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Researchers Believe Vitamin D May be an Effective Way to Treat Heart Failure E-mail
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Activated vitamin D protects the heart against avoid overwork and enlargement, two of the hallmarks of heart failure, a University of Michigan study in animals shows. The results, the first to show vitamin D can prevent the damaging effects of heart failure, add heart health to the growing list of vitamin D's benefits.

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.

About Cardiovascular Disease

Cardiovascular disease is a broad term that includes several more specific cardiovascular conditions. Cardiovascular disease is the leading killer in the US.

Common heart conditions include: 
  • Arrhythmias. Irregular, or abnormally fast or slow, beating of the heart. The heart beat is controlled by electrical impulses. When the timing or frequency of these electrical impulses are disrupted, arrhythmias develop. Some arrhythmias are quite serious. An example is ventricular fibrillation, a severely abnormal heart rhythm that causes death unless treated right away by providing an electrical shock to the heart (called defibrillation). Others are less severe but can develop into more serious conditions over time. A particular concern is atrial fibrillation. Atrial fibrillation is rapid, irregular beating of the upper chambers of the heart. The chambers can quiver instead of beating in a regular pattern. Blood is not fully pumped out of them and may pool and clot.
  • Cardiomyopathy. A weakening of the heart muscle or a change in heart muscle structure. It often results in inadequate heart pumping or other heart function abnormalities. These can result from various causes, including prior heart attacks, viral or bacterial infections, and others.
  • Congenital Heart Disease. Malformations of heart structures, present during pregnancy or at birth. These may be caused by genetic factors or by adverse exposures during pregnancy. Examples include holes in the walls that divide the heart chambers, abnormal heart valves, and others. Congenital heart defects can disrupt the normal flow of blood through the heart. Congenital heart defects are the most common type of major birth defect.
  • Coronary Heart Disease (CHD). CHD is the most common type of heart disease. CHD occurs when the coronary arteries, that supply blood to the heart muscle, become hardened and narrowed due to the plaque buildup. The plaque buildup and the narrowing and hardening of the arteries is called atherosclerosis. Plaques are a mixture of fatty substances including cholesterol and other lipids. Blood flow and oxygen supply to the heart can be reduced or even fully blocked with a growing plaque. Plaques may also rupture and cause blood clots that block arteries. CHD can lead to a heart attack. Angina, the most common symptom of CHD can also occur. Angina is chest pain or discomfort that occurs when the heart muscle is not getting enough blood. Irregular heart beats, called arrhythmias, can develop.Over time, CHD can weaken the heart muscle and lead to heart failure, a serious problem where the heart cannot pump blood the way that it should.
  • Heart Attack. A heart attack , also called a myocardial infarction may occur when blood supply to the heart is severely reduced or completely blocked. When blood flow is restricted the heart muscle cells do not receive enough oxygen and begin to die. The more time that passes without treatment to restore blood flow, the greater the damage to the heart. This damage can cause irregular heart rhythms or even sudden cardiac arrest or stopping of the heart beat. Death can result. Coronary artery disease is the chief underlying cause of a heart attack. A less common cause of a heart attack is a severe spasm of a coronary artery that reduces the blood supply to the heart.
  • Heart Failure. This may also be called congestive heart failure or chronic heart failure. Heart failure is a condition where the heart cannot pump enough blood and oxygen to meet the needs of other body organs. Heart failure does not mean that the heart has stopped, but that it cannot pump blood the way that it should. Heart failure is a serious condition. There is no cure for heart failure at this time, except a heart transplant. Once diagnosed, medicines are needed for the rest of the person's life.
  • Peripheral Arterial Disease (PAD). Hardening of the arteries that supply blood to the arms and legs. PAD is usually the result of atherosclerosis, the buildup of plaque and narrowing of the arteries. Blood flow and oxygen to the muscles in the arms and legs can be reduced or even fully blocked. Painful leg muscles, numbness, swelling in the ankles and feet, and weak pulse in the feet are some of the signs and symptoms of PAD.
  • Rheumatic Heart Disease.This condition is damage to the heart valves and other heart structures due to inflammation and scarring caused by rheumatic fever, which occurs from streptococcal infection.Heart disease is an umbrella term for a number of different diseases affecting the heart.Heart disease is a number of abnormal conditions affecting the heart and the blood vessels in the heart.

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.

Funding for the study came from the National Institutes of Health.


Citations:
 
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