Vitamin D is the name given to a group of fat soluble steroids, the two major physiologically relevant forms of which are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). 

Sources and metabolism of vitamin D 

Unlike other nutrients, vitamin D is a conditionally required nutrient being obtained from two sources – predominantly by skin production upon exposure to natural ultraviolet (UV) solar radiation, and to a lesser extent by oral intake. Being a fat soluble vitamin, it has a long half-life of about two weeks and is stored in fat tissues. 

For nearly six months of the year from October to March in Ireland, skin production of vitamin D is absent and the population is dependent on oral intake from natural foodstuffs (which are consumed in small quantities only), fortified foodstuffs (most notably some milk products for the past 25 years) and vitamin D supplements, either in multivitamin tablets or in combination with calcium tablets.

Vitamin D is carried in the bloodstream to the liver, where it is enzymatically converted to 25-hydroxyvitamin D (25OHD). Further hydroxylation by the kidney results in the formation of the active form of the vitamin: 1,25-dihydroxyvitamin D [1,25(OH)2D]. This is the hormonal form of vitamin D; its production is tightly regulated by parathyroid hormone (PTH) and the recently described phosphate-regulating hormone, fibroblast growth factor 23 (FGF23). The hormonal form promotes absorption of both calcium and phosphorus from the small intestine.

The hormonal form is also produced in other tissues in the body, such as the placenta during pregnancy, skin, gastrointestinal tract, lymphatic tissue, prostate and breast. At these sites, it is thought that 1,25(OH)2D only has a local effect. But overproduction such as in diseases like sarcoidosis and lymphoma may cause hypercalcaemia. Also, it is thought that this local production and action of 1,25(OH)2D may have other beneficial effects (see ‘Health consequences’ below).

Assessment of vitamin D status

The serum concentration of 25OHD is typically used to determine vitamin D status. It reflects vitamin D produced in the skin as well as that acquired from the diet, and has a fairly long circulating half-life of 15 days. It does not, however, reveal the amount of vitamin D stored in other body tissues. 

The measurement of serum 25OHD is technically complex and as with any analytical technique the value delivered by laboratories is only an estimation of the true value, due to inherent measurement uncertainty. Nonetheless, assays of high standard for 25OHD are now widely available in Ireland. The key challenge is the correct interpretation of the 25OHD result. First, it must be understood that the 25OHD result is a measure of supply but is not an indicator of disease. A result should never be used to state that a patient has ‘vitamin D deficiency’, although this is commonly misstated in clinical practice.  Essentially, it is a measure of supply and estimate of risk of bone disease. It is also an excellent means of assessing compliance for those on supplementation.

The simplest interpretation of a serum 25OHD result in line with an international report from the Institute of Medicine (IOM)¹ is:

• A level below 30nmol/L indicates risk of disease
• A level of 30-50nmol/L is satisfactory for the population at large
• A level above 50nmol/L guarantees adequacy in 97.5% of the population.

Any individual who is sun deprived is at risk of low vitamin D status. Predisposing factors contributing to risk of deficiency include age, ethnicity linked to wearing concealing clothing, residential latitude and seasonal differences in solar UVB availability. In Europe and Ireland in particular, our high residential latitude puts children and adults at high risk of 25OHD deficiency. Also at risk are pregnant and lactating women and their infants.

Recommended dietary intakes for North Americans

The IOM in North America, covering the US and Canada, recently updated its 1997 dietary reference intakes for both calcium and vitamin D for all life stages, except infants (see Table 1 and 2). It used two terms: the estimated average requirement (EAR), which specifies the average requirement; and the recommended daily allowance (RDA), which specifies the requirement that meets the needs of 97.5% of the population. 

 (click to enlarge)

 (click to enlarge)

The requirements specifically refer to individuals who are completely sun deprived. The IOM assumed minimal sun exposure when establishing intakes. It determined that North Americans need on average 400IU (10µg) daily. For those aged one to 70 years, the RDA is 600IU daily. For those over 70 years, the RDA rises to 800IU daily. 

It is noteworthy that most surveys in North America report that the average intake of vitamin D is less than the EAR but that the majority have 25OHD levels above 50nmol/L. This indicates that sunlight exposure, not surprisingly, contributes to vitamin D status. Therefore, with few exceptions, they concluded that most North Americans were receiving enough vitamin D.  

Impact of new North American recommendations on Ireland

There are two major differences in vitamin D supply in Ireland compared to North America: 

• Fortification of milk with vitamin D is mandatory in North America, whereas in Ireland it is optional and until recently was only available in some low-fat milk products which are usually more expensive
• Ireland is a higher latitude region and has a longer spell of absent ultraviolet irradiation. 

All age groups should be encouraged to consume fortified milk, pending fortification of all milk with vitamin D. Those who avoid milk should be encouraged to take low dose vitamin D supplements (about 400IU daily) during the winter months. Those who are housebound or sun deprived should remain on the supplement all year. At risk groups should be assessed by measurement of 25OHD prior to recommending higher doses than those recommended by the IOM. Indeed, poor compliance should be considered prior to recommending a higher dose. Pharmacologic doses of vitamin D given once or twice yearly as a means to prevent or correct privational vitamin D deficiency should be avoided in all cases especially the elderly because it is related to falls and fractures. 

Particular attention should be paid to the breast-fed infant, and the mother who is likely to be 25OHD deficient at the time of birth. The Food Safety Authority of Ireland (FSAI) recently launched a campaign recommending that all infants under the age of one-year-old be given vitamin D3 200IU (5µg) daily in order to satisfy the infant’s requirements. This is an important public health initiative targeting one of the most vulnerable and at risk groups for vitamin D deficiency in Ireland. The current policy of supplementing all infants from birth to one year with 200IU daily should be effective at improving vitamin D status in infants. In our experience the duration of dosing is important because prolonged intake of 400IU daily leads to levels well in excess of 50nmol/L.

Health consequences of inadequate vitamin D intake

Vitamin D deficiency culminates in rickets in childhood (which has re-emerged in Ireland in the children of immigrants from Africa and Asia) and osteomalacia in adults (which is now extremely rare). In adults, milder degrees of vitamin D deficiency predispose to low bone mass and fragility fractures in the aged population.

There has been a marked increase in reports in the literature suggesting a link between 25OHD levels and non-skeletal outcomes such as associations with cancer prevention, innate immunity, auto-immune disorders, diabetes mellitus and vascular disease of heart and brain. A role for vitamin D in cancer prevention has also been postulated because 1,25(OH)2D has been shown to control over 200 genes (both directly and indirectly) responsible for the regulation, differentiation, apoptosis and angiogenesis. It can increase the cellular proliferation of both normal and cancer cells and induce terminal differentiation. A practical example of this is in the use of 1,25(OH)2D and its active analogues in the treatment of psoriasis. Latterly, 25OHD deficiency has been linked with a host of disorders, from cardiovascular disease to schizophrenia and depression.

Studies on the non-calcaemic actions of vitamin D are intriguing but hampered by reverse causation. Reverse causation means that the attributed illness results in poor vitamin D status, principally due to sun deprivation as part of the chronic illness in question. The IOM report concluded that evidence of a link between vitamin D status and these extraskeletal benefits was inconclusive and inconsistent with respect to causation.

Reference

1. 1. Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC; National Academies Press 2011