Saturday, July 20, 2013

New Research in Prostate Cancer - Exercise Good, Soy Bad, Walnuts Good; Smoked/Salted Fish Bad, Fish Oil Good, Or Not

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in men in the United States and other Western countries. In general, if we live long enough, all men get some form of prostate cancer, 90% of which are largely non-aggressive.

It is believed that exercise is important in limiting the recurrence of prostate cancers (and breast cancers, for that matter) after initial treatment. There have also been several studies showing a preventative effect of exercise in those with benign prostate hypertrophy (BPH). Now there is a study that identifies in real time the bio-chemical response that inhibits prostate cancer cell growth and/or proliferation.

There have been a few observational studies linking the intake of soy products with reduced risk and/or reduced recurrence of prostate cancer. However, there also have been several studies suggesting the estrogenic properties of soy (particularly the isolflavones genistein, daidzein) can not increase the risk but also the aggressiveness of prostate tumors.

On the other hand, walnuts have been shown to be an effect prevention food, which would be part of a good anti-inflammation diet (one of the top ways to delay or prevent the occurrence of most cancers). Similarly, oily fish and fish oil supplements have also demonstrated strong prevention properties.

However, a recent study found that high levels of EPA, DPA, and DHA (the primary omega-3 fatty acids in fish) are associated with a serious increase in risk for aggressive prostate cancers.

Presented below are all of these articles or summaries of the research.

Effect of Acute Exercise on Prostate Cancer Cell Growth 

Helene Rundqvist, Martin Augsten, Anna Strömberg, Eric Rullman, Sara Mijwel, Pedram Kharaziha, Theocharis Panaretakis, Thomas Gustafsson, Arne Östman 
Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum) and after completed exercise (exercise serum). The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.
Full Citation: 
Rundqvist H, Augsten M, Strömberg A, Rullman E, Mijwel S, et al. (2013) Effect of Acute Exercise on Prostate Cancer Cell Growth. PLoS ONE, 8(7): e67579. doi:10.1371/journal.pone.0067579
* * * * * * *

Soy protein supplementation does not reduce risk of prostate cancer recurrence

Posted on July 9, 2013 

Among men who had undergone radical prostatectomy, daily consumption of a beverage powder supplement containing soy protein isolate for 2 years did not reduce or delay development of biochemical recurrence of prostate cancer compared to men who received placebo, according to a study in the July 10 issue of JAMA.

"Prostate cancer is the most frequently diagnosed malignancy and the second most frequent cause of male cancer death in the United States and other Western countries but is far less frequent in Asian countries. Prostate cancer risk has been inversely associated with intake of soy and soy foods in observational studies, which may explain this geographic variation because soy consumption is low in the United States and high in Asian countries," according to background information in the article.

"Although it has been repeatedly proposed that soy may prevent prostate cancer development, this hypothesis has not been tested in randomized studies with cancer as the end point. A substantive fraction (48 percent - 55 percent) of men diagnosed as having prostate cancer use dietary supplements including soy products, although the exact proportion is not known. However, no evidence exists that soy supplementation has any prostate cancer-related benefits for these men. Soy contains several constituents, including isoflavones, which possess anticancer activities in laboratory studies."

Maarten C. Bosland, D.V.Sc., Ph.D., of the University of Illinois at Chicago, and colleagues examined whether daily consumption of a soy protein-based supplement would reduce the rate of recurrence or delayed recurrence of prostate cancer in men at high risk of recurrence after radical prostatectomy. The randomized trial was conducted from July 1997 to May 2010 at 7 U.S. centers and included 177 men. Supplement intervention was started within 4 months after surgery and continued daily for up to 2 years, with prostate-specific antigen (PSA) measurements made at 2-month intervals in the first year and every 3 months thereafter. Participants were randomized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate (n=87) or as placebo, calcium caseinate (n=90).

The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group. Overall, 28.3 percent of participants developed biochemical recurrence (defined as development of a PSA level of ≥0.07 ng/mL) within 2 years of entering the trial. Twenty two (27.2 percent) of the participants in the intervention group developed confirmed biochemical recurrence, whereas 23 (29.5 percent) of the participants receiving placebo developed recurrence. "Among participants who developed recurrence, the median [midpoint] time to recurrence was somewhat shorter in the intervention group (31.5 weeks) than in the placebo group (44 weeks), but this difference was not statistically significant," the authors write.

Adherence was greater than 90 percent. There were no differences in adverse events between the 2 groups.

"The findings of this study provide another example that associations in observational epidemiologic studies between purported preventive agents and clinical outcomes need confirmation in randomized clinical trials. Not only were these findings at variance with the epidemiologic evidence on soy consumption and prostate cancer risk, they were also not consistent with results from experiments with animal models of prostate carcinogenesis, which also suggest reduced risk," the researchers write.

"One possible explanation for these discrepant results is that in both epidemiologic studies and animal experiments, soy exposure typically occurred for most or all of the life span of the study participants or animals; there are no reports of such studies in which soy exposure started later in life. Thus, it is conceivable that soy is protective against prostate cancer when consumption begins early in life but not later or when prostate cancer is already present. If this is the case, chemoprevention of prostate cancer with soy is unlikely to be effective if started later in life, given the high prevalence of undetected prostate cancer in middle-aged men."

Source: The JAMA Network Journals

* * * * * * *

Several studies over the years have found that walnuts decrease the risk of prostate cancers and the incidence of aggressive cancers. Here is another study in that lineage.

Prostate Cancers Are Fewer, Smaller On Walnut-Enriched Diet

July 16, 2013 — New research from the School of Medicine at The University of Texas Health Science Center San Antonio indicates that eating a modest amount of walnuts can protect against prostate cancer.

The study is described in the journal Cancer Investigation. Researchers at the UT Health Science Center injected immune-deficient mice with human prostate cancer cells. Within three to four weeks, tumors typically start to grow in a large number of these mice. The study asked whether a walnut-enriched diet versus a non-walnut diet would be associated with reduced cancer formation. A previous study found this to be true for breast cancer.


Three of 16 mice (18 percent) eating the walnut-enriched diet developed prostate tumors, compared with 14 of 32 mice (44 percent) on the non-walnut control diet. Also of note, the final average tumor size in the walnut-fed animals was roughly one-fourth the average size of the prostate tumors that developed in the mice eating the control diet.

"We found the results to be stunning because there were so few tumors in animals consuming the walnuts and these tumors grew much more slowly than in the other animals," said study senior author Russel Reiter, Ph.D., professor of cellular and structural biology at the Health Science Center. "We were absolutely surprised by how highly effective the walnut diet was in terms of inhibition of human prostate cancer."

Percentage of diet

The mice consumed a diet typically used in animal studies, except with the addition of a small amount of walnuts pulverized into a fine powder to prevent the rodents from only eating the walnuts. "The walnut portion was not a large percentage of the diet," Dr. Reiter said. "It was the equivalent to a human eating about 2 ounces, or two handfuls, a day, which is not a lot of walnuts."

Study co-author W. Elaine Hardman, Ph.D., of the Joan C. Edwards School of Medicine at Marshall University, published a study in 2011 that showed fewer and smaller tumors among walnut-fed mice injected with human breast cancer cells. Dr. Hardman formerly was a faculty member at the Health Science Center.

"The data to date suggest that using walnuts on a regular basis in the diet may be beneficial to defer, prevent or delay some types of cancer, including breast and prostate," Dr. Reiter said.

Full Citation:
Russel J. Reiter, Dun-Xian Tan, Lucien C. Manchester, Ahmet Korkmaz, Lorena Fuentes-Broto, W. Elaine Hardman, Sergio A. Rosales-Corral, Wenbo Qi. (2013, Jul). A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice. Cancer Investigation, 31 (6): 365 DOI: 10.3109/07357907.2013.800095

Russel J. Reiter, Dun-Xian Tan, Lucien C. Manchester, Ahmet Korkmaz, Lorena Fuentes-Broto, W. Elaine Hardman, Sergio A. Rosales-Corral, and Wenbo Qi. 
It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet.

* * * * * * *

Several studies over the past couple of decades have shown that oily fish or fish oil can help reduce the risk of prostate and other cancers. A few smaller studies have found the opposite. 

First up here is a study that looks at the consumption of fish or fish oil over the lifespan. After that is a recent study that suggests high levels of EPA, DHA, and DPA (constituents of fish oil) increases the risk of aggressive prostate cancers by up to 70%. Scary stuff. 

Consumption of Fish Products across the Lifespan and Prostate Cancer Risk

Johanna E. Torfadottir, Unnur A. Valdimarsdottir, Lorelei A. Mucci, Julie L. Kasperzyk, Katja Fall, Laufey Tryggvadottir, Thor Aspelund, Orn Olafsson, Tamara B. Harris, Eirikur Jonsson, Hrafn Tulinius, Vilmundur Gudnason, Hans-Olov Adami, Meir Stampfer, Laufey Steingrimsdottir



To examine whether fish and fish oil consumption across the lifespan is associated with a lower risk of prostate cancer.


The study was nested among 2268 men aged 67–96 years in the AGES-Reykjavik cohort study. In 2002 to 2006, dietary habits were assessed, for early life, midlife and later life using a validated food frequency questionnaire. Participants were followed for prostate cancer diagnosis and mortality through 2009 via linkage to nationwide cancer- and mortality registers. Adjusting for potential confounders, we used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for prostate cancer according to fish and fish oil consumption.

Among the 2268 men, we ascertained 214 prevalent and 133 incident prostate cancer cases, of which 63 had advanced disease. High fish consumption in early- and midlife was not associated with overall or advanced prostate cancer. High intake of salted or smoked fish was associated with a 2-fold increased risk of advanced prostate cancer both in early life (95% CI: 1.08, 3.62) and in later life (95% CI: 1.04, 5.00). Men consuming fish oil in later life had a lower risk of advanced prostate cancer [HR (95%CI): 0.43 (0.19, 0.95)], no association was found for early life or midlife consumption.


Salted or smoked fish may increase risk of advanced prostate cancer, whereas fish oil consumption may be protective against progression of prostate cancer in elderly men. In a setting with very high fish consumption, no association was found between overall fish consumption in early or midlife and prostate cancer risk.
Full Citation: 
Torfadottir JE, Valdimarsdottir UA, Mucci LA, Kasperzyk JL, Fall K, et al. (2013, Apr 17). Consumption of Fish Products across the Lifespan and Prostate Cancer Risk. PLoS ONE, 8(4): e59799. doi:10.1371/journal.pone.0059799

See also:
Zhennan Gu, Janel Suburu, Haiqin Chen, and Yong Q. Chen. (2013). Mechanisms of Omega-3 Polyunsaturated Fatty Acids in Prostate Cancer Prevention. BioMed Research International, vol. 2013, Article ID 824563, 10 pages. doi:10.1155/2013/824563
On the other hand, a major study published by the Journal of the National Cancer Institute argues that high blood levels of omega-3 fats correlates with a 70% increased risk of aggressive prostate cancer - a frightening proposition for those of us who eat a lot of fish or take fish oil supplements.

The flaw with this study is that they only measured blood levels of fatty acids without any correlation to diet or supplement intake. Further, it only looked at associations with aggressive or non-aggressive prostate cancers. This isn't the only study to show these results, so it's worth taking into consideration. However, there needs to be more effort to assess confounding variables that may have influenced the results.

Fish oil supplements linked to prostate cancer

Thursday July 11 2013

There is little evidence to support the use of omega-3 supplements

"Taking omega-3 fish oil supplements may increase the risk of aggressive prostate cancer by 70%," the Daily Mail reports.

The story, covered widely in the media, comes from a large and well designed study that also found that high blood levels of omega-3 fatty acids were associated with a 44% increase in the risk of slow growing prostate cancer.

Supporters of fish oil supplements have claimed that they can reduce the risk of stroke, heart attack, and dementia as well as improving cognitive function and mental health. But there is little conclusive evidence to justify these claims.

The findings match previous studies that have found a similar link between high blood levels of omega-3 fatty acids and prostate cancer.

It is worth bearing in mind that this study did not assess participants’ diet and use of supplements. Researchers measured blood levels of fatty acids and analysed the association with prostate cancer risk. However, it is likely that the very high levels of fatty acids found in some participants’ blood came from supplements.

If you are considering taking an omega-3 supplement get medical advice first.

Where did the story come from?

The study was carried out by researchers from the Fred Hutchinson Cancer Research Center, Ohio State University and was funded by the National Cancer Institute. It was published in the peer-reviewed Journal of the National Cancer Institute.

It was covered fairly in the papers, with the Daily Mail including comments from independent experts.

What kind of research was this?

This was a case-control study that looked at the association between blood levels of long-chain omega-3 fatty acids and the risk of prostate cancer.

In this type of study, cases of people who have a particular outcome – in this case, prostate cancer – are matched against a random group of people who do not develop the condition.

The research was part of a large randomised controlled trial called SELECT, looking at whether selenium and vitamin E supplements reduced the risk of prostate cancer. (It found no benefit from selenium and an increase in prostate cancer in men who took vitamin E.)

The researchers point out that omega-3 supplements are widely used and that ongoing trials are looking at their possible benefits for cancer and heart disease prevention. Their previous study from 2011 suggested a link between high blood levels of long-chain omega-3 fatty acids and high grade (aggressive) prostate cancer.

What did the research involve?

The researchers included 834 men from the original trial, who had been diagnosed with prostate cancer, of which 156 were diagnosed with high-grade (aggressive) cancer.

The researchers randomly selected 1,393 men who matched the case subjects on age and race, with a ratio of 1:3 for black men and 1:1.5 for other men. The men completed questionnaires about their backgrounds and health at the start of the study, while staff measured height and weight to calculate body mass index (BMI). Blood samples were also collected and blood levels of long-chain omega-3 fatty acids (also called polyunsaturated fatty acids, or PUFAs) were assessed. These were:

  • eicosapentaenoic acid (EPA)
  • docosapentaenoic acid (DPA)
  • docosahexaenoic acid (DHA)

They categorised blood levels of these fatty acids into quartiles (four equal groups of 25% of the study group).

Researchers also looked at blood levels of omega-6 fatty acids – linoleic acid (LA) and arachidonic acid (AA) – and of trans fatty acids.

Using standard statistical methods, the researchers analysed the associations between overall blood levels of omega-3 fatty acids and prostate cancer risk overall, and by grade. They also looked at the association between prostate cancer risk and blood levels of individual omega-6 fatty acids. They adjusted their results for other confounders that might affect the risk of prostate cancer, such as family history.

They also carried out a meta-analysis to compare their results with similar studies.

What were the basic results?

The researchers found that, compared with men whose blood levels of omega-3 fatty acids were in the lowest quartile, men in the highest quartile had:

  • 44% increased risk of low grade prostate cancer (HR (hazard ratio) = 1.44, 95% CI (confidence interval) = 1.08 to 1.93)
  • 71% increased risk of high grade prostate cancer (HR = 1.71, 95% CI = 1.00 to 2.94)
  • 43% increased risk of total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88)

These associations were similar for the individual omega-3 long-chain fatty acids, EPA, DPA and DHA.

A higher blood level of linoleic acid was associated with a reduced risk of low grade prostate cancer (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01). Linoleic acid is found in various vegetable oils.

How did the researchers interpret the results?

The researchers say their study confirms previous reports of increased prostate cancer risk among men with high blood concentrations of omega-3 fatty acids. They say the consistency of these findings suggests that these fatty acids are involved in the growth of prostate tumours.

Recommendations to increase omega-3 intake “should consider its potential risk”, they argue.

They also say that the findings are surprising, given that omega-3 fatty acids are thought to have anti-inflammatory properties, pointing out that inflammation plays a role in the development of many cancers. Further research is needed into the possible mechanisms, they say.


This was a large, well designed study that supports previous research linking high blood levels of omega-3 fatty acids with prostate cancer risk. However, it cannot show that fish oil supplements cause prostate cancer and it is possible that other confounders affected men’s risk (although the researchers tried to take these into account).

The research did not look at the participants’ diets or whether they took omega-3 supplements. Still, it is unlikely that the high levels of these fatty acids found in the highest quartile would be the result of diet alone. Adults are advised to eat two portions of fish a week, one of them oily, as part of a healthy balanced diet.

Despite claims that fish oil supplements can help prevent numerous conditions including cancer, dementia, arthritis and heart problems, there is little hard evidence for them. Although they are “natural” products (albeit in a processed form), this does not mean they are safe or suitable for everyone.

While omega-3 supplements are sometimes advised for people who have had a heart attack this supplement is typically used under supervision of a healthcare professional.

If you are thinking of taking omega-3 supplements, talk to your GP or the healthcare professional in charge of your care first.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links to the headlines

Links to the science

Brasky TM, Darke AK, Song X, et al. Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. Journal of the National Cancer Institute. Published online July 10 2013

Oily fish

Long-chain omega-3 fatty acids may be good for the heart, but you can obtain enough from your diet. It’s not common for someone to need supplements for their health.

A healthy diet should include at least two portions of fish a week, including one of oily fish (such as mackerel). Babies, children and women who are pregnant, breastfeeding or planning to have children should have no more than two portions of oily fish a week.

Those not in these groups can eat up to four portions a week. This maximum level is recommended to avoid overexposure to marine pollutants. Read more about eating fish and shellfish and your health.

Here is the abstract for the article presented above:

Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial

Theodore M. Brasky, Amy K. DarkeXiaoling Song, Catherine M. TangenPhyllis J. Goodman, Ian M. Thompson, Frank L. Meyskens JrGary E. GoodmanLori M. MinasianHoward L. Parnes, Eric A. Klein and Alan R. Kristal

+Author Affiliations
Affiliations of authors: Department of Internal Medicine, Division of Cancer Prevention and Control, The Ohio State University College of Medicine, Columbus, OH (TMB); Cancer Prevention Program (TMB, XS, GEG, ARK) and SWOG Statistical Center (AKD, CMT, PJG), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Urology, University of Texas–San Antonio Health Science Center, San Antonio, TX (IMT); Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA (FLM); Department of Environmental Health (GEG) and Department of Epidemiology (ARK), University of Washington, Seattle, WA; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (LMM, HLP); Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH (EAK).

Correspondence to: Theodore M. Brasky, PhD, Ohio State University Comprehensive Cancer Center, 1590 N High St, Ste 525, Columbus, OH 43201 (e-mail:


Background Studies of dietary ω-3 fatty acid intake and prostate cancer risk are inconsistent; however, recent large prospective studies have found increased risk of prostate cancer among men with high blood concentrations of long-chain ω-3 polyunsaturated fatty acids ([LCω-3PUFA] 20:5ω3; 22:5ω3; 22:6ω3]. This case–cohort study examines associations between plasma phospholipid fatty acids and prostate cancer risk among participants in the Selenium and Vitamin E Cancer Prevention Trial.

Methods Case subjects were 834 men diagnosed with prostate cancer, of which 156 had high-grade cancer. The subcohort consisted of 1393 men selected randomly at baseline and from within strata frequency matched to case subjects on age and race. Proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between fatty acids and prostate cancer risk overall and by grade. All statistical tests were two-sided.

Results Compared with men in the lowest quartiles of LCω-3PUFA, men in the highest quartile had increased risks for low-grade (HR = 1.44, 95% CI = 1.08 to 1.93), high-grade (HR = 1.71, 95% CI = 1.00 to 2.94), and total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88). Associations were similar for individual long-chain ω-3 fatty acids. Higher linoleic acid (ω-6) was associated with reduced risks of low-grade (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01); however, there was no dose response.

Conclusions This study confirms previous reports of increased prostate cancer risk among men with high blood concentrations of LCω-3PUFA. The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis. Recommendations to increase LCω-3PUFA intake should consider its potential risks.

No comments: