Vitamin supplements — do they help prevent cardiovascular disease?

One of the most respected cardiology journals in the world is the Journal of the American College of Cardiology. In a very recent addition of this journal (JACC, Vol 71, Issue 22) there was an article entitled, “Supplemental Vitamins and Minerals for CVD Prevention and Treatment”.

The researchers reviewed just under 1500 different papers on the subject and published analyses of 179 randomised controlled clinical trials after excluding studies they felt were not adequate to provide the requisite information.

The three key conclusions of this trial were as follows.

1) There was moderate to low quality evidence for the use of folic acid in preventing cardiovascular disease. There was also moderate to low quality evidence for folic acid and B group vitamins to help prevent stroke

2) There was no effect in regard to cardiovascular prevention for Multivitamins, Vitamin C, Vitamin D, Beta-carotene, Calcium and Selenium

3) There was an increased risk for antioxidants and in particular niacin, in studies that also used statin drugs, to increase all cause death.

So, that’s the end of the story. These conclusions are definitive and should be taken as gospel. Firstly, I need to make the point that I do have my own supplement company developing high quality pharmaceutical grade supplements targeting Asia and the Middle East. But, none of the supplements mentioned in this article are in my range and therefore I’m arguing without bias and no conflict of interest. Secondly, I must comment that this is a well-designed, scientifically validated analysis that needs to be read objectively but also, as with all science, questioned for its relevance.

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Before I give my full analysis, I am reminded of the parable of the three blind men asked to describe an elephant. To explain this parable fully, I went to a source many of us use but often not honest enough to admit i.e. Wikipedia.

Wikipedia describes the parable thusly:

“The parable of the blind men and an elephant originated in the ancient Indian subcontinent, from where it has been widely diffused. It is a story of a group of blind men, who have never come across an elephant before and who learn and conceptualize what the elephant is like by touching it. Each blind man feels a different part of the elephant body, but only one part, such as the side or the tusk. They then describe the elephant based on their partial experience and their descriptions are in complete disagreement on what an elephant is. In some versions, they come to suspect that the other person is dishonest and they come to blows. The moral of the parable is that humans have a tendency to project their partial experiences as the whole truth, ignore other people’s partial experiences, and one should consider that one may be partially right and may have partial information.”

I believe both this parable and this report from Journal of the American College of Cardiology highlight the bigger issue of the orthodox, conservative medical profession and scientific world wanting to prove beyond a doubt that complementary medicine has no value, especially when compared against our stronger, evidence-based orthodox medical treatment strategies.

There is no doubt that strong medicine has strong effects but unfortunately also has strong side-effects. As an example, every year in the United States alone, there are over 100,000 deaths from the appropriate prescription of pharmaceutical medications. All modern drugs are tested in rigid, well conducted, randomised controlled clinical trials to prove their efficacy and also their safety. But, here’s the problem — because these trials are enormously expensive and involve typically thousands of participants, their length of time is usually less than five years.

Many pharmaceutical drugs cause minimal harm over the short-term i.e. less than five years but once taken for 10 years or longer, start to cause problems. We have seen this with the withdrawal of drugs such as Vioxx which was removed from the market in 2004 after it was shown to increase the rate of heart attacks with long-term ingestion; the increasing long-term side-effects from the PPI drugs to treat indigestion and the ever present concern over the excessive prescription of statin therapy to lower cholesterol, purely to give a few examples.

Now, here is the relevance to this particular report. 179 randomised clinical trials involving supplements were analysed. There was no mention in the article of the average length of time of these trials but as they were randomised controlled clinical studies I am assuming they were mainly less than five years, because of all the reasons I mentioned above. So, a key and vital point here is that supplements should not be regarded using the same methods as pharmaceutical drugs.

I often make the analogy between the high-performance motorcar and a bicycle. The high-performance motorcar gets you from A to B very quickly but with the potential for crashing and causing significant harm. Thus the need for strict road rules, seat belts and very well designed safety mechanisms within the car to minimise harm. This is why randomised controlled trials are necessary for pharmaceutical drugs which are like the high-performance motorcar i.e. very effective but also with a small, but significant element of harm.

With a bicycle, you will get from A to B much slower but with much less harm and much less need for rigid rules and safety mechanisms apart from a helmet. Unless, of course, you start to mix bicycles with high-performance motorcars and unsurprisingly it is the cars that do the damage, not the bicycle. Vitamin supplements can be compared to the bicycle when you don’t take the “blind men and the elephant” approach but rather look at the totality of studies performed over many years.

I often quote one of the longest epidemiological studies, with the largest numbers, i.e. The Nurses Health study and the Male Physicians trial from Harvard University. When examining the multivitamin component of these studies, there was no benefit whatsoever from taking a multivitamin on a daily basis up until 10 years. But, when you examined the data from 10 years and beyond, the significant benefits with taking a multivitamin and on a daily basis starts to accrue.

For example, the 20 year data from the Male Physicians trial showed that those doctors who persisted with taking a multivitamin on a daily basis for 20 years demonstrated a 44% reduction in cardiovascular disease compared with those doctors who didn’t. These data were not included in the recent analysis in the Journal of the American College of Cardiology.

Now to examine each of the conclusions of this study with the short time course kept in mind for these 179 randomised controlled trials.

1) Folic acid and B group vitamins do not have reasonable evidence for the prevention of cardiovascular disease and stroke. Again, these were all short-term trials but still some showed a significant benefit for the supplements. The suggested mechanism is through effects on the MTHFR gene and again the researchers showed little knowledge in this area because many people across the world have mutations in this gene where standard folic acid alone has no effect and specific variants of folic acid need to be used. In the trials mentioned, standard folic acid was the only vitamin used, along with some other B group vitamins and there has (to date) never been a large scale trial of targeting MTHFR gene abnormalities using specific forms of folic acid, regardless of the longer time frame necessary to show a significant effect, again not even considered in this trial.

2) Multivitamins, vitamin C, vitamin D, beta-carotene, calcium and selenium had no effect. Again, the short time frame is not long enough to show any benefits. But for example, many studies looking at a variety of vitamins use the lower quality synthetic vitamins such as dl-alpha-tocopherol which is synthetic vitamin E (which has already been proven to be ineffective and potentially harmful in a number of trials). It is my view that vitamin E does not work without vitamin C and it must be the natural version of vitamin E (d-alpha tocopherol) to be effective. There have only been two trials in the history of evidence based medicine combining natural vitamin E with vitamin C and both of these trials demonstrated a 25% reduction in the progression of atherosclerosis using carotid ultrasound which is a surrogate marker for cardiovascular disease risk. One trial only went for 12 months, the other six years but again the number of people in the trial and the length of time, in my view, is too short to demonstrate reduction in cardiovascular events.

For some bizarre reason, the researchers performed the analysis with and without the selenium data, claiming that selenium did appear to have somewhat of an effect. This appears to be cherry picking the data purely to suit your argument.

Also, the most striking trends towards harm came from the use of oral calcium supplements for which a recent meta-analysis showed no benefits for the reduction of osteoporosis or bone fracture but a potential 30% increase risk for heart attack. So, in isolation, I believe it is better to avoid oral calcium supplementation and obtain your calcium from organic sources of dairy.

3) Finally, the most bizarre part of this analysis was talking about three studies using the pharmaceutical version of vitamin B3, slow release nicotinic acid and then inferring that this drug is a vitamin. I have been using immediate release nicotinic acid in thousands of patients for 40 years with incredible benefits. It is my clinical experience that 10% of patients cannot tolerate statins at all and in these patients I have found the combination of immediate release nicotinic acid (a drug, not a vitamin ) combined with Bergamot polyphenol fraction — a natural substance from citrus fruits grown on the southern Ionian strip of Calabria in Italy, still affords patients excellent control of the vascular risk when combined with healthy lifestyle principles.

I agree that the evidence for slow release nicotinic acid (I repeat, a drug, not a vitamin) is concerning and certainly does not justify its use in the majority of patients.

Thus, I see this most recent report, one of many such reports over the past 20 years to be an excellent analysis of the short term trials of supplementation but really saying nothing about the long-term benefits for people who are conscientious enough to continue healthy lifestyle practices, along with evidence based supplementation for the long haul i.e. 10 years and beyond. It is my view that the totality of evidence still supports high quality supplementation but, don’t expect to see the results within five years.

To re-quote Wikipedia, “humans have a tendency to project their partial experiences as the whole truth, ignore other people’s partial experiences, and one should consider that one may be partially right and may have partial information.” I believe this most recent offering from the Journal of the American College of Cardiology is a great example of this statement.