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Back: Vitamin D Deficiency

“Vitamin D Deficiency and All Cause Mortality"

Jeff Unger Picture

 Jeff Unger, MD
   PCMG Steering Committee Member
   Charlotte, North Carolina 
   The Unger Primary Care Medical Center
   Associate Director for Metabolic Studies
   Catalina Research Institute
   Chino, Californina

A large population-based study published this month in the Archives of Internal Medicine supports a well established link between low levels of vitamin- D (25[OH]D) to mortality.  Subjects in the lowest quartile of vitamin-D levels (<17.8 ng/mL) had a 26 % higher risk of all-cause mortality and a similar risk of cardiovascular disease mortality. No association was noted between low vitamin-D levels and cancer mortality.

Risk factors for vitamin-D deficiency in the general population include:

  • Advancing age
  • Female sex
  • Smokers
  • Patients with diabetes
  • Higher Body mass indexes (BMI)
  • Non-white race/ethnicity

During 8.7 years of follow-up of over 13, 000 subjects, 1806 deaths were recorded including 777 from cardiovascular disease. The mortality ratio for CVD for subjects in the lowest vs. the highest quartile of vitamin D levels was 1.20. In fact, the authors of the study noted that cardiovascular disease may be progressive in patients with low vitamin D levels. The risk of heart disease was more prominent in patients with low vitamin D levels who had no evidence of CVD at the beginning of the study. This also suggests that vitamin D plays a role in the pathogenesis of CVD before the disease becomes well established.

Humans get vitamin D from exposure to sunlight, from their diet and from dietary supplements. A diet high in oily fish prevents vitamin D deficiency. Sunlight penetrates the skin and converts 7-dehydrocholesterol to pre-vitamin D3, which is rapidly converted to vitamin D3. Excess exposure to sunlight also destroys vitamin D3 so that vitamin D3 intoxication does not occur. Vitamin D from the skin and diet is metabolized in the liver to 25-hydroxyvitamin D, which is used to determine a patient’s vitamin D status.

Vitamin D deficiency is defined by most experts as a 25-hydroxyvitamin D level of less than 20 ng per ml. Approximately 1 billion people worldwide have vitamin D deficiency or insufficiency.  More than 50 % of postmenopausal women talking medications for osteoporosis have suboptimal levels of 25-hydroxyvitamin D (< 30 ng/ml).

Vitamin-D deficiency can cause the following clinical problems:

1) Osteoporosis. Without vitamin-D, only 10-15 % of dietary calcium and 60 % of phosphorous is absorbed. The interaction of 1,25 dihydroxyvitamin D with the vitamin D receptor increases the efficiency of intestinal calcium absorption to 30-40 % and phosphorous absorption by approximately 80 %.

2) Secondary hyperparathyroidism.  As vitamin D deficiency progresses, the parathyroid glands become maximally stimulated resulting in secondary hyperparathyroidism. Clinically, these patients experience severe bone pain and osteomalacia. Patients are often misdiagnosed as having fibromyalgia, chronic fatigue syndrome or depression.

3) Muscle weakness and falls. Skeletal muscles have a vitamin D receptor and require vitamin D for maximum function. A meta-analysis of 5 randomized clinical trials (a total of 1237 subjects) revealed that increased vitamin D intake reduced the risk of falls by 22 %.

4) Insulin resistance. Vitamin D deficiency promotes insulin resistance, decreased insulin production and is associated with the metabolic syndrome. One study showed that combined daily intake of 1200 mg of calcium and 800 IU of vitamin D lowered the risk of type 2 diabetes by 33 % as compared with a daily intake of less than 600 mg of calcium and less than 400 IU of vitamin D (Pittas, et al. Diabetes Care. 2006; 29:650-656).

5) Cardiovascular disease. In a study of patients with hypertension who were exposed to ultraviolet B radiation 3 times a week for 3 months, 25-hydroxyvitamin D levels increased by 180% while both systolic and diastolic blood pressure was reduced by 6 mm Hg (Krause, et al. Lancet 1998;352;709-710). Vitamin D deficiency is also associated with congestive heart failure and elevated levels of inflammatory cytokines (c-reactive protein and interleukin-10).

6) Mental illness. Low levels of vitamin D have been associated with a higher risk of depression and schizophrenia.  This suggests that vitamin D may be necessary for brain development and neuronal stability.

Recommended daily intake of vitamin D are 200 IU for children and adults up to age 50, 400 IU for adults 51-70 years of age and 600 IU for adults 71 years of age and older. However, without adequate sunlight exposure children and adults will require up to 1000 IU per day of vitamin D.

Unless contraindicated, patients should be encouraged to spend at least 15 minutes in the sun daily. Consuming diets rich in “oily fish” should be advised. Vitamin –D levels should be assessed in patients at risk of osteoporosis, cardiovascular disease as well as in those with diabetes. Vitamin D supplements should be provided to those with low levels of serum 25-hydroxyvitamin D.

Are you obtaining serum vitamin D levels routinely in your patients with cardiovascular disease, osteoporosis and diabetes?

Are you advising patients at high risk for CVD to spend at least 15 minutes daily outside exposed to sunlight?

Let us know your answers to these questions by visiting our blog by clicking here. 

Jeff Unger, MD

Further reading:

1) Melamed ML, Michos ED, Post W, et al. 25-hydroxyvitamin D levels and the risk of mortality in the general population.  Archives Intern Med. 2008; 168: 1629-1637.

2) Holick M. Vitamin D deficiency. NEJM. 2007.357:266-281.