Phytosterol Supplement Reduces Hearing Loss in Mice

A new study in mice has shown that phytosterol, a common dietary supplement, may help to reduce age-related hearing loss. The research is published in PLOS Biology.

Cholesterol as part of hearing function

Age-related hearing loss is incredibly common, affecting a third of adults over the age of 65. It is associated with an increased risk of cognitive decline and dementia, so can have important health implications.

Hearing loss with age is thought to be caused by loss of connections between inner hair cells (IHCs) in the inner ear that detect sound and fibers in the auditory nerve, or loss of outer hair cells (OHCs) in a region of the inner ear.

Cholesterol is key to the function of these hair cells, helping them to stretch in response to sound. It has been shown that levels of cholesterol in some areas of the brain can decrease with age, leading the researchers in the current study to investigate if hearing loss could also be related to reduced cholesterol in OHCs.

Phytosterol supplements in models of hearing loss

The researchers analyzed the ears of both young and aged mice, measuring cholesterol content and levels of the enzyme CYP46A1, which helps to break down and recycle cholesterol. Aged mice had more CYP46A1 and less cholesterol in their inner ears than the youngsters.

Next, they over-activated CYP46A1 in the young mice using efavirenz, a drug used to treat HIV/AIDS patients that is also known to activate CYP46A1. Treatment with the drug affected the output of the young mice’s inner ears and induced hearing loss, confirming its cause and effect.

But could increasing cholesterol in the brain counter this effect? The researchers gave the mice plant-based cholesterols, called phytosterols, as these can travel through the blood–brain barrier, whereas “normal” circulating cholesterol cannot.

They found that young mice that received both the CYP46A1-activating drug and three weeks of phytosterol supplementation in their diet had improved OHC function.

Further studies needed to confirm

Overall, the findings suggest that aging triggers cholesterol loss from sensory cells found in the inner ear, which can be partly reversed by supplementation with phytosterols. “Altogether, our findings point towards the importance of cholesterol homeostasis in the inner ear as an innovative therapeutic strategy in preventing and/or delaying hearing loss,” the authors write in the paper.

As phytosterols can be found in many over-the-counter supplements, the authors note that they could be a convenient way to combat age-related hearing loss. However, further testing in older mouse models as well as in humans will be necessary before more confident conclusions can be drawn.

Reference: Sodero AO, Castagna VC, Elorza SD, et al. Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging. PLOS Biology. 2023;21(8):e3002257. doi: 10.1371/journal.pbio.3002257

This article is a rework of a press release issued by PLOS. Material has been edited for length and content.