Statins and Prostate Cancer - Don't Believe What You Read

Every few years, it seems, there is renewed interest in using statins (hydroxy-methyl-glutaryl CoA reductase inhibitors - drugs that lower cholesterol) to treat (or prevent) prostate cancer. WebMD reported on a 2009 study suggesting an almost 2/3 reduction in death rate with the use of statins:

Statins and Prostate Cancer Death

The new study involved 380 men ages 55 to 79 who died from prostate cancer between 1999 and 2001 and who had living spouses who could verify their medical histories. They were compared to 380 married men in the same age group who were still alive.

A total of 63 men who died from prostate cancer had taken statins, as had 109 of the men who were alive.

After taking into account other risk factors for dying from prostate cancer, men taking statins were 63% less likely to die from the disease than men not taking statins.

Stephen Marcella, MD, assistant professor of epidemiology at the University of Medicine and Dentistry of New Jersey in Piscataway, presented the findings at the 2009 Genitourinary Cancers Symposium.

Further analysis showed that high-potency statins like Lipitor, Zocor, and Crestor were linked to a lower risk of dying from prostate cancer even more than weaker statins like Mevacor, Pravachol, and Lescol.

"The high-potency statins were about 2.5 times more effective at preventing prostate cancer death than the weak statins," Marcella says.

"That makes sense," Klein says. "The more potent the drug, the bigger the biologic effect."

That doesn't mean high-potency statins are better than weaker statins, he stresses. "Their primary purpose is for cholesterol lowering and you typically want to use the least aggressive therapy you can to achieve the desired effect," Klein says.

While the studies were not designed to examine how statins might protect against dying from prostate cancer, Klein notes that they are potent anti-inflammatory drugs. "There's a lot of evidence that inflammation contributes to the development of prostate cancer." Alternately, statins may directly kill cancer cells, Klein says.

The anti-inflammatory model of the reduction of cancer severity in those who use statins may be true for some patients. We don't know. But we do that a diet rich vegetables, antioxidants, fruits (especially berries), and anti-inflammatory herbs (curcumin, olive leaf extract, oregano oil), combined with regular exercise and an avoidance of too much red meat (or, more precisely, flame-cooked meat) and too much sugar and other simple carbs, all work in synergism to reduce inflammation, which is the primary driver of cancer growth.

Why use statins when we can get the same benefit (and may others as well) from a proper diet?

In a 2010 paper (Di Stasi, MacLeod, Winters, and Binder-Macleod¹) on how physical therapists can be useful for those taking statins, the authors outline some of the issues with statins and muscle damage:

Approximately 25 million Americans use statins,¹³ and 5% to 18% of these patients report some form of myalgia.¹⁴ Skeletal muscle side effects that are associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death (ie, rhabdomyolysis).^15,16 Side effects have been associated with all commonly used statins and are dose dependent.^17,18

Other research has suggested the percentage of people who experience side effects (especially in muscle) is not really so tiny. Parker, Capizzi, Grimaldi, Clarkson, et al. (2013²) found that even non-symptomatic patients express increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects.

However, this is not the most serious with statins and prostate cancer. 

Earlier this year, the research surfaces again. This is a lengthy article, and I am including all of it - it comes via the Prostate Cancer Foundation.

Statins and Prostate Cancer

As the science comes together, risk of aggressive disease may be abated with use, but little effect on indolent, early prostate cancers

March 4, 2014 -- Statins are a group of widely prescribed drugs used to lower cholesterol levels in the body. Common statin medications include well-known brands such as Zocar, Lipitor, and Crestor. Statins work by inhibiting an enzyme in our bodies (HMG-CoA reductase) that is used to manufacture cholesterol, and the drugs can also help clear already formed cholesterol from the bloodstream. High cholesterol is a known cause of cardiovascular disease, and it’s well-established that statins reduce the rate of death and illness caused by cardiovascular disease. And while statins can help prevent the risk of heart attack or stroke, some studies have also suggested that statins may have an effect on prostate cancer.

Whether the effect would be beneficial or harmful has been the subject of ongoing studies for some time. When statins first became widely available to the public in the 1980s, concerns erupted that these drugs might spur some cancers. Those fears are now widely dispelled, and this past year, a massive meta-analysis of 135 randomized studies that included over a quarter million study participants, found that statin use did not increase the risk of developing cancer.

Statins and Prostate Cancer

However, whether or not statins had a positive impact on cancer risk remained an open question. Research has suggested that statins can slow cancer cell growth in certain cancer types such as breast, colorectal, and skin cancers, and may lower the risk for the latter two. And some research has also suggested that statins might lower the overall risk for prostate cancer, but because of inconsistent findings, it was clear more research was needed. From such ongoing research, what is emerging is that statins may indeed reduce the risk of death from prostate cancer, but likely have little effect on whether or not a man develops prostate cancer in the first place.

Statins and Advanced Prostate Cancer



Dr. Elizabeth A. Platz of the Johns Hopkins Bloomberg School of Public Health and a Prostate Cancer Foundation-funded researcher.
Dr. Platz and colleagues have twice found that individuals with lower levels of cholesterol (within the normal ranges, not the super low ranges) had a lower risk of developing more aggressive disease, as defined by high Gleason scores. This is yet another reason for men to put aside that plate of fried chicken and head for the salad bar, in order to naturally lower their cholesterol levels.

This January, research out of Canada published in the Journal of Clinical Oncology found that men who used statins after a diagnosis of prostate cancer had a 24% decreased risk of death from the disease compared to men who did not take statins. The longer the men took statins, the greater the protective effect. For example, men who took statins for less than one year post-diagnosis had a 1% lower risk of death from prostate cancer compared to non-users. But men who had taken statins for three or more years post-diagnosis lowered their risk of death from their cancer by 39%.

Interestingly, the study also found that statin use prior to a diagnosis of prostate cancer was even more protective to the men, in terms of both mortality specifically from prostate cancer, or from any other cause. Pre-diagnostic statin use reduced the men’s risk of death from prostate cancer by 45%, and conferred a 34% reduced risk of death from any cause, compared to men not taking statins.

All the men in the study had been newly diagnosed with non-metastatic prostate cancer at the time of their enrollment into the study; men who used statins after their diagnosis were 23% less likely to develop distant metastatic cancer spread during the study period.

This study adds to other recent research showing reduced prostate cancer-specific mortality among men who used statins. Dr. Janet Stanford, of the Fred Hutchinson Cancer Research Center in Seattle and a Prostate Cancer Foundation-funded researcher, and colleagues published a study this past summer in The Prostate demonstrating that men who took statins prior to their diagnosis of prostate cancer experienced an 81% reduced risk of prostate cancer-specific mortality compared to men who did not take statins. At 10 years of follow-up, only 1% of statin users had succumbed to prostate cancer, compared to 5% of non-users. However, that study also found that statin use prior to prostate cancer diagnosis did not affect whether or not prostate cancer recurred or progressed. At the time the study was published, Stanford called for confirmation study to validate her findings, and suggested that such research could pave the way for a large, randomized, placebo-controlled study that will yield the most definitive results on whether or not men with prostate cancer should or should not be prescribed statins to lessen their risk of death from the disease.

In response to last month’s study in the Journal of Clinical Oncology (JCO), Drs. Lorelei A. Mucci and Meir J. Stampfer from the Harvard School of Public Health and both Prostate Cancer Foundation-funded researchers, penned an editorial on the subject: Mounting Evidence for Prediagnostic Use of Statins in Reducing Risk of Lethal Prostate Cancer. In this article, Mucci and Stampfer point out that much of the inconsistency among studies on statins and prostate cancer “disappears" when the research distinguishes between risk of overall incidence of prostate cancer and risk of advanced or lethal disease. In reviewing the current “mounting" evidence, Mucci and Stampfer pointed to Stanford and colleagues findings of lower risk of death from prostate cancer in statin users, as well as a Danish study showing lower rates of death for statin users, and a Norwegian study finding that risk of lethal prostate cancer also dropped with statin use.

The authors noted that Prostate Cancer Foundation researchers were the first to focus on risk of lethal disease and statin use in a prospective, observational study published in the Journal of the National Cancer Institute (JNCI) , in 2006. (Men at risk for prostate cancer were observed over the course of several years; their use of statins was recorded, as was their incidence of prostate cancer.) That study, with first author Dr. Elizabeth A. Platz of the Johns Hopkins Bloomberg School of Public Health and a PCF-funded researcher, found that men diagnosed with prostate cancer who used statins halved their risk of developing advanced disease during the study period, and lowered their risk of lethal disease (having metastatic disease at time of diagnosis or succumbing to prostate cancer during the study’s follow up period) by 61 percent. Furthermore, the study found that the risk of developing advanced prostate cancer was lower with longer durations of statin use.

Dr. Mucci says that the Canadian study was a particularly good study for a number of reasons. “It is one of the larger studies to date with the ability to study lethal cancer during the follow-up period," says Mucci, referring to the fact that a large number of men in the study developed lethal disease during the study’s follow-up. Because smaller studies may pick up outcomes that happen just by chance rather than due to the effect of the drug, this study allows far greater confidence in the findings that statin use did have a positive effect on risk of dying from prostate cancer. Also, says Mucci, “A really unique feature of this study is that the researchers looked at statin use both before and after diagnosis." That may be important in helping to determine the mechanism of action statins have on prostate cancer. “One can think about statin use after a diagnosis, and that the drug will probably influence tumor cells after they’ve left the prostate, whereas, statin use before diagnosis could influence the tumor itself," says Mucci.

Knowing when and where statins act on prostate cancer can help determine which patients are most likely to benefit, as well as lead to new drug development specific to prostate cancer once the cellular pathways of action are determined.

Dr. Mucci and colleagues are now working out how statins may affect genes and other molecular pathways for better or worse in prostate cancer patients. They will examine prostate tissue samples taken from men who’ve just undergone radical prostatectomy. “We want to determine if there are differences in gene expression between men who use statins and those who don’t," says Mucci. They examine both tumor tissue samples and normal tissue samples taken from the prostate of each man in their study.

Statins and Overall Risk of Prostate Cancer – unlikely to work as chemopreventive agent

While statin use may have an effect on survivability of prostate cancer in some men, the evidence to date does not point to a protective effect from the drug in terms of overall risk of prostate cancer. In the 2006 JNCI study by Platz and colleagues, while risk of lethal disease was lowered among statin users, there was no risk reduction for the overall occurrence of prostate cancer in men who were taking statins.

On the heels of that study, Platz and colleagues decided to further investigate overall risk of prostate cancer and statin use. “Most of overall prostate cancer is early stage disease, and we did not see an association between statin use and prostate cancer overall" says Platz, “and we were worried maybe we might be missing an association because of a particular study bias—detection bias." Men who regularly seek care through their primary-care doctor are more likely to be screened for both high cholesterol and PSA levels. “If a man has high cholesterol he may well be prescribed a statin to lower his cholesterol levels, and if his PSA levels are elevated, his doctor might recommend a biopsy," says Platz. Regular screening can lead to both a high incidence of statin use and prostate biopsy. And because biopsy if quite sensitive to picking up early prostate cancer, this can create a false association between statin use and prostate cancer, says Platz.

“We wanted to study early prostate cancer in a setting where such detection bias is very unlikely to be operating," said Platz.

To that end, her group studied statin use in a group of men enrolled in the Prostate Cancer Prevention Trial, a study that called for annual PSA screening and digital rectal exams for prostate cancer. This eliminated the variability in screening that likely colored other studies. And, because Platz wanted to focus on early cases of prostate cancer, a setting where all men are screened equally also favored early disease detection that gave the researchers a more homogenous group of diagnosed men, weeding out most cases of late stage disease. In a study just published online in the Journal of Urology, Platz and colleagues again found no association between statin use and early prostate cancer among some 10,000 men enrolled in the Prostate Cancer Prevention Trial who were followed for a period of seven years.

“Overall," says Platz, “if you take all of the literature together, it appears as though statin drugs may be inversely associated with aggressive disease—meaning the cancer progresses to the point of distant metastatic spread, or death of the patient—but not associated with the development of the most common form of prostate cancer in men, which is very early disease."

Why and how might statin use affect development of aggressive prostate cancer?

Clearly this needs to be better understood, but there are several likely avenues of action statins can exert on cancer cells. Pre-clinical research has shown that these cholesterol-lowering drugs can inhibit prostate cancer cell growth, and may encourage cancer cell death and prevent tumor blood vessel growth as well as modulate immune system factors. Additionally, it has been suggested that statins may tamp down the activity of certain oncoproteins. Dr. Mucci’s team, in their work just beginning on tumor tissue samples and statin use, will help suss out such molecular activity and pathways involved.

Dr. Platz and colleagues have now twice found, in two different study groups of men, that individuals with lower levels of cholesterol (within the normal ranges, not the super low ranges) had a lower risk of developing more aggressive disease, as defined by high Gleason scores. (This is yet another reason for men to put aside that plate of fried chicken and head for the salad bar, in order to naturally lower their cholesterol levels.)

Moving forward to better answers

And while the indications are fairly ripe for an interventional randomized clinical study of statins as one agent in the treatment of men with advanced prostate cancer, it is very important to do the groundwork to best determine which subset of men and at what time in their treatment scope, statin use may yield the best results, says Dr. Howard Soule, chief science officer at PCF. Large randomized studies are very costly and if not properly set up, may not bring forth the best information.

From a public health standpoint, it doesn’t make sense to give healthy men, who do not have elevated cholesterol levels, statins for prevention of cancer, says Platz. “Even though these drugs are quite safe, they are not without side effects," she says.

Dr. Jonathan Simons, president and CEO of the Prostate Cancer Foundation, says, “This tantalizing possibility that statins may be used in conjunction with other therapeutics to lower a man’s risk of death from aggressive prostate cancer is well worth further exploration." Simons adds: “Finding that subset of men who might most benefit from statin use in order to hold their cancer in check, or discovering what genes and molecular pathways might be targeted with other new drugs, is a definite goal." And with the recent advent of blood tests that use genetic signatures to help separate out risk of less aggressive from risk of more aggressive disease, and the discovery of constellations of single point mutations—changes in DNA sequence called SNPs—that add up to a higher risk of lethal disease , it may be that evaluating statin use in men who are deemed at higher risk of aggressive disease may be ideal candidates in whom to study statin use as a treatment option. In fact, says Platz, such a research strategy would be feasible because in a high-risk group of men the likelihood of having an event of aggressive prostate cancer is higher, so the study would be more manageable in term of size and duration—fewer men would need to be enrolled and follow up time could be shorter in order to get actionable data.

If you noticed in the article, these studies were conducted on non-metastatic cancer patients, and the studies did not progress far enough to see if any of the patients did suffer from metastasis. Although in one of the studies mentioned, "men who used statins after their diagnosis were 23% less likely to develop distant metastatic cancer spread during the study period." But how long was the study period?

Statins, Metastasis, and Red Blood Cells

One of the emerging theories for the metastasis of prostate cancer is that the cancer stem cells have found a way to "hijack" red blood cells, which allows them to move through the body undetected by the immune system and to eventually hide out in bone morrow, where they are safe from radiation and chemotherapies, and where they also have a steady blood flow to keep them alive.

So the question, then, is how do they get into the red blood cells?

Research (Honda, Yamada, Endo, Ino, Gotoh, et al., 1998³) demonstrates that regulation of the actin cytoskeleton of erythrocytes (red blood cells) likely plays a central role in cell motility and cancer invasion. These authors believe that nonmuscle actinin-1 associates with cell adhesion molecules, such as integrin β1 and α-catenin, and is plays an important role in stabilizing cell adhesion and regulating cell shape and cell motility (Otey et al., 1990, 1993; Glück et al., 1993; Glück and Ben-Ze'ev, 1994; Knudsen et al., 1995).

Their research found that cytoplasmic actinin-4 (a novel isoform of nonmuscle α-actinin) regulates the actin cytoskeleton and increases cellular motility. However, it becomes inactivated when it is transferred to the cell nucleus, which "abolishes the metastatic potential of human cancers." So, in essence, activation of actinin-4 increases cell motility. But how?

It's long been known that inflammatory substances in the immune system can damage erthrocytes, which creates an opening for cancer stem cells to enter. The above study showed that actinin-4 was markedly induced in cells along the edges of a wound to the cytoskeleton.  

Actinin-4 was expressed in a limited population of normal cells, including erythrocytes, endothelial cells, and epithelial cells in various tissues at their border with stromal connective tissue.

So where I am going with all of this?

Simvastatin (Zocor), one of the more common statins, has been shown (Clapp, Ellsworth, Sprague, and Stephenson, 2013⁴) to increase erythrocyte deformability, which means red blood cells are more easily deformed, as in the research above. It is highly likely that other statins produce the same risks.

Deformed erthrocyes, whether from cytokines or statins, increase the risk that cancer cells, including prostate cancer, can invade the damaged blood cells and metastasize throughout the body.

So when you read that statins might be an effective treatment for prostate cancer, please keep this in mind.


References

1. Di Stasi, SL, MacLeod, TD, Winters, JD, and Binder-Macleod, SA. (2010, Oct). Effects of Statins on Skeletal Muscle: A Perspective for Physical Therapists. Physical Therapy; 90(10): 1530–1542.
2. Parker, BA, Capizzi, JA, Grimaldi, AS, Clarkson, PM, Cole, SM, et al. (2013). Effect of Statins on Skeletal Muscle Function. Circulation; 127: 96-103. doi: 10.1161/​CIRCULATIONAHA.112.136101 
3. Honda, K, Yamada, T, Endo, R, Ino, Y, Gotoh, M, Tsuda, H, Yamada, Y, Chiba, H, and Hirohashi, S. (1998, Mar 23). Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion. Journal of Cell Biology; 140(6):1383-93.
4. Clapp, KM, Ellsworth, ML, Sprague, RS, and Stephenson, AH. (2013, Mar 1). Simvastatin and GGTI-2133, a geranylgeranyl transferase inhibitor, increase erythrocyte deformability but reduce low O2 tension-induced ATP release. Am J Physiol Heart Circ Physiol.; 304(5): H660–H666.

In the late 1990s and early 2000s, selenium and vitamin E were being touted as the potential cure for prostate cancer. In fact, the most influential study was conducted at the University of Arizona - SELECT (the Selenium and Vitamin E Cancer Prevention Trial) - just a few miles down the road from here. The SELECT study found no benefit by the time it ended in 2008, but over the following years, they found an increased risk in men who took only the vitamin E supplement (2011):

After an average of 7 years (5.5 years on supplements and 1.5 off supplements), there were 17 percent more cases of prostate cancer in men taking only vitamin E than in men taking only placebos.

Specifically, for every 1,000 men who took placebos there were 65 cases of prostate cancer over 7 years; for every 1,000 men who took vitamin E, there were 76 cases of prostate cancer.  This difference, an absolute increase of 11 cases per 1,000 men, was statistically significant and therefore is not likely due to chance.  These results were published in the Journal of the American Medical Association October 12, 2011 (see the paper ).

Now a new study is out showing that in men who take high dose vitamin E and selenium, there is a nearly two-found risks of developing prostate cancer. This new report seems to be using the same men who participated in the SELECT study.

Via Live Science:

Selenium, Vitamin E Supplements May Double Prostate Cancer Risk

By Bahar Gholipour, Staff Writer | February 21, 2014 

 

Selenium supplements are popular, but do they work?

Men who take selenium and vitamin E supplements may increase their risk of prostate cancer, researchers have found.

The new study examined about 1,700 men with prostate cancer and 3,100 healthy men. These men had previously participated in a large trial in 2001, in which they had been randomly assigned to take either high doses of vitamin E and selenium supplements, or a placebo. Researchers had measured the amount of selenium in the men's toenails before they started taking the supplements.

Now, the results showed that selenium supplements did not benefit men who had lower levels of the element at the start of the study, and nearly doubled the risk of prostate cancer in those who had higher levels of selenium (but still within ranges common among U.S. men).

In addition, vitamin E more than doubled the risk of the most aggressive type of prostate cancer, but only among men with low selenium levels at the beginning of the study. [5 Things You Should Know About Prostate Cancer]

"Men should avoid selenium or vitamin E supplementation at doses that exceed recommended dietary intakes," Dr. Eric Klein, chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic, and his colleagues wrote in their study, published today (Feb. 21) in the Journal of the National Cancer Institute.

The study is, in fact, a second look at a previous large, randomized trial, which aimed to investigate whether high doses of selenium and vitamin E supplements could lower a man's risk for prostate cancer, something that earlier studies had suggested.

However, that trial, which included 35,000 men, ended early with concerns that the treatments may do more harm than good. In fact, more users of vitamin E were getting prostate cancer than men who were on placebo. "Vitamins are not innocuous…they can be harmful," Klein told Live Science at the time in 2011.

The doses used in that trial were 200 micrograms of selenium and 400 international units of vitamin E. These doses are higher than most multivitamins, which contain about 50 micrograms of selenium and 30 to 200 international units of vitamin E.

Previous studies have suggested that the effects of nutrition supplements depend on how well-nourished a population is. Similarly, it is possible that the U.S. population is already getting adequately high levels of selenium through diet, and supplementing them with more selenium results in an unnaturally high amounts of the element, and has either no effect or increases cancer risk, the researchers said.

The findings also point to a complex interaction between selenium and vitamin E, the researchers said. The study showed that vitamin E increased the cancer risk in men who had low levels of selenium.

This was unexpected because both vitamin E and selenium have antioxidant roles and one could reasonably expect the opposite -- that supplemental vitamin E could compensate for an antioxidant deficit resulting from lower selenium, wrote Paul Frankel, a biostatistician at City of Hope Comprehensive Cancer Center, in an accompanying editorial.

It is unlikely that there will be another trial looking at these supplements and their role in preventing prostate cancer, the researchers said. Given the risks and lacking evidence of benefits for other diseases, men older than 55 should avoid supplementation with either vitamin E or selenium at doses that exceed recommended dietary intakes, the researchers said.

Email Bahar Gholipour or follow her @alterwired. Follow us @LiveScience, Facebook & Google+. Original article on Live Science.

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 

Abstract 

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

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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

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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.

Results

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

A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice

Russel J. Reiter, Dun-Xian Tan, Lucien C. Manchester, Ahmet Korkmaz, Lorena Fuentes-Broto, W. Elaine Hardman, Sergio A. Rosales-Corral, and Wenbo Qi. 

ABSTRACT 

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

Abstract 

Objective

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

Design

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.

Results

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.

Conclusions

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.

Conclusion

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

• Taking omega-3 fish oil supplements may increase the risk of aggressive prostate cancer by 70%. Daily Mail, July 11 2013
• Omega-3 supplements 'could raise prostate cancer risk'. The Daily Telegraph, July 10 2013
• Omega-3 capsules ‘raise risks of prostate cancer’. Metro, July 10 2013
• Omega 3 fatty acids 'play a role' in prostate cancer. ITV News, July 10 2013. 
• Prostate cancer risk linked to 'healthy' fish oil fatty acids. Daily Mirror, July 11 2013

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. Darke, Xiaoling Song, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, Frank L. Meyskens Jr, Gary E. Goodman, Lori M. Minasian, Howard 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: Theodore.Brasky@osumc.edu).

Abstract

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.

Exercise Inhibits Prostate Cancer Cell Growth

The common wisdom (in this case, an actual truth) is that every man will eventually develop prostate tumors if he lives long enough. Prostate cancer is the most common type of cancer in men and the second leading cause of death among men in the U.S. In 2008, the National Cancer Institute recorded 186,000 new cases and 28,600 deaths - those numbers are likely to have increased around 10% since 2008, in part due to better detection.

A 2012 meta-analysis of studies up to the that year identified a modest but significant protective factor for exercise (a reduction in risk for developing cancer). Further, several studies examining physical activity in relation to aggressive prostate cancer (about 10% of all PCa) and prostate cancer mortality also reported a significant risk reduction.

This new study shows that changes in the body chemistry during and immediately after exercise create a more aversive environment for PCa, inhibiting its growth.

As if we need another reason to exercise regularly, this is surely a good reason to do so.

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

Abstract

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 acuteendurance 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, Jul 5). Effect of Acute Exercise on Prostate Cancer Cell Growth. PLoS ONE 8(7): e67579. doi:10.1371/journal.pone.0067579

Introduction

Prostate cancer is the second most frequent cancer diagnose in men in the world today. The highest incidence rates are found in the developed western countries and are 20 fold higher than the incidence rates found e.g. in South Central Asia and western Africa [1]. The discrepancy is partly due to the established use of PSA testing but lately a significant impact of life-style effects are being recognized [2]. Physical activity is an adjustable life-style factor associated with a reduced risk of several cancers, including prostate cancer [3].

A recent meta analysis comprising studies until 2012 suggests that being physically active is associated with a modest but significant reduction in risk of prostate cancer [4]. In addition, studies examining physical activity in relation to high-grade prostate cancer and prostate cancer mortality also reported a significant risk reduction [5]–[7].

The mechanisms mediating the effects of physical activity are not yet understood, although some candidates including weight control, improved immune cell function and modifications of endogenous hormone levels such as leptin, insulin and insulin like growth factor -1 (IGF-1) have been put forward [8]. Elevated serum levels of leptin, insulin and IGF-1 are all associated with high risk of prostate cancer incidence and progression [8]–[12] and long-term exercise is known to reduce serum levels of these and other endogenous hormones [13], [14].

Serum from endurance trained individuals on a low-fat, high-fiber diet has been shown to inhibit growth of an established prostate cancer cell line when compared to control serum [15]. More recent studies from the same group suggest that the mechanism behind the effect is mediated through the IGF-1 axis [16].

In contrast to long-term exercise, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as growth hormone (GH) [17], various cytokines [18]including IL-6 [19], [20] and also increased bioavailability of IGF-1 [21], [22].

It can be speculated that the increase in serum growth factors induced by acute exercise 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.

Read the whole study.