Vitamin D and calcium supplementation in primary care: an update

How much sunlight is enough?

To prevent vitamin D deficiency, a daily walk in the early morning or late afternoon from September to April in the Southern hemisphere with face, arms and hands exposed is recommended.¹ At the height of summer as little as six to eight minutes of sun exposure may be sufficient to produce 1000 IU of vitamin D.² From May to August outdoor activity is best scheduled around noon as approximately 30 – 50 minutes of sun exposure is required to produce the same amount of vitamin D.^{1, 2} Dark skin pigmentation is correlated with decreased rates of vitamin D production and people with darker skin may require three to six times more sun exposure to achieve equivalent levels of vitamin D production.² It is not possible to develop vitamin D toxicity due to exposure to sunlight.¹

The use of sun beds to boost vitamin D levels is not recommended as this practice is associated with an increased risk of melanoma which rises with greater use and earlier age of first use.¹

Diet is a secondary source of vitamin D

Diet contributes approximately 5 – 10% of a person’s vitamin D requirement.² Diet can be an important source of vitamin D during winter months or when sun exposure is reduced. Cod liver oil is the best dietary source of vitamin D while oily fish, e.g. salmon, tuna, eel and warehou, are rich whole food sources.¹ Milk, yoghurt and margarine fortified with vitamin D are now available in New Zealand.

Prescribing of vitamin D is increasing

As in 2011, guidance continues to recommend prescribing vitamin D supplements based on risk of deficiency (see below).¹ However, the number of people prescribed vitamin D each year is increasing (Figure 1) and it is questionable whether all of those prescribed supplements are at risk of long-term deficiency. Colecalciferol (vitamin D₃) is the predominant formulation prescribed; in 2015 it was the 12^th most frequently prescribed medicine in New Zealand.⁴

Benefits versus risks of vitamin D supplementation

Severe vitamin D deficiency reduces bone mineralisation which causes osteomalacia and increases fracture risk. This can be prevented by empiric supplementation of people who are at risk. Since 2011, evidence has accumulated that only a limited number of patients benefit from supplementation with vitamin D.

The benefits of supplementation on bone health and falls prevention have been overstated

More than 50 meta-analyses have examined the effects of vitamin D on falls or fractures.⁶ This research now confirms that vitamin D supplementation for the general population provides no benefit and is a waste of resources. Key findings from studies include:

• The United States Preventative Services Task Force concluded, in 2013, that daily supplementation with 400 IU (10 micrograms) of vitamin D₃ and 1000 mg of calcium has no effect on fracture incidence in post-menopausal women.⁷
• A meta-analysis involving more than 50 000 participants concluded that vitamin D taken without calcium has no effect on fracture incidence and that vitamin D taken in combination with calcium has weak and inconsistent effects on fracture risk; benefits were restricted to frail, older females living in institutions.⁸
• Analyses of randomised controlled trials involving almost 30 000 participants found that vitamin D with or without calcium has no effect on the risk of falls.⁸

Adverse effects associated with vitamin D supplementation have been reported

Vitamin D taken at recommended doses, i.e. 1.25 mg per month or 10 – 20 micrograms (400 – 800 IU) per day, is generally well tolerated and considered to be safe. There is no evidence of toxicity at doses of vitamin D₃ below 25 micrograms (1000 IU), daily, however, hypercalcaemia and hyperphosphatemia can occur at substantially higher doses, e.g. 50 000 IU daily.¹⁰ Vitamin D supplementation in combination with calcium supplements is reported to increase the risk of renal tract stones.⁷

In a randomised controlled trial it was found that single high doses of colecalciferol, e.g. 12.5 mg (500 000 IU) given annually, were associated with an increased risk of falls and fractures in older women who were considered at high risk of fracture (see: ”High and low levels of vitamin D can cause bone weakness”).⁹

Inconclusive research has created confusion

In addition to preventing osteomalacia, there are a plethora of health claims associated with vitamin D supplementation. This has created confusion both for patients trying to make informed treatment decisions and for clinicians guiding their care.

Numerous studies have examined associations between vitamin D deficiency and a range of conditions including: cardiovascular disease, cancer, autoimmune and inflammatory diseases, neurodegeneration, cognitive impairment and mood disorders.¹⁰ Association does not equate to causation, however, and randomised controlled trials show that vitamin D supplementation has little or no effect on the non-skeletal illnesses studied; the meta-analyses reported also do not support the observational findings.¹¹ It is more likely that vitamin D deficiency is a marker of reduced health, rather than a cause of it.¹¹

Risk factors for vitamin D deficiency

Groups considered to be at high risk of vitamin D deficiency who may benefit from supplementation include people:¹

1. With very dark skin pigmentation
2. Who completely avoid the sun for medical reasons, e.g. they have had skin cancer or are using photosensitising medicines long-term
3. With reduced mobility who are frail or housebound and at risk of musculoskeletal pain and osteomalacia

People who completely cover their skin with clothing or veils will be at greater risk of vitamin D deficiency.¹ Living in southern regions means that transitory vitamin D deficiency is more likely to occur between the months of May and August.¹

The symptoms of vitamin D deficiency

In children, vitamin D deficiency is associated with delayed tooth eruption and rickets.¹⁴

In adults, severe vitamin D deficiency causes osteomalacia with symptoms of bone pain and muscle weakness.¹⁴

Physiological changes consistent with osteomalacia in adults who are vitamin D deficient include:¹⁴

• Elevated alkaline phosphatase levels; often the earliest finding
• Low calcium levels
• Elevated parathyroid hormone levels, i.e. secondary hyperparathyroidism
• Low phosphate levels

Vitamin D testing is only indicated if severe deficiency is suspected

Vitamin D supplementation can be initiated in people at risk of deficiency without the need for testing.¹ Testing of vitamin D levels is usually only indicated in patients with features of severe deficiency.¹ This includes patients who may have:^{15, 16}

• Metabolic bone disease or features such as unexplained fractures or bone pain
• Unexplained raised alkaline phosphatase, low calcium or phosphate levels
• Chronic kidney or liver disease
• Osteoporosis secondary to endocrine disorders, e.g. Cushing syndrome
• Malabsorption of dietary fat, due to conditions such as coeliac disease, previous intestinal surgery or gastric bypass

When vitamin D testing is requested serum 25-hydroxyvitamin D (vitamin D) is measured as it is a stable metabolite with a plasma half-life of three weeks.² The optimal serum vitamin D level is contentious: a serum level ≥ 50 nmol/L is generally considered to be sufficient to maintain adequate bone health,² and levels below 25 nmol/L are considered to be deficient.¹ Day-to-day variations in serum vitamin D are small (5%), although levels may decrease by as much as 20 nmol/L over winter compared to measurements taken during summer.² Where severe symptomatic vitamin D deficiency is suspected serum calcium, phosphate and alkaline phosphatase should also be tested.¹

There is limited clinical value in testing vitamin D levels in patients without symptoms of deficiency because the results of testing are difficult to interpret, as the optimum level of vitamin D is unknown and levels can vary substantially between seasons.