Pak J Med Sci 2012 Vol. 28 No. 2 www.pjms.com.pk 283
The most frequent entrapment neuropathy of
the upper limbs is carpal tunnel syndrome (CTS).
There are several conservative or surgical op-
tions available for the treatment of CTS. The most
common conservative treatments include wrist
splinting, non-steroidal anti-inammatory drugs
(NSAIDs), corticosteroid injection into the carpal
tunnel, systemic steroids, pyridoxine (Vitamin B6),
Some researchers have suggested that Vitamin
B6 deciency can lead to CTS, and that pyridoxine
is a suitable conservative option for the treatment
However, other researchers have not
found any obvious benet with pyridoxine in CTS.
1. Fariborz Khorvash, MD,
Assistant Professor, Department of Neurology,
Isfahan Neuroscience Research Center, School of Medicine,
2. Bahador Asadi, MD,
Assistant Professor, Department of Neurology,
University of AJA, Tehran, Iran.
3. Rasul Norouzi,
Neurology Assistant, Isfahan Neurosciences Research Center,
Department of Neurology,
4. Mohammad Mehdi Shahpoori, MD,
5. Adibnejad Mohammad,
Department of Biochemistry, Falavarjan Branch,
Islamic Azad University, Isfahan, Iran.
1,3,5: Isfahan University of Medical Sciences (IUMS), Isfahan, Iran.
Mohammad Mehdi Shahpoori,
* Received for Publication: February 2, 2012
* Revision Received: February 28, 2012
* Revision Accepted: March 1, 2012
Treatment of carpal tunnel syndrome:
A trial of Vitamin B6
, Bahador Asadi
, Rasul Norouzi
Mohammad Mehdi Shahpoori
, Sonbolestan Ali
, Adibnejad Mohammad
Objective: Carpal tunnel syndrome (CTS) is a common disorder that can be treated with surgery
or conservative options. There have been several studies of Vitamin B6 as a conservative
treatment for CTS, but its effectiveness remains controversial. Our objective was to compare
the efcacy of splinting and placebo with splinting and VitaminB6 in patients with CTS.
Methodology: We conducted a randomized case-control trial in the neurology clinic of Alzahra
hospital, Isfahan, Iran, between March 2009 and March 2010. Ninety outpatients who were at
least 18 years old and who had clinically and electrophysiologically conrmed idiopathic CTS
were included in the study. The patients were randomly allocated to two groups: placebo plus
wrist splinting (control) or VitaminB6 supplementation (for six months) plus wrist splinting
(case) for at least three months. Eighty-six patients (95%) completed the study. The primary
endpoint was improved sensory nerve conduction by the median nerve.
Result: Evaluations performed at three months follow up revealed a signicant difference in
the mean peak sensory latency between the case and control groups (p=0.002). A total of 65% of
patients in the case group reported subjective symptom relief compared with 58% of patients in
the control group. These data suggest that splinting combined with VitaminB6 supplementation
is more effective than splinting alone in improving electrophysiological parameters and
subjective symptoms of CTS.
Conclusion: Vitamin B6 is an effective treatment in mild and moderate CTS and could be
considered as a conservative treatment.
KEY WORDS: Vitamin B6, Carpal tunnel syndrome, Splinting, Electrodiagnosis.
Pak J Med Sci January - March 2012 (Part-II) Vol. 28 No. 2 283-286
How to cite this article:
Khorvash F, Asadi B, Norouzi R, Shahpoori MM, Ali S, Mohammad A. Treatment of carpal tunnel
syndrome: a trial of Vitamin B6. Pak J Med Sci 2012;28(2):283-286
Fariborz Khorvash et al.
284 Pak J Med Sci 2012 Vol. 28 No. 2 www.pjms.com.pk
To the best of our knowledge, there have been no
randomized clinical trials comparing splinting alone
with splinting plus Vitamin B6 for the treatment of
The aim of this study was to compare the effect
of splinting alone with splinting plus Vitamin B6 in
This randomized clinical trial was performed
at the neurology clinic of Alzahra Hospital, Isfa-
han, Iran, between March 2009 and March 2010.
The study was approved by the ethics committee
of Isfahan University of Medical Sciences. Written
informed consent was obtained from all patients
who participated in the study. Out patients with
clinically and electrophysiologically conrmed CTS
who attended our health center and who met the
selection criteria for the trial were enrolled. Clini-
cal conrmation of CTS was achieved by noting
compatible symptoms such as numbness, burning,
and tingling or pain in the wrists, hands, or ngers,
which are suggestive of median nerve involve-
Electrodiagnostic conrmation of CTS was
based on the guidelines of the American Associa-
tion of Electrodiagnostic Medicine.
exclusion criteria were specied with the aim of en-
suring a relatively uniform group of patients with
Inclusion criteria were:
* Clinically and electrophysiologically conrmed
* Patients age ≥ 18years
* Available for the three-month period of the
Exclusion criteria were:
* Pregnant women
* Previous treatment with a wrist splint
* History of previous carpal tunnel release
* Currently receiving other treatment for CTS
* History of wrist or median nerve injury due to
trauma (e.g. contusion, fractures) or prior wrist
* History suggestive of possible underlying causes
of CTS such as diabetes mellitus, thyroid disease,
rheumatoid arthritis, anatomic abnormalities of
the wrist or hand, and pregnancy
* Clinical signs and symptoms or electrodiagnostic
studies suggesting conditions that could mimic
CTS or interfere with its validation, such as
cervical radiculopathy, brachial plexopathy,
polyneuropathy, among others.
A group of 90 CTS cases was selected for the
trial based on the inclusion and exclusion criteria.
Afterward, a primary evaluation of baseline
electrophysiological values and possible prognostic
factors such as age, sex, dominant side, and bilateral
symptoms was made.
The patients were then randomly divided into
two groups. The rst group of patients (case group)
were treated with 80 mg/day VitaminB6 plus
splinting, and the second group (control group) re-
ceived a placebo along with splinting. The placebo
and VitaminB6 tablets were the same shape, color,
In patients with bilateral symptoms, splinting was
prescribed for the most affected hand. At present,
there are no standard guidelines for the wearing of
splints, but in this study, the patients were directed
to wear the splint continuously at night for at least
three months. The only other therapy allowed dur-
ing the study was Naproxen 250 mg/day, which
was prescribed by the neurologist for pain relief if
required. To avoid wrist and nger stiffness, pa-
tients were educated in the performance of a num-
ber of mild range-of-motion exercises throughout
The patients were permitted to continue their nor-
mal activities without any limitations. They were
followed up by telephone throughout the study
to see if they had continued with their prescribed
therapy or not, and to ask about possible side ef-
fects. After three months, 86 patients completed the
study. The electrophysiological assessments were
repeated at the end of the trial. Based on the nerve
conduction study (NCS) ndings, patients were di-
vided into three categories: Mild (3.5<distal sensory
latency <4.5); Moderate (4.5< distal sensory laten-
cy<5.5); and Severe (distal sensory Latency ≥ 5.5). In
addition, the patients were asked about subjective
Outcome Assessment: Although there is currently
no agreement on the best means of assessing treat-
ment effects, in this study, the results of the elec-
trodiagnostic study were considered the primary
endpoint. Subjective assessments of symptom im-
provement were based on the patients reporting of
their symptoms as ‘improved’ (complete recovery or
signicant recovery) or ‘not improved’ (mild recov-
ery, no change, mildly worse, or much worse),and
were considered the secondary end point.
Statistical Analyses: The results are presented as
mean ± standard deviation (SD). The mean NCS
values were calculated before and after the inter-
vention. Independent sample t tests were used to
Pak J Med Sci 2012 Vol. 28 No. 2 www.pjms.com.pk 285
identify differences between the analyzed case and
control groups. A Pvalue ≤ 0.05 was considered
statistically signicant. Statistical analyses were
performed using SPSS 14 for Windows (SPSS, Inc.,
Chicago, IL, 1996).
Eighty-six patients completed the study. They
ranged in age from 38 to 67 years. The mean age
of the patients in the case and control groups was
48.18±2.93 years and 45.89±3.56 years, respectively;
there was no signicant difference between the
groups in terms of age (p=0.25). Thirty patients in
the case group (69.87%) and 33 patients in the con-
trol group (76.7%) were women; there was no sig-
nicant difference between the groups in terms of
sex (p = 0.47) as summarized in Table-I.
The mean sensory peak latency of the median
nerve before and after the intervention was 5.2±1.1
and 4.8±1.2, respectively, in the case group (p
=0.002), and 5.1±1.1 and 4.9±1.3, respectively, in the
control group (p = 0.98). Improvement in median
distal sensory latency was observed in both groups;
however, the improvement was not statistically
signicant in the control group. Furthermore, a
signicant difference in mean peak sensory latency
was found between the case and control groups
A total of 65% of subjects reported subjective
symptom relief (improved)after the use of a splint
plus Vitamin B6 whereas only 58% of patients
reported symptom improvement from the splint
alone. No serious side effects were reported by the
CTS is the most common entrapment neuropathy
with a total lifetime risk of 10%.
It usually occurs
after the third decade of life, and tends to affect more
women than men (3: 1 ratio).
The majority of CTS
cases are idiopathic; however, many predisposing
factors for CTS have been suggested, including
diabetes mellitus, thyroid dysfunction, pregnancy,
and some rheumatologic diseases.
progressive ischemia and mechanical deformation
of the median nerve as a consequence of elevated
pressure within the carpal tunnel is believed to
be the underlying pathophysiology of CTS.
Symptoms consist of sensory complaints such as
tingling, a burning sensation, and numbness in
the territory of the median nerve, pain in the hand,
and motor decits such as weakness and atrophy
of the thenargroup of muscles, and reduction in the
dexterity of hand movements.
and clinical ndings
are both essential for diagnosing CTS. The most
sensitive electrodiagnostic test for CTS is the me-
dian nerve sensory conduction study, which pro-
vides evidence of a distal delayed sensory latency
in 70–90% of cases.
Several conservative and sur-
gical alternatives have been used for the treatment
There is currently no agreement on the
selection criteria for each treatment methodology,
but in severe cases the recommended treatment is
Patients with mild symptoms are
usually managed with nonoperative and alterna-
Initially, conservative treatments
are effective in approximately 80% of cases of CTS;
however, the rate of recurrence of symptoms is re-
ported to be close to 80% after one year.
Conservative options should be tried for those
who are not able to undergo surgery or for those
who do not wish to undergo surgery. The most
frequently used conservative treatments are
splinting, corticosteroid injection into the carpal
tunnel, NSAIDs, systemic steroids, pyridoxine
(Vitamin B6), and diuretics.
To the best of our
knowledge, few well-designed trials have evaluated
and compared these treatments
, and high quality
Treatment of carpal tunnel syndrome
Table-I: Mean sensory peak latency of the median nerve in the case and control groups before and after intervention.
Groups Before treatment After treatment Pvalue of within group comparison Pvalue of between group comparison
Case 5.2±1.1 4.8±1.2 0.002 0.002
Control 5.1±1.1 4.9±1.3 0.98
Table-II: Frequency distribution of
disease severity in the two groups.
Severity Case Control All patients
n % N % n %
(3.5< latency <4.5) 13 30.2 17 39.5 30 34.9
(4.5< latency<5.5) 18 41.9 16 37.2 34 39.5
Latency >5.5 12 27.9 10 23.3 22 25.6
All of the patients 43 100 43 100 86 100
Table-III: Comparison of NCS
changes between the two groups
Severity Case Control P value
Mean + SD Mean + SD
Mild 0.25 0.19 0.025
Moderate 0.52 0.15 0.005
Severe 0.35 0.14 0.87
286 Pak J Med Sci 2012 Vol. 28 No. 2 www.pjms.com.pk
supporting evidence is only available for splinting
There is conicting evidence as to
the benets of oral pyridoxinein the treatment of
CTS. It has been assumed that idiopathic CTS may
be a manifestation of VitaminB6 deciency, and
some investigators have declared that Vitamin B6
supplementation can reduce symptoms and others
have claimed that pain alleviation is a consequence
of Vitamin B6’s anti-nociceptive nature.
In 1973, Ellis and Presley
suggested a relationship
between Vitamin B6 deciency and CTS. Thereafter,
several additional studies emerged
suggestive of a causal association in many CTS
patients. However, numerous reports have failed
to prove an exact causal relation between Vitamin
B6 deciency and CTS.
Indeed, the connection
between pyridoxine deciency and CTS is
multifaceted and remains poorly understood.
The cause of this complexity may be the fact that
pyridoxine has numerous biological functions
separating the contributions of these to CTS is not
Our data suggest that combined treatment
with splinting and Vitamin B6 is more effective
than splinting alone in terms of the effects on
electrophysiological parameters and subjective
improvement in clinical status, especially among
patients with mild and moderate forms of CTS.
The main concern regarding the therapeutic
use of Vitamin B6 in CTS is its safety as it can be
Vitamin B6-related sensory neuropathy has
been reported several times and was most often
associated with dosages >1000 mg/day.
Overall, most studies recommend a dose of
between 40 and 500 mg/day for safety, and to avoid
the development of neuropathy. In our study, the
assessment of side effects was not well designed,
but oral questioning of patients during follow-up
revealed no signicant side effects related to the
use of Vitamin B6, suggesting that doses < 200 mg/
day can be safe. Finally, the ndings of this trial are
supported by the results of several studies that have
used Vitamin B6 for CTS. A large, well-designed
study should allay concerns as to the effectiveness
and safety of Vitamin B6 in CTS.
Although the effectiveness of VitaminB6 in CTS
is controversial, our clinical trial results indicate
thatVitaminB6 is a suitable conservative treatment
for CTS, especially among patients with mild and
The authors wish to acknowledge the contribution
of Dr. Hemaseh Tavahen, who helped to prepare
1. Stevens J, Beard C, O’Fallon W, Kurland L. Conditions associated with
carpal tunnel syndrome. Mayo Clinic 1992;67(6):541-548.
2. Pal B, Morris J, Keenan J, Mangion P. Management of idiopathic carpal
tunnel syndrome (ICTS): A survey of rheumatologists’ practice and
proposed guidelines. Rheumatology 1997;36(12):1328-1330.
3. Scholten RJPM, de Krom MC, Bertelsmann FW, Bouter LM. Variation in the
treatment of carpal tunnel syndrome. Muscle Nerve 1997;20(10):1334-1335.
4. Folkers K, Ellis J. Successful Therapy with Vitamin B6 and Vitamin B2 of
the Carpal Tunnel Syndrome and Need for Determination of the RDAs for
Vitamins B6 & B2 for Disease Statesa. Ann NyAcad Sci 1990;585(1):295-301.
5. Bernstein A, Dinesen J. Brief communication: effect of pharmacologic doses
of vitamin B6 on carpal tunnel syndrome, electroencephalographic results,
and pain. J Am Coll Nutr 1993;12(1):73-76.
6. Guzmán FJL, Gonzalez-Buitrago J, de Arriba F, Mateos F, Moyano J, López-
Alburquerque T. Carpal tunnel syndrome and vitamin B6. J Mol Med
7. Franzblau A, Werner R, Valle J, Johnston E. Workplace surveillance for
carpal tunnel syndrome: a comparison of methods. J Occup Rehabil
8. Atroshi I, Gummesson C, Johnsson R, Ornstein E, Ranstam J, Rosén I.
Prevalence of carpal tunnel syndrome in a general population. JAMA
9. Dawson DM. Entrapment neuropathies of the upper extremities. New Engl
J Med 1993;329(27):2013-2018.
10. Werner RA, Andary M. Carpal tunnel syndrome: pathophysiology and
clinical neurophysiology. Clin Neurophysiol 2002;113(9):1373-1381.
11. Gerritsen AAM, de Vet HCW, Scholten RJPM, Bertelsmann FW, de Krom
MC, Bouter LM. Splinting vs surgery in the treatment of carpal tunnel
syndrome. JAMA 2002;288(10):1245-1251.
12. Gerritsen A, Scholten R, Assendelft W, Kuiper H, de Vet H, Bouter L.
Splinting or surgery for carpal tunnel syndrome? Design of a randomized
controlled trial [ISRCTN18853827]. BMC Neurol 2001;1(1):8.
13. De Krom M, Knipschild P, Spaans F, Kester A. Efcacy of provocative tests
for diagnosis of carpal tunnel syndrome. Lancet 1990;335(8686):393-395.
14. Katz J, Simmons B. Clinical practice. Carpal tunnel syndrome. New Engl J
15. Bradley WG, Daroff RB, Fenichel G, Jankovic J. Neurology in Clinical
Practice. 5th ed. Butterworth Heinemann; 2008.
16. Splints W. Management of carpal tunnel syndrome. Am Fam Physician
17. Edward A, Weiss A. Carpal tunnel syndrome: aetiology and endoscopic
treatment. Orthop Clin North Am 1995;26(4):769-778.
18. Goodyear-Smith F, Arroll B. What can family physicians offer patients
with carpal tunnel syndrome other than surgery? A systematic review of
nonsurgical management. Ann Fam Med 2004;2(3):267-273.
19. Katz RT. Carpal tunnel syndrome: a practical review. Am Fam Physician
20. Weiss A, Akelman E. Carpal tunnel syndrome: a review. R I Med
21. Kanaan N, Sawaya R. Carpal tunnel syndrome: modern diagnostic and
management techniques. Br J Gen Pract 2001;51(465):311-314.
22. Verdugo RJ, Salinas RA, Castillo JL, Cea JG. Surgical versus non-surgical
treatment for carpal tunnel syndrome. Cochrane Database Syst Rev 2008;4.
23. Marshall S, Tardif G, Ashworth N. Local corticosteroid injection for carpal
tunnel syndrome. Cochrane Database Syst Rev 2007;2.
24. Auero E, Stitik TP, Foye PM, Chen B. Pyridoxine hydrochloride treatment
of carpal tunnel syndrome: a review. Nutr Rev 2004;62(3):96-104.
25. Ellis JM, Presley J. Vitamin B6: the doctor’s report: Harper & Row; 1973.
26. Ellis J. Treatment of carpal tunnel syndrome with vitamin B6. SMJ
27. Spooner G, Desai H, Angel J, Reeder B, Donat J. Using pyridoxine to treat
carpal tunnel syndrome. Randomized control trial. Can Fam Physician
28. Wu S, Chan R, Hsu T. Electrodiagnostic evaluation of conservative
treatment in carpal tunnel syndrome. Zhonghua Yi XueZaZhi (Taipei)
29. Franzblau A, Rock CL, Werner RA, Albers JW, Kelly MP, Johnston EC.
The relationship of vitamin B6 status to median nerve function and carpal
tunnel syndrome among active industrial workers. Occup Environ Med
30. Jacobson MD, Plancher KD, Kleinman WB. Vitamin B6 (pyridoxine)
therapy for carpal tunnel syndrome. Hand Clin 1996;12(2):253-257.
31. Nathan PA, Keniston RC, Lockwood RS, Meadows KD. Tobacco, caffeine,
alcohol, and carpal tunnel syndrome in American industry: a cross-
sectional study of 1464 workers. Occup Environ Med 1996;38(3):290-298.
Fariborz Khorvash et al.