Life Extension Magazine June 2009
Physician’s Guide: Using Blood Test Findings To Safely Induce Weight Loss
By William Faloon
Restoring Youthful Metabolic Parameters From the Inside
At this point, the patient has erected a multi-pronged barrier to impede the excess absorption of unwanted calories. These include:
For many people, sticking to the above program for the time period we suggest should provide optimal fat-loss benefits. As discussed already, we prefer that patients not use orlistat for more than 60-90 days because it may interfere with the absorption of fat-soluble nutrients like vitamins D, E, and K. It will also impede absorption of critical omega-3 fatty acids. Certain patients, however, who are successfully benefiting from orlistat may continue it longer.
The 60-90-day program we have suggested thus far will dramatically reverse many of the metabolic imbalances that are underlying causes of excess fat accumulation and increased vascular disease risk. Overweight and obese patients expect to see a rapid reduction in body weight and abdominal inches. The 60-90-day program outlined so far will help facilitate immediate fat-loss results and provide substantial patient incentive to follow a reduced-calorie regimen that involves Mediterranean diet-type food choices along with plenty of dietary fiber.
The long-term objective is to restore a more youthful metabolic pattern that will last a lifetime. This most often requires hormonal balancing and enzymatic modulation at the cellular level. For men, replacing free testosterone lost to normal aging is usually required. Women deficient in estrogen are encouraged to restore estrogen to more desirable ranges. Both sexes should maintain TSH (thyroid-stimulating hormone) and T3 (tri-iodothyronine) thyroid hormone levels in the optimal ranges described later in this article.
Normal aging results in reduced insulin signaling throughout the body that disrupts healthy glucose metabolism. The prescription drug metformin helps correct several mechanisms involved in glucose impairment by increasing insulin sensitivity, enhancing peripheral glucose uptake in energy-producing cells, decreasing intestinal absorption of glucose, and suppressing excess glucose synthesis from the liver.69-71 Metformin also increases a satiety hormone called glucagon-like peptide 1, thus helping to induce a long-term appetite-suppressing effect that will better enable patients to adjust to a life-long reduced-calorie diet.72,73
Effects of Sex Hormones on Adipose Tissues
Sex hormones are involved in the metabolism, accumulation, and distribution of body fat. Adipocytes (fat cells) have receptors to bind testosterone, estrogen, and progesterone, thus enabling these sex hormones to exert a direct action.
Sex steroid hormones carry out their function in adipose tissues by both genomic and non-genomic mechanisms.74 In the genomic mechanism, the sex steroid hormone binds to its receptor on the adipocyte and can regulate the transcription of genes involved in obesity. Leptin is a hormone secreted from adipocytes that regulates appetite and induces beneficial triglyceride breakdown in adipocytes. Lipoprotein lipase is an enzyme that breaks down circulating triglycerides into free fatty acids that are readily stored in adipocytes (fat cells). Both leptin and lipoprotein lipase exert control over adipose (fat) tissues and are genomically regulated by sex hormones.
In the non-genomic mechanism, sex hormones can activate certain hormone-sensitive lipases, ultimately leading to lipolysis (fat breakdown). In the presence of certain sex hormones, a normal distribution of body fat exists. On the other hand, with an imbalance of certain sex hormones (as occurs with aging), there is a tendency towards an increase in abdominal obesity: a major risk factor for cardiovascular disease,75,76 type 2 diabetes,77 and cancer.76,78-80
Since sex hormones regulate the amount and distribution of adipose tissues, they are key elements of a comprehensive program to eliminate obesity. When properly prescribed, bioidentical hormone replacement therapy in postmenopausal women and older men often reduces the degree of abdominal obesity.74,81-83
Testosterone Prevents Triglycerides From Accumulating in the Male Abdomen
In men, a testosterone deficit is often accompanied by visceral obesity. When deficient men are supplemented with testosterone, the result is a region-specific decrease in the visceral (abdominal) adipose tissue mass.74,84 This suggests that testosterone is exerting its effects by inhibiting lipid uptake and/or enhancing lipid mobilization from adipocytes, particularly abdominal fatty tissues.
To assess the effect of testosterone on fat mass, a study was done using labeled triglyceride fatty acids and measuring their incorporation into adipose tissues in two different regions of the body. The study subjects were all abdominally obese and divided into three groups. Group one received topical natural testosterone cream, the second group received a testosterone metabolite called dihydrotestosterone, while the third group was given a placebo cream. After two months, the testosterone group exhibited a 34% reduction in triglyceride uptake and increased turnover rate of triglycerides in abdominal adipose tissue.85
Interestingly, the uptake of labeled triglyceride at baseline was 20% greater in abdominal fat compared with upper leg fat, which helps explain why so many men suffer expanding waistlines as they age, especially in the presence of less than optimal testosterone. This study shows that testosterone replacement diminished triglyceride uptake by fat cells in the abdomen, while simultaneously promoting a more rapid release of abdominal triglyceride stores.85
The underlying mechanism proposed by the study’s authors was a significant 47% decrease in lipoprotein lipase activity in the abdominal region. As discussed earlier, lipoprotein lipase is involved in the deposition of triglycerides in adipocytes, thus causing fat cells (and people) to become bloated.
Triglyceride is the predominant form of fat that bloats adipoctyes. Excess fat in the bloodstream after eating (postprandial lipemia) is often described as postprandial hypertriglyceridemia. Interestingly, testosterone supplementation can reduce blood triglyceride levels by increasing their breakdown in the liver (via increased hepatic lipase activity). Testosterone also improves insulin sensitivity and can facilitate a reduction in postprandial hyperglycemia.86 Several additional mechanisms have been identified that enable testosterone to reduce triglyceride levels in abdominal adipocytes (fat cells) of men.85,87
A number of studies document a reduction in belly fat after men with low testosterone are supplemented with testosterone.88-90 If a blood test reveals less-than-optimal testosterone level (below 20 pg/mL), consider prescribing the patient a topical testosterone cream after first ruling out prostate cancer using a PSA (prostate-specific antigen) blood test and digital rectal exam. (Refer to the sidebar "How to Safely Restore Youthful Testosterone in Aging Men" below for prescribing information.)
Some men will convert (aromatize) too much of their testosterone to estrogen. Optimal estradiol levels in men range from 20 to 30 pg/mL of blood. Excess estradiol can be easily suppressed by prescribing an aromatase-inhibiting drug like Arimidex® in the dose of 0.5 mg two times a week.
Make sure that estradiol levels are not lowered below 20 pg/mL of blood as this may disable testosterone’s ability to induce abdominal fat loss. Some studies suggest that the decrease in abdominal lipoprotein lipase that occurs in response to testosterone replacement therapy may have to do with the conversion of some of the testosterone to estrogen.91 These studies are contradicted when observing abdominally obese men whose blood tests reveal low free testosterone and excess estradiol. These overweight men often present with enlarged breasts (gynecomastia) induced by this excess estradiol. Since much of the excess estradiol in these aging men is a result of the aromatization of testosterone to estradiol in abdominal adipocytes, it is difficult to comprehend that testosterone’s benefit in reducing belly fat is reliant on significant aromatization to estradiol.
These subtle nuances, which vary considerably amongst individuals, are why regular blood testing to ensure optimal free testosterone and estrogen levels is so important.
Low Estrogen Promotes Weight Gain in Women
Menopause causes a large decrease in estrogens and progesterone with a corresponding increase in total and abdominal obesity. Several studies show a reduction in abdominal obesity in women in response to estrogen replacement therapy.74,83
Analogous to the way testosterone reduces male abdominal fat mass, estrogen in females reduces lipoprotein lipase activity in abdominal adipocytes. Lipoprotein lipase converts circulating triglycerides into free fatty acids that are readily stored in adipocytes (fat cells).
The control of lipoprotein lipase is very complex and involves several hormones. In women, cortisol,94-96 testosterone,97,98 and insulin99 promote lipid accumulation in adipocytes by increasing lipo-protein lipase activity, whereas growth hormone and estrogen decrease lipoprotein lipase (and thus facilitate abdominal weight loss).12,98,100,101
Conventional estrogen drugs list side effects that include weight gain. One reason for this is that until recently, the most commonly prescribed estrogen drugs were Premarin® and Prempro®, which are horse urine-derived compounds that are not identical to the estrogen naturally produced in a woman’s body. The dose of these drugs was seldom individualized, meaning that women often received too much (or too little) estrogen to meet their particular needs.
With the advent of bioidentical estrogen drugs that are individually dosed, women whose blood tests reveal low estrogen can precisely restore estrogen levels to a range that may induce a reduction in abdominal fat mass, along with other benefits.
Natural estrogen compounds are available by prescription from compounding pharmacists. These types of estrogen are bioidentical—this term means that the hormones are chemically the same as the natural estrogen produced in a woman’s body. The types of estrogens commonly used in bioidentical hormone replacement therapy are estradiol and estriol.
Bioidentical estrogen drugs are prepared using different percentages of estriol and estradiol compounded into a topical cream. The most popular compounded bioidentical estrogen used today is bi-estrogen or bi-est. It is prescribed as a topical cream that may consist of 80% estriol and 20% estradiol, or a percentage ratio individualized to the patient’s need. Based on a women’s estradiol blood test reading, and the body composition changes that occur, the dose of estradiol and estriol in bi-est may be increased or decreased.
An individualized approach to bioidentical hormone restoration is best. A woman will need to carefully monitor and assess her individual responses and report them to her prescribing physician so that adjustments can be made to her hormone regimen. In general, experts in the field of bioidentical hormone restoration suggest that most women feel their best when estradiol blood levels are in the range of 90-250 pg/mL, a range of estradiol that is common during the majority of the menstrual cycle for most healthy young women.
In addition to natural estrogen, natural progesterone is an important hormone for women. Natural progesterone cream or ointment is available as a compounded prescription or OTC (over-the-counter) product. The benefit of using a topical product over an oral form is that the topical form avoids the ‘first pass’ effect of metabolism through the liver, and therefore the dosage is lower (than oral forms).
Progestins such as Provera® are not natural progesterone. Provera® is a type of chemical that bears some similarity to natural progesterone but is chemically distinct. Natural progesterone is believed to be a safer option for women seeking hormone restoration.
There are studies showing increased risks of certain cancers in response to estrogen drug therapy and higher estrogen levels.102,103 Many of these studies used Premarin® or Prempro®, drugs that many women today avoid because of the lethal risks that were revealed. In response to concerns about estrogen and cancer, Life Extension® compiled an article titled “Is Fear of Cancer a Reason to Be Deprived of Hormones?” This article discusses healthy dietary and lifestyle alterations that have been shown to substantially reduce the risk of estrogen-induced cancers. Anyone contemplating estrogen replacement therapy should review this article at www.lef.org/estrogen Refer to the sidebar on the page 3 (How To Prescribe Bioidentical Estrogen Drugs to Aging Females) for specific information prescribing bioidentical female hormones and blood levels to strive for.
Some obese women have elevated testosterone levels.104,105 Studies show that certain subgroups of obese women (for example, obese women suffering from polycystic ovary syndrome [PCOS], characterized by excess visceral body fat, insulin resistance, and high levels of testosterone) can improve metabolic profiles, reduce visceral fat accumulation, and reduce testosterone levels with a combination of metformin and low-dose flutamide, a specific anti-androgen drug available by prescription.106,107 For example, a study in 40 obese women suffering from elevated testosterone levels and insulin resistance treated with metformin (850 mg twice daily) and flutamide (250 mg twice daily) showed decreased visceral fat, total cholesterol, and low-density lipoprotein (LDL), and reduced excess testosterone concentrations.108 If a blood test reveals excess free testosterone in the presence of excess visceral fat in a woman, consider prescribing 250 mg of flutamide twice daily with concomitant metformin treatment in addition to a low-calorie diet and physical exercise.