Archive for the ‘Omega-3s’ Category

DHA Supplements and Prostate Cancer

Thursday, July 25th, 2013

A study was released this month that correlated a higher percentage of omega-3 fatty acids in the blood, especially DPA and DHA, with an increased risk for prostate cancer. This made big news and the merits of the study have been debated and people have been asking me if it would make me change my recommendations for taking DHA.

The study by Braskey et al (1) was funded by the National Cancer Institute and was a case-control analysis. It was also an offshoot of the Selenium and Vitamin E Cancer Prevention Trial (SELECT). There were numerous statistically significant findings with the strongest being for DHA. A DHA percentage of >3.62 was associated with a 39% increased risk of prostate cancer when compared to a DHA percentage of < 2.33 (1.39, 1.06-1.82). The finding was stronger for low-grade prostate cancer while insignificant for high-grade.

Interestingly, ALA levels were not associated with an increased risk of prostate cancer and the omega-6 fatty acid, linoleic acid (LA), was slightly associated with a reduced risk.

Additionally, the researchers performed a meta-analysis of 7 similar studies and again found that DHA was associated with an increased risk of prostate cancer (1.16, 1.03-1.31). In the 5 studies that separated low-grade versus high-grade, both low (1.20, 1.04-1.38) and high (1.48, 1.10-1.99) were associated with an increased risk.

As I see it, the strengths of the study are:

– Percentage of fatty acids in the blood is possibly a better indicator of actual intake (or absorption) than a food frequency questionnaire.

– The follow-up was about 8 years, which seems long enough to eliminate the possibility of reverse causation in which DHA levels might be elevated due to the prostate cancer.

The potential weaknesses of the study are:

– Measuring fatty acids as a percentage rather than an absolute amount could be misleading. One person might have a higher percentage of DHA, but a lower total amount of DHA. For example, if you eat a very low-fat diet but with a bit of fish, then your DHA will be high as a percentage, but could possibly be lower, in total, than someone who eats a large amount of fat including fish. In other words, it could be that people with a higher percentage of DHA actually have a lower absolute amount of DHA. I don’t know how likely this is, but it doesn’t seem to be out of the question if many fish-eaters are on low-fat diets. Given some of the findings from other studies I’m about to discuss, this might be plausible.

– The whole project of associating the percentage of various fatty acids with various cancers has been fraught with null, inconsistent, and weak findings. When this is the case, it’s a good indication, in my opinion, that there is nothing really there.

This study was criticized by Dr. Michael Murray in his July 22, 2013 article, Does Fish Oil Really Boost Prostate Cancer? One interesting point he makes is that the omega-3 levels in those with prostate cancer were not very high. Those without cancer had an average DHA level of 2.91% (95% CI: 2.86-2.96) while those with cancer had a level of 3.01% (95% CI: 2.95-3.08). People taking fish oil supplements tend to have amounts quite a bit higher than that.

I will go a step further than Dr. Murray and suggest that the differences between the two groups, while statistically significant, are so minor as to be practically meaningless: a DHA level of 2.91% is pretty much the same as 3.01%. Even when you add EPA + DPA + DHA together, the difference is hardly anything (4.48% for the no cancer group vs. 4.66% for the cancer group).

What about studies measuring intake?

A 2006 meta-analysis of 7 cohort studies found no significant association with the incidence of prostate cancer and intake of EPA or DHA (2). A 2010 meta-analysis of fish consumption and prostate cancer, which included most of the studies from the 2006 meta-analysis plus many more, found no association between fish consumption and prostate cancer incidence, and a reduced risk for prostate consumption mortality (3).

Speaking of fish, there is a question as to whether the association between omega-3 percentage and prostate cancer found in Braskey et al could be explained by mercury contamination of fish. While I found a study indicating that mercury levels in humans are correlated with fish consumption (4), I could not find any examining an association between mercury and prostate cancer. I did find two sources which indicate that if mercury causes prostate cancer, no one seems to know about it yet (5, 6).

So where does this leave us? I have a friend who pointed out that the mere idea that DHA could cause prostate cancer is ridiculous given what an important component of brain tissue DHA is. That’s an interesting perspective, though something good for the brain is not necessarily good for the prostate. I do think his point should increase the burden of proof needed before concluding that DHA causes prostate cancer.

One final point is that vegans who do not supplement with DHA tend to have DHA levels around 1%. As I reported recently, we have an anecdotal report of a 60-year old vegan man who raised his DHA levels from 1.0% to 4.8% using 320 mg of DHA plus 130 mg of EPA per day. My recommendations are for vegetarians 60 and under to supplement with 200-300 mg every other day and for vegans over 60 to supplement with that much every day. If you are someone who is at high risk for prostate cancer, I can see supplementing on the lower side of these recommendations (though I cannot tell any given individual what amount they personally need) to keep your levels below the 3.6% cutoff in Braskey et al.

In summary, I’m skeptical that DHA causes prostate cancer, but if you are at high risk, it might be prudent to stick to the lower end of the daily recommendations until more is known.

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References

1. Brasky TM, Darke AK, Song X, Tangen CM, Goodman PJ, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Klein EA, Kristal AR. Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. J Natl Cancer Inst. 2013 Jul 10. [Epub ahead of print] | link

2. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim YW, Traina SB, Hilton L, Garland R, Morton SC. Effects of omega-3 fatty acids on cancer risk: a systematic review. JAMA. 2006 Jan 25;295(4):403-15. Review. Erratum in: JAMA. 2006 Apr 26;295(16):1900. | link

3. Szymanski KM, Wheeler DC, Mucci LA. Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr. 2010 Nov;92(5):1223-33. doi: 10.3945/ajcn.2010.29530. Epub 2010 Sep 15. | link

4. Yoshizawa K, Rimm EB, Morris JS, Spate VL, Hsieh CC, Spiegelman D, Stampfer MJ, Willett WC. Mercury and the risk of coronary heart disease in men. N Engl J Med. 2002 Nov 28;347(22):1755-60. (I only read the abstract.) | link

5. Landrigan PJ. Occupational and community exposures to toxic metals: lead, cadmium, mercury and arsenic. West J Med. 1982 Dec;137(6):531-9. | link

6. Järup L. Hazards of heavy metal contamination. Br Med Bull. 2003;68:167-82. | link

DHA Case Study

Monday, July 1st, 2013

Just added this to Omega-3 Fatty Acid Recommendations for Vegetarians at VeganHealth.org:

A 60 year old, male, long time vegan forwarded his fatty acid lab reports to me. In August 2012 his EPA levels were .3% and DHA was 1.0% (of fatty acids in blood). He had been using “a lot of” canola oil but it apparently wasn’t increasing his EPA and DHA levels. After six months of daily supplementation of 320 mg DHA plus 130 mg of EPA (one capsule of Ovega-3 vegan supplement), his EPA levels went to 1.0% (about average for omnivores) and DHA to 4.8% (towards the higher average range for omnivores). It appears that this regimen was adequate.

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DHA Recommendations Follow-Up

Thursday, May 30th, 2013

After I published my last post, DHA Recommendations Updated (A Bit), I received comments from a reader saying that there is no evidence that vegans need to supplement with DHA. So, I went digging for the evidence.

The first bit comes from the experience of Joel Fuhrman, MD, which I blogged about in November of 2010 in the post DHA Supplements: A Good Idea, Especially for Older Vegan Men, in which Dr. Fuhrman said that he has been seeing numerous elderly vegans with severe DHA deficiency, and he believes it may have exacerbated Parkinson’s disease and tremors in some of his patients.

Is there any evidence for a connection here? I’m not an expert on the literature regarding DHA and the brain, but here is an excerpt from a 2005 study that indicates it’s plausible:

“Docosahexaenoic acid (DHA), a dietary essential omega-3 fatty acid concentrated in membrane phospholipids at synapses and in retinal photoreceptors is decreased in [the Alzheimer disease] brain. This deficiency may be due to enhanced free radical–mediated lipid peroxidation, decreased dietary intake, and/or impaired liver DHA shuttling to the brain. Decreased DHA serum content correlates with cognitive impairment. Moreover, epidemiologic studies suggest neuroprotective consequences of diets enriched in omega-3 fatty acids (1).”

Note the part, “impaired liver DHA shuttling to the brain.” I would assume, then, that an important way that DHA gets to the brain is by being produced by the liver (or eaten) and shuttled via the blood. So if vegans have low blood levels of DHA (as they do, without supplementation), that could mean they are not getting enough to the brain.

The second bit is less strong, but comes from the paper, Mortality in British Vegetarians, a 2002 report showing that vegetarians in the Oxford Vegetarian Study had twice the risk of dying from a mental or neurological disease as did non-vegetarians (see Disease Rates of Vegetarians and Vegans). A different report, from the Adventist Health Study, found the opposite: vegans and lacto-ovo vegetarians had half the risk of dementia (2).

I tend to think the culprit in these disparate findings is vitamin B12 (not DHA), as Seventh-day Adventists have traditionally known to supplement with vitamin B12 whereas other populations of vegans have neglected it. But I would not completely rule out DHA at this time.

My sense is that kids who are raised vegan are rarely supplemented with DHA and to our knowledge most of them develop normally. This would indicate that dietary DHA is not necessary for optimal health. But none of these children have made it to old age (that I am aware of) to know if the situation changes as they get older. It could be that people born without a source of DHA past infancy become highly efficient at converting ALA to DHA, an ability that might not be developed in people who become vegetarian as adults.

While I would love nothing more than to dispense with the entire DHA/omega-3 issue, I just don’t believe we can do that unless future research proves there is nothing to be concerned about.

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References

1. Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest. 2005 Oct;115(10):2774-83. | link

2. Giem P, Beeson WL, Fraser GE. The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study. Neuroepidemiology. 1993;12(1):28-36. | link

DHA Recommendations Updated (A Bit)

Wednesday, May 29th, 2013

A reader was questioning whether the amount of DHA I recommend is adequate. He sent me a list of studies on DHA supplementation in vegetarians, all of which I had previously read and were cited in my article, Omega-3 Fatty Acid Recommendations for Vegetarians. However, I had never actually taken the data from those studies to try to mathematically come up with an amount of DHA supplementation that would provide the same level of DHA in vegetarians as in omnivores. Instead, I had been taking more of an educated guess as to what might be a good supplementation level.

After doing the math, which you can see under the new section, DHA Supplementation in Vegetarians, it appears that supplementing with 300 mg per day will provide enough DHA to give your average vegetarian the same DHA levels as the average omnivore. A lot of vegans were included in that average, so I consider it a good approximation for both vegans and lacto-ovo vegetarians.

In the past I have recommended 200-300 mg every 2-3 days for vegetarians under 60, and 200-300 mg every day for vegetarians 60 and over. Due to the fact that we don’t really know if vegetarians need higher DHA levels, and given the expense of DHA supplements, I still consider this amount to be a viable option as a bit of insurance.

I have modified my recommendations to provide both of these options so that people will know what it might take to have DHA levels the same as your average omnivore, but also what might provide some insurance without necessarily having levels as high as omnivores. Here is a link to the recommendations which have 3 steps (DHA supplements being only one of them): link.

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Update on ALA & Eyesight

Wednesday, May 1st, 2013

A study came out earlier this year (thanks, Tom!) shedding some light on the issue of the short-chain omega-3 fatty acid, alpha-linolenic acid (ALA), and eye damage. Previous research from the Nurse’s Health Study had linked ALA intake to age-related macular degeneration (AMD) and cataracts. My suspicion is that this was due to confounding, but until more is known, I have been discouraging vegans from taking large amounts of ALA.

This new study from France (1) measured ALA levels in the blood, rather than from the diet, and found that higher blood levels of ALA were associated with a reduced risk of late-AMD.

This gives me quite a bit of confidence that the association of ALA with AMD in the Nurse’s Health Study was probably due to confounding. However, we are not out of the woods on yet on AMD and definitely not on cataracts. I hope we know more soon.

You can read more details in the section Eyesight of the VeganHealth.org article, Omega-3 Fatty Acid Recommendations for Vegetarians.

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Reference

1. Merle BM, Delyfer MN, Korobelnik JF, Rougier MB, Malet F, Féart C, Le Goff M, Peuchant E, Letenneur L, Dartigues JF, Colin J, Barberger-Gateau P, Delcourt C. High concentrations of plasma n3 fatty acids are associated with decreased risk for late age-related macular degeneration. J Nutr. 2013 Apr;143(4):505-11. | link

Evidence for Nutrition Recommendations: DHA & Prostate Cancer

Sunday, January 20th, 2013

A reader sent me a link to this study, DHA inhibits differentiation of prostate fibroblasts into myofibroblasts and tumorigenesis, and asked me if it changed my recommendations that vegans (under age 60) don’t need to supplement with DHA every day.

The study is in vitro and animal research, and indicates that DHA can prevent prostate cancer growth. I told him that it did not change my recommendations and he asked me to make a blog post to explain why.

Creating nutrition recommendations is not something that should be taken lightly. The United States government calls upon the National Academy of Sciences to make nutrition recommendations for the nation. This is done through the Institute of Medicine’s Food and Nutrition Board and the recommendations are referred to as the Dietary Reference Intakes (DRI).

All known essential nutrients are given a DRI. In most cases, these are based on a large body of research and arrived at by a panel of experts in the area. The research they have reviewed for most nutrients has been based on acute symptoms of deficiency and toxicity; they are rarely based on long-term, chronic disease prevention. This may be changing as more research becomes available and acute deficiencies are no longer the problem they once were.

So, with that background, a very good reason would be needed for me to overrule the Institute of Medicine and set my own “DRI.” But because the DRI are not set with vegans in mind, we have to fill in the gaps and most of my recommendations are to get vegans in compliance with the spirit of the DRI.

The study on DHA and prostate cancer, mentioned above, is only a test-tube and animal study. The results may or may not translate for humans, and even if they do, there is no way to know how much humans need to take to achieve such results or if there are negative side effects from taking whatever level of DHA we might determine is appropriate. The Food and Nutrition Board would not make recommendations based on one in vitro or animal study. There are many studies looking at DHA intake and levels in humans and associated diseases and these studies are fraught with confounding variables with no clear answer as to how much DHA humans should be taking on a regular basis to prevent overall chronic disease.

Some vegan RDs do not think it’s necessary to recommend DHA for vegans; I choose to do so, but err on the conservative side. The Food and Nutrition Board has not created a DRI for DHA, but given that studies have shown that vegans have much lower levels of DHA in the blood than your average person, I recommend DHA to make sure that we are not at a disadvantage compared to non-vegans. If you want to see the reasoning behind my DHA recommendations, you can read it in Omega-3 Fatty Acid Recommendations for Vegetarian.

For more information on the types of studies that provide more evidence for nutrition recommendations than others, please see my article Basics of Nutrition Research.

In conclusion, I try not to supersede the Food and Nutrition Board in formulating nutrition recommendations and I do not change recommendations based on in vitro or animal studies.

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Sad Story of Fish Oil and Small Sample Sizes

Thursday, January 17th, 2013

Interesting, short post by Kevin Drum about fish oil, sample size, and publication bias:

The Sad Story of Fish Oil and Small Sample Sizes

Excerpt:

“Small studies do a poor job of reliably estimating the effects of medical interventions. For a small study [snip] to get published, it needs to show a big effect — no one is interested in a small study that found nothing.”

And:

“It’s still possible that fish oil has a slight beneficial effect, but it’s unlikely.”

Even if fish oil does not reduce all-cause mortality, it does not change my recommendations regarding DHA supplementation in vegans because it’s one thing to say that supplementing with DHA to increase DHA blood levels above average does not improve health, and another to say that there are no problems with having much lower than average DHA levels.

Thanks, Matt.

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VeganHealth.org Update: ALA Not Associated with Prostate Cancer

Friday, December 7th, 2012

I’m a bit late in adding this info to the Prostate Cancer section of Omega-3 Fatty Acid Recommendations for Vegetarians.

There has been a question as to whether the short-chain omega-3 fatty acid, alpha-linolenic acid (ALA), might cause prostate cancer as a few early studies suggested. But from 2004 to 2010 there were three meta-analyses not finding this to be the case. The 2010 meta-analysis I just added to the site found that subjects who consumed more than 1.5 g/day of ALA had a significantly decreased risk of prostate cancer (0.95, 0.91-0.99) compared to those who ate less.

Reference

Carayol M, Grosclaude P, Delpierre C. Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis. Cancer Causes Control. 2010 Mar;21(3):347-55. Review. (Abstract)   |   Link

2002 Study of MPV in Vegans

Monday, October 22nd, 2012

A reader asked me about a 2002 study that showed vegans to have a higher mean platelet volume (MPV) than high and moderate meat-eaters and lacto-ovo vegetarians (1). I had not previously reviewed this study and decided to do so here.

The exact measurements were not given for the four diet groups, but the chart indicates that vegans had an average MPV of about 9 fl while the other groups had an MPV of about 8 fl. A normal MPV is between 7.2 and 11.7 fl (2).

MPV is a measure of the size of platelets and a high level can indicate a state of platelet activation or increased propensity for blood-clotting.

In the 2002 study, MPV was inversely correlated with the percentage of docosapentaenoic acid (DPA) and dihomo gamma linolenic acid (DGLA). DPA is an intermediary fatty acid that can be produced from EPA and that can be turned into EPA or DHA. DPA has not been studied like EPA and DHA because it is not as prevalent in fish oil and isolated supplements have not been readily available – it is not known if it has any unique functions.

The higher MPV of the vegans is likely due to a lower intake of omega-3 fatty acids and/or a higher intake of omega-6 fatty acids. The lower omega-3 fatty acid status of vegans who do not ensure a regular source of omega-3s is not news, and the vegans’ MPV levels were well within the normal range (a fact not pointed out in Li’s paper which was supported by Meat and Livestock Australia).

In other words, there is nothing really new or surprising here.

1. Li D, Turner A, Sinclair AJ. Relationship between platelet phospholipid FA and mean platelet volume in healthy men. Lipids. 2002 Sep;37(9):901-6. | link

2. Demirin H, Ozhan H, Ucgun T, Celer A, Bulur S, Cil H, Gunes C, Yildirim HA. Normal range of mean platelet volume in healthy subjects: Insight from a large epidemiologic study. Thromb Res. 2011 Oct;128(4):358-60. Epub 2011 May 28. | link

Omega-6s: Not So Bad?

Friday, July 13th, 2012

For background on the discussion below, please see Omega-3s in Vegetarian Diets.

The July 2012 issue of the Academy of Nutrition and Dietetics (AND) contained a meta-analysis of studies examining the intake of the omega-6 polyunsaturated fat, linoleic acid (LA), and whether it increases markers of inflammation (1). The AND recommends that people get 3-10% of calories as omega-6s, most of which will be in the form of LA. There is concern that large amounts of LA will be converted to arachidonic acid (AA) and will also prevent the conversion of alpha-linolenic acid (ALA) into EPA and DHA, both of which could increase inflammation.

The meta-analysis found no evidence that intakes of LA up to 10% of calories increased markers of inflammation. Adding LA to the diet did reduce levels of EPA in the blood, but this did not increase inflammation. Adding LA to the diet did not decrease the amount of DHA in the blood, but this is probably due to the fact that so little ALA is effectively converted all the way to DHA in the first place.

In a study from 1992 (2), vegans ate 9-10% of their calories as LA and, of course, had no natural dietary source of DHA. Whether large amounts of LA harm the DHA status of vegans has yet to be determined, but this meta-analysis indicates that reducing LA, a recommendation vegan health professionals have long suggested as a way to reduce inflammation and increase the conversion of ALA to DHA, might not be effective. It also provides more evidence that a DHA supplement might be the only reliable way for vegans to increase DHA levels, since reducing (or, actually, “not increasing”) LA intake does not appear to matter.

I have not changed my recommendations to limit LA based on this meta-analysis alone, but I’m leaning in that direction. Hopefully, there will be more research to come.

References

1. Johnson GH, Fritsche K. Effect of Dietary Linoleic Acid on Markers of Inflammation in Healthy Persons: A Systematic Review of Randomized Controlled Trials. Journal of the Academy of Nutrition and Dietetics. 2012 Jul;112(7):1029-41. | link

2. Sanders TA, Roshanai F. Platelet phospholipid fatty acid composition and function in vegans compared with age- and sex-matched omnivore controls. Eur J Clin Nutr. 1992 Nov;46(11):823-31. | link