Cholesterol – friend or foe? The damaging effects of high levels of cholesterol are well-known: coronary heart disease, atherosclerosis, heart attack, stroke. Just the mention of the word conjures up visions of a stealthy but persistent enemy, an unexpected collapse, the ER and intensive care. But cholesterol is not always – or even mostly – a villain. Cholesterol is a major component of the membranes that surround each cell in our bodies and it plays an important and indispensable role in the structural integrity and rigidity/fluidity of these membranes, besides facilitating cell-to-cell communication and stabilizing proteins within these membranes. In its capacity as an integral component of the membrane, cholesterol interacts with membrane-based proteins and could possibly exert a regulatory effect on the functions of these proteins. And this is where its relationship to hearing comes in.
Hearing at the Molecular Level
Sound waves that enter the outer ear strike the eardrum and thereby transmit vibrations to the bones of the middle ear.These specialized bones conduct these vibrations into the inner ear, or the cochlea, where they miniature electromechanical motors: they receive the sound vibrations traveling through the cochlear fl uid and convert them into electrical impulses.These amazing mini-machines then convert the electrical signals back into mechanical motions of the cell, so that the cells act as tiny feedback amplifiers within the cochlea. The feedback amplification occurs at the frequency of sound and prevents any loss of clarity that might occur due to sound waves traveling through the cochlear fl uid.The ability of outer hair cells to convert electrical impulses into mechanical motion is based in an intriguing and unique protein found in the membranes’ cells – a molecular motor called prestin.
Prestin is a large protein that resides in the outer hair cell membrane and has the unique property of being able to “sense” voltage differences across the membrane. When sound waves are converted by the hair cell into electrical signals, prestin responds by producing a mechanical change in its molecular conformation. The exact nature of this change is not yet known but is believed to cause, roughly speaking, a lengthening and shortening of the prestin molecule. In combination with the membrane environment surrounding prestin, along with other molecular participants in the process (such as cellular ions and possibly other proteins), the individual conformational change of each prestin molecule results in a concerted lengthening and shortening of the entire outer hair cell that occurs at the frequency of sound – a remarkable feat powered by this tiny motor molecule! Prestin’s activity “peaks” at a specifi c voltage (about -60 mV), which in fact closely corresponds to the middle of the voltage range observed in outer hair cells as they convert sound vibrations to voltage fluctuations. In other words, prestin is somehow fi ne-tuned to operate most efficiently in the voltage environment that naturally surrounds it.
Cholesterol Levels and Hearing
For years, cholesterol levels in the membranes of cochlear outer hair cells have been thought to be lower than those in other cells of the body. Recent research confirms this thinking. Early clinical studies indicated a link between cholesterolemia (high blood cholesterol) and hearing loss. Other studies indicated that an intake of compounds (such as statins) that reduce overall cholesterol levels delays or reverses hearing loss. For several years, it had been assumed that such effects were due to cholesterol-induced blockages in the blood vessels that supply the ear, leading somehow to diminished hearing.
However, until recently, a direct connection had not been made between hearing and cochlear hair cell cholesterol levels. New research indicates that the low membrane cholesterol levels that are natural to outer hair cells might provide the ideal environment for the functioning of the prestin protein, and thereby for the optimal functioning of outer hair cells in the process of hearing. Researchers found that directly increasing or depleting cholesterol in the cochlea of live mice resulted in almost immediate declines in the hearing ability of these animals.This was determined by measuring inaudible sound waves emitted by the animals’ ears as they respond to sound. In effect, the quantity of cholesterol naturally present in the outer hair cell membrane is precisely controlled so that it somehow electrically “tunes” the prestin protein. This allows prestin to function at or close to its maximum efficiency in the predetermined voltage range that is present in these cells. As cholesterol is either increased or decreased, the maximum efficiency of prestin moves out of its available operational voltage range, causing a decline in hearing. Exactly how cholesterol exerts this tuning effect on prestin is still unknown.
Implications
So what does this mean for the average person? Is it possible that someone with high cholesterol levels could, in addition to affecting the health of their heart and blood vessels, also be jeopardizing their hearing? Will cholesterol-lowering drugs like Lipitor or Caduet be able to restore or improve hearing in people with mild to moderate hearing loss?
Not quite. The current knowledge only points to a relationship between hearing and the levels of cholesterol in outer hair cell membranes.What we generally refer to as “high cholesterol” is the level of cholesterol present in the blood (measured in milligrams per deciliter, or one-tenth of a liter). How blood cholesterol levels translate into the amount of cholesterol seen in outer hair cell membranes is as yet unknown.We can safely assume that outer hair cells have mechanisms that keep the levels of cholesterol in their membranes low. This is evident from the fact that the cholesterol level in these cell membranes is, on the whole, lower than in other cells of the body, even though all cells receive the same supply of cholesterol from the blood. Therefore, elevated cholesterol levels in the blood may not necessarily translate into higher cholesterol levels in hair cell membranes.That being said, an early study did indeed show a relationship between the use of statins (drugs that lower cholesterol) and an improvement in the degree of hearing loss in mice. Similar studies in humans have yielded ambiguous results. This is likely due to the fact that these drugs lower overall cholesterol levels, and their effect on hair cell membrane cholesterol levels is probably highly diluted.
Clearly, however, this is an area of investigation worth pursuing. Different routes of application of cholesterol-lowering drugs – topical, for example, as in some form of direct intracochlear administration – might yield more emphatic results in humans. Precautions would have to be taken, of course, to ensure that such administration is carefully controlled and targeted and does not introduce adverse side effects. In any case, maintaining a healthy diet and keeping one’s cholesterol under control is a desirable goal, regardless of its implications for the treatment of hearing loss.
Gender-Specific Hearing Differences – A Role for Cholesterol?
Pre-menopausal women generally have lower blood cholesterol levels than men of the same age. After menopause, however, cholesterol levels in women tend to increase and the gender difference is erased. Does this translate into a difference in hearing thresholds in younger men when compared to women?
Studies show that hearing thresholds deteriorate with age for both men and women. However, the deterioration begins earlier in men (under age 30) and later in women (postmenopausal). This may or may not be correlated with the observed increase in cholesterol levels seen in post-menopausal women – again, an area of investigation worth following. Further research on the mechanisms used by outer hair cells to keep their membrane cholesterol levels low is an obvious and necessary line of investigation to pursue. This is probably the most promising route to treating cholesterol-related hearing loss or decline. If we understand how healthy hair cells maintain their low cholesterol levels so that hearing is maximally efficient, we would be well on the way to understanding how to help individuals whose hair cells have lost or are losing this ability. However, such knowledge is not within our immediate grasp, given the complexity and variability of all things biological. In the meantime, it won’t hurt – and probably would help quite a bit – to eat well, exercise right and don’t forget that bowl of oatmeal every morning.
Lavanya Rajagopalan, Ph.D., is a researcher at the Baylor College of Medicine in Houston, Texas. She currently studies the structure-function relationships of prestin, a key cochlear protein that is essential for hearing.
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Everybody knows that high cholesterol is something to be concerned about. But what does it really mean when your doctor tells you that your cholesterol levels are high, and what should you do about it? If you’re worried about your cholesterol, here’s your chance to get the answers you need from a top expert at the Harvard Medical School. A complete guide to managing cholesterol and staying healthy for life, The Harvard Medical School Guide to Lowering Your Cholesterol explains: what cholesterol is and the difference between “good” and “bad” cholesterol; how to assess your risk for high cholesterol; how to work with your doctor to develop the best treatment plan, cholesterol-lowering drugs – who should take them, what to look out for and how to be sure your doctor is monitoring you properly; how to manage your cholesterol through diet and exercise; and the latest scientifi c fi ndings on alternative therapies. Written by the founder and chief of the prestigious Lipid Metabolism Unit at Massachusetts General Hospital, Mason W. Freeman, M.D., treats hundreds of patients each year and oversees breakthrough cholesterol research.
Reducing Cholesterol
According to the National Heart, Lung and Blood Institute (NHLBI), healthy diet choices can reduce cholesterol. Following are simple tips that can have a big payoff: All meat has cholesterol and saturated fat, Aso it’s best not to eat more than six ounces per day. Of course, chicken and turekey
are naturally lean, but they’re most healthy when eaten without skin. Fish is even leaner than poultry
and is a healthy option to consider.
Beans and tofu are low in cholesterol and other sources of protein such as dry peas, Obsaturated fat, and make tasty additions sto pasta, soups, casseroles and vegetable dishes. Peas and beans are also high in fiber, which aids in the lowering of cholesterol.
Egg whites have no cholesterol and a goodEgg yolks are high in cholesterol and no moreEthan about four should be eaten per week.tEsolution is to use cholesterol-free egg substitutes, such as Egg Beaters®, instead of regular eggs. It’s often difficult to tell the difference in the final product.
“Often when people cut back on NHLBI, “thinking they are cutting back on saturated fat and cholesterol.” But while a serving of most cheeses has less cholesterol, it has more than six times the saturated fat in a serving of chicken without the skin and almost twice that of lean round steak.
meat they eat cheese instead,” says the mNButter is high in saturated fat and cholesterol, while soft tub or liquid margarine and vegetable spreads are better choices. Regarding the now well-known “trans” fats, the NHLBI says, “Trans fats raise blood cholesterol more than other unsaturated fats but not as much as saturated fats. The harder the margarine or shortening, the more likely it is to contain more ‘trans’ fat. Read the ingredient label to choose margarine that is ‘trans’ fat free or contains liquid vegetable oil as the first ingredient.”
The Harvard Medical School Guide to Lowering Your Cholesterol, McGraw-Hill 2005, 978-0071444811, Paperback 272 pp., $16.95. Also available in audio bookand
