Vitamin B6 for Carpal Tunnel Syndrome
April 1999; Volume 2: 43-46
By Joya Tillem, MD, Jay K. Udani, MD, and Mary L. Hardy, MD
Carpal tunnel syndrome (cts) vexes patients and health care providers alike. Despite the prevalence of this disease (99 per 100,000),1 its cause is still not fully understood. CTS may be the result of repetitive motion injury or secondary to one of many medical conditions. Short of surgery, there is no proven cure. Some studies have suggested that vitamin B6 (pyridoxine) may help alleviate the symptoms of CTS. However, other clinical trials have found no clinical benefit from vitamin B6 supplementation.
CTS History and Conventional Therapy
Numbness, tingling, and burning in the first three fingers, particularly at night, characterize the onset of this disease. A well-described complication of diabetes, hypothyroidism, pregnancy, amyloidosis, rheumatoid arthritis, acromegaly, obesity, and trauma, CTS is also commonly found in typists, carpenters, and others who perform repetitive work with their hands. Rest, wrist splinting, NSAIDs, corticosteroid injections, and surgical decompression of the median nerve comprise the range of available therapy.
Mechanism of Action/Laboratory Analysis
Pyridoxine, an essential water-soluble vitamin, serves as a coenzyme for many decarboxylation and transamination reactions and has a role in hyaluronic acid maintenance in joint space. After ingestion, pyridoxine is converted to its active form pyridoxal-5’phosphate (PLP) in the liver.
Indices for vitamin B6 status are divided into direct and indirect measures. Plasma PLP is considered the most relevant direct measure, and is the most frequently used assay.2 Plasma PLP is the primary form of circulating vitamin B6, representing approximately 70-90% of the total vitamin B6 in the plasma.2 Unfortunately, it is not a perfect measure because other factors such as protein intake have been shown to alter plasma PLP measures. For example, an increase in dietary protein intake will decrease the plasma levels of PLP.
By measuring the rate of pyridoxine-dependent enzymatic reactions, pyridoxine also can be indirectly assayed. The measurement of erythrocyte glutamic oxaloacetic transaminase (EGOT) activity is a commonly used indirect measure. A deficiency of vitamin B6 results in a decrease in the activity of EGOT.
Clinical Studies
All the clinical studies examined rely on the assumption that serum levels of pyridoxine are reduced in patients with CTS, and that raising those levels reduces CTS symptoms. Neither assumption is established.
In 1976, the first study to correlate pyridoxine deficiency and CTS showed that a "deficient" EGOT, in the presence of symptoms consistent with CTS, when treated with oral vitamin B6 (300 mg/d), increased by 55-68%.3 The percent "deficiency" of EGOT decreased from 26.8% to 1.6% after only two weeks of supplementation (P < 0.001). But this small study (N = 10) failed to show any significant clinical improvements.
In 1977, the same author showed a significant correlation between EGOT "deficiency" and CTS (P < 0.001), and reported significant clinical improvement based on self-reported symptom scales (P < 0.01) after 11 weeks of supplementation with vitamin B6.4 This too was a small study (N = 11). Electromyographic (EMG) readings before and after supplementation were inconclusive, though the author was able to show an increase in range of motion using the Preston pinch gauge.
In 1983, a study of six patients with CTS who were also found to have a deficiency of vitamin B6 by measurement of EGOT demonstrated significant decreases in distal motor latency and increases in conduction velocity of the median nerve in patients who were receiving pyridoxine supplementation compared with EMG reading when receiving placebo.5 Clinical symptoms related to CTS were not used as outcome measures in this trial.
In 1984, investigators in a study of 33 CTS patients categorized subjects by CTS symptoms and standardized EMG criteria into four groups: normal, CTS, peripheral neuropathy, and CTS and peripheral neuropathy.6 No difference between EGOT levels was noted when the populations were controlled for the presence of peripheral neuropathy. In other words, once all the patients with peripheral neuropathy were removed from the study, there was no difference in EGOT level between control patients and those with CTS symptoms.
In 1989, a study of 14 female patients (controls, CTS patients, and CTS patients post-surgical decompression) found a significant correlation between the presence of CTS and pyridoxine deficiency (P = 0.01) when measured by tyrosine decarboxylation assay.7
In 1996, a cross-sectional analysis of 125 employees chosen at random from two work sites was conducted.8 Each employee submitted to EGOT and PLP analysis, electromyelography of median and ulnar nerve function, and self-reported symptom questionnaires. CTS diagnosis was established by both EMG and self-reported symptoms. No correlation between serum pyridoxine levels and CTS could be demonstrated.
The largest study examined 441 community dwelling persons.9 Patients had nerve conduction studies, completed symptom questionnaires, and had serum PLP levels evaluated. A comparison was made between serum PLP measures, prevalence and severity of median nerve slowing, and frequency of self-reported hand/wrist symptoms. After a multivariate analysis that controlled for age, body mass index, sex, use of tobacco, alkaline phosphatase levels, and vitamin use, the authors found that the pyridoxine levels in males were inversely correlated with the prevalence of pain, the frequency of tingling and nocturnal awakening, and the Phalen test result (P < 0.05). Though this is again a random cross-sectional population without intervention or definitive diagnosis of CTS, a multivariate analysis was used to control for a number of potentially confounding variables.
Adverse Effects
As a general rule, water-soluble vitamins have little toxicity. Vitamin B6 does not, however, enjoy this luxury. Gradually progressive sensory nerve toxicity (affecting senses of touch, temperature, and pain) has been associated with vitamin B6 when it is taken in doses of 2 g/d.10 Furthermore, there have been reports of at least three patients who took vitamin B6 doses of less than 1 g daily for 8-36 months and experienced symptoms of neuropathy.11 In this report, one patient claimed never to have exceeded 200 mg/d but had taken this dose for three years. Prolonged low-dose intake of vitamin B6 may result in a cumulative toxicity.
Last year a governmental body established a maximum safe level called tolerable upper intake levels (UIL) for vitamin B6. The Standing Committee on the Scientific Evaluation of Dietary References Intakes, determined that the UIL for vitamin B6 is 100 mg/d for persons over age 19, including women who are pregnant or lactating.12
Formulation and Dosage
The Reference Daily Intakes (RDI) for B6 for adult males and adult females are 2.0 mg and 1.6 mg, respectively. Recommended dosing of pyridoxine for CTS is 50 mg/d increasing to 100 mg/d for up to three months. The safe therapeutic range is small (from 50-100 mg/d), given pyridoxine’s potential toxicity. Longer treatment intervals at higher doses are not recommended.
There are also many readily available food sources of vitamin B6 including wheat germ, brewer’s yeast, seeds, nuts, soybeans, lentils, bananas, whole grains, and brown rice. A 3.5 oz serving of brewer’s yeast (perhaps the least appetizing way to get B6) contains 2.5 mg of vitamin B6.13 (See Table 1 for food sources and typical multivitamin content.)
| Table 1 | ||
| Sources of vitamin B6 _______________________________________ | ||
| Food | Serving Size | B6 Content |
| Wheat germ | 1 cup (crude) | 1.495 mg |
| Yellowfin tuna | 3 oz | 0.882 mg |
| Skinless chicken breast | 1 cup (cooked) | 0.840 mg |
| Banana | 1 medium | 0.682 mg |
| Spinach | 1 cup (cooked) | 0.436 mg |
| Avocado | 1 cup (sliced) | 0.409 mg |
| Sunflower seeds | 1 cup with hulls | 0.354 mg |
| Soybeans | 1 cup (dry, roasted) | 0.387 mg |
| Halibut | 3 oz | 0.337 mg |
| Multivitamin | B6 Content | |
| One-A-Day® Essential | 2.0 mg | |
| Centrum® | 2.0 mg | |
|
Source: Online USDA Nutrient Database for Standard Reference __________________________________________________________________ |
||
Conclusion
Several studies have shown clinical improvement in the symptomatology and serum pyridoxine levels in patients with CTS. These studies suffer from small numbers, erratic or absent controls, and lack of comparison with conventional treatments. These are, however, pilot studies from which larger randomized controlled trials may be justified. Economics suggest that such trials are unlikely as pyridoxine cannot be patented, and thus manufacturers must have another incentive to fund such studies.
Recommendation
Whether vitamin B6 is effective for CTS remains to be seen. Very limited evidence implies that a therapeutic trial of 100 mg of vitamin B6 daily for three months may be of benefit, but too few data are available to endorse its use at this time. Although dosing in individual studies was higher than 100 mg/d, it would not be prudent to exceed this limit. Until more conclusive data emerge on the relationship between vitamin B6 and CTS there is no reason to routinely measure serum vitamin B6 indices, including PLP or EGOT.
Dr. Tillem is Senior Resident, Department of Internal Medicine; Dr. Udani is a Fellow in Integrative Medicine and Health Services Research; and Dr. Hardy is Director of Integrative Services at Cedars-Sinai Medical Center in Los Angeles. Dr. Hardy is an Associate Clinical Professor of Medicine at the University of Southern California.
References
1. Stevens JC, et al. Carpal tunnel syndrome in Rochester, Minnesota, 1961 to 1980. Neurology 1988;38:134-138.
2. Leklem J. Vitamin B-6: A status report. J Nutr 1990;120(Suppl 11):1503-1507.
3. Ellis JM, et al. Vitamin B6 deficiency in patients with a clinical syndrome including the carpal tunnel defect. Biochemical and clinical response to therapy with pyridoxine. Res Commun Chem Pathol Pharmacol 1976;13:743-757.
4. Ellis JM, et al. Survey and new data on treatment with pyridoxine of patients having a clinical syndrome including the carpal tunnel and other defects. Res Commun Chem Pathol Pharmacol 1977;17:165-177.
5. Wolaniuk A, et al. Electromyographic data differentiate patients with the carpal tunnel syndrome when double blindly treated with pyridoxine and placebo. Res Commun Chem Pathol Pharmacol 1983;41: 501-511.
6. Byers CM, et al. Pyridoxine metabolism in carpal tunnel syndrome with and without peripheral neuropathy. Arch Phys Med Rehabil 1984;65:712-716.
7. Fuhr JE, et al. Vitamin B6 levels in patients with carpal tunnel syndrome. Arch Surg 1989;124:1329-1330.
8. Franzblau A, et al. The relationship of vitamin B6 status to median nerve function and carpal tunnel syndrome among active industrial workers. J Occup Environ Med 1996;38:485-491.
9. Keniston RC, et al. Vitamin B6, vitamin C, and carpal tunnel syndrome. A cross-sectional study of 441 adults. J Occup Environ Med 1997;39:949-959.
10. Schaumburg H, et al. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-448.
11. Parry GJ, Bredesen DE. Sensory neuropathy with low-dose pyridoxine. Neurology 1985;35:1466-1468.
12. Standing Committee on the Scientific Evaluation of Dietary References Intakes, Institute of Medicine. National Academy Press. In press.
13. Murray M, Pizzorno J. Encyclopedia of Natural Medicine. 1st ed. Rocklin, CA: Prima Publishing, 1996.
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