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A meta-analysis published in the July 29, 2010 issue of the British Medical Journal¹  deserves special mention for exemplifying—to the point that one wonders if the subtext is to point out the idiocy of our current research paradigm—the shortcomings of the “isolate one variable” approach to studying human physiology or providing dietary supplements for real human beings.

 The stated objective of said meta-analysis was “To investigate whether calcium supplements increase the risk of cardiovascular events.” To accurately report what was investigated, however, this should be rephrased “To investigate whether calcium supplements—≥500 mg/day of elemental calcium given in isolation for ≥3.6 years, without consideration of the body’s requirements for magnesium, vitamin D and vitamin K to beneficially utilize the mineral—increase risk of MI and cardiovascular events.”

Study authors specifically excluded from consideration trials that compared co-administered calcium and vitamin D supplements with placebo and trials in which calcium was administered in the form of dietary modification or a complex nutritional supplement.

No one reading this will be surprised by the researchers’ revelation that supplements containing only calcium significantly increased risk for MI (~31%) and CVD events.  The number needed to treat (NNT) with calcium for five years to cause one incident event was 69 for myocardial infarction, 100 for stroke, 61 for any of myocardial infarction, stroke, or sudden death, and 77 for death. 

Nor will the educated reader have a problem understanding why high dietary calcium intake does not increase CVD event risk. Not only does Mother Nature not isolate nutrients, but the nutrient matrix found in whole foods virtually always contains a mix of the compounds needed for their beneficial use by the human body. Just a few examples of the nutrients found—together—in commonly eaten calcium-rich foods illustrates why isolated supplemental calcium, but not dietary-derived calcium, would be problematic.

 

Commonly Eaten Calcium-Rich Foods
Food	Serving	Ca	Mg	K	Vit D	Vit K	Boron
Cow’s milk	1 cup	~300mg	~35mg	~380mg	~100iu	~10mcg	~4 mcg
Sardines	3.25 oz. can	~355mg	~40mg	~365mg	~250iu
Spinach	1 cup, cooked	~245mg	~160mg	~840mg			225mcg
Sesame seeds	¼ cup	~350mg	~130mg	~170mg

 

Calcium-rich foods—and intelligently formulated supplements containing calcium—always deliver a mix of the nutrients required for calcium’s beneficial use, not only in bone metabolism, but in blood clotting, nerve conduction, muscle contraction, regulation of enzyme activity, and cell membrane function.  Only when extracted from the matrix of nutrients in which it contributes to optimal physiological function does calcium act as a contributing factor to hypertension and arterial calcification.

What will be surprising is that the study authors’ clinical takeaway is not: when supplemented, calcium should be accompanied by its metabolic partners. Instead they, and an accompanying BMJ editorial, suggest that calcium should not be given to women at risk of osteoporosis!   

In the editorial, Cleland et al., write:  “In the meantime, on the basis of the limited evidence available, patients with osteoporosis should generally not be treated with calcium supplements, either alone or combined with vitamin D, unless they are also receiving an effective treatment [italics added] for osteoporosis for a recognized indication. Research on whether such supplements are needed as an adjunct to effective agents is urgently required.”²  

By “effective treatment/agents,” Cleland et al. are referring to “bisphosphonates, raloxifene, and thiazides.” Unfortunately, however, “biphosphonates and raloxifene were generally given in addition to calcium and vitamin D supplements,” so that’s a problem.  (For reasons why bisphosphonates might rationally be considered a problem in their own right, please see the LMR review:  Building Bone: Part I, The Case Against Bisphosphonates.)

In an interview with heartwire³, senior author Dr. Ian R. Reid of the University of Auckland, recommends that women should discuss the finding from this meta-anaysis with their doctors, but that in most cases, "discontinuation of calcium would seem appropriate."

Also thought provoking is the comment made by Dr John Schindler (University of Pittsburgh Medical Center, PA), who, although not a co-author of the meta-analysis, was interviewed by heartwire. As an apologist for the absence in the meta-analysis of the Women's Health Initiative, perhaps the largest study that has yet looked at the role of calcium supplementation in reducing osteoporotic fracture, and which recently reported that calcium and vitamin D had no effect on risk of coronary heart disease or stroke,⁴ Schindler said, "There are a lot of data that show that vitamin D is protective from a cardiovascular standpoint. They [Bolland et al.] excluded studies with vitamin D probably because they are trying to isolate one variable. They didn't want to cloud the picture."³

(For a review of the research and discussion of the ways in which vitamin D and vitamin K work together to lower CVD risk, please see the LMR reviews: Vitamin D and Vitamin K Team Up to Lower CVD Risk: Part I and Vitamin D and Vitamin K Team Up to Lower CVD Risk: Part II.)

Sorry to rain on Bolland et al’s parade, but pretending one artificially inflated variable can accurately inform us about anything more than what will go wrong with human metabolism when co-active nutrients are not supplied is absurd.  To repurpose Al Gore: it’s an inconvenient truth that our bodies do not function one variable at a time! An inconvenient truth researchers and clinicians ignore at patients’ peril.

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