Fish oil doesn't seem to help treat Alzheimer's Disease.

A recent study from Oregon Health and Sciences University casts doubt on whether fish oil may help patients with Alzheimer’s Disease. For 18 months, patients with the illness where given either 2 grams a day of docosahexaenoic acid (DHA, an omega-3 fatty acid found in fish oil) or a placebo. Those who received the DHA did no better in cognitive tests than the placebo group, and MRI scans showed no improvement in brain atrophy either. These results were recently published in the Journal of the American Medical Association. While Joseph Quinn, leader of the study, admits in the paper to JAMA that there are limitations to the conclusions that can be drawn from his experiment, his work seriously challenges those who hoped that fish oil could have a restorative effect on those with Alzheimer’s. Sadly, it looks like fish oil has failed us…again.

Fish oil, which contains omega-3 fatty acids which seem key to mental and physical health, has long been thought to have some potential to combat degenerative mental diseases. Alzheimer’s Disease forms amyloid plaque on the brain, and tests with transgenic mice who have Alzheimer’s have shown that fatty acid supplements can have a preventative and even curative effect for those with plaque buildup. At the same time we know that most humans don’t get as much fatty acid as used in experimental conditions, so it seemed natural to believe that relatively strong doses of DHA could have as yet unseen positive effects on people with the disease. This recent failure with human models is disappointing as it suggests that humans don’t seem to be affected in the same way as the mice, and that there may be little benefit (to Alzheimer’s patients) of upping their DHA intake.

But wait, you say, is this experiment really so cut and dry? Didn’t Quinn admit that his test isn’t a death knell for fish oil, just a mark against it? Good points, my vocal and imaginary reader. Indeed, the study at Oregon HSU had its limitations. First was its brevity – 18 months is a decent length of time for a nutritional/drug study but perhaps DHA takes longer to reduce plaque buildup on the brain and improve cognition scores. Likewise, this test can only really deny that DHA may work as a curative agent for Alzheimer’s. Prevention is still up in the air. The average age for the patients was 76 – maybe we need to focus on younger people who are at high risk for Alzheimer’s. Perhaps DHA is only going to delay the onset and severity of the disease.

Critics have also pointed to the exclusion of eicosapentaenoic acid (EPA) from the study. EPA is the other important omega-3 typically found in fish oil besides DHA. Can we really call this study a fail for fish oil if only half the fishy components were used? Quinn says yes. In the opening remarks of the JAMA paper, EPA is discussed and dismissed. In repeated tests using fish oil, it was found that only DHA, not EPA, makes it to the brain in appreciable quantities. It seems reasonable then to focus on DHA for fish oil studies looking to explore brain health and disease.

In the end this recent work at Oregon should only encourage us to explore the possibilities with fish oil further. The study only really addressed a single question: will patients in their mid to late 70s with Alzheimer’s see fairly quick benefits from taking fish oil supplements? The answer there seems to be a regrettable no. However, there are still many other related questions to answer if we want to understand how DHA can affect amyloid plaque buildup and Alzheimer’s Disease.

We also need to learn more about fish oil and health supplements in general. Quinn and his team studied 400 patients from 51 different testing sites across the US (only 295 completed the 18 months). The upcoming VITAL study we’ve discussed in the past will look at 20,000 patients taking fish oil and vitamin D and will have $20 million in funding. Chances are that VITAL will be able to tell us much more about the general effects of these supplements (though it won’t address Alzheimer’s). DHA may have failed this round, but there are many more to go. Good luck fish oil fans…it looks like you’re going to need it.

[image credit: Aaron Saenz/Singularity Hub]
[source: Quinn et al 2010 JAMA]

The debate on fish oil supplements rages on.

A new study by Dutch scientists found that low doses of omega-3 fatty acids provided little to no help preventing future heart attacks in patients with a history of heart disease. As published in the New England Journal of Medicine, researchers followed 4837 patients for 40 months and gave each supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), as found in fish oil, and/or alpha-linolenic acid (ALA), as found in certain nuts and vegetables. All patients had previously had a myocardial infarction (heart attack). By examining which patients had (another) MI during the 40 months of observation, the researchers determined that these fatty acids weren’t helping. Does this spell the end for fish oil supplements? Hardly. The Dutch work is important, but still leaves many questions unanswered.

This research comes in contrast with previous experiments which showed that fatty acids could significantly reduce the risks of heart attacks when taken regularly as a supplement. The nearly 5000 patients in the Dutch study received the Omega-3s in amounts comparable to previous tests (400mg for DHA/EHA or 2g for ALA per day – disguised in identical tasting sticks of margarine). But when comparing the recipients of supplements to those of placebo, the fatty acids didn’t seem to provide protection against MI. Of the 4800+ patients, 671 had a heart attack during the trial. The Dutch scientists, led by Daan Kromhout of Wageningen University, gave several reasons in their paper for why the discrepancy may have arisen.

The first idea is that the Dutch patients were mostly old men. Average age was 69 (range of 60 to 80) and 78% were male. Other tests for fatty acid supplements covered different ranges of age, and many focused on women. In fact, the Dutch researchers did find some indication that the women in the study benefited slightly from receiving ALA.

Another possible culprit (perhaps the most likely) is that all patients were receiving top of the line medical care. As all previously had experienced MI, they were being dosed with start of the art medications to prevent further heart attacks. 85% of the patients were taking statins. Kromhout and his colleagues suggest that this medical care may have had a profound enough life-saving effect that the bonuses from fatty acid supplements were negligible. If so, the experiment would not have been particularly insightful into the effects of omega-3s, but it would be a good sign that modern medicine really helps with MI.

The final major possibility is that the Dutch patients were outside the time in which fatty acids may have helped with heart disease. Patients had experienced their heart attacks an average of 4 years before the study began. Other trials for fatty acids had begun treating patients with supplements much closer to the original MI. There may be some optimal time after (or before) MI for taking fatty acids as a supplement.

I encourage you to read the NEJM article on this study – as far as medical publications go it’s pretty accessible. But I don’t think we can draw any definitive conclusions from this work. Yes, 4837 patients over 40 months is a good data set, but the study had its limitations as the authors discussed. As we mentioned earlier, a much larger study (20,000 patients) is forthcoming from the US National Institute of Health which should shed much needed light on the effects of fish oil and vitamin D. That study, however, will have its own limitations in terms of patient selection, just like the Dutch research. The truth is that while each study provides new data, we’re likely to need years of more trials before we can write the definitive word on fish oil. Hopefully, however, we’ll eventually collect enough information that we can reasonably understand if and when fatty acids will help protect your heart. When that happens we’ll have another tool in our kit for keeping us healthier and happier longer.

[image via thinkorthwim.com]
[source: Kromhout et al, NEJM 2010]

Adequate levels of vitamin D may make the elderly three times less likely to die of heart disease.

In case you were wondering about whether or not to take that walk outside today, a new study has shown that vitamin D is linked to lower death rates among the elderly. The University of Colorado Denver, and Massachusetts General Hospital (MGH) recently published findings that patients over 65 with low levels of vitamin D are three times more likely to die of heart disease than their peers with adequate amounts. The same group was two and half times more likely to die no matter the cause. Holy crap! This research makes it sound like not taking vitamin D supplements is a guaranteed death sentence.

The study was quite appropriately published in the Journal of the American Geriatric Society, but it could have wider implications outside of geriatrics. Vitamin D’s ability to prevent heart disease and stroke could be useful for those in middle age or younger. UC Denver and MGH also completed an earlier study (in the Archives of Internal Medicine) that demonstrate how vitamin D could boost the immune system against colds and flu. The National Institute for Health is currently ramping up VITAL, a five year study to determine the effects of long term use of supplements of vitamin D and fish oil. VITAL is going to be huge.

Not that this trial was particularly small. UC Denver and MGH studied the data from the Third National Health and Nutrition Examination Survey conducted by the National Center for Health Statistics and the Center for Disease Control. In that survey, 3,400 volunteers over 65 years of age were selected to represent a cross section of America’s 24 million older adults. They were followed, on average, for more than seven years.

While the study highlights the connection between vitamin D and mortality, this doesn’t mean there’s necessarily a causal relation. As stated in the MGH press release, it is likely that one third of all older adults in the US have low levels of vitamin D, probably due to limited outdoor sun exposure. How do you get sun exposure? By being active. So connections between vitamin D and mortality may simply be demonstrating that active old people live longer. Or it could be that vitamin D supplements are the fountain of youth. We don’t know, and very wisely the authors of the study are calling for larger randomized trials.

Which is probably where VITAL is going to fit in. We have plenty of inconclusive proof that vitamin D (and fish oil) are linked to longer, healthier living. Inconclusive only because causal relationships can’t be determined in many of the studies. What we need now is a greater understanding of whether vitamin D and fish oil supplements can really help us, or if the behavior that naturally raises levels of these substances is the real cure-all. VITAL will help with that understanding, but in the following five years you and I can run our own experiment. Let’s enjoy more outdoor activities, eat a diet with more lean proteins from small fish and see where that gets us. Maybe we’ll create new Blue Zones.

Do I need to catch more sun and vitamin D?

The western world faces three very notorious killers: heart disease, cancer, and stroke. Just this week Michael Jackson (heart attack??) and Farah Fawcett (cancer) were struck down, and the media is waiting on baited breath for another celebrity to die and fulfill the “rule of threes.” Stroke, we’re looking at you. But what if it didn’t have to be this way? What if there were just a few simple things you could eat or take that would protect you from all three killers?

That’s what the U.S. government is going to find out. The National Institute for Health (NIH) is funding a $20 million dollar study with 20,000 test subjects to explore how vitamin D and fish oil affect health. The Vitamin D and Omega-3 Trial (or VITAL) will be a five year study and will be one of the first to specifically target African Americans as test subjects. With darker skin producing less vitamin D in the body from sun exposure, scientists theorize there may be a link between a vitamin D deficiency and higher rates of stroke, heart disease, and cancer in the Af.Am. community.

Vitamin D and Fish Oil. Not quite the names for a buddy cop movie, but for the last decade, they’ve each been toted as the way to combat the killer diseases of our time. Vitamin D has been inconclusively linked to heart health and cancer prevention, not to mention bone strength. Fish Oil, with high levels of vitamin D and omega-3 fatty acids is supposed to good for everything from good skin to memory loss. When it comes to preventing stroke, heart attack, or cancer, these two guys seem like the ideal dietary supplements to take.

And in five years, we’ll hopefully know for certain. In the meantime, Dr. JoAnn Manson and Dr. Julie Buring, the heads of VITAL are gearing up for the trials. Starting in January of next year, they will recruit men over the age of 65 and women over 60 to take daily supplements and report on their health. These supplements will be either placebos, vitamin D, or fish oil. While the studies will be centered at Harvard Medical School and the Brigham and Women’s Hospital in Boston, the subjects will cover the entire U.S. With a relatively huge sampling (20,000 subjects) and double blind methodology, VITAL hopes to once and for all settle the long term benefits, or risks, of vitamin D and omega-3 fatty acids.

If the tests can conclusively prove the health benefits for these supplements they’ll be a fixture in the diets of all those seeking longevity or immortality, such as Singularity Hub regular Ray Kurzweil. Even if vitamin D and fish-oil aren’t shown to be miracle drugs the VITAL study could still reveal important facts about our health. Terrifying or wonderful surprises come standard with studies this large. For instance, who could have predicted that chemotherapy would help with wrinkles? In five years, we may all be rushing outside to soak up more sun or eating more sushi to prevent cancer. Personally, I’ll be waiting for the day you can get vitamin D from the glow of your computer screen.