Authors

Witham M, Kennedy G, Belch J, Hill A, Khan F

Institution

Ageing and Health, Division of Cardiovascular & Diabetes Medicine, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK

Background

Low circulating 25 hydroxyvitamin D (25OHD) levels have been associated with increased blood pressure, impaired vascular health and an increased risk of cardiovascular events. We have previously shown that patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) have vascular dysfunction, which is related to increased levels of low grade inflammation and oxidative stress. Vitamin D may affect the cardiovascular system through multiple pathways, and the aim of this pilot investigation in CFS/ME patients was to explore the association between serum 25-hydroxyvitamin D (25(OH)D) and markers of cardiovascular disease risk.

Results & Conclusion

Forty one participants (19–63 years old) were included in the study (mean length of illness 9.7 years). There were significant correlations between 25(OH)D levels and markers of inflammation, oxidative stress, endothelial function and arterial stiffness. Levels of 25(OH)D correlated significantly with age, but not with gender or BMI. These results extend findings in other populations to patients with CFS/ME, who have recently been shown to have impaired vascular function, and provide a rationale for proceeding to randomized controlled trials to examine the effects of vitamin D supplementation on cardiovascular disease risk in patients with CFS/ME.

Funding

The study was funded by a grant from ME Research UK, and GK received support from the Sir John Fisher Foundation (SJFN142).

Publication

Int J Cardiol, 2014 Jun 1; 174(1): 139-40

Comment by ME Research UK

Rickets is commonly thought of as the classic disease of vitamin D deficiency, but science is recognising that it is merely the extreme end of a spectrum of possible disorders, in effect the tip of the vitamin D-deficiency iceberg. The reality is that vitamin D deficiency remains common in the population. In young people, at both the foetal stage and during childhood, vitamin D deficiency can cause skeletal deformities and growth retardation, and increase the risk of hip fracture in later life. In adults, it can result in osteopenia and osteoporosis, and muscle weakness.

Recent scientific work, centering on the discovery that vitamin D receptors are widely distributed in the body and can be found in most cells and tissues and cells, has thrown new light on this vitamin and its role in a variety of key functions. Most interest, however, concerns the part played by vitamin D or its deficiency on the risk of chronic illnesses, including autoimmune and infectious diseases, the common malignancies, and cardiovascular disease.

Why might this be important in ME/CFS? Well, as a chronic illness with immune, infectious and cardiovascular aspects, there is at least a possibility that vitamin D deficiency/insufficiency could be involved in the development or maintenance of the condition or its specific symptoms. For example, vitamin D is known affect vascular smooth muscle cell proliferation, inflammation, vascular calcification, and blood pressure, all of which are involved in cardiovascular risk, while there is evidence that ME/CFS patients have associated cardiovascular symptoms, including attenuated heart rate and blood pressure regulation and – as a report from the University of Dundee showed – increased arterial stiffness. Again, vitamin D inadequacy has been linked with impaired neuromuscular functioning and chronic pain, two import facets of the day-to-day experience of ME/CFS patients.

These considerations, including the fact that vitamin D is known to influence inflammatory processes – whether as an inhibitory influence on TNFα and interleukin-1 production, or by reducing the activation of macrophages – intrigued researchers at the Institute of Cardiovascular Research, Ninewells Hospital Medical School, Dundee. And their interest was further stimulated by a 2007 report of improvement in endothelial vascular function in vitamin D-deficient patients with type 2 diabetes after a single large dose of oral vitamin D2 – suggesting, albeit tentatively, that there might even be a therapeutic role for vitamin D in ME/CFS patients whose endothelial vascular function has been found to be dysregulated by previous work in the unit.

The first step in determining whether there was an association between vitamin D and vascular function in people with ME/CFS was to find out if the vitamin D levels really are lower than normal (since if not, there is no point in looking further). To investigate this, ME Research UK gave a small “extension funding” award to Dr Faisel Khan of the Institute of Cardiovascular Research to test vitamin D levels in already-collect samples acquired from two separate studies previously funded by our charity. The aim was to measure the main circulating form of serum vitamin D (25-hydroxy-vitamin-D3), and the active hormone 1,25-dihydroxy-vitamin D3. These measures would then be related to previously-assessed vascular function in the two ME/CFS and control populations. If an association was found, a subsequent intervention trial might show whether vitamin D supplementation could be a relatively simple, effective way of contributing to reducing risk of cardiovascular disease in ME/CFS patients. In other illnesses, small scale intervention studies, aimed at increasing levels of 25-hydroxy-vitamin D in populations at risk of cardiovascular disease, have reported beneficial effects, and the same might be true for ME/CFS.

The study published in the International Journal of Cardiology reports these results of this pilot investigation on the associations between vitamin D levels and cardiovascular risk markers in ME/CFS patients. On the basis of these results, the team at the University progressed to a clinical trial of vitamin D.