Hormones for Wellness

Published on July 3, 2013 by

Hormones are our internal chemical messengers that regulate cellular function and metabolism. Ideally, hormones maintain a protagonist and antagonist balance over our bodily functions. For example, glucagon and insulin are secreted by the pancreas and work in concert to raise and lower our blood sugar levels in response to dietary change. This critical balance within our endocrine system changes with age creating degenerative processes that we all recognize as undesirable sequellae to getting older.

Hormonal levels may be favorably or adversely effected by diet, exercise, stress, and the sheer process of growing older. The first step in wellness is in understanding and practicing daily routines that influence favorable changes in our hormone levels which in turn contribute to longevity.

Insulin

The first hormone to consider is insulin. Its level is directly influenced by what we eat. Furthermore, it has a far-reaching effect on the other hormones in our body. For these reasons, the insulin level has become a key biologic marker for aging, wellness, and longevity.

The two key hormones that direct the utilization of food are insulin and glucagon. Insulin drives nutrients into the cells for either immediate use or future storage. Glucagon mobilizes stored nutrients from cells to circulate in the blood stream as a source of energy. The two work in concert to precisely control blood sugar levels. Should anything upset this balance between insulin and glucagon, especially increased insulin, then accelerated aging will occur.

The more calories we eat (especially if they are carbohydrate), the more our insulin levels increase. Insulin levels also increase with age owing to increasing cellular insulin resistance and to decreasing glucose intolerance. Insulin resistance means that target cells in the muscles don’t respond well to the amount of insulin in the bloodstream, forcing the pancreas to make more insulin. An elevated blood insulin level is called hyperinsulinemia and is your worst aging nightmare.

  • Hyperinsulinemia is associated with
  • excess caloric intake
  • inhibition of glucagon secretion
  • increase cortisol secretion
  • increase DNA turnover shortening the telomere length of the DNA
  • increase “bad” eicosanoids
  • decrease cyclic AMP
  • increase in insulin resistance
  • increase in stored fat with negative effect on the metabolism of sex hormones

Are there ways you can be checked for hyperinsulinemia? YES!

  • Fasting insulin will directly measure your insulin level
  • Fasting triglyceride/HDL cholesterol ratio is a surrogate marker for your insulin level
  • Increase in percentage of body fat is an indication of increasing insulin level
  • Glycosylated hemoglobin measurement indicates your degree of glucose intolerance

Cortisol

Corticosteroids are synthesized in the adrenal glands and are critical to the management of stress. An imbalance of corticosteroid levels can play a significant role in the aging process. Low levels reduce the ability to handle stress and produce chronic exhaustion and fatigue. Lack of cortisol production (Addison’s disease) may be fatal. Cortisol overproduction (Cushing’s disease) stimulates gluconeogenesis (glucose production from protein) and leads to muscle wasting. It also suppresses the production of both good and bad eicosanoids leading to severe compromise of the immune system. High levels are cytotoxic to the thymus and to certain neurons in the hippocampus.

Light to moderate exercise has no effect on cortisol levels. On the other hand, extreme exercise produces stress and raises cortisol levels. With the concomitant increase in free radicals, physically fit individuals, as a consequence of intense exercise, may be less healthy than those doing light to moderate exercise.

Meditation has been shown to reduce stress and thereby reduce cortisol levels. Maintaining cortisol levels in the normal range is one of the keys to longevity and wellness.

Eicosanoids

Eicosanoids are made by every cell in the body rather than a single gland. As autocrine hormones, eicosanoids don’t travel through the bloodstream, work at incredibly minute concentrations, and self-destruct in seconds. The subgroups of eicosanoids are as follows:

  • Prostaglandins
  • Thromboxanes
  • Leukotrienes
  • Lipoxins
  • Hydroxylated fatty acids
  • Isoprostanoids
  • Epi-isoprostanoids
  • Isoleukotrienes

An eicosanoids mission is to be secreted by the cell to test the external environment and then to report back to the cell what is just outside its boundaries. Based on that information, the cell can take the appropriate biological action to respond to any change in its environment. Any change in the environment of a cell can be considered a stressor. That’s why eicosanoids can be viewed as the molecular mediators of stress for a cell.

Eicosanoids that generate increased levels of cyclic AMP in the cell are the key to anti-aging and are considered “good” eicosanoids. Their production of cyclic AMP serves as a booster signal to work in concert with other endocrine hormones insuring that the desired biologic response is achieved. This “booster” effect is critical as we age since most endocrine hormone levels are decreasing. The balance of these endocrine hormone systems (insulin and cortisol) profoundly influence the dynamic balance of the autocrine system (good and bad eicosanoids).

  • “Good” Eicosanoids
  • Inhibit platelet aggregation
  • Vasodilators
  • Anti-inflammatory
  • Control cellular proliferation
  • Enhance the immune system
  • “Bad” Eicosanoids
  • Promote platelet aggregation
  • Vasoconstrictors
  • Pro-inflammatory
  • Promote cellular proliferation
  • Suppress the immune system

The more the balance is shifted toward bad eicosanoids, the more likely the development of chronic disease. The more the balance is shifted toward good eicosanoids, the greater one’s wellness and longevity.

Many of the disease conditions associated with an aging population are conditions associated with eicosanoids imbalance:

  • heart disease
  • hypertension
  • type 2 diabetes
  • inflammatory diseases
  • auto-immune diseases
  • cancer
  • depression

So, what can we do to improve our eicosanoid balance?

  • Avoid trans fatty acids (partially hydrogenated vegetable oil) due to their inhibition of eicosanoid synthesis
  • Take supplemental fish oil in order to get adequate levels of eicosapentaenoic acid (EPA)
  • Avoid hyperinsulinemia (carbohydrate loading)
  • Regular mild to moderate exercise (avoid stress inducing exercise)

Estrogen

There is no single compound known as estrogen. Rather, estrogen is a family of three compounds: estrone (E1), estradiol (E2), and estriol (E3). It is the balance of estrogens and progesterone that is the key to sex hormone equilibrium in females, since they exert opposing effects on each other primarily by altering each other’s receptor sites. Estrogen increases the number of receptor sites for both estrogen and progesterone, whereas progesterone decreases the number of receptor sites for both hormones. Many of the problems of menopause and postmenopause are caused by an imbalance of estrogen and progesterone, leading to estrogen dominance.

Estrogen seems to be a profound governor on the secretion of insulin. As total estrogen levels decrease, insulin resistance and insulin levels begin to rise. Increasing insulin levels causes the overproduction of “bad” eicosanoids and cortisol. It is not surprising that after menopause, the incidence of “chronic illness” increases.

This important link between estrogen and the other hormones explains the many benefits of estrogen replacement. Unfortunately, replacement estrogen produces a bimodal response. At low doses of estrogen, insulin resistance is reduced while at high doses, insulin resistance is increased. Many of the contradictory studies on the value and safety of estrogen replacement do not take this bimodal response into consideration. If a small dose of estrogen is beneficial, won’t larger doses produce even greater benefits? This is simply not the case. Combination replacement (estrogen + progesterone) further compounds the problem since progesterone also increases insulin resistance.

The most common estrogen supplement is Premarin, a synthetic analog made from Pregnant mare urine consisting of different types of estrogens only about half of which are found in humans. Of those only estrone and estradiol are present. Estradiol and estrone, the “stronger” estrogens, potentiates breast cancer while estriol, the weaker estrogen, protects against breast cancer. Since estriol is not present in Premarin, the unopposed effects of estradiol are generally countered by combination therapy with progestins (synthetic progesterone) to offset the cancer promoting effects and bone loss effects (osteoporosis) caused by estradiol. It is arguable whether these progestins add to the safety of Premarin. In fact, a recent study in the New England Journal of Medicine showed that women taking estrogen and progestin had a 32-46% increase in their risk for breast cancer. Additionally, many women stop taking progestins because of their numerous side effects including PMS, bloating, irritability, and depression. Risks of estrogen/progestin therapy include:

  • weight gain
  • abnormal clot formation
  • increased risk of gallstones, fibroid tumors, headaches
  • pre-menstrual-type symptoms

Recent studies indicate the advantages of natural hormone replacement with estriol and progesterone as opposed to their synthetic counterparts, Premarin and Porvera. Estriol provides the anti-aging benefits of estrogen replacement without the increased risk of cancer. These anti-aging benefits include:

  • enhanced skin smoothness, firmness, and elasticity
  • enhanced moistness of skin and mucus membranes
  • enhanced muscle tone
  • reduced genital atrophy and enhanced sex drive in women
  • reduced menopausal symptoms
  • reduced risk of heart disease and osteoporosis
  • reduced risk of colon cancer
  • improved memory and overall neurologic function
  • protection against Alzheimer’s disease
  • enhanced immune function
  • a greater feeling of well-being

The lowest dose of estrogen capable of producing the desired effect should be used, so as to avoid its bimodal effect on insulin. Since estriol is a weak estrogen, larger amounts must be used for estrogen replacement. Estriol is used in doses of 2-8 mg per day. A dose of 2-4 mg of estriol is equivalent to, and as effective as, 0.6 to 1.25 mg of Premarin.

When maximum doses of estriol prove ineffective, combination estrogen therapy using 80% estriol, 10% estrone, and 10% estradiol (TriEst) may be indicated. Doses of TriEst range from 1.25 mg twice daily t 2.5 mg twice daily.

Progesterone

It is the balance of estrogens and progesterone that is the key to sex hormone equilibrium in females. Progesterone works by decreasing the number of estrogen receptor proteins in the nucleus. Through this process, progesterone is thought to decrease the likelihood of breast cell proliferation by limiting the estrogen effect. However, studies on combination estrogen/progestin replacement therapy have demonstrated an increased risk for breast cancer.

The most commonly prescribed “progesterone” is Provera which is actually a synthetic progestin. Progestins typically have more side effects than natural progesterone and include:

  • PMS
  • bloating
  • irritability
  • depression

Progestins were initially introduced as oral contraceptives since increased progesterone levels blocked the release of eggs from the ovary.

Until recently one of the major problems with natural progesterone is that it was not orally absorbed without extensive degradation. Today, a new form of natural progesterone called micronized progesterone has solved these early problems. A comparison of natural progesterone to progestin was made in the PEPI study and revealed a much lesser degree of side effects and better disease outcome with natural progesterone.

Testosterone

Testosterone is the hormone of strength and desire. It is an aphrodisiac for both males and females. It is also required to develop muscle mass and strength. Testosterone is what makes men look, feel, and think differently than women, but it also makes both genders sexually attracted to each other. Aside from its impact on sexual differentiation, it has a major impact on the growth of muscle and the amount and distribution of body fat (it makes you leaner).

Males make about 5 mg per day of testosterone (about 50 times more than females). Women make two to three times more estradiol than men. This difference between males and females is in part coupled with the relative inactivity of the aromatase enzyme (in males) which converts estradiol to testosterone.

The aromatase enzymes are found in fat cells. As males age and their fat cell population increases, testosterone levels fall with a corresponding increase in estradiol levels (an unfavorable direction for males).

Testosterone levels accelerate rapidly at puberty and then slowly decrease with age. The gradual drop-off of testosterone levels as you age is known as andropause and is the corollary to menopause in the female.

Growth Hormone

Growth hormone is the one hormone most likely to reverse the aging process. Growth hormone promotes growth, increases lean body mass, decreases stored body fat and increases skin thickness. Each decade that we age the secretion of this hormone decreases 10-15 percent. The hormone release is controlled by exposure of the pituitary to good eicosanioids, by normal (not elevated) blood levels of insulin , by reduced caloric intake with adequate provision of protein, by receiving adequate deep sleep (Stages III and IV) which occurs just before REM sleep, and by anaerobic exercise (weight lifting and wind sprints, in particular). Once growth hormone is released into the bloodstream, where its half-life is only 5-6 minutes, it has two target sites : 1) fat cells and 2) the liver. When fat cells are activated by growth hormone stored fat is released to provide growth and new muscle mass. When the liver is activated by growth hormone a new set of hormones are released, called insulin-like growth factors (IGF). IGF-1 has a half-life of 12-15 hours in the blood ( unlike the 5-6 minutes of growth hormone) and maintains and/or increases muscle mass formation. Diet, calorie restricted, yet balanced amounts of carbohydrates, protein and fat (40-30-30) maintains the levels of growth and IGF hormones most optimal for heath and longevity.

Pharmacologic ways (pills and the longer-used injections) of increasing growth and IGF hormones are now available, however the increased cancer risks and the alteration of the body’s natural hormone secreting capabilities are still being evaluated.

Serotonin

Serotonin, the so-called morality hormone, influences whether or not you are depressed, prone to violence, irritable, impulsive or gluttonous. It acts as a traffic controlling policeman by inhibiting some of our most base/animal-like instincts. Low serotonin levels are associated with violence and aggression and depression. High serotonin levels ultimately lead to high insulin levels, which is not only a pathway to negative aging consequences, but also to weight gain.

Serotonin levels may be raised by taking drugs, such as Prozac, which inhibit the re-uptake of serotonin by the original nerves sending messages so that serotonin lifetime is increased. Other drugs increase the amount of Serotonin, i.e.: fenfluramine and desfenfluramine–the basis of the phen/fen and Redux weight-loss program that increased the incidences of malfunctioning heart valves and pulmonary hypertension. Serotonin may be consumed, however it increases platelet aggregation (clotting of the blood), which increases the chance of heart attack, among other things. The best option may be to increase consumption of the serotonin precursor: tryptophan. This is not FDA approved as a supplement, however it is naturally occurring in food : turkey and milk.

When serotonin is at low levels in the body, the blood levels of the bad eicosanoids are at elevated levels. One way to monitor/maintain the delicate balance of serotonin in the body is to better balance the bad and good eicosanoids using diet manipulation.

DHEA

DHEA (dihydroepiandrosterone), produced by the adrenal gland, is the most abundant steroid hormone produced by the body and is synthesized in the range of 25-30 mg per day. DHEA provides the balance for cortisol. For example, if DHEA production is decreased for any reason, cortisol production increases wreaking havoc on eicosanoid synthesis. This inverse relationship between DHEA and cortisol is directly related to eicosanoid balance (i.e.: as DHEA increases, there is improved eicosanoid balance whereas when cortisol increases, eicosanoid balance is destroyed.)

It is true that DHEA levels drop with age and that men with higher DHEA levels appear to have less heart disease and lower overall mortality. Impotence is also associated with lower DHEA levels. Nevertheless, most of the touted benefits of DHEA may be explained by its inhibitory effects on cortisol, high levels of which adversely effect insulin and the sex hormone systems. Accordingly, the ratio of cortisol to DHEA is a more critical parameter in aging than simply measuring the amount of DHEA in the bloodstream.

Melatonin

The main function of melatonin has always been assumed to be the control of circadian rhythms based on light and dark cycles. Cortisol, testosterone, growth hormone and many others are strongly influenced by such rhythms. By the age of 80 the serum levels of melatonin are only about 10% of what they were at age 20. Accordingly, it might be assumed that the circadian rhythms that govern these other hormones might be thrown out of kilter.

The real interest in melatonin began with the observation that supplementation of this hormone could increase the maximum life span of animals. Like DHEA, many of the benefits of melatonin are strikingly similar to those achieved through better eicosanoid balance: more energy, better sleep, reduced risk of heart disease, and immune function improvement.

Another potential role of melatonin was discovered in 1993 when it was found that melatonin was an antioxidant with some unique properties. Mankind has lost the ability to make some very basic antioxidants such as vitC, vitE, and betacarotene. Melatonin is incredibly successful in quenching the hydroxl free radical if it is formed. If hydroxl free radicals are formed, they will exert their greatest damage in the brain. If there is one area of the body you want to prevent from free radical damage, it is the brain, which is nearly 50% fat by weight and more than one-third of that fat is polyunsaturated (which is exceptionally prone to free radical attack). In essence, melatonin is your free radical defense of last resort for the brain.

You need melatonin to protect essential fatty acids so that they can be made into “good” eicosanoids”. You need good eicosanoids to maintain adequate levels of cyclic AMP to convert serotonin into melatonin. Hence, melatonin has a significant role in maintaining eicosanoid balance, which is the real key to anti-aging.

Nitric Oxide

Nitric oxide, a “protohormone” which needs no receptors, aids in controlling the cardiovascular, immune and nervous system. Nitric oxide, a nitrogen free radical, is a relatively stable free radical, which diffuses as a gas into the body. It can be found naturally occurring in air pollution and cigarette smoke, however its usable, beneficial form is made in the body when nitric oxide is combined with the amino acid arginine. Rather than the receptor site that other hormones seek, nitric oxide information is halted at the proper location by any iron-bearing enzymes or proteins.

Nitric oxide can control vasodilation. For example: at the first signs of flow disturbance or turbulence in arteries, the endothelial cells begin to make nitric oxide which produces a very localized vasodilation. Once the increase blood flow brings by enough iron-containing hemoglobin these iron-rich cells absorb this new nitric oxide and the vasodilation effect is controlled so that blood pressure does not become too low. Nitroglycerin, a pharmaceutical drug, stimulates the production of nitric oxide to temporarily relieve angina. Viagra is another drug that works on this premise of nitric oxide release.

Nitric oxide, the free radical that it is, can also be used by the body to kill invading organisms by attacking the iron-containing enzymes of the bacteria. Most anaerobic bacteria depend on the iron-containing enzymes for survival.

Nitric oxide helps to form and reinforce new neural pathways in the brain. It accomplishes this job by being very fat soluble and diffusing easily between lipid structures. The brain, with the largest concentration of fats of any organ in the body, reaps the benefit of nitric oxide primarily in the form of increased short-term memory. As we age long-term memory is seemingly unaffected, however short-term memory capabilities are lessened. It is possible that the neural cells are not able to make adequate levels of nitric oxide to form the new pathways necessary for short-term memory.

Reaping all the benefits of nitric oxide can be accomplished by eating a protein-adequate diet containing arginine-rich foods like turkey and soy protein products.

Thyroid

Thyroid hormones, a collection of three, are secreted by the thyroid gland. They control the body’s heat production by increasing oxygen consumption, affect metabolism (primarily cholesterol metabolism), control brain maturation in neonates, affect behavior in children and adults, and control growth and development. Thyroid hormones are the most prescribed hormones, after estrogens, in the United States. It is the free thyroid hormones circulating in the bloodstream that seek out their receptor sites in the cells where they are delivered to the nucleus (cell control center) to regulate genes to increase or decrease the production of messenger RNA. The messenger RNA then leaves the nucleus, proceeds to the outer cell and here various proteins are synthesized from it.

One of the proteins released causes increased body heat production. This energy is needed to simply keep your body warm. The brain and human body run best in a very narrow temperature zone. Not only does this particular thyroid hormone stimulate the increased heat energy, it ideally stimulates the release of energy from a particular kind of fat cell so that stored fat will be used as a form of heat production. Therefore if there are low amount of thyroid hormones or the hormones are not able to get a message through to the cell nucleus then metabolism slows and this can make it difficult to lose excess fat.

When thyroid hormones were first “discovered” in the early nineteenth century they were not discovered due their effects on slow metabolism but rather on their role in heart disease. Pathologists, through the use of autopsies, found a high correlation between atherosclerosis and low thyroid hormone levels (hypothyroidism). In the early 20th century tests established this link further by removing the thyroids in animals and totally preventing the usual occurrence of atherosclerosis by giving them thyroid extracts. Near this same time a study was also carried out that fed large amounts of cholesterol to rabbits which also led to atherosclerotic lesions. The ensuing scientific frenzy which assumed that cholesterol intake lead to heart disease has lasted until very recently. In fact, it was demonstrated that feeding high levels of cholesterol to rabbits would not cause atherosclerosis if they were given thyroid hormones at the same time. As more time has passes and more studies regarding thyroid hormone levels have been done we now know that, in addition to low thyroid levels being correlated to heart disease, hypothyroidism increases triglyceride levels and lowers HDL (good) cholesterol levels. Since triglyceride/HDL cholesterol ratio is a surrogate marker for insulin, this would suggest that hypothyroidism increases insulin or that increased insulin lowers thyroid levels. Note here also, that increased cortisol levels (found through blood testing) further strengthen the link between hypothyroidism and hyperinsulinemia.

Blood tests that measure thyroid hormones are simply a quick, single look, not a truly telling result of thyroid function. You are not able to get a true indication of thyroid efficiency or inefficiency at the cellular level. Most experts require 24 hour urine collection and analysis of thyroid and adrenal hormone levels AND exhaustive collection of patient of symptoms being experienced. The symptoms most often stated (cold intolerance, depression, fatigue, muscle weakness, brittle fingernails and hair, dry skin and weight gain) are also those found with poor eicosanoid function.

Hyperthyroid function, known as Graves disease, is usually treated with removal of the gland and life-time supplementation with thyroid hormones.

Hypothyroid function can be improved through diet management: adequate level of low-fat protein, low-glycemic carbohydrates, and enough monounsaturated fats to produce satisfaction.

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