In a recent narrative review published in Nutrients, researchers discuss the evidence arguing for the efficiency and safety of 2000 international units (IU), i.e., 50 micrograms (µg) of vitamin D supplementation per day to prevent and treat vitamin D deficiency in the general adult population.

Study: Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 µg) of Vitamin D for Adults in the General Population. Image Credit: FotoHelin/Shutterstock.com

Background

Vitamin D deficiency has many adverse clinical consequences, including poor musculoskeletal health, manifesting as diseases like rickets and osteomalacia.

Moreover, vitamin D may be crucial for preventing extra skeletal diseases like cancer and diabetes.

Vitamin D is biologically inactive in the human body; thus, in laboratory detection of vitamin D deficiency, they measure serum concentrations of 25-hydroxyvitamin D (25(OH)D), a vitamin D metabolite utilized by the body and that reflects the overall supply from different sources, including ultraviolet-B (sunlight) and food sources, such as fish or mushrooms.

Worldwide, the prevalence of low serum levels of 25(OH)D, i.e., below 25-30 nmol/L and 50 nmol/L, occurs in ~5-18% and 24-49% of people, respectively, underscoring the need for prompt action to reduce vitamin D deficiency burden globally.

At a dosage of 50µg per day, the whole 25(OH)D distribution of a given population could rise to higher levels; however, there are safety concerns with such dosage as it may also increase the risk of vitamin D overdosing for those at the higher end of the distribution.

Moreover, given the extra skeletal health effects of vitamin D, it is crucial to focus on the attainment of 25(OH)D levels needed to prevent them rather than safety concerns for targeting 75 nmol/L (30 ng/mL), which are optimal target serum 25(OH)D concentrations for skeletal health.

So, researchers additionally investigated whether attaining serum 25(OH)D levels ≥50 nmol/L should be the target.

Current Vitamin D supplementation guidelines

Guidelines for vitamin D intake establish target serum 25(OH)D concentrations and recommend the required doses to achieve those levels, assuming adequate intake of other nutrients and seasons (winters or summers).

Accordingly, current guidelines recommend a daily vitamin D intake of 400-800 IU; however, individuals from different ethnicities or regions may require even higher intakes of 2008-2672 IUs for attaining 25(OH)D serum levels of ≥50 nmol/L.

What should be the target serum 25(OH)D levels: 75 nmol/L (30 ng/mL) or 2000 IU (50 µg)?

Many observational studies have suggested that while ≥50 nmol/L serum 25(OH)D levels can prevent rickets and osteomalacia, concentrations ≥75 nmol/L are needed for improved health outcomes in diabetes and cancer.

The optimal concentration needed may also vary depending on the study population and outcome of interest.

Further, the authors noted that randomized controlled trials (RCTs) testing 25(OH)D needs may be biased towards healthy people who may not accurately represent the general population, especially those with obesity.

In fact, optimal serum 25(OH)D concentrations for most chronic diseases are slightly above 75 nmol/L (30 ng/mL).

Thus, obese individuals, individuals with higher body mass index (BMI), and patients with malabsorption syndromes may require higher doses of vitamin D to increase their serum 25(OH)D levels. 

Some may not meet the threshold even after supplementing with daily 2000 IUs of vitamin D, like patients with inflammatory bowel disease during episodes of high disease activity.

Even medications, like antiepileptic drugs, can affect lower serum 25(OH)D concentrations by modulating its metabolism.

When serum 25(OH)D concentrations exceed 150 ng/mL, vitamin D toxicity may lead to hypercalcemia; thus, clinicians advise caution for those on vitamin D supplements.

Recent RCTs like the Vitamin D and OmegA-3 Trial (VITAL) gathered safety data on using 2000 IU of vitamin D/day in general adult populations who showed no signs of vitamin D toxicity for 5.3 years, indicating the safety of this daily dosage.

Further, a meta-analysis of 15 vitamin D RCTs found no increase in kidney stones when supplementing with ≥70 µg of vitamin D for at least one year.

Another meta-analysis found that daily vitamin D supplementation of 3200-4000 IUs for six months increased the risk of hypercalcemia, hospitalizations, and falls; however, this did not occur in chronic kidney disease patients.

Conclusions

Adherence to conservative dosing regimens not exceeding 800 IU (20 µg) of vitamin D per day may not sufficiently treat vitamin D deficiency, considering the heterogeneity in inter-individual dose-response and accounting for the multiple clinical factors involved, such as obesity, malabsorption syndromes, and medications that impair vitamin D metabolism.

This review revealed that daily vitamin D supplementation was more effective than intermittent bolus dosing in adults. However, precaution is needed for older and diseased individuals, who are more prone to adverse effects of vitamin D overdosing. 

In real-world settings, clinicians should consider tailoring the vitamin D dosage according to the patient’s needs and characteristics.

Instead of following the ‘one-size fits all’ approach, they may adopt a personalized treatment approach and prescribe a dosing range from 800-2000 IUs (20-50 µg). 

It is a narrative review lacking a pre-registered systematic review. Yet, based on the evidence outlined in this review, the authors argue in favor of a daily vitamin D supplement dose of 2000 IU (50 µg) to raise and maintain serum 25(OH)D concentrations >50 nmol/L (20 ng/mL) and >75 nmol/L (30 ng/mL) in >99% and >90% of the general adult population, respectively.

Furthermore, they found no significant safety concerns in supplementing such a dose for several years, even in individuals with a sufficient vitamin D status at baseline. 

This could be the perfect remedy for addressing the vitamin D pandemic in the general adult population.