Vitamin D and combined supplementation with calcium

Globally, the incidence and prevalence of vitamin D insufficiency or deficiency is on the rise (1). Approximately more than half of the world’s population have vitamin D insufficiency or deficiency (1). Fortunately, this disorder can be easily modified with minimal cost. Recently, Wimalawansa et al (2018) published a review on the function of vitamin D and its supplementation in various populations.

Summary | Eating foods containing vitamin D and exposure to sunlight are essential to maintain a healthy vitamin D level. Both the Institute of Medicine (IOM) and the European Food Safety Authority (EFSA) recommend a daily vitamin D dose of 15 mcg (600IU) for adults (2,3). According to the review by Wimalawansa et al (2018), populations with difficulty obtaining sufficient sunlight exposure for vitamin D production may need supplementation with vitamin D as natural food sources generally does not provide enough of said vitamin. Wimawalansa et al (2018) noted that 1000-2000 IU/day of vitamin D, in addition to adequate calcium intake, may be necessary to maintain serum 25(OH)D levels over 75 nmol/L (1). For high-risk individuals, vitamin D levels as high as 4000IU/day may be advisable.

Vitamin D plays a role in the maintenance of serum ionized calcium level, calcium absorption and mineralization of osteoid tissue. Wimalawansa et al (2018) wrote that vitamin D also plays a role in other functions such as neuromuscular coordination, hormone release, subduing autoimmunity, muscle strength and preventing the development of several cancers. When vitamin D inadequacy occurs, the functions mentioned in the table will not be carried out efficiently.

Skeletal effects Non-skeletal effects
·         Essential for calcium homeostasis ·         Improved immunity
·         Enhanced GI absorption of calcium ·         Decrease severity of autoimmunity and neurological disorders
·         Enhanced osteoblast function ·         Prevention of type 1 and type 2 diabetes
·         Necessary for bone mineralization ·         Prevention of cancer
·         Prevent rickets and osteomalacia ·         Decreased cardiovascular diseases
·         Decrease sarcopenia ·         Decreased all-cause mortality
·         Improve balance and prevention of falls ·         Decreased pulmonary morbidities
·         Prevention of osteoporosis and fractures ·         Less morbidities and improved survival

Table shows skeletal and non-skeletal beneficial effects of vitamin D (1).

According to the EFSA, the normal targeted serum level of vitamin D is around 50 nmol/L (3). Similarly, the IOM recommends serum levels of 30-50 nmol/L for vitamin D as that is the range that supports maximum calcium absorption (2). In the review by Wimawalansa et al (2018), the authors defined normal serum level as 75 nmol/L and noted there are debates surrounding this figure (1). They also wrote that teenagers, pregnant and breastfeeding women, and those with certain diseases, require higher levels of vitamin D. In the review, the authors used the range of 40-75 nmol/L for vitamin D insufficiency and ≤39 nmol/L for deficiency.

Vitamin D inadequacy and the role of supplement

Improving vitamin D inadequacy is easy and cost effective (1). Safe sunlight exposure is the best method to achieve sufficient vitamin D levels on a regular basis. Only a limited number of foods contain meaningful quantities of vitamin D, and some examples are fatty fish and sun-exposed mushrooms. Some foods such as milk and butter are fortified with vitamin D (3). However, most regulatory bodies do not allow the optimal level of fortification of food with vitamin D, which can lead to an insufficient dietary intake of the vitamin. As such, Wimalawansa et al (2018) are in favor of vitamin D supplementation for specific groups of people.

Some individuals may benefit from vitamin D supplementation. For instance, those who are unable to obtain optimal sunlight exposure due to institutionalization (eg, nursing homes, prisons), unable to  efficiently generate vitamin D in the skin and have conditions that cause decreased intestinal absorption or increased catabolism of vitamin D. Further elaborating, the researchers wrote that among those who may benefit from vitamin D supplementation are patients who experienced rapid weight loss due to natural causes or secondary to gastric bypass surgery, those who are taking anti-epileptic and anti-retroviral drugs, people living in northern and southern latitudes during winter months, those with darker skin and those who avoid the sun (1).

The Institute of Medicine’s (IOM) report on vitamin D suggests that doses of 600IU/day is sufficient to achieve serum 25(OH)D levels up to 50 nmol/L in healthy persons with minimal exposure to sunshine (2). Conversely, many studies noted that at least 75 nmol/L is necessary to prevent most disorders, including secondary hyperparathyroidism. Moreover, to obtain a serum level of 75 nmol/L, supplementation with doses between 1000 and 2000 IU/day is necessary (1).

Risk of toxicity

Wimalawansa et al (2018) wrote that a supplement dose of 5000 IU/day is considered the safe daily upper limit for supplementation. The risk of toxicity is non-existent when the dose of vitamin D supplement is lower than 5000 IU/day. To stay cautious on potential toxicity, they recommended to maintain serum 25(OH)D levels between 75-125 nmol/L and not to go above 150 nmol/L. In their conclusion, the authors mentioned moderation is the way to go for calcium and vitamin D. This is in line with the advice that many people may need calcium supplements—not exceeding 600 mg/day—to achieve the recommended daily calcium intake of 1200 mg. However, for vitamin D, the authors noted that higher levels of  1000-4000 IU may be necessary and this range is much higher than the recommendation by national or international organizations.

Conclusion from Wimalawansa et al (2018)

Safe sunlight exposure is the best method to obtain optimal vitamin D levels. However, supplementation may be necessary for certain groups of people such as those who are institutionalized or have disorders related to vitamin D generation, absorption or catabolism.

Bolland et al (2018): Vitamin D plus calcium supplementation

Another review on vitamin D, by Bolland et al (2018), suggests that vitamin D supplementation does not prevent fractures or falls, and has no clinically significant effects on bone mineral density (4). The results were consistent regardless of the vitamin D dosage. The authors noted that there is little justification to use vitamin D supplements to maintain or improve musculoskeletal health.

However, it is important to note that when there is sufficient vitamin D, the beneficial effects of vitamin D supplementation on bone health are less or not visible (5). In the Bolland et al (2018) review, only a few studies involving vitamin D deficiency were included.

In addition, for vitamin D supplementation to have beneficial effects, it should be given together with calcium supplement (6-8). 25% of the studies included in Bolland et al (2018)’s review provided calcium supplementation in addition to vitamin D. Nevertheless, as the studies were analyzed based on different outcomes, there is insufficient power to form a conclusion on the effect of calcium plus vitamin D supplementation.

References:

1.       Wimalawansa SJ et al. (2018) Calcium and vitamin D in human health: Hype or real? J Steroid Biochem Mol Biol 2018; 180: 4-14. 

2.       Institute of Medicine, Dietary Reference Intakes for Calcium and Vitamin D, Food and Nutrition Board, Washington DC. (2011).

3.       European Food Safety Authority (EFSA). (2016) Dietary reference values for vitamin D. Available at: https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2016.4547

4.       Bolland MJ et al. (2018) Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol 2018; 6(11): 847-858. 

5.       Scragg R. (2018) Emerging Evidence of Thresholds for Beneficial Effects from Vitamin D Supplementation. Nutrients 2018; 10(5): 561.

6.       The DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 2010; 340: b5463.

7.       Avenell A, Gillespie WJ, Gillespie LD, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2009; 15: CD000227. 

8.       Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab 2007; 92: 1415–1423.