Does the timing of taking Vitamin D3 (Cholecalciferol) matter?

From the Guidelines

The timing of taking Vitamin D3 (Cholecalciferol) does not significantly matter, as its half-life is 2 weeks to 3 months and it is stored primarily in adipose tissue, allowing for flexible dosing schedules. According to the study by Demer et al. 1, the use of the terms "daily" and "per day" in vitamin D recommendations may give a false impression that a day without sunshine requires a dose of supplement. The study suggests that vitamin D-hormones may not require daily, weekly, or even monthly replenishment, and that summer sun exposure may provide enough for the winter.

Key Points to Consider

• The half-life of 25(OH)D3 is 2 weeks to 3 months, allowing for stored sources of vitamin D to be released back into the plasma 1
• Vitamin D is stored primarily in adipose tissue and, to a lesser extent, in the liver, enabling flexible dosing schedules 1
• Major institutions have used dosing schedules as infrequent as once every 1–4 months, highlighting the flexibility in timing 1
• The requirement for vitamin D may vary depending on age (< 70 years or > 70 years) or season (i.e., summer vs. winter) 1

Practical Considerations

• For most people taking a standard daily supplement (typically 1,000-4,000 IU), consistency is more important than specific timing
• Morning or evening dosing is fine as long as a regular schedule is maintained
• If taking high doses (prescribed by a healthcare provider), following their specific instructions becomes more important
• Potential interactions with other supplements or medications should be considered, and healthcare providers consulted if necessary

From the FDA Drug Label

The in vivo synthesis of the major biologically active metabolites of vitamin D occurs in two steps. There is a time lag of 10 to 24 hours between the administration of vitamin D and the initiation of its action in the body due to the necessity of synthesis of the active metabolites in the liver and kidneys.

The timing of taking Vitamin D3 (Cholecalciferol) does matter in the sense that there is a time lag of 10 to 24 hours between administration and the initiation of its action in the body.

• The delay in action is due to the necessary synthesis of active metabolites in the liver and kidneys. 2

From the Research

Vitamin D3 Absorption and Meal Conditions

The timing of taking Vitamin D3 (Cholecalciferol) may matter in terms of absorption, as several studies have investigated the effect of meal conditions on vitamin D3 absorption.

• A study published in 2013 3 found that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low-fat meal, compared with a high-fat meal and no meal.
• However, another study published in 2015 4 found that the presence of fat in a meal significantly enhances absorption of vitamin D3, but the monounsaturated-to-polyunsaturated fatty acid ratio of the fat in the meal does not influence its absorption.
• A 2011 study 5 also found that a high-fat meal increased the absorption of vitamin D3, as measured by serum 25-hydroxyvitamin D levels.

Fat Content and Vitamin D3 Absorption

The fat content of a meal may play a role in vitamin D3 absorption, as several studies have investigated this relationship.

• A study published in 2015 4 found that absorption of vitamin D-3 is greater when the supplement is taken with a meal containing fat than with a fat-free meal.
• Another study published in 2011 5 found that a high-fat meal increased the absorption of vitamin D3, as measured by serum 25-hydroxyvitamin D levels.
• However, a 2013 study 3 found that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low-fat meal, compared with a high-fat meal and no meal, suggesting that the relationship between fat content and vitamin D3 absorption may be more complex.

Clinical Implications

The clinical implications of these findings are not entirely clear, as the optimal timing and meal conditions for taking vitamin D3 supplements have not been established.

• A 2012 review 6 noted that the decision by young, otherwise healthy adults to take vitamin D in doses of 2000 IU/day or lower is unlikely to cause harm, but the optimal dosing regimen and timing are not well established.
• A 2019 study 7 found that long-term supplementation with vitamin D3 in doses ranging from 5000 to 50,000 IUs/day appears to be safe, but the study did not investigate the effect of meal conditions on absorption.