(Bioidentical Hormone Replacement or Corrective Therapy)
Understanding Pharmacokinetics Allows Optimal Hormone Replacement
By Doctors Richard Lippman and Russell Laudon
Mother Nature employs a “pulsing schedule” in our endocrine glands
Taking hormones and nutrients only once a day does not promote optimal health. Ideally, we should consume them six times daily since Mother Nature employs this “pulsing schedule” in our endocrine glands. In nature, many hormones are repeatedly “pulsed” from endocrine glands as our bodies’ physiological demands wax and wane. For example, the pituitary gland pulses HGH about six times a day. Copying Mother Nature means that, ideally, patients over fifty should inject micro amounts of HGH together with its vital metabolite, IGF-1, twice daily (0.08mg HGH and 0.04mg IGF-1 eventual maintenance doses) (1). For a more optimal circadian rhythm and pituitary hormone release, we may employ a third dose of a suitable secretagogue (other hormones, especially melatonin and testosterone). For optimal exercise performance, a fourth dose is preferably injected a half-hour before heavy exercise. In the over-fifty crowd, sufficient HGH, combined with IGF-1, results in the increased muscle mass, strength, hard buttocks, and firm back muscles usually seen only in young athletes (2, 3).
A second pulsed hormone of interest is testosterone. The testis and other glands pulse testosterone in a similar manner. Indeed, both testosterone and HGH are pulsed in high output when we exercise heavily and produce lactic acid. Subsequently, lactic acid induces endocrine gland pulses – a fact often overlooked.
For best effect, copy nature and consume only physiologic amounts of combined bioidentical testosterone, HGH, and Armour Thyroid combined. These three perform especially synergistically during periods of heavy exercise. Testosterone acts even as an efficient HGH pituitary releaser. Unlike synthetic drugs, individual natural hormones do not act as “one trick ponies.” They work best when synergistically combined with one another.
Performing like a twenty-five-year-old
According to new research in my book, “Stay 40” (2), consuming synergistically micro amounts of these four hormones a half hour before heavy exercise allows a sixty-five-year-old body to perform like that of a twenty-five-year-old! Post-exercise recovery is also quick. I have proven this remedy time and time again while weight lifting or working heavy labor as a lumber jack in my forest of iron wood trees. I now am able to reinvigorate my body temporarily with the strength, speed, and stamina of a twenty-five-year-old by judicious use of micro amounts of these four natural hormones*.
*For many years, I carefully balanced adrenal and thyroid outputs and ingested sufficient protein while avoiding a high sugar diet since these initial steps are critical to the support of the above-mentioned four hormones. Adequate cortisone is especially critical and should not be steady-state released since nature demands a three-fold peak in the morning relative to the late afternoon. During nocturnal hours, elevated cortisol may result in tissue wasting as seen in seniors suffering from insomnia. On the other hand, HGH must be cycled which means one to three days abstinence every week in order to “reboot” endogenous production of HGH.
Renewed early-morning vigor
A temporary burst of early-morning vigor may be achieved by employing the previously mentioned three-hormone cocktail combined with supporting breakfast nutraceuticals such as probiotics, ubiquinol, PQQ, Vitamin D3, sublingual methylcobalamine, methylfolate, N-acetylcysteine (300mg max.), DHEA, DIM, “Living Fuel,” and magnesium.
Early morning lethargy dissipates, and even a sixty-five-year-old body becomes refreshed and motivated to engage in vigorous and enthusiastic exercise. Mental acuity, plasticity, and information processing speed improve, and one meets the day with a calm and resolute manner.
Better Appreciation of Pharmacokinetics and Steady-State Concentrations
If we truly appreciate the pharmacokinetics and half-lives of hormones and nutrients, it would compel us to copy nature and consume them at least two to three times daily, or alternatively, consume them in time-release capsules or liposomal gels.
For example, in men, DHEA deficiencies should be remedied by twice daily use of time-released lipid matrix DHEA, 10mg tablet every 12 hours, or DHEA gel. Men should avoid consumption of 50mg DHEA taken bolus (all at one time) as advocated by some Ivy League professors. This unfortunate regimen systemically spikes testosterone levels and insures a consequent estradiol (E2) spike (aromatization) in men. This unfavorable action necessitates the use of Arimidex, an aromatase inhibitor with significant side effects in some people, such as bone and joint pain (4). In men, DHEA blood levels up to an optimal (1) 400 µg/dl may be achieved by using 10mg tid or 15mg bid without appreciable rise in E2 and relatively stable SHBG. Women should use lower DHEA doses in a similar manner to avoid androgen dominance. Steady-state DHEA release counters the catabolic or tissue-wasting effects of cortisol. The pharmacokinetic principle of slow and steady release applies to both men and women, although the doses are clearly different in accordance with gender needs.
According to recent clinical double blind crossover studies summarized by Dr. Jonathan Wright, berberine was found to be superior to metformin in controlling type 2 diabetes (5). 500mg regulates glucose and lipid metabolism superior to metformin and a steady-state optimal blood level is maintained by dosing three times daily. This efficacious, steady-state treatment increases the number and activity (expression) of insulin receptors 24/7 (6,7). A third example is NAC or N-acetyl cysteine. Employing non-invasive, in vivo monitoring, my pharmacokinetic studies indicate that NAC and glutathione** have approximate half-lives of six hours (2). Thus, low physiologic doses of only 300mg three times daily should be consumed efficaciously to mop up unwanted free radicals. Again, don’t use NAC qd; Small doses of 300mg tid are preferred.
**Glutathione also modulates cell proliferation and immune response due to its non-free radical scavenger function.
A fourth example is time-released melatonin that prevents cancer when used in steady-state physiologic doses. Blind people have high steady-state amounts of melatonin in their blood streams 24/7, and they rarely acquire cancer. Consuming bolus high-dose melatonin may well cause a barbiturate-like hangover. Use only time-released melatonin. See http://melatoninznse.com/ for MelatoninZnSe.
A fifth example employs the use of the natural hormone, Aldosterone. In deficient patients with hearing loss, it will enhance hearing by 20 to 40 decibels. Taken orally with water, aldosterone’s half-life is only four hours. However, consuming it with a cup of grapefruit juice more than doubles its half-life. Hearing is further enhanced by alternating aldosterone with fludrocortisone (only 20µg) on alternative days (First day: fludrocortisone, then second and third days: aldosterone. see ref. 8).
A sixth example is the use of bioidentical testosterone for optimal health. Dr. Thierry Hertoghe suggests liposomal testosterone. Now available in the USA, liposomal testosterone cream applied only once a day gives twenty-four hour steady-state effects verified with steady blood levels. Intramuscular testosterone cypionate in customary doses of 200mg every two weeks yields a huge estradiol spike with large peak-trough testosterone variation and resultant deficiency symptoms at the end of two weeks. More consistent relief with lower risk can be obtained by taking 100mg every week. Better yet, Dr. Eugene Shippen has suggested SUBCUTANEOUS injection on a similar schedule, which further reduces the testosterone and estradiol spikes (9).
Lastly is nature’s own example of a time-release hormone, namely Armour Thyroid that is processed from pig thyroids. Natural Armour Thyroid contains the most active of thyroid analogs, thyroxine or T3, that is bound to globulin, thus forming thyroglobulin. Synthetic T3 is unbound. The bound thyroglobulin slowly releases T3 over many hours during the day, whereas synthetic T3, the drug, is quickly metabolized. Thus, Mother Nature herself has designed a long-acting, steady-state, time-release hormone critical to life. According to Dr. Thierry Hertoghe, thyroid deficiency increases mortality by about 43%. Thus, for optimal health, copy nature and choose time-released Armour Thyroid or other brands of natural desiccated pig thyroid.
Old Habits Are Hard to Break
Deliver gently natural hormones, and supporting nutrients, in efficacious tiny amounts
Recently, two physician friends were skeptical and feared changing their old habits of recommending hormone replacement only once daily. They asked me why I bothered with multiple blood draws from patients.
“Why not just do what everyone else does?” they asked. I answered them with a question: “What makes better medical sense: determining the steady-state concentration of hormones in patients, or accepting patient over-dosing and under-dosing due to unknown pharmacokinetics?” The question flummoxed them. I continued by stating that the pharmacokinetics of the well-studied drug, “AndroGel” are not necessarily the same as the bioidentical testosterone gels that compounding pharmacists custom manufacture for individual patients. In addition, natural substances, familiar to the human body and found in nature, often perform better than synthetic drugs cooked up by Big Pharma. For optimal health, copy nature using only physiologic amounts of natural hormones and supporting nutrients delivered gently 24/7 in efficacious tiny amounts (except for cortisone), and not delivered in a quick-fix bolus manner.
Thierry Hertoghe, 2010. The hormone handbook, 2nd ed., Int. Med. Pub., Chapter 9, etc.
(2) Richard Lippman, 2009. Stay 40, Outskirts Press Inc., Denver (CO), Available on Amazon.
(3) Wells, H. et al. 1996. Growth hormone increases muscle mass and strength but does not
rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old. J. Clin. Endocrinology Metabolism, September 1996. 81(9): 3239-3243. (4) Richard Lippman, 2010. AMMG meeting, November 2010, Las Vegas, (NV).
(5) Yin, J., Xing, H. et al. 2008. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 57(5): 712-717.
(6) Zhang, H., Wei, J. et al. 2009. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism 59(2): 285-192
(7) Kong, W. J., Zhang, H. et al. 2009. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism 58(1): 109 -119.
(8) Richard Lippman, 2010. New method of enhanced hearing without hearing aids. British Longevity Society, October 2010.
(9) Eugene Shippen, 2006. Master Series. A4M.