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Breaking News: High Homocysteine Levels May Increase Hearing Loss

Loprinzi, Paul D. PhD; Brown, Kent PhD; Gilham, Ben AuD

doi: 10.1097/01.HJ.0000416274.98729.66

Dr. Loprinzi (left) and Dr. Brown (right) are assistant professors in the department of exercise science at Bellarmine University in Louisville, KY. Dr. Gilham is an audiologist at the Hearing, Speech and Deafness Center in Seattle, WA.



A significant association was found between homocysteine and high- and low-frequency pure-tone averages, suggesting that higher levels of homocysteine adversely affect hearing function. We found that participants with higher homocysteine levels were 74 percent more likely to have mild hearing loss, and these data may be used to develop interventions to help preserve hearing function.





Strategies should target changes in homocysteine levels, perhaps through regular physical activity, likely by increasing methionine catabolism and vitamin B. (Med Sci Sports Exerc 2011;43[5]815; Ann Nutr Metab 2003;47[3-4]:114; Psychogeriatrics 2011;11[2]:105.) High homocysteine levels, a sign of vascular disease, may also increase the risk of hearing dysfunction because of the effect on blood flow to the cochlea, a highly vascularized organ of the auditory system. (J Int Adv Otol 2009;5[3]340; Auris Nasus Larynx 2004;31[1]19.)

Homocysteine is considered an atherogenic and thrombogenic risk factor, with elevated levels associated with vascular-related diseases. (Auris Nasus Larynx 2004; 31[1]19; Opin Lipid 1992;3[4]:295.) Elevated homocysteine may also negatively influence hearing through its associated oxidative stress, particularly lipid peroxidation and by directly damaging neurons. (Atheroscler 1994;105[2]:165; Auris Nasus Larynx 2004;31[1]19.)

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We examined the association between homocysteine and hearing function in a nationally representative sample of U.S. adults from the 2003 to 2006 National Health and Nutrition Examination Survey cycles, which is a representative sample of U.S. citizens. The study was approved by the National Center for Health Statistics ethics review board, with informed consent obtained from all participants prior to data collection.

We limited our analyses to 2,119 participants 20 and older who did not have missing audiometry or homocysteine data, impacted cerumen, or missing data on the covariates used in the models (i.e., folate, vitamin B12, age, gender, body mass index, ethnicity, cotinine, and self-report of coronary heart disease or stroke). Homocysteine was measured from blood samples using the Abbott homocysteine assay, a fully automated fluorescence polarization immunoassay. High homocysteine levels, coded as 1 in the analyses, were defined as more than 10.4 µmol/L for women and more than 11.4 µmol/L for men. (Ann Intern Med 1999;131[5]:331.)

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Hearing threshold testing was conducted on both ears of participants at seven frequencies (500, 1,000, 2,000, 3,000, 4,000, 6,000, and 8,000 Hz) across an intensity range of 10 to 120 dB. Low-frequency pure-tone average was obtained by calculating the average air conduction pure-tone thresholds at 500, 1,000, and 2,000 Hz. High-frequency pure-tone average was obtained by calculating air conduction pure-tone thresholds at 3,000, 4,000, 6,000, and 8,000 Hz. (Arch Intern Med 2008;168[14]:1522; J Amer Med Assoc 1998;279[14]:1071; Pediatrics 2001;108[1]:40; J Amer Med Assoc 2010;304[7]:772.)

Consistent with previous studies, hearing loss measures were categorized according to sensitivity in the worse ear:

  • Good hearing: Low- and high-frequency pure-tone average less than 16 dB.
  • Some hearing loss: Low- or high-frequency pure-tone average 16 to 24 dB.
  • Mild hearing loss: Low- or high-frequency pure-tone average 25 to 39 dB.
  • Moderate to severe hearing loss: Low- or high-frequency pure-tone average more than 40 dB.
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An adjusted and unadjusted linear regression was computed to examine the association between homocysteine and low- and high-frequency pure-tone averages. The first adjusted model controlled for age, gender, body mass index, cardiovascular disease status, ethnicity, folate, and vitamin B12. Cotinine was not controlled for because it is not significantly associated with hearing function. The second adjusted model only controlled for covariates that significantly contributed (i.e., P< 0.10).

These linear regression models were followed by a multinomial logistic regression, examining the association between homocysteine and each of the four hearing classifications, with good hearing serving as the reference point. The same procedure was applied to the multinomial logistic regression regarding which covariates to include in the models. Homocysteine and low- and high-frequency pure-tone averages were transformed using a square root transformation to normalize the data. Means for these variables are presented for the untransformed data. The table shows the participants’ characteristics across hearing function. A significant linear trend across the four hearing classifications was observed for age, height, weight, and homocysteine levels.

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Our results, which are in accordance with other studies, suggest that homocysteine is a potential risk factor for hearing loss among adults. The cross-sectional study design is a limitation, which prevents any causal effects to be analyzed.

Evaluating homocysteine levels may be a sensible strategy to identify individuals at risk for hearing loss. Although speculative, one potential strategy to reduce homocysteine levels may be through physical activity. Studies have demonstrated an inverse association between physical activity and homocysteine. (HJ 2011;64[4]:40; Med Sci Sports Exerc 2011;43[5]815; J Amer Med Assoc 1995;274[19]:1526.) (See FastLinks.)

An increase in protein turnover may lower homocysteine levels, and homocysteine may be lowered through its influence of methionine catabolism, assuming folate and B vitamins are adequate, as a result of activity-induced protein metabolism. (Int J Sport Nutr Exerc Metab 2006;16[4]:341.) Future prospective and randomized controlled trials are needed, of course, to determine whether reduced homocysteine levels from physical activity can result in auditory benefits.

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© 2012 Lippincott Williams & Wilkins, Inc.