Approach

The optimal serum concentration of 25-hydroxyvitamin D remains debated, but there is broad agreement that serum 25-hydroxyvitamin D concentrations <20 nanograms/mL are suboptimal for health.[1][79]​​​[117][67]​​​​​​​​​ Furthermore, many guidelines and experts recommend a serum 25-hydroxyvitamin D concentration >30 nanograms/mL, particularly in older adults, in order to maximize vitamin D effects on the skeleton and on calcium and phosphate metabolism.[118][119][83][84]​​​​ Newer evidence suggests that vitamin D may offer significant extraskeletal health benefits, including reducing the risk of complications during pregnancy, preventing the progression of prediabetes to diabetes, and lowering the risk of autoimmune disorders, along with other chronic health conditions.[4]

The amount of vitamin D required to achieve optimal concentrations depends on a wide variety of factors, including age, baseline 25-hydroxyvitamin D, body mass index, sun-exposure history, and the use of drugs that can affect vitamin D metabolism and intestinal absorption.

Correction of vitamin D deficiency and insufficiency in children will promote growth and deposition of calcium into the skeleton. Children with skeletal manifestations of rickets should be aggressively treated. The earlier the intervention, the more likely a favorable prognosis, with resolution of many of the associated skeletal deformities. This is especially true for deformities in the legs. See Rickets.

Correction of vitamin D deficiency in adults improves bone mineral density and stimulates mineralization of the collagen matrix, resulting in resolution of bone pain associated with osteomalacia.

Vitamin D replacement

The mainstay of treatment is the provision of vitamin D to correct the causative deficiency. Some experts recommend a goal of reaching and maintaining a serum 25-hydroxyvitamin D concentration in children and adults of >30 nanograms/mL, although the optimal goal remains debated.[3]​​​[118][119][83][84][120]​​​​ 

A child or adult may be considered vitamin D-insufficient if the serum 25-hydroxyvitamin D concentration is between 21 and 29 nanograms/mL or if history suggests lack of adequate daily vitamin D from supplements (400 IU/day for children <1 year of age; 600 IU/day for children ≥1 year of age; and 600-800 IU/day for adults depending on age, but possibly up to1500-2000 IU/day), diet, and/or adequate sun exposure.[79][85][86]​​ These patients may be considered for vitamin D replacement following shared decision-making.

Vitamin D deficiency in adults and children is corrected by treatment with vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) given orally for 6-8 weeks, followed by a lower maintenance dose continued throughout childhood and adulthood.[7][121][122]

Retesting serum 25-hydroxyvitamin D concentrations (e.g., after 2-3 months) is typical to assess effectiveness and adjust doses as needed. Once taking maintenance doses of vitamin D, the serum 25-hydroxyvitamin D concentration can typically be measured annually. See Monitoring.​​

High-dose vitamin D treatment

  • Some patients, for example, those with intestinal or fat malabsorption syndromes (including liver failure and obesity), or who have a history of gastric bypass surgery, do not respond to standard doses of vitamin D replacement. Therefore, higher daily oral doses may be required under specialist supervision.​ Patients taking anticonvulsants, glucocorticoids, or other drugs that activate the steroid and xenobiotic receptors (e.g., antiretroviral therapy [ART], rifampin, St. John's wort) may also require higher doses of vitamin D.

  • The threshold at which vitamin D becomes toxic is not well defined. The National Academy of Medicine sets the tolerable upper intake level (UL) for vitamin D at 4000 IU/day for healthy adults and children ages 9-18 years.[79] The UL is lower for infants and children up to 9 years, varying by age.

  • Vitamin D intoxication is rare and typically occurs only after very high doses are ingested consistently, often inadvertently. Toxicity generally develops with prolonged use of doses >50,000 IU/day over several months or years, although the exact threshold can vary from person to person based on factors such as kidney function, body weight and individual metabolism.[123] In the author’s opinion, patients may be given doses exceeding the National Academy of Medicine’s UL to correct deficiency (e.g., people with malabsorption syndromes). However, given the potential for toxicity, especially with long-term use, this requires specialist (endocrinology) oversight and close monitoring (e.g., calcium concentrations and for symptoms of hypercalcemia such as nausea, vomiting, mental cloudiness, and kidney damage which may indicate toxicity).

Older adults

  • Many guidelines recommend a serum 25-hydroxyvitamin D concentration >30 nanograms/mL in older adults.[118][119][83][84] However, other experts recommend a goal of >20 nanograms/mL in this age group.[67] 

  • Vitamin D given in conjunction with calcium supplementation to reduce fractures is recommended in the older population.[67] 

  • There have been concerns regarding safety, particularly the potential increased risk of falls and fractures in older people, at serum 25-hydroxyvitamin D concentrations > 50 nanograms/mL, although data are inconsistent.[87] According to one international consensus statement, daily low-dose regimens reduce the risk of falling in older people, compared with infrequent large bolus doses that may increase it.[67]

Pregnancy

  • Several studies in recent years have highlighted that women are at high risk for vitamin D deficiency, and that this is associated with adverse pregnancy outcomes including preeclampsia and gestational diabetes.[124][125]

  • Vitamin D supplementation has been shown to reduce adverse pregnancy outcomes when higher serum concentrations of 25-hydroxyvitamin D are achieved, with increased efficacy as the target level rises from 20 nanograms/mL to 40 nanograms/mL or 50 nanograms/mL.[126][127]

  • Currently, data on the optimal dose for vitamin D deficiency in pregnancy is lacking.[116][128]​ If deficiency of vitamin D is identified during pregnancy, supplementation with 1000-2000 IU/day of vitamin D is generally considered to be safe, according to the American College of Obstetricians and Gynecologists (ACOG).[116] Doses above 2000 IU/day of vitamin D are sometimes required, and may be recommended by the patient’s obstetrician, but are typically only used under specialist medical supervision, with appropriate monitoring for potential risks such as hypercalcaemia and toxicity.[129]

  • Seek specialist advice before starting treatment if a woman is pregnant.

Calcium and phosphate replacement

The National Academy of Medicine recommends an intake of 1000-1200 mg/day of elemental calcium in adults, depending on sex and age.[130] The Dietary Guidelines for Americans provides more information on recommended intake by sex and age including children: Dietary Guidelines for Americans, 2020-2025. Because inadequate calcium intake may contribute to vitamin D deficiency and many patients do not meet daily calcium requirements from dietary sources alone, all patients at risk of calcium deficiency should be given calcium supplementation.[88][131]​​​ This should continue indefinitely or until adequate intake is achieved through dietary sources. While some studies suggest no significant cardiovascular risk associated with calcium supplements, other research indicates potential concerns, particularly at higher doses.[132][133][134][135]​​​​​​​

Phosphate supplementation is not usually necessary unless there is an acquired or inherited disorder causing phosphate wasting in the kidneys, such as hypophosphatemic rickets or oncogenic osteomalacia.[8][9]​​​ These patients require phosphate supplementation in addition to vitamin D replacement and vitamin D metabolite. Caution should be exercised when giving phosphate supplements, because high-dose phosphate multiple times a day causes a reduction in ionized calcium, resulting in an increase in parathyroid hormone production and tertiary hyperparathyroidism. Therefore, smaller doses of phosphate should be taken more frequently throughout the day to maintain a normal serum phosphate level without causing significant hyperparathyroidism.

Disorders of vitamin D metabolism

Patients with acquired and inherited disorders of metabolism of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, or a defective recognition of 1,25-dihydroxyvitamin D, should receive vitamin D along with either 1,25-dihydroxyvitamin D3 (calcitriol) or one of its active analogs (e.g., paricalcitol or doxercalciferol), depending on the cause of the abnormality.[3]

Patients with chronic kidney disease have high-normal or elevated serum phosphate levels and a decreased capacity to produce 1,25-dihydroxyvitamin D, which causes secondary hyperparathyroidism. Therefore, they need to maintain a serum 25-hydroxyvitamin D of between 30 and 100 nanograms/mL and control their serum phosphate level by using a phosphate binder (e.g., calcium carbonate). In addition, if the estimated GFR is <50% of normal, they may also require 1,25-dihydroxyvitamin D3 or one of its active analogs (to treat and prevent secondary hyperparathyroidism).[3][14]

Ultraviolet B (UV-B) radiation exposure

Given that there are no defined safe exposure limits for UV-B exposure, people with vitamin D deficiency are not routinely treated with UV-B radiation.[136]

Use of this content is subject to our disclaimer