Friday, October 21, 2011

Ask Dr. Andro: Are Vitamin Supplements Bad For Me (2/2)? 3+1 = 666! The Raw Data Truth about the "Vitamins Kill!" Offspring of the Iowa Women's Health Study

Image 1: "Please Dr. Andro tell me I can keep taking my essential multivitamin! I am just too busy to eat healthy..."
I must admit that I feel kind of awkward as I am about to defend one of those supplements, I consider to be the most dispensable within the dietary regimen of a physical culturist: the so-called multi-vitamin! In essence these small, and lately more often than not large pills do not even fall into the category supplement. With dose-equivalents way beyond what you would actually need, "multivitamins" are not even "replacements", they are madness or, I should say, the mad outgrowth of the prevalent "more is more" mentality that is beginning to harm us on every level of our society... but I am digressing, here. Let's take a look at the actual study which brought about such an upheaval in the supplement-addicted health community on the Internet.

Dietary Supplements and Mortality Rate in Older Women

Image 2: Is this you? No? Maybe she is "The Average American", then? No? Well, but the study says "vitamins are bad for YOU" and she could be one of the subjects (img. medscape.org)
The title alone, actually made me click the study away, back in the day when I first hit upon it, on one of my regular searches for new stories on the medical databases of the World-Wide-Web; and unless you are an old women (I would hope there were some older women reading the SuppVersity, but I guess there are none), you should have disregarded the study, as well. After all, we all know how the game changes after menopause and guess what, of those women, 98.6% were post-menopausal (in case you ever see studies done on ovariectomized rodents, remember that those are "menopausal", too ;-). Ah, and in case you are a post menopausal women with Africa-American or Hispanic background, there is likewise little reason for you to read on, because 99.2% of the women in the study were white (if you question whether or not ethnicity really matters, when it comes to the health effects of vitamins, I suggest you take a look at some reviews like Carmel. 1999).

Now, if you are still with me at this point, I guess that you either are a post-menopausal white woman, or - and I suppose that this will be the case for the majority of you - you have been agitated by the heated debate on the net (and even regular mass-media) in the last couple of days and want someone to tell you that you did not reduce your life-expectancy by -15% by religiously taking your "essential" *rofl* multi-vitamin, everyday. We will see, whether I can be this person (in case it turns out I am not, I have seen more than enough "gurus" you will tell you exactly that, if you promise to buy their "all natural" or "superior source" product in the future).

The Iowa Women's Health Study - Mrs "not so average" American

So, let's see. What we have here is an offshoot of the Iowa Women's Health Study (IWHS), which is one of those highly over-estimate surveys, the media loves, because they boast of ten-thousands of "participants". In the case of the IWHS, "41836 women aged 55 to 69 years"... well, at least that were the women the scientists send their little questionnaires to back in 1986. Interestingly, this is also where the first bias (i.e. a deviation from "objectivity") came into play:
Respondents were slightly younger, had lower body mass index (calculated as weight in kilograms divided by height in meters squared), and were more likely to live in rural areas compared with nonrespondents.
So instead of the average American "older woman", the scientists suddenly had the "slightly younger" not just as obese, better off American older women, as their study object. Moreover, the number of participants dropped to 38772 women or, in other words, the scientists "lost" 7.3% of their study population even before the study actually began. Now, of those, the Mursu et al. selected 29230, who were the "elite" which responded to both the initial 1986 and the 2nd 1997 follow-up questionnaire.

Failure 1: Not representative of "The Average American"

"Ladies, give me as little information about your supplements as possible, please!"

The latter, i.e. the questionnaire, assessed the use of 13 supplements:
  • multi-vitamins; 
  • vitamins A, beta-carotene, B6, folic acid, B complex, C, D, and E; 
  • iron, calcium, copper, magnesium, selenium, and zinc
Now, the scientists show off their wealth of knowledge and state that "[d]ifferent forms of vitamin D, cholecalcif-erol (D3) or ergocalciferol (D2), were not distinguished". While this is obviously important, it would have been even more important to distinguish between different forms of vitamin B6 (pyridoxin vs. P5P), B complex (you can have a complete one, one with equal doses, one particularly high in one B vitamin, etc.), vitamin E (I suppose you read the first installment?), iron (heme, non-heme, chelated, etc.), copper / magnesium, selenium, and zinc (oxide, chelated, etc.), because we know that these different forms of vitamins and minerals are not only differentially absorbed, but also exhibit differential effects on our health and well-being.

Failure 2: Ignorance towards the fact that
not all vitamins / minerals with the same label are created equal

And as if this had not been enough, the scientists did not even care if the ladies popped 1 or 23 of their beta carotene (I hope you do not still believe you can take endless amounts of that orange poison), magnesium, folic acid and B-complex pills.

Failure 3: Careless ignorance towards dosages

Raw foods are dangerous and so is raw data

Hence, the scientists got a set of data that was full of holes from a group of women who are by no means representative of "The Average American" (let alone every human being) - what did they do next? Well, obviously "raw data" is as dangerous as raw meat (or even raw milk), that is why the next step for every good scientists is data processing. In that Mursu et al. were particularly skilful as far as not revealing what they actually did was concerned:
In the minimally adjusted model, we adjusted the association for age and energy intake; in multivariable adjusted model, version 1, we additionally adjusted for educational level, place of residence, diabetes mellitus, high blood pressure, body mass index, waist to hip ratio, hormone replacement therapy, physical activity, and smoking status. For multivariable adjusted model, version 2, we added intake of alcohol, saturated fatty acids, whole grain products, fruits, and vegetables.
Even, or I should say, especially for a physicist, who is a 75% mathematician, the idea that by some sort of mathematical magic you could reliable subtract out all those influence, so that you get the "real picture" of what is going on, with an average human being is so hilarious that I avoid any further comment. Everything that goes beyond the "minimal adjustment" is so full of speculative hypothesis and mainstream paradigms (like "Whole grains are good for you! The more, the better!") that I will simply ignore this data... unfortunately these results of "3+3 = 666" mathematical manipulation were what the scientists (in their press releases) highlighted as their main results and what was accordingly taken up by the laymen (initially I wanted to write idiots, but that would be unfair, because laymen they are) in the editorial offices of the mass media.

Failure 4: Over-"analysis" of the data

Let's get to the raw truth

This would not be the SuppVersity, if I did not have something to offer that goes beyond the angry rants and criticism (see above) you probably have read elsewhere, anyways. So, I went through the pains of compiling and comparing the "real", i.e. the N=X data and not the calculated hazard ratios for you.
Figure 1: Raw data and minimally adjusted (age and caloric intake) data on the effect of taking vitamin A, beta carotene, vitamin C, vitamin D, vitamin E, and finally the multivitamins on overall mortality (data calculated based on Mursu. 2011)
Now, I want you to take a close look at the data for vitamin A, beta carotene, vitamin C, vitamin D, vitamin E, and finally the multivitamins. I don't know what you see, but I see only vitamin A and beta carotene scratching at the increased mortality margin of 1.0 (cf. dotted red line in figure 1). And, just for a better understand, two examples:
  • the 1.04 as for vitamin A (minimally adjusted) in 2004-08 indicates a +4% higher risk and 0.80,
  • the 0.80 for vitamin E (raw data) in 2004-08 indicates a -20% decrease in mortality risk
So, what would you say, how "dangerous" is taking vitamin pills if you do not process the data to death? Interestingly, things get really nasty, from here. And moreover, they get nasty, where you probably would not have expected it unless you are a very diligent student of the SuppVersity and are thus aware that messing with the methylation cycle via B6 or folic acid supplementation for no reason is not a good idea.
Figure 2: Raw data and minimally adjusted (age and caloric intake) data on the effect of taking vitamin B6, folic acid, B-complex, calcium, and magnesium on overall mortality (data calculated based on Mursu. 2011)
Given the fact that an increasing amount of "old" people are taking magnesium supplementation, I would say that in this case the age-adjustment is probably necessary - if you also consider that back in the 1980s this bias was smaller, since people were not told that taking mg supplements would be necessary for older folks, the respective adjustment will be "too small" and thus I would simply ignore the fact that the 1996 value still signifies a +2% greater risk of dying when you take a magnesium supplement (add to that that the study participants could have taken magnesium in the 10x recommended dosage and the scientists would not know that /see comment on dosage, above). What really surprises me, though is the enormous benefit that is (even in the raw data) associated with calcium supplements - 22% reduced risk according to raw data and 21% reduced risk with age/energy adjustment - impressive!
Figure 2: Raw data and minimally adjusted (age and caloric intake) data on the effect of taking iron, copper, zinc, and selenium on overall mortality (data calculated based on Mursu. 2011)
Last but not least - the worst offenders, the dreaded "heavy metals" ;-) Ok, I guess iron really is a bad guy (at least for post-menopausal women), but even copper, which has gotten such a bad rep, lately turns out to come pretty handy in the female part of the aging American population, ... interestingly only in the early to late 2000s - how come? I'll leave it up to you to make up your mind on this and other questions, but I assume that now, that you know the raw truth, you will not blindly follow Bjelakovic's campaign to "wake up [regulatory authorities] to their responsibility to allow only safe products on the market" (Bjelakovic. 2011), but rather scrutinize his "invited comment" to the Mursu study, which was published in the same issue of the Archives of Internal Medicine and has caused such an upheaval among the increasingly health conscious American and International public.