Controversies surrounding vitamin D deficiency

Vitamin D is essential for healthy bone formation and maintenance — and, it is claimed, has a host of other benefits. But can we safely regard supplementation as a panacea, or is it time to take a more balanced view?

Vitamin D deficiency can affect people of any age, and it is estimated that approximately 1 billion people around the world suffer from it.¹ In the US, a population study found that 41.6% of adult subjects were deficient, with the highest rates found among blacks and Hispanics,2 while closer to home, a recent survey in the UK found that more than 50% of the adult population were found to have vitamin D insufficiency, with 16% having severe deficiency during the months of winter and spring.³ Despite these high prevalence figures, the deficiency is believed to be undiagnosed in many affected people,¹ but does it actually matter? Recent evidence suggests that vitamin D deficiency may not really be as detrimental as previously thought.

WHY THE CONCERN?

Vitamin D deficiency is often a silent condition,⁴ which may explain the number of undiagnosed cases. Left untreated it is thought to be linked to a number of chronic conditions (Box 1), including cardiovascular disease and certain cancers. Given the reported prevalence of the condition, underdiagnosis therefore has wide ranging implications both for the health of those affected and for healthcare costs. Prevention is generally seen as better than cure and NICE has therefore published guidance aimed at improving implementation of existing recommendations on vitamin D to prevent deficiency, and increasing access to supplementation for at-risk groups.⁵ Practice nurses can therefore play an important part in educating patients and identifying those at risk (Box 2) so that screening and treatment, where appropriate, can be put in place.

DIAGNOSING DEFICIENCY

Diagnosis of the condition is made on blood testing for serum concentrations of 25 hydroxy vitamin D (25[OH]D). The first controversy surrounds the optimum level of serum 25(OH)D in a healthy population, with some experts suggesting that a serum level below 20nmol/ml represents deficiency, while others suggest that levels should be maintained above 30nmol/ml.

CAUSES

Vitamin D deficiency is most frequently caused by insufficient exposure to sunlight. From mid October to the beginning of April in the UK there is no ambient ultraviolet sunlight of the appropriate wavelength, so during the winter months the body relies on stores built up from exposure to sunshine during the summer months and dietary sources to maintain vitamin D levels.⁵ In addition, anything that interferes with the penetration of UVB radiation into the skin will affect the body's ability to synthesise vitamin D.¹ Melanin is very efficient in absorbing UVB radiation, so that increased skin pigmentation markedly reduces vitamin D3 synthesis and has been shown to reduce cutaneous vitamin D3 production as much as 99.9%.⁷ One study conducted among Asian women found that over the year 10-49% of white women had levels below 40 nmol/l while 89—91% of Asian women were found to be deficient.⁸ Research has also found that obesity, smoking, inflammation and poor diet can also result in low circulating levels of vitamin D.⁹

SIGNS AND SYMPTOMS

Vitamin D deficiency manifests itself differently in adults and in children. In adults symptoms may be vague, and mimic a number of other conditions leading to potential misdiagnosis. In adults, the principal condition associated with deficiency is osteomalacia, which causes symptoms of bone and muscle pain: these symptoms may be misdiagnosed as fibromyalgia, chronic fatigue syndrome, or arthritis.¹⁰ In children, vitamin D deficiency can cause rickets, symptoms of which include bone pain and muscle weakness, leading to reluctance to walk or weight bear. A child with rickets may present with skeletal deformities (bowed limbs), fragile bones, poor or delayed growth and development, or dental problems.

LONG-TERM HEALTH EFFECTS

The second controversy relates to the possible links between vitamin D deficiency and a number of long term conditions with wide ranging consequences. The issues here include the interpretation of study findings, potential bias in favour of a positive association, and reluctance to publish negative findings.¹¹ The authors of a review published in the BMJ earlier this year warn of the problems of confounding and 'reverse causality' — that is, that disease believed to be caused by vitamin D deficiency may actually be causing the deficiency in the first place.¹¹

Increased cancer risk

Vitamin D is thought to play a role in decreasing the risk of many chronic illnesses, including common cancers,¹ and this is the third controversy. One study, which followed patients over a 19 year period, found that those with a vitamin D level below 50nmol/l had a 30—50% increased risk of developing colorectal, breast, prostate, and many other cancers.¹² However a meta analysis of eight prospective cohort studies from Europe and the USA found that low vitamin d levels and increased cancer mortality was only observed if subjects had a past history of malignancy.¹³

Cardiovascular disease (CVD)

Cardiovascular disease is a major cause of morbidity and mortality in many countries and there is now concern that there may be an association between vitamin D deficiency and life threatening cardiovascular events. Vitamin D is thought to have a protective effect against cardiovascular diseases although the way in which this is achieved is not fully understood. One study demonstrated that vitamin D deficiency increased the chance of coronary artery disease and the association between ischaemic heart disease and vitamin D deficiency was significant even after adjustment for cardiovascular risk factors such as diabetes, smoking, obesity, physical activity, high blood cholesterol.¹⁴ Shottker and colleagues reported increased all-cause and cardiovascular mortality, with a curvilinear association between 25(OH) D concentration and these outcomes.¹⁵

Osteoporosis

Osteoporosis is a disease characterised by reduced bone mass and deterioration of bone tissue, with a well-documented increased fracture risk. Insufficient vitamin D levels have been thought to contribute to the development of osteoporosis by decreasing intestinal absorption of calcium.¹⁵ Benefits of treatment to correct deficiency have been extensively studied with conflicting results. While some studies have shown improved bone mineral density when treatment is commenced, a post-mortem study showed that on examination, a substantial number of bodies with very low vitamin D levels were found to have normal bone histology.¹⁶

Falls

Vitamin D levels have recently been linked to the risk of falls in the elderly with several studies demonstrating that treatment of the condition decreases the risk. In one study vitamin D supplementation resulted in a reduction in falls of about 22% in ambulatory and institutionalised elderly subjects, when compared with controls.⁴ However, it is thought likely that this improvement was not due to any intrinsically preventive effect, but might be due to the fact that higher vitamin D levels are associated with improved muscle function.⁶

Fractures

Effect on fracture risk is also controversial. Although not shown in all studies, there is some evidence to suggest that reduced vitamin D levels (or inadequate vitamin D intake) may be associated with an increased risk of hip and other non-vertebral fractures. Oral vitamin D supplementation was shown in one study on the prevention of hip and other non-vertebral bone fractures in individuals aged 65 years or older to offer fracture protection, suggesting that supplementation may therefore be useful in the prevention of hip and other bone fractures.¹⁵ However, in another study, high doses of a vitamin D supplement were associated with an increased fracture risk.¹⁶

Diabetes

Vitamin D may also play a role in the homeostasis of glucose metabolism and the subsequent development of both type 1 and type 2 diabetes (T2D).⁶ There is some evidence that increased vitamin D intake by infants may reduce the risk of the development of type 1 diabetes.¹⁷ In adults vitamin D has also been shown to be associated with several of the factors known to contribute to the development of T2D, including abnormalities in pancreatic beta cell function, insulin sensitivity, and systemic inflammation.⁶ However, this is again controversial, in that other risk factors for T2D, particularly obesity and low levels of physical activity, are also linked to low vitamin D3 levels.¹⁰ Thus is it is not possible to determine whether low vitamin D levels per se are the cause of, or are caused by other risk factors for diabetes.

COST EFFECTIVENESS

The cost effectiveness of implementing interventions to prevent vitamin D deficiency also remains unclear. Testing for vitamin D insufficiency has reportedly increased 2- to 6-fold in recent years and at £20 per test (2012 prices), represents a considerable cost to the NHS.⁵ Primary care spending on vitamin D supplementation has also increased significantly, from £28 million in 2004, to £76 million in 2011.⁵ Nontheless, NICE recommends targeted supplementation for at-risk groups, including infants, children, older people, pregnant and lactating women and those with limited sun exposure.⁵ Vitamin D supplements are readily available over the counter (OTC) — and on prescription — but there is a further controversy over the quality and price of OTC products, which may not be suitable for all groups. Healthy Start vitamins, available from children's centres, Sure Start centres etc used to be available to purchase by people who were ineligible for Healthy Start, at a lower cost than commercial products — but this facility was withdrawn in April 2013.

RISKS AND BENEFITS OF TREATMENT

The decision to treat or not, based on current evidence remains under scrutiny. Recently, Chowdhury et al reported that supplementation with D2 did not reduce cause-specific mortality (in cardiovascular disease, cancer, non-vascular and non-cancer); however, supplementation with D3 did.¹⁸ However, vitamin D treatment may not be without harm:patients may experience anorexia, nausea and vomtting, headaches, thirst, vertigo and raised concentrations of calcium and phosphate in plasma and urine.¹⁹

TREATMENT OPTIONS

When treatment is thought to be beneficial there are several drugs available to treat the deficiency and they are available in either tablet or liquid form. Oral calciferol in the form of either ergocalciferol or colecalciferol, is the treatment of choice for children with rickets, and for adults calciferol treatment, in a daily dose of 10,000iu will restore body stores of vitamin D over an 8 to 12 week period, at which time the dose can be reduced to 1,000-2,000iu daily or 10,000iu weekly.³ For those in whom risk factors cannot be reversed treatment may need to continue long term.

CONCLUSION

There are still unanswered questions surrounding the impact of vitamin D deficiency, its association with long term problems and its true impact on health. Research is ongoing, with several studies in progress at the present time. However, as a recent article in the BMJ suggested, clinicians should avoid costly measurement of blood levels in asymptomatic patients and concentrate on encouraging better lifestyles and targeting risk factors in those at increased risk.²⁰ This is something that practice nurses can do with confidence, and there is no controversy over their vital role in raising awareness of vitamin D insufficiency, educating and identifying those at risk and influencing on health improvements for those affected.

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