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Hormones are not nutrients. Yet they are being used as supplements by growing numbers of people ostensibly to increase energy levels, for anti-aging effects, to mask symptoms, make up for unhealthy lifestyle choices, build muscle, promote athletic prowess, and more. Hormones like melatonin, DHEA, human growth hormone, and others have been portrayed as quick-acting and safe remedies. But manipulation of hormones is not as simple as adding Hamburger HelperTM to one's own glandular meat!
Hormones are "catalytic factors," powerful devices that set in motion, speed up, control or regulate effects on cells, tissues, or organs. Hormones are secreted by endocrine glands directly into the circulation to exert their effects by binding to receptors in or on target cells. But it has recently been found that virtually every tissue can produce substances that act like hormones, and that hormones can act within the same cell, on neighboring cells, or on distant cells. Further, innumerable interconnections are being discovered among bodily systems such as among the endocrine, immune, and nervous systems. It is not simply matter and force, a one-way push or mechanical action. Hormonal processes are dynamic, complex, intercommunicational, potent networks working in open, fluid systems where there is a constant exchange of information involving at least a two-way ‘conversation' with countless known and unknown functions. It is impossible to specify or classify hormones or place a limit on their applicability. No one yet understands all their functions and implications. Who can claim to know how to precisely prescribe or administer exogenous, imitation, or precursor Hormone Helpers? Look at three examples. i
Melatonin traveled a swift pathway from "obscure molecule to international fame," but it is losing popularity as a supplement. Melatonin is recommended for jet lag, insomnia, arthritis, stress, alcoholism, migraine, symptoms of aging or menopause, premenstrual symptoms, and the prevention of heart disease and cancer. Melatonin is produced by the pineal gland which is located deep in the brain and performs as a biological clock. Production of melatonin rises at night, falls by day, and affects the internal body clock and sleep cycles. Adequate levels are associated with healthful sleep patterns and decreased risk for certain forms of cancer. Low levels are connected to coronary artery disease, depression, anxiety, bulimia, fibromyalgia, nerve pain, possibly prostate cancer, insulin resistance, and glucose intolerance. Working with the pituitary gland, melatonin acts as a modulator of ovarian function, and is involved in regulating thyroid, digestive, reproductive, and immune functions.
As a drug, melatonin, used for jet lag, may work for symptoms "if taken correctly, in small doses." If taken at the wrong time, it is liable to cause drowsiness, sleepiness, and delay adaptation to local time. "Occasional short-term use appears to be safe." However, some researchers argue that benefits to jet-lag symptoms "have never been clear." In fact, jet lag itself is difficult to measure. Some studies on jet lag have incorporated the use of natural sunlight in addition to melatonin, so specific effects of the hormone cannot be determined. Possibly "light is more effective than melatonin." A study on physicians flying between Oslo and New York showed no benefit against jet lag. In a very large controlled study in 1999, there were no significant differences between the three treatment groups (each receiving different doses of melatonin) and the placebo group in terms of jet-lag symptoms, when participants fell asleep or awakened, or how long they slept or napped. Taking melatonin did not appear to help workers on rotating shifts adjust to working nights, although it may help people on permanent night shifts. So far, "good clinical trials have never been done on melatonin treatment for insomnia." It appears to help people fall asleep faster, but does not necessarily help them stay asleep. Like sleeping pills, it can produce a "hangover" and drowsiness the next day. Results from use of melatonin for enhanced sleep and jet lag "have been far from universally effective." Many clinicians find melatonin to be successful in a "select few" of their patients but not the majority.
Melatonin may be a treatment for tardive dyskinesia (a common drug-induced movement disorder), although its effect appears to be "modest." It may have anticonvulsant activity for epileptics, but it can also increase seizure activity. Low doses appear to lengthen the lives of laboratory animals by as much as 30%. There are hints it could be helpful to treat people with Parkinson's disease, Alzheimer's disease, and AIDS. But it is still not known if frequent use will decrease the pineal gland's ability to produce the hormone, or if resistance will develop, requiring dosage increases over time. Melatonin is sometimes viewed as superior to benzodiazepine drugs (such as Valium or Halcion) prescribed for insomnia, other sleep disorders, or anxiety. Such drugs are addictive, decrease restorative REM sleep, can cause rebound insomnia, and suppress the pineal's production of melatonin.
It had been thought that melatonin production by the pineal gland declined with age. But a study on healthy people taking no medications or drugs (including nicotine, alcohol, and caffeine) found no differences in melatonin levels between the young and the old. Melatonin levels can be depressed by medications commonly taken by older people (such as aspirin, beta-blockers, tranquilizers), so earlier studies showing diminished melatonin levels in the elderly may have been less tightly controlled for these drugs and other melatonin-influencing factors.
Tests to measure melatonin levels are not very useful since levels vary from person to person and from hour to hour. The melatonin sold by supplement companies, health food stores, or pharmacies is a synthetic version. There are no published long-term data beyond six months, so long-term safety is still a question. In test tubes, melatonin is a "powerful antioxidant," but "nobody knows what this means." It has "subtle effects" on mood and performance (some positive, some negative) depending on "various factors present to variable degrees in different people at different times." The melatonin available over-the-counter and used in studies comes in pharmacological doses (3 to 5 mg/day) which can produce blood levels more than 10 times higher than normal. Cases of mental impairment, headaches and hypothermia have been reported with use of such doses. Doses above physiologic (normal) levels of virtually ANY hormone supplement usually turn out to be more harmful than helpful. Physiologic doses of 0.3 mg/day are found to be "effective," but much is not yet known. Additionally, many inferior products have been found on the market. Melatonin should be used "cautiously and/or avoided" by persons with compromised immune systems, cardiovascular disease (vasoconstriction potential), depression, and neurological conditions including epilepsy. The drug can disrupt thyroid and sex organ actions, change dopamine function, and inhibit prostaglandin E1 release, among many other "mixed-blessing" actions.
There are other ways to assist melatonin levels. Obtaining sufficient sleep at night is a big factor. Even brief exposure to light in the middle of the night can cause a "dramatic reduction in the activity of one of the enzymes needed to produce melatonin." Adhering to Nature's light and dark cycles as well as lessening stress will go far in maintaining proper levels. Certain types of meditation increase melatonin levels. Drinking coffee late in the day may reduce both the quality and length of sleep by lowering the production of melatonin. Melatonin levels in regular coffee drinkers are only half those of decaf drinkers. Evidently, caffeine blocks synthesis of an enzyme needed to produce melatonin.
Melatonin molecules have been found in many plant tissues so "abundant use" of vegetables and fruits "may increase circulating melatonin." In animal experiments, the feeding of melatonin containing foods raised blood levels of the hormone to proper physiological amounts. Melatonin has also been discovered in insects, unicellular organisms, and bacteria. Naturally-fermented foods, rich in "good" bacteria, might be helpful in this regard. Healthy soil with its abundance of microorganisms may be a factor since plants might take up its melatonin. Some herbs such as huangquin, St. John's wort, and feverfew, contain higher levels of melatonin than other herbs. But foods and herbs do not necessarily have to contain large amounts to be effective. For example, consumption of whole grains (with relatively low levels) increases blood concentrations. Of the foods tested so far, oats, corn, rice, barley, ginger, tomatoes, banana, celery, Montmorency tart cherries, mustard seed, sunflower seeds, and others have been found to contain various but bioactive and effective (potent) melatonin levels. The estimated total amount of melatonin in the blood of an average human at any one time of the day (average 5 to 10 picograms - a picogram is one trillionth of a gram), is equivalent to the quantity of melatonin in one Montmorency tart cherry. How much is actually assimilated can vary, but the point is that whole, natural foods are a much better source - valuable, powerful, safe -- than a synthetic drug. Living in harmony with Nature rather than trying to fight it, control it, or fool it, always works better for total well-being. ii
DHEA (dehydroepiandrosterone) is a steroid hormone converted by the body into DHEAS, the sulfate form most predominant in circulation. DHEA is produced primarily in the adrenal glands (the gonads make small amounts). From cholesterol, pregnenolone is formed and, from it, DHEA and other steroid hormones are made. Fetuses produce large amounts of DHEA, but levels drop steeply at birth, increase around age six or seven, peak in the mid-20s, and then gradually decline. By the time people are in their 60s or 70s, levels have dropped to 10-20% of their peak levels possibly due to lower production of enzymes needed to make conversions from cholesterol to pregnenalone to DHEA. The physiological role of DHEAS "is still unclear." It is known that DHEAS serves as a precursor in the synthesis of testosterone, estradiol, and estrone; and that both DHEA and DHEAS are metabolized to potent androgens such as dihydrotestosterone and testosterone. DHEA helps to regulate various other hormones and enzymes. DHEAS affects fat formation, protein production, thyroid hormone function, peroxisome proliferation, mitochondrial respiration, and substrate cycling. DHEA stimulates some immune-system cells and protects the thymus gland.
As a drug, DHEA(S) is touted to slow down aging, increase libido, burn fat, build muscle mass, alleviate depression and insomnia, assist chronic fatigue, aid brain function, ease arthritis, improve menopausal symptoms, strengthen the immune system, treat lupus; increase general stamina, strength, and well-being; help prevent Alzheimer's disease and other dementias, diabetes, obesity, heart disease, cancers, and more. Periods of stress and serious illnesses lower DHEA levels. Alcohol and tobacco increase levels. Decreased levels are accompanied by reduced levels of other steroid hormones including androstenedione and testosterone. People with high blood pressure have low urinary DHEAS levels, but high DHEA(S) secretion rates. Decreased levels are found in chronic fatigue, hypothyroidism, prostate cancer, cardiovascular disease, breast cancer (increased levels also occur), menstrual irregularities, adrenal dysfunction, Alzheimer's disease, osteoporosis, rheumatoid arthritis, systemic lupus erythematosus, and any decline in immune competence. Reduced DHEAS (and increased cortisol) production can occur in the adrenal cortex due to almost ANY maladaption to stress, from mild to severe physical or psychological forces that disrupt equilibrium.
Animal trials indicate the hormone may have anti-obesity effects by decreasing fat tissue, lowering blood insulin levels, and influencing food intake. Human studies have mixed results, some showing decreases in body fat, lower cholesterol and LDL (so-called "bad") cholesterol, and others showing no effect on obesity or energy or protein metabolism. Supplementation with DHEA may relieve depression in some individuals, may have some positive effects on the immune system, may assist symptoms of adrenal insufficiency, may improve some menopausal symptoms, may stimulate bone formation in women, may decrease basal serum glucose and insulin levels, may increase muscular mass. A drug containing prasterone and DHEA appeared to stabilize or improve some symptoms of lupus, but HDL (so-called "good") cholesterol levels decreased. Other studies do not find these beneficial effects. Data suggest that lowered DHEAS levels are "a nonspecific indicator of aging and health status rather than a risk factor for a specific disease."
Synthetic forms of DHEA are sold as dietary supplements in the US. Some new analogues "offer the best hope for the development of a clinically useful drug," though potentially very toxic. "Natural" forms of DHEA and pregnenolone sold in health food stores are indirectly derived from plants such as soy or Wild Yam. They do not contain DHEA or pregnenolone, but contain substances that can be converted into human-like hormones in the laboratory by long, complex manufacturing processes. These products are no longer natural foods, but drugs. They supposedly provide "starting materials" or precursors for the synthesis of DHEA and pregnenolone, but it is not known if the body can convert them into DHEA. Other precursors include food derivatives or herbs, yet there is a question regarding the body's diminishing ability to convert them with age.
Human studies with DHEA reveal "it sometimes works and it sometimes doesn't." Its uptake varies among individuals and its mechanism of action is unknown. Some researchers contend that studies using DHEA have been too short and used doses that are too high. Even when it seems to have beneficial symptomatic effects, there are questions as to how long symptom improvements will be maintained and its long-term side effects (unwanted effects). Concentrations of DHEA(S) vary greatly among individuals, so differences in those treated with the hormone and those not treated are hard to detect. Although some people swear that they feel better after taking it, several studies found no improved sense of well-being or measurable psychological changes in men or women compared with those taking placebo. A review of studies involving elderly people concluded "there is insufficient evidence yet to support the use of DHEA in this population." Studies of DHEA and immunity "have had disappointing results." Supplementation "cannot be recommended as an evidence-based therapeutic option for relief of menopausal symptoms." Cases of heart palpitations or irregular heartbeats in people taking DHEA are reported. Although DHEA may alleviate symptoms of adrenal insufficiency, it is "pharmacologic replacement", not nutritional therapy. It does not improve the function or health of the adrenal glands. It may mask symptoms, but does not approach the underlying cause.
In some people the drug remains as DHEA; in others it is converted to testosterone or estrogen. This raises concern that supplementation may promote the development of prostate or breast cancer. Testosterone levels can significantly increase in women who take DHEA (with common side effects including menstrual irregularities, acne, male pattern baldness, growth of unwanted facial hair, deepening voice). Metabolism of DHEA in men appears to be different, with a tendency to increased production of estrogen (and side effects that include enlarged breasts). Unlike nutrients, there is not a wide range of safe dosages. Optimal serum concentration is not known. Even though it is available over the counter, DHEA has "profound effects on the body." Other potential side effects include oily skin, a decrease of serum HDL and an increase in total cholesterol levels, fatigue, insulin resistance, irritability, aggressiveness, insomnia, mood swings, nervousness, headaches, heart rhythm disturbances, liver abnormalities, and the development of chemical hepatitis.
Men (even those over 60) with the highest levels of DHEAS in their bodies have less body fat, more testosterone, higher HDL cholesterol levels, and are more physically fit than those with lower levels. These relationships do not seem to exist in women. Baseline levels of DHEAS are higher in people who meditate compared to non-mediators. Stress is obviously a component. General health, fitness, and, specifically, adrenal gland health seem to be essential to good DHEA/DHEAS production. Decreases in DHEA levels were noted in South African men when switched from their customary vegetarian diet to a "cafeteria-fed western diet." This emphasizes the importance of a natural, whole-food diet including an abundance of fresh fruits and vegetables for nutrients that support adrenal health. Needed are the vitamin C complex, B vitamins, essential fatty acids, certain enzymes, minerals like copper and potassium, and other nutrient complexes. Additionally, lowering excessive stress levels, getting regular physical exercise, and making other sensible lifestyle choices all appear to be more significant to DHEA/DHEAS levels than any manufactured hormone supplements. iii
Interest in growth hormone therapy has expanded from use by athletes for enhancing performance to use by baby boomers for prevention and even reversal of the effects of aging. The claimed benefits of growth hormone include increased energy, better muscle tone, sounder sleep, improved sexual stamina, fewer wrinkles, and hair regrowth. "Stop aging" and "turn back your body's biological time clock 10-20 years" are tempting marketing claims.
In the body, human growth hormone (hGH), also called somatotropin, is produced by the pituitary gland. During childhood, its primary role is to support growth for reaching adult height. In healthy adults, production of hGH begins to drop off in the mid-20s and continues to decrease with age. An 80-year old man has about 5% of the amount he had at age 20. Release of hGH occurs in pulses and is regulated by growth hormone releasing hormone and growth hormone releasing peptides. The greatest secretion occurs between 12 AM and 4 AM. Although hGH acts on cells directly, most of its growth-promoting effects are evoked through insulin-like growth factor type 1 (IGF-1) which is stimulated by the release of hGH. IGF-1 was believed to be the best indicator of hGH release from the pituitary, but recent research indicates that IGF-1 assessment is not as straightforward as previously thought. Research has "not adequately distinguished" the different biological actions of hGH and IGF-1.
Growth hormone increases with intense physical exercise, fasting, and certain levels of other hormones such as testosterone. Stimulation of neurotransmitter receptors by neurotransmitters or other substances will stimulate hGH release. There are interactions with the hypothalamus, various peptides, insulin, thyroid hormone, sex hormones; ultimately, hGH "interacts with all other hormones." Acute stress raises hGH levels, but if prolonged, stress inhibits its release. Sleep deprivation (particularly slow wave sleep) causes an increase in cortisol (adrenal stress hormone) and a decrease in hGH. High blood levels of glucose inhibit hGH release. Alcohol intake, especially at night, suppresses hGH release and elevates cortisol levels. People who are obese generally have normal to high IGF-1 levels and low hGH levels.
Growth hormone (GH) injections are approved by FDA for use in short children with very low levels of hGH. For adults, GH therapy is FDA approved only for severe deficiency or complete absence of hGH due to damage to the pituitary gland and for AIDS-associated weight loss. Also, use in severe burn cases is "widely accepted as effective." Nowadays doctors and anti-aging clinics engage in "off-label" use of GH for fatigue, fibromyalgia, obesity, infertility, loss of muscle tone, improved athletic performance, and other areas. "But there are too many unknowns about GH therapy to warrant its use among people who are generally healthy but don't feel as energetic as they did 15 years ago. No convincing scientific studies exist showing that people who experience the normal drop-off in hGH [will] benefit from GH therapy."
Various forms of GH therapy exist. Most often synthetic versions using recombinant DNA are used for injections. These may be "identical in terms of the amino acids and their sequence," but they are artificial manipulations, combinations of genetic material from different sources. This medically-prescribed therapy is very expensive and patients give themselves injections at home, usually twice a day. Studies with injections have had mixed results. One study reported 8.8% more lean body mass, 14.4% less fat tissue mass, and a 1.6% increase in lumbar vertebral bone density. Another study found no change in fat distribution in women, and a reduction of subcutaneous fat but not visceral fat in men. A similar study reported "beneficial changes" in biochemical markers of bone metabolism in women given GH but not in those given GH plus hormone replacement therapy. A complex study revealed that GH alone had no significant effect on muscle strength, size, power, or fiber size, but did produce changes in myosin heavy chain composition "consistent with more youthful muscle." Fat mass was reduced, but there was no change in bone mineral content. A recent study found that GH with or without sex steroids in older women and men increased lean body mass and reduced fat mass. But, because "adverse effects were frequent (importantly, diabetes and glucose intolerance), GH interventions in the elderly should be confined to controlled studies." It is important to note that "improvements in body composition do not mean that aging has been stopped or reversed."
Patients given GH must be monitored regularly for insulin resistance and glucose intolerance. GH can cause hypothyroidism which, if untreated (by another hormone!) can interfere with the action of the GH drug. Other side effects include rash, fluid retention, joint disorders, carpal tunnel syndrome, loss of lean mass, atrophy of fat tissue, high blood pressure, increased risk of congestive heart failure, reduced HDL (so-called "good") cholesterol levels, pigmentation, blood in the urine, easy bleeding, inflammation, headache, flu-like symptoms, increased liver enzymes, mild hyperglycemia or even worsening of diabetes, and possibly leukemia or stimulation of tumor growth. Use of GH can lead to signs and symptoms similar to those of acromegaly, a severe systemic disease of excess hGH due to a pituitary tumor that shortens life-expectancy due to cardiovascular, metabolic, and respiratory complications or cancer. A small study showed that risks of death from colorectal cancer and Hodgkin's disease were higher in persons who had received GH than those who had not. The common practice of administering high doses of GH to critically ill patients was discouraged when it was found that this treatment actually increases the rate of complications and death.
There is a preparation of "recycled" hormone recovered from cadavers, but this easily-contaminated drug is associated with Creutzfeldt-Jakob disease, the human equivalent of mad cow disease. An oral drug seemed improbable since stomach acid can destroy the GH molecule, but in 1998, a "viable means to deliver the hormone orally" was developed. The product was designed to enter the bloodstream via the blood vessels under the tongue. However, the drug molecules are too large to pass through the aqueopheres in the mouth's mucous membranes. Homeopathic hGH "does not work", according to a researcher who found that, in human tests, not one person experienced an increase in hGH levels.
Then there are secretagogues, compounds that do not contain GH but are supposed to increase the release of hGH. They include sleeping pills, imitations of neurotransmitter receptors, amino-acid fractions, isolated amino-acids, and synthetic amino-acid manipulators (which interfere with normal amino acid breakdown). "The majority of these compounds do not work." Many have numerable possible side effects. For example, high doses of amino acids can lead to dyspepsia, nausea, or diarrhea. Ingestion of several amino acids, particularly arginine, lysine, and ornithine, may help elevate hGH levels. "However, the response is transient and highly variable, and reduced with aging." Results are inconsistent. Clinical significance is unknown. Studies with elderly people have not found hGH-boosting effects. Increased hGH levels among athletes after taking amino acids do "not lead to improved muscle mass or strength or any other beneficial changes in body composition." Even if hGH release is slightly increased, this does not mean health is improved. And the question remains as to what exactly these high doses of amino acids will do to the rest of the cells, tissues, and organs in the body. Other supplement formulations are available, but none can claim they stop aging or cause "youthing." Vitamin A and zinc have been shown to increase hGH levels. However, "it is likely that a combination of nutrients would increase growth hormone levels more effectively than any single nutrient could." Nutritional support to the pituitary with whole food complexes may assist optimal function and release of proper amounts of hGH.
"Patients should be reminded that the best ways to increase their chances of living a longer, healthier life are to adhere to well-established advice on nutrition, exercise, and smoking." For example, regular exercise enhances production of hGH. Even if short-term "gains" with drugs are viewed as desirable, it should be remembered that hGH is "part of an intricate web of hormones and growth factors. Manipulating one part of this system most likely leads to counter-balancing changes in other metabolites. This increases the risk of unexpected adverse effects." Adverse effects are "relatively common" and there are theoretical concerns that use of these drugs will produce an artificial, higher-than-normal level of hGH which may actually shorten lifespan. iv
THE NUTRITIONAL APPROACH
In 1921, Sir Robert McCarrison observed that the endocrine glands were among the first structures to atrophy or degenerate following nutritional deficiencies. Glands must have vitamins A, B, C, and E complexes, potassium, zinc, manganese, calcium, magnesium, enzymes, essential fatty acids (including omega-3s), total protein, and all other nutrients to function and produce hormones as they should. Dr. Royal Lee questioned the logic of treating a person who had starved, atrophic endocrine glands with hormone drugs when the proper nutrition might revive those glands "into something like normal activity." Before atrophy becomes irreparable, real nutrition can produce profound improvements by feeding the glands so they perform properly. "Certainly the nutritional approach is the best if it offers any practical possibility of results, for it cannot do harm while the hormone approach may."
Consumption of altered fats (trans fats) can upset hormonal systems. Refined oils, partially hydrogenated fats, fried foods, and other fat fiddlers adversely affect glands and the hormones they produce. Steroid hormones are formed from cholesterol; food sources are often avoided due to the modern cholesterol hoax. Refined sugars and flours as well as altered fats may wreak havoc on cholesterol composition and metabolism and increase chances of glucose intolerance.
Some studies indicate that advancing age does not necessarily affect some hormones. Other hormones which are affected by time perhaps should not be manipulated - there may be good reasons why they decline. Lassitude, insomnia, depression, or plummeting potency may be among the signals to lose some weight, eat more wholesome foods, take whole-food supplements, exercise more, and/or stop smoking - rather than inexorable signs of aging. Increasing levels of and exposure to pollution and toxic chemicals disrupt hormones. Turning to organically-raised foods and avoiding as many toxins as possible may go far in preserving healthy hormonal levels.
No one has shown that hormone drugs or supplements containing high-potency, synthetic or isolated ‘nutrients' will add years to people's lives. Many of these potions can cause harmful side effects. "The right balance of hormones helps us stay healthy, but the wrong amount can be dangerous." Instead of taking something into the body that may stimulate, suppress, imbalance, or disrupt, it makes more sense to supply the body with whole, natural foods and food concentrates that will allow the body itself to build and balance whatever it needs. No one knows as much about an individual's body as that individual's body. v
i C Niewoehner, Endocrine Pathophysiology, Maidson: Fence Creek, 1998: 1; C Pert, Molecules of Emotion, NY: Simon & Schuster, 1997:255-9, 349.
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Originally published as an issue of Nutrition News and Views, reproduced with permission by the author, Judith A. DeCava, CNC, LNC.