Journal of the American College of Nutrition, Vol. 26, No. 4, 317-320 (2007)
Published by the American College of Nutrition
Lack of Effect of Walnuts on Serum Levels of Prostate Specific Antigen: A Brief Report
Joel A. Simon, MD, MPH, FACN,
Jay S. Tanzman and
Joan Sabaté, MD, DrPH
General Internal Medicine Section, Medical Service, Veterans Affairs Medical Center (J.A.S)
Division of Clinical Research, Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco (J.A.S.)
Department of Nutrition, School of Public Health, Loma Linda University (J.S.T., J.S.), Loma Linda, California
Address correspondence to: Dr. Joel A. Simon, General Internal Medicine (111A1), San Francisco VA Medical Center, 4150 Clement Street, San Francisco, California, 94121. E-mail: joel.simon{at}ucsf.edu
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ABSTRACT
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Objective: To examine whether the short-term consumption of walnuts, a food rich in 
-linolenic acid, affects levels of serum prostate-specific antigen (PSA), a marker of prostate enlargement, inflammation, and cancer.
Methods: Using data from a 12-month randomized crossover study examining the effect of walnut consumption on body composition, we examined whether increased walnut consumption (mean 35 grams daily, 12% total energy) affected serum PSA levels among 40 middle-aged men.
Results: There was no significant difference between mean PSA level at the conclusion of the 6-month walnut-supplemented diet (1.05 µg/L, 95% CI [0.81, 1.37]) and the conclusion of the 6-month control diet (1.06 µg/L, 95% CI [0.81, 1.38]) (P = 0.86) (or a mean proportional decrease in PSA of –1%).
Conclusions: Our results suggest that short-term consumption of walnuts is unlikely to affect PSA levels adversely among otherwise normal men.
Key words: -linolenic acid, diet, prostate cancer, prostate specific antigen, walnuts
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INTRODUCTION
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Although prostate cancer risk is associated with increasing age, African American race, and a family history of prostate cancer [1–4], its causes remain largely unexplained. Some studies suggest that dietary factors, such as fat and meat consumption, may influence the development of prostate cancer [5–7]. Among the dietary factors that have been potentially linked to prostate cancer are lycopene, selenium, vitamin D, and vitamin E as protective factors and total fat, saturated fat, calcium, and -linolenic acid (ALA) as risk factors [1,6,8,9]. There have been at least 10 observational studies examining the relation between ALA and prostate cancer, 8 of which found increasing dietary intake or blood levels of ALA associated with increased prostate cancer risk [10,11]. The Lyon Diet Heart Study, however, a secondary coronary heart disease (CHD) prevention trial, examined the effect of a Mediterranean diet that included high dietary intakes of ALA and reported no increased risk for prostate cancer after 4 years of follow-up [12] and a small feeding study of flaxseed in 25 men awaiting surgical prostatectomy for cancer likewise detected no adverse effects from short-term increased consumption of ALA [13].
This report presents the results of a secondary analysis of data collected from the Walnut Body Weight Study that examines the effect of walnuts, an important dietary source of ALA, on serum prostate-specific antigen (PSA) levels, a marker of prostate inflammation, enlargement and cancer.
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METHODS
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Subjects
Details of the Walnut Body Weight Study, a 12-month crossover trial examining the effect of increased walnut consumption on body composition, have been reported elsewhere [14]. In brief, 90 men and women from several southern California communities were recruited to participate in trial where they were initially assigned to either a control diet or a walnut-supplemented diet for 6 months. After 6 months, participants switched over to the other dietary intervention. Whole walnuts were provided in individual packets every 2 months and the allotment was adjusted for each participant based on their daily energy intake. The walnut supplemented diet provided an additional 3.68 g/day of ALA (see Table 1). Because the relation of walnut consumption to PSA was not an apriori hypothesis, no specific physical, ultrasound, or biopsy examinations of prostate were performed as part of the study. Exclusion criteria included weight change >1 kg during the previous 6 months, BMI >35 kg/m2, an habitual diet that included nut consumption more often than once a week, and metabolic disorders that can affect weight, such as diabetes.
Data Collection
Participants were randomly assigned to 1 of 2 diet sequences: control/walnut or walnut/control. This analysis of the Walnut Body Weight Study includes PSA data from men at baseline, 4, 6, 10, and 12 months. The treatment groups received 
12% of their total energy from walnuts for 6 months. No additional dietary advice was given. Observations from months 4 and 6 were treated as replicate measurements from treatment period 1, and observations from months 10 and 12 as replicates from treatment period 2. Data from one participant whose PSA values increased from 1 µg/L to >12 µg/L were excluded from the main analyses as were two other observations because the values appeared spuriously high when compared with the other observations from these participants. PSA measurements were performed at the Loma Linda University Medical Center Clinical Laboratory using the microparticle enzyme immunoassay technology. The main report is based on a total of 150 observations from 39 men, but we also re-analyzed the data for all 40 male participants without exclusions. We collected 7 24-hr dietary recalls from each participant during each diet period. To capture daily variations in intake, all days of the week (2 weekend days and 5 weekdays) were covered by the recalls. Compliance with the walnut and control diets was confirmed by measuring red blood cell levels of ALA, which increased on average 39% on the walnut diet [15]. Red blood cell ALA was measured at baseline and from blood samples taken during the last week of the sixth month of each diet period. The study had an effective washout period of 4 months since data from the fourth and sixth month of each dietary treatment were used in these analyses and any potential carryover effect of the initial diet had 4 months to wash out prior to measurements being taken on the second diet.
Statistical Analysis
Residual analysis indicated non-normality of the data, which was corrected by using a log transformation. The transformed data were analyzed as a 2 x 2 crossover study, using mixed linear models with fixed terms for diet and period, and a random term for subjects. Carryover effect was tested by adding an interaction term for diet x period and was non-significant (P > 0.99). Treatment effects among groups based on age and PSA level were assessed separately by adding a dichotomous variable for the baseline value and a term for its interaction with diet. Results are presented on their original scale (Table 3), after being back-transformed. Table 3 presents geometric means and treatment effects expressed as relative differences, i.e., the serum PSA levels during the walnut diet divided by serum PSA during the control diet.
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Table 3. Effect of Walnut Diet vs. Comparison Diet on Serum Prostate Specific Antigen (PSA) Levels (in µg/L) from the Walnut Body Weight Study (n=39)
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RESULTS
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Data from 39 men, age 30 to 70 years were analyzed for the main analyses. Participants were, on average, 53-year-old, overweight, Caucasian men (Table 2). On the control diet, male participants consumed a total of approximately 1.63 g/day of ALA (of which 1.56 g was derived from non-walnut food sources) compared with 5.10 g/day on the walnut diet (P < 0.0001). Participants on the walnut diet consumed 1.42 g/d from non-walnut food sources. As expected, the daily consumption of total fat and polyunsaturated fatty acids was greater during the period of walnut consumption (both P < 0.0001).
We examined the PSA levels of participants at the end of the control diet and the end of the walnut diet and found no significant difference in mean PSA levels (Table 3). The mean proportional change in PSA from the walnut intervention was –1%. We also examined the relation stratified by median baseline PSA and by median age. When analyzed in this fashion, there was no evidence of a differential effect on serum PSA levels based on age or baseline PSA level. Of the 39 participants, 19 (49%) had increased PSA levels on the walnut diet and 20 (51%) had decreased PSA levels. The two largest increases in PSA levels on the walnut diet were 0.76 and 0.46 µg/L in men who had control diet levels of 5.74 and 0.54 µg/L, respectively.
We performed additional analyses that included data from the one participant whose PSA levels rose from 1 µg/L to >12 µg/L and two other excluded observations that we deemed of questionable validity. In these new analyses, we detected no significant diet effect either for the total sample or for the analyzed subgroups. However, among participants with a baseline PSA of <0.83 µg/L and among participants age 55 years and older, there was a trend toward decreased PSA levels on the walnut diet (both P = 0.05).
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DISCUSSION
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We found no effect of walnut consumption on the PSA levels among the men enrolled in the Walnut Body Weight Study. Because walnuts contain high concentrations of ALA, we were interested to determine whether increasing consumption of walnuts might raise serum PSA levels. A recent meta-analysis of 9 observational studies by Brouwer et al. reported that ALA, the parent omega-3 fatty acid, was associated with a decreased CHD risk, but an increased prostate cancer risk [10] and a report from the Health Professional Follow-up Study that enrolled over 47,000 non-physician health professionals found that plant-based ALA, although not associated with the total risk for prostate cancer, was however, associated with an approximately two-fold increased risk for advanced prostate cancer [11]. Our study had the advantage of random assignment and a crossover design, thereby eliminating confounding, but our conclusions are limited by the short duration of follow-up, the intermediate endpoint (i.e., serum PSA levels rather than incident or advanced prostate cancer), and a small sample size with limited statistical power. Hence, we cannot be certain that a larger study with a longer duration of follow-up and clinical endpoints may have produced different findings. Furthermore, we cannot exclude the possibility that the individual changes might be of clinical relevance for some subjects. While the walnut intervention group had higher intakes of ALA (and total polyunsaturated fatty acids) and lower intakes of eicosapentaenoic acid and docosahexaenoic acid compared with the control intervention, there is inconclusive evidence that these changes in dietary fatty acid intake affect the risk for prostate cancer [8, 11].
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CONCLUSION
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We found no effect of 6 months of walnut consumption on the serum PSA levels of men participating in a small walnut consumption clinical trial. The short-term consumption of walnuts appears unlikely to affect prostate health adversely in otherwise healthy men.
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FOOTNOTES
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This study was supported by a grant from the California Walnut Commission.
Received March 1, 2006.
Accepted May 10, 2006.
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ABSTRACT
INTRODUCTION
