The Recent Headlines About Multivitamins: Fact or Fiction?

Keith I. Block, MD

Quite a stir has been created by the December 2013 publication by the Annals of Internal Medicine of two placebo-controlled trials that found vitamin and mineral supplements did not prevent repeat heart attacks or cognitive decline.  Adding to the controversy was an accompanying editorial that said, essentially, that multivitamin supplements are a waste of money.  Most of the headlines that followed were of a similar theme, suggesting that multivitamins are basically useless.  While I do agree with them that not much of any value came out of these trials, I don’t agree that multivitamins – correctly formulated and used for appropriate goals – are a waste of consumers’ money.  What likely WAS a waste of money, however, was the money taxpayers’ spent funding these big trials.  And, I must point out that these trials do not in any way represent, or have anything to say about, the practice of true integrative medicine.

Let’s take a closer look at the research…

To begin with, there were a few problems with the execution of these studies.  In the study on cognitive decline, patients were classified as having “adhered” to the multivitamin program, or successfully implemented the study plan, if they took their study pills just two-thirds of the time.  While perhaps many of us forget to take our pills from time to time, forgetting to take them one day out of three really sets the bar unreasonably low.  Furthermore, the researchers assessed adherence by simply asking subjects once a year how often they took their vitamins.  Asked them only once a year?  It’s easy to see how this method of assessing participants’ adherence is commonly error-prone.  Finally, again in the study on cognitive decline, the potency of the multivitamins was quite low, with, for instance, only 60 mg of vitamin C.  This level of dosing is, practically speaking, enough to counter scurvy, but otherwise, one wouldn’t expect such a low dose of this vitamin to have a measurable health benefit.

Conversely, when you look at studies that have used more substantive doses of supplementation, you find more favorable results.  For instance, an Australian study of a multivitamin, multi-mineral and herbal formula found improvements in what is termed episodic memory and declines in homocysteine levels (high homocysteine indicated an elevated risk for Alzheimer’s disease and heart attacks).  In addition, two observational studies have found improved mortality in breast cancer patients who took multivitamins – in one case the best survival was for women who were taking multivitamins and eating plenty of vegetables and fruits.  The Physicians Health Study, a randomized trial with over 14,000 male doctors as participants, found a significant 8% reduction in overall cancers in the men who took multivitamins.  This same study also found that multivitamins reduced the risk of cataracts.

There are also some concerns with the study on repeat heart attacks.  As was the case with the study on cognitive decline, there was a problem with the participants’ adherence. In fact, 46% of subjects actually stopped multivitamin supplementation during the study.  This study used a multivitamin the researchers characterized as “high-dose” (though if one takes a close look at the dose of each of the vitamins in the formulation, some would be considered “high dose,” others would actually be considered “low dose.”).  This multivitamin was given as 6 pills a day, and was actually part of a larger study that involved intravenous chelation therapy (chelation therapy was shown to have a modest effect on repeat cardiac events, but the data on chelation therapy were published in other papers and not discussed in this publication).  It has been suggested that the combination of the multivitamins with regular intravenous therapy may have been too logistically burdensome for the patients, and contributed to the low adherence levels.  Although the differences were not statistically significant, multivitamin users did experience a reduction in deaths due to cardiovascular diseases (11% less among the multivitamin users).  And patients who did not use statin drugs or could not tolerate them had a better response to multivitamin therapy, although not enough to make a firm recommendation for their use.  But both the study investigators and outside critics have pointed out that the low adherence to the regimen was a problem for the study, and one can’t help but wonder if better adherence to the regimen would have resulted in a statistically significant difference in cardiovascular deaths.

Another problem with the study is that it was designed to detect a difference in cardiovascular deaths of 25% or greater.  This absurdly high benchmark may have been an issue of study practicality: to use a smaller measurement in cardiovascular deaths – say, 11% — the authors would have had to include many more people in the study for statistical relevance, which rapidly adds to study costs.  In addition, it was difficult to get enough patients to enroll in this specific study, and thus, the study size actually had to be decreased part-way through. Nevertheless, the idea that a multivitamin could prevent a quarter of deaths from repeat heart attacks, even if it’s combined with chelation therapy, would be a very impressive result to accept, even for us proponents of supplementation.  And, the investigators themselves admitted that this 25% may have been an overly optimistic goal.  On the other hand, the 11% decline in cardiovascular disease certainly is quite provocative, even if it wasn’t statistically significant.  One can’t help but wonder if a series of trials of multivitamins (without chelation) in cardiovascular disease patients who were otherwise similar to the patients in the chelation study, or in patients who were intolerant to statins, might give us interesting – perhaps even significant – findings.  Of course, such a trial would have to be done using a correct sequence of preliminary trials to investigate factors such as treatment adherence and supplement formulation.  It would be a truly spectacular finding if we could find a statistically significant difference of 11% in cardiovascular deaths with a well-formulated supplement.  And one definitely comparable to findings from drug therapy.

Now, let’s look at the premise behind these multivitamin studies, and whether or not it was realistic to begin with.  The idea that multivitamins alone could possibly prevent a major disease like a repeat heart attack or cognitive decline certainly does not come from integrative medicine.  No reputable integrative medicine practitioner would ever suggest to a patient that a daily multivitamin would be the only intervention necessary following a heart attack.  Nor would they suggest that a multivitamin alone would prevent cognitive decline.  So where did this idea come from?  It’s likely related to the single intervention/single pharmaceutical mindset so prevalent and core to decades of mainstream medical practice.  However, the idea that a single intervention is “the” answer to prevent or cure any disease simply doesn’t hold water.  And of course this remains true whether that intervention is a drug or a nutraceutical.  However, what single-nutrient supplements and low-dose multivitamin supplements CAN do is this: they can work very nicely as manageable interventions in big clinical trials that are impressive to government granting agencies.  Unfortunately, trials on the highly individualized interventions of integrative medicine, which usually tend to be smaller due to the need for more complex treatment regimens, just don’t impress grant review committees the same way, making them less likely to get funding in the first place.  The preference for large-scale, single-formula, reductionist studies has perpetuated what is really an unsuitable approach to the evaluation of dietary supplements in the first place.  And while it would be great if all it took to prevent cognitive decline, heart attacks and other major afflictions was to pop a single multivitamin pill, the problem, of course, is that this is beyond wishful thinking, it’s simply nonsensical.  There is no evidence to even remotely suggest that any single intervention, in and of itself, is sufficient to prevent any serious disease.

I must also mention that it’s important to use a supplement as it was intended:  as a supplement!  In other words, there is no supplement regimen that can substitute for eating a healthy, balanced diet, one that includes fruits, vegetables, quality proteins, healthful fats and whole grains.  Once that foundation is laid, a supplement should come as close as possible from a whole plant.  And a tailored whole plant-based supplement regimen built atop of a whole foods diet will have benefits beyond the diet itself.

Not All Supplements Are Created Equal 

Most people are not aware that while the FDA oversees the labeling and “claims” of supplements, it does NOT ensure the potency, purity or the biologic activity of the ingredients in supplements.  As a result, there are products on the market that have contaminants, excessive lead levels and/or do not contain the level of the active ingredient (s) as stated on their label.  While this is a concern for the general population, it is, of course, potentially more problematic for cancer patients.  Unless your practitioner formulates and tests on their own, it may be useful to utilize a website such as www.consumerlabs.com, which does independent testing of supplements for quality and purity.

What is also important for cancer patients to be aware of is what shouldn’t be included in their multivitamins.  Though both iron and copper are commonly found in most multivitamin formulas, at routine dosing they can both lead to potential problems:  Iron can exacerbate oxidative stress, and copper is a critical element in angiogenesis, or the formation of blood vessels that nourish tumors.  In addition, multivitamins commonly use just a single form of vitamin E, alpha-tocopherol.  Natural vitamin E contains 8 different compounds, including gamma-tocopherol and the tocotrienols.  Dosing patients with alpha-tocopherol alone drives down gamma-tocopherol, which can have negative effects on health.  One example of a trial where this may have occurred is the SELECT trial in prostate cancer patients, in which men were given daily alpha-tocopherol in an attempt to prevent prostate cancer.  Some of the men also received selenium.  The men who received alpha-tocopherol (the form of vitamin E most commonly used in supplements) wound up with a higher risk of prostate cancer than the men who did not receive it, or who received it along with selenium.  While it’s not entirely certain why this happened, one thing that was observed was that men receiving alpha-tocopherol incurred reductions in their levels of a related compound, gamma-tocopherol.  Several lab studies have shown gamma-tocopherol can inhibit prostate cancer.  Therefore, had gamma-tocopherol or mixed tocopherols been used, the study outcome may have been very different.  This is one more reason why I highly recommend cancer patients undergo testing so their nutraceutical regimen – as well as every component of their integrative treatment program – can be individually tailored to their unique needs.

The Bottom Line: My Take on the Use of Multivitamins

So, given how many significant flaws there were in the execution of these studies, it’s easy to understand why one shouldn’t accept their conclusions at face value.  Among the concerns identified in this article:

• An unreasonably low level of compliance that was considered “adherence” to the cognitive study’s protocol.
• A method for assessing adherence in the cognitive trial that is known to be error-prone.
• The potency of the vitamins used in the cognitive decline study was quite low; it simply isn’t realistic to expect these levels to provide a measurable health benefit.
• An unrealistically high benchmark was used to measure the effectiveness of the multivitamin in the chelation/repeat heart attacks trial.
• The idea that any single intervention alone – in this case, a multivitamin – is enough to prevent repeat heart attacks or any major disease is not grounded in either logic or science.

So, do I believe there is value in taking a multivitamin supplement?  Yes I do, but only when it is correctly formulated and used in the context of a healthful diet and lifestyle – particularly for those who are struggling with serious illnesses.  I am not comfortable with people taking whatever multivitamin may be on sale or has the most compelling advertising campaign.  However, I can and do recommend a serious conversation with an integrative health professional about how a multivitamin, or a specifically formulated multivitamin, fits into an optimal health or disease-fighting program of care, and how a multivitamin and/or other nutraceuticals may be of value when used in the context of a healthy diet and lifestyle.