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Vitamin D Deficiency Is a Genetic Disease

Hundreds of different studies show that lack of vitamin D is associated with increased risk for many diseases and premature death. A recent paper shows that people who have a genetic defect in their ability to respond to vitamin D are the ones who are at increased risk for hip fractures, heart attacks, certain cancers, and premature death (JAMA, November 14, 2012;308(18):1898-1905).

The researchers analyzed the vitamin D receptor in 304 patients (mean age of 74) with low vitamin D levels and compared them with 1,210 patients with normal concentrations of vitamin D and followed them for 15 years.

Their results show that people who are able to respond normally to vitamin D are not at increased risk for these diseases. VITAMIN D DEFICIENCY DID NOT INCREASE RISK FOR DISEASE OR DEATH IN PEOPLE WITH NO GENETIC DEFECT IN THEIR ABILITY TO RESPOND TO VITAMIN D.

Known genes that prevent the body from responding adequately to vitamin D include:
• genes encoding the vitamin D-binding protein,
• megalin,
• cubilin,
• CYP27B1,
• CYP24A1, and
• the vitamin D receptor (VDR)

Before vitamin D can do its job of helping the body respond to insulin, it must first attach to special hooks in cells called vitamin D receptors. This study shows that among people with low blood levels of vitamin D, those who have one genetic defect in their ability to respond to vitamin D are at a 40 percent increased risk for hip fractures, heart attacks and certain cancers. Those with two genetic defects are at an 82 percent increased risk for these diseases. People who have no genetic defects in their vitamin D receptors are not at increased risk for these diseases. There also was no increased risk for heart attacks and premature death in people who had defects in their vitamin D receptor but had NORMAL BLOOD LEVELS OF VITAMIN D.

This important research promises a whole new approach to treatment of vitamin D deficiency and our understanding of the many diseases associated with it. Other studies on vitamin D, including the two reported below, will need to be re-evaluated in light of the new information on genetic defects. At this time, tests for the defective genes are not available through any commercial laboratories, but that should change very quickly.

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Lack of Vitamin D Leads to Plaques in Diabetics

People with diabetes are at very high risk for heart attacks, and lack of vitamin D appears to be a major risk factor (Journal of Biological Chemistry, Nov. 9, 2012;287 (46):38482- 38494). Low levels of vitamin D are associated with entrance of white blood cells called macrophages into the walls of arteries, the first phase of developing the plaques that cause heart attacks. The authors checked heart attack risk factors:
• blood pressure,
• cholesterol,
• diabetes control,
• body weight,
• race, and
• low levels of vitamin D.
Only low levels of vitamin D correlated with macrophages stuck to walls of blood vessels.

THE STEPS THAT LEAD TO A HEART ATTACK: Inflammation, not cholesterol, causes heart attacks. Cholesterol deposition into arteries occurs late in the formation of plaques. Inflammation means your immune system is overactive. Immunity is supposed to be good for you. When a germ gets into your body, your immunity produces chemicals that dissolve the walls of invading bacteria and other germs, and your white blood cells and proteins are supposed to attack and kill that germ.

However, it is harmful when a person's immunity turns on and stays on. Certain white blood cells called monocytes flow in your bloodstream.

• When your immunity turns on, these monocytes become different cells called macrophages that invade your own tissues to search out and kill germs.
• They punch holes and cause an erosion in the inner linings in arteries.
• Then you bleed into that erosion and a clot forms.
• As the erosion starts to heal, a plaque starts to form.
• Only then does cholesterol start to deposit in that plaque.
• The plaque extends to cover larger areas of the inner lining of arteries.

WHAT HAPPENS DURING A HEART ATTACK?
• A heart attack occurs when a piece of the plaque breaks off from its mooring on the inner lining of the artery.
• The broken-off plaque then travels down the ever narrowing artery until it stops and blocks completely all blood flow through that artery leading to the heart muscle.
• Blocking blood flow to the heart muscle deprives the muscle of oxygen and that part of the heart muscle dies to cause a heart attack.
THE NEW DISCOVERY FROM THIS STUDY: In this study, of all the known heart attack risk factors, only low levels of vitamin D was associated with the first phase of forming plaques in arteries. A LOW LEVEL OF VITAMIN D WAS ASSOCIATED WITH MACROPHAGES ENTERING THE INNER LININGS OF ARTERIES. HIGHER LEVELS OF VITAMIN D HELPED PREVENT MACROPHAGES FROM ENTERING THE ARTERIES. The other heart attack risk factors were not associated with macrophages entering arteries.

This study shows that diabetics with blood levels of vitamin D below 75 nmol/L (30 ng/mL) had macrophage cells that were far more likely to stick to and enter the walls of arteries, which starts the processes that lead to a heart attack.

This would be another explanation why diabetics are at such high risk for suffering heart attacks. Many studies show that low levels of vitamin D are associated with increased risk for heart attacks in diabetics. The next phase is to set up a study and see if giving vitamin D to diabetics reduces their chances of suffering heart attacks.

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Low Vitamin D Linked to Heart Attacks, Hip Fractures and Cancers

Blood levels of hydroxy-vitamin D below 50 nmol/L (20 ng/mL) are associated with a 25 percent increase in the rate of heart attacks, hip fracture, cancer, and death (Ann Intern Med, May 1, 2012;156(9):627-634).

Since you get vitamin D primarily from sunlight, you would expect higher blood levels of vitamin D during the sunny months and reduced risk for heart attacks, hip fractures, some cancers, and premature death. The results of this study show exactly that finding. Vitamin D levels by season correspond to the 25 percent increased risk for these diseases:
• winter 43nmol/L (17ng/mL),
• spring 50nmol/L (20ng/mL),
• summer 61nmol/L (24 17ng/mL), and
• fall 55nmol/L (22 17ng/mL).

This study shows that when sunlight is lowest, vitamin D blood levels are lowest, and therefore heart attacks, hip fractures, and some cancers are highest.

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This week's medical history:
Wilt Chamberlain's Heart Attack

For a complete list of my medical history biographies go to Histories and Mysteries

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Recipe of the Week:

Artichoke-Wild Rice Salad

You'll find lots of recipes and helpful tips in The Good Food Book
- it's FREE

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November 25th, 2012
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About the Author: Gabe Mirkin, MD

Sports medicine doctor, fitness guru and long-time radio host Gabe Mirkin, M.D., brings you news and tips for your healthful lifestyle. A practicing physician for more than 50 years and a radio talk show host for 25 years, Dr. Mirkin is a graduate of Harvard University and Baylor University College of Medicine. He is board-certified in four specialties: Sports Medicine, Allergy and Immunology, Pediatrics and Pediatric Immunology. The Dr. Mirkin Show, his call-in show on fitness and health, was syndicated in more than 120 cities. Read More
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