ClinicalClinical FeaturesEndocrine/Metabolic

What is our Understanding of Vitamin D

Written by Dr Kevin McCarroll, Consultant Physician, St James’s Hospital, Dublin

Vitamin D has become the focus of huge interest in recent years, with an increasing number of studies identifying a high prevalence of deficiency. Vitamin D is widely regarded as being important for a healthy immune system and is implicated in the pathogenesis of cancer, autoimmune, cardiovascular and respiratory diseases as well as depression and cognitive impairment. More recently a large body of circumstantial evidence supports a role for vitamin D in ameliorating the symptoms or severity of Covid-19. In fact, to date there are nearly 1000 peer-reviewed studies published on the topic of ‘Vitamin D and Covid-19’. Vitamin D is not a nutrient in the traditional sense as it is a hormone that is largely derived from cutaneous synthesis after UVB exposure. Furthermore, dietary sources are limited and make a small contribution to overall intake but include fortified foods (milks, breakfast cereals), oily fish and eggs.

What constitutes vitamin D deficiency?

This has only been defined in relation to optimal bone health. A 25-hydroxyvitamin D level of less than 30 nmol/L is generally considered to represent deficiency and can cause rickets in children, osteomalacia in adults and result in secondary hyperparathyroidism. A level between 30-50 nmol/L represents possible deficiency and may be deleterious to bone health though other factors such as calcium and phosphate intake interact with vitamin D and play a role. For this reason, levels in the 30-50 nmol/L range are generally categorised as “insufficient”.

Despite this, higher calcium intake appears to partially compensate for lower vitamin D status by reducing secondary hyperparathyroidism. To ensure that one is vitamin D replete, it is prudent to maintain a level of ≥50 nmol/L. Vitamin D levels up to 75 nmol/L have been associated with more optimal suppression of serum parathyroid hormone (PTH), bone turnover markers and bone density in several studies though evidence is mainly observational and definitive data is lacking.

The Endocrine Society defines vitamin D insufficiency as a level between 50-75 mol/L but this is not widely accepted. Vitamin D levels of up to 60 nmol/l may reduce falls risk in some adults and levels up to 75 nmol/L are associated with better performance in tests of physical function including gait speed. For this reason, a target level of 75 nmol/L is recommended for older adults by some bodies including the American Geriatric Society, particularly for those who are frail and at risk of falls and fractures. Several studies report positive associations between higher levels of 25(OH)D and other health outcomes but definitive data is lacking. Levels above 125 nmol/l may be deleterious though toxicity is rare and generally only found with levels above 300 nmol/l.

How common is deficiency?

Deficiency is common in Ireland and countries above above 37° N latitude, where little or no vitamin D synthesis occurs between the months of November to March giving rise to the so-called “vitamin D winter”. In fact, vitamin D levels are typically highest in August/ September at the end of the summer and lowest in February/March. Indeed, the level usually drops by about 30 per cent between seasons.

In Ireland, overall, 13.1 per cent of the population older than 50 are vitamin D deficient (<30 nmol/L) based on findings from The Irish Longitudinal Study of Ageing (TILDA). In the same study, deficiency affected nearly one in four (24.1%) in the winter with the greatest prevalence (37%) in those aged over 80. Furthermore, more than half (59.2%) had levels below 50 nmol/l in the Winter. There were also regional variations with higher rates of deficiency in the north and west of the country. Using TILDA data, it is also estimated that 27 per cent of over-70s that were cocooning may be deficient.

Several other Irish studies report similar rates of deficiency. For example, In in the West of Ireland the overall prevalence of deficiency using a lower cut-off (<25 nmol/l) in a large cohort (n=24,302) was 17%. More specifically, deficiency affected 42% in nursing homes, 37% of outpatient attendees and 13% of community dwellers. More than half (54%) also had vitamin D levels below 50 nmol/l. Similarly, in a study of frail, older Irish adults (n=1,316) attending geriatric outpatient clinics in Dublin, 33% were found to be deficient (<30 nmol/L) with 75 per cent of non supplemented patients having levels below 50 nmol/L.

One of the the largest Irish studies of vitamin D status to date included 36,466 people aged 18- 90+ in the Leinster area who had vitamin D checked by request of their GP. It identified an on overall rate of deficiency of 13% rising to 23% in the Winter. Furthermore, up to half of adults had levels below 50 nmol/L. Unlike many studies which included older adults, it identified the highest rate of deficiency (21%) in those who were younger (18-39 years) with the lowest rate of 10-11% in those aged 60-79 but rising to 17% in the 80+ age group.

A similar ‘U” shaped relationship has been identified in the West of Ireland. The highest prevalence of deficiency in a population group in Ireland was found in those of South East Asian ethnicity living in Dublin (n=186) where 66.7% were found to be deficient all year round and with only 6.7% having a level above 50 nmol/l .

Factors affecting vitamin D status

Vitamin D status varies by geographical area in Ireland. For example, those living in Leinster have the the lowest rate of deficiency while a higher prevalence is found in all other provinces. In the largest study to geomap vitamin D status in Europe (n=34,466) based on vitamin D samples from Irish adults mainly in Dublin, there was a striking difference in vitamin D status between postal codes areas. Notably, in winter, areas in South Dublin (Dublin 4, Dublin 6/6W, Dublin 14/16) were found to have greater levels when compared to west, central and north Dublin. In Dublin city centre (Dublin 1 and Dublin 2) there were also greater levels of deficiency (34- 37%) versus nearby areas of Dublin 4 and Dublin 6 where prevalence was nearly half this at 19%.

Several factors may account for these study findings including area differences in levels of UVB irradation, dietary vitamin D intake, sun exposure, ethnicity and lifestyle factors such as smoking. In particular, lower socioeconomic status (SES) is linked with lower vitamin D status in several studies including in the Irish TILDA sample, where lower asset wealth was associated with a 50% increased risk of deficiency. Lower consumption of vitamin D rich or fortified foods which are more expensive, less use of supplements and sun holiday travel in poorer socioecomic areas are factors. Lower SES is also associated with higher rates of obesity which probably lowers vitamin D levels as a result of sequestration in fat tissue. Smoking is also a factor, as it has been independently associated with lower vitamin D in most studies, though the mechanism is not understood.

Vitamin D testing

Vitamin D deficiency is often picked up on blood tests in those who either have no or nonspecific symptoms. However, severe deficiency can give rise to generalised aches and pains and osteomalacia, which can be exacerbated by low calcium intake. So who should be tested? Guidelines vary though ‘at-risk’ groups should be considered for testing. These include frail older adults, those with minimal sun exposure, malabsorption syndromes, unexplained musculoskeletal symptoms and low bone density. Consider rechecking levels to ensure adequate response to treatment, especially if compliance with supplements is in question or in those with osteomalacia or metabolic bone disease.

However, there is no need for routine testing or retesting. If using daily supplements, levels should not be checked for at least three months — the time taken to reach steady state. Its also important to factor in the season of testing when interpreting results. For example, vitamin D levels can typically vary by up to 15 nmol/l between seasons. A recent study in Dublin (n=36,458) found that nearly one in four patients were retested though 12.2% were done too early (within 3 months) or too frequent (29% had two or more retests annually) and 57% were in those who were initially vitamin D replete (≥50 nmol/l).

Prevention and Treatment

Whilst dietary sources of vitamin D are limited they account for a small but significant contribution to overall status, especially in the winter. Rich sources include oily fish, sundried mushrooms, vitamin D-fortified milk and breakfast cereals. Some fortified foods also have the added advantage of containing additional calcium, which along with vitamin D is important for bone health. However, diet alone is not enough to maintain adequate vitamin D status in the Irish population.

In most cases, oral supplementation with 800- 1,000 IU vitamin D3 daily will be sufficient to maintain a level of 50 nmol/L, though higher doses may be required if there is poor gut absorption, obesity or liver disease. A variety of vitamin D tablets are licensed to treat or prevent deficiency and include daily (800 IU or 1,000 IU), onceweekly (7,000 IU) or once-monthly (25,000 IU).

Therapy with 50,000 IU once weekly for about six weeks can be used for more rapid correction of deficiency followed by maintenance supplements. The dose response to supplements ranges from about 2.0 -2.5+ nmol/L per 100 IU, so 800 IU daily should result in a minimum increase of about 20 nmol/L. If additional calcium is required, combined vitamin D / calcium supplements can be used, aiming for total calcium intake (dietary and supplemental) of 1000 mg daily. While there are different recommendations for daily or equivalent daily vitamin D intakes, the National Academy of Medicine advises 600 IU/day for those aged between 1–70 and 800 IU/ day if older than 70.

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