Monday, May 04, 2009

Calcium and weight loss - barking up a dubious tree?

Here is a some more dismal behavior by scientists back in my own area of voyeuristic interest (skeletal medicine and calcium physiology). This bit of jiggery pokery involves a study looking at calcium supplementation as an aid to losing weight.

The study was published (1) with much media fanfare (3,4,5,6,7) a few weeks ago. It suggests, based on a supposedly randomized and blinded placebo-controlled trial, that calcium supplements help some obese individuals lose weight. Study funding was from Wyeth.

Big time stuff, and also very controversial. It is certainly possible - but needs some proper science with reasonable numbers.

The worry comes from the same pot of dubiousness described in my previous post (the Wang case). Scientific authors, having published some findings and having enjoyed a media blitz, refuse to convey what they actually did ("method"), how they analyzed data (more "method"), the study protocol ("method") or even a rudimentary plot of the data to allow basic plausibility evaluation.

The particular refusal in this case is the most bizarre I have personally encountered from supposedly "scientific" authors. These authors refuse to reveal what the calcium supplement and placebo contain!

They state that this is "confidential".

As I will discuss, this is hardly a trivial matter. It also makes me wonder whether peer-reviewers should sometimes be named and shamed for failing to ask the most obvious questions (as well as for raw data when necessary).

Before discussing the authors' refusal, it is necessary to know a little about calcium supplements. As anyone who has ever conducted a calcium RCT will know, it is a headache trying to create a placebo. The placebo has to look and taste the same as the calcium. The problem is particularly acute when supplements are supplied in a solid form, because calcium supplements are BIG......

The participants in this study were given 1200mg of elemental calcium per day (about 3 grams of calcium carbonate plus flavorings and some vitamin D). Here is what a slightly lower dose of calcium (2 x 500mg) looks like (in the form of Cacit - P&G's supplement).

Those are mighty big chewy or effervescent tablets. Now the placebo has to consist of something, and that something cannot be pure air. It may be sorbitol, some other sugar, or something else altogether.

So, what do we know about this study. Well, in the two so far published papers about this small RCT (1,2), both in prestigious nutrition journals, the authors write

What is the placebo?

Now that's none too helpful. Even small timed doses of a variety of nutrients can have some big effects on gastrointestinal function, bone turnover, gut hormone release and satiety. Given the very modest weight "effect" in this study (calcium versus "placebo") the question of placebo composition is hardly arcane.

I also worried about the statistical analysis. The authors conducted a critical retrospective subgroup analysis on a small subgroup of participants. I don't plan to discuss statistical issues in this post, but the relevant questions should be obvious to any modestly critical reader or honest peer-reviewer. So I wrote to the authors asking about the composition of the placebo, and for the weight/calcium data (or at least a scatter plot of their key "finding").

This was the first letter I wrote:
Date: Mon, 23 Mar 2009 09:21:56 +0000
Subject: Re:Calcium and weight study


a) Can you tell me the nature of the placebo since
this is not clear from the manuscript.

b) Can I please have a copy of the raw data giving
only the weight before, weight after, calcium
intake and placebo/treatment assignments of each

Yours Sincerely

Dr Aubrey Blumsohn
This was met with a straightforward refusal to supply any raw data, and no response at all on the question of the placebo.

So I wrote again
Date: Tue, 24 Mar 2009 15:12:57 +0000
Subject: Re:Calcium and weight study


Can you:

a) At least tell me what the placebo was

b) Send me a scatter plot showing all data points
for weight change versus baseline calcium intake for
placebo and treated arms separately. That is
directly related to what you published and not
different information.

Kind Regards

Dr Aubrey Blumsohn
And this is what I received

Date: Tue, 24 Mar 2009 15:12:57 +0000
To: Aubrey Blumsohn
Subject: Re:Calcium and weight study

Bonjour Dr. Blumsohn,

I take once again several additional minutes to give you an
additional reply in an environment which is more and more demanding,
mainly because of electronic communication. My specific answers to
your specific questions can be summarized as follows:

1. The placebo: The placebo was prepared by the company (Wyeth
Consumer Healthcare) who provided the financial support to this
study. We know what is the composition of the placebo but this
information is confidential.

2. Scatter plot of data points: As I told you, we might consider that
and publish this information in the future.


Kind regards,

Angelo T
A subsequent request for the study protocol was also met with refusal.

Is this science and can these authors be held to be in any way "scientific" authors? Watch this space.

Incidentally, "Tremblay A" appears to have published 8 papers in the past six weeks.


  1. Major GC, Alarie FP, Doré J, Tremblay A. Calcium plus vitamin D supplementation and fat mass loss in female very low-calcium consumers: potential link with a calcium-specific appetite control. Br J Nutr. 2009 Mar;101(5):659-63.
  2. Major GC, Alarie F, Doré J, Phouttama S, Tremblay A. Supplementation with calcium + vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations. Am J Clin Nutr. 2007 Jan;85(1):54-9.

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Anonymous said...

err, are not references 2 and 3 identical ?

Anonymous said...

welcome back to blogging activity !

Roy M. Poses MD said...

Very glad to have you back!

Aubrey Blumsohn said...

Fixed duplicate reference

Thank you :)

Anonymous said...

The journals should be approached

Aubrey Blumsohn said...

I have. Will report back in due course.

Anonymous said...

Dear Dr. Blumsohn, Sorry for the late response, but I only just now got a copy of this study. I couldn't help but laugh. The most obvious flaw I saw (table 1): the 7 women they pulled from the calcium group was consuming about 691.4 kcal/day, compared to the 6 women they selected from the placebo group who were eating 1014.5 kcal/day. [This secondary analysis of just 13 of the 63 women in the original cohort was not randomized, nor an intervention trial; nothing more than observational correlations. Compound that by a RCT that didn't control for caloric intakes, exercise levels or a vast array of other confounding factors.] Multiple that by 15 weeks and the difference in the short-term weight loss reported was almost precisely what would be attributable to caloric restriction alone. The calcium or some other magical dietary component had nothing to do with it. We can all make cherry pie.