Jul 30 2010

Calcium and the Law of Unintended Consequences

Biological systems are extremely complex. This nugget of wisdom may seem trivial but it is a lesson the scientific and medical communities have been learning over and over again for a couple of centuries. Every time we think we understand a biological system we find there is a deeper level of complexity, or another layer of interactions we had not previously taken into consideration.

This is why we need high quality clinical trials to feel confident about the net health effects of any intervention. A treatment may make sense based upon our current understanding of human biology, but that’s not enough. We need to know what it actually does to people.

This is a lesson, however, that the supplement industry has not learned (and does not appear interested in learning). I have nothing against supplements themselves, only how they are regulated and marketed. I prescribe supplements all the time, when they are evidence-based. But the supplement industry has pulled off a marketing coup – the holy grail of marketing: turning their hype into accepted conventional wisdom. For example, the public generally believes that “natural” is always better, that supplements are always safe, and that we all need to take supplements – the more the better. None of these things are true.

A more subtle marketing deception often employed by the supplement industry is the use of pre-clinical basic-science evidence to support clinical claims for their products. In other words, they cite studies in which some marker in a petri dish is increased in the presence of their supplement, then extrapolate several steps to an ultimate clinical application. One of the most common manifestations of this I encounter is looking at some marker of immune function, claiming that it is increased, then extrapolating from this that the supplement “boosts the immune system” and then further extrapolating that it will therefore help the body fight off cancer.

Antioxidants are another example – extrapolating wildly from pure basic science evidence that antioxidants reduce oxidative stress. When clinical studies started coming in showing no benefit the antioxidant sellers claimed that the doses weren’t high enough. Now we have data showing that high doses of antioxidants are associated with increased risk of heart disease. It turns out (gasp) that the biological system was more complex than we though. Oxygen free radicals are also used as signaling chemicals that trigger important cell functions, and suppressing them has – unintended consequences.

Now we potentially have another story to add to the law of unintended consequences – calcium supplements and heart disease. Osteoporosis – the thinning of bones through loss of calcium – is a serious medical problem for the geriatric population. After about age 50 (and post-menopause for women) men and women start to lose calcium from their bones. The best way to prevent this from becoming a problem is to maximize your bone density by age 50, and this is done through weight-bearing exercise. Exercise after age 50 will also help stave off bone loss to a lesser degree.

There is an ongoing controversy about the use of calcium supplements, calcium plus vitamin D, and the use of prescription medications to increase bone density and reduce osteoporosis. This is a complex area of medical evidence, but the quick version is that calcium supplements by themselves are likely not of any significant benefit in preventing and treating osteoporosis and reducing fractures. Calcium plus vitamin D has modest benefit for bone density. In some patients with osteoporosis and not responding to supplements and exercise alone, pharmacological treatment may be necessary to reduce the risk of fractures. It also is likely true that calcium and vitamin D supplements are only helpful if a person is deficient in one or both. If you are getting sufficient calcium and vitamin D from your diet, taking additional supplements is likely of no benefit.

This is a quick summary of a lot of evidence, and there are still many open questions that need to be addressed by further research. Meanwhile the pharmaceutical industry is doing what they can to push prescriptions for osteoporosis and osteopenia (a milder form of bone loss). And the supplement industry is pushing calcium and vitamin D supplements.

In addition to the fact that there is little evidence to support the use of these supplements in most people, there is the question of safety. Again – there is the common assumption that supplements can do no harm, so even if the evidence for efficacy is weak there is nothing to lose from taking supplement for nutritional “insurance.” This is not a good assumption.

A new study published in the BMJ, in fact, suggests that calcium supplements are associated with a 30% relative increased risk of heart attack (but not death, and only a tiny increase in stroke risk). This is a meta-analysis of previous studies, and the authors found:

Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.

So calcium supplements are of questionable benefit, and may increase the risk of heart attacks. The authors point out that prior studies did not find the same increased risk from a diet high in calcium, so it only seems to apply to calcium supplements. This is yet more evidence for the general principle, supported by clinical evidence, that it is better to get your nutrition through a healthful varied diet than through supplements.

This study also demonstrates the utility for researchers to keep going back and asking questions about interventions. Biological systems are complex, and we have to look at interventions from multiple angles before we get a handle on their net health effects. And this study is not the final word – it takes many studies over years of research for a consistent picture to emerge. All we can say at any point in time is the best interpretation of existing research. Right now for osteoporosis it seems that the best strategy for bone health is to have a healthful diet with sufficient calcium and to exercise regularly (funny how evidence seems to be coming back to that same conclusion). Regular doctor visits will also determine if this is insufficient and you need further targeted therapy.

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