The “sunshine vitamin”
Vitamin D is sometimes referred to as the “sunshine vitamin” as it is produced by the body when skin is exposed to direct sunlight outdoors. Deficiencies in this essential nutrient can lead to issues such as muscle aches and weakness, persistent fatigue, mood swings, and dental problems. Vitamin D deficiency is a common global health issue, with a UK government estimate suggesting that 1 in 6 adults in the UK are deficient. Groups at higher risk include the elderly, those with darker skin, people who are housebound, and those with limited sun exposure.
Vitamin D deficiency in ME/CFS
Given that vitamin D deficiency is common and that ME/CFS often limits the time individuals spend outdoors, it is not a surprise that researchers from Japan determined that most participants who developed ME/CFS following SARS-CoV-2 (COVID-19) infection, or post-vaccination, also had vitamin D insufficiency/deficiency.
The study
The same group of researchers conducted a randomised controlled trial evaluating the efficacy of vitamin D replacement therapy guidance (as opposed to just vitamin D replacement) in 91 participants with ME/CFS following SARS-CoV-2 infection or vaccination and co-existing vitamin D insufficiency or deficiency. Participants were individuals aged 18 years or older and met the Canadian Consensus Criteria for ME/CFS.
Participants were randomised into two groups: an intervention group and a control group. The “investigational treatment” was a combination of daily vitamin D supplementation, dietary counselling, sun exposure, and exercise therapy. The control treatment was daily vitamin D supplementation alone and general ME/CFS guidance.
Important note: The details of what the exercise therapy entailed are not provided. This study was conducted in Japan but UK NICE guidance advises against recommending Graded Exercise Therapy (GET) and further states “Do not advise people with ME/CFS to undertake exercise that is not part of a programme overseen by an ME/CFS specialist team, such as telling them to go to the gym or exercise more, because this may worsen their symptoms.” Furthermore, the paper does not specify what the general ME/CFS guidance entailed.
The intervention group received investigational treatment for 24 weeks. The control group received the control treatment for 12 weeks, followed by the investigational treatment for 12 weeks to observe the response after switching. The researchers refer to this as a crossover design and plan to publish the results of the second 12 weeks in another paper.
Findings
- The intervention group demonstrated significant symptom reduction along with improvement of vitamin D levels at Week 12, whereas the control group showed minimal change in symptoms.
- “In the intervention group, immune symptoms showed the highest improvement rate (45.5%), followed by pain symptoms (39.1%) and sleep problems (37.0%).”
- Additionally, significantly more participants in the intervention group achieved <8 symptoms (no longer meeting ME/CFS diagnostic criteria), with 16 participants in the intervention group achieving this threshold compared to 1 in the control group.
According to the researchers, “These findings suggest that correcting vitamin D insufficiency or deficiency through comprehensive vitamin D replacement therapy guidance—including [vitamin D] supplementation with dietary counseling, sun exposure recommendations, and exercise therapy—may represent an effective therapeutic approach for ME/CFS following [COVID-19] or COVID-19 vaccination.”
Discussion
Both the intervention group and the control group received vitamin D for the first 12 weeks, therefore the findings would suggest that the differences in outcomes are more likely related to the differences in guidance offered rather than the vitamin D supplementation itself. These study findings should be interpreted with caution due to the lack of clarity around the therapy and advice provided, and the fact that it suggests that a proportion of individuals recovered following vitamin D supplementation plus guidance.
NICE guidance states: “Be aware that people with ME/CFS may be at risk of vitamin D deficiency, especially those who are housebound or bedbound … Explain to people with ME/CFS that there is not enough evidence to support routinely taking vitamin and mineral supplements as a cure for ME/CFS or for managing symptoms. If they choose to take a vitamin or supplement, explain the potential side effects of taking doses of vitamins and minerals above the recommended daily amount.”
Limitations
Additionally, the researchers are transparent with the limitations of the study, including:
- Open-label design (no blinding): Participants and researchers knew who received the intervention, therefore the effects of placebo response, observer bias, expectancy effects, and self-reporting bias could have influenced results. “However, the nature of the intervention … presented inherent challenges to blinding.”
- Single site/enrolment bias: 83.5% of participants came from one hospital/clinic, which limits generalisability of findings
- Simple symptom count: Using symptom count as primary outcome measure does not take into account symptom severity or overall quality of life.
- Intervention complexity: The treatment combined several elements (vitamin D supplementation, diet, sun exposure, exercise), making it difficult to isolate which component produced the effect.
The researchers mentioned: “To address these limitations, this study employed a crossover design, in which the control group received the control treatment for 12 weeks, then switched to the investigational treatment (the same comprehensive guidance provided to the intervention group) for the subsequent 12 weeks. If the control group also demonstrates symptom improvement during weeks 12–24 when receiving the comprehensive guidance, this crossover design will provide further evidence supporting the treatment effect beyond the primary 12-week comparison. … Results through Week 24, including the control group’s crossover response and Performance Status outcomes, will be reported in a separate publication.”
They concluded: “Future studies with larger sample sizes, longer follow-up periods, and double-blind placebo-controlled designs are warranted to further confirm the efficacy of vitamin D replacement therapy guidance and to assess the durability of treatment effects” in patients with ME/CFS following SARS-CoV-2 infection or vaccination.
Should individuals with ME/CFS take vitamin D supplementation?
It is important to consult a healthcare professional to determine whether supplementation is needed and, if so, the appropriate dosage to address any nutrient deficiency, including vitamin D.
Although a study may show minimal or mixed effects of vitamin D supplementation on ME/CFS symptoms, vitamin D remains an essential nutrient involved in key physiological processes such as bone health, immune function, and muscle function. The NHS provides detailed information on vitamin D on its website.
