We investigated the clinical usefulness of oral supplementation with a combination product containing alpha-lipoic acid, curcumin phytosome, and B-group vitamins in 180 patients with carpal tunnel syndrome (CTS), scheduled to undergo surgical decompression of the median nerve. Patients in Group A (
Peripheral nerve compression syndromes (also known as tunnel syndromes or entrapment neuropathies) are common disabling conditions that occur when nerves are compressed through bony, fibrous, osteofibrous, and fibromuscular tunnels, impairing nerve function [
Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy in the upper extremity, with a lifetime risk of approximately 10% [
The mainstay of definitive therapy for severe CTS is surgery [
Alpha-lipoic acid [
In this report, we sought to analyze the clinical usefulness of oral supplementation with a combination product (Axin C) containing such active compounds in a sample of CTS patients who were scheduled to undergo surgical decompression of the median nerve. The primary aim of this study was to compare the magnitude of symptoms reduction (hyperalgesia, paresthesia, nocturnal symptoms, and limitations to everyday life) in CTS patients who received oral supplementation both before and after surgery compared with those who did not. Secondary endpoints were the numbers of positive and negative results in Tinel’s and Phalen’s tests, compliance, and patients’ subjective satisfaction with oral supplementation.
This research was designed as a prospective, observational study of 180 consecutive CTS patients (44 males and 136 females, mean age: 57.9 ± 14.8 years) who were scheduled to undergo surgical decompression of the median nerve at the IRCCS MultiMedica (Sesto San Giovanni, Italy). The enrollment period was 6 months, with a planned minimum follow-up period of 3 months. The inclusion criteria were as follows: (1) a diagnosis of CTS based on nerve conduction studies and electromyography; (2) positive results in Tinel’s [
Test materials were supplied by Agave Farmaceutici srl (Prato, Italy). The oral supplement tested in this study (Axin C) was in tablet form and contained alpha-lipoic acid (300 mg), curcumin phytosome (500 mg), and B-group vitamins (vitamin B1, 1.05 mg; vitamin B2, 1.2 mg; vitamin B5, 4.5 mg; vitamin B6, 1.5 mg). The concentrations of the actives were based on previous studies.
The study participants (
All patients underwent an endoscopic carpal tunnel release procedure under a same-day surgery regimen. Local anesthesia (without epinephrine) was performed with levobupivacaine 2% (5 mL) under median and ulnar nerve blocks at the wrist. A pneumatic tourniquet was positioned over the arm. A single-portal endoscopic carpal tunnel release system (Arthrex Inc., Naples, FL, USA) was used for this study. A single short (1 cm) transverse incision was performed at the level of the distal cutaneous crease on the volar side of the wrist. The incision was situated 1 cm proximal to the pisiform and 1 cm medially to the radial side of the wrist. After opening the brachial fascia proximal to the transverse carpal ligament and entering into the carpal tunnel space with a dissector, the endoscope was introduced and the white, transverse fibers of the ligament were visualized. Under clear vision, the ligament was cut by a retrograde release blade located at the extremity of the optic. A complete section of the ligament was confirmed after the detection of a “U” image in the monitor (Figure
Progressive retrograde ligament section (panels a and b).
The primary endpoint of the study was the magnitude of symptoms reduction (hyperalgesia, paresthesiae, nocturnal symptoms, and limitations to everyday life) in the three study groups. Each endpoint was evaluated at each visit on a 6-point Likert scale ranging from 0 (minimum) to 5 (maximum). Secondary endpoints were the numbers of positive and negative results in Tinel’s and Phalen’s tests, compliance, and patients’ subjective satisfaction with the oral supplementation.
Categorical variables were assessed as counts and percent frequency and compared using the chi-squared test. The data were checked for normality using the Kolmogorov-Smirnov test for continuous variables. Normally distributed variables were compared across different time points (
The baseline characteristics of the three study groups at
Baseline characteristics of the three study groups at
Variable | Group A ( |
Group B ( |
Group C ( |
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Age, years |
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0.14 |
Male sex, ( |
12 (20%) | 15 (25%) | 17 (28.3%) | 0.56 |
Hyperalgesia |
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0.34 |
Paresthesia |
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0.32 |
Nocturnal symptoms |
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Limitations to everyday life |
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Positive Tinel’s test, ( |
60 (100%) | 58 (96.6%) | 57 (95%) | 0.21 |
Positive Phalen’s test, ( |
56 (93.3%) | 51 (85%) | 53 (88.3%) | 0.34 |
Hyperalgesia, paresthesia, nocturnal symptoms, and limitations to everyday life were rated on a 6-point Likert scale ranging from 0 (minimum) to 5 (maximum). Data are expressed as counts and percentages or means and standard deviations, as appropriate. Statistically significant differences across the study groups are marked in bold.
The efficacy data for the primary study endpoints are shown in Table
Primary study endpoints in the four study visits.
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Hyperalgesia |
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Paresthesias |
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Nocturnal symptoms |
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Limitations to everyday life |
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Data are expressed as means and standard deviations. Statistically significant differences between Group A and Group B at the
Changes in nocturnal symptoms observed in Groups A and B in the four study visits. The results indicated that patients in Group B had significantly lower nocturnal symptoms scores compared with Group A subjects at both
Table
Results of Tinel’s and Phalen’s tests (secondary study endpoints) in the four study visits.
Group A | Group B | Group C | ||||||||||
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Positive Tinel’s test, ( |
60 (100%) | 60 (100%) | 18 (30%)* | 10 (16.6%)* | 58 (96.6%) | 57 (95%) | 14 (23.3%)* | 8 (13.3%)* | 57 (95%) | 57 (95%) | 15 (25%)* | 12 (20%)* |
Positive Phalen’s test, ( |
56 (93.3%) | 57 (95%) | 16 (26.6%)* | 12 (20%)* | 51 (85%) | 51 (85%) | 12 (20%)* |
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53 (88.3%) | 55 (91.7%) | 13 (21.7%)* | 8 (13.3%)* |
Data are expressed as counts and percentages. Statistically significant differences between Group A and Group B at the
The results from the present study indicate that CTS patients who received oral supplementation with alpha-lipoic acid, curcumin phytosome, and B-group vitamins twice a day both before and after scheduled surgery, for 3 months each (totaling 6 months of supplementation), had a reduced burden of nocturnal symptoms (as assessed at 40 days post-surgery) and were less likely to have positive Phalen’s test at 3 months after surgery. The treatment was associated with high satisfaction levels and good compliance.
In comparison with subjects suffering from radiculopathy (who generally show day-time pain with arm use), night pain is a common complaint of CTS patients [
Previous studies have suggested that the neuroprotective effects of alpha-lipoic acid may limit and correct the clinical course of CTS. In a study of 112 subjects with moderately severe CTS, Di Geronimo et al. [
Curcumin, a major active polyphenolic compound of turmeric (
Although their effectiveness as a monotherapy is still controversial, B-group vitamins are often used as a conservative and adjunct therapy in the treatment of CTS. In a Cochrane review, Ang and coworkers [
The results of our study indicate that the clinical benefits of supplementation with alpha-lipoic acid, curcumin phytosome, and B-group vitamins were evident only in patients who received the supplements twice a day both for 3 months before and a further 3 months after scheduled surgery (Group B). In contrast, we did not observe significant improvements in patients in Group C, who received oral supplementation twice a day for a total of 3 months before surgery only. These data indicate that maintaining supplementation after surgery clearly results in better outcomes as opposed to discontinuing treatment. We, thus, believe that the lack of adequate supplementation of CTS patients after surgery may lead to poor control of symptoms, lost productivity, reduced quality of life, and an increased incidence of complications. The management of CTS after surgery, thus, requires continued supplementation to improve the clinical outcomes. We also hypothesize that prolonged supplementation may improve symptoms by increasing blood supply to the nerve. In this regard, the blood supply needs of peripheral nerves are known to be related to their conducting function [
There are several limitations to this study which need to be mentioned. First, this study was conducted in Caucasian individuals, so results cannot be simply extrapolated to populations with different ethnic backgrounds. Second, our study should be considered as an exploratory analysis and independent replication is needed to extend and confirm our results. CTS patients should be treated on an individual basis according to each patient’s disease characteristics, based on clinical trial data and influenced by the personal experience of the surgeon. Third, although we showed that a combination treatment is effective in reducing nocturnal pain associated with CTS, our study did not compare the effect of the combination product with that of each compound alone (i.e., alpha-lipoic acid, curcumin phytosome, and B-group vitamins alone).
These caveats notwithstanding, the results of the present study suggest that CTS patients who receive oral supplementation with alpha-lipoic acid, curcumin phytosome, and B-group vitamins twice a day, for 3 months both before and after surgery, have a reduced burden of nocturnal symptoms at 40 days after surgery and are less likely to have a positive Phalen’s test at 3 months after surgery. The treatment was associated with high satisfaction levels and good compliance, suggesting the potential clinical usefulness of this supplementation before and after surgery in CTS patients scheduled for the surgical decompression of the median nerve.
The authors declare that there is no conflict of interests regarding the publication of this paper.