Was recently asked to discuss whether there is evidence to support the use of B vitamins in managing different aches and pains. Here's my talk delivered last 16 Sept 2016 at the 12th Post Graduate Course of the East Avenue Medical Center Department of Internal Medicine.

1. VITAMIN B
Sidney Erwin T. Manahan, MD FPCP FPRA
16 September 2016
In Musculoskeletal
Diseases
WHAT’S THE EVIDENCE?

2. Disclosures
Received grants and honoraria from Pfizer,
Roche, Ajanta Phils and Wyeth.

3. Prescriptions for Neuropathic Pain
Vitamin
B
complex
40%
Anti-
epileptics
31%
NSAIDs
16%
Analgesics
13%
IMS Philippines Data , June 2011

4. Vitamins
WATER SOLUBLE
Vitamin B
• Thiamine (B1)
• Riboflavin (B2)
• Niacin (B3)
• Pantothenic Acid (B5)
• Pyridoxine (B6)
• Biotin (B7)
• Inositol (B8)
• Folic Acid (B9)
• Cobalamin (B12)
Vitamin C (Ascorbic Acid)
FAT SOLUBLE
• Vitamin A (Retinol)
• Vitamin D (Calciferol)
• Vitamin E (Tocopherol)
• Vitamin K (Phytonadione)
Schellack G, et al. B complex vitamin deficiency and supplementation. S Afr Pharm J 2015; 82 (4): 28-33

5. Physiologic Functions of Vitamin B
Vitamin B
Complex
Metabolic Effects
Thiamine, Riboflavin
Niacin, Pantothenic Acid
Pyridoxine, Biotin
Inositol, Folic Acid
Cobalamin
Hematinic
Pyridoxine, Folic Acid
Cobalamin
Nervous System
Functions
Thiamine, Niacin
Pyridoxine, Cobalamin
Homocysteine levels
Folic acid, Pyridoxine
Cobalamin
Schellack G, et al. B complex vitamin deficiency and supplementation. S Afr Pharm J 2015; 82 (4): 28-33

6. Dietary Sources of Vitamin B
RECOMMENDED DAILY ALLOWANCE
Male Female
Thiamine (B1) 1.2 – 1.4 mg 1 – 1.1 mg
Riboflavin (B2) 1.4 – 1.7 mg 1.2 – 1.3 mg
Niacin (B3) 16 – 19 mg 13 – 14 mg
Pantothenic Acid (B5) 4-7 mg
Pyridoxine (B6) 2 – 2.2 mg 2 mg
Folic Acid (B9) 400 mcg
Cobalamin (B12) 3 mcg

7. DIETARY Vitamin B Deficiency
• A specific B vitamin deficiency is not likely to occur
in insolation.
• If at least one B vitamin is found to be deficient,
the full spectrum should be considered deficient,
unless proven otherwise.
• B vitamin supplementation only in deficiency states
in the presence of adequate nutrition.
Schellack G, et al. B complex vitamin deficiency and supplementation. S Afr Pharm J 2015; 82 (4): 28-33

8. Factors That Cause Vitamin B Deficiency
• Malnutrition
• Strictly Vegan Diets
• High intake of milled rice
• Chronic alcoholism
• Chronic dialysis
• Post-gastrectomy/ GI
surgery
• Intestinal parasitism
• Patients on TPN
• Anticonvulsants
• Steroids
• Theophylline
• Hydralazine, diuretics
• Estrogen pills
• Isoniazid
• Metformin
• Colchicine
• Proton-pump inhibitors
and H2 blockers

9. Differences in Presentation of
Vitamin B Neuropathies
Thiamine
Present initially as muscle cramps followed by distal
sensory loss; Left untreated, may result in ascending
weakness of the legs and sensorimotor neuropathy of the
hands
Pyridoxine
DEFICIENCY - Numbness, paresthesia and burning
sensation in the feet which ascends to the legs &
eventually the hands
TOXICITY - sensory ataxia, areflexia and impaired
cutaneous sensation (burning and paresthesias) 
severe toxicity affects motor nerves as well
Cobalamin
Sensory symptoms appear first (“Numb Hand
Syndrome”); May involve upper and lower extremities;
may also present with myeloneuropathy (with
concomitant copper deficiency)
Hammond N, et al. Nutritional Neuropathies. Neurol Clin 2013; 31 (2): 477-89

10. Pyridoxine in Carpal Tunnel Syndrome
Pyridoxine 2mg/d improved symptoms but longer durations of Pyridoxine
100mg/d allowed patients to avoid hand surgery
Folkers K, et al. Biochemical evidence for a deficiency of vitamin B6 in CTS
based on a crossover clinical study. Proc Nat Acad Sci USA 1978; 75 (7): 3410-2
Rate of symptoms alleviation was higher (68% vs 14.3%) among those who
took pyridoxine 100mg BID than those who didn’t receive it
Kasdan M, et al. Carpal tunnel syndrome and vitamin B6. Plast Reconstr Surg 1987; 79: 456-8
In 14 supplementation trials, 8 studies supported vitamin B
supplementation. (None were RCTs and half of these were in patients
found to have vitamin B6 deficiency)
Aufiero E, et al. Pyridoxine treatment of Carpal Tunnel Syndrome. Nutr Rev 2004; 62(3): 96-104.
Ryan-Harshmann M, et al. Carpal tunnel syndrome and vitamin B6. Can Fam Phy 2007; 53: 1161-2.

11. Pyridoxine in Carpal Tunnel Syndrome
Patient 46 Adult patients with clinical / EP diagnosis of carpal
tunnel syndrome
Intervention Pyridoxine 200 mg/d for 10-12 weeks
Methods 2 Randomized blinded controlled Trials
Results No significant improvement in symptoms, nocturnal
discomfort, hand coordination, Phalen’s test or Tinel’s
sign.
Improvement in finger swelling and movement
discomfort after 12 weeks of intervention.
O’Connor D, et al. Non-surgical treatment for carpal tunnel syndrome. Cochrane Database of Sys Rev 2003, Issue 1, Art No.
CD003219.

12. Cobalamin in Diabetic Neuropathy
Patients 336 Adult patients with diabetic neuropathy
Intervention Vitamin B12 or combination treatment (includes vitamin B) or
methylcobalamin given for 4-16 weeks
Methodology Systematic review of 7 randomized controlled trials
Results 6/6 trials showed significant improvement in pain or
somatosensory symptoms compared to placebo or BL; 3/4 trials
showed improvement in vibration perception threshold and
autonomic symptoms.
Only 1/4 clinical trials showed improvement with vitamin B
combination while 2/3 studies showed improvement with
methylcobalamin in electrophysiologic measures.
Methylcobalamin was better than conventional vitamin B12 in
improving somatosensory, autonomic symptoms and EP results
Sun Y, et al. Effectiveness of vitamin B12 in diabetic neuropathy: systematic review of clinical controlled trials. Acta Neurolo
Taiwan 2005; 14(2): 48-54.

13. Cobalamin in Diabetic Neuropathy
Patients 363 Adult patients with diabetic neuropathy
Intervention Various vitamin B12 interventions for 12-24 weeks
Methodology Systematic review of 4 randomized controlled trials
Results Only 1 trial showed more improvement in neuropathic symptoms
with vitamin B interventions compared to non-vitamin B
interventions, placebo
Only 1 trial showed improvement in EP changes with
intervention
In 1 trial, there was improvement in somatic, sensory and
autonomic symptoms with methylcobalamin after 4 months but
no comparison made to placebo
No clear advantage in using vitamin B12 in DM
neuropathy
Jayabalan B, et al. Vitamin B supplementation for diabetic peripheral neuropathy. Singapore Med J 2016; 57 (2): 55-9.

14. Alcoholic and Diabetic Neuropathy
Patients 741 Adult patients with either diabetic or alcoholic neuropathy
Intervention Vitamin B12 given for 2-8 weeks
Methodology Systematic review of 7 randomized controlled trials
Results Two trials showed no improvement in pain intensity
One trial showed a small improvement in vibration threshold
with benfotiamine versus placebo
Higher doses of vitamin B complex resulted in short term
reduction in pain and improvement in paresthesias, pain and
numbness.
Evidence for vitamin B in treating peripheral
neuropathy is limited and insufficient to determine
whether it is beneficial or harmful
Ang CD, et al. Vitamin B for treating peripheral neuropathy. Cochrane Database Sys Rev 2008, (3), CD004573.

15. Vitamin B for Peripheral Neuropathy
• Vitamin B appears to improve some of the symptoms in
peripheral neuropathy compared to placebo.
• Larger studies are needed before its efficacy in treating
patients who do not have a deficiency can be established
Onysko M, et al. Targeting neuropathic pain: consider these alternatives. J Fam Prac 2015; 64 (8): 470-5.

16. Beyond Supplements, Going Analgesic
• Interaction with pain mediators
• Increasing NE and 5-hydroxytriptamine in pain inhibitory
descending pathway
• Regeneration of damaged nerve fibers
• Stabilizing neurons – inhibiting ectopic discharges
• Improved axonal transport
• Increasing nerve conduction velocity
Gazoni FM, et al. B complex vitamins for analgesic therapy. Rev Dor Sao Paulo 2016; 17 (1): 52-6

17. Vitamin B in Acute Pain
Author Patients / Interventions Results
Ponce-Monter
HA, et al 2012
122 patients with lower limb
fracture, initial VAS >50mm
Diclofenac + vitamin B IV versus
Diclofenac IV 2x/day1
>30 mm decreased in pain VAS
within 4 hours. More effective
analgesia with combination
therapy from 8 hours post
application & maintained for 48
hours
Mibielli MA, et
al 2009
372 patients with acute low
back pain (DOLOR Study)
Diclofenac + vitamin B PO
versus Diclofenac BID x 7 days2
More effective pain relief (>20
mm) after 3 days, better
functionality and mobility with
combination therapy.
Gazoni FM, et al. B complex vitamins for analgesic therapy. Rev Dor Sao Paulo 2016; 17 (1): 52-6
1 Thiamine 100mg + Pyridoxine 100 mg + cyanocobalamin 1 mg
2 Thiamine 50 mg + Pyridoxine 50 mg + cyanocobalamin 1 mg

18. Vitamin B in Knee Osteoarthritis
Author Patients / Interventions Results
Garg S, et al
2013
30 patients with Knee OA
Benfotiamine+pyridoxine+methy
lcobalamn TID vs placebo for 24
weeks
Significant improvement in pain,
improved functionality and joint
mobility with vitamin B complex
Magana-Villa
MC et al 2013
48 patients with severe knee OA
in the pre-arthroplasty period
Diclofenac + vitamin B1versus
Diclofenac IM 48 hours prior to
OR and evaluated 12 hours later
Superiority of analgesia and
increased analgesic duration
with combination treatment
Gazoni FM, et al. B complex vitamins for analgesic therapy. Rev Dor Sao Paulo 2016; 17 (1): 52-6
1 Thiamine 100mg + Pyridoxine 100 mg + cyanocobalamin 5 mg

19. Vitamin B in Knee Osteoarthritis
Author Patients / Interventions Results
Dehghan M
2015
120 patients with Knee OA
Diclofenac + Vitamin B vs
Diclofenac + Vitamin E vs
Diclofenac
*Diclofenac 50 mg BID
** No dose of vitamin B and E
specified.
All groups had significant
improvement in parameters 3
weeks after initiating therapy.
Decrease in pain, improvement
in function was (statistically)
greater in those who received
vitamin B. More satisfaction
from patients on vitamin B but
not statistically significant.
Dehghan M. Comparative Effectiveness of B and E vitamins with diclofenac in reducing pain
due to osteoarthritis of the knee. Med Arh 2015; 69 (2): 103-106.

20. Vitamin B in Post Herpetic Neuralgia
Author Patients / Interventions Results
Xu G et al
2014
98 patients with subacute
moderate to severe PHN of 120
days duration
Methylcobalamin SC vs
Methylcobalamin PO vs
lidocaine SC for 4 weeks
SC methylcobalamin
progressively reduced pain
(including paroxysms and
allodynia) compared to other
arms.
Xu G et al
2014
90 patients with PHN of 120
days in dermatomes T6-10
TENS+lidocaine SC vs
TENS+cobalamin SC vs triple tx
for 8 weeks
Significant improvement in pain
with TENS+cobalamin and triple
therapy. There was no
improvement with
TENS+lidocaine
Gazoni FM, et al. B complex vitamins for analgesic therapy. Rev Dor Sao Paulo 2016; 17 (1): 52-6

21. ADD ON Vitamin B in Diabetic PN
Author Patients / Interventions Results
Fonseca VA et
al 2013
214 Type 2 DM with neuropathy
documented as abnormal VPT
Pyridoxine 35 mg +
Methylcobalamin 2000 mcg +
methylfolate 3 mg BID vs
Placebo as ADD ON to
pregabalin, gabapentin or
duloxetine x 24 weeks
More patients receiving add on
vitamin B complex experienced
reduction in pain symptoms
(26% vs 15%) beginning Week
16 and sustained until week 24.
However no improvement in
VPT.
Improvement was greatest in
patients with low levels of
vitamin B6 and B12 and those
receiving metformin
Gazoni FM, et al. B complex vitamins for analgesic therapy. Rev Dor Sao Paulo 2016; 17 (1): 52-6

22. Methylcobalamin in Low Back Pain
• 120 Adults with non-specific low
back pain of 6 months duration
• Randomized Double Blind Placebo
Controlled Trial
• S1: Methylcobalamin 1000 mg IM
OD for 2 weeks
• S2: Methylcobalamin 500 mcg
3x/week for 2 weeks
Mauro GL, et al. Eur Rev Med Pharmacol Sci 2000; 4: 53-58
Chiu CK, et al. The efficacy and safety of IM methylcobalamin in patients with chronic non-specific
low back pain. Sing J Med 2011; 52 (12): 868-73

23. Methylcobalamin in Low Back Pain
75.53
70.63
56 54.8
9.53
36.83 38.6
51.5
MCbl Placebo MCbl Placebo
Mauro GL et al 2000 Chiu CK et al 2011
Pain VAS (in mm)
Pre-tx Post-tx
Mauro GL, et al. Eur Rev Med Pharmacol Sci 2000; 4: 53-58. Chiu CK, et al. The efficacy and safety of IM
methylcobalamin in patients with chronic non-specific low back pain. Sing J Med 2011; 52 (12): 868-73

24. Methylcobalamin in Low Back Pain
13.27
11.53
2.43
5.8
MCbl Placebo
Disability
Pre-tx Post-tx
64
60.5
47
55.3
MCbl Placebo
Disability Index
Pre-tx Post-tx
Mauro GL, et al. Eur Rev Med Pharmacol Sci 2000; 4: 53-58. Chiu CK, et al. The efficacy and safety of IM
methylcobalamin in patients with chronic non-specific low back pain. Sing J Med 2011; 52 (12): 868-73

25. Methylcobalamin in Low Back Pain
LOWER mean paracetamol use in
patients who received cobalamin
• Mauro GL 2000: B12 9.9 + 8.04 tabs/
15 days versus Placebo 28.9 + 11.32
tabs/15 days
• Chiu CK 2011: B12 65.7 + 75.2 g
versus Placebo 87.6 + 57.3 g
Mauro GL, et al. Eur Rev Med Pharmacol Sci 2000; 4: 53-58. Chiu CK, et al. The efficacy and safety of IM
methylcobalamin in patients with chronic non-specific low back pain. Sing J Med 2011; 52 (12): 868-73

26. Comparison of Available Vitamin B
Complex Preparations
Preparation Thiamine (mg) Pyridoxine (mg)
Cobalamin
(mcg)
Brand N 100 200 200
Brand P 500 500 250 1000
Brand M 300 300 100 100
Brand M 1000 500 250 1000
Brand NE 300 100 1000
Brand Ph 100 5 50
Brand Rh 10 1 2
Polyneuropathy 10-30 50-100 1000-2000
MIMS Philippines Drug Reference 2016 Issue 1
Schellack G, et al. B complex vitamin deficiency and supplementation. S Afr Pharm J 2015; 82 (4): 28-33

27. Summary
• Non-dietary factors contribute to
vitamin B deficiency despite
adequate dietary intake
• Some symptoms in peripheral
neuropathy improve with vitamin B
administration
• There are small trials suggesting a
potential role for vitamin B in acute
pain, osteoarthritis, back pain and as
add on to anticonvulsants in DPN
• Larger trials are needed to establish
efficacy in patients without deficiency
state