Vitamin D

Vitamin D is the hormone that enhances intestinal absorption of calcium and insures healthy bone formation. The best way to obtain vitamin D is through direct exposure of the skin to sunlight, because ultraviolet B rays stimulate the skin to synthesize vitamin D3. 

Some people do not have adequate exposure to sunlight and are at higher risk of developing vitamin D deficiency. Examples include individuals who:

• Live in latitudes >35^o from the equator 
• Live in heavily polluted cities
• Belong to cultures that require clothing that covers their entire body
• Are institutionalized or homebound
• Have dark skin
• Apply sunscreen compulsively
• Are elderly (decreased skin synthesis)
• Are obese (vitamin accumulates in fat)

Individuals living under these conditions can only receive adequate vitamin D by ingesting vitamin D rich foods or supplements. Individuals ingesting a balanced diet obtain 200 to 300 IU of vitamin D per day. In 2010, The Institute of Medicine recommended a daily intake of 600 IU for children and adults less than 70 years and 800 IU for adults older than 70 years. 

The Endocrine Society recommends a higher daily intake of 1500 to 2000 IU daily. In the United States, most vitamin D supplements contain vitamin D3 while prescriptions consist of vitamin D2.  Daily intake of 1000 IU of vitamin D increases plasma 25-hydroxyvitamin D (25-OHD) levels by 6-10 ng/mL. The prescription of 50,000 IU per month increases 25-OHD levels by 2 ng/mL. 

Vitamin D is inert and must be converted to its active form. The liver metabolizes it to 25-25-OHD, which is the major storage and circulating form of the hormone. The kidney converts 25-OHD to 1,25-dihydroxyvitamin D (1,25-OHD) under the regulation of parathyroid hormone. Therefore, normal vitamin D metabolism is dependent on sunlight exposure, intestinal absorption, and liver and kidney function. Vitamin D malabsorption may be associated with several GI disorders including Crohn disease, celiac disease, and pancreatic insufficiency.  

As vitamin D levels fall, the initial compensatory mechanism is increased PTH secretion, which stimulates the kidneys to increase phosphate excretion and decrease calcium excretion. Blood calcium levels remain normal until the very late stages of vitamin D deficiency. Alkaline phosphatase is usually elevated in response to the effect of PTH on calcium absorption from bone. The combination of a normal serum calcium, low phosphate, and elevated alkaline phosphatase is suggestive of disturbed vitamin D metabolism. If creatinine and BUN are also increased, the problem probably lies with the renal production of 1,25-OHD. If liver function tests are abnormal or serum albumin is low, the problem may be a low 25-OHD level due to liver disease or malnutrition.  

 When 1,25-OHD levels are low, either due to deficient vitamin D stores or renal disease, the parathyroid glands release more PTH to try to synthesize more 1,25-OHD. Since this cannot happen, increased PTH promotes calcium absorption from skeletal bone, which may result in severe bone disease. Children develop rickets, while adults develop osteomalacia. Osteomalacia may present as a diffuse, dull, aching pain affecting many areas of the body including ribs and sternum. Vitamin D deficiency is a major risk factor for bone loss, weakness and fracture in the elderly.  

Some patients taking long-term antiepileptic drug therapy develop a syndrome of low plasma 25-OHD, intestinal malabsorption of calcium, slight decrease in plasma calcium, secondary hyperparathyroidism and cortical osteopenia. In one study of inpatients on a medical ward, the most common disorders associated with vitamin D deficiency were anticonvulsant therapy, renal dialysis, nephrotic syndrome, and winter season.  Cirrhosis, malabsorption and glucocorticoid therapy were also contributory factors (NEJM 1998; 338:777).  

 In 2011, the Institute of Medicine (IOM) conducted a thorough analysis of existing studies on vitamin D and health. The IOM concluded that a plasma 25-OHD range of 12 to 16 ng/mL was a adequate to prevent rickets and osteomalacia and there was no benefit to increasing 25-OHD levels above 20 ng/mL. 

About the same time, the Endocrine Society issued guidelines that stated vitamin D levels below 20 ng/mL indicated deficiency and that levels between 21 to 29 ng/mL should be considered insufficient. These guidelines were interpreted by many clinicians to mean that everyone needed to have 25-OHD levels of 30 ng/mL or higher. 

The Endocrine Society justified these guidelines because an observational study had found that 21% of individuals with vitamin D levels between 20 and 30 ng/mL had osteomalacia. 

Many experts believed that the optimal concentration of 25-OHD was at least 30 ng/mL because parathyroid hormone begins to increase when 25-OHD levels decrease below this threshold (JAMA 292:1416-18, Sep 22/29, 2004). The American Association of Clinical Endocrinology recommends that physicians target a 25-OHD concentration between 30 and 50 ng/mL.

According to the National Health and Nutrition Examination Survey, 30 to 35% of individuals in the United States had vitamin D levels below 20 ng/mL in 2011. Individuals with intense sun exposure have a mean 25- hydroxyvitamin D level of 36 ng/mL and a range of 20 to 70 ng/mL.

A decade ago, physicians ordered vitamin D levels to assess bone health. In the early 2000s, observational studies suggested that vitamin D deficiency played an important role in the pathogenesis of cancer, cardiovascular disease, dementia, depression, diabetes, autoimmune disease, fractures, respiratory illnesses, and Parkinson’s disease. (J Am Coll Cardiol 2008;52:1949-56). Accordingly, demand for 25(OH) vitamin D testing and supplements skyrocketed.

However, subsequent randomized controlled trials have shown that vitamin D supplementation did not decrease the rates of cancer, cardiovascular disease, dementia, diabetes, bone fractures, or respiratory illnesses. 

More than 10 million vitamin D tests are still being performed annually in the United States, despite the fact that these tests are not recommended by the Endocrine Society, the National Academy of Medicine, or the U.S. Preventive Services Task Force. The Choosing Wisely campaign has endorsed the recommendation to not order population-based screening for vitamin D.