Carpal tunnel syndrome (CATS) is one of the most common peripheral neuropathies affecting the anatomy of the wrist. It causes compression of the median nerve, a large nerve that innervates the arm, forearm, and hand. This compression causes the affected individual to feel pain, numbness, or tingling along the area of the upper extremity affected by the pressure. Furthermore, CATS often leads to a weakening of grip and hand function. CATS typically affects individuals between the ages of 40 and 60; however, the condition can also affect individuals of other ages. Obesity, diabetes, repetitive stress injury, rheumatoid inflammation, pregnancy, and genetic factors interact to increase the risk of CATS.
Women are twice as likely to contract CATS as men, with 193 and 88 women and men affected respectively per 1,000,000. Vitamin D is a fat-soluble vitamin that regulates calcium and phosphorus metabolism and immunological function. It is also critical for endocrine, cardiovascular, skeletal, and skin health and is associated with metabolic and antioxidant/anti-inflammatory properties. Therefore, vitamin D deficiency could potentiate several neuropathic or pain syndromes associated with increased inflammation. Vitamin D deficiency also increases the severity of symptoms in CATS. To date, it is unclear how vitamin D supplementation can help manage CATS.
A very recent study included 14 patients with CATS from two centers. All participants had carpal tunnel on one or both wrists and low vitamin D levels, and none had consumed vitamins for six months prior to the study period, nor did any of the participants have a history of medical or surgical treatment for this problem. Study participants were screened for other conditions that could cause CATS or similar symptoms, such as neuropathies, inflammatory syndromes, trauma to the affected limb, poorly managed diabetes, thyroid and parathyroid disease, cervical problems and obesity. All study participants were women with an average age of 51 years.
Participants were randomized to receive corticosteroid therapy alone or with vitamin D supplementation. Block randomization was used to ensure homogeneity within the cohort. Among CATS patients with low vitamin D levels, adding vitamin D to corticosteroid therapy led to improved pain relief, a reduction in symptom severity, and some electromyographic (EMG) parameters. At baseline, Phalen and Tinel tests were conducted on all patients, with positivity rates of 86% and 71%, respectively. When stratified by group, the intervention group had 100% Phalen positivity at baseline, which reduced to 75% after three months. By comparison, Phalen positivity rates in the corticosteroid-alone group were 67% and 33%, respectively.
At baseline, subjects treated with corticosteroids alone had a 50% positive Tinel test, which dropped to 33% within three months. Compared to baseline levels of 88%, vitamin D supplementation led to a Tinel test positivity of 75% within three months. Pain relief was greater in the intervention group compared to controls, which corresponds to increased vitamin D concentrations. Symptom severity was reduced in both groups without significant improvement in functional status. With EMG, median nerve motor latency and sensitive driving speed improved in the intervention group. Previous studies have indicated that vitamin D deficiency increases the risk of CATS and the severity of symptoms.
This new investigation confirms previous findings and suggests that vitamin D supplementation in CATS patients with low vitamin D levels may reduce levels of innervation and hypersensitivity, thus reducing the sensation of pain and tingling in the nerves. Lower levels of vitamin D were associated with greater severity of symptoms, which improved after three months of supplementation alongside corticosteroid therapy. There is still doubt whether the vitamin D receptor (VDR) may only be related to disease progression. A 2018 investigation explored the correlation of VDR expression with clinical characteristics of carpal tunnel syndrome, such as age, duration/severity of symptoms, and electrophysiological severity.
A diverse range of vitamin D receptor expression was observed. VDR expression was independently associated with distal motor latency, suggesting that its expression may be associated with disease progression, as prolonged distal motor latency reflects the severity of the disease. illness. Therefore, vitamin D protects against neuropathies such as CATS by regulating vitamin D receptors, cellular antioxidant activity, and suppressing the expression of L-type calcium channels. The latter event may be responsible for controlling pain sensitivity. Furthermore, control over cellular redox status would imply that oxidative stress could be a significant local component in the development or progression of CATS.
Ischemic reperfusion injury is thought to be a cause of idiopathic CATS. The gene expressions of NF-κB, eNOS, superoxidase dismutase (SOD), and TGF-β receptor in fibroblasts and vascular endothelial cells of subsynovial connective tissues of patients were significantly higher than those of controls. A significant positive correlation was found between the subjective severity of CATS symptoms and the immuno-reactivities of NF-κB and eNOS. Increased total oxidative stress (TOS) and oxidative stress index (OSI) and decreased total antioxidant status (TAS) could stimulate fibrosis through a disturbed signaling pattern in the tenosynovium and median nerve. It is no coincidence that one of the most used painkillers for neuropathic pain is lipoic acid, which is also a powerful antioxidant.
Patients with mild disease also show lower levels of SOD, nitric oxide, IL-6, and TNF-α than patients with severe disease, leading scientists to think that CATS is likely a disease of sterile inflammation and stress imbalance oxidative. Sterile inflammation, in turn, would implicate the role of the NLRP3 inflammasome in this condition and an influence of vitamin D on this protein complex has been demonstrated. Two very recent investigations demonstrated that vitamin D negatively regulates the NLRP3 inflammasome via VDR-dependent signaling to effectively inhibit IL-1β secretion. With this information, vitamin D supplementation could be considered capable of positively influencing the clinical course of carpal tunnel.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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