By Dr. Willemina Rietsema
In restless legs syndrome, (sometimes written as RLS), people get a feeling like their legs are crawling with ants, tingling, burning, itching or cramping. These feelings get worse when the legs have been motionless for a while, especially at night and improve on movement. This leads to sleep disturbance, and results in further problems such as fatigue, mental health problems and high blood pressure. Therefore, it is important to find all possible causes of restless legs.
Restless legs syndrome has been associated with lack of iron, kidney disease, diabetes, Parkinson’s disease, rheumatoid arthritis, underactive thyroid, as well as with pregnancy.
A study two years ago showed an association between low B12 levels and restless leg syndrome [Possible association between vitamin B12 deficiency and restless legs syndrome – PubMed]. The authors compared 80 people with restless legs syndrome, and 80 people of the same age and sex but without the condition. The restless legs syndrome was carefully diagnosed by a neurologist, they used internationally agreed diagnostic criteria, and even conducted sleep studies on the study participants. They excluded other underlying diseases that could also cause restless legs, such as chronic kidney disease, renal failure, iron deficiency, pregnancy, peripheral neuropathy, Parkinson’s disease, and medication that could cause restless legs. They also excluded conditions that could cause similar symptoms such as sleep apnoea and other sleep disorders, and they excluded other conditions that could be associated with low B12 levels, including inflammatory bowel disease, metabolic syndrome, osteoporosis, heart disease, diabetes, lung disease, thyroid disease, liver and kidney disease. Further they excluded anyone who took medication that could affect B12 levels, and those with mental illness.
They found that the average B12 level in participants with restless legs was 168 pg/mL [this is the same unit of measurement that we use in the UK], while in people without restless legs it was 419 pg/mL. They also measured homocysteine, which was higher in the participants with restless legs than in those without, further indicating that the low B12 was the culprit, especially because folate levels [which also determine homocysteine] were equal in both groups. Further, kidney function, liver function, blood sugar, and iron status were similar in the two groups.
The 2024 NICE guideline on B12 deficiency recommends diagnosing B12 deficiency at levels below 180 pg/mL, and to do a further test for people with levels between 180-350 pg/mL. Therefore, with an average of 168pg/mL, over half of the participants in this study with restless legs would be considered B12 deficient according to the NICE guideline.
This study suggests that low B12 levels and/or B12 deficiency may be one of the causes of restless legs, but it does not prove it. There is a plausible mechanism. B12 deficiency leads to breakdown of the myelin, the protective sheath around the nerves. Nerves with broken myelin do not function as they should and could well cause symptoms like restless legs. But to prove that B12 deficiency causes restless legs ideally would require a randomised controlled trial, where one half of people with restless legs get vitamin B12, the other half do not. However, it is ethically difficult to defend withholding B12 from people who are deficient.
It is quite possible that low B12 levels and B12 deficiency cause restless legs. It is known that B12 deficiency causes breakdown of myelin, the protective fat sheath around the nerves. Nerves with broken myelin don’t function as they should and could result in symptoms like restless legs. However, this study doesn’t prove that the low B12 levels are the cause of the restless legs. If restless leg syndrome improves or disappears after treatment for B12 deficiency, this is another indication that B12 is a causal factor.
This study was done in China, in a population with different genetic makeup, different nutrition and different environmental influences. Ideally we need more studies like this in other populations to confirm these results.
PAS comment: thanks to Willemina for reviewing this topic for us. Quality research and critical evaluation are cornerstones of scientific progress and evidence-based decision-making. They help us separate fact from fiction, build a strong foundation of knowledge, and make informed choices that impact our lives and society.
Sources:
NHS website on restless leg syndrome: Restless legs syndrome – Causes – NHS
Geng, C. et al. (2022) Possible association between vitamin B12 deficiency and restless legs syndrome. Clinical neurology and neurosurgery..
NICE guideline on B12 deficiency in adults: Overview | Vitamin B12 deficiency in over 16s: diagnosis and management | Guidance | NICE
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