Insomnia and Its Implications

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

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Sleep Disorders and the implications to the general health

Sleep apnea is a very prevalent disorder with rising incidence in the United States. It is estimated that greater than 6% of women and 4% of men suffer from sleep apnea, or the temporary stopping of breath during sleep. This may be an underestimation, as persons with mild sleep apnea usually will not seek a medical diagnosis. An apnea episode is defined by at least a ten second interval between breaths, with either a momentary neurological arousal from sleep, or a blood oxygen desaturation resulting. These episodes are normal in sleep, especially in people that snore, but create a serious disorder when there are greater than five episodes per hour during sleep, and are clinically designated as needing therapeutic measures when there are over twenty episodes per hour in sleep. Clinical diagnosis is achieved with an overnight sleep study called a polysomnogram. State of the art clinics are now using a device that is sent home with the patient called an at-home device with web-based diagnostics, created by Watermark Medical, which accumulates the polysomnogram data with less expense and patient inconvenience. A polysomnogram measures the extent of deep sleep, or REM, by monitoring brain function with EEG, rapid eye movements, muscle firing with EMG, and heart rhythm with ECG. All of these important bodily functions coordinate with breathing and blood oxygen levels, and when breathing is disrupted too often in deep sleep states, or when deep sleep states are interrupted or decreased in frequency, health problems may occur over time. The challenge to understanding this complex disorder for the patient is one of understanding the entire health mechanism responsible, and the implications that this whole, complex disorder has on your health.

When you are diagnosed with sleep apnea, you should realize that this is almost always signifying a complex health problem that you should learn about and treat with a more holistic approach than standard allopathic medicine generally prescribes. The Complementary Medicine physician, or Licensed Acupuncturist and herbalist, can help you understand this problem and address the variety of health issues that you may need to correct. Recent studies at UCSF have shown that the risks of developing cognitive impairment and neurodegenerative disorders are doubled after 5 years of sleep apnea. Simply depending on a continuous airway pressure device (CPAP) to control apnea will not remove the underlying health problems or serious health implications of these underlying problems and the chronic airway obstruction.

Chronic sleep apnea may present a wide spectrum of health concerns. The implications of sleep apnea are foremost a lack of deep sleep and a sense of fatique, but there is a high association with cardiovascular disease, metabolic syndrome, adrenal fatique, hormonal imbalance, weight gain, ovarian cysts, neuroendocrine imbalance, hypertension and depression/anxiety disorders. Recent evidence also shows a strong relationship to neurodegenerative states and cognitive impairment, perhaps due to decreased oxygen causing buildup of beta amyloid plaques or increasing inflammation and oxidative damage (Yaffe, UCSF 2011). While each patient presents uniquely in such a complicated scenario, a diagnosis of sleep apnea should be a sign to the patient that a holistic assessment of their health is in order. Allopathic medicine tends to oversimplify the implications of sleep apnea, ignoring the underlying causative imbalance and utilizing treatment to control symptoms, while suggesting that weight loss is in order. This approach will not address the various systemic imbalances that led to the onset of sleep apnea, and underly this diagnosis, and patients with an underlying metabolic disorder and insulin resistance will have much trouble losing weight with normal exercise and dieting. While many patients with sleep apnea may need to utilize an airway machine, mouthpiece, or even surgery, these treatments do not address the underlying causes of sleep apnea, and probably do not significantly reduce the associated risks if these underlying disorders are not addressed. For many patients, sleep apnea may be a warning sign that serious underlying health problems now need to be assessed and dealth with.

As the incidence of sleep apnea has grown in the United States, so has the scientific understanding of the mechanisms that create this condition. Of course, we have looked for the simplest explanation, but the truth is that for many patients with sleep apnea, a simple explanation has not produced a clear understanding of the pathology. Research into the pathology of sleep apnea has instead revealed an increasingly complex set of causes and effects. Since modern allopathic medicine has little to offer therapeutically to correct this complex set of physiological causes, a simplistic explanation is usually offered the patient, more to fit the treatment than to address the actual individual health problems. The truth is that for most patients with a serious sleep apnea there is complex set of obstructive and neurohormonal causes.

There are three categories of sleep apnea, central, obstructive, and complex (a combination of central and obstructive). There is ample evidence now that most cases are a complex disorder, although if there is no obvious serious hormonal disease, standard medicine is reluctant to diagnose the patient with a central sleep apnea. Central sleep apnea implies that the origin of the apnea episodes is in the central nervous system, and is usually associated with a neurohormonal disorder. Since we now know that many neurohormonal disorders are subclinical, meaning that they do not fit the prior definitions of serious clinical disease presentation, this aspect is still not addressed properly with standard diagnostic assessment in many hospitals and clinics. Obstructive sleep apnea is thus the most prevalent diagnosis in standard medicine, although most experts in this realm now agree that a majority of disorders fit the complex category, and are a combination of obstructive and central health problems. Assessment of subclinical endocrine and metabolic disorders may be the key to reversal and cure of sleep apnea for most patients.

While standard medicine continues to diagnose most cases of sleep apnea as an obstructive type, the obstructive causes are complex, with airway obstruction related to unnatural relaxation of the muscles around the soft palate, or base of the tongue, enlarged structures in the upper throat, such as the tonsils and uvula, increased fatty tissues around the pharynx, and sleep posture. Even nasal polyps and nasal septum deviation have been implicated in some cases. Assessment often is determined by the specialist favoring a surgical or pharmacological approach, and since these treatments have a poor rate of success, control of symptoms rather than treatment of causes is by far the most prevalent approach in standard medicine. By far, though, in research, the most prevalent assessment of sleep apnea concerns changes in the tissues related to weight gain with metabolic syndrome, insulin resistance and hormonal imbalance. These issues may also be related to neurohormonal imbalances that affect the nervous system's response to changes in the oxygen and carbon dioxide content in the blood, oxygen content of the red blood cells, and changes in regulatory responses of respiration related to serotonin and norepinephrine diurnal levels. Poor function of the hypothalamus in relation to corticotropin releasing hormone neurons and adrenal stress appear to central to the underlying cause of sleep apnea (see the article cited below). The subject of sleep apnea has thus become another prevalent disorder that is difficult to understand, and thus difficult to treat. The proactive patient is taking the time to both better understand the disorder, and to seek out the knowledgeable Complementary Medicine physician to help deal with these dysfunction with a holistic approach.

Standard therapy for obstructive sleep apnea is still centered on cumbersome means of allowing the patient to achieve decreased incidence of apnea, with the use of a machine and mask to push increased air flow into the lung, and custom made mouth pieces that hold the airway open. The machine is called a continuous positive airway pressure device (CPAP), and is recommended when the respiratory disturbance index exceeds 20 episodes per hour. The noncompliance rate for this therapy, though, is very high, with complaints of excess noise, dry nose and throat, increased allergy symptoms, mask discomfort, cold or warm sensations disturbing the sleep, disturbance from the tubing with sleep movements, excess air in the stomach, and problems with reconnecting the device when waking to urinate and being too sleepy to reconnect. Many patients also report that these discomforts prompt them to remove the mask during the night in their sleep, or in a sleepy state. Often, the prescribing M.D. will also prescribe various medications to counter the increased allergy symptoms expected, sleep medications, etc. There are few studies that examine compliance and effectiveness of the machine and mask in the general population, although, studies in a controlled environment prove effectiveness in reduction of apnea. In other words, we know that CPAP is effective in the clinic, but we don't really know if it is effective at home. For this reason, many patients opt for a custom fitted mouthpiece to decrease sleep apnea and maintain an open airway. Satisfaction with custom made mouthpieces are high, but often these prove to decrease snoring but have not been proven to have enough effect to significantly reduce serious sleep apnea, and therefore are generally prescribed for mild to moderate obstructive sleep apnea. For many patients, a surgical approach is also recommended, with removal of enlarged tonsiles as well as reduction in the enlarged tissues of the soft palate. As is often the case, standard therapeutic methods often lack a complete solution for many patients, and these patients often look to Complementary Medicine to both enhance the effectiveness of therapies to control sleep apnea, as well as to address the underlying causes, and decrease the serious health risks.

What is still lacking from this equation is the treatment for the underlying causes of obstructive sleep apnea, which include metabolic syndrome, insulin resistance, weight gain, hormonal changes, andrenal fatique, poor hypothalamic function, and possibly subclinical hypothyroid conditions. Also, the prevalence of jumping to the conclusion that the disorder is completely an obstructive sleep apnea often means that the patient is not sufficiently assessed for a diagnosis of central sleep apnea. The term central sleep apnea, as stated, implies that a disorder in the central nervous system, or regulatory brain centers, is involved in the apnea process. Central sleep apnea could explain the scientific findings of unnatural relaxation of the muscles around the soft palate, that may relate to altered dopamine metabolism in the part of the brain called the substantia nigra, which controls muscle coordination. Patients and physicians should always consider that the problem of sleep apnea that occurs during the premenopausal to postmenopausal states, when hormonal and metabolic imbalances are common, are probably complex. Patients with sleep apnea and obesity, or metabolic syndrome, should also realize that the apnea is a complex type, even if signs of obstructive changes are evident. By failing to address the implications of central sleep apnea in the complex syndrome, the patient and physician may be making a mistake that has serious consequences in the future.

While the patient naturally seeks a simple solution to sleep apnea, these simple solutions are usually inadequate to address the health risks associated and restore the patient fully to an optimum state. Even surgical approaches usually do not achieve the success hoped for. This is often accounted for by an assumption that there is more tissue obstruction present than is treated by the surgery, but in reality, the underlying causes probably are singificant in many of these cases, contributing to the sleep apnea. In addition, surgical approaches do not stop the physiological mechanism that created the enlarged tissues in the first place, and there is an expectation that this enlarged airway tissue will regrow. The patient that undergoes tissue reduction should also consider a more comprehensive and integrated protocol to reduce the underlying causes to prevent this regrowth of obstructive tissue.

There is often no magic pill, or simple solution, to sleep apnea and the associated symptoms of fatique, weight gain, anxious depression, hypertension, cognitive impairment and neurodegeneration, etc. The wise patient seeks to better understand this complex disorder, and take a proactive step-by-step approach to correcting it, utilizing an integrated team and Complementary Medicine. Simple decrease in the symptoms of fatique and less waking during the night do not mean that all of the negative health issues are now resolved. This article, and other articles on the website, such as those addressing Metabolic Syndrome, seek to help the patient better understand sleep apnea and the related syndrome of health problems. Of course, as you read the article, you must understand that each patient is unique, and not all of these health problems are seen in each individual. You need to apply the information to your specific array of health issues when formulating a better proactive approach to help solve the problem and decrease the future health risks.

The relationship between obstructive sleep apnea, insulin resistance, and metabolic syndrome

It is widely acknowledged that increased accumulation of fatty tissue in the upper airway tissues is responsible for obstructive sleep apnea. While utilizations of machines to force more air throught these airways, mouthpieces that open the airways more, and even surgical correction to reduce these tissues may indeed temporarily open the airways and relieve symptoms, the thinking patient wonders what has actually led to this condition. Fatty tissue accumulation is regulated by our hormonal system, or endocrine function, which needs to be in balance for us to maintain optimal health. By separating sleep apnea from the associated hormonal and metabolic imbalances that underly the condition, we ignore serious health risks that threaten our health as we age.

The control of fatty tissues in our bodies is a complex issue, but is tied to the hormonal regulation by insulin, and affected by a host of other hormones. The pioneer of bioidentical hormone therapy, Dr. John Lee, found that progesterone deficiency was often intricately tied to insulin resistance, which is a hallmark of metabolic syndrome. This is one piece of the puzzle when looking at this problem holistically. In Metabolic Syndrome and obesity, insulin resistance, or resistance to the effects of insulin hormone at cell receptors, which is due to a variety of factors, is the focal issue. This insulin resistance creates an episodic excess response of insulin secretion. Insulin is a steroid hormone secreted by the pancreas that affects our sugar and fat metabolism in a complex manner, and has a host of effects in our bodies. Hormones are simple molecules that do nothing on their own, but act by affecting a wide variety of cell receptors. Insulin does have a direct impact on the regulation of fatty tissue accumulation, and insulin resistance does have the effect of increasing the density of fat cells and tissues to compensate, which is central to the pathology of obstructive sleep apnea. In addition, a number of other hormones have a strong synergistic relationship to insulin in the regulation of fat metabolism, and tissue changes, and some of this physiology is explained below. Abnormalities of adiponectin metabolism have been directly linked to fatty tissue accumulation in muscle, as well as in organ tissues. A 2009 study (cited below) at the Prince of Wales Hospital Research Laboratories in Sydney, Australia, found that fat mass and high molecular weight, or altered, steroid hormones, as well as insulin resistance were directly related to adiponectin metabolism. The researchers found that insulin resistance was higher with imbalances of fat mass, estradiol (the most active estrogen) and progesterone, and lower when adequate adiponectin was observed. The researchers concluded that there were strong negative associations between circulating adiponectin, and some of its high molecular weight isoforms (variations), and progesterone, and that progesterone and estrogens are likely to affect insulin sensitivity through modulation of adiponectin and body fat.

Adiponectin is the hormonal molecule found to be the link between abnormal fatty accumulation in tissues, insulin resistance, and the steroid hormones, especially progesterone and the balance between progesterone and estrogen, with relative estrogen dominance. Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid breakdown (catabolism). Adiponectin is secreted from fat cells and is usually found in abundance in circulating blood, where is must stay in balance with other circulating hormones to achieve correct homeostasis of the fatty metabolism. Adiponectin has been found to play a major role in the body in suppression of metabolic imbalances, including metabolic syndrome (type 2 diabetes), obesity, fatty liver disease, and atheroclerosis. Like all hormones, this molecule is simple, and the activity generated from adipose is related not to the molecule itself, but to the hormonal receptors that it stimulates. Expression of these receptors is correlated with insulin levels, and has been found to be reduced when there is diabetes or metabolic syndrome present.

Insulin sensitivity and the homeostasis of blood sugar regulation are negatively impacted by both intermittent hypoxia (decreased blood oxygen) and sleep disruption. This presents a viscious cycle in sleep apnea. Some scientific studies have also linked insulin resistance and metabolic syndrome to complex sleep apnea independent of obesity. Patients that are not visibly overweight are not exempt from problems of sleep apnea related to metabolic dysfunction and insulin resistance. These studies have shown that insulin levels and the immune mediator cytokines interleukin-6 (IL-6) and TNFalpha are elevated in sleep apnea syndromes independently from obesity. Insulin is a hormone secreted by the pancreas that does more than just regulate blood sugar. Insulin, TNFalpha, IL-6, and isoproterenol have all been found to effect the regulation of fatty tissue creation and degradation by downregulating the enzyme activity of adipose triglyceride lipase in fat cells. The depression of the normal enzyme function results in increased accumulation of fatty tissue in the upper airway structures. We see from such analysis that a variety of factors may work synergistically to create the tissue growths in obstructive sleep apnea.

To better understand how insulin dysfunction is related to abnormal tissue growth in obstructive sleep apnea, we may look at the immune dysfunctions, to adrenal stress and fatique syndromes, and potentially to the use of medications, to see how an array of problems might be involved in this airway tissue hypertrophy. Isoproterenol is a synthetic sympathomimetic beta adrenergic agonist, meaning that it is a drug that acts like an andrenal hormone and affects the body like a sympathetic neurotransmitter. This drug is used mainly to treat racing heart (tachycardia), fibrillation, and hypertension, but is now also used to treat asthma, bronchitis and emphysema (COPD), often in combination with other drugs. Studies like the one cited above show clearly how chronic adrenal stimulation, inflammatory conditions, and metabolic imbalance can directly work together to create the fatty tissue growths seen in obstructive sleep apnea. It is widely accepted in the last few years that this combination of adrenal stress syndrome, chronic inflammatory dysfunction, and metabolic syndrome are probably responsible for the rising incidence we see in obstructive or complex sleep apnea. We see that this scenario could form a vicious cycle, with decreased intermittent blood oxygen negatively impacting insulin sensitivity, and changes in insulin sensitivity disrupting the normal regulation of fatty tissue accumulation, or in other words, insulin resistance and metabolic disorder eventually causing sleep apnea, with sleep apnea worsening the insulin resistance and metabolic syndrome.

Hormonal imbalances may also change the sleep cycle and create added stress on the regulation of breathing at night and apnea. In pregnancy, a number of hormones are secreted at much higher levels, and these hormonal effects have been well studied. Increased estrogens may inhibit REM sleep, and increased progesterones may promote more non-REM sleep time. Cortisol, an adrenal hormone, may also modify sleep patterns, and increases in hormones stimulated by the hypothalamus and secreted by the pituitary, such as prolactin and oxytocin, may also alter the sleep cycle. Prolactin increases prolong the duration of REM sleep time, and oxytocin may lead to excessive sleepiness. Studies of increased hormone levels in pregnancy also show that increases in estogen secretion may cause mucosal edema and upper airway resistance. Estrogen drives the weight gain and tissue growths in pregnancy, and often the pregnant woman develops snoring patterns and may then develop obstructive sleep apnea. Increased progesterone secretion in pregnancy may also act on the brain respiratory control centers (ventrolateral medulla) to reduce blood CO2, which may contribute to sleep apnea onset. These studies in pregnancy may be applied to the general population as well. When changes in the levels of estrogens and progesterone occur, both the sleep cycle and tissue growth and edema may be affected, as well as respiratory regulation. Especially in perimenopausal and menopausal states, levels of estrogens and progesterones change, and this is the time when many women experience the onset of sleep apnea. Throughout life, especially for women, subclinical hormonal pathologies may occur, causing premenstrual symptoms, infertility, polycystic ovarian syndrome, subclinical hypothyroidism, and hypothalamic dysfunction. Sleep apnea occurs most frequently in the female population, and these subclinical hormonal changes and stresses may play a significant role in the pathology.

Most patients acquire the health problems that lead to sleep apnea gradually, but when faced with the consequences to their health, such as the now noticeable fatique that results from unrecognized sleep apnea, they look to the physician for a quick and easy fix to the problem. For the acupuncturist, the patient may ask if it is possible to cure their sleep apnea with a few acupuncture sessions. Obviously, the patient and the physician should look further than the surface with this problem and correct the underlying conditions, and well as the problems with general health that both worsen the sleep apnea as the sleep apnea worsens the underlying health problems. While standard medicine is helpful to decrease the incidence of sleep apnea with devices or surgery, it does not adequately address these chronic underlying health problems that will perpetuate the condition and add to future health risks. This is why the patient must try to gain some understanding of the problem and work with an integrated team of physicians, utiizing Complementary Medicine to regain a health homeostasis and stop the problems that cause and worsen the condition of obstructive or complex sleep apnea.

Numerous sleep studies have investigated the connection between increased weight, increased fatty tissues in the airway that lead to obstructive sleep apnea, and metabolic changes. A study cited below shows that sleep deprivation consistently leads to reduced leptin and elevated ghrelin, resulting in poor appetite control, excess appetite, craving for simple carbohydrates, and increases in BMI (body mass index), or fatty tissues. Leptin is a protein hormone that is created by fat cells to control appetite, affecting the regulatory centers in the brain, especially the hypothalamus, and is integral to insulin resistance and Metabolic Syndrome. Much research has now been conducted concerning leptin, and animal studies indicate that leptin is a stimulant of ventilation, as well as a role player in tissue development of the respiratory system. Leptin is being investigated not only as an important regulatory hormone affected by sleep deprivation, but as a potential causative factor in the pathology of sleep apnea when leptin deficiency or leptin resistance is evident. The Curie Institute in France has studied the subject of obesity thoroughly and concluded that chronic inflammatory dysfunction appears to be at the heart of this problem, the inability of the body to use stored fats in the metabolism, thus creating weight gain that is impossible to reduce, or a high BMI index. When this occurs, the white fat cells, which produce most of our leptin, become dysfunctional, resisting the insulin signals, and not producing sufficient leptin. We see how a number of factors work together, or holistically, to create this bad situation. Allopathic medicine looks to one step in this cycle to alter to correct the problem. An intelligent analysis concludes that we must affect the whole cycle of metabolic and inflammatory dysfunction to achieve real success.

Ghrelin is a hormone that is produced in the stomach lining, as well as the pancreas, that has a wide variety of effects. Chiefly, ghrelin is produced to stimulate appetite when we need food, but excess secretion of the hormone would drive appetite unnaturally, as well as affect mental function, memory, increase the concentration of the neurotransmitter dopamine in parts of the brain, promote intestinal wall cell proliferation and increase bowel motility, and affect the immune responses in the intestines. Chronically elevated ghrelin may be associated with GI dysfunction, such as irritable bowel syndrome, increased colon and pancreatic cancer risk, and poor short term memory, as well as having effects on mood. Stomach dysfunction may play a part in ghrelin imbalance, as well as increased oxidative states and inflamamtory dysfunction. Once again, a holistic approach to health in treating sleep apnea may work to resolve these various health problems in each individual case to restore balance and homeostasis, eventually decreasing fatty tissue accumulation and obstructive sleep apnea. This approach will work with long-term improvement in overall health, and the Complementary Medicine physician can help the patient improve these various aspects of their health to eventually cure the underlying cause of sleep apnea.

Metabolic Syndrome is a complex problem that is more fully explored in another article on this website. When this metabolic imbalance worsens in the body, increased stress is created on the metabolic processes, and insulin resistance, weight gain at the midsection, and poor liver metabolic function may result. If the liver is too stressed, triglyceride levels will be abnormal on blood tests, and cholesterol and lipoprotein levels, as well as circulating blood sugars may also be off. Insulin is a steroid hormone, and thus is part of the endocrine system and affected by other hormonal irregularities. This is perhaps one reason we see a higher incidence in women of sleep apnea, especially during the period of perimenopause to postmenopause. Restoration of hormonal balance with holistic treatment may have a very positive effect in the long term on sleep apnea disorder.

Metabolic syndrome is highly associated with estrogen dominance and relative deficiency of progesterone. Research in recent years has found that estrogen dominance with progesterone deficiency is highly associated with metabolic syndrome and insulin resistance. This problem may be worsened with the use of synthetic estradiol and progestins (see research cited below), with a high association between excess circulating estradiol and metabolic syndrome. These drugs may also affect the regulation of inflammation in the body, which could have a direct relationship to tissue hypertrophy in the airways. Studies have found that synthetic progestins exert a negative effect on the level of circulating adiponectin, and disequilibrium between proinflammatory cytokines (high interleukin-6/C-reactive protein) and the anti-inflammatory adipokine (low adiponectin). Since this inflammatory modulation is important in low-grade inflammatory states of fatty tissues, such an imbalance could promote tissue hypertrophy, leading to obstruction airways. The link between these various problems is becoming more and more evident over time.

Countering the health risks associated with chronic sleep apnea

Besides reducing sleep apnea and working to correct the underlying health problems that cause the central and obstructive sleep apnea, the patient with sleep apnea should consider a holistic regimen to protect against the serious health problems associated with the disorder. Cardiovascular risk is the main concern. Much research has uncovered the mechanisms by which increased cardiovascular risk is generated by sleep apnea disorders, and the smart patient seeks to understand the connection and do what is necessary to decrease the risk. Study at Columbia University (cited below) has concluded that obstructive sleep apnea (OSA) directly affects the vascular epithelium (lining of the arteries) by promoting inflammation and oxidative stress while decreasing nitric oxide (a vasodilator) availability and repair capacity of the blood vessels. Expression of the inflammatory mediators COX-2 (cyclooxygenase enzyme) and nitrotyrosine was found to be five-fold greater in sleep apnea patients in study, and nitric oxide synthase was found to be 56% greater in OSA patients than in control subjects. This contributes greatly to the poor health of the arteries, and to accumulation of plaque, or atherosclerosis.

A variety of therapies in Complementary Medicine offer the patient safe and effective therapies to increase antioxidant effects, increase healthy inflammatory regulation, inhibit COX-2, increase nitric oxide bioavailability, and modulate the systems responsible for maintenance and repair of vascular endothelium. Often, these various effects are combined in an herbal formula. Herbs contain a variety of medicinal chemicals, and a formula of herbs contains a wide variety of medicinal chemicals to achieve a complex goal. These chemicals have been well documented and studied, and comprise the modern science of herbal medicine and phytopharmacology. Naturopathic medicine also provides a wealth of research that is ongoing that addresses therapeutic protocol with nutrient medicines. While these therapies can be complex, they generally work to achieve the goal of reestablishing a healthy mechanisms within the body, and restore the homeostatis that protects against cardiovascular risk, and do not require chronic use of the herbs and supplements like pharmaceutical medicines.

Another focus of research into the cardiovascular negative effects seen in obstructive sleep apnea patients is the reduction of blood flow in the brain and increased reactivity to lowered blood pressure, which increases the risk of an eventual stroke, especially in the aging population. Sleep apnea is highly associated with increased stroke risk, and not only the decrease in healthy maintenance of the arterial vessels, but also neurochemical imbalances created in sleep apnea, either as a result of sleep apnea, or perhaps as part of the cause of sleep apnea, are implicated in the increases stroke risk. A study at Yale Center for Sleep Medicine, Yale University School of Medicine, found that there was a consistent decrease in cerebral blood flow velocity in sleep apnea patients during the waking hours, with an slower cerebrovascular response to hypotension. This slow response to hypotension was not attributed to a slow response to increased CO2 in the blood, which occurs when apnea results in decreased oxygenation and increased clearing of carbon dioxide by decreased breathing. The cause of the slow reactivity to hypotension and subsequent exagerrated response occurred because of other chemical imbalances associated with the sleep apnea disorder.

Nitric oxide (NO) is a potent vasodilator and important modulator of cardiovascular health and blood pressure. NO balance is intricately tied to the balance of oxygen and carbon dioxide in the body, as well as to oxygen radicals, or oxidants. Sleep apnea therefore has a clear effect on this oxygen metabolic balance. Red blood cells take up and carry oxygen, and sleep apnea has been shown to affect the oxygen concentration in red blood cells, mainly because of the imbalance of these various oxygen gases. A number of chemicals in the body are important as bioreactants and precursors to nitric oxide metabolism. Thees include glutathione, our main antioxidant and detox chemical, Cysteine, nitrates that are absorbed from food in our small intestine, L-arginine, and the various Vitamin B3 metabolites, or niacin molecules. As stated, there is a stress on the body in sleep apnea that leads to poor bioavailability of nitric oxide and increased nitric oxide synthase as a response. Nutrient and herbal medicine offers sound research and treatment to address such concerns.

New research is revealing how the body regulates fatty accumulation in muscles, and will lead to a more specific targets for herbal and nutrient medicine

Increased fatty accumulation and tissue growth is the most direct cause of obstructive sleep apnea. What causes this fatty accumulation and growth is rarely discussed with the patient, but this is a key consideration when trying to reverse chronic sleep apnea. Besides insulin and adiponectin, there are a variety of growth factors that are related to such tissue hypertrophy.

A study completed by the Swedish medical university Karolinska Institutet in 2010, and published in the scientific journal Nature, shows that hormonal signalling from muscles via the VEGF-B protein hormone (vascular endothelial growth factor) allows increased fatty acids to be transported throught the blood vessel membranes to be utilized by the muscles for energy. VEGF-B signalling created more fatty acid transport proteins in the blood vessel walls, and normally these fatty acids would be utilized by the muscles for energy. In animal studies, subjects that lacked VEGF-B expression in the muscles or VEGF-B receptors in the blood vessel walls had difficulty transporting fatty acids to the muscles and instead these fatty acids accumulated in white adipose tissues, the fat cells that are implicated in insulin resistance. VEGF expression in the muscles increases when the muscle is not receiving sufficient oxygen, triggering increased blood vessel formation. VEGF-B is a member of this family of molecules that does not respond to oxygen insufficiency, or hypoxia, directly, but is affected by VEGF stimulation. Binding of VEGF-B to the receptors on the blood vessel walls triggers a response that is also shared by the inflammatory mediators in the body, the tyrosine kinase pathway, and there is a close relationship between various inflammatory mediators, that also respond to hypoxia, and VEGF, as well as a protein hormone called platelet-derived growth factor. As research continues into this complex cascade of chemicals, we will gain an increased understanding of the holistic mechanisms that result in the accumulation of fatty tissues in airway muscles. All of this research reveals the complex workings of the body, and the need to target multiple systems and holistically promote a healthier homeostatic metabolism.

Another VEGF protein has been the subject of much research in cancer studies. VEGF-A is linked to tumor growth and the stimulation of increased blood vessel formation in tumors to meet the high energy needs. A number of pharmaceuticals have been created to inhibit VEGF formation, including Avastin. Naturopathic medicine has researched natural nutrient chemicals to achieve, or help achieve these goals, without side effects. This research may be important in the treatment of pathological fatty accumulation in muscle tissue. IP6 is one of these therapeutic nutrient medicines studied. Inositol hexaphosphate is found in high fiber foods, and has been proven in scientific studies to inhibit tumor growth via inhibition of VEGF production, as well as exerting strong antioxidant effects. Such effects will probably be found to also affect VEGF-B overexpression, and may be an effective addition to holistic and integrative therapy to reduce fatty accumulation in obstructive sleep apnea.

Another area of naturopathic research that may relate directly to inhibition of fatty accumulation in muscles is the subject of advanced glycation endproducts, or AGEs, that are implicated in the poor health of blood vessel walls and the accumulation of plaque and development of atherosclerosis. AGEs are also implicated in the physiological dysfunctions related to insulin resistance and metabolic syndrome, and the A1C index is now highly utilized in the diagnosis of diabetes type 2, or metabolic syndrome. AGEs could be implicated in the problems with VEGF-B signalling in the blood vessel walls, resulting in increased fatty acids transported to white adipose tissues rather than muscles for conversion to glucose energy. A number of nutrients have been studied in relation to improved fatty acid metabolism and clearing of AGEs. One company, Vitamin Research, has combined these nutrients and herbs into a product that includes R-Lipoic Acid, P5P, L-Carnosine, L-Histidine, N-Acetyl-Cysteine, Benfotiamine, and Guava and Yerba Mate leaf extracts. While this prescription is recommended for arterial health, macular degeneration and neurodegenerative conditions, future research may find this nutrient medicine formula very helpful in fatty tissue accumulation in obstructive sleep apnea in the future.

VEGF-B is also related to various inflammatory mediators, both in pathways that stimulate expression, and in sharing of receptors. Chronic low-grade inflammatory states may eventually have much to do with dysfunction of the VEGF-B metabolism and pathway. VEGF and interleukin-8 (IL-8) have been linked in studies, and problems with VEGF expression or receptor function could relate to excess IL-8, which is a pro-inflammatory mediator in epithelial and endothelial cells, and secreted by neutrophils and lymphocytes. Allergic responses in the airway could be related to eventual dysfunction of the VEGF-B pathway, as well as chronic tissue inflammation related to myofascial problems. A thorough approach to treatment of obstructive sleep apnea may include therapy that resolves myofascial problems, clears tissues of irritants and fibrin accumulations, and stimulates an improved immune response. When a number of interrelated health problems may work together to create an eventual complex pathology, such as fatty tissue accumulation in the airway creating obstructive sleep apnea, the therapeutic protocol must sometimes address these problems in a more complex manner. Complementary Medicine offers such holistic and intensive approaches with relatively inexpensive therapy. The end result of such therapy may be the eventual resolution of the causes of sleep apnea, as well as much improvement in overall health.