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Vitamin D
Charles J. Glueck MD, Medical Director, Alliance Cholesterol Center Cincinnati OH.
ABC Building, 3200 Burnet Avenue, Cincinnati OH, 45229
Email: [email protected] Phone 513-­924-­8250 Fax 513-­924-­8273
Introduction
Vitamin D is a fat-­soluble vitamin. Vitamin D is found in many dietary sources such as fish, eggs, fortified milk, and cod liver oil.
The sun also contributes significantly to the daily production of vitamin D, and as little as 10 minutes of exposure is thought to
be enough to prevent deficiencies.
The term "vitamin D" refers to several different forms of this vitamin. Two forms are important in humans: ergocalciferol (vitamin
D2) and cholecalciferol (vitamin D3). Vitamin D2 is synthesized by plants. Vitamin D3 is synthesized by humans in the skin
when it is exposed to ultraviolet-­B (UVB) rays from sunlight. Foods may be fortified with vitamin D2 or D3.
Function of Vitamin D in the Body
The major biologic function of vitamin D is to maintain normal blood levels of calcium and phosphorus. Vitamin D aids in the
absorption of calcium, helping to form and maintain strong bones. Recently, research also suggests vitamin D may provide
protection from osteoporosis, hypertension (high blood pressure), cancer, and several autoimmune diseases.
Vitamin D Deficiency
Prevalence
Vitamin D deficiency seems to be common in the U.S. It is estimated the 25% of U.S. adults have less than 18 nanograms per
milliliter of vitamin D (severe vitamin D deficiency). Overall, 40% of men and 50% of women are thought to be lower than the
healthy level of vitamin D (28 nanograms per milliliter). The people most at risk are anyone who spends a lot of time indoors
(the elderly and the homebound, for example) and people with dark skin (dark skin absorbs less sunlight).
Major Causes of Vitamin D Deficiency
Aging: With advancing age, people are more likely to stay indoors. Persons in rest homes or similar institutions are at extremely high
risk of vitamin D deficiency symptoms without supplementation.
Covering all exposed skin or using sunscreen whenever outside: Applying sunscreen with an SPF factor of 8 reduces production of vitamin D by 95%. Applying sunscreen with higher SPF
reduces vitamin D production even more.
Dark skin: Dark skin produces less vitamin D than light skin. The risk of vitamin D deficiency is especially high in dark-­skinned people
who live far from the equator.
Exclusively breast fed infants: African-­American who are exclusively breast fed and do not receive vitamin D supplementation are at high risk of vitamin D
deficiency symptoms, particularly if receive little sun exposure. The vitamin D content of mother's milk simply isn't enough for
the infant.
Fat malabsorption syndromes: Vitamin D deficiency symptoms are also common in cystic fibrosis and many forms of liver disease impairing the absorption of
vitamin D from food.
Inflammatory bowel disease: People with inflammatory bowel disease such as inflammatory bowel disease or Crohn's disease are at increased risk of
vitamin D deficiency symptoms, especially those who have had small bowel resections.
Obesity: Vitamin D deficiency symptoms increase in people who are obese. Since vitamin D is fat-­soluble, it can accumulate in body
fat, making it less available to other parts of the body.
Health Risks associated with Vitamin D Deficiency
When vitamin D levels are low, body just doesn’t seem to work as well. Vitamin D deficiency has been linked to
Rickets and osteomalacia (In children, vitamin D deficiency causes rickets, which results in skeletal deformities.
In adults, vitamin D deficiency can lead to osteomalacia, which results in muscular weakness in addition to
weak bones).
High blood pressure
Insulin problems
Diabetes risk-­-­ Receptors for vitamin D have been found on pancreatic cells that make insulin (leading to a
theoretical connection between vitamin D and diabetes).
Obesity
Proximal myopathy and muscle pains may occur in moderate or severe vitamin D deficiency
Less well known is the impact of vitamin D deficiency on depression, immunity and autoimmunity.
Vitamin D Upper Limit
If you absolutely avoid the sun, you should have your 25(OH)D level measured and remember that a maximum of two pills a
day (50 ug or 2,000 IU) is the upper limit (UL) currently listed by the Food and Nutrition Board as the amount not to exceed
unless under the care of a physician. When it comes to vitamin D, the right amount is good—a lot is not better and can be
dangerous. However, 2,000 IU a day is simply not enough for many people to get the full benefit of vitamin D, nor is it enough
to keep vitamin D levels around 50 ng/mL, especially in the winter.
How to Treat Vitamin D Deficiency
The easiest way to correct vitamin D deficiency is to take an oral dose of 50,000 IU of vitamin D once per week for 8 weeks. To
maintain vitamin D sufficiency, the patient should receive either 50,000 IU of vitamin D once or twice per month thereafter.
There is an intramuscular form of vitamin D that is usually not very bioavailable and can cause significant discomfort;; therefore
it is not recommended. However, in Europe, intramuscular injection of 500,000 IU of vitamin D twice per year has appeared to
be effective in preventing vitamin D deficiency.
A multivitamin containing 400 IU of vitamin D is inadequate to satisfy the body's requirement. It is estimated that at least 1,000
IU of vitamin D per day is needed to satisfy the body's requirement.
Vitamin D excess
Taking very high daily doses of vitamin D—for example, 50 or more times the recommended daily allowance (RDA)—over
several months can cause toxicity and a high calcium level in the blood.
Who is at risk to overdose on Vitamin D?
Anyone who takes Vitamin D supplements CAN take too much Vitamin D. But those most at risk for Vitamin D toxicity are:
Children whose parents accidentally give them too much Vitamin D
Elderly people following incorrect instructions for supplementation
Adults who take more than 10,000 IU's per day for long periods of time.
These 3 categories comprise the largest numbers of people in the literature who get Vitamin D overdose symptoms.
Symptoms of Vitamin D Excess
Early symptoms are loss of appetite, nausea, and vomiting, followed by excessive thirst, weakness, nervousness, and high
blood pressure. Because the calcium level is high, calcium may be deposited throughout the body, particularly in the kidneys,
blood vessels, lungs, and heart. The kidneys may be permanently damaged and malfunction, resulting in kidney failure.
Diagnosis of Vitamin D Excess
Vitamin D excess is usually diagnosed when blood tests detect a high calcium level in a person who takes high doses of
vitamin D. The diagnosis is confirmed by measuring the level of vitamin D in the blood.
Treatment of Vitamin D Excess
Treatment consists of the following:
Stopping vitamin D supplements
Following a low-­calcium diet for a while to offset the effects of a high calcium level in the body
Taking drugs (such as corticosteroids or bisphosphonates) to suppress the release of calcium from the bones
Role of Vitamin D Deficiency in Statin Induced Myalgia
Statin drugs are the most commonly used medications for reducing cholesterol levels. They help prevent cardiovascular
disease through their cholesterol reducing effects. Statins are not free from side effects. They are well known to have the
ability to induce muscle pain (myalgia).
There has been a recent study which looked at the relationship between vitamin D levels and myalgia in more than 600
individuals taking statins. Some of the study subjects had myalgia, while some did not. In those with myalgia, blood vitamin D
levels were generally lower (28.6 v 34.2 ng/mL). Also low blood levels of vitamin D were found in 64 per cent of patients with
myalgia, compared to 43 per cent of symptom-­free individuals.
After this, some of the myalgic patients with vitamin D deficiency were treated with vitamin D at a dose of 50,000 IU each week
for 12 weeks. Vitamin D levels rose from an average of about 20 ng/ml to an average of 48 ng/ml.
But perhaps most importantly of all, this led to a resolution of myalgia in more than 92 per cent of the individuals treated.
This research suggested that vitamin D deficiency may be an underlying factor in myalgia in statin-­treated individuals.
Study
Low serum 25 (OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-­myalgia in statin-­treated
patients ¹.
Our specific aims were to determine whether low serum 25 (OH) vitamin D (D2 + D3) (<32 ng/mL) was associated with
myalgia in statin-­treated patients and whether the myalgia could be reversed by vitamin D supplementation while continuing
statins. After excluding subjects who took corticosteroids or supplemental vitamin D, serum 25 (OH) D was measured in 621
statin-­treated patients, which consisted of 128 patients with myalgia at entry and 493 asymptomatic patients. The 128 myalgic
patients had lower mean +/-­ standard deviation (SD) serum vitamin D than the 493 asymptomatic patients (28.6 +/-­ 13.2 vs
34.2 +/-­ 13.8 ng/mL, P < 0.0001), but they did not differ (p > 0.05) by age, body mass index (BMI), type 2 diabetes, or creatine
kinase levels. By analysis of variance, which was adjusted for race, sex, and age, the least square mean (+/-­ standard error
[SE]) serum vitamin D was lower in the 128 patients with myalgia than in the 493 asymptomatic patients (28.7 +/-­ 1.2 vs 34.3
+/-­ 0.6 ng/mL, P < 0.0001). Serum 25 (OH) D was low in 82 of 128 (64%) patients with myalgia versus 214 of 493 (43%)
asymptomatic patients (chi(2) = 17.4, P < 0.0001). Of the 82 vitamin-­D-­deficient, myalgic patients, while continuing statins, 38
were given vitamin D (50,000 units/week for 12 weeks), with a resultant increase in serum vitamin D from 20.4 +/-­ 7.3 to 48.2
+/-­ 17.9 ng/mL (P < 0.0001) and resolution of myalgia in 35 (92%). We speculate that symptomatic myalgia in statin-­treated
patients with concurrent vitamin D deficiency may reflect a reversible interaction between vitamin D deficiency and statins on
skeletal muscle.
Reference
1. Ahmed W, Khan N, Glueck CJ, Pandey S, Wang P, Goldenberg N, Uppal M, Khanal S. Low serum 25 (OH) vitamin D
levels (<32 ng/mL) are associated with reversible myositis-­myalgia in statin-­treated patients. Transl Res. 2009
Jan;;153(1):11-­6. Epub 2008 Dec 6.