[e-drug] Vitamin A supplements may damage bones

[graya1@nu.ac.za]

E-DRUG: Vitamin A supplements may damage bones
----------------------------------------------------
[interesting piece on side-effects of vitamin A, when taken unnecessarily.
Thanks to Andy of DRUGINFO for picking this up. Copied as fair use. WB]

Hi all

This is not intended as evidence against Vit A supplementation in a
developing country context, or in situations where Vit A levels are known
to be low and supplementation has proven to be of benefit. Nevertheless, it
is a salutary lesson to those who consider vitamins in general to be
inherently safe and useful, regardless of dose or need. The NYT/AP story is
here as "fair use", with the original NEJM abstract appended below.

regards
Andy Gray
graya1@nu.ac.za
~~~

http://www.nytimes.com/aponline/national/AP-Vitamin-A-Fractures.html
Vitamin A Supplements May Hurt Bones
By THE ASSOCIATED PRESS
Filed at 8:09 p.m. ET

Taking vitamin A supplements can weaken the bones and increase the risk of
fractures up to seven times, according to a large Swedish study.

The research, conducted on men, confirms three earlier studies in women
showing that high intake of vitamin A raises the risk of broken hips and
weak bones. The latest study is the first to measure levels of the vitamin
in blood, rather than just asking about diet and supplement use.

The three-decade study and other evidence suggest that daily vitamin A
consumption of more than 1.5 milligrams can be dangerous, and that most
people should not take vitamin A supplements.

Current dietary recommendations call for only 0.7 mg of vitamin A for women
and 0.9 mg for men a day. That is easily supplied by a healthy diet. But
many popular multivitamins contain 0.75 mg to 1.5 mg of vitamin A,
generally listed on labels as 2,500 international units and 5,000 IUs,
respectively.

``Vitamin A is potentially harmful,'' said Dr. Donald Louria, chairman
emeritus of preventive medicine at the University of Medicine and Dentistry
of New Jersey in Newark, N.J. ``Unless there is a known medical reason like
certain diseases of the eye, people should not be taking vitamin A
supplements.''

The study by doctors at University Hospital in Uppsala was reported in
Thursday's New England Journal of Medicine. It involved 2,322 men.

Vitamin A is known as an antioxidant. Antioxidants are believed to reduce
the risk of cancer and heart disease. Government studies show one-third to
one-half of Americans take vitamin A or multivitamins containing it.

Vitamin A can interfere with cells that produce new bone, stimulate cells
that break down old bone and interfere with vitamin D, which helps the body
maintain normal calcium levels.

In the study, about one-fifth, or roughly 465 of the men, were found to be
at risk because they had the highest levels of vitamin A. The men were
about 2 1/2 times more likely to break a hip and 65 percent more likely to
suffer any fracture than those with lower levels of the vitamin in their
blood.

Those in the 99th percentile were about seven times more likely to break a
bone.

Louria said that people should not take fish oil supplements or eat liver
more than once a week, but that multivitamins containing 0.1 mg or less of
vitamin A are fine for people eating a healthy diet.

Large amounts of vitamin A are found in beef liver and fish liver oils;
smaller amounts are in egg yolks, butter and cream. Milk and some cereals
are fortified with vitamin A and, per serving, provide about 10 percent of
daily needs. And substances in dark green, leafy vegetables and yellow
vegetables and fruits are converted to vitamin A in the body.

Annette Dickinson, acting president of the trade group for supplement
makers, the Council for Responsible Nutrition, said the Swedish men had an
unusually high intake of vitamin A, even though very few were taking
supplements.

``I don't think there's a reason now from the studies we have before us to
say that multivitamins containing ordinary amounts of vitamin A are
harmful,'' Dickinson said. She said that in many multivitamins, much of the
vitamin A is in the form of beta-carotene, which studies have shown does
not weaken bones.

The study had some shortcomings: Blood levels of vitamin A were measured
only once, and the participants' reports of diet and supplement use 20
years later did not match well with their earlier vitamin A blood levels.

^------

On the Net:

National Osteoporosis Foundation: http://www.nof.org

Trade group for supplement makers: http://www.crnusa.org

American Dietetic Association: http://www.eatright.org

~~~
http://content.nejm.org/cgi/content/short/348/4/287
Serum Retinol Levels and the Risk of Fracture

Karl Michaëlsson, M.D., Hans Lithell, M.D., Bengt Vessby, M.D., and Håkan
Melhus, M.D.

Volume 348:287-294  January 23, 2003  Number 4

ABSTRACT

Background Although studies in animals and epidemiologic studies have
indicated that a high vitamin A intake is associated with increased bone
fragility, no biologic marker of vitamin A status has thus far been used to
assess the risk of fractures in humans.

Methods We enrolled 2322 men, 49 to 51 years of age, in a population-based,
longitudinal cohort study. Serum retinol and beta carotene were analyzed in
samples obtained at enrollment. Fractures were documented in 266 men during
30 years of follow-up. Cox regression analysis was used to determine the
risk of fracture according to the serum retinol level.

Results The risk of fracture was highest among men with the highest levels
of serum retinol. Multivariate analysis of the risk of fracture in the
highest quintile for serum retinol (>75.62 µg per deciliter [2.64 µmol per
liter]) as compared with the middle quintile (62.16 to 67.60 µg per
deciliter [2.17 to 2.36 µmol per liter]) showed that the rate ratio was
1.64 (95 percent confidence interval, 1.12 to 2.41) for any fracture and
2.47 (95 percent confidence interval, 1.15 to 5.28) for hip fracture. The
risk of fracture was further increased within the highest quintile for
serum retinol. Men with retinol levels in the 99th percentile (>103.12 µg
per deciliter [3.60 µmol per liter]) had an overall risk of fracture that
exceeded the risk among men with lower levels by a factor of seven
(P<0.001). The level of serum beta carotene was not associated with the
risk of fracture.

Conclusions Our findings, which are consistent with the results of studies
in animals, as well as in vitro and epidemiologic dietary studies, suggest
that current levels of vitamin A supplementation and food fortification in
many Western countries may need to be reassessed.

Source Information

>From the Department of Surgical Sciences, Section of Orthopedics (K.M.),
the Department of Public Health and Caring Sciences, Sections of Geriatrics
(H.L.) and Clinical Nutrition Research (B.V.), and the Department of
Medical Sciences, Section of Clinical Pharmacology (H.M.), University
Hospital, Uppsala, Sweden.

Address reprint requests to Dr. Michaëlsson at the Department of Surgical
Sciences, Section of Orthopedics, University Hospital, S-751 85 Uppsala,
Sweden, or at karl.michaelsson@surgsci.uu.se.

~~~~~~~~~~~~~~~~~~~
Andy Gray MSc(Pharm) FPS
Senior Lecturer
Dept of Experimental and Clinical Pharmacology
Nelson R Mandela School of Medicine
University of Natal
PBag 7 Congella 4013
South Africa
Tel: +27-31-2604334/4298 Fax: +27-31-2604338
email: graya1@nu.ac.za or andy@gray.za.net


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