On The Shelf
Mary Warner
Cholecalciferol, a fat-soluble compound also known as vitamin D3, is one of two forms of vitamin D used to treat and prevent vitamin D deficiency and associated diseases, such as rickets. Vitamin D has properties of both a hormone and a vitamin and is necessary for bone formation and maintaining homeostasis of serum calcium. Vitamin D has also been shown to reduce inflammation in the lungs as well as lower viral replication in vitro, making it of clinical interest for treating COVID-19.
Function
As the naturally occurring form of vitamin D, cholecalciferol is produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. It is naturally present in very few foods, though it is commonly added to milk, cereal, and other food and is available as a dietary supplement.
Ergocalciferol (vitamin D2), commonly used as a food additive, differs only slightly in structure from cholecalciferol. The two forms are biologically equivalent, based on their ability to cure rickets, and most steps involved in the metabolism of cholecalciferol and ergocalciferol are identical. However, it appears that at high doses vitamin D2 is less potent than vitamin D3.
Both forms of vitamin D, whether obtained from sun exposure, food, or supplements, are biologically inert and must undergo hydroxylation twice for activation. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D, also known as calcidiol; this is followed by a second hydroxylation in the kidney that forms the physiologically active 1,25-dihydroxyvitamin D, also known as calcitriol.
Daily requirements and dietary sources
The RDA for vitamin D range from 400 IU for infants to 600 IU for children, teenagers, and adults. Adults older than 70 years should receive 800 IU per day, as the metabolism of cholecalciferol in the liver and kidneys may be compromised. In addition, older patients may experience less sunlight, and their aging skin may not synthesize cholecalciferol efficiently.
Most people get sufficient cholecalciferol from exposure to sunlight. However, because regular use of sunscreen to prevent skin cancer limits vitamin D synthesis in the skin, careful consideration of vitamin D intake from dietary sources is necessary. In the United States, milk and milk products are routinely supplemented with 100 IU of vitamin D per cup, making them the major sources of dietary vitamin D.
Vitamin D supplements and deficiency
Vitamin D deficiency may result not only from inadequate sunlight or dietary intake, but also from GI diseases, chronic renal failure, obesity or gastric bypass therapy, or long-term use of antiepileptic medications.
Vitamin D increases calcium and phosphate absorption from the small intestine, mobilizes calcium from bone, permits normal bone mineralization, improves renal reabsorption of calcium, and maintains serum calcium and phosphorus levels. The classic signs of vitamin D deficiency are rickets and osteoporosis.
While the incidence of rickets in the United States is low, it can occur in children who don’t drink milk and in infants who are breastfed by mothers who receive an inadequate intake of vitamin D.
If vitamin D supplementation is appropriate because of poor dietary intake or inadequate exposure to sunlight, a multivitamin supplement containing 600 IU to 800 IU of cholecalciferol taken daily is generally sufficient. The current upper level for vitamin D is 4,000 IU daily.
What to tell your patients
Ensure patients understand that taking more than 4,000 IU of vitamin D daily may lead to adverse effects, including anorexia, hypercalcemia, soft tissue calcification, kidney stones, renal failure, and increased risk of certain types of cancer.
Patients receiving doses of more than 4,000 IU daily as treatment for vitamin D deficiency should be under medical supervision and closely monitored for adverse effects. In addition, patients with renal or hepatic dysfunction require a hydroxylated vitamin D preparation, available only by prescription.
Patients may ask about taking vitamin D to prevent COVID-19 disease. Some studies show that vitamin D supplements can enhance immune response and that vitamin D deficiency can harm immune function and increase the risk of developing respiratory illnesses. However, to date, no research has been done on the effect of vitamin D supplements or vitamin D deficiency on the risk of contracting the new coronavirus that causes COVID-19. Caution patients not to take high doses of vitamin D as a way to protect against COVID-19.