Study: Vitamin B12 and tinnitus

Relation

Singh C, Kawatra R, Gupta J, Awasthi V, Dungana H. Therapeutic role of vitamin B12 in patients with chronic tinnitus: a pilot study.Noise health. 2016;18(81):93-97.

Draft

Double-blind, randomized, placebo-controlled prospective study

Participant

Participants included men and women aged 18 to 60 years from northern India who had chronic subjective tinnitus with or without sensorineural hearing loss for more than 6 months. The mean age was 38.37 years, the male-to-female ratio was 2:3, and the mean duration of tinnitus was 1.36 years. Tinnitus occurred in both ears in 27.5% of cases and unilaterally in 72.5% of cases (right ear 32.5% and left ear 40%). Participants were excluded if they had any of the following:

• objektiver (pulsierender) Tinnitus
• angeborene Anomalie, die zu otologischen Problemen beigetragen hat
• Infektion
• psychiatrische Krankheit
• andere otologische Probleme als Tinnitus
• akutes akustisches Trauma oder chronische Lärmbelastung
• systemische Erkrankungen wie Anämie, Bluthochdruck, Diabetes mellitus und Hypothyreose
• Verwendung von Medikamenten, von denen bekannt ist, dass sie eine Wirkung auf Tinnitus haben, wie Steroide, Cyclendalate und Vasodilatatoren, innerhalb von 4 Wochen vor Studienbeginn
• Vorgeschichte einer Ohroperation, Tinnitusstatus nach einer Kopfverletzung oder einer organischen Erkrankung im Kopf- und Halsbereich

intervention

Forty patients who met the selection criteria were randomly divided into 2 groups. Group A (n=20) received 1 mL of intramuscular methylcobalamin (2,500 µg) once per week for 6 weeks. Group B (n=20) received 1 ml of intramuscular isotonic saline as placebo once a week for 6 weeks. Both the patient and the investigator were blinded to the treatment given.

Study parameters assessed

Primary outcomes included pure-tone audiometry, tinnitus matching (pitch and loudness), pre- and post-treatment vitamin B12 testing by chemiluminescence, and self-report using the Tinnitus Severity Index Questionnaire. Patients were followed up for 1 month after the procedure and again underwent all of the above assessments.

Key insights

Seventeen (42.5%) of all patients suffering from tinnitus had vitamin B12 deficiency, with levels above 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 with vitamin B12 deficiency showed an improvement in 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 vitamin B12 deficiency and patients in group B who received placebo showed no improvement in their severity index scores. The visual analogue scale (VAS) showed that patients in group A, who had vitamin B12 deficiency, significantly improved in tinnitus loudness after therapy (t=2.13,P=0.04,df=18). Group B patients showed no significant improvement. Vitamin B12 had no effect on pitch or volume.

comment

Based on recent epidemiological data, tinnitus affects up to 600 million adults worldwide, with approximately 20% of cases classified as severe and debilitating.¹The most accepted mechanism of tinnitus is Jastreboff's neurophysiological model, which proposes that tinnitus is a subcortical perception and results from aberrant neuronal 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.³The reduced methylation is due to an inhibition of methionine synthase (a vitamin B12-dependent enzyme), which leads to a deficiency of S-adenosylmethionine (SAMe) and thus to an impairment of methylation reactions in the myelin sheath. In addition, homocysteine ​​is a neurotoxin and a vascular toxin that accumulates in vitamin B12 deficiency states, and an association has been found between impairment of homocysteine ​​metabolism in the cochlea and resulting oxidative stress.⁴Therefore, the authors proposed that the mechanism by which vitamin B12 deficiency contributes to tinnitus lies in the demyelination of neurons in the cochlear nerve, with associated axonal degeneration and ultimately apoptotic neuronal death.

In addition, vitamin B12 deficiency has been associated with destruction of the microvasculature of the stria vascularis, potentially leading to a decrease in endocochlear potential, which in turn can lead to tinnitus.⁵In 1993, Shemesh et al. observed that many tinnitus patients were indeed vitamin B12 deficient and that subsequent vitamin B12 supplementation improved their condition.⁶Note that the prevalence of cobalamin deficiency in tinnitus patients in the study by Shemesh et al. is similar to the prevalence in this present study conducted 23 years later.

Limitations of the present study include the sample size, which is why it is a pilot study. Additionally, the patients in this study were from northern India, where vitamin B12 deficiency may be significantly more common compared to the general population in the United States.

Not surprisingly, the authors concluded that tinnitus may be the only symptom of 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 benefits. Additionally, although the study demonstrated the effectiveness of injectable methylcobalamin, it raises the question of whether high doses of oral, sublingual, transdermal, intranasal, or other routes of administration of methylcobalamin would produce similar results.

While the authors suggest performing a serum cobalamin test only in patients with chronic tinnitus, it would be prudent to also add a complete blood count with differential as well as tests for folate, homocysteine, and methylmalonic acid levels in serum and red blood cells. When treating tinnitus, vitamin B12 is a safe and promising option; however, more studies with larger group sizes would be welcomed.