Vitamin D

What it is

Vitamin D comes in two main forms. Vitamin D3, cholecalciferol, is made in human skin from 7-dehydrocholesterol and is found in animal foods. Vitamin D2, ergocalciferol, is largely made commercially and added to foods. Both are used in supplements and fortified foods. They differ only in a side chain, and the Institute of Medicine described them as activated the same way and reported to give identical responses in the body.^[1] Replenish uses vitamin D3, cholecalciferol.

Neither form does anything until it is activated. The liver converts vitamin D to 25-hydroxyvitamin D, the main form in the blood and the one a blood test measures. The kidney then converts that to calcitriol, the active hormone.^[1] Calcitriol keeps blood calcium in range, mainly by stimulating calcium and phosphate absorption along the intestine and, together with parathyroid hormone, by releasing calcium from bone.^[1] For how vitamin D sits beside the calcium in Replenish, see calcium.

Few foods contain much vitamin D naturally: fatty fish, fish liver oil and egg yolk. In the United States, fluid milk is voluntarily fortified, at 400 IU per quart.^[1] Because vitamin D is fat-soluble, it is stored in fat tissue.^[1]

How much adults need

Source: Institute of Medicine, Dietary Reference Intakes for Calcium and Vitamin D (2011), Table S-2.^[2] Values assume minimal sun exposure. 1 mcg of vitamin D = 40 IU. RDA = Recommended Dietary Allowance; UL = Tolerable Upper Intake Level.

Amount in Replenish: confirmed at launch

Vitamin D is unusual among nutrients because the body can make it. The committee could not build sun into the RDA, because public health concerns about skin cancer rule out recommending it, so the values assume minimal sun exposure.^[2] The RDA is the intake expected to keep a blood level of 25-hydroxyvitamin D of about 50 nmol/L (20 ng/mL), which the committee judged enough for nearly everyone. Others have proposed cut-points ranging up to above 125 nmol/L (50 ng/mL); the committee warned that cut-points set higher than appropriate make deficiency look more common than it is.^[2]

The UL of 4,000 IU is not a target. The committee noted that intakes below 10,000 IU a day are not usually associated with toxicity, while 50,000 IU a day or more for weeks or months often is, with high blood calcium. It treated 10,000 IU as the level with no observed adverse effect and set the UL lower for public health protection, noting that the data did not show benefit above it. Some observational studies had also linked the highest blood levels with higher death rates.^[3]

What the evidence says

Bone. When the Institute of Medicine set the 2011 values, bone health was the only outcome with evidence strong enough to base requirements on. Proposed links to cancer, heart disease, diabetes, falls, immune function and other outcomes could not be tied reliably to vitamin D intake, and the studies often conflicted.^[2] Large trials since then have mostly agreed.

Cancer and heart disease. VITAL randomized 25,871 US men aged 50 and older and women aged 55 and older to 2,000 IU of vitamin D3 a day or placebo. Over a median of 5.3 years, vitamin D did not lower the rate of invasive cancer (hazard ratio 0.96) or of major cardiovascular events (hazard ratio 0.97).^[4]

Fractures. In the same trial, people were not chosen for low vitamin D or weak bones. Vitamin D3 did not reduce total fractures (hazard ratio 0.98), nonvertebral fractures or hip fractures, and the result did not change with baseline blood vitamin D level.^[5]

Mortality. The Australian D-Health trial gave 21,315 adults aged 60 and older 60,000 IU of vitamin D3 or placebo once a month for 5 years. During follow-up, average blood levels were 115 nmol/L in the vitamin D group and 77 nmol/L on placebo, but deaths from any cause did not fall (hazard ratio 1.04).^[6]

These trials tested vitamin D in people who were mostly not deficient. They do not show that correcting a real deficiency is pointless; the requirement exists because too little vitamin D harms bone. They show that adding vitamin D on top of an adequate level has not prevented these diseases. Why protein and activity matter more than any vitamin for keeping strength is covered in keeping muscle while on a GLP-1.

Safety and interactions

Too much. Vitamin D toxicity shows up as high blood calcium and high urine calcium.^[3] Symptoms can include loss of appetite, passing a lot of urine, heart rhythm problems, fatigue and calcium deposits in soft tissue.^[3] In VITAL, 2,000 IU a day for about 5 years showed no excess of high blood calcium or other adverse events.^[4] In three large US cohorts, vitamin D intakes of 1,000 IU a day or more were not significantly linked to kidney stones in two, with a suggestion of higher risk in the third; the authors could not rule out a higher risk at larger doses.^[7]

Thiazide diuretics. Thiazides reduce the calcium lost in urine and can raise blood calcium slightly, according to the hydrochlorothiazide label.^[8] Vitamin D raises calcium absorption from the gut.^[1] Anyone on a thiazide who adds vitamin D and calcium should let their prescriber know, so calcium can be checked if needed.

Glucocorticoids. In a US national survey of 22,650 people, those who had used oral steroids in the past 30 days were about twice as likely to have very low vitamin D (below 10 ng/mL) as non-users. This was a cross-sectional association, not proof that the drugs caused it.^[9]

Fat-absorption blockers. The label for orlistat, which blocks fat absorption, advises a daily multivitamin containing fat-soluble vitamins, taken at least 2 hours before or after the drug, such as at bedtime, because orlistat reduces absorption of some fat-soluble vitamins.^[10]

Anticonvulsants. The Institute of Medicine noted occasional reports of drug classes such as anticonvulsants speeding the breakdown of vitamin D.^[1]

If you take prescription medicine, ask your pharmacist or prescriber before adding a supplement.

In Replenish

Replenish contains vitamin D as vitamin D3, cholecalciferol, one of its six vitamins. It is part of how Replenish provides key vitamins and minerals.^† The amount per serving is published with the Supplement Facts panel on the Replenish page. The formula's other vitamins include vitamin C, and how vitamins fit around smaller meals is in which vitamins matter on a GLP-1 and what supplements to take with a GLP-1.