Fish oil cut heart attacks by 28% and reduced cancer death rate in huge trial; vitamin D cut cancer deaths 11/15/2018
Once again, many major media outlets misreported the outcomes of a clinical trial.
Some accentuated the negative findings — and downplayed the very positive results — of a clinical trial published earlier this week.
We attribute the misleading headlines to three things: reporters often lack time, many aren’t equipped to evaluate clinical studies, and negative headlines draw more online “eyeballs”, clicks, and ad revenue.
Sadly — despite the major positive findings of this unusually large, lengthy clinical trial — many headlines declared or implied that it had found omega-3s of little value for guarding heart health.
A few outlets ran more accurate headlines, such as this from CBS News, “Eating more fish or taking omega-3 fish oil supplements can cut heart attack risk, studies find”, and this headline from the Washington Post: "Fish-oil drugs protect heart health, two studies say".
But this was the misleading headline on National Public Radio’s report: “Vitamin D and Fish Oil Supplements Mostly Disappoint in Long-Awaited Research Results”.
And the Independent UK ran with this egregiously erroneous headline: “Omega-3 Fish oil supplements do nothing to prevent heart attacks or stroke, major study finds”.
In fact, the clinical trial’s positive findings contradict the negative headlines.
Omega-3 fish oil produced dramatic heart-risk reductions among people who reported eating little or no fish, and among all African-Americans.
And those findings fit with the highly positive outcomes of the recent REDUCE-IT trial — see Omega-3s’ Heart Value Vindicated in Long, Large Clinical Trial.
The negative media stories focused on the fact that fish oil supplements didn’t reduce heart risks much among the participants who were already eating significant amounts of fish — a description that fits only a minority of people in America and the world.
Large, lengthy VITAL trial further vindicates omega-3s
The newly published results come from the VITamin D and OmegA-3 TriaL (VITAL).
This unusually large, long-term clinical trial comes from Brigham and Women’s Hospital, an affiliate of Harvard Medical School (Manson JE et al. 2018).
The study was designed and led by Professor JoAnn Manson, M.D., Dr.PH and epidemiologist Julie Buring, Sc.D., and its results have been long-awaited.
Their study was the largest, longest randomized clinical trial to test the ability of daily, high-dose vitamin D3 and omega-3 fish oil to prevent cancer and cardiovascular disease.
As they wrote, “VITAL is one of only two large (10,000 participants or more) randomized clinical trials of vitamin D for the prevention of cancer, heart disease, and stroke — and the only such trial in a racially and ethnically diverse study population — in the world.”
And they described another feature that makes it unusual among clinical trials testing the effects of omega-three fish oil: “It is also the only large trial of fish oil supplements in a generally healthy population.”
That feature matters because many prior clinical trials focused on heart patients who were already taking statins or other heart drugs — factors that rendered their results unreliable as guides to the general cardiovascular benefits of omega-3s.
Five-Year VITAL trial finds meaningful reductions in heart attack risk
The results of this trial provide considerable confirmation of the heart-health value of relatively high doses of omega-3s.
The trial included 25,871 generally healthy adults — 12,786 men aged 50 years and older and 13,085 women aged 55 and older.
The participants randomly assigned to take 1000 mg of fish oil were given capsules of Omacor® (Lovaza®): a prescription-only supplement containing 840mg of omega-3s (465mg EPA plus 375mg DHA).
The omega-3 dose deliberately matched the dose recommended by the American Heart Association, which was clinically proven to help prevent a second heart attack in the landmark GISSI-Prevenzione clinical trial. The placebo capsule contained refined (not virgin) olive oil.
The participants included roughly equal amounts of men and women and more than 5,000 African Americans. All the volunteers were free of cancer or heart disease at the outset and agreed to forgo use of fish oil supplements, starting three months before the beginning of the trial.
Participants assigned to take omega-3 fish oil showed these benefits over the course of the five-year trial:
• 28% less likely to suffer a heart attack
• 50% less likely to suffer a fatal heart attack
• 22% less likely to undergo an angioplasty procedure
The participants who reported “low fish consumption” — less than 1½ servings of 3-4 ounces each per week — were 19% less likely to suffer a major cardiovascular event and 40% less likely to suffer a heart attack.
And the fish-avoiders also showed what the researchers characterized as “a trend toward a reduction in death from any cause”.
In contrast, the participants who reported eating at least 1½ servings of fish per week showed no reduction in the risk of adverse cardiovascular events, including heart attacks, or in the risk of death from any cause.
As lead author JoAnn Manson, M.D., said in a press release, “The results indicate that people with low dietary intake of fish will likely obtain a heart benefit from omega-3 fatty acid supplementation. On the other hand, those with higher fish consumption do not appear to benefit, perhaps because they are already meeting their omega-3 requirements by eating fish.”
Rush to judgment?
The very positive effects seen among fish-avoiders confirms long-held suspicions that supplemental fish oil can produce the fish-related cardiovascular benefits seen in most epidemiological studies.
Unfortunately, Dr. Manson’s comment about the relative uselessness of omega-3s for fish-eaters failed to acknowledge the relatively brief duration of the five-year trial, in comparison to average life span in the United States.
In other words, although this trial was longer than most, the full benefits of adding omega-3 fish oil to a diet that already includes a significant amount of fish might not manifest within five years.
Those benefits likely include the brain and immune health improvements seen in many studies.
And the trial did not account for the effects of omega-6 fat intakes, despite substantial evidence that the very high intakes of omega-6 fats typical of the American diet neutralize some of the health benefits of omega-3 intake.
African-Americans benefited most
The most consistent cardiovascular benefits of supplemental omega-3 fatty acids occurred among African-Americans.
In a startling finding, African-Americans in the omega-3 fish oil group were 77% less likely to experience heart attacks, regardless of how much fish they reported eating routinely.
African-Americans taking fish oil were also 51% less likely to undergo a coronary revascularization and 47% less likely to develop coronary heart disease.
It’s not clear why African-Americans enjoyed greater benefits from omega-3 fish oil, but a 2014 study from the University of California (Davis and Southern California) provides a possible clue.
The results of that study linked a staple of traditional African-American diets — leafy greens like collards and mustard greens — to enhanced absorption of omega-3 fats from fish oil (O'Sullivan A et al. 2014).
On average, the study participants who showed enhanced omega-3 absorption ate 1/3 cup of dark, leafy greens daily.
It’s possible that the presence of the plant-form omega-3 (ALA) in leafy greens somehow facilitates absorption of the far more valuable omega-3s (DHA and EPA) found in fish oil and seafood.
Dark, leafy greens rank among the few sources of ALA, albeit much less than in flaxseed, chia seed, hemp seed, or walnuts.
What explains the negative headlines?
Certainly, sloppiness and/or the desire to run click-inducing headlines explain the misleading nature of some media reports.
But much of the negative coverage likely stems from the fact that the trial found no significant overall reduction in “major cardiovascular disease events” (e.g., stroke, heart attacks, angina, and sudden cardiac death).
However, those averages mask the big differences seen between people who reported that they ate fish routinely and those who said they didn’t.
So, a media report's choice to focus on the lack of heart-risk-benefit among habitual fish-eaters ignores the dramatic heart-risk reductions seen among the participants who reported eating little or no fish.
No effect seen on cancer risk or overall death rates
Omega-3 fish oil did not reduce the risk of breast, prostate, or colorectal cancers, cancer-related deaths, or deaths from any cause.
Oddly, subsequent analyses that excluded the first two years of the trial linked omega-3 fish oil to “a suggestive increase in cancer risk” in the fish oil group.
Given the huge amount of evidence suggesting that diets rich in omega-3s discourage cancer development and growth, this was probably a meaningless statistical artifact.
Vitamin D reduced cancer deaths but had no impact on heart risks
The VITAL trial also tested the effects of supplemental vitamin D3, with mixed results.
As the trial authors said in a press release, “The findings indicate that high-dose vitamin D does not lower the risk of developing cancer or cardiovascular disease in generally healthy men and women, although it appears to lower the risk of cancer death.
Official U.S. guidelines advise adults to consume 600 IU of vitamin D daily and advise those aged 71 and older to consume 800 IU daily.
The participants assigned to take vitamin D received capsules containing 2000 IUs of the D3 form, which is the best-absorbed and most efficacious form.
Fatty fish — especially wild salmon, sardines, and albacore tuna — are the only good food sources of vitamin D3. The less-effective D2 form is found in plant foods (mostly mushrooms) and most D-fortified foods, such as milk.
Modest reduction in cancer deaths; most benefit seen among African-Americans
The participants assigned to take vitamin D3 did not show lower rates of breast, prostate, or colorectal cancers.
However, the participants assigned to take vitamin D were 17% less likely to die from cancer during the five-year trial.
And that benefit grew to a 25% reduction when the authors conducted analyses that excluded the first two years of follow-up.
As the authors noted, excluding cancer-related data from the first year or two of a dietary supplement trial is a common practice, because cancer is a slow-developing disease and the effects of nutritional factors can take several years to manifest.
And, as in the omega-3 part of the trial, African-Americans showed more benefit from vitamin D, versus other participants, being 23% less likely to develop cancer over the course of the trial.
No effect on death or cardiovascular disease risk
The trial participants assigned to take vitamin D3 showed a small but non-significant reduction in the risk for major cardiovascular events (heart attack, stroke, or death from cardiovascular causes).
However, supplemental vitamin D did not significantly reduce the risk of heart attack, stroke, or cardiovascular death, nor did it reduce the risk of death from any cause.
There were few side effects of high-dose vitamin D, nor were there any significant increases in the risk of hypercalcemia (high blood calcium level), kidney stones, or gastrointestinal symptoms.
- GISSI-Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Lancet. 1999;354:447-455
- Keaney JF Jr, Rosen CJ. VITAL Signs for Dietary Supplementation to Prevent Cancer and Heart Disease. N Engl J Med 2018;Nov 10:[Epub ahead of print].
- Manson JE, Cook NR, Lee IM, et al., on behalf of the VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med 2018;Nov 10:[Epub ahead of print].
- Manson JE, Cook NR, Lee IM, et al., on behalf of the VITAL Research Group. Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med 2018;Nov 10:[Epub ahead of print].
- O'Sullivan A, Armstrong P, Schuster GU, Pedersen TL, Allayee H, Stephensen CB, Newman JW. Habitual diets rich in dark-green vegetables are associated with an increased response to ω-3 fatty acid supplementation in Americans of African ancestry. J Nutr. 2014 Feb;144(2):123-31. doi: 10.3945/jn.113.181875. Epub 2013 Nov 20.