Vitamin D
In the last few years there has been some interest in whether vitamin D might have something to do with CTS. Vitamin D deficiency is very common, especially in northern populations, and there are several possible relationships with CTS:
- Vitamin D deficiency might subtly impair nerve function and, like any other neuropathy, predispose to the development of CTS
- Vitamin D deficiency might specifically be a risk factor for CTS in some way
- Vitamin D supplementation might be beneficial even in the absence of deficiency to start with, either as a treatment for CTS in itself, or to aid recovery after surgery
There are some theoretical reasons for believing that vitamin D might be relevant. Firstly it is a steroid (or at least nearly so – one of the chemical bonds of the core steroid structure is broken in the vitamin D family of molecules) – sharing some of the same chemical structure with molecules about which you will read a lot in the treatment section of this site. Apart from its well known role in calcium metabolism vitamin D does have some anti-inflammatory effects including suppression of prostaglandin action and several pro-inflammatory cytokines. Some of these molecules have previously been shown to be elevated in samples from carpal tunnel syndrome patients. It has also been suggested to reduce the action of the enzyme aromatase, which is important in oestrogen metabolism and is the target of several of the drugs which are used in breast cancer – however it is worth noting that the breast cancer drugs have been associated with an increased risk of CTS, so if vitamin D is having a similar action one might expect high levels to also increase the risk of CTS if this is a relevant mechanism, quite the opposite of vitamin D deficiency being a risk factor for CTS.
The following papers are relevant, and predictably they have received a fair amount of publicity from organisations that sell vitamin D supplements:
(Oh 2013) – A very small study (6 patients and 6 controls) looking at the levels of many proteins in blood samples from the subjects found lower levels os vitamin-D-binding protein in the CTS patients. This paper seems statistically dubious to me. Ten different proteins were identified as having significantly different levels between the CTS patients and controls, but over 600 proteins were assessed and it is probable in such a small sample that a few would be significantly different in all 6 CTS patients by chance. Furthermore this is not vitamin D but a protein that acts as a transporter for vitamin D, as well as having other functions. Whether this study really says anything about vitamin D and CTS is very doubtful.
(Tanik 2016) – This group measured vitamin D levels in 90 patients with ‘mild to moderate’ CTS. The degree of severity was defined from the nerve conduction studies with moderate cases being those with delayed motor latency to APB but a preserved finger/wrist sensory potential – thus in terms of Canterbury grading the ‘mild’ cases would have been grade 1 or 2 and the ‘moderate’ cases grade 3. 60 of the subjects were found to be vitamin D deficient They found that vitamin D levels were correlated with the severity of the CTS, severity of pain from the CTS, and body mass index. However the relationship between vitamin D state and severity of CTS was not what one would expect if deficiency was leading to CTS – 25% of the vitamin D deficient group had ‘moderate’ CTS, while 53% of the group with normal vitamin D levels had ‘moderate’ CTS – ie the CTS seemed to be more severe in the patients with normal vitamin D levels. In a sub-group analysis of just the vitamin D deficient group they reported a positive correlation between vitamin D level and ‘severity of CTS’ though they do not explain in detail exactly how this particular analysis was conducted. Overall the various results reported seem to be internally inconsistent and one suspects that many are statistical artefacts resulting from over-analysis of a small data set.
(Lee 2016) – Measured vitamin D levels in 135 women with NCS confirmed CTS - vitD 20.8 (11.9) , 135 healthy control women – vit D 23.2 (9.2) and 135 women with other upper limb disorders – vitD 23.8 (9.7), all figures are mean (Standard deviation) in ng/ml. The reason for excluding men from this study is described as being because there were too few of them for statistical analysis but that would not have prevented them being included in the overall study and I find this explanation unconvincing. No significant difference in mean vitamin D level was found between the three groups. Having failed to find support for their primary hypothesis these authors went on to torture their data with sub-group analysis and were able to find a much smaller sub-group, women under 50 (35 subjects in each group), in whom the vitamin D level was lower in the CTS group than in the other two groups, though the p-values for these sub-group tests were not very impressive, p=0.035 and p=0.023. In a further sub-group analysis they divided their CTS patients and healthy controls (excluding the other disorders group for some reason) into vitamin D deficient and non-vitamin D deficient categories and found a higher incidence of CTS in the deficient group (60% vs 40%). This would be more convincing if the study started out from a random sample of the population categorized by vitamin D state and then looked at the incidence of CTS in the two groups.
(Gursoy 2016) – measured vitamin D levels in 108 CTS patients, only 57 of whom had NCS confirmation of the diagnosis) and 52 health controls. Vitamin D levels below 20 ng/ml, the working definition of deficiency, were found in 96% of the group with symptoms but negative NCS, 95% of the NCS confirmed CTS cases and 74% of the normal controls, which goes to show just how common vitamin D deficiency is, even in sunny Turkey where this study was performed. Unfortunately the control group for this study, who were opportunistically recruited from hospital staff and patient relatives was not entirely well matched, being a little younger and having significantly lower body mass index than the patient groups so it is not clear whether the difference in vitamin D levels was related to the presence of CTS or to some other factor.
(Demiyurek 2017) – Another study from Turkey, this time of 76 patients with symptoms of possible CTS, 40 of whom had normal NCS and thus may or may not have had CTS. Most laboratories would find evidence of CTS in a considerably higher proportion of subjects than this given a population of people with typical CTS symptoms. The authors term the subgroup with normal NCS ‘healthy subjects’ within this manuscript but in the tables the number seem to be reversed as there are said to be 36 healthy and 40 CTS subjects in the study and as they had all been referred for NCS for suspected CTS the term ‘healthy’ seems a little suspect – this does not inspire confidence in the investigators. 52% of the ‘healthy subjects’ were found to be vitamin D deficient compared to 19% of the CTS cases. This seems to contradict Gursoy et al. In the CTS group there was an inverse correlation between vitamin D level and the score on a visual analog scale for pain as a symptom but there are many possible explanations for this correlation which do not involve vitamin D playing a direct role in the causation of pain in CTS.
All of these papers have significant flaws is either design or analysis and in some cases they produce contradictory results or results of questionable relevance. Notwithstanding this however there is enough here to justify some better studies to try and resolve the questions that have been raised and in any case vitamin D deficiency is so common that many people might benefit from a modest supplement in any case, whether or not they have CTS.
Revision date - 23rd October 2017
