Vitamin
D Called the ‘Heart Tranquilizer’ in New Treatment for Heart Failure
Treatments with activated vitamin D prevented heart
muscle cells from growing bigger
By Anne Rueter, University Michigan
June 12, 2008 – Strong bones, a healthy immune
system, protection against some types of cancer: Recent studies suggest
there’s yet another item for the expanding list of Vitamin D benefits.
Vitamin D, “the sunshine vitamin,” keeps the heart, the body’s
long-distance runner, fit for life’s demands.
University of Michigan pharmacologist Robert U. Simpson, Ph.D.,
thinks it’s apt to call vitamin D “the heart tranquilizer.”
In studies in rats, Simpson and his team report the
first concrete evidence that treatment with activated vitamin D can
protect against heart failure. Their results appear in the July issue of
the
Journal of Cardiovascular Pharmacology.
In the study, treatments with activated vitamin D
prevented heart muscle cells from growing bigger – the condition, called
hypertrophy, in which the heart becomes enlarged and overworked in
people with heart failure. The treatments prevented heart muscle cells
from the over-stimulation and increased contractions associated with the
progression of heart failure.
About 5.3 million Americans have
heart failure, a progressive, disabling condition in which the heart
becomes enlarged as it is forced to work harder and harder, making it a
challenge even to perform normal daily activities.
Many people with heart disease or poorly controlled
high blood pressure go on to experience a form of heart failure called
congestive heart failure, in which the heart’s inability to pump blood
around the body causes weakness and fluid build-up in lungs and limbs.
Many people with heart failure, who tend to be older, have been found to
be deficient in vitamin D.
“Heart failure will progress despite the best
medications,” says Simpson, a professor of pharmacology at the
U-M Medical School. “We think vitamin D retards that progression and
protects the heart."
The U-M researchers wanted to show whether a form
of vitamin D could have beneficial effects on hearts that have developed
or are at risk of developing heart failure. They used a breed of
laboratory rats predisposed to develop human-like heart failure.
The researchers measured the effects of activated
Vitamin D (1,25 dihydroxyvitamin D3, a form called calcitriol) in rats
given a normal diet or a high-salt diet, compared to control group rats
given either of the same two diets, but no vitamin D treatment. The rats
on the high-salt diet were likely to develop heart failure within
months.
The rats on the high-salt diet, comparable to the
fast food that many humans feast on, quickly revealed the difference
vitamin D could make.
“From these animals, we have obtained exciting and
very important results,” Simpson says.
After 13 weeks, the researchers found that the
heart failure-prone rats on the high-salt diet that were given the
calcitriol treatment had significantly lower levels of several key
indicators of heart failure than the untreated high-salt diet rats in
the study.
The treated rats had lower heart weight. Also, the
left ventricles of the treated rats’ hearts were smaller and their
hearts worked less for each beat while blood pressure was maintained,
indicating that their heart function did not deteriorate as it did in
the untreated rats.
Decreased heart weight, meaning that enlargement
was not occurring, also showed up in the treated rats fed a normal diet,
compared to their untreated counterparts.
Simpson and his colleagues have explored vitamin
D’s effects on heart muscle and the cardiovascular system for more than
20 years. In 1987, when Simpson showed the link between vitamin D and
heart health, the idea seemed far-fetched and research funding was
scarce. Now, a number of studies worldwide attest to the vitamin D-heart
health link (see citations below).
The new heart insights add to the growing awareness
that widespread vitamin D deficiency—thought to affect one-third to
one-half of U.S. adults middle-aged and older—may be putting people at
greater risk of many common diseases.
Pharmaceutical companies are developing anti-cancer
drugs using vitamin D analogs, which are synthetic compounds that
produce vitamin D’s effects. There’s also increasing interest in using
vitamin D or its analogs to treat autoimmune disorders.
In more than a dozen types of tissues and cells in
the body, activated vitamin D acts as a powerful hormone, regulating
expression of essential genes and rapidly activating already expressed
enzymes and proteins. In the heart, Simpson’s team has revealed
precisely how activated vitamin D connects with specific vitamin D
receptors and produces its calming, protective effects. Those results
appeared in the February issue of
Endocrinology.
Sunlight causes the skin to make activated vitamin
D. People also get vitamin D from certain foods and vitamin D
supplements. Taking vitamin D supplements and for many people, getting
sun exposure in safe ways, are certainly good options for people who
want to keep their hearts healthy.
But people with heart failure or at risk of heart
failure will likely need a drug made of a compound or analog of vitamin
D that will more powerfully produce vitamin D’s effects in the heart if
they are to see improvement in their symptoms, Simpson says.
Vitamin D analogs already are on the market for
some conditions. One present drawback of these compounds is that they
tend to increase blood calcium to undesirable levels. Simpson’s lab is
conducting studies of a specific analog which may be less toxic, so
efforts to develop a vitamin D-based drug to treat heart failure are
moving a step closer to initial trials in people.
Editor’s Notes:
In addition to Simpson, other U-M authors include
Peter Mancuso, Ph.D., of the U-M Department of Environmental Health
Sciences; Ayesha Rahman, Ph.D., Stephen D. Hershey, M.D., Loredana Dandu
and Karl A. Nibbelink, M.D. of the Department of Pharmacology in the U-M
Medical School.
Vitamin D deficiency related to an increasing number
of conditions and to total mortality
After 13 weeks, the researchers found that the
heart failure-prone rats on the high-salt diet that were given the
calcitriol treatment had significantly lower levels of several key
indicators of heart failure than the untreated high-salt diet rats in
the study.