Natural Medicine Journal Podcast

Natural Medicine Journal's interviews with thought-leaders in the field of natural and integrative medicine dig deep into the most important topics in the field. Whether it's a one-on-one with top researchers in integrative medicine or a conversation with a practitioner about treating hard-to-tackle conditions, each episode promises to provide trusted, cutting-edge, evidence-based knowledge about natural medicine that you won't find anywhere else.
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Now displaying: February, 2019
Feb 6, 2019

The Centers for Disease Control and Prevention has called insufficient sleep a public health epidemic. And yet, many of the commonly prescribed medications are not helping most patients. In this interview, John Neustadt, ND, explains why an integrative approach to treating insomnia provides a much more effective alternative to commonly used sleep medications.


About the Expert

John Neustadt, ND

John Neustadt, ND, received his naturopathic doctorate from Bastyr University. He was founder and medical director of Montana Integrative Medicine and founder and president of Nutritional Biochemistry, Inc. (NBI) and NBI Pharmaceuticals. He’s a medical expert for TAP Integrative, a nonprofit organization educating doctors about integrative medicine. He has published more than 100 research reviews and was recognized by Elsevier as a Top Ten Cited Author for his work.

Neustadt’s books include A Revolution in Health through Nutritional Biochemistry and the textbook Foundations and Applications of Medical Biochemistry in Clinical Practice. Neustadt is an editor of the textbook Laboratory Evaluations for Integrative and Functional Medicine (2d Edition). He was the first naturopathic doctor ever voted Best Doctor among all physicians in his area.

Neustadt received 15 Orphan Drug Designation by the US Food and Drug Administration for the use of natural products for the potential treatment of rare diseases.

About the Sponsor

Nutritional Biochemistry, Inc.

Nutritional Biochemistry, Inc. (NBI) formulates and manufactures products that give results. Started by John Neustadt, ND, in 2006 when he couldn’t find formulas he needed to help his patients and family, NBI products solve 2 problems he was having. Existing products didn’t contain the dose or combination of nutrients used in clinical trials and actually shown to work. Equally frustrating, other companies would cite studies on their websites, but then use lower amounts of nutrients than what was used in the study, or use entirely different nutrients that weren’t supported by the research.

Neustadt’s latest creation is Sleep Relief. NBI’s Sleep Relief is a breakthrough in sleep technology. Its bi-phasic, time-release technology delivers NBI’s proprietary formula with clinically validated nutrients in two stages—a quick-release first stage and a slow-release second stage to help you gently fall asleep, stay asleep and wake refreshed and ready for your day. NBI's Osteo-K delivers the clinical dose of nutrients shown in more than 25 clinical trials to grow stronger bones and reduce fractures more than 80%.

NBI is and always has been a family-owned company. We don’t manufacture anything we wouldn’t take ourselves or give to our own family. No matter what we do, our promise to physicians using our products is to help their patients, and to customers purchasing directly from NBI, is uncompromising quality.

NBI is a name you can trust. But don’t take our word for it. Spend some time on our website, learn about our products, and educate yourself on the hundreds of research citations and studies that they’re based on.


Karolyn Gazella: Hello. I'm Karolyn Gazella, publisher of the Natural Medicine Journal. Thank you so much for joining me. Today, our topic is the integrative approach to insomnia. During this interview, we will learn that insomnia is a significant problem for many patients that can have far reaching physical, mental and emotional health ramifications. We will also learn how to successfully treat this condition by using a combination of diet, lifestyle recommendations, and dietary supplements.

My expert guest today is Dr. John Neustadt. Dr. Neustadt received his naturopathic doctorate from Bastyr University and he was the founder and medical director of Montana Integrative Health.

Before we begin, I'd like to thank the sponsor of this topic who is Nutritional Biochemistry Incorporated, or NBI, manufacturers of high-quality dietary supplements for health care professionals.

Dr. Neustadt, thank you so much for joining me today.

John Neustadt, ND: Thank you for having me on.

Gazella: Well, so the Centers of Disease Control and Prevention calls lack of sleep a public health epidemic. Now, that seems pretty significant so today we're going to talk specifically about insomnia. How common is insomnia in particular?

Neustadt: Well, the CDC is absolutely correct. It is a public health epidemic. Up to 80% of people struggle at some point with what's considered transient insomnia, less than two weeks of duration and insomnia effects 10 to 15 percent of the general population.

In primary care settings, it's estimated that up to almost 70 percent of primary care patients have insomnia so it is incredibly common.

Gazella: Oh, yeah that is. So how does lack of sleep impact a patient's overall health from like a physical, mental, emotional standpoint?

Neustadt: It has devastating impacts. There are two ways to think of it. One is short-term impacts and the other are the long-term impacts. So, short term it can impact decreased job performance, impact social and family life by creating greater fatigue. I mean, just you're more tired during the day. Decreased mood and depression, increases in anxiety and stress. Decreased vigor and just not being able to cope with the demands of daily life and be able to complete tasks. That's only short term. Devastating just in the short term.

But in the long term, it can be a killer. There, if people are sleeping an average of less than six hours per night, it can increase the ... or decrease the quality of life at the same magnitude of a similar condition such as congestive heart failure and major depressive disorder. It's an early symptom for Alzheimer's Disease and Parkinson's Disease and Huntington's Disease and there's a sweet spot for sleeping of about eight hours. That research shows is the healthiest, and if you're sleeping less than six, or longer than nine hours, it increases your risk for diabetes, metabolic syndrome, and death and, in fact, for metabolic syndrome, there's a 45 percent increase in risk compared to people who are sleeping seven to eight hours a night.

Gazella: Wow, so yeah, so this is a very important topic for clinicians to have on their radar. So, when you're evaluating a patient with a sleep disorder such as insomnia, how do you approach the work up?

Neustadt: Well, insomnia's really a qualitative diagnosis. It's how are they ... how do they feel that they're sleeping? How do they feel that it's impacting their health? Now the DSM official diagnosis, there is a quantitative or a couple of quantitative aspects to that and that is it's occurring at least three nights per week, and present for at least three months. So understand the difference between transient insomnia, less than two weeks, versus the diagnosis, official diagnosis, needs to be going on for greater than three months.

So there's a huge discrepancy there and in time periods and clinically it's important to be aware of that because these detrimental and dangerous effects of insomnia and sleep deprivation definitely are occurring in shorter than three months period of time. They're happening pretty quickly if someone's not getting enough sleep and even over a few days the short term consequences.

And so what I ask people about is how many hours, on average, do they think they're sleeping a night? Do they have any difficulty with falling asleep or staying asleep called sleep phase delay or sleep phase advance? Are they waking refreshed in the morning? What's going on with them psychosocially? Are there any stresses going on at work or in relationships or financially that's increasing their anxiety and could be impacting their sleep? Are they are risk for any hormonal abnormalities or imbalances because the research is clear that low estrogen, low or high testosterone, elevated TSH, those are all things that can create insomnia. Abnormal progesterone, as well.

And then looking at medications because there are some medications that can impact sleep, as well.

Gazella: Yeah, let's talk about the medications that can impact sleep. What are some of those medications that can impact sleep?

Neustadt: Well, prednisone, that can cause hyper-arousal, or can cause somebody to not sleep, not be able to fall asleep, or have fragmented sleep. Beta-blockers, very common heart medications, can decrease melatonin production. So we know what the mechanism of action ... their interaction of sleep is they decrease melatonin and can cause poor sleep.

Some antidepressants, actually, can cause poor sleep. Antidepressants can, depending on the antidepressants, can either cause somebody to not be able to sleep enough or can cause hypersomnolence, somebody to be sleeping too much. So looking at those, looking up ... it's very easy to look up whatever medication they're taking quickly and see, besides the ones that I mentioned, could it be potentially interfering and impacting with their sleep.

Gazella: So I've been hearing about hyperarousal, or the hyperarousal hypothesis, which I find quite fascinating. What is the hyperarousal hypothesis and how can it affect what is recommended to patients?

Neustadt: Great question. So the hyperarousal hypothesis I like to refer to as "wired-but-tired." And it occurs to people typically who are under a lot of stress, they have elevated cortisol, and when they end up trying to fall asleep they just can't turn their mind off, or even if their mind isn't racing, they just can't calm down. Their body can't relax and settle into sleep. They're staring at the ceiling, it can cause fragmented sleep. And that wired-but-tired, again, typically occurs in people who are under chronic stress.

Gazella: Yeah. And you know the other day when you and I were talking as it related to the hyperarousal hypothesis, you were telling me about something else that was new to me and it was called social jet lag. Talk a little bit about social jet lag and the research associated with social jet lag.

Neustadt: I'm so happy you brought this up because I love this as well. Fitbit, that maker of the wearable tracking devices, and tracking people's sleep as well, they had access, because of their users, to over six billion data points of sleep. And they looked at those. And they looked at the data and determined that the biggest predictor of healthy sleep, restful sleep, is going to bed at about the same time every night. Basically training our body that it's bedtime, getting that routine.

Social jet lag occurs when people are going to bed at about the same time every night during the week but then the weekend comes. Friday night they go out, hang out with friends, stay out late. Saturday night maybe do the same thing, and then Sunday comes around and they try to go to bed again at their weekday, or their work week time, and they can't fall asleep. And essentially what they've done is it's as if they've flown to another time zone and their body thinks that it's not time to go to sleep yet. And they've induced their own jet lag called social jet lag.

And so one of the things that Fitbit found, and I think one of the most impactful things, is showing that getting that regular bedtime, being in that routine, going to bed at about the same time every night is one of the best things people can do for improving their sleep.

Gazella: And even on the weekend, and I'll tell, you, when you put this on my radar I, of course, had to do a little research and there's a lot of studies on this that actually show that the physical effects that you talked about with sleep deprivation earlier also occur with this social jet lag. So I think it's really important for clinicians to be aware of that. So thank you for bringing this to my attention.

So now doctors often prescribe benzodiazepine or benzodiazepine-like drugs to help patients sleep. What are some of the potential risks of these particular medications?

Neustadt: Well, the potential risks are very well documented and they increase risk for falling, dizziness, light-headedness, those risks are increased in people who are 60 years or older because their ability to metabolize the drug tends to decrease. And so because it increases the risk for falls and dizziness and light-headedness, it then increases the risk for fall-related injuries, such as osteoporotic fractures, such as concussions, such as death, even. But even beyond those risks associated with increased risks for falling, the research has shown that cancer risk is actually increased in people who take over about 132 doses of benzodiazepine a year. So that's even ... that's less than half of a year worth.

And in fact some of these risks are increased with very small and limited exposure. So you know from half a dose to 18 doses per year, the hazard risk for death is increased 3.6 times. 18 to 132 doses, the hazard risk for death increased 4.43 times in a study that looked at this. And for greater than 132 doses, it increases 5.32 times. That's 532 percent greater than somebody not taking these medications for death. And the research has shown to actually get one benefit, the number needed to treat, to have one patient benefit is 13 patients. But the number to treat to create harm is only 6 patients.

Gazella: Yeah, that's problematic. So what about the newer class of medications, like the orexin receptor antagonist Belsomra?

Neustadt: Belsomra came on the market in 2015, it's a schedule 4 drug and it's a CNS depressant. So, like other CNS depressants, like benzodiazepine, it can have similar adverse effects. Some of the benzodiazepine drugs like Lunesta or Ambien can also cause, like Belsomra, can cause daytime impairment including impaired driving skills, risk of falling asleep while driving, abnormal thinking and behavioral changes are part of the adverse events spectrum, including amnesia, anxiety, hallucinations, other neuropsychiatric symptoms, even complex behaviors like sleep-driving. I mean, you're driving while not fully awake, after taking the hypnotic. Or other complex behaviors have been documented, like preparing and eating food, making phone calls, or even having sex, without remembering it.

And so the drug has some serious risks, including worsening of depression and suicidal ideation, and the benefits of that, it can increase ... or the benefits of the medication, because all medication, it's a risk-reward calculation ... it can decrease sleep latency, that is, the amount of time to fall asleep by about eight to 10 minutes and increase sleep duration by 17 to 20 minutes.

So at the most beneficial end of that, maybe it's 30 extra minutes of sleep. But you get all of those risks associated with it.

Gazella: And are patients getting good sleep when they're on these prescription and over-counter medications? Are they getting good quality sleep?

Neustadt: Well, you raise a great point. That's one of the problems with all of these medications is they tend to increase sleep duration, sleep quantity, but they're not increasing sleep quality. They're not getting patients into that deep, restorative phrases of sleep, the slow-wave sleep, phase 3 and into phase 4, to get that good, restorative sleep.

So the quantity of the sleep may be increased but the quality has not been shown to be increased.

Gazella: So you've made a pretty compelling case that a more integrated, holistic approach is needed. And integrative practitioners often recommend melatonin for insomnia with their patients. Can you talk a little bit about melatonin and why for some patients, many even many patients, it may not be enough?

Neustadt: Melatonin is one of the first things I find that people with whom I speak, they've tried. They've reached for that. If they're going to try a natural product, they've reached for the melatonin, you know, first, almost universally.

The challenge with melatonin is that it's got a very short half life, 40 to 50 minutes. And so while melatonin is considered a circadian modulator, meaning it helps the body recognize day from night, and it is a natural hormone, a natural product that our body uses to help us fall asleep, it's not really used for sleep maintenance. And so when somebody takes melatonin to help them fall asleep, because it's got such a short half life, well 50 percent of the melatonin is eliminated from the body in less than an hour, so let's just be generous and say an hour for easy calculations. So common doses out there is a 3 mg dose. So in an hour, they've got a one and a half milligrams left. An hour later they've got .75 milligrams left. And on down.

And so 3, 4 hours later, essentially most of that melatonin is out of their body and they wake up again. I hear so often people who take melatonin, they end up waking up in the middle of the night, still. And so what do they do? Well, they might need more melatonin. And so they keep taking higher and higher doses until they're sleeping through the night and then they wake up feeling drugged in the morning. Groggy, hungover and it takes them hours to actually feel fully awake.

So the natural rhythm of melatonin in our body is that the rise in melatonin occurs around 10 PM and then it peaks at about 2 AM in the morning, and it declines at approximately 6 AM, it's declined back to baseline. And that makes sense because that's sort of the rhythm of when we start to fall asleep and when our body then starts to wake up. Of course melatonin is balanced with other hormones as well that the body is producing during sleep, but the immediate release of melatonin that people are taking is not mimicking the body's cycle of melatonin production during the night. And it's also not a complete solution because it's not dealing with the other phases of sleep, we're looking at the other hormones in sleep, GABA for example. Or the other variables that can impact sleep such as poor blood sugar. When blood sugar can drop, hormones are secreted like cortisol and epinephrine to increase the body's blood sugar and we wake up.

And so that's why melatonin for a lot of people doesn't work, because it's just not a complete enough solution.

Gazella: I think that's a really good point, that it's not a complete solution for many people and that's why you use such an integrative approach. So I'd like to really dig into your integrative approach, I'd like to talk about dietary supplements, diet, and other lifestyle factors. So as long as we're talking about melatonin, let's keep on that subject and talk about dietary supplements. Are there specific dietary supplements that you use in your clinical practice specifically for insomnia?

Neustadt: There are and it depends typically on the clinical picture. So for example if somebody has muscle aches or tight muscles that's keeping them from sleeping, magnesium can help, that can be a gentle muscle relaxant. If there's some anxiety that may keep them from sleep, well, glycine is an amino acid that's also an inhibitory neurotransmitter, that can be helpful. GABA also an inhibitory neurotransmitter used in the body available as a dietary supplement. That can be helpful. Botanical extracts such as alphianine increases alpha-wave production in the brain which is associated with calming, alert calmness. Then there are some sedative botanicals that can be helpful such as hops or skullcap, also called Scutellaria. And others.

So that's part of it and for potential, looking at decreasing the response to stress, I like using, if they're under a lot of stress, some adaptogenic herbs like ashwagandha, or jujube, magnolia bark extract. If there is vaso ... if there's an issue with hot flashes and perimenopause, pine back extract. There's a clinical trial on that showing that it improved sleep quality and sleep quantity.

And so I typically, you know, this monotherapy approach of one symptom, 1 pill, it really doesn't work when we're looking at complex pathologies like insomnia or many other chronic issues. And so I tend to like products that combine those different nutrients shown in clinical trials to work that target the underlying pathology, the underlying biochemical pathways at work and sleep and affected by insomnia in a time release or a biphasic time release delivery system because it more closely mimics the body's natural rhythm of the 2 major categories of your sleep. One is helping somebody fall asleep, you know how do we do that, and the other, over ... you know, the subsequent 6, 7 hours later after they've fallen asleep, how do we help them stay asleep?

And so that's how I conceptualize it and that's the overall approach with dietary supplements when they're indicated.

Gazella: So before I move on to diet, I know that you helped formulate and create a specific sleep supplement. I want you to tell me the name of that supplement but I also want you to tell me why you created it, because let's face it, there are a lot of sleep supplements in the market. So why did you want to create the supplement that you created?

Neustadt: So the name of the product is NBI's, my company, NBI's Sleep Relief is the name of the product. And I created it for a couple reasons.

One, just like all the products that I've created in NBI and formulated, I couldn't find the combination of nutrients or the dose and form of nutrients in a product shown in clinical trials to actually work. And I personally suffered from insomnia for years and years. And I tried a lot of different things. It wasn't helping me. I'd work with a lot of my patients trying to different things, having to dispense different bottles of products, in addition of course to working with diet and lifestyle and other psychosocial factors involved. And I couldn't find something that worked consistently.

And so I started digging into the sleep research, the pathophysiology of sleep, the clinical trials, what are the underlying mechanisms affecting sleep. And after over a year of research and formulating and working, trying over a dozen different combinations and doses, that's when I created Sleep Relief.

Gazella: Okay perfect, Sleep Relief. So now let's talk a little bit about diet. What are some of the things that you recommend to your patients when it comes to sleep, associated with diet that may not be on the radar of some practitioners?

Neustadt: So one of the big things that I see over and over is a lot of people have, may have acid reflux and they don't know about it. And because maybe it's not ... maybe they have a cough when they lay down, maybe they are just not aware that that's going on. And so evaluating for that because that can wake people up.

The other thing that I find with diet that's very important, and with acid reflux, you know, that can be diet related. There are 5 most common foods that can contribute to that and interrupt sleep, that's raw garlic and onion, chocolate, coffee, and citrus. Although other things can do it for other people. An infection can do that, H. Pylori can cause that as well. And then if they have a hernia, a hiatal hernia, that can cause it as well. So looking at that, looking at those underlying potential causes if that is involved.

The other thing is poor blood sugar control which I already mentioned. And one of the things I like to ask that can indicate if they might have poor blood sugar control is if they get that afternoon, postprandial tiredness. You know, about 3, 4 o'clock in the afternoon, a couple hours after lunch do they just get that energy slump. And that can be an indication that they're having a little bit of blood sugar control issues. Or are they waking up at the same time every night. Both of those questions can give clues.

And if that does seem to be involved, one thing that I love to try with patients ... it doesn't work very often but when it does, it's really a home run, and that is ask them to eat 8 to 10 grams of protein before bed. Protein's one of the best ways to regulate blood sugar. And so if they do that and it stabilizes their blood sugar and they then are sleeping through the night, well, again, it's a home run. I mean, there are no pills, no powders, it's just natural doing it with food and it also opens the door for even more discussions with helping them understand how they can improve their diet during the day to help, to eat, to promote ... to help them understand how they can eat, changes they can make to eat, the promote their health for the rest of their life.

Gazella: Yeah, those are some great suggestions when it comes to diet. Now let's talk a little bit about lifestyle. What are some things that may not be on the radar of some practitioners when it comes to lifestyle aspects?

Neustadt: So we talked about going to sleep at about the same time every night, that's really important. The other thing is ... and most practitioners, or hopefully all of them have heard of sleep hygiene. The research shows that about the 69 to 70 degrees for most people is the ideal temperature for sleep. Some people who, if they're in a relationship with their partner, they may like different temperatures may be most comfortable for them.

So there are wonderful things out there now, it's call the ChiliPad, that you can get, it's a pad you can put on your bed, where you can control the temperature on each side of the bed. So that can be really helpful.

Stress of course is a big issue in our society, a lot of people are under chronic stress, so anything that we can do to help people decrease their stress or better deal with stress is really important. And a fantastic study came out recently that showed that a lot of the impact of stress is not the actual event happening to us, it's how we view it. So if people view stress as a good thing, meaning "I gotta learn something from it and what can I take from this," the health impacts from stress are mitigated. If somebody sees a stressful event and they're internalizing it and they're not seeing it as a growth opportunity, then it magnifies the negative stress impacts.

So, A) getting them to just understand that mindset is really important, just when it comes to stress happening, and then what can they do to have more control over those events that may be causing them stress to decrease that stress. And that could mean creating healthy boundaries for themselves. That could mean doing any yoga or mind-body techniques. You know there's lots of things that we can offer to patients that can be incredibly, incredibly helpful.

Gazella: Yeah, I would agree. And now your approach focuses on diet, lifestyle, and dietary supplements. How important is it to focus on all 3? So some practitioners might be really focused on the person's diet, or some might be looking at their stress level, and some might be focused on just melatonin. Why is it so important to look at this from an integrative standpoint?

Neustadt: Well I think if we want to do the best job we possibly can for our patients and give them the best results, looking at it through a more integrative approach is important. And I like the approach of trying dietary supplements to give people benefit quickly. So if somebody is sleep deprived, it's gonna increase their tendency to reach for those comfort foods. I think we've probably all experienced that. And especially because what happens with insomnia and sleep deprivation, it decreases mood. It can cause depression. And sugary foods, for example, when we reach for those, it can increase our serotonin production and temporarily lift mood. But it causes this rollercoaster of insulin and blood sugar that's hard to get off of.

So just getting people sleep can help improve their mood. So I like the dietary supplement approach for triage to get them feeling better so they can make healthier decisions, have a more present mindset, be more proactive instead of reactive, while I'm working with them also on improving their diet. Transitioning to a healthier way of eating, which, the research has shown, unambiguously is the Mediterranean pattern of eating. And also stress reduction and exercise and those things as well.

Gazella: Yeah, I mean that all makes a lot of sense. And this is a very important topic and I want to thank you, Dr. Neustadt for a very interesting conversation and once again, I'd also thank today's sponsor, Nutritional Biochemistry Incorporated, or NBI. Thanks again, Dr. Neustadt, for joining me.

Neustadt: Thank you for the opportunity.

Gazella: Have a great day.

Neustadt: Thank you.

Gazella: I'd like to remind readers of the Natural Medicine Journal that we now offer free continuing education credits for naturopathic physicians. Our list of podcasts and research guides that have free CE credits is growing. For more information, just click the Continuing Education tab at the top of our Natural Medicine Journal website.

Feb 5, 2019

Statistics indicate that hearing loss is on the rise. In this interview, board certified otolaryngologist Dr. Ford D. Albritton IV describes the magnitude of the problem, as well as the research associated with key nutrients that can help reduce the risk of hearing loss. It's critical that all practitioners, not just hearing specialists, put this topic on their radar so they can help patients who already have hearing loss and those who are at risk.


About the Expert

Ford Albritton

Ford D Albritton IV, MD, FACS, is the director of sinus surgery at the Sinus and Respiratory Disease Center at the Texas Institute for Surgery. He has served as chairman of the board of directors at the Texas Institute for Surgery and chairman of the Department of Otolaryngology-Head & Neck Surgery at the Texas Health Presbyterian Hospital of Dallas. Innovation and creative solutions to long standing problems in his field have been a focus of his practice since completing his training at the Emory University School of Medicine. He holds patents in the fields of nutritional compounds for targeting prevention of sensorineural hearing loss based on research initiated in the early 2000s. He also holds patents and expertise in the field of sinus disease and surgery with several publications to his credit. He remains active in clinical research and has been requested as a lecturer on the subject for surgeons domestically and internationally. Current interest exists in linking dietary methods of hearing preservation to cognitive function maintenance in patients with hearing disability, defining intervention strategy, and establishing modes of prevention.


Karolyn Gazella: Hello, I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today we have a fascinating topic. We'll be talking about how certain nutrients can help reduce the risk of developing hearing loss, and we have the perfect expert to help us with this topic. Dr. Ford Albritton, IV is a board certified otolaryngologist with the Sinus and Respiratory Disease Center at the Texas Institute.

Dr. Albritton, thank you so much for joining me.

Ford Albritton, IV: It's my pleasure, Karolyn. Thanks for having me.

Gazella: Yeah. So, how common is hearing loss, and have we actually seen an increase over the past decade or so?

Albritton: Hearing loss is incredibly common, and it's been pretty consistent if we look at the prevalence. The National Institutes of Health actually has its own group that looks at communication disorders, and they estimate the prevalence of about 15% of residents in the US having a diagnosis of hearing loss, and currently that puts us at about 38 to 40 million.

And you asked the question has there been an increase, and it's sort of a tricky answer. Yes, there's been an increase, but so has the population increased. In 1971, that number was 13.2 million and basically one third the current number.

So, why are we seeing such an increase? Well, it's a combination of population growth and the basic dynamics of our population age. If we look at aging as a criteria for hearing loss, we can compare people that are between the ages of 45 and 54. Only about 2% of those people are going to have a diagnosis of hearing loss, but if we go up to 75 years or older, almost one half to two thirds of the population will be having a hearing loss diagnosis depending on the studies you look at. And the World Health Organization has currently estimated hearing loss at about 466 million, but by 2050 they do predict that number should hit 900 million.

So, there's certainly an increase, but it's tricky to say that that's because of something changing in the environment or our susceptibility is increasing, and their point of fact is a few years ago, pediatrics journals documented that adolescents were having an increased rate of hearing loss from comparing data between '94 and 2006. They reviewed that data again in 2010 and found that that was just simply a statistical error and that they had erroneously just compared two points of data instead of contiguous and that actually the rate of hearing loss has not increased in that age group.

Gazella: Okay, that's interesting. So, what is considered a normal hearing range, and at what range does there begin to be a problem?

Albritton: The way we measure hearing is using something called an audiogram or audiometry, and it measures sound intensity. The official measurement unit is called the decibel, which is a logarithmic measurement of sound intensity, and we define normal hearing as a threshold where a subject can recognize a presented tone at a specific frequency less than 20 decibels. So, if you're presented a tone at a low frequency or a high frequency and you can perceive it, recognize it at a sound energy level quieter or equal to 20 decibels, that's normal.

Furthermore, we use some tricks of averaging and statistics to have some simple ways of measuring. Like we will average two tones or three tones or pitches on the hearing test and come up with a number of sound intensity, and we consider anything less than 20 normal, and anything above 25 we start to believe is abnormal and probably would benefit from some sort of intervention.

Gazella: Okay, great. So, let's talk a little bit about risk factor. Who's at risk of developing hearing loss?

Albritton: Probably a number one factor is family history. So, genetics play a larger role than we really can appreciate at this point in our mapping of the human genome, but family history is probably the most important question we ask patients into mapping their risk for hearing loss.

The second one would be noise exposures, people with a high occupational noise exposure. OSHA measures that as greater than eight hours exposed at 90 decibels, so noise exposure at that rate can cause hearing loss.

And then drugs; certain chemotherapy agents, some antibiotics are notorious for being toxic to the inner ear. Certain infections; one of the great benefits of immunizations and the reason we recommend immunizations is to prevent some of these preventable causes of hearing loss. Maternal infection of mumps, measles, rubella, for instance, can have devastating consequences on a fetal ear development and could have consequent hearing loss.

And then finally, sort of our chronic illnesses, diabetes, hypertension, heart disease can compromise blood flow and health to the inner ear causing problems. Inflammatory conditions such as rheumatoid arthritis, certain inner ear inflammatory conditions can also cause problems.

So, it's a pretty broad area of the things that can cause hearing loss, but the biggest risk, again, being family history.

Gazella: So, when we think of hearing loss, it's understood that it obviously affects communication and how we communicate with each other, but does hearing loss have any physical impact on a patient's life?

Albritton: That's an interesting question, and I think that 20 years ago we probably would not have directly thought so. It obviously does affect sense of wellbeing and ability to interact with others, but it can affect a lot of other things.

An interesting study from last February demonstrated a correlation of hearing impairment severity and the incidence of fractures to the radial forearm, to the hip, to the spine, and it showed that patients with severe hearing impairment actually had an increased risk of fracture that was greater than the normal hearing group, and basically you had 1.4 to 1.6 greater risk of having one of those types of fracture from a fall if your hearing was severely affected. There's lots of further digging that needs to be explored such as severe hearing loss also contribute to injuries to the balance system. That's sort of outside the scope of the research at this time.

But really the most newsworthy research in the past decade is focused on the correlation of hearing loss, severity of the hearing loss, with cognitive impairment and dementia. In 2013, a paper out of Johns Hopkins authored by Dr. Lin out of their department of otolaryngology and his colleagues demonstrated in just under 2000 patients that patients with a pure-tone average, that's that average we discussed earlier, of several frequencies of over 25 decibels, they had rates in decline in their cognitive function testing that was 30% to 40% greater than their normal hearing peers. And not only that, there was a linear relation between the hearing loss severity and the degree of decrease in their cognitive function test scores.

So, that data really set off alarm bells, and health organizations throughout the world, the British health system, the French health system, Danes, Italians began looking at their population, and probably the most robust examination has been the English, many thousands of patients, have agreed with this information. They put a cognitive impairment risk of 1.6 times greater than normal hearing population with hearing impairment.

Interestingly, some of these studies took the next step and tried to assess, well, if we do something for the hearing, such as a hearing aid or a Cochlear implant, something that will restore hearing, does that make a difference in the cognitive impairment testing? And it actually does.

An Italian study was one of the preliminary studies to look at this, and they demonstrated that either a hearing aid or a Cochlear implant could actually reverse some of this cognitive impairment seen on the testing with improved scores. The French study was pretty astounding in terms of its result. Greater than 80% of their lowest scoring cognitive impairment patients tested, they showed improvement after the Cochlear implant, which was quite surprising.

So, there's a question as to how hearing loss, how is this leading to dementia? And I don't think we fully understand that yet, though there are some hypotheses, and Dr. Lin laid out about four of these. First one being is there some common physiologic pathway that's contributing to both brain damage and inner ear damage? Something like blood pressure elevations where we see some chronic ischemic changes to the brain on MRIs or diabetes or something along those lines.

The second theory is something called the cognitive load theory. Basically, it surmises that the effort of constantly trying to comprehend what is being heard takes memory resources, whether it be a neurotransmitter or other nutritive resources, and the chronicity and cumulative nature of this leads to issues and errors in ongoing brain function, the ability to maintain memories in an ongoing manner.

A third theory is that hearing loss may affect brain structure. We do know that in brains of patients without stimulation, stroke patients, et cetera, that there's certain areas of the brain that shrink, and it isn't necessarily that we lose cells there, but there are some changes in the simple [inaudible 00:11:38] of those cells and that hearing loss patients do appear to show some of those similar findings on their MRIs.

And then finally, social isolation. We know that social isolation happens with hearing loss, and we also know that social isolation is a known risk for cognitive impairment. One theory that a lot of fellow ENTs and otolaryngologists specializing in ear have known about since the '90s is that if we fit a patient with hearing aids earlier, they do better long term, and a large study in the VA looking at World War II veterans in the '90s established that patients that obtained hearing aids earlier did better with those hearing aids long term. They were able to accurately repeat words presented to them at a higher rate than their peers who had not obtained a hearing aid and had similar hearing test results. They would have basically the same level of hearing loss, but their ability to interpret speech was impaired, and the ability for the hearing aid to function with those patients was just suboptimal and were not able to get the same level of functionality from their hearing aid.

And what the theory was is that the stimulation of certain areas of the cortical brain kept those areas healthy and functioning and that the old use it or lose it hypothesis, the patients who weren't using it did not maintain that brain and it therefore degenerated, never to really fully improve.

This takes it to another level and seems to suggest that it's not just those areas of brain corresponding to speech recognition; it's rather the brain as a whole that is suffering from the lack of input.

Gazella: Yeah. Early intervention is always best, so that makes a lot of sense. Now, you mentioned social isolation. Are there other areas that are affected with hearing loss that negatively impact the quality of the life of the patient?

Albritton: Well, I'm sure that there are, and I'm sure that we're going to discover more, but I think the most obvious is isolation and its consequential potential for depression. People that can't hear, they eventually will isolate themselves in social situations because it just becomes too embarrassing or futile for them to continue trying to participate in a conversation they can't hear. And I think we all can appreciate what that feels like. If we've ever been to a noisy restaurant and we can't hear the conversation across the table or slightly away from us, we tend to withdraw. Imagine that for patients with significant hearing loss being a daily ongoing issue, and that ends up contributing to further self-isolation, but depression, and several studies have demonstrated that there is an increased incidence of associated depression with hearing loss.

Gazella: Yeah, that makes a lot of sense. Now, you mentioned genetics. So, what is the difference between hereditary hearing loss and age-related hearing loss?

Albritton: I would suggest that almost all forms of hearing loss that we attribute to age probably have some genetic component. As we look at just genetic programming for your resilience, your resilience of your skin, your eyes, your hair, your ears, all of those things are sort of pre-programmed, and most people accept multi-hit hypothesis to hearing loss. In other words, that it's not one thing; it's a multitude of things over time that lead to the cumulative and irreparable damage and that there are certain susceptibilities imparted by our genetics.

So, we would guess that most age-related hearing loss does have some genetic, if not total genetic, predisposition, and the fact that it's not 100% of patients over the age of 75 with hearing loss, rather one half to two thirds, sort of backs that up.

But in terms of congenital or hereditary hearing loss, there are certain conditions and syndromes which we know are hearing loss related, and we can diagnose those fairly young. It's the patients over the age of 40, 50, 60 that we're less able to determine. And there are some studies, though, that have looked at what we term age-related hearing loss and looked at their genetics and have identified some mutations that are fairly specific for a family group but not universally represented in other genomic studies, and they show up in certain areas of the gene pool where we know that genes dedicated to hearing messaging are present.

So, there's probably a multitude of issues with mutations over our family histories that does lead to the age-related hearing loss, so I would look at them mostly in the same way.

Gazella: Yeah. It'll be interesting to see how that research kind of plays out from an epigenetic standpoint.

Now, there's early evidence showing that antioxidants, specifically beta-carotene, vitamins A, C, and E and magnesium can be protective. Tell us about that research.

Albritton: Sure. I want to add one more little point to the last question as it'll tie into this. We do know that insulin-like growth factor 1 is something that's important in our homeostasis and our ability to fight off reactive oxygen species or free radicals, and some studies have demonstrated that this decreases with age, and some other studies have taken it a step further and looked at does this have a role in some of the age-related hearing loss, and it does appear to have some role in that.

So, it's been a natural thing for antioxidants to have been targeted as a potential therapeutic arm against the aging of the ear. You mentioned vitamin A, C, E, magnesium, and I would caution drawing conclusions to these individual compounds at this time because the data is really all over the place.

There are numerous studies in mice that have demonstrated some general improvements using a group of different antioxidants versus control groups. Some of those antioxidants include things like cysteine or acetylcarnitine. Longitudinal studies, though, looking at humans with vitamins A, E, C, B12, folate have showed different results. For instance, in men, they didn't find any difference with any of those vitamins used except in men over the age of 60 they did note that folate may have given some protective benefit. In women, they found that vitamin A and folate also helped not necessarily an age dependent result, but this is interesting; vitamin C, which has been shown to be helpful in some animal models, was actually harmful and actually worsened things in some women studies.

We know that folate is an effective cofactor. We know that it helps balance out homocysteine levels, which can protect ischemic vascular damage, so that makes sense to us that it would work. The roles of vitamin C are just straight antioxidant properties, so that suggests that there's something more than just straight antioxidant benefits.

One interesting study in Finland that was done about 10 years ago, and they call it the disco study, and it wasn't a very large study; about 20 people were given either an antioxidant vitamin or a placebo. They had their hearing tested before a night exposed to loud music and then they had their hearing tested short term and long term afterwards, and they definitively showed that the group with the antioxidants had less impact from the noise exposure than the control group.

Gazella: That's interesting. I like they called it the disco study. That speaks to the era or the timing of that study, I think. So, when we're talking about studies, the research that I read I believe also included magnesium. What would be the connection with magnesium and why would magnesium help our ears? Am I correct? Was magnesium a part of that study?

Albritton: Magnesium's a part in several of these studies, and magnesium and the metals probably have a bigger role in enzymatic cofactor, enzymes that can control either the release of certain natural antioxidants or enzymes that have some role in keeping a biochemical process in its favorable state as opposed to going to its unfavorable state. Those metals are essential to these enzymes functioning theoretically, and yes, in some military studies, the use of magnesium has been shown to be effective.

Gazella: Now, you mentioned a lot of nutrients, A, C, E, just talked about magnesium. Is the combination of nutrients important and are there other nutrients that you wish researchers would be looking at?

Albritton: Now, you're getting to what my interest is. I think yes. I think very much there is combination therapy that makes a difference. I think we're still trying to figure out what that precisely is.

There are a host of readily available organic compounds that are something we may have picked up through ethnobotany or traditional Chinese medicine or just from the vitamin industry at large, but we have found that several of these compounds do appear to help in the protection of the inner ear, the heart, the kidney, et cetera.

One of those is N-acetylcysteine in rat models, which has proven to be effective at protecting the outer hair cells of the inner ear, and one of the methods we think it works is just by scavenging the free radicals, but it does turn on the body's natural production of glutathione synthesis. So, it doesn't just target the free radicals with its own ability to neutralize them. It actually turns on the body's ability to keep producing those free radical fighters.

But there's something else that goes on. It seems to regulate the nitric oxide in the inner ear, and one of the things that nitric oxide can do is, depending on its concentrations, it can trigger a cell to commit cell suicide. We call that apoptosis. In damage that may be sublethal, damage that shouldn't cause a cell to destroy itself, sometimes that misregulation allows the nitric oxide to get so high that it ends up allowing that cell to die. And as you may or may not know, these cells can't regenerate at this time, and so that regulation of the nitric oxide is one unexpected benefit of the N-acetylcysteine.

And that's something we see in several other compounds. Some compounds, for instance ... I'm just going to give you a brief list. Resveratrol. We know resveratrol as a miracle compound that has some anti-aging properties in animals, turns on some anti-aging genes, but we found in several studies that it has a highly effective role in reducing inner ear damage in animal studies. It has not been studied in humans to date. We believe that's a real key chemical.

CoQ10 has been also very effective in guinea pig models. We know that the mitochondria stabilization appears to be important, and CoQ10 is important in the function of our energy production in the mitochondria. Replacement does appear to have beneficial effects.

One independent observation as I see patients in my office all the time with a balance disorder that we can attribute to a medication being used for their high cholesterol, and a class of medications HMG-CoA reductase inhibitors, such as the statin drugs, are notorious for depleting the body's natural production of CoQ10. So, replacement of that in patients has helped with balance preservation, and anything that helps balance preservation we can assume is also working in other areas of the inner ear as well.

There are a number of elements and compounds that we discussed. We put together in 2006 a group of compounds we thought were going to be important that included the resveratrol, the N-acetylcysteine, N-acetyl-carnitine, alpha lipoic acid, green tea extracts, flavonoids from citrus, the CoQ10, B complex, and the trace minerals such as selenium, manganese, magnesium, and have found that to be effective in some pilot studies that we have performed on patients with their hearing loss showing some actual improvement in their hearing using the compound versus not using the compounds.

We've not had the opportunity yet to complete a double blinded study at this time, but there is certain promise with this. I think the holy grail is a compound that would be able to be taken on a daily basis that would offer protective benefits to the whole body, not just the inner ear.

Gazella: Right, and when you're talking about protection, you're even talking about protection in a patient that has some hearing loss; that it can also work in that patient population.

Albritton: Yes. In fact, our pilot study really only targeted patients with hearing loss. We compared patients that had many years of hearing loss, and we had multiple hearing tests on them and then started therapy with them and measured several hearing tests on the medication, were able to compare their hearing test pre and post, and were able to make those comparisons based on a preexisting condition. And so we did see some improvements in patients with existing hearing loss.

Gazella: What about reversal? Is that on the radar or is that a little bit too pie in the sky to actually reverse damage, to have a hearing be regained?

Albritton: There's research being done in terms of hair cell regeneration. That's several decades away at best. That, if it does prove possible, would reverse it.

Now, in terms of nutritional therapy, that's an unknown. We don't have the data yet to determine that. I think it is promising that we can see improvements in cognitive function with hearing aids and with Cochlear implants, but we can't know that by correcting some of the metabolic issues or protecting the interior from damage from its own physiologic stressors or noise exposures whether that's going to actually reverse the hearing loss that has occurred. I think that's probably pretty hopeful on our parts, but never rule anything out.

Gazella: Yeah. Yeah, that's for sure. Now, given how common hearing loss is, it's likely that the readers of our journal have patients in their practice who are at risk. So, in addition to the nutrients that you mentioned, what else should doctors be recommending to their patients to help protect hearing?

Albritton: I think first and foremost is recognize how common of a condition this is and screen for it. Ask patients, "Have you had any problems hearing? Has your spouse indicated that you may be having trouble hearing you?" It's interesting that spouses tend to be the ones that send patients for hearing tests more often than the patient seeks testing on their own. And it's a known fact that only one in five patients with hearing loss is going to seek help for it on their own typically. It can take 10 years or so before patients seek help for the symptoms.

So, it can lay dormant, it can be hiding and be attributed to mumbling or volume not being turned up loud enough before a patient truly begins to embrace there may be a problem they need to evaluate.

Refer patients for hearing tests if there is a presumed hearing loss or if there's a family history of hearing loss. Any patient that is on those medications, chemotherapy drugs, certain types of antibiotics, those patients should be monitored.

One other thing that I think is very important and I think most practitioners are very good about doing, but let's remind them that noise exposure can be prevented. If you can't prevent the noise exposure, then protect yourself from it and that people that have hobbies or occupational risks should be wearing some degree of hearing protection, and just like smoking cessation's important for us to counsel, the use and adoption of protective devices should be something we continually discuss at our meetings with these patients.

Gazella: Yeah, it's such a good point that you bring up that one in five seek help on their own and a lot just kind of let it go, let it go, and yet early detection, the earlier it's caught, the better off they'll be. So, I'm so glad that we're putting this on the radar of the doctors who are reading our journal. This has been very interesting, and I really appreciate you for joining me today.

Albritton: Well, thank you. It's been a pleasure.

Gazella: Have a great day.

Albritton: You as well.