Correcting vitamin D levels improves fatigue severity?

I was interested to read the paper by Satyajeet Roy and colleagues [1] (open-access here) concluding that: "Normalization of vitamin D levels with ergocalciferol therapy significantly improves the severity of... fatigue symptoms". Ergocalciferol by the way, means vitamin D2, which is distinct from cholecalciferol (vitamin D3), the seemingly more desirable form of vitamin D supplementation (see here).

"It's beyond my control"

The Roy paper is open-access but a few details might be useful:

• "This study was a prospective non-randomized therapeutic study" which, from a bank of some 170 participants (aged between 18-75) presenting "with fatigue as their chief complaint" were whittled down to just over 130 with "low serum 25-hydroxyvitamin D (25-OHD) levels" (below 30 ng/ml).
• Said participants were included for study consisting of 50,000 IU (international units) of vitamin D2, 3 days a week for 5 weeks. As the authors note: "The prevalence of low vitamin D was 77.2% in all 171 patients, despite the fact that 51.5% patients with low vitamin D levels were regularly taking over-the-counter vitamin D-3 between 1000 and 2000 international units". Before and after supplementation data was collected including 25-OHD levels and scores on the Multidimensional Fatigue Symptom Inventory- Short Form (MFSI-SF).
• Results: authors noted: "a significant reduction in the severity of fatigue (fatigue symptom scores) after normalization of vitamin D levels". Various sub-scales of the MFSI-SF showed significant changes between pre- and post-intervention measurements.
• Authors concluded that when patient fatigue presents at a clinician's door, there may be some merit in testing vitamin D levels and supplementing appropriately.

The eagle-eyed out there will no doubt have already caught on to the fact that this was a straight forward before-and-after observation trial with no control group and no double-blind element to it. We'd like to think that vitamin D2 supplementation was the deciding factor when it came to the changes in fatigue scores but thinking about something does not necessarily make it so. That also vitamin D2 (ergocalciferol) was the supplement of choice over and above vitamin D3 might also raise some eyebrows [2].

Still, I remain interested in these findings and in particular, their potential relevance to conditions exemplified by fatigue such as Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS / ME). Indeed, a while back I discussed the paper by Berkovitz and colleagues [3] (see here) and their conclusions: "25-OH vitamin D levels are moderately to severely suboptimal in CFS patients" implying supplementation might be in order for some. The meta-analysis by Tomlinson and colleagues [4] suggesting that: "Vitamin D supplementation increases upper and lower limb strength" might also be relevant bearing in mind the participant group included for study.

Of course the clinical description of fatigue does not just cover CFS / ME but potentially a wide variety of different conditions. A quick browse of PubMed with the search term ' vitamin D and fatigue' reveals a whole slew of diagnoses which may be relevant to the Roy findings. I note that some of the literature talks about fatigue and depression as being something to examine further [5] specifically with something like multiple sclerosis (MS) in focus. I'm minded to bring readers back to a post I wrote not-so-long-ago about depression and vitamin D (see here) as possibly also being relevant to this area.

Some music then. America by Razorlight.

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[1] Roy S. et al. Correction of Low Vitamin D Improves Fatigue: Effect of Correction of Low Vitamin D in Fatigue Study (EViDiF Study). N Am J Med Sci. 2014 Aug;6(8):396-402.

[2] Romagnoli E. et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008 Aug;93(8):3015-20.

[3] Berkovitz S. et al. Serum 25-hydroxy vitamin D levels in chronic fatigue syndrome: a retrospective survey. Int J Vitam Nutr Res. 2009 Jul;79(4):250-4.

[4] Tomlinson PB. et al. Effects of vitamin D supplementation on upper and lower body muscle strength levels in healthy individuals. A systematic review with meta-analysis. J Sci Med Sport. 2014 Aug 11. pii: S1440-2440(14)00163-7.

[5] Knippenberg S. et al. Vitamin D status in patients with MS is negatively correlated with depression, but not with fatigue. Acta Neurol Scand. 2011 Sep;124(3):171-5.

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Roy S, Sherman A, Monari-Sparks MJ, Schweiker O, & Hunter K (2014). Correction of Low Vitamin D Improves Fatigue: Effect of Correction of Low Vitamin D in Fatigue Study (EViDiF Study). North American journal of medical sciences, 6 (8), 396-402 PMID: 25210673