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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 online ahead of print in 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.
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.
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