THE GROWTH HORMONE
Let’s now talk about a hormone which is more and more used, especially in the USA, in anti-aging therapy. It is the human growth hormone (hGH, or simply GH). As for its chemical structure, basically it is a protein (that is, a chain of amino acids). Therefore, it has nothing to do with steroids. GH is secreted by cells called “delta acidophilic”, in the anterior lobe of the pituitary gland (a gland located just underneath the brain, which regulates the secretion of other glands such as the thyroid, suprarenal gland and testicles). In order to better understand the utility of the theory and of the indications for the use of GH in anti-aging, let’s go through the physiological principles which regulate the production of the very hormone and its actions, that is, what it does in the body.
Actually, plentiful stimuli from various parts of the body “convince” the pituitary gland to release the precious hormone into the circulation. Let’s mention some “physiological”, totally natural stimuli:
1) sleep: the hormone is cyclically produced at night, especially in the first hours of sleep;
2) physical exercise: moderately intense or maximal exercise produces an increase of GH in the blood. This varies a lot according to people, and there is often no increase at all.
3) intake of food rich in protein: a diet rich in proteins stimulates GH production;
4) intense environmental heat.
Among the “paraphysiological” conditions leading to high production of GH, let’s mention:
- a) stress of any kind, even emotional;
- b) low calorie intake, especially carbohydrates, up to abstinence from food.
On this point, it is important to consider that many of the above-mentioned factors can “add” to one another, causing a more intense production of the hormone. Rigorous scientific studies have demonstrated that physical exercise in condition of humid heat causes a higher increase in GH compared to the same exercise performed in a windy environment. The same happens if the exercise is performed in the morning on an empty stomach.
Then, there are artificial conditions, that is, conditions which are not natural, where the pituitary gland produces more GH: it is the case of all the pharmacological stimuli often used as tests to assess the secretory capacity in short children who may be suffering from GH-deficiency dwarfism, also called “pituitary” dwarfism.
Among these, insulin induced hypoglycaemia, beta blockers, glucagon, vasopressin, clonidine. In particular, a derivative amino acid is used: LevoDopa.
As for single amino acids, it is known that basically all of them stimulate the secretion of GH, both when given intravenously and, in a lower way, orally.
Action in the body
3) The growth hormone stimulates the growth in length of long bones, which leads to higher height as adults. Yet, this effect is impossible after the closure of growth cartilages (under the action of endogenous testosterone in men and of estrogens in women): this happens at 15-18 years of age.
4) Stimulus of the growth of cartilage cells in the joints and increase in the development of flat bones. These bone effects remain even in adults.
5) Anabolic effect in a broad sense (nitrogen retention). On this point, the action of GH is quite evident (especially in subjects with low levels). The intake of the hormone causes a decrease of the amino acids in the blood and a reduction of azotemia (this proves that the proteins of one’s diet are mainly used for anabolic purposes and are not eliminated, unlike it usually happens). It is important to consider that the increase in anabolism caused by GH partially takes place in synergy (that is, in collaboration) with insulin, whose production is in turn stimulated by physiological doses of GH. Nitrogen retention is quite general, that is, unlike steroid anabolizer hormones, it affects everything: muscles, cartilage, internal organs, bones, skin, blood vessels, heart, etc.. In particular, the GH causes – unlike steroids – hypertrophy of muscle connectives (sheaths, tendons), reinforcing them and protecting them from lesions. Also, it seems that, as for bone growth (see above) and muscular growth, the hormone acts together with testosterone (endogenous, obviously). This is why boys are generally taller and naturally more muscular than girls: since women have similar insulin levels and GH levels even higher than men, this means that testosterone and GH probably collaborate to higher body development in men.
6) At the same time, GH also has an anticatabolic action, that is, it opposes the destruction of body proteins both in case of metabolic stress (physical exercise, calorie restriction, abstinence from food). This probably justifies the increase in the production of GH typical of these conditions (see above): that is, mother nature controls the damage.
7) Calorigenous effect: not well-know yet very clear, this action (which leads to an increase in body temperature and, above all, in metabolism and in the production of heat) seems to act independently from the thyroid hormone.
8) Marked lipolytic effect: that is, GH tends to stimulate the use of fat deposits for energy purposes. This is why it also has a glycogen-saving action (in case of abstinence from food or in case of severe diet, it contributes to burn mainly the calories of the adipose tissue, keeping the precious and limited supplies of the “noble fuel” of the muscles). Actually, men lacking GH tend both to hypoglycaemia (because they consume more sugars) and to obesity (because they burn fewer fats). It is important to underline that probably GH acts together with androgens: on average, women tend to be fatter than men, and in case of diet they are more prone to hypoglycaemia and lose less fat. That is, even being rich in GH they endure severe diets less.
9) Finally, it is important to stress that– even if in many cases it acts together with androgens, GH is NOT a steroid hormone, as its chemical structure shows.
GH and ANTI-AGING
The production of GH after the age of 20 decreases by 14% every ten years, so the production of GH at the age of 60 is halved. If at 20 the GH produced daily increases to 500mg and at 40 it is of 200mg, at the age of 80 the levels of this hormone are of about 25mg. People with age-related GH deficiency are more prone to become overweight, to be flaccid, frail and lethargic; they have sleep problems, concentration and memory problems, problems with sexual interest, and get tired easily. With anti-aging therapies based on GH these symptoms recede.
GH can make one’s life longer by protecting from cardiovascular diseases. Bengtsson et al. have published a study carried out on 333 patients suffering from hypopituitarism (the pituitary gland can no longer generate the necessary hormones). The patients underwent hormonal substitutive therapy including cortisol, thyroid hormones and sexual hormones. The only non-reintroduced hormone was GH. The study lasted 30 years, and during this time the mortality of the subjects was twice as much as the average life-expectancy of the normal population. The main cause of death was cardiovascular.
The GH protects against cardiovascular diseases in many ways. It reduces visceral abdominal fat, which is connected to insulin resistance and to cardiovascular risk. GH in an anti-insulin hormone, that is, a hyperglycaemising hormone. In the first weeks of GH intake there is a worsening of insulin sensitivity, with a tendency to hyperglycaemia, but after some months of treatment with physiological doses, not only do the values of insulin sensitivity go back to their previous levels, but they even improve thanks to the effect of GH on body composition. Studies carried out on adult subjects lacking GH show that the intake of the growth hormone caused an improvement in their lipid level, leading to an increase of “good” cholesterol (HDL) and causing a decrease of “bad” cholesterol (LDL). Moreover, GH proved to be particularly effective in restoring the contractility capacity of the cardiac muscle, improving the systolic ejection fraction in patients with cardiac decompensation. GH improves body composition. One of the most important milestones in the history of anti-aging medicine is the discovery produced by the NEW ENGLAND JUOURNAL OF FUNCTIONAL MEDICINE on 5th July 1990, through which RUDMA et al. presented the first clinical study on the use of GH in elderly men. Comparing 12 men between 61 and 81 years old in substitutive therapy with biosynthetic GH to an analogous group for six months, the researchers noticed an average 8.8% increase in lean mass and a 14% loss of fat mass (with no diet or physical exercise), an improvement in skin elasticity and tone and an increase in bone density in the GH therapy group. In a study carried out in 2000, Vender Lely et al. observed that six weeks of treatment with GH significantly accelerated the velocity of progression in accidental hip fracture in elderly patients. GH can increase the pulmonary functions in patients with chronic obstructive diseases, improving maximum oxygen consumption and forced expiratory volume (FEV), that is, the capacity to exhale air out of the lungs in one second. The GH is fundamental for brain activity. It also has an action on the cells of the nervous system thanks to the presence of receptors for this hormone and of IGF-1 on their membrane.
Many researchers believe that the decline in GH production connected to aging can be responsible for the loss of volume in the brain, above all in the hippocampus. Researchers at the University of Auckland, New Zealand, have discovered that IGF-1 can stop apoptosis, that is, cell death of the neurons. Apoptosis occurs with higher frequency in the aging process, above all together with brain degenerative diseases such as stroke, Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Neuron apoptosis causes severe functional damage such as loss of memory, of concentration, as well as motor difficulties. Several studies have demonstrated that as IGF-1 levels decrease, so does cognitive capacity, and significantly lower IGF-1 levels have been found in patients with memory loss. Treatment with GH is currently the most effective in making people appear younger. The skin in the elderly tends to become thinner and to lose its texture. GH increases its thickness and has a “lift-like” effect. In the above-mentioned study by Rudman, the skin thickness increased by 17%; after self-assessment, 66% showed an improvement in skin texture and elasticity, and 38% showed hair re-growth. After few weeks of treatment, the deeper wrinkles decrease, as do face fat and adipose bags under the eyes. The facial muscles are toned up and make the skin adhere more to them. The GH has this “lift-like” effect on the skin also by increasing collagen and elastin synthesis, which are at the basis of the skin structure.
This improvement in skin elasticity can be demonstrated with the “pinch” test: take a skin plica of the back of the hand between thumb and index. Normally, the skin takes about 1 second for every ten years of age to go back to its condition. This method is useful to assess the biological age of one’s skin. In GH therapies this time diminishes by 30 to 50%. Since the levels of GH are quite fluctuating, in order to assess its secretion it is necessary to consider the values of IGF-1, which are more stable and are produced by the stimulus of GH in the liver. Values of IGF-1 lower than 100 μg correspond to a condition of hyposomatostatism; values lower than 150 indicate a lack in GH production. The GH therapy must be effective to restore IGF-1 in the range typical of 30-40 years old which, for the majority of people, corresponds to 250μg -350μg.
Therapeutic dosage is related to body weight. The average weekly dose for an anti-aging therapy is approximately between 2 and 8 UI a week (1 mg corresponds to about 3UI). Many experts in anti-aging medicine divide the daily dose in two intakes: one in the morning and one before going to bed at night, so that they correspond to the normal endogenous production.
Generally, the above-mentioned therapeutic dosage does not have side effect. Yet, in case of over-physiological doses or in subjects who are particularly sensitive, prolonged intake can lead to: edema, carpal tunnel syndrome, gynecomastia, insulin resistance, pressure increase and decrease in the production of thyroid hormones.
These effects are reversible by decreasing the dose or suspending treatment. As for the possibility that – since GH stimulates cell proliferation – it can favour not the genesis but the growth of an existing tumour, there is no scientific evidence. Instead, there are conditions indicating that in people suffering from hyposomatism, it can have a preventive effect in tumour genesis thanks to its capacity to enhance the immune system, more specifically lymphocytes, natural killers which protect the body against tumour cells. However, since there are no final answers, it is better not to treat oncological patients with GH substitutive therapy.
L’Accademia del Fitness-Wellness-Antiaging / October 2015