Showing posts with label prostate cancer. Show all posts
Showing posts with label prostate cancer. Show all posts

Monday, July 15, 2013

The Facts About Omega-3 Fatty Acids and Increased Prostate Cancer Risk

A study released this week, “Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial,” published in the Journal of the National Cancer Institute (JNCI)) suggests that the omega-3 essential fatty acids EPA, DPA, and DHA - but not the omega-3 fatty acid ALA, found in flax, chia, hemp seeds, and nuts that have repeatedly been shown to lower prostate cancer rates - are somehow associated with increased risks of high-grade prostate cancer. At the same time, higher amounts of normally harmful trans fats in these subjects were associated with lower rates of advanced prostate cancer. [1] Because of the known limitations of this particular kind of study, all of these reported results were completely unproven, highly questionable, and highly unlikely to be true.

What kind of study was this? It is data mining of a previously published population study in which important variables and endpoints for fish oil's relationship to prostate cancer were not controlled, nor any cause and effect demonstrated. Because it is a secondary analysis of a largely epidemiological (population) study, it represents the lowest level of evidence in human studies because most relevant variables, confounding factors, and clinical endpoints are not systematically collected for proper analysis as they would be in an actual controlled clinical trial. Instead, the limited goal was to look for possible associations that were admittedly not rigorous enough to be considered as actual evidence of a causal relationship. As a preliminary study, it was consciously designed only to raise questions, rather than to provide answers, and it did accomplish that goal but also created a messy splash of misleading and over-emphatic headlines inaccurately suggesting that this one study somehow trumps many more robust clinical trials. So much for the media knowing of and respecting the Scientific Method. [2]

Dr Marilyn Glenville PhD, the UK’s leading nutritionist specializing in women’s health and former President of the Food and Health Forum at the Royal Society of Medicine, has noted some deficiencies in the current JNCI report; some examples: [3]
  • “This is not a randomised controlled trial but a trial comparing Omega 3 levels in men with prostate cancer with healthy men. The men with prostate cancer had higher levels of Omega 3. But you cannot extrapolate cause and effect from this finding. It is like saying that if the majority of men with prostate cancer played tennis compared to healthy controls then tennis could trigger prostate cancer.”
  • In 2009 the Harvard School of Public Health reported that “Omega 3 deficient diets cause up to 96,000 preventable deaths a year in the US. The researchers estimated the number of deaths resulting from 12 preventable causes and Omega 3 deficiency ranked as the sixth highest killer of Americans. A deficiency in these fats was classed as a bigger killer than high intake of trans fats.” [4]
  • “…there are many cultures such as the Japanese who eat high amounts of oily fish containing Omega 3 fatty acids and yet have one of the lowest prostate cancer death rates in the world.”
Duffy MacKay, N.D., vice president, scientific and regulatory affairs of the Council for Responsible Nutrition, also noted some concerns with the report: [5]
  • “Hundreds of studies over the past two decades have shown omega-3 fatty acids to have positive effects associated with cardiovascular health, perinatal health, inflammation, cognitive function, or cancer. Collectively, this body of research serves as the basis for numerous recommendations from respected organizations, scientific boards and healthcare practitioners that Americans get omega-3 fatty acids in their diets.”
  • “While we encourage researchers to continue to study omega-3 fatty acids with an open mind, it is counterproductive when studying nutrition for researchers to promote their study as if it were the only piece of research that counts. In this case in particular, it is especially disingenuous for the researchers to make the kinds of assertions we've seen in the press, given their results are in stark contrast to previous epidemiologic studies that not only demonstrate no correlation between omega-3 consumption through fish and/or supplementation and the risk of prostate cancer, but in many cases also showed a protective effect against prostate cancer.”
  • “One should also consider whether this study could have simply been measuring a biomarker reflecting recent intake of fish or fish oil supplements in a group of high risk cancer patients that had been told to increase their EPA and DHA levels, as compared to a group of non-cancer patients that had not been told to consume more EPA and DHA. Plasma levels of EPA and DHA reflect very recent intake and are considered a poor biomarker of long term omega-3 intake especially when compared to red blood cell levels, which reflect medium term intake. A single fish oil dose (or hearty serving of fish at lunch) results in >100 percent increase in plasma omega-3 levels. So looking at plasma levels in healthy and sick people may only provide insight into the recent habits of these individuals.”
  • “The American Heart Association, the World Health Organization (WHO), the U.S. Institute of Medicine’s Food Nutrition Board (IOM FNB) and the 2010 Dietary Guidelines all have current policies advising Americans to eat more fatty fish to get the benefits of omega-3 fish oils. It is highly unlikely this one study will change that advice. Omega-3s can also be obtained by taking one of the many supplement products on the market. For those consumers who have concerns about prostate cancer or other questions about omega-3 fatty acids, we recommend speaking with your doctor or other healthcare practitioner.”
If you are a man and believe this report, then you’ll probably want to eat partially hydrogenated artificial trans fats instead of omega-3 fats for prostate health; though that change would greatly increase your risk of suffering far deadlier cardiovascular diseases, based on evidence from many clinical trials. But that would be ridiculous. In fact, many cultures around the world consume far more fish oil than Americans without having increased risks of aggressive prostate cancer; these include the Inuit people ("Eskimos"), Scandinavians, Southeast Asians, Pacific Islanders, Japanese, Filipinos, and others. 

In any case, in the absence of proper controls or any evidence of causation, we actually can’t know what these study results really mean. For example:
  • Were DHA levels related to diet, supplementation, or both?
  • Were fish and/or fish oils perhaps consumed as a deliberate health choice because of prior knowledge of prostate issues, rather than actually causing or aggravating those issues? In other words, could the consumption represent an attempt to improve a pre-existing condition by improving one’s nutritional status and be unrelated to the disease itself? Perhaps even suggested by medical teams as potentially helpful for patients' diet?
  • If they had been collected, what would key inflammatory and oxidative markers, that are much likelier to be related to prostate health problems than long-chain omega-3 fatty acids such as DHA, have told us about these men’s state of health and disease?
  • Where is the biochemical evidence that DHA itself may negatively contribute to prostate concerns? None is presented, even theoretically.
The Global Organization for EPA and DHA Omega-3s (GOED) also criticized these and numerous other some aspects of the JNCI report, among them these important points: [6]
  • “The difference in mean blood plasma phospholipid fatty acids blood level for omega-3s was 4.66% in the combined cancer group versus 4.48% in the control. They are basing their results on just ca. 0.2% difference in omega-3 levels.”
  • “Plasma phospholipid fatty acids as measured in this study are not a good index of long term intake and are influenced dramatically by a single meal, or even timing of a fish oil dose. A single fish oil dose massively increases LC omega 3 (typically increasing levels by 100% or more) in about 4-12 hours and then washes out around 48 hours.”
  • “The study was not designed to look at omega-3 and confounded with selenium and Vitamin E used in the treatment arms.”
  • “The test cohort included sick and healthy people. It is possible that sick people were taking fish oil supplements at a higher rate than the healthy individuals.”
  • “A recent meta-analysis of fish consumption and prostate cancer by Szymanski et al. (2010) reported a large reduction in late stage or fatal prostate cancer among cohort studies." [7]
  • "Several population based studies have shown a benefit of increased omega-3 fatty acid intakes to reducing prostate cancer risk.” [8], [9]
As I said earlier, this type of study raises questions about possible associations; but due to its built-in limitations, and results conflicting with most other related studies, provides no real answers.  Unfortunately, its counter-intuitive results generate sensational press coverage rarely accompanied by any true perspective on what this new study really means (not much).

In real life, most Americans and others in Western societies no longer consume the ideal amount or ratio of omega-3 fatty acids in their diet as our ancestors did a century or two ago. This reduction reportedly contributes to the large increase in chronic health problems that plague these societies. It is a public disservice to inappropriately scare people away from healthy foods and supplements, which help balance the diet in these many cases where the lack of essential nutrients is actually causing harm, based solely on such flimsy “evidence”. 

After reviewing this study I, a vegetarian, will continue to take my vegan DHA supplement twice a day with absolutely no concerns that it will negatively affect my own prostate health. Why am I not at all concerned? Because there is still no hard evidence explaining how long-chain omega-3 fatty acids like EPA and DHA may promote prostate cancer. There is still no demonstrated mode of action for this concern, and there are still no plausible explanations of any biological mechanisms that could justify the theory that long-chain omega-3 fatty acids may promote prostate cancer. My lack of concern is evidence based, after carefully reviewing the studies in question. Contrast this with the fear-mongering about fish, fish oil, and omega-3 fatty acids in foods and supplements that is overwhelmingly based on speculation, flimsy data, ignorance (on several levels), and maybe even some bias.

By Neil E. Levin, CCN, DANLA

REFERENCES:


[4] The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors" study, April 2009, PLoS Medicine
[7] Szymanski KM, Wheeler DC, Mucci LA. Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr. 2010;92(5):1223–1233
[8] Terry P, Lichtenstein P, Feychting M, et al. Fatty fish consumption and risk or prostate cancer. Lancet, 2001,357:1764-6.
[9] Lietzman MF, Stampfer MJ, Michaud DS, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr 2004;80:204-216.

Friday, November 16, 2007

A Tale of Two Studies: Vitamin E - Food vs Supplements

Vitamin E: Food vs Supplements Here is an illustration of the apparent contradiction between whether food sources of vitamin E are better to prevent prostate cancer than supplemental vitamin E sources: Two large studies, both published in the same technical journal at the same time, seem to reach contradictory results as to whether supplemental vitamin E is valuable in relation to prostate cancer. But are they both equal and contradictory? Actually, one is far more rigorous, and thus presumably more valid, than the other. In the first one (Serum and Dietary Vitamin E in Relation to Prostate Cancer Risk <1>), definite and large benefits were shown for supplemental alpha-tocopherol vitamin E, but not for food sources (containing mostly gamma-tocopherol). In the second one (Supplemental and Dietary Vitamin E Intakes and Risk of Prostate Cancer in a Large Prospective Study <2>), only food sources containing gamma-tocopherol were effective, but not supplemental vitamin E as alpha-tocopherol. A closer look reveals that the first study responsibly looked at serum levels and food plus supplemental vitamin E intake, then related that data to prostate cancer rates over up to 19 years afterward. This study's conclusion was that, "In summary, higher prediagnostic serum concentrations of alpha-tocopherol, but not dietary vitamin E, was associated with lower risk of developing prostate cancer, particularly advanced prostate cancer." The second study looked only at questionnaires related to subjects' intake of vitamin E from food and supplements at the start of the 5-year study, then compared the number of cancers over a 5-year period to data obtained from that questionnaire. The incubation period for cancers is estimated to be in the decades, rarely a period of 5 years or less. That, along with the lack of any data on serum antioxidant status and the use of a questionably reliable survey to determine intake of vitamin E from food or supplements, makes the second report far less meaningful than the first one. Don’t get me wrong, I am not against food sources of nutrients and routinely recommend vitamin E sources containing gamma-tocopherol, along with the full range of tocopherols and tocotrienols. But when preliminary or sketchy science is all-too-often reported as if it’s definitive when it’s really not, and when it is contradicted by better science, I am compelled to put things into a more realistic perspective. The measurement of serum levels in the body, along with careful reporting of a nutrient’s intake from various sources, is much more compelling than relying on a questionnaire that may be done by memory. It is well-known among nutritionists that daily food diaries are notoriously different than weekly food surveys done by memory recall, which almost always seem to conveniently forget the junk food, snacks and extra calories. A cancer study lasting nearly 4 times as long is also far more compelling than a shorter one because it will be more likely to encompass the cancer’s incubation period and allow for the development of symptoms that will allow detection. As the National Cancer Institute reports: “Prostate cancer often does not cause symptoms for many years.” <3> The use of supplemental alpha-tocopherol is supported by other reputable studies. For example, The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated a 32% reduction in prostate cancer incidence in response to daily alpha-tocopherol supplementation. <4> Levels of Vitamin E above 100 IU daily are associated with decreased risk of coronary heart disease and certain types of cancer, as well as enhancement of immune function. These increased vitamin E intakes (100 I.U. and above) are considerably above levels obtainable from diet alone. <5-7> In the case of supplemental vitamin E, the results for prostate cancer in the more rigorous, better designed and better implemented study shows that it is more beneficial for prostate health than only food sources of vitamin E, which also tend to be much weaker amounts (often far below 100 IU daily, with Americans’ typical intake being only around 9.5 IU (6.4 mg) of alpha-tocopherol, below the RDA of 22.5 IU (15 mg). <8-9> This indicates our general need for supplemental vitamin E, unless by some miracle we all suddenly decide to eat wholesome natural foods containing a lot more vitamin E. But in the meantime, it would be nice if these studies were put into perspective so we could accurately assess their value to our health habits. Unfortunately, media coverage of negative reports, especially regarding vitamins, tends to drown out the positive ones, even when the good news is backed by studies with better design and implementation. In this case, supplemental vitamin E was the clear winner over the abysmal amounts in our diet, which ideally should be increased to healthy levels. REFERENCES: 1. Weinstein, SJ, et al. Serum and Dietary Vitamin E in Relation to Prostate Cancer Risk. Cancer Epidemiol Biomarkers Prev 2007 16: p. 1253-1259 http://cebp.aacrjournals.org/cgi/content/abstract/16/6/1253?ct 2. Wright, ME, et al. Supplemental and Dietary Vitamin E Intakes and Risk of Prostate Cancer in a Large Prospective Study. Cancer Epidemiol Biomarkers Prev 2007 16: p. 1128-1135 http://cebp.aacrjournals.org/cgi/content/abstract/16/6/1128?ct 3. National Cancer Institute’s Web site http://www.cancer.gov/cancertopics/factsheet/Detection/early-prostate 4. Weinstein SJ, et al. Serum alpha-tocopherol and gamma-tocopherol in relation to prostate cancer risk in a prospective study. J Natl Cancer Inst. 2005 Mar 2;97(5):396-9. PMID: 15741576 5. Bauernfeind, J. Tocopherols in Foods. In: Vitamin E: A Comprehensive Treatise. Marcel Dekker, Inc., New York and Basel, pp. 99-167, 1980 6. Horwitt, M.K. The Promotion of Vitamin E. J. Nutr. 116:1371-1377, 1986 7. Weber, P., Bendich, A. and Machlin, L.J. Vitamin E and Human Health: Rationale for Determining Recommended Intake Levels. Nutrition 13:450-460, 1997 8. Ervin RB, Wright JD, Wang CY, Kennedy-Stephenson J. Dietary intake of selected vitamins for the United States Population: 1999–2000. Advance data from vital and health statistics; no 339. Hyattsville, Maryland: National Center for Health Statistics. 2004 9. Vitamin E, Office of Dietary Supplements • NIH Clinical Center • National Institutes of Health http://ods.od.nih.gov/factsheets/vitamine.asp