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The magic pill - the increasing use of vitamin D outside of recommendations

Isobel Sims looks at the increasing use of vitamin D for non-musculoskeletal conditions

 

Vitamin D has had a tumultuous time over the last couple of years. The volume of recent research is giving it a reputation as a panacea for everything from pre-eclampsia to depression. But confusion about what it does and who should be taking it has led to negative press, with some areas of the national media declaring it ‘pointless’ and ‘bunkum’.

The Grocer, a trade magazine for the grocery industry in the UK, reported last year that Brits spent £7m on vitamin D in 2017, a 30% increase in sales, making it the fastest-growing vitamin and mineral supplement in terms of sales in the UK.1

National guidelines recommend that all adults take vitamin D supplements in the winter months, but when it comes to recommending vitamin D for non-musculoskeletal indications, the waters become muddier, especially when research hits the mainstream media.

Research in the media

A landmark in vitamin D’s rise to fame was a 2017 study, backed by the then Department of Health and covered by the national news outlets, which found in a large meta-analysis that vitamin D protects against colds and flu, halving the risk of acute respiratory illness in patients with the lowest baseline vitamin D levels. Researchers suggested that vitamin D increases levels of antimicrobial peptides in the lungs – potentially explaining why it also has beneficial effects in asthma.2

The findings and coverage led to a massive spike in vitamin D sales, with Waitrose reporting a 70% increase in sales in the two weeks after the study was published. Waitrose also saw a 22% increase in sales of tinned red salmon – a dietary source of vitamin D – in the fortnight after the study came out. And head of Health and Wellbeing Brands Jonathan Evans acknowledged the fact that vitamin D had been ‘well-documented in the news’ before launching a vitamin D spray later that year.

Ade Williams, superintendent pharmacist at Bedminster Pharmacy in Bristol, says that a holistic approach to vitamin D is important given the greater media coverage and increase in people asking about supplementation.

‘We are seeing a lot more people coming in and asking about vitamin D as the media coverage of research publications gets more prominence.

‘Taking a holistic approach is key, focused on why the vitamin is needed and if it is safe and appropriate. We need to make sure patients aren’t turning to vitamins in place of adopting healthy lifestyle measures.’

And the research finding its way into the public domain is not just limited to DH-backed papers on respiratory illness.

A 2016 Cochrane review concluded that vitamin D was ‘likely’ to reduce the risk of severe asthma attacks by half when taken alongside regular asthma medication, although the study noted that more research was needed on whether the results could be generalised to children.3

More recent research found that higher blood concentrations of vitamin D were associated with a decrease in breast cancer risk. The study, pooling results from three different clinical trials and looking at more than 1,100 women, found that women who had a blood serum vitamin D concentration of >60ng/ml had an 82% lower risk of breast cancer than those who had a serum concentration of >20ng/ml. The researchers suggested that women increasing their vitamin D levels to 55ng/ml could help modify their risk of developing breast cancer.4

Another 2018 study found similar results for liver cancer, with the highest vitamin D levels 22% less likely to get cancer of any type than those with the lowest vitamin D levels.5

More tests

With more patients aware of vitamin D and its potential ‘benefits’ than ever before, it’s also not surprising that clinicians are ordering more vitamin D blood tests.

Research by the University of Oxford showed that the overall number of tests ordered by GPs, for any condition, increased three-fold between 2001 and 2016, with the number of vitamin D tests ordered showing a 53% annual increase. In absolute terms, this equated to 182 more tests per 10,000 population in 2015 compared with 2001 – the second highest annual increase out of the 44 tests looked at in the study (see below).6

There is evidence that around two-thirds of vitamin D tests requested from primary care came back normal, and that 20% of tests were ordered within three months of a patient starting supplementation for vitamin D deficiency – going against evidence in the NICE clinical knowledge summary that retesting should occur after three to six months. 

BMA GP Committee clinical and prescribing policy lead Dr Andrew Green feels clinicians need to go back to basics, rather than testing patients on a whim.

He said: ‘The indications for vitamin D have been the subject of some controversy but are laid out in the NICE guideline [on increasing supplement use in at-risk groups]. Testing outside these indications is likely to lead to overdiagnosis and overtreatment, as well an increasing workload for primary care staff.

‘Rather than testing indiscriminately, clinicians should concentrate on highlighting the Public Health England advice to routinely supplement diets in the dark months of the year, or longer for those who are unlikely to gain enough vitamin D through exposure to sunlight.’

But if there is one benefit to testing and subsequent supplementation, it is that hospital admissions for vitamin D deficiency have been cut. NHS Digital data for England show that admissions due to vitamin D deficiency fell in 2017/18 – the financial year after the introduction of the PHE guidance – and that overall, admissions for vitamin D deficiency have shown a downward trend over the last seven years.

In an attempt to address the issue of testing, the National Osteoporosis Society (NOS) updated its guidance on vitamin D and bone health in December 2018 to clarify which patients should receive vitamin D blood tests and which should be treated for deficiency.

NOS recommends testing only for patients who have osteoporosis, confirmed or suspected osteomalacia, musculoskeletal symptoms that could be due to vitamin D deficiency, or a risk of deficiency due to age or lack of exposure to the sun. It also recommends testing before starting antiresorptive treatment for osteoporosis.

The guideline update, NOS said in a press release, could potentially lead to a reduction in the number of vitamin D blood tests being requested.7

It’s not all positive

However, many studies suggest that there are actually no benefits to supplementing in patients who are not at a clinical risk of bone disease – a finding in line with the current guidelines – which raises the question of whether the public spend on vitamin D is justified.

A 2016 study published in the BMJ said that patients who were not at risk of deficiency did not benefit from taking vitamin D supplements to prevent falls or fractures, or conditions like cardiovascular disease and cancer.8 Randomised controlled trial data from 2017 backed up the claims, with a study of over 5,000 patients finding that monthly high-dose vitamin D didn’t make patients less likely to have a cardiovascular event than those taking placebo.9 

A 2018 study found that antenatal vitamin D levels had no association with gestational hypertension during pregnancy and only a weak association with pre-eclampsia.10 This backs up the 2014 guideline from the Royal College of Obstetricians and Gynaecologists, which says that although reduced vitamin D levels may be associated with increased risk of conditions like hypertension and pre-eclampsia, there are no data to suggest that supplementation will reduce these risks, and pregnant women should not be routinely screened for deficiency.11 

What the guidelines say

Public Health England issued guidance in 2016 stating that everyone needs a daily intake of 10μg of vitamin D to protect bone and joint health. The government body recommends that people should consider taking a vitamin D supplement in the autumn and winter months in order to prevent deficiency, and those who live in care homes or who always cover their skin when they are outside are advised to supplement year-round. The guidance was based on a report by the Scientific Advisory Committee on Nutrition (SACN), which reviewed evidence for setting daily reference values of vitamin D for adults. 

But more recent research published earlier this year sparked confusion over whether anyone should supplement at all.12 The large meta-analysis found that vitamin D supplementation didn’t prevent fractures or falls or increase bone mineral density, with the authors concluding that clinical guidelines shouldn’t recommend vitamin D for musculoskeletal health, and the Daily Mail describing PHE’s advice as ‘total bunkum’.

Importantly though, only four studies included patients considered vitamin D deficient at baseline. PHE stood by its guidance in response and critics have pointed out that supplementation won’t produce benefits in people with healthy vitamin D levels.

The scope of the NICE guidance on supplementing is broader, recommending that the Department of Health, PHE and commissioners work together to ensure that patients, particularly those in hard-to-reach groups, have accurate information on how and when they should supplement with vitamin D.

The NICE guidance particularly focuses on increasing supplementation in population groups who are at risk of deficiency, including pregnant and breastfeeding women, children under four years of age and people with darker skin.

Although recommendations are clear that everyone should be taking vitamin D in the darker months, there is little official guidance clarifying the slew of recent research on the effects of vitamin D on non-musculoskeletal conditions.

Freelance consultant dietitian Rebecca MacManamon believes that discretion is important when considering indications where there is less evidence for the benefits of vitamin D, but that ultimately the guidelines win out.

‘I think a lot of people take vitamin D of their own volition for non-musculoskeletal conditions, and I am sometimes asked for my opinion about this. If they had a condition where there wasn’t strong evidence for the benefit of vitamin D, I’d be making an assessment about how much vitamin D they’re exposing themselves to,’ she says.

‘I think that because we don’t have sufficient evidence for recommending vitamin D for things like asthma or heart disease, we have to default to the general recommendations.’

The 2016 SACN report upon which the PHE guidance is based noted that trials did not show any effect of vitamin D on cancers and that most trial data for the vitamin’s effects on cardiovascular outcomes should be interpreted ‘with caution’. It also said that data were ‘lacking’ or ‘inconsistent’ for the effects of vitamin D on atopic and autoimmune conditions such as asthma and type 1 diabetes.

In light of this, Louis Levy, head of nutrition science at PHE, says: ‘The SACN found insufficient evidence to support recommendations outside of maintaining adequate levels of vitamin D to reduce the risk of poor musculoskeletal health.

‘Health professionals should be giving consistent advice in line with government advice that can be found on the NHS Choices website.’

 

References

1 Brown R. Vitamin D supplement sales boosted by medical reports. The Grocer 2018 tinyurl.com/ybgyl844

2 Martineau A, Jolliffe D, Hooper R et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583. 

3 Martineau A, Cates C, Urashima M et al. Vitamin D for the management of asthma. Cochrane Database Syst Rev. 2016;5:9:CD011511.

4 McDonnell S, Baggerly C, French C et al. Breast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations ≥60 vs <20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort. PLOS ONE. 2018;13:e0199265.

5 Budhathoki S, Hidaka A, Yamaji T et al. Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort. BMJ 2018;360:k671.

6 O’Sullivan J, Stevens S, Hobbs F et al. Temporal trends in use of tests in UK primary care, 2000-15: retrospective analysis of 250 million tests. BMJ 2018;363:k4666.

7 Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management. National Osteoporosis Society; 2018 tinyurl.com/ychjhckx

8 Bolland M, Avenell A, Grey A. Should adults take vitamin D supplements to prevent disease? BMJ 2016;355: i6201.

9 Scragg R, Stewart A, Waayer D et al. Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study. JAMA Cardiology 2017;2:608.

10 Magnus M, Miliku K, Bauer A et al. Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study. BMJ 2018;361:k2167.

11 Vitamin D in Pregnancy. Scientific Impact Paper No. 43. Royal College of Obstetricians and Gynaecologists; 2014. tinyurl.com/ybbva5bz

12 Bolland M, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. The Lancet Diabetes & Endocrinology 2018;6:847-58.