High Homocysteine and Hearing LossApril 2018
By Clyde Simmons
Hearing loss is considered to be a normal part of aging, but recent studies indicate otherwise.
Research published over the past two years has identified an underlying cause of hearing loss not routinely considered by physicians.
These findings reveal that age-related hearing loss involves damage not just to the cells in the ear itself, but to nerve cells that support hearing.1 This suggests that proven nervous system-protective strategies could be beneficial for hearing as well.
Most importantly, it reveals that elevated homocysteine—long associated with cardiovascular and neurological conditions—also contributes to hearing loss.2
Fortunately, research shows that supplementing with folate helps lower homocysteine while also protecting against the damage that it causes.2
This represents a novel approach to potentially mitigating hearing loss.
What you need to know
Homocysteine is a harmful form of an amino acid that has been shown to increase the risk of cardiovascular and neurological conditions. Surprisingly, new research shows that it also has a connection with hearing loss. A recent large-scale clinical trial of older adults showed that when homocysteine was lowered using folate, there was significantly less hearing loss compared with placebo after three years.
An Unexpected Cause of Hearing Loss
Sensorineural hearing loss, the kind associated with aging, reduces the ability to hear faint sounds while also making louder noises sound muffled.
The discovery that this type of hearing loss is caused by damage to nerve cells as well as to sound-sensing cells in the ear led scientists to look for factors common to both age-related hearing loss and brain degeneration.1
An article published in 2017 reported on the growing epidemiological evidence of a strong association between elevated homocysteine and hearing loss.2
The 2017 study showed:
- High total plasma homocysteine is strongly associated with age-related hearing loss.
- Rare genetic diseases that cause high homocysteine levels are also strongly associated with sensorineural hearing loss.
- Animal studies demonstrating that high homocysteine levels—as well as deficiencies in vitamins required to clear homocysteine—produce the type of hearing loss seen in older people.
These findings bring together a clear relationship between hearing loss and homocysteine. They also highlight the role for nutritional supplementation as a potential means of preventing age-related deafness.
The Homocysteine/Folate Connection
Another recent article showed that a dietary deficiency in folic acid, a B vitamin necessary for clearing homocysteine from the blood, is associated with hearing loss.3 This is one of the key connections between homocysteine and hearing loss.
This study showed that after eight months of feeding healthy mice a diet deficient in folic acid, the animals started showing signs of hearing loss. Closer examination showed that their cochleae (the part of the ear where sound is converted to nerve impulses) was damaged and there was a loss of outer hair cells.3
Human studies have shown similar connections. When researchers evaluated people over 60 years old, they found that those with normal hearing had normal folate levels, while those with hearing loss had low folate levels.4
In a study involving nearly 3,000 people age 50 or older, those with elevated total homocysteine levels were 64% more likely to have hearing loss compared with those having lower homocysteine levels.5 Again, most of that elevated risk was related to low plasma folate levels.
Other studies have shown similar hearing problems associated with low levels of vitamin B12, which is also required for lowering homocysteine.6
Mysterious Epidemic Causes Hearing Loss
The first indication that restoring folate levels could impact hearing came nearly a quarter-century ago. At the time, a mysterious epidemic swept through Cuba, leaving more than 50,000 people suffering from a range of maladies related to poor nerve function. The most prominent included sensorineural hearing loss and deafness.7
No one ever found a cause. But when the government began treating victims with folate and other B vitamins, most patients had near-miraculous improvement, leaving less than one-tenth of one percent with permanent deficits.
Investigators concluded that micronutrient deficiencies—including thiamine, folate, and B12—were the root of the problem.7
Since that dramatic event, evidence has continued to reveal that folate supplementation can prevent, slow, and possibly even reverse age-related hearing loss.8
Folate Reverses Hearing Loss
A mouse study showed that high homocysteine levels led to significant leakage from blood vessels in brain areas associated with hearing, and surrounding tissues suffered severely from homocysteine-induced chemical stress.9 But when those mice were supplemented with folate for four weeks, the tissue levels of homocysteine plummeted, and the leaky blood vessels completely healed.
This suggested that reducing homocysteine levels with folate could potentially reverse ongoing hearing loss.9
A human study confirmed the hearing-related benefits.
More than 700 older adults with high homocysteine (but no hearing problems) were given 800 mcg of folate per day or placebo for three years.10 While all subjects experienced mild hearing losses during the three-year period, the placebo group experienced a greater loss of hearing in low frequencies than the folate-supplemented group.
This helps demonstrate that regular folate supplementation is capable of slowing age-related hearing loss.10
Rising levels of homocysteine are now closely associated with both brain-cell injury and hearing loss. Strategies aimed at lowering homocysteine levels, such as folate supplementation, convincingly slow hearing loss.
Supplementing with folate offers a unique strategy for combatting the dangers of elevated homocysteine—and represents a novel solution for preventing age-related hearing loss.
An issue for older individuals is that they lack the internal enzymes to convert folate from food and folic acid supplements to bioactive 5-methyltetrahydrofolate (5-MTHF).
For a long time, the only way of gaining access to this metabolically active folate (5-MTHF) was through an expensive prescription drug called Cerofolin® that cost over $150 a month.
Fortunately, the 5-MTHF patents expired several years ago. This enables consumers to gain access to optimized folate supplements that provide 1,000 to 5,000 mcg of 5-MTHF, along with other B-vitamins (methylcobalamin B12, pyridoxal-5-phosphate B6 and vitamin B2), that work together and individually to reduce homocysteine via two detoxification pathways in the body.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Liberman MC. Noise-induced and age-related hearing loss: new perspecti
- Partearroyo T, Vallecillo N, Pajares MA, et al. Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss. Front Mol Neurosci. 2017;10:107.
- Martinez-Vega R, Murillo-Cuesta S, Partearroyo T, et al. Long-Term Dietary Folate Deficiency Accelerates Progressive Hearing Loss on CBA/Ca Mice. Front Aging Neurosci. 2016;8:209.
- Lasisi AO, Fehintola FA, Yusuf OB. Age-related hearing loss, vitamin B12, and folate in the elderly. Otolaryngol Head Neck Surg. 2010;143(6):826-30.
- Gopinath B, Flood VM, Rochtchina E, et al. Serum homocysteine and folate concentrations are associated with prevalent age-related hearing loss. J Nutr. 2010;140(8):1469-74.
- Park S, Johnson MA, Shea-Miller K, et al. Age-related hearing loss, methylmalonic acid, and vitamin B12 status in older adults. J Nutr Elder. 2006;25(3-4):105-20.
- Roman GC. An epidemic in Cuba of optic neuropathy, sensorineural deafness, peripheral sensory neuropathy and dorsolateral myeloneuropathy. J Neurol Sci. 1994;127(1):11-28.
- Auerhahn C. Daily folic acid supplementation for 3 years reduced age related hearing loss. Evid Based Nurs. 2007;10(3):88.
- Kundu S, Munjal C, Tyagi N, et al. Folic acid improves inner ear vascularization in hyperhomocysteinemic mice. Hear Res. 2012;284(1-2):42-51.
- Durga J, Verhoef P, Anteunis LJ, et al. Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial. Ann Intern Med. 2007;146(1):1-9.
- Iso H, Moriyama Y, Sato S, et al. Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese. Circulation. 2004;109(22):2766-72.
- Nygard O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997;337(4):230-6.
- Spence JD. Patients with atherosclerotic vascular disease: how low should plasma homocyst(e)ine levels go? Am J Cardiovasc Drugs. 2001;1(2):85-9.
- Available at: https://www.cdc.gov/nceh/hearing_loss/public_health_scientific_info.html. Accessed 13 July, 2017.
- Available at: http://www.asha.org/uploadedFiles/AIS-Hearing-Loss-Types-Degree-Configuration.pdf. Accessed January 26, 2018.
- Tavanai E, Mohammadkhani G. Role of antioxidants in prevention of age-related hearing loss: a review of literature. Eur Arch Otorhinolaryngol. 2017;274(4):1821-34.
- Moser T, Starr A. Auditory neuropathy--neural and synaptic mechanisms. Nat Rev Neurol. 2016;12(3):135-49.
- Brosel S, Laub C, Averdam A, et al. Molecular aging of the mammalian vestibular system. Ageing Res Rev. 2016;26:72-80.
- Calabrese V, Cornelius C, Mancuso C, et al. Redox homeostasis and cellular stress response in aging and neurodegeneration. Methods Mol Biol. 2010;610:285-308.
- Moore E, Mander A, Ames D, et al. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr. 2012;24(4):541-56.
- Sharma M, Tiwari M, Tiwari RK. Hyperhomocysteinemia: Impact on Neurodegenerative Diseases. Basic Clin Pharmacol Toxicol. 2015;117(5):287-96.
- Xie Y, Feng H, Peng S, et al. Association of plasma homocysteine, vitamin B12 and folate levels with cognitive function in Parkinson’s disease: A meta-analysis. Neurosci Lett. 2017;636:190-5.
- Bogdanski P, Miller-Kasprzak E, Pupek-Musialik D, et al. Plasma total homocysteine is a determinant of carotid intima-media thickness and circulating endothelial progenitor cells in patients with newly diagnosed hypertension. Clin Chem Lab Med. 2012;50(6):1107-13.
- Zhang D, Fang P, Jiang X, et al. Severe hyperhomocysteinemia promotes bone marrow-derived and resident inflammatory monocyte differentiation and atherosclerosis in LDLr/CBS-deficient mice. Circ Res. 2012;111(1):37-49.
- Dionisio N, Jardin I, Salido GM, et al. Homocysteine, intracellular signaling and thrombotic disorders. Curr Med Chem. 2010;17(27):3109-19.