prostate biopsy was recommended for participants with abnormal DRE results or a PSA (adjusted for the effect of finasteride) of 4.0 ng/mL or greater. At the final study visit in the seventh year (2000–2003), all men not previously diagnosed with prostate cancer were offered a biopsy consisting of at least 6 core samples taken under transrectal ultrasound guidance. Biopsies were examined for adenocarcinomas with full consensus by both the pathologist at the local study site and a central pathology laboratory. Clinical stage was assigned locally and tumors were graded centrally using the Gleason grading system.

Of the 18,880 participants, 7,615 (40.3%) who did not have a biopsy at the end of the study were excluded, including 1,225 men who died, 6,381 men who were unable or refused to have a biopsy for medical reasons, and 9 who underwent prostatectomy for reasons other than cancer; 2,401 cases and 8,864 non-cases remained. Researchers then excluded 173 cases diagnosed on or after the study end date (June 24, 2003), 92 cases diagnosed 180 days or more after their scheduled study completion, and 140 cases who were missing Gleason scores. Of the 10,860 men remaining for the study, researchers also excluded 102 men who were missing body mass index data, 770 men who were missing dietary data, and 429 men whose dietary information was judged unreliable due to a reported energy intake of less than 800 kcal/day or more than 5,000 kcal/day. Some men did not complete the nutritional questionnaires because the physicians at their clinic site decided not to participate in the nutritional studies or because prostate cancer was diagnosed before the questionnaire was administered. This analysis was based on 1,703 diagnosed cases of cancer in 9,559 men.

Participant

9,559 Canadian and American men

Evaluated study parameters

Details on demographic and health-related characteristics were collected at baseline using self-completed questionnaires. Physical activity level was assessed using a 6-item questionnaire. Height and weight were measured at the first clinic visit.

One year after randomization, participants completed a 15-page booklet containing two questionnaires about diet and supplement use. Diet was assessed using a food frequency questionnaire (FFQ) designed specifically for this population of older men. The FFQ consisted of questions about 99 foods and 9 beverages, as well as 18 questions about food preparation and 2 questions about fruit and vegetable consumption. On the questionnaire, participants reported: the usual number of tablets taken per day for multivitamins and antioxidant blends; both the number of pills taken per day and the dose for beta-carotene, vitamin C, vitamin E, calcium and zinc; and whether they took stress multivitamins, vitamin D, fish oil or selenium at least three times a week. Multivitamin consumption and additional intake of specific nutrients (the sum of individual supplements plus multivitamins) were categorized as low (corresponding to no or infrequent use of a dietary supplement), moderate (corresponding to the amounts generally obtained from multivitamins), and high (corresponding to amounts generally only possible from high-dose individual supplements). Because data for fish oil, selenium, and vitamin D were only available on whether these supplements were taken at least three times per week, fish oil was coded as 0 or 0.5 g of docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) per day, selenium was coded as 0 or 200 μg/day, and vitamin D was coded as 0 or 10 μg/day. The vitamin D content of multivitamins is also 10 µg; Therefore, men who took both multivitamins and individual vitamins were placed in the high-dose vitamin D category.

In an inter- and intra-method reliability study conducted among 150 randomly selected men, we compared nutrient intakes calculated from the first FFQ, intakes from six 24-hour recalls conducted the following year, and intakes from an additional FFQ completed after all 24-hour recalls. One-hour recalls were conducted. Based on the 128 men who completed the study, the correlations between the first FFQ and 24-hour recalls (adjusted for energy and adjusted for measurement error) were: total fat, 0.71; polyunsaturated fat, 0.66; monounsaturated fat, 0.66; saturated fat, 0.75; alcohol, 0.84; carbohydrates, 0.70; protein, 0.50; vitamin C, 0.62; lycopene, 0.58; beta-carotene, 0.68; vitamin D, 0.57; EPA + DHA, 0.87; calcium, 0.62; and zinc, 0.51. Correlations between repeated FFQs were above 0.60 for all nutrients, except 0.54 for EPA + DHA.

Key findings

• Krebs wurde bei 1.703/9.559 Männern festgestellt, von denen 127 eine hochgradige Erkrankung aufwiesen (Gleason-Score 8 bis 10).
• Es gab keine Hinweise auf einen Zusammenhang zwischen der Verwendung eines bestimmten Nährstoffs und dem Gesamtrisiko für Prostatakrebs.
• Das Risiko für hochgradigen Prostatakrebs war mit einer hohen Aufnahme mehrfach ungesättigter Fette verbunden.
• Nahrungskalzium war positiv mit dem Befund eines geringgradigen Prostatakrebses verbunden.
• Umgekehrt war die Aufnahme von Kalzium in der Nahrung umgekehrt mit dem Befund von hochgradigem Prostatakrebs verbunden.
• Die Aufnahme mehrfach ungesättigter Fettsäuren war positiv mit dem Risiko für hochgradigen Krebs verbunden. Es gab keine Hinweise darauf, dass die Ernährung oder die Verwendung von Nahrungsergänzungsmitteln, die häufig zur Vorbeugung von Prostatakrebs eingesetzt werden (z. B. Lycopin, langkettige n-3-Fettsäuren, Vitamin D, Vitamin E, Selen), das Risiko für Prostatakrebs signifikant beeinflusst.

Effects on practice

Using an FFQ to assess the association between food/supplement use and disease has been shown to have low validity.¹As shown in studies of dietary fat and breast cancer risk, there is a distinct possibility that moderate or weak associations between diet and cancer risk cannot be detected using FFQs, but can be detected using multi-day food records.²

Lycopene is a major component of tomatoes and is highly associated with beneficial effects against prostate cancer. Lycopene supplementation has had mixed results in the literature. It seems reasonable to obtain lycopene from food, which could provide additional synergistic value, rather than from supplements, which show inconsistent results in studies.³

This study does not clarify what type of vitamin E participants use. However, the study cites the SELECT study, a large population study that found no reduced risks after supplementing with vitamin E, selenium, or both. It is important to note that the type of vitamin E used in the SELECT study was exclusively alpha-tocopherol. In high doses, alpha-tocopherol “spins out” the vital gamma-tocopherol in the cells. While alpha-tocopherol inhibits free radical production, it is the gamma-tocopherol form of vitamin E that is needed to capture and neutralize free radicals. In a study published in the Proceedings of the National Academy of Sciences, researchers reported that it could be dangerous to take high amounts of alpha-tocopherol vitamin E without also taking gamma-tocopherol.⁴The reason for this finding appears to be that too much alpha-tocopherol could deprive cells of the gamma form of vitamin E, which is needed to neutralize existing oxidants such as the peroxynitrite radical, which can be particularly harmful. In a study of 10,456 men conducted at the Johns Hopkins School of Public Health, men with the highest gamma-tocopherol blood levels were five times less likely to develop prostate cancer. In addition to finding that higher gamma-tocopherol levels significantly reduced the risk of prostate cancer, the study also showed that selenium and alpha-tocopherol also reduced prostate cancer incidence, but only when gamma-tocopherol levels were high.⁵

With regard to calcium consumption, it is unclear why dietary calcium was positively associated with the finding of low-grade prostate cancer but inversely associated with the finding of high-grade prostate cancer.

With regard to calcium consumption, it is unclear why dietary calcium was positively associated with the finding of low-grade prostate cancer but inversely associated with the finding of high-grade prostate cancer. It is not defined whether those who took calcium supplements also consumed any amount of vitamin D3. At least in dairy products, calcium may increase prostate cancer risk by suppressing circulating 1,25-D levels.⁶Overall, dairy products appear to increase the overall risk of prostate cancer and should be avoided by prostate cancer patients or those with a family history of prostate cancer.⁷

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