Faith justified? – a vital tale

By John Pickering 19/10/2012 7

Expensive pee or elixir of life?  The two extreme views of multivitamins.  I’ve been taking multivitamins for a number of years now.  I’ve taken them on faith backed by a little evidence.  This week, I think for the first time, a randomised controlled trial has provided high quality evidence that my faith is justified.  More on that in a minute.

Most trials of vitamin supplements to date have tested vitamins in isolation.  The trials were justified on the observation that people with certain diseases lacked specific vitamins and/or the scientists’ understanding of biochemical pathways that require the vitamin in question to work well.  This is well and good.  From what I understand most of these trials have failed to show a clinical difference (ie in health outcomes) (see, eg, my report on the Vitamin D trial in Christchurch).

Vitamins (and trace minerals), of course do not exist in us in isolation.  They work together with each other and along with all the other chemicals in us with names that only a biochemist could love.  The theory, which I’ve accepted largely by faith, is that vitamin supplementation works best when it is multiple vitamins together.  Studies of multivitamin supplementation have largely been short term or retrospective observational.  That is, scientists have surveyed people on vitamin use and drawn conclusions based on that.  One such study, the Iowa women’s study(1), caused me to pause and reassess last year when it seemed to indicate supplementation including copper increased mortality in post-menopausal women. Being neither a woman nor post-menopausal I did not panic.

The prospective randomised controlled trial (RCT) is regarded as a much higher level of evidence than retrospective observational studies.  Published this week in the Journal of the American Medical Association (JAMA) is an RCT of multivitamin supplementation in men (2).  Briefly, 14641 men aged 50+ were enrolled in a trial in 1997 and followed until 2011. Participants were randomly chosen to receive either a multivitamin or a placebo.  Neither the participants nor the people running the study knew which people received placebo and which received multivitamin.  This is known as “double-blind.”  Only a statistician knew and he or she did not reveal anything until all the data was in.  The primary outcome was to compare the rates of cancer and cardiovascular disease in both groups.  Secondary outcomes (ie ones that the statistics can not be so precise about because of the numbers) were the rates of some specific cancers (eg prostate cancer).  There was amongst the 14641 men a subgroup of about 1300 men with a pre-existing history of cancer.

The results:

Men taking multivitamins had a modest reduction in total cancer incidence (HR, 0.92; 95% CI, 0.86- 0.998; P = .04)

My interpretation:  Those taking multivitamins were about 8% less likely to get cancer.  The statistics show that they are 95% confident that the amongst all men with the same characteristics as the men in their sample the true reduction in probability of getting cancer over the 11 year follow up period is between 0.2 and 14%.

A little frighteningly whilst major cardiovascular events were mentioned as part of the primary outcomes they were not reported on!

The strengths of the study are its size, that it is an RCT and double-blind, that it has good length, that all participants who received the multivitamin received the same one and that the multivitamin manufacturer had no role in designing or running the study, or analysing the data.

The weaknesses are that it is all men, all over the age of 50, and all physicians.

S0, is my faith justified?  If by that do you think I mean “proven” then think again. Proof or proven are words that should never be used in the company of good scientists.  Rather, I think there is some more good quality evidence to support the taking of multivitamins – so I shall continue to do so.  I must, though, remain open to evidence of the opposite variety and be aware that like all studies there is a probability that the conclusions will not be backed up by future studies.

Of course not all multivitamins are created equal (beware of fillers), they have different compositions and some are less likely to be absorbed than others, so do some homework before you rush out an buy some.

(1)  Mursu J, Robien K, Harnack LJ, Park K, Jacobs DR. Dietary supplements and mortality rate in older women: the Iowa Women’s Health Study. Arch Intern Med 2011;171(18):1625–33.

(2) Gaziano JM. Multivitamins in the Prevention of Cancer in MenThe Physicians’ Health Study II Randomized Controlled TrialMultivitamins in the Prevention of Cancer in Men. JAMA : the journal of the American Medical Association 2012;:1.

[Conflict of interest:  My wife’s business includes the selling of multivitamin supplements]

Tagged: cancer, double blind, multivitamins, Randomised controlled trial, RCT, vitamins

7 Responses to “Faith justified? – a vital tale”

  • Hi John,
    It could be very useful to have more details about design parameters and data stemming from this long-term study.
    Likewise, from your lead sentence, I too have wondered how much of one’s Vitamin intake is lost in urine. Your summary seems to substantiate taking a complex Vitamin mixture is advantageous. After all, beneficial effects were found for <14% of 1,300 men with cancer, and therefore <182 people with cancer experienced some beneficial effect .

    Incidentally, in reference to you report, plural is "data" while singular is "datum"

    Well done! Cheers, Anthony

    • Thanks Anthony. The paper is open access :) and certainly contains a heap of detailed information including the secondary analysis which I didn’t report. I was attempting to say in my summary that for me this study is simply a stronger piece of evidence than I have had previously for my taking of multivitamins. I think of these things as a weighing of evidence – for and against, where some evidence weighs more than others (negatively or positively) depending on the quality of the research. With respect to how much ingested vitamins come straight out again the other end – the answer is “that depends.” I’ve heard rumours about some (cheap?) vitamin capsules that don’t dissolve well (I guess one could test this at home). I’m aware that some companies wrap their minerals in amino acids to help the absorption process.

      I shall absorb that datum with respect to data.

  • “Those taking multivitamins were about 8% less likely to get cancer.”

    This wants to be set against whether these men had a deficiency. (I haven’t time to verify if this was covered in the paper, sorry.)

    • Don’t believe it was Grant. Of course it would need to be an assessment of all 14000 odd against a control group and to look at each of the vitamins included in the multi individually. Alternatively, they could have looked at some “recommended” levels – I’m pretty skeptical about the quality of these. The participants were physicians aged over 50. I’d be surprised if they had less Vits than other possible cohorts of males of 50+. The sub cohort with cancer may have had deficiencies of course.

  • While multivitamins may be better than single vitamins, real fruit & vegs – with vitamins and all sorts of other stuff – may be as good or even better, at least for the statistical risk of developing shingles (for which the greatest risk factors are age and immune deficiency). A 2006 study of 243 cases and 483 matched controls found that fresh fruit is associated with a reduced risk of developing shingles–people who consumed less than one serving of fruit a day had a risk three times as great as those who consumed more than three servings, after adjusting for other factors such as total energy intake. For those aged 60 or more, vitamins and vegetable intake had a similar association. But for the under 60 year olds it was the fresh fruit that apparently made the difference.
    Thomas SL, Wheeler JG, Hall AJ (2006). “Micronutrient intake and the risk of herpes zoster: a case-control study”. Int J Epidemiol 35 (2): 307–14.

  • Hi Lynley…thanks for that, interesting. Even 3 servings a day is low…current recommendations are 5 to 10. In the trial described both the placebo & multi groups v had a median of ~4.2 servings per day.

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