Correcting hormonal imbalances can greatly improve your immune function. In this chapter, we study the link between hormones and the immune system. With all that we know about hormones and disease, it is unfortunate that most conventional physicians rarely look at hormone levels when evaluating immune-related conditions, whether they are allergies, autoimmune diseases, inflammatory conditions, chronic fatigue syndrome, or chronic viral illness.
From my clinical experience in the anti-aging field and the treatment of immune-related disorders, I know that without evaluating hormone status an important piece of the diagnostic picture is missing. The following sections explain how you can optimize your immune performance with natural hormones, but first let's review how hormones interact with your immune system.
Hormones play vital roles in maintaining immunity, especially during severe long-term stress and in chronic illness. In step 1, I discussed the deleterious effects of our modern lifestyles, stress, and aging on immunity and showed how these factors negatively influence hormone production and disturb hormonal balance. In addition to causing anxiety and depression, stress interferes with hormone regulation, one influence triggering another, perpetuating illness in a vicious cycle.
Though doctors and scientists have accepted the connection between hormones and immunity for more than a hundred years, it is still far from clear how this connection works. For example, when the stress hormones adrenaline and cortisol increase, T-lymphocyte and cytokine function is altered, but we are unclear which cells are inhibited and which ones are activated. We only know the function is altered.
On the other hand, we know that steroid drugs suppress immune reactions and that due to this effect, corticosteroid drugs like prednisone, prednisolone, and methylprednisolone are used to treat conditions characterized by aggressive inflammation and autoimmune reactivity, such as multiple sclerosis and rheumatoid arthritis. However, when steroids are used in very high dosages, they suppress immune reactions and in turn create severe side effects that eventually can be worse than the disease—but we don't know why.
Another example is growth hormone. We know that natural immunity tends to decline with age, and that lower growth hormone levels are associated with aging. Though little immune research has been done on human growth hormone (HGH), it is known that increasing HGH levels improves lymphocyte function, but exactly what the connection is between aging, immunity, and HGH is uncertain.
An immune challenge, such as an infection, triggers activity in the cells of the innate immune system, causing the release of cytokines, primarily interleukin-1 ß. This dynamic process proceeds at a rapid pace, critical for survival. In a normally functioning immune system, inflammation starts almost immediately, causing the release of additional cytokines. Many of these chemicals serve as messengers that influence the brain, the liver, and the endocrine system—including the adrenal, thymus, thyroid, hypothalamus, and pituitary glands.
The hormones discussed in this next section have immune-modulating effects. There are many other hormones, such as estrogen and progesterone, that influence immune activity, but the ones discussed here are the most important for a well-functioning immune system.
Though most doctors do not test for hormone function in chronic viral disease or autoimmune conditions, accurate testing is readily available to evaluate the function of all of the hormones discussed below. If hormonal deficiencies are identified by clinical evaluation and lab testing, it is relatively easy to improve their function with natural hormone replacement or nutritional supplementation. If replacement is necessary, each of the hormones has a naturally occurring form, so you can avoid the use of foreign synthetic molecules such as prednisone.
In some cases, substances called secretagogues can stimulate hormonal secretion, or hormonal precursors (the chemical building blocks from which hormones are constructed) can be added to your nutritional supplement program to improve hormonal status. In addition, if hormonal activity is very low, each hormone has a bio-identical pharmaceutical counterpart that can be prescribed, if necessary, by a medical or osteopathic doctor.
Therefore, if you have hormone imbalances, there is no need to go untreated. You may gain relief either by careful self-treatment or under the supervision of a knowledgeable doctor.
The Adrenal Hormone Cortisol: Stress and immune challenges trigger a cascade of hormones that eventually affects immune function. One of the first responses by the endocrine system to an immune challenge is the release of cortisol and other adrenal steroid hormones. Therefore, for the immune system to be in optimal condition, the adrenal glands must also be functioning properly.
In addition to cortisol, adrenaline (epinephrine), excreted by the adrenal medulla, is also activated by a stressful situation and causes the “fight-or-flight” response, turning on the sympathetic nervous system. This system is also referred to as the arousal system, the opposite of the parasympathetic system that conserves energy and promotes harmonic balance. In an arousal response, our heart rate speeds up and we feel sweaty.
However, when adrenaline is in excess, the hormones and brain communicate in a way that tells the pituitary gland in the brain to down-regulate adrenal activity to control excess adrenaline, in other words, to shut down production.
In this way our stress hormone levels and autonomic nervous systems stay in balance. However, with chronic inflammation, ongoing or repeated infection, and unrelenting stress, the adrenal gland becomes worn down. Fatigue sets in and production of both cortisol and DHEA, another adrenal cortical hormone, can be severely affected, even diminished, causing symptoms of adrenal insufficiency.
Cortisol is the most potent of the glucocorticoid steroid hormones. Following daily cycles, it is naturally secreted in the body with the highest production in the morning and the lowest in the afternoon. At about one in the morning, your cortisol levels begin to rise; followed by a progressive increase during sleep until maximum levels are reached between seven and nine in the morning. The lowest levels of the day are around four in the afternoon.
Cortisol's role is to help maintain appropriate levels of glucose in the blood, thereby ensuring energy production for metabolic activity. Cortisol also helps our bodies fight off infections and manage inflammation, and it has profound effects on the immune system. It influences cytokines and immune cells at the site of infection and inflammation, but when elevated, it suppresses immune activity and inflammation. However, if cortisol levels are low, you will feel very tired with a profound flu-like fatigue and be prone to infections. William Jefferies, M.D., in his book, Safe Uses of Cortisol (1996) documents numerous clinical cases of low cortisol levels in cases of influenza and other viral infections, and the rapid improvement in those cases when cortisol was taken.
Like adrenaline, cortisol (hydrocortisone) is also produced in response to stress, though it is made in a different part of the adrenal gland—the adrenal cortex, or exterior portion. Hydrocortisone, available as an over-the-counter cream, is commonly used for skin rashes and swellings. It is effective because it reduces inflammation, and in our bodies, cortisol works in a similar way to help manage inflammatory reactions.
Stress or massive infection stimulate the release of larger amounts of cortisol which in turn activates the immune system. After the infection is resolved or the stressful event is over, the cortisol level returns to normal. If you have a chronic infection or inflammation, or are under constant stress, the adrenal glands will produce cortisol over an extended period of time and may eventually become exhausted. Cortisol levels will then become lower than normal. Chronic fatigue patients tend to have low cortisol levels, which causes them to feel tired all the time and to have a tendency to have minor recurrent viral, bacterial, and fungal infections.
The Adrenal Hormone DHEA: DHEA (dehydroepiandrosterone) is an androgenic hormone (one that causes masculine features like facial hair growth) secreted by the adrenal cortex. It is the most abundant androgen in the body. Its production declines with age, in response to long-term stress, in autoimmune conditions like rheumatoid arthritis, and it is frequently low in patients with chronic infections and viral diseases. DHEA helps to manage inflammation and has been shown to inhibit interleukin 6 (IL-6), a pro-inflammatory cytokine whose levels tend to increase with age and in people with chronic inflammatory diseases.
The effects of DHEA supplementation include improvement of mood and energy, deepening of sleep, increases in bone mineral density, improvements in muscle mass and strength, and promotion of hair growth. DHEA supplementation has been shown to improve immune function. This hormone has become widely popularized in the last few years, and though it is a prescription drug in most European countries, it is available in the United States as an over-the-counter nutritional supplement. I frequently recommend it as a hormonal optimizer, along with other specific natural hormones, in the treatment of menopausal symptoms, in anti-aging programs, and for chronic fatigue and chronic viral diseases.
Evaluating Adrenal Function: Conventional medical doctors rarely test for adrenal function in patients with chronic fatigue or chronic infections. The reason for this is that they are not taught functional or physiological approaches in medical school and do not look for conditions like adrenal insufficiency in their patients. Though you can order some tests on your own, for the accurate determination of adrenal function a naturopathic physician or a medical doctor who respects the importance of adrenal function and its role in chronic disease will best serve you.
DHEA and cortisol can be measured in blood, saliva, or urine. In my clinical practice, I use all three forms for testing adrenal function, but you will find that the easiest is salivary testing. Saliva testing is quite reliable, and measures the free, or bio-available hormone, making this test valuable in assessing adrenal function. Since the adrenal gland secretes hormones on a rhythmical basis each day (called the diurnal cycle), the patient takes four samples of saliva at regular intervals throughout the day and night. The DHEA and cortisol results are plotted on a chart and the doctor evaluates their relationships. (There are several reliable labs that offer salivary testing; the ones I recommend are listed in the resource section.)
Urinary tests are valuable in a comprehensive evaluation of adrenal activity. For these studies, the patient collects all of his urine over a twenty-four-hour period and the sum total of hormones detected is reported as a daily average. I use these tests often if I want a comprehensive view of adrenal activity, testosterone, estrogens, and progesterone levels, along with other adrenal hormones. This test requires interpretation from your doctor. In general, for evaluating DHEA and cortisol only, the salivary method is preferable.
Blood testing is also available, but it measures only the total circulating levels, and these are rarely abnormal except in adrenal diseases like Cushing's syndrome, a condition of persistently elevated cortisol levels. Blood tests are also not sensitive enough to evaluate borderline adrenal insufficiency because of the wide range of values in normal people. I use them only in patients in which I suspect excess levels of cortisol, such as in Syndrome X, a condition characterized by abdominal obesity, insulin resistance, high triglycerides, and high blood pressure.
For blood testing, cortisol levels are measured around eight in the morning (the time of highest secretion activity) and again around four in the afternoon (the lowest). For increased accuracy and to see how poor adrenal function is affecting blood sugar metabolism, I suggest the morning level be taken before eating breakfast (between 7 A.M. and 9 A.M.) and that an insulin level also be taken, followed by a 2-hour glucose tolerance test. A 2-hour glucose tolerance test (GTT) is performed by first drawing blood from a patient who has fasted for at least 12 hours, usually in the morning before breakfast. Glucose levels are measured, and the patient is given 75 g of a glucose solution to drink. Blood is drawn again after two hours, and glucose levels are measured for a second time. The results before drinking the glucose solution and two hours after are then compared.
Normal values for blood glucose when fasting are between 70 and 110 milligrams/deciliter (mg/dL). Higher or lower glucose levels after drinking the solution indicate abnormal glucose metabolism. Concentrations lower than 70 mg / dL indicate hypoglycemia, and values higher than 200 are indicative of diabetes. Adrenal insufficiency is suspected if either cortisol or blood sugar levels are low (before or after the glucose drink). If insulin levels are high and blood sugar levels are also elevated, then Syndrome X (insulin resistance) is suspected.
Low fasting blood cortisol levels can be found sometimes in patients with truly underactive adrenal function, but the most accurate way to test for low adrenal function is to have your doctor perform an ACTH challenge test. ACTH (adrenal corticotropic hormone) is the pituitary hormone that controls the release of hormones (such as cortisol) produced by the adrenal cortex. To perform this test, your blood cortisol levels are measured and then you are injected with a dose of synthetic ACTH. Blood is then checked after the challenge test, and these should at least double in response to the stimulation by the ACTH. If the cortisol level remains low, you most likely have adrenal insufficiency.
As blood tests for DHEA are accurate, I often use this method to establish a baseline in a comprehensive evaluation of adrenal function. The consensus among doctors practicing functional medicine and hormone balancing is that the best test for the evaluation of DHEA status is the sulfate form, DHEA-S. Conventional medical doctors use DHEA-S primarily to evaluate cases of hirsutism (women displaying excessive facial hair growth). However, according to Thierry Hertoghe, M.D., of Brussels, Belgium, and an authority on hormone therapies, DHEA-S provides a better picture of functional activity (Hertoghe 2000).1
DHEA-S levels are measured in micrograms per deciliter (mcg/dL). The so-called “youthful” ranges are from 400–560 mcg/dL for men, and 350–430 mcg/dL for women. As people age or when they are suffering from chronic disease, their levels may be well below 150 mcg / dL. In my clinical practice, I never push for the optimal “youthful” levels, because I believe that the amount of hormone this requires places additional stress on other systems of the body—principally the liver since it has to process all steroid hormones. I am satisfied with attaining levels above 250 mcg / dL for both men and women.
If either DHEA-S or cortisol levels are low, and you have the correct symptom profile, replacement may be necessary. If levels of either of these hormones are elevated, this may indicate excessive adrenal stimulation often due to high stress; in such cases, serious stress reduction is necessary. Elevated levels in the absence of previous supplementation may also indicate a disease pattern, and you should discuss this promptly with your doctor.
How to Correctly Supplement Adrenal Hormones: You can supplement cortisol and DHEA by taking adrenal glandular extracts, natural hydrocortisone (a synthetic prescription), or pharmaceutical grade DHEA. Only supplement these hormones if your levels are low.
Glandular extracts are made from the adrenal glands of livestock such as cows or pigs, and contain low dosages of all the adrenal hormones, including cortisol, adrenaline, and DHEA. Though glandular extracts are the treatment of choice for supplementing borderline low adrenal activity, there are advantages and disadvantages to their use.
The advantage of using glandular extracts is that they are natural and provide low dosages of adrenal hormones as a corrective medication, rather than as a drug. This ensures that you are not over-dosing steroid hormones, since often only very small amounts are needed to re-establish normal adrenal function. Too much can suppress adrenal function. However, there are several disadvantages.
The first is that glandular substances may not contain any hormones at all or the amounts may be too low to do any good. Another disadvantage is that most of these products are made from whole tissue, containing both adrenaline and cortisol. Since adrenaline can cause hyperactivity and insomnia, I do not recommend whole adrenal extracts. Use only a product that is made from the adrenal cortex, the part that contains cortisol and DHEA.
The third disadvantage is that the amount of cortisol in extracts is not always the same. Most adrenal extracts available at health stores are not adequate for supplementation; however, your doctor can provide you with concentrated cortical extracts containing standardized amounts of naturally occurring cortisol. The typical dosage is between 1.25 and 2.5 mg of cortisol equivalent in divided dosages daily, usually taken in the morning, at noon, and in the later afternoon. Do not take them before bed, as your sleep could be affected.
Nutritional supplements and herbs are also helpful in restoring adrenal reserves. In most cases of borderline low adrenal function, stress reduction, rest, and improving your dietary habits will correct the problem. Pantothenic acid (vitamin B5), vitamin C, and ginseng are most commonly used. If you have followed steps 1 through 4, it is likely that you are already getting adequate vitamin C and some pantothenic acid in your multivitamin supplements. For adrenal nutrition, I generally recommend taking a total of 500 mg of pantothenic acid 2–3 times daily.
Doctors of Chinese medicine and acupuncturists are experts in improving adrenal function by natural methods. In their view, ginseng is an excellent medicine for enhancing and balancing adrenal function. You may already be using ginseng, and if you stay with the recommended dosage (described in the previous chapter), you will be taking enough to improve your adrenal function. Licorice root extracts are also considered helpful in improving adrenal activity. However, do not take ginseng or licorice if you have high blood pressure. In general, only use these two herbs if your cortisol levels are low.
If your cortisol levels are very low or you are not improving over a period of four to six months with the all-natural approach, you may need a prescription of hydrocortisone, a synthetic drug whose molecular structure is identical to human cortisol. The typical recommended dosage is 5–10 mg, two to four times daily. I recommend that you start with a low dose and gradually increase until you feel an increase in energy. For example, you could begin with 2.5 mg, two times daily, then increase this by 2.5 mg weekly and take the new dose four times daily.
For replacement therapy, 20 mg of cortisol daily should be the maximum dosage, divided into four equal dosages taken morning, mid-morning, noon, and late afternoon. If your adrenal function is very low, your doctor may want to put you on even higher dosages; however, keep in mind that more than 30–40 mg daily will cause suppression of your own adrenal hormone production.
DHEA is available over the counter, by prescription, or in a micronized form, which is the form I recommend. Since its particle size is smaller, the micronized form is easily absorbed and more efficient for the body to utilize. Though most doctors recommend dosages ranging from 25–50 mg for women and from 50–100 mg for men, I have found these to be too high for people with chronic disease and those who are very weak. Instead, I often recommend 5–10 mg for both men and women, and only under a doctor's supervision may you increase the dosage up to 20–30 mg.
A newer form of DHEA is 7-Keto DHEA, reported to have many of DHEA's benefits but none of the side effects. Though many doctors are recommending 7-Keto DHEA, I do not use it in my practice. It is much more expensive than regular DHEA and in my experience, it does not have the same hormonal benefits.
DHEA is best taken with food in the morning, at noon, and around four in the afternoon. Do not take cortisol-containing compounds in the evening or before bed, as they can cause insomnia. DHEA is considered safe in low dosages and is not associated with increased risk for disease. On the contrary, research indicates that it may be protective against cancer and cardiovascular disease.
However, as with all steroid hormones, there is some concern that extended use may cause liver damage. Patients with liver disease should take a sublingual form of DHEA or use a transdermal cream applied to the skin. This will prevent the first bypass effect in the liver; normally, when oral preparations are absorbed through the intestines, they pass directly to the liver through the portal vein. By avoiding this direct route, less stress is placed on liver.
Caution: Both DHEA and cortisol are steroid hormones and have considerable physiological activity in the body. In general, low dosages of cortisol are safe and without side effects, but do not use it for more than six months without re-testing your hormone levels. Since DHEA is an androgenic hormone, it can convert in the body to testosterone. In some cases this may be beneficial; however, it can also cause facial hair growth in women, and acne in both men and women. It has also been associated with high blood pressure.
Men should have their PSA (prostate-specific antigen) tested regularly if they are using DHEA. Do not use DHEA, except under medical supervision, if you have an enlarged prostate gland. Do not use DHEA if you have hypertension or are concerned about acne, and discontinue immediately if any of these occur. Too high a dose of hydrocortisone, above 30 mg for more than a few weeks, can suppress immune function. Do not take dosages of cortisol above 10 mg per day unless you are supervised by a physician.
Low adrenal function, also referred to as adrenal insufficiency, can cause chronic fatigue, low blood sugar, and a host of other symptoms as well as difficulty recuperating from colds and flu, lack of stamina, lowered immune function, and premature aging. If you have chronic fatigue, chronic viral infections, a bacterial infection that is difficult to eradicate, recurrent colds and flu, slow recovery from an illness, or immune deficiency, taking natural cortisol or DHEA may improve your condition.
Human growth hormone (HGH) plays a role in immunity, and if you are elderly, using it as part of your viral immunity program may benefit your ability to resist infection. However, it is still not known how HGH supplementation works. There are also potential risks with long-term use, such as irreversible acromegaly (abnormal enlargement of the bones), diabetes, edema, and the cancer risk from HGH has not yet been fully defined.
Low adrenal function, also referred to as adrenal insufficiency, can cause chronic fatigue, low blood sugar, and a host of other symptoms as well as difficulty recuperating from colds and flu, lack of stamina, lowered immune function, and premature aging.
The abnormal fluid retention that HGH can cause in some people may result in carpal tunnel symptoms (severe tingling of the forearms, inside of the wrists, and palms of the hands). Both psychological stress and the distress associated with chronic viral disease affect water balance in the body and kidney function, and both physical and psychological stress increase HGH production.
Therefore, HGH supplementation has the potential to aggravate fluid metabolism and should be used with care in patients with kidney disease. However, in the short term, and when using lower doses, HGH gives an increased sense of well being, improves energy, increases sexual vitality, and is used as an anti-aging hormone.
Testing for HGH: HGH levels are evaluated indirectly by testing for insulin-like growth factor (IGF-1), also called somatomedin C, in blood. Urinary tests that measure growth hormone are available, but are not in common use yet. IGF-1 is a hormone produced primarily in the liver in response to growth hormone, and its concentration range in blood varies depending on a person's age and gender, decreasing gradually by about 14 percent every ten years after the age of thirty. There is no universal standard for optimal IGF-1 levels; however, most anti-aging physicians believe that levels approximating those of a healthy twenty-nine- to thirty-two-year-old are a reasonable goal. The range for a male of this age is 114–492 nanograms per milliliter (ng / mL).2
For those suffering from chronic viral diseases and for middle-aged adults (those between roughly forty-eight and sixty-five years of age) aiming for levels of a thirty-year-old may be too high and the therapy to attain them too aggressive. I suggest more moderate goals. Two national experts, James Jamieson, Ph.D., a pharmacologist involved in growth hormone secretagogue research, and Allan Broughton, M.D., who developed the first commercial IGF-1 laboratory test, agree. In an article published in 1998, Jamieson suggests an upper limit of 250 ng/dL. In my practice, I have found that patients receive benefits from HGH enhancement if their levels are functionally low (less than 110–145 ng/dL), and then increased to 165–250 ng / dL.
How to Safely Supplement HGH: There are three ways to increase IGF-1 levels and enhance HGH: lifestyle and diet, oral secretagogues, and injections of synthetic HGH. A healthy diet, adequate exposure to sunlight, strenuous exercise, and plenty of deep sleep support the natural release of growth hormone, and detoxification and fasting also improve HGH levels. The amino acid arginine (discussed in step 2 as an immune-enhancing agent) assists growth hormone production.
Oral HGH secretagogues have become popular in the last few years. Unfortunately, very few of the hundreds sold on the market have any value in consistently raising IGF-1 levels, and many do not work at all. The one that I recommend is MediTropin. Research and clinical data have shown that MediTropin significantly raises IGF-1 levels. It is available through a physician's office or a pharmacy. Dissolve one to two tablets in one glass of water and drink before bed nightly, two hours after eating.
In some cases, such as in the very elderly, when IGF-1 levels are very low (less than 110 ng/dL), nutrition and oral secretagogues may not be enough to raise levels above 165 ng / dL. In this case, you may wish to use synthetic recombinant human growth hormone, also called somatropin, taken by injection. This is a prescription substance in the U.S., though it may be obtained in Mexico and other countries without a prescription.
Recombinant HGH is produced by a special purified strain of E. coli bacteria and contains the same 119 amino acids that constitute naturally occurring pituitary human growth hormone. I usually recommend Humatrope, manufactured by the French pharmaceutical company Eli Lilly, but there are other excellent brands such as Norditropin, made by Novo Nordisk in Denmark. The typical dosage for adults is by body weight, with an average replacement range from 0.5–1.0 IU per day. However, when applying all of the dietary, lifestyle, nutritional, and herbal recommendations in this book, you can achieve effective results with considerably lower dosages.
Thierry Hertoghe, M.D., one of the world's experts on hormone balancing and HGH replacement, promotes the concept that when balancing other hormones, a synergistic affect occurs. In these cases, daily dosages of 0.25 to 0.5 IU are often sufficient to achieve symptom improvement, enhance immunity, and raise IFG-1 levels. Often, a combination of daily use of an oral secretagogue combined with low-dose biweekly injections provide significant benefits at less cost and with less risk.
Caution: A prescription is required for recombinant HGH and you will also need instructions from your doctor on how to do the injections yourself. In the dosage I have recommended, HGH enhancement is safe and without side effects. However, like all of the stronger medications listed in this book, if you notice any unusual symptoms, discontinue immediately and discuss them with your doctor.
Although low-dose recombinant HGH injections or oral secretagogues are without significant risk, long-term use can cause receptor resistance making. This is a condition in which hormone receptors in the cells do not allow the hormone molecule to attach to them or in which they become immune to the effects of the hormone, requiring higher and higher levels (as in insulin resistance and Syndrome X) to achieve effects. Your doctor should monitor long-term use (more than one year) of HGH-enhancing substances, even in low dosages.
Melatonin is a substance produced by the pineal gland, situated deep within the brain, and in other tissues such as bone marrow cells. Suppressed by light and increased in darkness, it is associated with sleep induction, sexuality, longevity, the balancing of thyroid and other hormones, powerful antioxidant protection, viral replication inhibition, and immune system enhancement.
Researchers are not clear if melatonin is a hormone in the sense that cortisol or estrogen are, or if it is in a separate class of its own. William Regelson, M.D., in The Super-Hormone Promise, refers to it as a “buffer” hormone because unlike other hormones that have specific target sites, melatonin indirectly influences all organ systems, exerting a synergistic effect on many different hormones at the same time (Regelson 1996). Walter Pierpaoli, M.D., Ph.D., of the Italian National Research Center on Aging in Ancuna, Italy, and the world's leading authority on melatonin research, suggests that melatonin is not a hormone in the classic sense, but is rather a mediator of the biological clock, and as such directly influences health, aging, and immunity (Pierpaoli 1995).
Investigation of receptor sites on lymphocytes suggests that melatonin is a powerful immune-modulating substance (Rabin 1999). Inhibition of normal pineal gland activity due to stress, long hours under artificial light, lack of daylight exposure, and use of drugs that deplete melatonin (indomethacin, beta-blockers, steroids, and many antidepressant and anti-anxiety drugs) contribute to serious imbalances in melatonin. Pierpaoli has shown that inhibition of melatonin synthesis suppresses normal immune response.
Other researchers have found that melatonin has anti-inflammatory effects and is capable of reducing tissue damage during inflammatory reactions. Could it be that another link in the immune deficiency puzzle is abnormal melatonin synthesis, and thus another consequence of modern living?
Testing Melatonin Levels: Since all people living in modern urban areas are exposed to stress, unnatural lighting, and the other causes of the inhibition of melatonin synthesis, it is generally not necessary to test for melatonin levels in order to supplement this important anti-aging and immune-enhancing substance. Also, the laboratory tests for melatonin are not highly sensitive to its circadian secretion variations. Blood tests are available, but the best way to test for melatonin is by salivary studies; at least three samples are taken over a twenty-four-hour period and then plotted on a graph.
How to Supplement Melatonin: Melatonin is a prescription medication in many European countries, but is available over the counter as a nutritional supplement in the United States. I recommend melatonin supplements to all of my patients over sixty years of age, those on estrogen replacement therapy, and those with chronic hypothyroidism, breast cancer, and chronic viral infections. Pineal glandular extracts are available, but either contain only trace amounts of melatonin or none at all, so I do not recommend glandular substances for melatonin replacement.
In my clinical practice, I use synthetic melatonin in a sublingual form or in oral capsules in the range of 0.5–3.0 mg directly before sleep. The most common dosage and form that I use is a 1 mg sublingual preparation. Sublingual melatonin gets into your bloodstream very quickly, creating higher levels of melatonin in a short period.
I do not consider melatonin a sleep aid and only use it in higher dosages to reduce the effects of jet lag. A typical dose is 5–10 mg three days before your flight, during the flight, and three days after arrival. Doubling your cortisol dose during and immediately after a long flight also reduces jet lag; repeat the same schedule for the return trip.
For immune stimulation and the treatment of chronic viral diseases, dosages up to 20–50 mg may be taken on a cyclic basis (three weeks on, one week off). Since these dosages are considerably higher than those generally taken, I recommend that you evaluate melatonin levels before and during treatment, and that you be supervised by a doctor. If you choose to take melatonin in a higher dosage without supervision, start slowly, beginning with 1 mg nightly and gradually increasing 1 mg at a time, every three days until you are at 5 mg. From there, you can increase by 5 mg weekly until you reach 20 mg.
Melatonin is completely safe and non-toxic even in the higher dosage ranges. However, it can cause strange effects in some people, including vivid dreaming or nightmares. Some people taking melatonin experience stimulating effects and are unable to sleep—exactly the opposite effect that most people experience. Melatonin is a close cousin to the neurotransmitter serotonin, a substance that profoundly influences mood, so people sensitive to serotonin or those taking selective serotonin re-uptake inhibiting (SSRI) antidepressants (Prozac and Paxil) can experience exacerbations of depression and mental illness when taking melatonin. Therefore, I do not recommend taking melatonin while you are using antidepressant drugs.
Lymphocytes, one of the most important immune cell types, mature in the thymus gland (behind the sternum) through a complex molecular process involving thymic hormones. These hormones also circulate in the blood, and though little is known about how thymic hormones influence immunity, researchers consider them to be important for a well-functioning immune system.
Lifestyle, diet, and nutrition are the first line of therapy to improve thymus function. By following all the steps outlined in this book, including balancing all the hormones as discussed in this chapter, the activity of your thymus gland will naturally improve. Stress and increased levels of cortisol cause a marked decrease in the size of the thymus gland. A shrinking thymus is also associated with the aging process, as is declining immunity. Therefore, stress reduction and lifestyle changes that foster health and longevity also improve thymic function and benefit immunity.
Studies have shown that zinc supplementation restores thymic function in older experimental animals, as does melatonin. Since the thymus is innervated by both sympathetic and parasympathetic nerve connections, regulating the autonomic nervous system through acupuncture, yoga, and tai chi, can also rejuvenated the thymus.
Although there are blood tests that measure thymic hormones, these are used primarily for research purposes and not for clinical evaluation of thymic function. To evaluate thymus function, I order a comprehensive lymphocyte panel.
How to Use Thymic Extracts: Whole thymus glandular extracts for immune stimulation have been in use for decades. Made from bovine thymus glands, they are processed to produce a dry powder which is made into tablets or capsules. Though these products may contain trace amounts of thymic hormones and are commonly used by alternative health practitioners, I have not found them to be strong enough to produce any noticeable clinical results in viral conditions.
Other options for the enhancement of thymus function are concentrated thymic extracts, thymic protein, and synthetic thymosin. Thanks to modern pharmaceutical practices, we now have these potent thymic preparations, and I routinely recommend these for my patients with chronic viral diseases to improve immune status, prevent infections, and reverse immunosenescence. Thymic hormones are considered by some anti-aging experts to be the missing link in preventing age-related diseases.
Numerous research studies have been conducted on these products, and the general professional consensus is that they appear to work as immune modulators by improving cell-mediated immunity. They have been shown to be useful as adjunctive therapy in hepatitis B and C, in the treatment of AIDS, and in other viral infections. Several thymus medications are available, including oral and injectable preparations.
One of the new immunoceutical medications, Thymic Protein A, developed by Terry Beardsley, Ph.D., an immunologist and eminent researcher on the thymus gland, is endorsed by many physicians as one of the leading oral thymic immune-supporting medications. Thymic protein A has been shown to stimulate helper T-4 cell function. I use this product in my practice and have found it effective and safe. It is manufactured by BioPro and is sold as ProBoost in individual packets containing a white freeze-dried powder. I often advise taking one packet one to three times daily, emptied directly into the mouth and dissolved under the tongue.
The Canadian company, Atrium Biotechnologies, produces whole, live-cell tissue extracts from bovine thymus glands. Live cell therapy extracts, glandular injections from sheep or cow glands, have been popular in Europe for decades as a rejuvenation therapy. NatCell Thymus is an oral liquid that arrives frozen and must be kept frozen until just before use.
Though there is no question that live cell therapy is valuable in restoring organ energy reserves, these products are very expensive making them nearly prohibitive for the average patient. Still, I consider them important adjunctive therapy for immune enhancement and rebuilding the thymus gland. For treatment of viral infections, one to three vials are taken daily for a course of ten to twelve vials, which may be repeated monthly for several months. For maintenance, one to two vials per week are necessary.
Several high-quality, prescription-strength thymic extracts are produced in Germany. Thymomodulin, also known as Leucotrofina (an Italian version), is made by Ellen Pharmaceuticals, and research suggests it is useful in preventing recurrent respiratory infections, improving T-cell defects in AIDS patients, in treating chronic hepatitis B and C, relieving allergies, and restoring white blood cells in cancer patients after chemotherapy and radiation treatments.
A similar product, Thym-Uvocal (produced by Mulli in Germany), is a safe medicine of good quality and comes in both injectable ampoules or oral tablets. Though other oral preparations are available, including Thymomodulin and Thymus Mucos, injectables are the preferred form because the medication gets directly into the blood-stream. Since these substances are not licensed drugs in the United States, injectable medications are available only through alternative avenues such as buyers' clubs or International Anti-aging Systems over the Internet. The dosage is one ampoule injected intramuscularly every other day, and for oral forms two (240 mg) tablets taken on an empty stomach three times daily.
The synthetic immunomodulating drug Thymosin alpha-1 is used for the same purposes: as an immune modulator for adjunctive therapy in hepatitis B and C, AIDS, and cancer. Zaduxin, a proprietary form, is licensed in twenty countries worldwide (except the United States where it is classified as an “orphan drug” for the treatment of hepatitis B) for the treatment and prevention of influenza.
Several studies have shown that thymosin improves the outcome of HCV patients when given with interferon. HIV / AIDS patients have also reported benefits from taking thymosin. It increases the activity of interleukin-2 receptors on T cells, increases maturation of T cells, and increases the production of gamma and alpha interferon. Although it is an injectable drug and requires a prescription, some AIDS health groups import it from Italy or other countries. It may also be possible to obtain it over the Internet.
Safety Information on Thymus and Other Glandular Extracts Derived from Cows: Oral thymic extracts are considered safe and non-toxic and may be used for chronic viral conditions. However, there are several conditions in which their use is contraindicated: thymus tumors, myasthenia gravis, multiple sclerosis, untreated hypothyroidism, during pregnancy, and for people on immune-suppressive therapy to prevent organ transplant rejection.
With the exception of synthetic thymosin, thymic extracts are made from the thymus glands of calves, mainly in European countries. There is currently no evidence of contagion of BSE (bovine spongiform encephalopathy), or mad cow disease, pathogens through the use of bovine extracts for medicinal purposes. However, the German government issued a warning in 1994 stating the possibility of transmission of this disease through glandular tissue products. Before you use any glandular product, consult your doctor, the manufacturer, or a governmental agency that reports on current safety issues related to BSE.
Hypothyroidism, or underactive thyroid gland function, is the most common thyroid disorder and one of the most common of all endocrine conditions. It is characterized by a well-recognized set of symptoms and very specific abnormalities in lab testing. The gold standard is an elevated level of thyroid-stimulating hormone (TSH). Hyperthyroidism, or overactive thyroid function, is becoming more common, as are autoimmune-related thyroid conditions like Hashimoto's disease (thyroiditis resulting in thyroid hormone deficiency) and Grave's disease (also known as thyrotoxicosis).
The thyroid gland, located in the middle of the lower neck just above the collarbone (clavicle), is actually composed of two halves (lobes): the right and left lobes lying on either side of the trachea, which are joined together in the middle by a narrow segment called the isthmus. The thyroid gland secretes the hormones thyroxine (T4) and triiodothyronine (T3) that help the brain regulate many bodily functions including metabolism (including weight loss and gain), brain development, normal growth and development, heart function, temperature regulation (helps heat production), and nervous system function.
Most likely linked to immune dysfunction, thyroid imbalances are becoming increasingly common. Weakened hormone function, causing subclinical slow progression that does not reveal classic symptoms of hypothyroidism or show abnormal blood test results, and other hormonal imbalances are showing up at an increasing rate. Richard Shames, M.D., a primary care doctor, observes in Thyroid Power: 10 Steps to Total Health (2001): “Although extremely common, low thyroid is largely an unsuspected illness.”
Medical doctors practicing conventional allopathic medicine are unprepared for this epidemic. In my practice, I have worked with cases of low thyroid and autoimmune thyroid conditions since the early 1980s. As a rule of thumb, I have found that in most people with chronic fatigue, those who catch frequent colds and flu, who have female hormonal imbalances, allergies, and environmental sensitivities all have a thyroid component to their problems. They may not have hypothyroidism, but the function of their thyroid gland is below par, and when treated with natural medicine, the majority of these patients experience pronounced symptomatic improvement.
Since thyroid hormones control virtually every chemical reaction in your body, if your thyroid function is even slightly out of the normal functioning range, it will cause your metabolism to waver and your immunity to falter.
Thyroid Case Study: A case in point is Beverly, a thirty-two-year-old single woman without any children who formerly led an active professional life. When I first saw her she was on disability due to chronic environmental sensitivities, recurrent respiratory tract infections, severe menstrual problems, chronic unexplained pain, and multiple allergies. She had already tried conventional medicine, and her doctors could not find anything wrong with her other than a slightly low thyroid function, for which synthetic thyroxin was prescribed. She had also experimented with various alternative therapies.
Although she repeatedly told her primary care doctor that sometimes her symptoms improved markedly for a few hours when she took her synthetic thyroid medication, he dismissed it as a placebo effect. He was convinced that the majority of her problems were “all in her head.”
I worked with Beverly over several months to stabilize her response to the thyroid medication and improve her own natural thyroid function with acupuncture and nutrition. At the end of three months she began to show improvement. When I divided her thyroid dose into three equal parts, spread out during the day rather than all at once in the morning, her symptoms improved enough so that she was able to return to work.
Since thyroid hormones control virtually every chemical reaction in your body, if your thyroid function is even slightly out of the normal functioning range, it will cause your metabolism to waver and your immunity to falter. Frequent bacterial, yeast, or viral infections can be the result of low thyroid function. Here is the irony: low thyroid function may have a cause rooted in the immune system and low thyroid function causes lowered immunity.
The most likely causes in the hypothyroid epidemic are rampant environmental toxins, stress, poor diet, and infectious microorganisms including viruses. These are the same causes that appear to trigger immune deficiency crises as well. The clinical challenge is that if the homeostatic mechanisms of the brain shut the immunity down in order to protect the thyroid glandular tissue, will stimulating thyroid function improve or worsen immune reactions?
This is an unanswered question. However, if you approach the matter of improving your thyroid function carefully and gradually, you should not experience any harm or worsening of your symptoms. Working with a medical professional skilled and experienced in managing borderline thyroid dysfunction may be useful. I highly recommend this option if you have known thyroid disease, or under- or overactive thyroid function.
How to Evaluate Low Thyroid Function: The most common symptom of an underactive thyroid is fatigue. However, it is not the typical feeling of being just tired. Fatigue caused by low thyroid function creates a sense of utter exhaustion, both mentally and physically. Additionally, an underactive thyroid can cause many other complaints, such as anemia, heavier-than-normal menstrual bleeding, constipation, dry skin, hair loss, and cold in the extremities.
Begin evaluating your thyroid function by carefully reviewing your symptoms. Take the Low Thyroid Self-Test, and if you answer “yes” to any three of the questions, in addition to exhaustion, you may have low thyroid.
If you answered “yes” to at least three or four of these questions, the next thing to do is to check your body's basal metabolic temperature. To do this you will need a special thermometer called a basal thermometer, which you can readily buy in any drug store or pharmacy. Set a notebook and pen or pencil along with the thermometer next to your bed before sleep.
In the morning, when you awaken but before getting out of bed even to use the toilet, place the mercury bulb of the thermometer directly under your bare armpit. Rest comfortably in bed, not moving the covers, allowing the thermometer to stay snugly under your arm for several minutes. Read it directly upon removing it from your armpit and record the number in your diary. Repeat the same procedure for at least seven days.
I ask my patients to perform this test daily for one month to get a better average. Menstruating women should start on the first day of their periods. The average, “normal,” under-arm temperature is about 98º F first thing in the morning. If your temperature averages less than 97.6 degrees (and you have symptoms), you may have low thyroid. The next step is to find a doctor with experience in evaluating and treating sub-clinical hypothyroidism.
As a confirmation of low thyroid you will need a group of laboratory tests. In my clinical practice I use blood and urine testing to evaluate thyroid function. Of course, I order individual tests based upon the patient's specific history and symptoms, but if you or your doctor suspect low thyroid, I highly recommend that you have at least one comprehensive panel of tests performed. This is because the standard tests, usually limited to measuring thyroid-stimulating hormone by most HMOs, often miss borderline cases of low thyroid.
Your doctor may want to include one or more additional tests, and though they add more information, they are not substitutes for these tests. Additional tests include T-3U (T-3 resin uptake), FTI (free thyroxine index), RT-3 (reverse T-3), TRH (thyrotropin releasing hormone), and TBG (thyroid binding globulin).
Long used in Europe, urinary thyroid tests are only just becoming available in the United States. They are easy to use, relatively inexpensive, and are useful if levels must be monitored frequently. Urinary studies measure free T-3 and free T-4, and kits are available through your doctor from AAL Reference Laboratories.
If you have symptoms of low thyroid function, have an under-arm temperature that is consistently lower than normal, and have shown positive laboratory results for low thyroid function, you need to correct your thyroid imbalance before you can be well and enjoy optimal energy and immunity. Depending on the case, of course, I generally recommend beginning with a corrective approach using natural medications and alternative therapies.
How to Correct Low Thyroid with Natural Medicines: Review steps 1 through 4: lifestyle, antioxidants, detoxification, and a phytonutrient-rich diet. If environmental toxins are part of the problem, it makes sense to begin with detoxification. The same anti-inflammatory, anti-autoimmune, balanced diet outlined earlier in the book also works for correcting thyroid problems.
In addition, avoid foods (even though some are phytonutrient-rich) that inhibit thyroid function. These include large amounts of soy, cabbage-family vegetables (cabbage, broccoli, cauliflower, and mustard greens), rutabaga, turnips, walnuts, almonds, peanuts, pine nuts, millet, sorghum, and cassava (tapioca).
A low-carbohydrate diet and low calorie diets for weight loss can also inhibit thyroid function, resulting in the opposite affect, namely, difficulty in losing weight due to poor thyroid performance. Therefore, if you have low thyroid function, eat equally proportioned meals four to five times daily and include carbohydrates, such as rice or fruits, in each meal.
According to Ridha Arem, M.D., an endocrinologist and Associate Professor of Medicine at Baylor College of Medicine in Houston, Texas, stress can play a significant role in thyroid disorders (Arem 1999). If you are under serious stress and have a thyroid disease, I strongly suggest you start a stress reduction program, including lifestyle changes, meditation, yoga, massage, and other calming and unwinding activities.
Tyrosine, an amino acid, is the basic building block for thyroid hormone. You may safely take 500–1,000 mg, two to three times daily as a typical dosage. It is a safe supplement without side effects. Though adequate amounts of iodine, selenium, copper, and zinc are required for proper thyroid function, if you are following the recommended dosages in steps 1 and 2, you will be taking more than adequate amounts of these trace minerals.
Many alternative practitioners suggest extra iodine is needed, but most Americans have sufficient amounts in their diets and from multivitamin and mineral supplements, and too much iodine can suppress thyroid function. Remember that most modern thyroid conditions are caused from immune-related problems and not a deficiency of iodine as in times past.
Caution: Adding extra iodine or overdoing your intake of iodine-containing kelp and other seaweeds can cause an increase of dietary or supplemental iodine. Artificially increasing iodine levels can trigger autoimmune reactions, thereby worsening a thyroid condition. Do not take iodine supplements except under the advice of a qualified health professional and then only for short periods of time lasting no longer than two to four weeks.
After trying the nutritional approach for six to eight weeks, if your thyroid function still remains low, add a whole thyroid glandular supplement. Natural thyroid glandulars provide bio-available thyroid hormone and a range of intermediary substances that work similarly to the way your own thyroid hormones work; they can be very effective in normalizing thyroid function.
Most glandular products sold in health foods stores do not contain active thyroxine, and although some might contain trace amounts, preparations with active amounts of thyroxine (T4) and tri-iodothyronine (T3) can be obtained through a health professional or on the Internet. If you are taking an active form, start with ¼ grain (usually equivalent to one 250 mg capsule) and gradually increase up to 1 grain of thyroxine equivalence (two capsules, two times daily). Be sure to ask your doctor if the glandular you are taking has active thyroid hormone or if it is thyroxine-free.
Acupuncture and yoga postures are also useful in correcting thyroid weakness. I generally recommend twice-weekly acupuncture sessions over a course of six weeks. At the end of the course of treatments, have your blood studies rechecked. Generally, cases improve with one or two courses of treatment (twelve to twenty-four acupuncture sessions) and many improve in as few as six sessions.
If You Need Thyroid Hormone Replacement: The current standard for the treatment of hypothyroidism in the United States is replacement with synthetic T4 (commercially available as Synthroid, Levothroid, and Levoxyl), synthetic T3 (Cytomel), or a synthetic combination of T4 and T3 (Thyrolar). For most medical doctors there is no other option. However, natural prescription thyroid is available and should be the medication of choice for most people with borderline immune-related low thyroid.
Like whole glandulars, prescription natural thyroid is prepared from desiccated beef or pork thyroid glands. However, these glandulars contain standardized amounts of T4 and T3, and are highly purified and safe to use. The most commonly used brand is Armour Thyroid, but two other forms are also available: thyroid USP (generic desiccated thyroid) and Bio-Throid from Bio-Tech. Both use glands from animals raised without synthetic dietary hormones, and these may be a healthier choice in this age of feed contaminants. Have your pharmacist order these specially, or you can order them yourself from an Internet pharmacy or a compounding pharmacy as long as you have a prescription from your doctor.
Prescription natural thyroid is provided in tablets or very small capsules. For hormone balancing, different from hormone replacement which requires higher dosages, I recommend that you start with 15 mg (¼ grain) in the morning before ten and gradually increase every week until you are taking 60 mg (1 grain) daily in the morning on an empty stomach. You may find that you get more benefit by dividing the dosage between morning and noon.
Generally you will not need more than 1 grain to feel improvement in energy and to see many of the symptoms highlighted in the Low Thyroid Self-Test disappear. If you do not find that you are improving, your problem may not be thyroid-related or you may require a higher dosage. Consult your doctor if feel you need more than 1 grain of natural thyroid daily, and discontinue immediately if you experience insomnia, headaches, or rapid heart beat. People with low thyroid as a result of autoimmune problems often have poor conversion from T4, the form that the thyroid gland secrets directly and that circulates in the blood, to T3, the active form that directly affects the tissues. In these cases, higher dosages of T3 are required and must be prescribed by a physician.
Thyroid Balancing Involves Other Hormones: Thyroid hormone function is synergistic with the activities of other hormones discussed in this section, including HGH, cortisol, and especially melatonin. To benefit and balance hormone activity in the entire body, all of my patients with low thyroid take 0.5–1.0 mg of melatonin nightly, directly before bed, even if they do not have sleep problems.
Women with menstrual abnormalities like PMS or irregular cycles, infertility, and those experiencing the symptoms of perimenopause may to need balance their estrogens and progesterone before their thyroid functions normally; that subject is beyond the focus of this book. If you suspect other hormonal imbalances, consult a doctor qualified to evaluate your condition.
Both men and women over the age of fifty-five have lowered sex hormone levels. For men, testosterone deficiency predominates, and for women it is estrogen and progesterone, though many women also have lower levels of testosterone. Other hormones decline in aging as well. For many people, the levels of these hormones can be low enough to affect their energy, mood, sleep, and memory, and they may also impair immunity, creating a condition called immunosenescence, or age-related immune system deficiency.
Researchers have shown that aging causes a shift in subsets of T-helper cells, creating an imbalance between these immune cells. This imbalance results in fewer NK cells, fewer T cells, and changes in the types of interleukins that are secreted. A Japanese research team headed by Keizo Deguchi, M.D., at the University of Tokushima in Japan, has confirmed that estrogen replacement therapy in post-menopausal women may prevent some of these age-related immune declines (Deguchi 2001). If you are between the ages of forty-eight and fifty-two, it may be advisable to have your doctor check your levels of these important hormones. If they are low, consider natural hormone replacement or supplementation.
Hormones work synergistically with each other in a harmonious interplay of molecules. That is exactly the reason that doctors practicing functional medicine with natural biological medications can get better results with lower dosages. Hormones work well together.
Some examples of this are the following: Melatonin helps both thymus and thyroid function, HGH and thyroid help each other's function, DHEA can raise HGH levels. The reverse can be equally true: an excess of the adrenal hormone cortisol can cause the thymus to shrink, resulting in under-functioning immune activity. Therefore, I generally prescribe at least two hormones, and sometimes more, but never in high dosages.
Start by adding DHEA (5–10 mg) and melatonin (0.5–1.0 mg) into your viral immunity program. If your thyroid is underactive, add whole natural thyroid (¼–1 grain). If you are still fatigued and your cortisol is low, add natural adrenal cortex extract (1.25–2.5 mg).
At this point you should notice a considerable improvement in your energy, vitality, and general well-being. However, if you are not experiencing these positive changes, if you are over sixty years of age, and if you have tested low for IFG-1, try one of the HGH secretagogues. If the oral form does not improve your symptoms or raise your IGF-1 levels after three months, discuss a trial of injectable HGH with your doctor.
Finally, if you have HCV, are HIV positive or have AIDS, or if you have recurrent upper respiratory tract infections, add thymus extract. Start with Thymic Protein A; if this is not improving symptoms after several months, try a different form of thymus extract.