Reference
Singh C, Kawatra R, Gupta J, Awasthi V, Dungana H. Therapeutic role of vitamin B12 in patients of chronic tinnitus: a pilot study. Noise Health. 2016;18(81):93-97.
Design
Double-blind, randomized, placebo-controlled prospective study
Participants
Participants included men and women aged 18 to 60 from Northern India who had chronic subjective tinnitus with or without sensorineural hearing loss of more than 6 months’ duration. The mean age was 38.37, the male-to-female ratio was 2:3, and the mean duration of tinnitus was 1.36 years. Tinnitus presented in both ears in 27.5% of the cases, and unilaterally in 72.5% of the cases (right ear 32.5% and left ear 40%). Participants were excluded if they had any of the following:
- objective (pulsatile) tinnitus
- congenital anomaly that contributed to otological problems
- infection
- psychiatric illness
- otological problems other than tinnitus
- acute acoustic trauma or chronic noise exposure
- systemic diseases such as anemia, hypertension, diabetes mellitus, and hypothyroidism
- use of medications known to have an effect on tinnitus, such as steroids, cyclendalate, and vasodilators within 4 weeks prior to study start
- history of ear surgery, tinnitus status post-head injury, or any organic illness in the head and neck region
Intervention
Forty patients who met the selection criteria were randomly divided into 2 groups. Group A (n=20) received 1 mL intramuscular methylcobalamin (2,500 µg) once a week for 6 weeks. Group B (n=20) were given 1 mL intramuscular isotonic saline as placebo once a week for 6 weeks. Both the patient and the examiner were blinded to the treatment given.
Study Parameters Assessed
The primary outcomes included pure tone audiometry, tinnitus matching (pitch and loudness), pre-treatment and post-treatment vitamin B12 assays by chemiluminescence, and a self-report using the tinnitus severity index questionnaire. The patients were followed for 1 month after the intervention and were subjected again to all the above assessments.
Key Findings
Seventeen (42.5%) of the total patients suffering from tinnitus were vitamin B12-deficient, with levels greater than 250 pg/mL considered normal. The prevalence of vitamin B12 deficiency was 50% in Group A and 35% in Group B. In Group A, patients who had a vitamin B12 deficiency showed improvement in the mean tinnitus severity index score after receiving vitamin B12 injections (t=2.64, P=0.016, df=18). Patients in Group A who did not have a vitamin B12 deficiency, as well as patients in Group B who received placebo, did not show any improvement in their severity index scores. The visual analog scale (VAS) showed that Group A patients who had a vitamin B12 deficiency significantly improved with respect to tinnitus loudness after therapy (t=2.13, P=0.04, df=18). The Group B patients did not show significant improvement. Vitamin B12 did not have an effect on pitch or loudness.
Commentary
Based on recent epidemiologic data, tinnitus affects up to 600 million adults worldwide, with approximately 20% of the cases categorized as severe and debilitating.1 The most accepted mechanism of tinnitus is the neurophysiological model of Jastreboff, which proposes that tinnitus is a subcortical perception and results from aberrant neural activity in the periphery.2
This study sought to determine the therapeutic role of vitamin B12 in the treatment of tinnitus. Vitamin B12 deficiency causes neuropathy in the central nervous system due to hypomethylation.3 The decreased methylation is due to inhibition of methionine synthase (a vitamin B12-dependent enzyme), which results in a deficiency of S-adenosylmethionine (SAMe), and this leads to impairment in methylation reactions in the myelin sheath. Moreover, homocysteine is a neurotoxin and a vascular toxin that accumulates in vitamin B12 deficiency states, and a correlation involving the impairment of cochlear homocysteine metabolism and the resulting oxidative stress has been established.4 Thus, the authors proposed that the mechanisms by which vitamin B12 deficiency contributes to tinnitus is in the demyelination of neurons in the cochlear nerve, with associated axonal degeneration, and ultimately apoptotic neuronal death.
Additionally, vitamin B12 deficiency has been linked to the destruction of the microvasculature of the stria vascularis, and this possibly leads to a decrease in endocochlear potential, which may in turn result in tinnitus.5 In 1993, Shemesh et al observed that indeed, many tinnitus patients had a vitamin B12 deficiency and that subsequent supplementation with vitamin B12 improved their condition.6 Note that the prevalence of cobalamin deficiency in tinnitus patients in the Shemesh et al study is similar to the prevalence in this present study, which was conducted 23 years later.
Limitations of the present study include the sample size, which is why it is considered a pilot study. Also, the patients in this study were from Northern India, where there may be a significantly larger prevalence of vitamin B12 deficiency compared to the general population in the United States.
Not surprisingly, the authors concluded that tinnitus might be the only presenting symptom of a vitamin B12 deficiency. While methylcobalamin resulted in positive effects for tinnitus patients, it is unclear whether other forms of vitamin B12, such as cyanocobalamin, hydroxocobalamin, or adenosylcobalamin would provide similar benefit. Furthermore, although the study demonstrated the efficacy of injectable methylcobalamin, it raises the question of whether high doses of oral, sublingual, transdermal, intranasal, or other routes of delivery for methylcobalamin would yield similar results.
While the authors only suggest performing a serum cobalamin test in patients who have chronic tinnitus, it would be prudent to also add a complete blood count with differential, as well as tests for serum and red blood cell folate, homocysteine, and methylmalonic acid levels. In the treatment of tinnitus, vitamin B12 is a safe option that shows promise; however, more studies with larger group sizes would be welcomed.
