[Viva] Fwd: CATIE News - Concerns about calcium supplements

[Tami Starlight]

FYI

Tami
=============

*CATIE News - Concerns about calcium supplements*

Calcium is an important mineral used for building bones and is needed by
muscles, nerves and many other tissues to help them function properly.
Generally, bones reach their largest and thickest size in early adulthood.
After this, they slowly become thinner. In women, bone thinning accelerates
around the age of menopause; sometimes as much as 2% of bone mass is lost
each year for up to 14 years after the onset of menopause.

Adults require between 1,000 and 1,200 mg of calcium each day. If the body
does not get enough calcium from food, a calcium deficit occurs and the body
is forced to remove calcium from bones so that other tissues can use it. If
this calcium deficit continues over a period of years, bones gradually
become thinner (osteopenia), and in some cases they become severely thin
(osteoporosis). Having osteoporosis makes bones fragile and prone to
breaking when falls or accidents occur.

Not everyone can achieve the daily requirement of calcium, so
supplementation with this mineral is sometimes necessary. Since vitamin D
deficiency is common, supplemental vitamin D may also be necessary, as this
enhances the absorption of calcium and phosphorus (another mineral), which
is also necessary for bone health.

In 2008 a team of researchers in New Zealand suggested that the use of
calcium supplements *might* increase the risk of heart attacks in healthy
older women (average age: 74 years). They made this claim based on the
results of a randomized clinical trial that was primarily designed to assess
the impact of calcium supplementation on bone mineral density and subsequent
fractures in 1,471 women who had already undergone menopause.

Although the trial was designed to assess changes in bone mineral density
and fractures, the New Zealand team later decided to re-assess the trial’s
data to see if calcium supplementation was associated with an increased risk
for heart attacks. Doing such a reanalysis—taking data from a trial designed
for one purpose and then using this data for another purpose—is fraught with
risk because conclusions derived such an analysis can be skewed due to many
factors. Therefore, interpretations reached from such re-analyses are very
limited in their robustness and can *never *be definitive.

Nonetheless, the conclusions arrived at by the New Zealand team have caused
some doctors, researchers, bone societies and agencies as well as members of
the public to question the safety of calcium supplementation. Since the New
Zealand team’s conclusions are not definitive, heated debate and confusion
has erupted over its findings.

Bone thinning appears to be a problem in some people who have HIV infection
and in those who are exposed to certain anti-HIV drugs—so calcium
supplementation may be necessary. Therefore, it is worth critically
examining the methods used by the New Zealand team to help readers
understand the perceived strength of its claims and what further courses of
action are necessary.
Initial reanalysis

In 2008 the New Zealand team, led by professor Ian Reid, used data from a
five-year randomized controlled trial of calcium supplementation (taken at a
dose of 1 gram per day) designed to assess changes in bone density and
fracture. The team reanalyzed the data, looking specifically for
cardiovascular events and outcomes such as these:

   - death
   - sudden death
   - heart attack
   - chest pain
   - stroke
   - mini-stroke

The participants were 1,471 healthy women who had undergone menopause.

Based on reports of heart attacks (and other events) by patients, there was
a statistically significant increased link between the use of calcium and
subsequent heart attacks.
Flaws in the re-analysis

A critical reading of the re-analysis by an Australian research team with a
solid understanding of statistics, nutrition and cardiology has found flaws
undermining the claims made by the New Zealand researchers, as indeed have
leading researchers in several other countries. The Australian team notes
that after verifying the patient reports by examining hospital records and
noticing additional reports of heart attack unreported by patients but
captured in hospital databases and further statistical analysis, neither
heart attacks nor any of the events listed above were statistically
significantly linked to calcium intake.
Another attempt with some odd findings

In 2010 the New Zealand team conducted a review of 11,000 publications,
examined 190 of them and then selected 28 research papers that reported on
15 studies with 8,151 men and women. They used the data from these 15
studies to conduct a meta-analysis. This type of analysis combines related
studies and is a statistical tool used to assess the strength of a
relationship—in this case, between calcium and cardiovascular outcomes; a
meta-analysis is not an actual study.

In its meta-analysis, the research team found that only participants whose
calcium from the diet exceeded 805 mg per day *and* who took supplemental
calcium were at heightened risk of a heart attack.

What was odd about the meta-analysis findings was that the risk of a heart
attack did not increase when very high rates of calcium supplementation were
used (compared to lower doses of calcium). Furthermore, there were no
statistically significant effects of calcium supplementation on outcomes
such as stroke, sudden death and other events suggestive of cardiovascular
complications.

Moreover, there are other issues with the methods used by the New Zealand
team that render its conclusions problematic. To delve deeply into the
details of these problems is beyond the scope of our report, so we will
cover key points that have been raised by scientists who have investigated
and critically analysed the New Zealand team’s work.
An issue of design

None of the clinical trials used in the meta-analysis were primarily
designed to assess cardiovascular events—heart attack, stroke and so on.
This is an important point. Therefore, these trials cannot be reasonably
used to extract firm conclusions about the effect of calcium on heart
attacks and related events.
Imbalances

Although all of the studies used for the meta-analysis were randomized, by
itself randomization does not *eliminate* factors or personal
characteristics of participants (such as obesity, smoking and so on) that
could lead to biased interpretation of results. Randomization is merely a
tool that helps to reduce the likelihood of imbalances in how such factors
are distributed among a study’s volunteers.

For example, randomizing volunteers before a trial begins into two groups
where one will receive calcium supplementation and the other will receive
placebo should result in people having risk factors for heart attacks being
roughly evenly distributed or balanced between the two groups.

However, in the case of the New Zealand data, a critical review by
researchers not involved with the study found that the study groups (calcium
vs. placebo) were imbalanced. Specifically, the reviewers found that people
who were given calcium tended to have risk factors for cardiovascular
disease compared to people who did not receive calcium. This imbalance or
difference in the distribution of cardiovascular risk factors was
statistically significant. These imbalances were not adequately adjusted for
by the New Zealand researchers when they tried to interpret the data.
Therefore, the possibility arises that the team’s conclusions were
inadvertently biased. That is, the connection apparently found between
calcium supplementation and heart attacks is a false one.
Quality

The many methods of confirming an outcome, such as a heart attack, in the
New Zealand team’s studies is another source of problems. The researchers
relied a great deal on patients reporting if they did or did not have a
heart attack or were hospitalized. This use of self-reported data generally
does not produce high-quality conclusions. Indeed, other studies have found
that relying on self-reports of heart attack is not reliable. An example of
this unreliability is that in the 2008 reanalysis, 45 heart attacks were
reported by patients but medical evidence for only 31 heart attacks could be
found. There are additional problems (mostly statistical) related to the
self-reporting of heart attacks that we will not detail.
Calcium as a possible cause of heart attacks

Another issue with the New Zealanders’ work is that they claim that taking
calcium supplements in the studies they re-analyzed likely led to a large
and unnatural increase in the concentration of calcium in the blood. This
large and unnatural increase somehow predisposes some people to develop a
heart attack. There is currently no evidence to support such a claim.

Most of the studies re-analysed by the New Zealand team used a formulation
called calcium carbonate in doses of between 600 and 1,200 mg per day. At
these doses, calcium carbonate has not been shown to damage cells in people.

Increasingly, calcium is taken with vitamin D, as this vitamin helps the
body absorb calcium. A subsequent review by the New Zealand team of people
who took vitamin D with or without supplementary calcium found that vitamin
D might reduce cardiovascular outcomes and that calcium had minimal and
non-significant effects on outcomes such as heart attack.
Timing

A strange finding from the New Zealand reanalysis is that if calcium were
somehow linked to heart problems, such problems tend to occur within the
first year of supplementation but not afterward. This does not make
biological sense and therefore weakens the case for calcium causing harm.
A look at the real world

In many high-income countries there has been an increase in the use of
calcium supplementation in the past 20 years. However, a review of heart
attack data collected in one high-income country, Australia, suggests that
the rising use of calcium supplements has not been linked to rising rates of
heart attacks in the average person. Instead, what the review found was that
heart attack rates have been falling.

Taken together, a critical examination of several important problems
associated with the New Zealand reanalysis suggests that the team’s
conclusions are hardly robust. Yet, despite its questionable methods, it may
be plausible that the New Zealand team could have found a signal of harm
that needs investigation. Until well-designed clinical trials can resolve
this issue, approaches that balance the need for calcium against the remote
plausibility of its cardiovascular risk may be needed to help guide
decisions by doctors and their patients. Canada’s leading bone health
organization, Osteoporosis Canada has taken such an approach, which we
explain below.
What to do?

The New Zealand data have underscored an issue that nutritionists and
dieticians have been repeating for several years: It is best to get your
nutrients from food rather than supplements. In food, nutrients are
available in forms that the body can easily digest and is used to. However,
not everyone can obtain their daily requirement of calcium from food.

Osteoporosis Canada has a commonsense approach as well as a handy
guide<http://www.osteoporosis.ca/index.php/ci_id/5535/la_id/1.htm>to
helping people easily assess the amount of calcium in common foods.

Osteoporosis Canada has stated that in spite of the New Zealand data people
should *not* stop taking calcium supplements. However, the organization
prefers that people obtain their daily calcium intake from food “whenever
possible.” This organization discourages the use of “high doses of calcium
supplements (1,000 mg/day)” by people, particularly post-menopausal women,
who do not need extra calcium or who need just a modest amount of calcium.
Osteoporosis Canada also says that people who are not able to meet their
calcium needs from food may use “low-dose supplements” containing either
calcium carbonate or calcium citrate. Perhaps most importantly of all,
Osteoporosis Canada encourages people to discuss their need for calcium
supplements with their physicians. This is particularly excellent advice as
each person’s cardiovascular risk is different.

These approaches by Osteoporosis Canada are entirely reasonable and reduce
the risk of possible harm that might arise from excessive calcium
supplementation while still helping people get the calcium they need to keep
bones healthy. Hopefully, a large funding agency such as the American
National Institutes of Health (NIH) will conduct a well-designed clinical
trial to provide clear and firm conclusions about calcium supplementation
and cardiovascular health.
A final word

To build and maintain healthy bones the body requires several nutrients and
exercise. In the case of a chronic inflammatory condition such as HIV,
relying just on calcium and vitamin D intake for optimal bone
health—particularly in people who have been diagnosed with osteopenia or
osteoporosis—is not optimal. In cases of osteopenia and osteoporosis,
prescription medicines are available to increase bone density and reduce the
risk of fractures.

For further information about nutrients for bone health see CATIE’s *A
Practical Guide to Nutrition for People Living with
HIV<http://www.catie.ca/en/practical-guides/22-managing-effects-hiv-and-meds-body#bonehealth>
.*

*—Sean R. Hosein*

REFERENCES:

   1. Meier C, Kränzlin M. Calcium supplementation, osteoporosis and
   cardiovascular disease. *Swiss Medical Weekly*. 2011 Aug 31;141:w13260.
   2. Lewis JR, Calver J, Zhu K, et al. Calcium supplementation and the
   risks of atherosclerotic vascular disease in older women: results of a
   5-year RCT and a 4.5-year follow-up. *Journal of Bone and Mineral
   Research*. 2011 Jan;26(1):35-41.
   3. Wilson C. Calcium supplements and osteoporosis: the heart of the
   matter. *Nature reviews. Endocrinology*. 2011 May 31;7(7):373.
   4. Abrahamsen B, Sahota O. Do calcium plus vitamin D supplements increase
   cardiovascular risk? *BMJ*. 2011 Apr 19;342:d2080.
   5. Burckhardt P. Potential negative cardiovascular effects of calcium
   supplements. *Osteoporosis International*. 2011 Jun;22(6):1645-7.
   6. Nordin BE, Lewis JR, Daly RM, et al. The calcium scare—what would
   Austin Bradford Hill have thought? *Osteoporosis International*. 2011 Jun
   2. [Epub ahead of print].
   7. Aspray TJ, Francis RM. Calcium and vitamin D supplementation and
   cardiovascular disease: quo vadis? *Maturitas.* 2011 Aug;69(4):285-6.
   8. Reid IR, Mason B, Horne A, et al. Randomized controlled trial of
   calcium in healthy older women. *American Journal of Medicine*. 2006
   Sep;119(9):777-85.
   9. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy
   older women receiving calcium supplementation: randomised controlled trial.
   *BMJ*. 2008 Feb 2;336(7638):262-6.
   10. Biggs WS. Calcium supplementation: Data were misrepresented.
*BMJ**.*2008 Feb 23;336(7641):404.
   11. Lappe JM, Heaney RP. Calcium supplementation: results may not be
   generalisable. *BMJ*. 2008 Feb 23;336(7641):403.
   12. Bolland MJ, Grey A, Avenell A, et al. Calcium supplements with or
   without vitamin D and risk of cardiovascular events: reanalysis of the
   Women’s Health Initiative limited access dataset and meta-analysis. *BMJ*
   *.* 2011 Apr 19;342:d2040.
   13. Prince RL, Zhu K, Lewis JR. Evidence of harm is unconvincing. *BMJ**.
   * 2011 Jun 7;342:d3541.
   14. Bolland MJ, Grey A, Reid IR. Calcium supplements and cardiovascular
   risk. *Journal of Bone and Mineral Research*. 2011 Apr;26(4):899.
   15. Lewis JR, Calver J, Zhu, et al. Reply to “Calcium supplements and
   cardiovascular risk.” *Journal of Bone Mineral Research*.
   2011;26(4):900-901.
   16. Heiss G, Hsia J, Pettinger M, et al. Calcium and heart attacks. No
   evidence for increased risk. *BMJ.* 2010 Sep 15;341:c4995.
   17. Cleland JG, Witte K, Steel S. Calcium supplements in people with
   osteoporosis. *BMJ*. 2010 Jul 29;341:c3856.
   18. Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements
   on risk of myocardial infarction and cardiovascular events: meta-analysis.
   *BMJ*. 2010 Jul 29;341:c3691.
   19. Tang BM, Nordin BE. Calcium supplementation does not increase
   mortality. *Medical Journal of Australia.* 2008 May 5;188(9):547.
   20. Bolland MJ, Grey AB, Reid IR. Re: Calcium supplementation does not
   increase mortality. *Medical Journal of Australia*. 2008 Jul 7;189(1):55.
   21. Hsia J, Heiss G, Ren H, et al. Calcium/vitamin D supplementation and
   cardiovascular events. *Circulation*. 2007 Feb 20;115(7):846-54.
   22. Osteoporosis Canada. *Calcium intake statement*. April 2011.
   23. Osteoporosis Canada. Calcium is good – are calcium supplements bad?
   May 2011.
   24. Holick MF. Vitamin D deficiency. *New England** Journal of Medicine*.
   2007 Jul 19;357(3):266-81.
   25. Holick MF, Binkley NC, Hike A, et al. Evaluation, treatment and
   prevention of vitamin D deficiency: an Endocrine Society Clinical Practice
   Guideline. *Journal of Clinical Endocrinology and Metabolism*. 2011
   Jul;96(7):1911-30.
   26. Wang TK, Bolland MJ, van Pelt NC, et al. Relationships between
   vascular calcification, calcium metabolism, bone density, and fractures.
   *Journal of Bone and Mineral Research.* 2010 Dec;25(12):2777-85.
   27. Sutter JR, McDowell H, Brown WE. Solubility study of calcium hydrogen
   phosphate. Ion-pair formation. *Inorganic Chemistry*. 1971;10(8):1638-43.



*CATIE-News Subscription Information*

CATIE-News is a moderated mailing list operated by the Canadian AIDS
Treatment Information Exchange to distribute information about HIV/AIDS and
related infections in Canada.

To see a directory of archived messages, visit CATIE's Web site at
http://www.catie.ca/en/catienews

To subscribe to the list, visit
http://orders.catie.ca/subscription/subscribe.shtml

To cancel your subscription to the list, visit
http://orders.catie.ca/subscription/unsubscribe_news.shtml

For assistance with your subscription from a real human being, please send a
message to web at catie.ca

CATIE-News is written by Sean Hosein, with the collaboration of other
members of the Canadian AIDS Treatment Information Exchange, in Toronto.
Your comments are welcome.

*Permission to Reproduce*

This document is copyrighted by the Canadian AIDS Treatment Information
Exchange (CATIE). All CATIE materials may be reprinted and/or distributed
without prior permission. However, reprints may not be edited and must
include the following text:

>From Canadian AIDS Treatment Information Exchange (CATIE). For more
information visit CATIE's Information Network at http://www.catie.ca

For permission to edit any CATIE material for further publication, please
send an e-mail to info at catie.ca

If you are changing your e-mail address, please be sure to inform us of this
change so that we can update your records and ensure that you continue to
receive the latest HIV information.

E-mail us at info at catie.ca
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://lists.resist.ca/pipermail/viva/attachments/20110922/e7153b81/attachment-0001.html>