Editorials

Vitamin D deficiency: time for action

Evidence supports routine supplementation for elderly people and others at risk 

Vitamin D is both a vitamin and a hormone and has diverse actions. The major biologically active metabolite, 1,25-dihydroxyvitamin D, plays a central part in maintaining calcium and phosphate homoeostasis and also has antiproliferative, prodifferentiation, and immunosuppressive effects; its receptors are distributed in various tissues, including bone, pancreas, stomach, gonads, brain, skin, and breast.¹ Vitamin D is essential for skeletal health, and severe deficiency is associated with defective mineralisation resulting in rickets or its adult equivalent, osteomalacia. More subtle degrees of insufficiency lead to secondary hyperparathyroidism and increased bone turnover, which play an important part in age related bone loss and osteoporotic fractures.

Over recent decades a wealth of evidence has accumulated documenting vitamin D deficiency in elderly populations in Europe and elsewhere. ^{2 3} A recent study from the United States has added further evidence that vitamin D deficiency continues to be neglected and also raised questions about how best to combat it.⁴

Vitamin D status is most commonly assessed by measuring serum concentrations of 25-hydroxyvitamin D (25-OHD), the major circulating form of the hormone. These show marked seasonal variation, reflecting the importance in healthy subjects of cutaneous synthesis as a source of the vitamin. Natural dietary sources of vitamin D are limited, and their contribution to vitamin D status assumes importance only in individuals with reduced exposure to sunlight. Serum 25-OHD concentrations below 20 nmol/l are generally regarded as indicating severe vitamin D deficiency, but circulating concentrations up to 37.5 nmol/l may be associated with adverse skeletal effects,⁵ and even higher levels may be required for optimal skeletal health, particularly in elderly people.

Other populations at risk include housebound and institutionalised people; those who avoid exposure to sunlight for cultural reasons or because of skin disease; patients with intestinal, liver, renal, or cardiopulmonary disease; and those taking anticonvulsants. In their recent study of 290 patients on a general medical ward at Massachusetts General Hospital Thomas et al found that 57% had serum 25-OHD concentrations at or below 37.5 nmol/l and 22% of these had values below 20 nmol/l.⁴ Not surprisingly, low vitamin D intake, housebound status, and winter season were independent predictors of hypovitaminosis D. However, vitamin D deficiency was also seen in patients with vitamin D intakes above recommended levels and in some cases occurred in the absence of known risk factors.

This study thus suggests that the currently recommended intakes of vitamin D are inadequate; in the United States these are 400 IU (10 µg) daily for those aged 51-70 years and 600 IU (15 µg) daily for those aged 71 and over, while in the United Kingdom 400 IU (10 µg) daily is recommended for people aged 65 years or over. Correction of privational vitamin D deficiency is safe, effective, and cheap. There is thus a powerful case for preventive strategies, particularly in high risk populations, and there are several ways in which these might be implemented.

The limited natural supply of vitamin D in food makes any increase in the recommended intake unlikely to be successful unless foods are more widely fortified. Even then fortification may not be effective in people with restricted dietary intakes, and amounts of vitamin D present in fortified foods can be variable.⁶ Exposure to ultraviolet irradiation is effective in correcting vitamin D deficiency and secondary hyperparathyroidism in elderly people,⁷ but concerns about skin cancer make this practice unlikely to be widely adopted. The most rational approach to reducing vitamin D deficiency is supplementation; uncertainty exists, however, about the best dose and route of administration and whether calcium supplements are also necessary.

Two randomised controlled trials of oral vitamin D (800 (20 µg) and 700 (17.5 µg) IU/day respectively) and calcium supplements in elderly subjects showed significant reductions in the rate of non-vertebral fractures ^{8 9} and one also showed a significant reduction in the incidence of hip fracture.⁸ However, the relative contribution of vitamin D and calcium to these benefits is unknown. In contrast, administration of 400 IU (10 µg) daily of vitamin D to elderly subjects with a high calcium intake produced no reduction in fracture rate.¹⁰ An open, quasirandomised study of annual injections of 150 000-300 000 IU of vitamin D showed a significant reduction in overall fracture rate but not in the rate of hip fractures in treated subjects.¹¹ The key issue of whether vitamin D supplementation alone is effective in preventing hip fractures thus remains unresolved; this has important implications both for compliance and cost, since calcium supplements are not always well tolerated and add substantially to the costs of intervention.¹²

As the study by Thomas et al shows, hypovitaminosis D remains a common and neglected problem⁴ despite numerous reports of its high prevalence in susceptible populations and recognised adverse effects on bone mass and fracture risk. Resolving the current uncertainties about the optimal method of supplementation is an important research priority. In the meantime, the rationale for routine vitamin D supplementation in elderly and other high risk populations is compelling. The available evidence suggests that 800 IU (20 µg) daily should be advised; this dose is safe, free of side effects, and should have an impact on the enormous and increasing morbidity and cost attributable to osteoporotic fractures in elderly people.

J E Compston, University lecturer and honorary consultant physician. 

Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ

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