Homocysteine and Folic Acid Supplementation: Another Medical “About Face”

On March 15, 2015 JAMA published on line the results of a superbly designed and potentially practice changing trial. The China Stroke Primary Prevention Trial (CSPPT), tested whether or not the addition of folic acid to anti-hypertension medication could reduce the occurrence of a first stroke. As three quarters of all strokes are “first strokes” and as strokes are a leading cause of death and disability worldwide, the question posed by this trial had far reaching implications. The trial met its endpoint so quickly and incontrovertibly that for ethical reasons it was prematurely terminated. Folic acid can reduce the risk of stroke. Those of us who have open-mindedly interpreted prior studies expected this finding; many others found the results to be shocking.

Important homocysteine related trials like HOPE 2 and others had already demonstrated either statistically significant reductions in stroke with folic acid supplementation or at least signals toward such an outcome. Yet many of the most “vocal” researchers, physicians, and reporters proclaimed that since heart attacks were not reduced with folic acid, “the homocysteine hypothesis was dead.” This perspective always bothered me. We had observational and even interventional trial data supporting the use of folic acid in certain settings. And stroke, the disorder we could impact with a simple vitamin, is horrific. Strokes are terrifying, disabling, and deadly. They are also extraordinarily common. So why would these doctors, scientists, and media members snub data supporting a simple and safe vitamin treatment to potentially reduce such events? It would be helpful to know the reason, as the same phenomenon is currently occurring in relation to omega-3 fish oils.

Plenty of data support fish oil supplementation yet a few trials do not. And as with homocysteine, it seems that the media and many scientists/doctors have chosen to focus their attention on the limited neutral – and oftentimes overtly flawed – data rather than supportive experimental, biologic, physiologic, clinical trial, and common sense evidence. Interestingly, one of the vital lessons gleaned from CSPPT is that those individuals with either specific genetic mutations or very low levels of folic acid received the greatest benefit (reduction of stroke) from taking folic acid. In parallel fashion, one of the key trial limitations of fish oil studies has been the persistent failure to measure blood levels of the omega-3 fatty acids DHA and EPA. It certainly stands to reason that those with lower levels of these critical fats will also gain the greatest advantage from their supplementation. So why not simply measure them? Well, in clinical practice, some of us do. And some of us even advise correcting abnormally low levels with simple and safe fish and fish oil pill consumption.

I am at once elated and disturbed by the CSPPT findings. They prove the efficacy of a simple therapy; yet, they broadcast the hubris of many in my field. Time and again we have had to make an about face in our opinions and recommendations. I see nothing inherently wrong in changing our position as more data emerge. What I struggle with is the egg on our face, the about face that occurs far too late, long after adequate data have told us what to do. Perhaps we will learn though. Maybe as more trials like CSPPT emerge, as more scientists and doctors with the conviction and devotion to finding a greater truth push tirelessly along their paths we will finally learn to be more open minded and accepting of ideas and findings even when they go against our grain.

For more information about the supplements and vitamins critical to your everyday health visit www.vitalremedymd.com.

Learn more about preventive cardiology at www.preventivecardiologyinc.com.

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Hot Off the Press

In medical school we learned about a life threatening form of polydipsia. A subset of patients with schizophrenia consume so much water their sodium can fall to levels unable to sustain life. Twenty liters per day often leads to not just severe illness, but death. How could this be? Water is life’s elixir, and therefore more must be better; correct? Well, simply put, the answer is no. Our kidneys can only handle a water intake of less than one liter per hour. When people exceed this limit, blood becomes diluted; sodium levels fall; and cells swell. As our brain is encased in bone, it has nowhere to go when it swells. Consequently swollen brain cells can lead to permanent damage and even death. It’s not just the unfortunate schizophrenic patients who succumb to such a fate; others do as well. One woman died after drinking six liters in just three hours during a “water drinking competition.” Others have died similarly during college hazing. The point is that a rapid, excessive and unnatural intake of our most vital ingredient for life can kill us in a matter of hours. More is definitely not always better. Aristotle was correct in his dictum of moderation. So where am I going with this you might ask. Let’s consider the most recent “negative” fish oil study by Dr. Voest that was published in a most reputable journal. (For my take on other similar articles please see prior blog posts).

Based upon the fact that some cancer cells can produce long chain fatty acids, Dr. Voest hypothesized that the omega-3 fatty acids in fish could blunt the effect of chemotherapy (such a thought process itself lacks strong scientific validity). Testing his hypothesis he administered 100 microliters of fish oil to 20 gm mice. He was right; fish oil did blunt the effects of chemotherapy. And so his findings were published in the prestigious JAMA Oncology. But let’s look at his study in proper perspective. Ignore the fact that mice are not the optimal animals to study here. Also, ignore the fact that tumor cells produce many substances that have nothing to do with their “desire” to counteract chemotherapy.  Simply examine the administered dose. One hundred microliters of fish oil for a 20 gm mouse is equivalent to 400 ml of fish oil for an 80 kg (175 pound) man. Can you imagine guzzling nearly a half-liter of fish oil? The very thought is life threatening! That’s also tantamount to swallowing around 400 fish oil capsules. Who in his right mind would do that? I’d guess no one. The study therefore has no clinical relevance. The author’s conclusion that patients should avoid fish the day prior to receiving chemotherapy has no basis in science. Yet, the study is on the news; patients are concerned that fish causes cancer; doctors who don’t fully understand this area of medicine will become as alarmed as the patients; doctors’ offices will once again be flooded with unnecessary and distracting queries born of inappropriate trial conclusions; and some people who desperately need to consume fish will place themselves in harm’s way by eschewing vital nutrients. The fallout is, and will continue to be, monumental.

Why such studies are done, and why they are published in top-notch journals eludes me. I understand why the media exploits them; they are fodder for ratings. Still, I will continue to proclaim that such studies must be quelled, and the media must become more cautious. It is fine to conjecture, study, and test hypotheses no matter how outlandish they may seem. What is not acceptable however is perpetuating false conclusions as though they are hardened facts. Such a practice – which is prevalent today – leads both doctors and patients astray and pulls us from important issues, those that can truly save lives and help humanity. Let’s get back on track and re-emphasize honesty in medicine as our prime agenda. Honesty should always trump a good story.

For more information about the supplements and vitamins critical to your everyday health visit www.vitalremedymd.com.

Learn more about preventive cardiology at www.preventivecardiologyinc.com.

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