Casting light on the sunshine vitamin

You’ve got to stay out of the sun to avoid skin cancer, but too little sun leads to deficiency – Dr Keith Williams lets us in on the importance of vitamin D

It is estimated that approximately 1 billion people have a vitamin D deficiency or insufficiency1. Studies have indicated that deficiency of this vitamin can be particularly pronounced within the elderly population of the UK and the US, where between 40% and 100% of the population may have serum concentrations below the preferred lower level.

The vitamin D deficiency disease rickets was first fully described medically in 1650 but the active components were not completely understood until the first half of the 20th century. Most cells within the body have vitamin D receptors present and some cell types also possess the necessary mechanisms of producing the active forms.

The human body produces vitamin D from exposure to sunlight, or obtains it from diet (particularly oily fish) or dietary supplements like via multi-vitamin pills or, in some countries, foodstuffs such as milk, yoghurt and bread are fortified with vitamin D.

While the name implies a single compound, vitamin D is actually used to describe a group of fat-soluble secosteroids. From a health point of view, the most important substances are currently considered to be vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Vitamin D3 is the natural form in humans and vertebrates, while vitamin D2 predominates in fungi, invertebrates and plants.

In humans, the production of the active form of vitamin D is a four-stage process. 7-Dehydrocholesterol is converted to pre-vitamin D3 through photolysis in the skin. This conversion requires exposure to ultraviolet (UV) light in the range 290-315 nm (typically referred to as being UVB). Pre-vitamin D then spontaneously isomerises to vitamin D3, before being hydroxylated in the liver to form 25-hydroxyvitamin D3 (also known as calcidiol). Once produced calcidiol is stored in the liver until required. The ultimate active compound, 1,25-dihydroxyvitamin D3 (calcitriol), is produced either in the kidney, where it is released back into the blood stream to act like a hormone or within monocytes and macrophages (white blood cells) where it acts locally to fight microbial infection.

Vitamin D can be produced synthetically by UV irradiation of a suitable starting material. Vitamin D2 is produced in this way from ergosterol derived from yeast and vitamin D3 from 7-dehydrocholesterol derived from lanolin.

Vitamin D enhances the absorption of dietary calcium and phosphorus, both of which are essential for the production and maintenance of skeletal bones. Poor absorption of these elements can lead to rickets in children and osteomalacia (bone softening) in adults. There is significant evidence from numerous scientific studies which demonstrates that maintaining an appropriate level of circulating vitamin D will help to maintain a healthy skeleton and mitigate the effects of osteoporosis.

While vitamin D is essential for the maintenance of good skeletal health, vitamin D deficiency is now increasingly being linked to a range of other serious medical conditions. Vitamin D appears to be involved, directly or indirectly, in the regulation of more than 200 genes and its deficiency has been linked with cancer, autoimmune diseases, diabetes and cardiovascular conditions. Insufficient vitamin D in utero and during the first few years of life has been linked to an increased risk of schizophrenia and depression in later life.

As well as the more obvious causes of low serum concentrations of vitamin D such as liver disease, kidney disease and poor absorption from the gut, there are one or two surprising causes of low circulating concentrations of vitamin D. Many individuals are heeding government advice regarding reducing the risk of skin cancer by applying sunscreen to reduce skin damage through the absorption of UVB radiation. The use of such products has the unfortunate side effect of stopping the exact wavelengths of light required to produce vitamin D. A cream with Sun Protection Factor (SPF) of 8 or 15 will reduce vitamin D production by 92.5% and 99% respectively. Studies also show that living above a latitude of 35 degrees North or below 35 degrees South (i.e. Crete or Sydney respectively), will significantly reduce the production of vitamin D during the winter months as so little of the essential UVB radiation will reach the Earth’s surface in those areas.

With the developing body of evidence surrounding the effects of vitamin D insufficiency there has been a demand for the measurement of vitamin D levels in serum to monitor an individual’s status.

There is no current consensus on optimal serum concentrations of vitamin D, but a preferred range of vitamin D has been suggested: 30 to 60 nanograms per millilitre of the combined total of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2. Below 30 ng/ml, an individual may be deficient or insufficient, while greater than 150 ng/ml may cause vitamin D toxicity.

Measurement of serum vitamin D is typically carried out using immunoassay or liquid chromatography-mass spectrometry and its variants. The assumption that either methodology will provide 100% accurate results is flawed. Over time, the performance of immunoassays can change, for a number of reasons. The apparently greater specificity of liquid chromatography-mass spectrometry was also called into question when, in January 2009, the New York Times reported that Quest Diagnostics, the largest medical testing laboratory company in the US, had incorrectly reported elevated vitamin D test results in patient samples after using mass spectrometry. Although the total number of erroneous results was not reported, the problem data covered two years worth of testing, implying a relatively large number of results.

These issues highlight the importance of using appropriate controls and certified standards in the assessment of patient samples, as inaccurate reporting of results may cause harm to a patient through over or under prescribing of a treatment.

There are a small number of recognised producers of appropriately certified vitamin D reference materials in the world and LGC Standards has consolidated these materials into a range specifically designed for analytical laboratories. This collection of matrix-matched certified reference materials and certified pure materials (in solution and solid form) allows laboratories and other testing bodies to calibrate and monitor the performance of their assays (immunoassay or chromatographic) and ensure that data provided for clinical assessments are accurate and fit for purpose.

So, what is good advice to avoid having a low circulating vitamin D serum concentration?  The skin has a large capacity to produce vitamin D and the body can store material until required, so sensible exposure to sunlight during summer months should maintain appropriate serum concentrations of the vitamin.

Author: Dr Keith Williams from LGC Forensics