Breakthrough: Skin Cells Used to Build Heart Muscle

Reuters is report the following

Breakthrough: Skin Cells Used to Build Heart Muscle

Wednesday, May 23, 2012 7:06 AM

Scientists have for the first time succeeded in taking skin cells from patients with heart failure and transforming them into healthy, beating heart tissue that could one day be used to treat the condition.

The researchers, based in Haifa, Israel, said there were still many years of testing and refining ahead. But the results meant they might eventually be able to reprogram patients’ cells to repair their own damaged hearts.

“We have shown that it’s possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young the equivalent to the stage of his heart cells when he was just born,” said Lior Gepstein from the Technion-Israel Institute of Technology, who led the work.

The researchers, whose study was published in the European Heart Journal on Wednesday, said clinical trials of the technique could begin within 10 years.

Heart failure is a debilitating condition in which the heart is unable to pump enough blood around the body. It has become more prevalent in recent decades as advances in medical science mean many more people survive heart attacks.

At the moment, people with severe heart failure have to rely on mechanical devices or hope for a transplant.

Researchers have been studying stem cells from various sources for more than a decade, hoping to capitalize on their ability to transform into a wide variety of other kinds of cells to treat a range of health conditions.

There are two main forms of stem cells embryonic stem cells, which are harvested from embryos, and reprogrammed “human induced pluripotent stem cells” (hiPSCs), often originally from skin or blood.

Tissues Beating Together

Gepstein’s team took skin cells from two men with heart failure aged 51 and 61 and transformed them by adding three genes and then a small molecule called valproic acid to the cell nucleus.

They found that the resulting hiPSCs were able to differentiate to become heart muscle cells, or cardiomyocytes, just as effectively as hiPSCs that had been developed from healthy, young volunteers who acted as controls for the study.

The team was then able to make the cardiomyocytes develop into heart muscle tissue, which they grew in a laboratory dish together with existing cardiac tissue.

Within 24 to 48 hours the two types of tissue were beating together, they said.

In a final step of the study, the new tissue was transplanted into healthy rat hearts and the researchers found it began to establish connections with cells in the host tissue.

“We hope that hiPSCs derived cardiomyocytes will not be rejected following transplantation into the same patients from which they were derived,” Gepstein said. “Whether this will be the case or not is the focus of active investigation.”

Experts in stem cell and cardiac medicine who were not involved in Gepstein’s work praised it but also said there was a lot to do before it had a chance of becoming an effective treatment.

“This is an interesting paper, but very early and it’s really important for patients that the promise of such a technique is not over-sold,” said John Martin, a professor of cardiovascular medicine at University College London.

“The chances of translation are slim, and if it does work it would take around 15 years to come to clinic.”

Nicholas Mills, a consultant cardiologist at Edinburgh University, said the technology needs to be refined before it could be used for patients with heart failure, but added: “These findings are encouraging and take us a step closer to … identifying an effective means of repairing the heart.”

© 2012 Reuters. All rights reserved.

Galantamine May Help You Remain a Smart Cookie

Galantamine May Help You
Remain a Smart Cookie
3-Year study confirms its efficacy—and early intervention
for long-term prevention makes sense
By Will Block (Life Enhancement, http://www.life-enhancement.com)

There’s a birthday card that says, “You’re not really getting old until you start having trouble making sense of simple things . . . [and inside] . . . isn’t it?” We laugh, but perhaps with a twinge of apprehension. Getting old isn’t all that funny, especially if the body outlasts the mind. No one wants to contemplate the gradual erosion of memory and other cognitive functions that are such a characteristic (but largely unnecessary) part of the aging process. When you’ve seen it happen in others—perhaps a friend or a loved one—it makes you all the more determined to hang on to your own mental faculties for dear life.

But how do you do that? The mind is an abstraction, a will-o’-the-wisp, not something you can lasso and put in a box for safekeeping (besides, we’re always being admonished to “think outside the box”). You must use the very faculties you wish to protect to figure out what to do. Your thinking might go something like this: There are no certainties when it comes to protecting the mind. However, there are probabilities, based on current scientific knowledge, that I could act upon to maximize my chances of success. But where can I find that knowledge? . . . Hey, I’m reading this article, aren’t I? That’s a good start.

Supplementation Can Help Your Brain

So we’ve established that you’re a smart cookie, and you want to stay that way. Your mission is to take decisive action on your own behalf so as to preserve and protect the cognitive functions that are allowing you to read and understand these words, and that will allow you to remember, if not the words, then the central idea they convey, namely:

It is possible, through intelligent nutritional supplementation, to augment the benefits to your brain of a good diet and regular exercise, so as to enhance the probability that your brain will remain healthy and sharp for the rest of your life.

You Have a Cornucopia of Choices

If you could take but one supplement for your overall well-being, it should be the best multivitamin, multimineral, multiantioxidant formulation you can find. Those are the supplement building blocks not only for a healthy body, but also for a lucid mind. There is abundant scientific evidence of the beneficial effects on brain function (and, of course, heart function and other functions) of many of these vitally important compounds—especially vitamins E and C—and it’s hard to fathom why anyone would willingly forego the myriad health advantages they offer. (For more on this subject, see the article on page 21 of this issue.)

Thus, taking a “multi-VMA” to lay the groundwork for a healthy brain is a no-brainer, so to speak. But then what? Suddenly the options are varied, and the choices bewildering. Many different supplements have been shown to enhance memory or other aspects of cognitive function in one way or another, and all have something to recommend them.

The patients’ decline was delayed
by one full year compared with
the controls. By the end of the
36-month period, they had
gained about 18 months worth of
preservation of cognitive function
relative to the prediction.

There are, e.g., the natural amine choline and its derivative CDP-choline; the amino acids phenylalanine, arginine, acetyl-L-carnitine, and creatine; the lipids phosphatidylserine and phosphatidylcholine; the omega-3 fatty acids DHA and EPA; the phytonutrients vinpocetine, huperzine A, and resveratrol; and herbal extracts of Ginkgo biloba, Bacopa monniera, and Melissa officinalis (lemon balm).

Galantamine—a Supplement—Stands Apart

All these supplements have been discussed in past issues of Life Enhancement (the omega-3 fatty acids are discussed again in this issue—see page 29), and all are worthy of your serious consideration. This article, however, is about one supplement for cognitive enhancement—galantamine—that stands apart from the rest, for one compelling reason: it has been clinically proven to be a safe and effective treatment in mild to moderate cases of Alzheimer’s disease. Galantamine is, in fact, the active ingredient in an FDA-approved prescription medication (Reminyl®) for that purpose.

I know what you’re thinking: how can a supplement be a prescription drug? Aren’t they mutually exclusive? Actually, no. Before being declared a “drug” in 2001, galantamine had been sold as a nutritional supplement for many years, and its use as a folk remedy is believed to go back several thousand years. Because of its documented history of use as a supplement, it is still a supplement, and it can be obtained as such without prescription (at far lower cost than as a prescription drug) by anyone.

That’s the good news. The bad news is . . . uh . . . correction, there is no bad news about galantamine—but there is more good news! There is now clinical evidence that galantamine’s efficacy in preserving and protecting cognitive function against the ravages of Alzheimer’s disease extends for a much longer period (at least 3 years) than had previously been demonstrated.1 This is important, because a major problem with most of the other anti-Alzheimer’s agents is that they tend to lose their efficacy within 6 to 12 months.

Galantamine Slows Rate of Cognitive Decline

Obviously, the longer a therapeutic agent can remain effective in use, the better it is for the patient. Most of the clinical trials with galantamine conducted thus far have lasted one year or less, but even within that limited interval, galantamine’s superior efficacy has been evident.2 While other agents tend only to slow the patients’ rate of decline, galantamine typically halts it completely for several months, and in some cases even reverses it for a few months. Ultimately, however, the decline is inevitable, as is the patient’s end—there is no cure for this terrible disease.* The objective, therefore, is to retard its progress as strongly as possible for as long as possible.

*A recent study indicates that life expectancy in people suffering from dementia is much shorter than had previously been believed: 3.3 years after onset of the disease, rather than the previous estimate of 5 to 9.3 years.3

That’s where galantamine shines. This remarkable compound (which is extracted from certain flowers, such as the snowdrop, daffodil, and spider lily) has a unique, dual mode of action in the brain, the net effect of which is to maintain cholinergic function (those aspects of brain activity, including memory and other cognitive functions, that depend on acetylcholine as the neurotransmitter). Galantamine does this more effectively than any other anti-Alzheimer’s agent.

Galantamine Is Tested for 36 Months

Dramatic new evidence of galantamine’s ability is found in a 36-month study published by researchers from the University of Washington, Johnson & Johnson, and the J & J subsidiary Janssen Pharmaceutica Products (which markets Reminyl).1 They investigated the long-term safety and efficacy of galantamine in 194 patients (average age 76) with mild to moderate Alzheimer’s disease (AD).

The patients in the new study, who had been enrolled in either of two randomized, double-blind, placebo-controlled trials of galantamine for a 12-month period, subsequently received an additional 24 months of treatment (24 mg/day) on an “open label” basis, i.e., the trial was not blinded—they were all receiving galantamine during this extension phase, and they all knew it. (With serious diseases, ethical considerations preclude the long-term use of placebo—it’s not fair to the patients.)

Making Dumb Bunnies Smarter

Bunnies (OK, rabbits, if you must be technical) sure are cute, but let’s face it, they’re not exactly known for their high IQs. Heck, when you’re that endearing, you don’t have to be smart. Nonetheless, a tiny infusion of brains wouldn’t hurt. That is what two teams of researchers at American universities tried recently, in the form of galantamine.1,2 Using both young and old rabbits in similar studies, they administered galantamine by injection, at dosages roughly 10 times greater than those typically used by humans.

The purpose was to see whether the rabbits’ capacity for attention and learning could be improved through the biochemical actions of galantamine on their brains (these actions are the same in rabbits as in humans). The experiments involved the use of an eyeblink technique for Pavlovian conditioned responses to certain stimuli. The results: the galantamine-treated animals did indeed show significantly improved performance compared with age-matched controls.

So in effect, those dumb bunnies—whether old or young!—got a little smarter, thanks to galantamine. And if galantamine can do that for them, perhaps it could do the same for somewhat higher organisms as well.

Simon BB, Knuckley B, Powell DA. Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits. Learn Mem 2004;11:116-22.
Weible AP, Oh MM, Lee G, Disterhoft JF. Galantamine facilitates acquisition of hippocampus-dependent trace eyeblink conditioning in aged rabbits. Learn Mem 2004;11:108-15.

The researchers measured the patients’ performance on standardized tests of cognitive function and compared them with: (1) the test scores of a clinically and demographically similar control group of AD patients who had received placebo for 12 months in a previous clinical trial, and (2) the mathematically predicted rate of cognitive decline in untreated AD patients over a 36-month period, based on voluminous existing data.

It’s never too early to be
concerned about the possibility of
serious cognitive decline, even for
those of middle age.

Galantamine Buys 18 Months of Time

The results were gratifying: whereas the condition of the controls declined steadily from day one, that of the galantamine-treated patients actually improved during the first 3 months and only then began to decline slowly. The patients returned to their cognitive starting point 9 months later (i.e., 12 months from the outset of the trial), and their decline continued unabated—having been delayed, however, by one full year compared with the controls. By the end of the 36-month period, the extent of their cognitive decline was only half that of the mathematically predicted amount, and they had gained about 18 months worth of preservation of cognitive function relative to the prediction. In the authors’ words:

These data support the hypothesis that continuous galantamine treatment slows the rate of cognitive decline in AD patients for up to 3 years. . . . Together with findings from other studies, these results strengthen the argument for early diagnosis and treatment . . . .

It’s Never Too Early to Protect Your Brain

Surely early diagnosis and treatment make sense—but how early is early? One could argue that it’s never too early to be concerned about the possibility of serious cognitive decline somewhere down the road—it could be years in the future, or it could be just around the corner, even for those of middle age. Interpreting the symptoms can be tricky, though. After all, a certain amount of benign forgetfulness is a normal aspect of the aging process. No big deal, right?

Well, maybe, maybe not. Over a period of time, something more sinister can develop: the clinically defined condition called mild cognitive impairment (MCI), which exceeds normal forgetfulness but falls short of being outright dementia. MCI is a kind of “Alzheimer’s lite” that usually (but not always) leads to the real thing.* Just as there is no well-defined boundary between normal, age-related forgetfulness and MCI, there is none between MCI and AD. The transitions, if they occur, are seamless. By the time anyone notices that something is wrong, much damage may already have been done.

*By one estimate, more than 80% of patients with MCI develop AD within 10 years, at a rate of about 10–15% of patients per year.4

Because the symptoms of MCI are so similar to those of AD (just less severe), it seems reasonable to suppose that anything that retarded the progression of AD would do the same for MCI—and probably more effectively, since the cognitive deficits in MCI are smaller to begin with. That argues in favor of using galantamine early, as a kind of insurance policy against what could happen.

How to Be Smart

Well, you’ve read this far, so you must have been interested (thanks!). If you want more information, there’s a lot of it out there, in back issues of Life Enhancement (also available on our Web site) and elsewhere. Whether you’re man or woman, young or not so young, you’ll truly be a smart cookie if you decide to take appropriate action to help preserve and protect your precious cognitive functions from time’s erosion. Think of it as a way to help supplement the quality, and perhaps even the quantity, of your life.

References

Raskind MA, Peskind ER, Truyen L, Kershaw P, Damaraju CRV. The cognitive benefits of galantamine are sustained for at least 36 months. Arch Neurol 2004;61:252-6.
Olin J, Schneider L. Galantamine for Alzheimer’s disease (Cochrane review). In The Cochrane Library, Issue 2, 2001. Oxford: Update Software.
Wolfson C, Wolfson DB, Asgharian M, M’Lan CE, Østbye T, Rockwood K, Hogan DB. A reevaluation of the duration of survival after the onset of dementia. N Engl J Med 2001 Apr 12;344(15):1111-6.
Peripheral and Central Nervous System Drugs Advisory Committee of the U.S. Food and Drug Administration, as reported by Reuters Health, March 14, 2001.

SUPERHORMONES FOR ANTIAGING

You will find below a list broken down by what they assist in Antiaging.

 

DHEA

Increases energy
Improves mood
Enhances immune function
May help protect against cancer
Increases libido
Reduces stress
Increases fat loss (in some people)

Take early in the day.

Not recommended for people under age 30.

Men: 25-50 mg/day

Women: 10-50 mg/day

Pregnenolone

Improves memory
Improves mood
Increases energy
Helps relieve joint pain
Enhances mental clarity

Take early in the day

Dosage:10-50 mg/day; 100-400 mg/day for inflammation due to rheumatoid arthritis and other autoimmune diseases.*

Melatonin

Restores normal sleep pattern
Improves mood
Regulates other hormones
Enhances immune function
Yields antioxidant effects
Extends life span (in animal studies)
Helps with jet lag

Take before bedtime.

Dosage: 0.5-3 mg

(Endocrine Glandular Support with Thyroid)

Supports functions of the endocrine glands including: thyroid, pituitary, hypothalamus, adrenal, and sex glands.

Take one serving per day with breakfast

The Melatonin Miracle, Regelson, Pierpoli, Colman
Melatonin: Nature’s Sleeping Pill, Sahelian
DHEA: A Practical Guide, Sahelian
Pregnenolone: The Feel-Good Hormone, Sahelian
The Superhormone Promise, Regelson, Colman

Recommended Tests

Saliva test kit for hormone levels

*At levels above 50 mg per day, healthcare consultation advisable

CARDIOVASCULAR FUNCTION

Garlic-EDTA

Helps remove calcium deposits in arteries
Helps lower cholesterol
Improves blood flow
Helps prevent clotting

Use with multimineral/multivitamin formulation

Vitamin E

Proven antioxidant
Prevents lipid peroxidation of LDL-cholesterol
Reduces risk of heart attacks

Coenzyme Q10

Enhances heart muscle function and production of energy
Acts as a powerful antioxidant
Reduces lipid peroxidation

Acetyl-L-Carnitine

Reduces cholesterol and blood sugar

Lipoic Acid

Helps reduce cholesterol
Provides antioxidant protection for LDL cholesterol (reduces lipid peroxidation)

DHEA

Helps lower cholesterol levels
Helps thin the blood to prevent clotting

Inositol Hexanicotinate (IHN)

Non-flush niacin
Helps lower both cholesterol and triglycerides

Ginkgo Biloba

Inhibits platelet activating factor (PAF)
Enhances blood flow

Multivitamin/multimineral formulation
High in antioxidants
High in minerals necessary for optimal cardiac function

Green Tea Extract

Antiplatelet activity
Reduces cholesterol
May help lower blood pressure

Recommended Reading

The Chelation Answer, Gordon

GENERAL NUTRITION

BioEnhanceTM or any good Multi. GNC Men’s Formula etc

Multivitamin, multimineral antioxidant formulation supplement for health maintenance and protection

Green Tea Extract

Helps provide cancer protection
Provides antioxidant benefits
Enhances antibacterial activity

Coenzyme Q10

Enhances production of cellular energy
Helps protect muscle function including the heart
Powerful antioxidant action

Personal Radical Shield

Mulivitamin, multimineral, antioxidant formulation

Recommended Reading

Life Extension: A Practical Scientific Approach, Pearson & Shaw

MEMORY FUNCTION

Pregnenolone

100x memory improvement in animal studies
May improve general cognitive performance
Raises other “steroid” hormone levels

DHEA

Helps stimulate neuron growth
Exerts profound effects on long-term memory in animal and human studies

Phosphatidylserine

Helps improve memory in those with documented memory loss
Helps keep brain cell membranes flexible and functioning
Increases synthesis of acetyl-choline (ACh), an important neurotransmitter

Acetyl-L-Carnitine

Prolongs attention span
Improves memory & other cognitive functions
Improves inter-hemispheric communication in the brain and thus enhances creativity
Has been studied for effects on Alzheimer’s disease

Ginkgo Biloba

Improves blood flow in the brain, thereby helping to enhance memory
Supplies more O2

Memory Upgrade

Choline + vitamin B-5 increase ACh levels, an important neurotransmitter
Helps improve memory

DMAE see earlier post on this subject

Helps maximize mental ability
Helps prevent memory loss
Helps diminish lipofuscin buildup

Recommended Reading

Smart Drugs & Nutrients, Dean & Morgenthaler
Smart Drugs II: The Next Generation, Dean, Morgenthaler, & Fowkes
Life Extension: A Practical Scientific Approach, Pearson & Shaw

Recommended Tests

ThinkFast ProTM computer software to test the effects of smart drugs & nutrients

SEXUAL FUNCTION

Yohimbe

Acts as natural aphrodisiac
Helps increase libido
Helps promote fuller erections

Please read precautions on fact sheets for the supplement

Contains arginine + ginkgo biloba
Increases nitric oxide (NO) production which improves blood flow to genital organs

Please read precautions on fact sheet

Memory Upgrade

Increases ACh levels in the brain, which conrol penile arteries & spongy tissue
Helps improve muscle tone for enhanced energy, stamina

DHEA

Helps increase necessary levels of sex hormones
Increases libido for some people

Melatonin

Increases libido for some people

Recommended Reading

Better Sex Through Chemistry, Morgenthaler & Joy

Recommended Tests

Saliva test kits for testosterone and DHEA levels

Weight Maintenace helps Prevent Testosterone Loss

Healthy Weight Maintenance
Inhibits Testosterone Loss
Becoming obese produces a decline in the male sex
hormone equivalent to about 10 years’ worth of aging

By Will Block

In poking fun at his own kind, the great English poet was referring to what women have long thought was a certain, uh, immaturity of behavior in the stronger sex. Oh, the stories they could tell . . . but let’s leave that sensitive topic alone, shall we? Instead, let’s dwell on Dryden’s reference to size, a topic that men are also sensitive about. Naturally, men grow larger than women, but the real trouble begins when they grow larger than themselves, in a manner of speaking.

Being overweight is no joking matter if you stop and think about its myriad health consequences—especially if the overweight condition tends toward outright obesity. Looming large on the list of liabilities are increased risks for chronic degenerative diseases, such as cardiovascular disease, neurodegenerative disease, cancer, osteoarthritis, and, of course, type 2 diabetes, which is almost entirely preventable by maintaining a healthy weight.

There are other unfortunate consequences as well, such as social stigma, job discrimination, and a diminished capacity for physical activities (sports, recreational pursuits, playing active games with one’s children or grandchildren, etc.). None of this is to say that an overweight or obese person can’t live a happy, productive, and fulfilling life. Many—perhaps most—can and do. It’s just that their road toward those universal aspirations is steeper and bumpier than for others. It is also, unfortunately, shorter: statistics show that the overweight or obese will die younger than their leaner counterparts.

The above problems apply equally to men and women. But there is a special consequence of being overweight that applies to men only, and it strikes at the heart of what it means to be a man. Perhaps heart is not exactly the right organ to cite, because we’re talking about testosterone, the giver of all things masculine in a man’s physical and psychological makeup. Almost all of a man’s testosterone comes from his testicles. It’s responsible for his physical features, his virility, his boldness, his competitiveness, his aggressiveness (in the best and worst senses of that term), and almost everything else that distinguishes him, to one degree or another, from the fairer, kinder, gentler sex.

(It’s worth noting that men don’t have a monopoly on testosterone, any more than women have a monopoly on estrogen: just as men have some estrogen in their systems, women have some testosterone in theirs, and it’s largely responsible for their sex drive.)

Low Testosterone Is a Health Risk

It’s a fact of life that both men and women experience an inexorable decline in sex hormones with age. Women’s decline is precipitous, at menopause, whereas men’s is a gradual, ongoing process throughout middle age and beyond. But here are two intriguing questions: (1) Does declining testosterone contribute to poor health? (2) More importantly, perhaps, do poor health and adverse lifestyle factors contribute to the decline in testosterone?

“These results suggest the possibility that
age-related hormone decline may be
decelerated through the management of
health and lifestyle factors.”

The answer to the first question has been known for a long time: it’s yes. The most obvious example of the erosion of good health to which declining testosterone levels contribute is impaired sexual function, but there are others, including type 2 diabetes and loss of muscle mass and bone mass. This should provide a strong incentive to men to try to maintain healthy testosterone levels with advancing age. One way to do that is to stay as healthy as possible, because the answer to the second question is also, apparently, yes.

How to Tell Healthy Men from Unhealthy

Scientists at the New England Research Institutes in Watertown, Massachusetts, sought to establish the relative contributions of aging, health, and lifestyle factors to changes in testosterone levels in community-dwelling (i.e., not institutionalized) older men from the greater Boston area.1 To this end, they analyzed data on 1667 randomly selected men, aged 40 to 70 at baseline, who were enrolled in the Massachusetts Male Aging Study, a long-term epidemiological study of men’s health and endocrine function. By large margins, the men were: married, employed, white, and high school graduates.

The men’s testosterone levels and a variety of other factors, including weight, were measured at the beginning and the end of the study period, which lasted about 15 years, on average, and once in between, after about 9 years. Their medical histories were taken, of course, along with information on their health-related lifestyle choices (e.g., exercise, smoking, and drinking); dietary information was obtained through standardized questionnaires. They were also evaluated for symptoms of depression, and a comprehensive inventory of their medications was taken.

Men who were taking testosterone preparations were excluded from the study, for obvious reasons, as were men who had prostate cancer, because a common treatment for that disease is a type of hormone therapy that strongly suppresses testosterone levels.*
A man was considered: obese if his body mass index (BMI) was 30 or greater; sedentary if his daily energy expenditure through physical activity did not exceed 200 calories; a heavy drinker if he consumed more than six drinks daily; and depressed if he scored greater than a certain number on a standardized test of depressive symptoms. Men who had no chronic illness, did not smoke, did not drink heavily, were not obese, and used fewer than six medications were considered to be healthy.

Obesity Is a Risk Factor for Testosterone Loss

Over the 15-year period, many of the men were lost to follow-up—only 584 remained for whom the requisite data could be collected. After controlling for the different ages at baseline of the men in that group, the researchers found a 14.5% decline in total testosterone per decade of aging and a 27.0% per decade decline in free testosterone. Free testosterone is the most important component of total testosterone; the rest is not free—it’s chemically bound to proteins in the blood and has varying degrees of bioavailability. With age, free testosterone declines not only absolutely but also relatively, as a percentage of total testosterone—a double whammy.

When these trends were evaluated only in the men who were deemed healthy throughout the study period, the declines in total testosterone and free testosterone were significantly less severe: 10.5% per decade and 22.8% per decade, respectively. This suggested that a substantial proportion of testosterone loss was due to health- and lifestyle-related factors. Obesity, in particular, was identified as a major culprit. Analysis of the data indicated that a 4-to-5-point increase in BMI, if it crossed the obesity threshold value of 30, was associated with a loss of total testosterone comparable to that of about 10 years of aging; the loss of free testosterone was much less, however, corresponding to about 3 years of aging.

Other Health and Lifestyle Factors Also Pose Risks

Another major loss of testosterone (about 10 years’ worth for both total testosterone and free testosterone) was brought about by the death of one’s wife. Less severe, but still substantial, was the loss of testosterone (about 5 to 6 years’ worth for both forms) caused by type 2 diabetes. (See the sidebar for more on this.) Additional loss factors were hypertension and taking large numbers of medications. Smoking, on the other hand, raised testosterone levels significantly. If you are a smoker (although it’s hard to imagine that any reader of Life Enhancement would be), do not take this as an excuse to continue the habit. Smoking may help keep your testosterone levels up, but it will also kill you. It’s really not worth it.

Does Low Testosterone Lead to Diabetes?

Obesity, the primary risk factor for type 2 diabetes, is associated with significant declines in testosterone levels, as we’ve seen in the accompanying article. And diabetes, independently of obesity, is also associated with declining testosterone levels. But is the converse true—are low testosterone levels a causal factor in diabetes, independently of obesity?

The answer appears to be yes, based on data from a large epidemiological study, NHANES III (Third National Health and Nutrition Examination Survey), in which researchers evaluated the relationship between testosterone levels and diabetes in 1413 American men aged 20 or older.1 Dividing this group of men, 101 of whom had diabetes, into tertiles (thirds) based on their free testosterone levels, the researchers found that those in the lowest tertile were four times as likely to have diabetes as those in the highest tertile, whether they were obese or not. The correlation held even when all men with abnormally low testosterone levels were excluded from the data analysis, indicating that the effect was not caused primarily by those men. (Interestingly, no correlation with diabetes was seen for total testosterone levels.)

The authors concluded that men whose free testosterone levels are low but still within the normal range are at increased risk for diabetes, whether they’re obese or not, because testosterone and the other male sex hormones appear to influence glucose metabolism and the onset of insulin resistance, the precursor to diabetes.

Reference

1. Selvin E, Feinleib M, Zhang L, Rohrmann S, Rifai N, Nelson WG, Dobs A, Basaria S, Golden SH, Platz EA. Androgens and diabetes in men. Results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care 2007;30:234-8.

In evaluating the relative contributions of aging, health, and lifestyle factors in testosterone loss, the authors concluded,1

. . . although aging effects predominate overall, health and lifestyle outstrip aging effects in a substantial number of subjects. . . . The results presented here suggest that although hormone declines appear to be an integral part of the aging process, rapid declines need not be dismissed as inevitable. . . . These results suggest the possibility that age-related hormone decline may be decelerated through the management of health and lifestyle factors.

How to Lose Weight

All the advice in all the books on weight loss can be distilled into one simple precept: to lose weight, you must burn more calories than you consume, or consume fewer calories than you burn. Period. There are many ways to accomplish this objective, but they all boil down to the twin pillars of good health: diet and exercise. Without significant intervention in one arena or the other (or both), weight loss is impossible.

Exercise is a no-brainer: any kind of physical activity burns calories, so you simply can’t go wrong there. Diet, by contrast, is complicated, because the options are limitless, and the consequences can go either way. Although “diet” usually means eating less, it can also mean eating smart, resulting in one or more of three important consequences: (1) an intake of fewer calories, (2) a reduced absorption of the calories taken in, and (3) a more efficient burning off of the calories absorbed, through internal biochemical processes. If you’re really smart, you can accomplish all this while satisfying your hunger with good foods (and beverages) that you enjoy.

How to Eat Smart

One key to smart eating is to exert glycemic control by lowering the average glycemic index of your meals. You can do this by selecting low-glycemic-index foods and augmenting them with naturally beta-glucan-rich barley, as well as by using resistant starch instead of regular starch, and erythritol instead of sugar. Another way to shift your shape is to drink certain polyphenol-rich teas that inhibit fat synthesis and promote thermogenesis. Finally, you can enhance glucose metabolism and weight loss via a number of dietary supplements, such as 3-acetyl-7-oxo-DHEA, chromium polynicotinate, resveratrol, grape seed extract, and purple corn color.

© Copyright 2011 Life Enhancement Products, Inc. All Rights Reserved.

The Re-Discovered Spice Turmeric

Turmeric Is “The Spice of Life”
An old kid on the block demonstrates new capabilities in combating Alzheimer’s disease
By Will Block

Some colors, like the late Rodney Dangerfield, don’t get no respect. Take yellow, which has somehow acquired a bad reputation in some quarters. Yellow journalism is the pits (are you listening, C-BS?). Being yellow-bellied or having a yellow stripe down your back is shameful, although perhaps not as bad as having a yellow sheet (for you innocents, that’s slang for a criminal record). Either way, you surely wouldn’t want to come down with yellow fever or develop the blurry, yellowed vision characteristic of cataracts.

On the other hand, many good things are yellow, such as the sun, and daffodils and canaries and bananas. And gold. And blondes! Yellow highlighters are nifty, the Yellow Pages are useful, and yellow tennis balls are fun, especially if you have a yellow Labrador retriever who plays tennis. Yellowknife is a great town (it’s the capital of Canada’s Northwest Territories—remember that in case you ever get on Jeopardy). And yellow mustard is yummy—it gets its color from turmeric. Which is very yellow.

How Much Curry Do You Eat?

If you lived in India or in some other countries of Southeast Asia, you would probably eat turmeric (Curcuma longa) almost every day, because it’s one of the principal spices found in the curries that are such an important part of the diet in that part of the world. (Turmeric is also a well-known remedy in the ancient Indian tradition of Ayurvedic medicine.) You might also become part of an interesting statistic: the elderly (aged 70–79) residents of rural India, who eat large amounts of curry, appear to have the lowest incidence of Alzheimer’s disease in the world—significantly lower than that of Americans.

Does that prove that curry helps prevent Alzheimer’s? No, but there is good reason to think that it might, mainly because of the turmeric it contains. This yellow spice, a member of the ginger family, contains a class of polyphenolic compounds called curcuminoids. Research on these compounds has focused primarily on the one for which the group is named: curcumin, which is known to be a very potent antioxidant (as are several other curcuminoids as well). Curcumin is also a potent anti-inflammatory agent—it’s widely used in the treatment of arthritis—and for that reason it is described as an NSAID, a nonsteroidal anti-inflammatory drug (it’s a “drug” only in the same sense in which countless other nonprescription remedies sold in the drugstore are called drugs).

These two well-established properties of curcumin—antioxidant and anti-inflammatory—are believed to account in large measure for its demonstrated ability to help prevent the neurodegenerative changes seen in Alzheimer’s disease and Parkinson’s disease.* Particularly noteworthy is curcumin’s ability to inhibit both the formation of amyloid-beta (also called beta-amyloid) and the neurotoxicity of amyloid-beta that has already been formed. Amyloid-beta, a protein, is the principal constituent of senile plaque, the yellowish (there’s that color again!) gunk that destroys the brain cells of Alzheimer’s victims.

It’s worth noting that curcumin is also believed to have significant anticholesterol and antitumor effects, which may or may not be related to its antioxidant and anti-inflammatory effects. And here’s an odd fact: although curcumin is bright yellow, it has no flavor—turmeric’s flavor comes from other components.

It turns out, though, that there may be additional ways in which curcumin and its chemical cousins help protect our brains from the ravages of dementia. For example, in addition to being a direct antioxidant, i.e., a molecule that can neutralize harmful free radicals through direct chemical reaction, it turns out that curcumin may also be an indirect antioxidant by stimulating other chemical processes that tend to reduce oxidative stress. One such process, discussed in a recent review paper, is the generation of heat-shock proteins. These proteins are so named because our bodies produce larger-than-normal amounts of them in response to excessive heat, which the exquisitely tuned biochemical machinery of our cells cannot long tolerate without suffering irreversible damage. (Heat-shock proteins, of which there are many varieties, are also called stress proteins.)

The primary role of the ubiquitous, tough, and amazingly versatile heat-shock proteins is to try to control and repair the damage done to other proteins (including countless different kinds of enzymes that are vital for all life processes), which are notoriously vulnerable to the effects of heat and other forms of stress. Think of the heat-shock proteins as army medics, rushing onto the battlefield to tend to the wounded and save as many as they can. They do this not just when the “enemy” is heat, but also when it is various other forms of attack, such as infection, inflammation, oxidative stress, exposure to environmental toxins or cytotoxic drugs (drugs that are toxic to cells), tissue trauma, oxygen deprivation, or other processes that threaten to damage or even kill the cells. Such processes can be life-threatening, depending on which cells are affected.

Curcumin Induces Heat-Shock Proteins

This generalized stress response of the human body, like various other stress responses, has a hidden benefit beyond the immediate results of the intervention: it results in a certain amount of stress tolerance by conditioning us to cope with the daily barrage of biochemical “insults” upon our cells. Although prolonged exposure to severe stress will inevitably lead to cell damage or death, it is believed that lower, more benign levels of stress are actually good for us by keeping the biochemical machinery of cell repair in good working order. The net result is a cytoprotective effect against stress-induced molecular damage, such as that which leads to the formation of two of the hallmarks of Alzheimer’s disease: senile plaque (amyloid-beta) and its evil twin, neurofibrillary tangles.

In the brains of Alzheimer’s victims, researchers have found significant associations between plaques and tangles and the presence of a particular heat-shock protein called heme oxygenase-1 (HO-1).3 This enzyme (all enzymes are proteins, but not all proteins are enzymes) is apparently released in an effort to control a particular aspect of the damage associated with neurodegeneration, and its action results in the formation of antioxidant molecules called biliverdin and bilirubin. We know that HO-1 is triggered by the presence of free radicals as well as by depletion of glutathione, the body’s most important antioxidant. Thus it has become a matter of interest to determine whether any nutritional supplements might also induce the production of HO-1, for an added boost to the cytoprotective effect afforded by this enzyme.

You can see it coming, can’t you? Yup, it turns out that curcumin is a good candidate for this role, because studies have shown that it is a potent inducer of HO-1 in vascular endothelial cells (the cells that form the inside lining of blood vessels). Other evidence suggests that curcumin probably has this effect in the central nervous system as well, and it may therefore be able to help forestall the development of Alzheimer’s disease.

Metal Ions, Good! Bad! (It Depends)

Yet another way in which curcumin and the related curcuminoids may help protect our brains is through the process of metal chelation (see the sidebar), in which curcumin reduces the levels of certain metal ions by chemically scavenging them.* Metal ions of many kinds—mostly light metals, i.e., those of low atomic weight—are ubiquitous in the human body. (Fortunately, this is not true of heavy metals, most of which are toxic.) At one extreme of the “freedom scale,” the metal ions are dissolved, as free ions, in all of our bodily fluids, including the aqueous interiors of our cells; at the other extreme, they are chemically bound in large, complex molecules, such as metalloproteins (e.g., hemoglobin).

*A metal ion is a metal atom that has lost one or more of its electrons and thus carries a positive electric charge. Calcium atoms, e.g., characteristically lose two electrons and thus have a charge of +2. Iron ions can be either +2 or +3. In metal-containing chemical compounds, the metal atoms are always ionized.

How Does Chelation Work?

Claw. Quick—what does that make you think of? Chances are, you thought first of a lion or tiger, or maybe your own sweet little kitty. Or perhaps you thought of a bear (especially if you have a sweet tooth for pastries). If you like seafood, maybe you thought of lobster or crab—and now we’re getting somewhere (you’ll see in a moment). Unless you’re a terminally nerdy chemist, however, it’s a cinch that you didn’t think of a chelating agent, such as EDTA (a synthetic diamino acid) or curcumin (a polyphenolic alpha,beta-unsaturated diketone).

A chelating agent is a kind of molecular claw (the word comes from the Greek khele, claw), in which two similar groups of atoms within the same molecule, acting like tiny pincers, “grab” a metal ion by forming chemical bonds to it (think of a crab seizing and holding a prey item between its claws). When this occurs, the metal ion becomes a chemical link between the pincer atoms, and a stable, ringlike molecular structure is formed. In this example, the chelating agent is said to be bidentate, because the pincer action consists of two “teeth” (yes, the metaphor is hopelessly mixed, but that’s the way the terminology evolved). Many other chelating agents have more than two teeth; EDTA, e.g., has six, so it’s hexadentate and can grab a metal ion with six bonds coming from six different directions.

The secret to chelation is in the nature of the individual atoms that constitute the teeth, in the juxtaposition of these atoms within the larger molecular structure, and in their ability to form a special kind of bond, called a coordinate covalent bond, with the ions of certain metals. If all the requirements are met, then bingo—the metal ion is grabbed and “locked up” in the chelator’s clawlike embrace. The resulting molecular entity, called a coordination complex, is typically very stable and will not easily yield back the metal ion. Thus, if this complex is excreted in the natural course of things, the metal ion goes with it.

Coordination complexes formed from chelated metal ions are common in living organisms. Three examples are heme (the iron-containing nonprotein portion of the hemoglobin molecule), chlorophyll (the magnesium-containing green pigment that plays a central role in photosynthesis), and cyanocobalamin (vitamin B12, which contains a cobalt ion).

Metal ions are vital for many life processes (our hearts and brains, e.g., could not possibly function without them), but sometimes they can be harmful, as when calcium ions become incorporated into atherosclerotic plaque, a process called calcification

Another way in which metal ions can be harmful is when they catalyze unwanted chemical reactions, such as some of the oxidative reactions that are responsible for the formation of amyloid-beta in the brains of Alzheimer’s victims, or subsequent reactions that are responsible for the oxidative damage caused by amyloid-beta (it’s curious that oxidative stress is both a cause of, and an effect of, amyloid-beta). Certain metal ions, notably copper, iron, and zinc, are known to induce the aggregation of amyloid-beta molecules into senile plaques, and they are found in much greater concentrations in the vicinity of the plaques than elsewhere. (Bear in mind that senile plaque is totally different from atherosclerotic plaque. And then there’s dental plaque …)

Curcumin Chelates Alzheimer’s Metals

Intrigued by the “metal connection” and the fact that curcumin, a known anti-Alzheimer’s agent, is also known to be a chelating agent for some metals, researchers at the Chinese University of Hong Kong decided to investigate whether the former property might result, at least in part, from the latter property, i.e., they wanted to know whether curcumin could slow the development or progression of Alzheimer’s disease by chelating some of the metals believed to play a role in it.

In laboratory experiments, they established that curcumin is an effective chelator of copper and iron, but not of zinc. Actually, they used a turmeric extract of curcuminoids, consisting of a typical mixture: about 80% curcumin, 15% desmethoxycurcumin, and 5% bisdesmethoxycurcumin. The concentrations of the metals that could be chelated were lower than those in Alzheimer’s brains, and lower even than those in normal brains, which means that chelation of the actual (higher) concentrations would also occur. The ability of curcumin to be an effective chelator in a human being would then depend on whether its own concentration in brain tissue could be made high enough, through supplementation with turmeric, to provide effective chelation—and that remains an open question.

Turmeric Is Unburied Treasure

Not open to question, however, is the indisputable fact of turmeric’s beneficial effects, through its curcuminoid content, on human health. One of life’s best yellow things, turmeric (often called “the spice of life”) also serves as a reminder that the natural world holds medicinal treasures galore. Many have already been revealed to us through the wisdom of the ancients, but many others are surely still undiscovered—waiting, like buried gold, to be unearthed by us or by generations yet unborn. Let us hope that we will have the collective wisdom to preserve and protect our priceless natural heritage forever.

Studies on Aging

How Effective Are Aging Theories?
Of increasing interest is the study of specific compounds suggested by specific molecular aging theories to lengthen lifespans and improve age-related biomarkers in mice specifically bred for these purposes
By Will Block
The secret of genius is to carry the spirit of the child into
old age, which means never losing your enthusiasm.
— Aldous Huxley

B iological aging is a physiologic state in which there is a progressive decline of organ functions, accompanied by the development of age-related diseases that lead to premature death. Unfortunately, at the end of the first decade of the 21st century, a comprehensive knowledge of the aging process is still in the future. Even so, aging researchers agree that there is substantial variability in aging rates among different species and that genes are important. Findings, especially in the gene arena, are paving the way to greater understanding, and this in turn will lead to applications that determine their effectiveness.

Scientists have been able to show, through the use of model organisms, that alterations in specific genes can extend lifespan. This has been found to be true in a number of different species, including yeast, nematodes, fruit flies, and in mice, although less so as the complexity of the organisms increases. Gene manipulation is not currently feasible in most humans, although it soon may be.

In spite of the value of gene changes, even in relatively simple organisms, the mechanisms of aging remain to be clarified. In the higher model organisms such as in mice (with a lifespan of about three years), there have been few experiments that have directly tested the variety of mechanisms hypothesized to explain biological aging. Consequently, much of the evidence to date is correlative.

Specific Compounds to Counter Aging

Of great interest is the study of specific compounds suggested by specific molecular aging theories to lengthen lifespans and improve age-related biomarkers in mice specifically bred for these purposes. What works in mice is likely to work in humans. Nevertheless, age-related testing of mammals has frequently not been reproducible. This is due to the relatively small numbers of animals used in most studies, along with the difficulty of maintaining strict protocols. However, progress is now speeding up, due to a number of technological advances, including the running of parallel experiments at several internationally recognized centers. Before something can be tested, however, it is useful to have a theory of aging, of which many have been hypothesized. The most promising biological theories, with descriptions of the underlying mechanisms and findings to date, follow:

Free-Radical Theory

This is a big idea, and one of the most momentous. It holds that free radicals (unstable and highly reactive organic molecules, also called reactive oxygen species) create oxidative stress damage that gives rise to symptoms we recognize as aging. Denham Harmon, MD, PhD, formally proposed this theory in a 1956 paper.1 Since then, many thousands of papers have been published on this subject, including a summing up by Dr. Harman in 2009: “Origin and Evolution of the Free Radical Theory of Aging: a brief personal history, 1954–2009.”2

In “Origen and Evolution …,” Dr. Harman—who takes supplements and is now 94 years of age—states that:

[T]he basic chemical process underlying aging was first advanced as the free radical theory of aging (FRTA) [by himself] in 1954: the reaction of active free radicals, normally produced in the organisms, with cellular constituents initiates the changes associated with aging. The involvement of free radicals in aging is related to their key role in the origin and evolution of life.
The rate of oxygen radical generation
in tissues, rather than the antioxidant
capacity, is what limits lifespan.

As early as 1957, it was demonstrated that the mean lifespan of mice could be increased by antioxidants.3 Indeed, in one of the earliest studies, a 20 per cent increase in the half-survival time of a particular strain of mice was achieved by adding either the amino acid cysteine, 2-mercaptoethylamine, or 2,2’-diaminodiethyl disulfide to their diet. The half-survival time of the controls was about 8 months, whereas that of the animals treated as above was about 10 months.

Maximum Lifespan Potential

Regardless of this, in the many years that have passed, while antioxidants have been shown to have many healthful properties and may reduce the risk of cancer and atherosclerosis, most studies with antioxidants have not found antioxidants to determine maximum lifespan. A review published in 2002 proposed that this evidence strongly suggests that the rate of oxygen radical generation in tissues, rather than the antioxidant capacity, is what limits lifespan.4 In 16 studies on lifelong experimental modifications of antioxidant levels by supplements, drugs, or transgenic techniques, only four found some increase in maximum lifespan potential (MLSP), whereas in the other 12, MLSP did not change. Consequently, they suggested that while antioxidants can help to avoid premature death and increase mean lifespan, they are not likely to be effective in extending maximum lifespan.

The Rate of Free Radical Generation as Cause

However, the rate of the generation of free radicals by mitochondria has been identified by many researchers (including Dr. Denham Harman) as a probable major cause of aging. And in caloric restriction studies in rodents, researchers have found significant decreases of free radical generation by mitochondria without a consistent effect on antioxidant capacity. It is strongly suggested that a far better strategy for MLSP enhancement is to take supplements that are capable of reducing the generation of free radicals by mitochondria, rather than simply taking antioxidants that disarm excess free radicals.

Quercetin has been shown to reduce free radical havoc in mitochondria by uncoupling mitochondrial respiration,5 as has conjugated linoleic acid (CLA).6 It is interesting to note that olive oil as a food induced the highest uncoupling mechanisms in rat brown adipose tissue, as compared to sunflower oil, palm oil, and beef fat. This may be a significant factor in the health benefits of the “Mediterranean Diet.”

According to Durk Pearson & Sandy Shaw, “The bottom line is that this new perspective does not undermine the free radical theory of aging; in fact, it supports it. Taking the right amounts of the right antioxidants is still a good idea, but in the long run, it appears it will be necessary to reduce the free radicals created by mitochondria to increase maximum lifespan.”

Thyroid Hormones

After Reading this Article I thought it important for everyone to understand just what the Thyroid does and what can be done to correct the problem:

The Benefits of Whole
Natural Thyroid
When it comes to thyroid therapy, nature’s product beats synthetic drugs
By Dr. Edward R. Rosick

First appeared in the January 2004 issue

. . . the results [of whole thyroid], as a rule, are most astounding—unparalleled by anything in the whole of curative measures.

— Sir William Osler
Principles and Practice of Medicine, 1898

he pharmaceutical options available to doctors of today are certainly different from those available to their peers of just a hundred years ago. It seems that new drugs are being introduced every day, and most people assume that these new drugs are better than the old ones. But what if that’s not always true? Are some older medications being driven off the store shelves and the pages of medical journals for economic reasons rather than new scientific evidence? In the case of thyroid hormone replacement therapy, some physicians—especially those who tend to have a holistic medical philosophy—would say yes.

Fortunately for us, the human body is a redundant system in many ways: we have two arms, two legs, two lungs, two kidneys, etc. However, we have only one thyroid gland, and we’d better watch carefully for any sign of thyroid trouble, because this small, bowtie-shaped organ found just below the larynx has profound and wide-ranging effects on our health.

Thyroid Hormones—Vital to Health, and Life Itself

The thyroid gland exerts its powerful actions through at least four hormones, two of which—thyroxine (T4) and triiodothyronine (T3)—are predominant. Two other hormones (appropriately called T1 and T2) are known to be secreted by the thyroid gland, but their functions are not yet clear. The secretion of thyroid hormones is controlled, via a biochemical feedback loop, by the pituitary gland and a hormone it secretes known as thyroid-stimulating hormone, or TSH. If the pituitary detects low levels of thyroid hormones in the bloodstream, it secretes more TSH, which stimulates the thyroid to increase its output.

Although this output consists mainly of T4, the more physiologically active thyroid hormone is actually T3, about 80% of which is produced by conversion from T4 in the liver and other organs (the other 20% is produced by the thyroid gland itself). T3 plays a central role in regulating normal growth and development in infancy and childhood, as well as regulating the body’s energy metabolism throughout life. In terms of overall physiology, the thyroid hormones affect everything from your weight and mood to your cholesterol levels and heart function. Without thyroid hormones, you would not just feel bad—you would die.

Hypothyroidism Can Be Overlooked but Is Easy to Treat

With merely subnormal levels of thyroid hormones, however—a disease called hypothyroidism (or just “low thyroid”)—you could still feel pretty bad. The most common symptoms are dry skin, fatigue, dulling of mental faculties, depression, weight gain, constipation, aching joints, low blood pressure, high cholesterol, low libido, brittle nails, hair loss, and sensitivity to cold. Most cases of hypothyroidism, it is believed, go undiagnosed because the symptoms can so easily be ignored, regarded as normal aspects of aging, attributed to something else, or not even noticed because they develop so slowly and subtly. In a word, they’re ambiguous.

What’s even worse is that hypothyroidism predisposes the patient to more serious disorders, such as heart disease, in part through its cholesterol-elevating effect. The good news, though, is that low thyroid is easy to treat by administering thyroid hormones, preferably in the form of whole natural thyroid. The virtue in this approach is that whole thyroid, by definition, contains all the hormones produced naturally by the thyroid gland, in their biologically normal proportions. Since the actions of all these hormones and their interrelationships with each other and with other bodily systems are not fully understood, it’s reasonable to think that providing all of them is preferable to providing just one (T4), as is customary in modern medical practice.

Subclinical Hypothyroidism Can Be Very Subtle

A problem that has been described in the medical literature for over a century yet is still being debated today is subclinical hypothyroidism. As the word subclinical implies, this is a form of hypothyroidism that does not manifest itself clinically. For one thing, the lab tests for thyroid hormone levels are normal (although typically near the lower end of the normal range). The giveaway that something is amiss, however, is that the individual’s TSH levels are elevated, indicating a greater than normal need for more thyroid hormones.

But what about symptoms? The traditional view has been that, by the very definition of the word subclinical, there are no symptoms with this disorder. Indeed, many people with subclinical hypothyroidism, as determined by the lab tests, feel fine and have no symptoms. Others do have symptoms, however, although most of the symptoms can so easily arise from other causes, or from no apparent cause at all, that it’s often difficult, at least without the TSH test, to ascribe them reliably to subclinical hypothyroidism.

Subclinical Hypothyroidism—To Treat or Not to Treat?

In any case, subclinical hypothyroidism is believed to have an overall incidence of 4–10% in the general population and 7–26% in the elderly population; it’s especially common in elderly women.1 Despite the prevalence of this condition, however, there are still physicians who believe that treating it is a waste of time. In fact, a recent, widely cited paper by researchers at the Stanford University School of Medicine was provocatively entitled, “The Treatment of Subclinical Hypothyroidism Is Seldom Necessary.”2 (To be fair and balanced, however, the journal printed an opposing point of view back-to-back with this paper.1)

One of the reasons cited for believing that this is a disease not in search of a treatment is the ambiguous nature of its symptoms. And it’s true that people with normal thyroid function often have similar complaints, especially as they grow older. Yet there have been studies (see the sidebar) showing that people with subclinical hypothyroidism experience these symptoms at a significantly greater rate than those who do not have the condition. Furthermore, recent studies have shown that people with subclinical hypothyroidism have a greater incidence of peripheral arterial disease,3 hyperlipidemia and coronary artery disease,4 and musculoskeletal disorders.5

Subclinical Hypothyroidism Should Be Treated

Mainstream physicians who believe that subclinical hypothyroidism does not need treatment often state that there have been no large-scale studies that would justify such treatment. The fact is, however, that there have been several large-scale studies showing that people with subclinical hypothyroidism suffer from a myriad of symptoms.

One of the largest such studies, the Colorado Thyroid Disease Prevalence Study, measured serum TSH levels and conducted symptom surveys in over 25,000 Colorado residents.1 The 2336 people diagnosed with subclinical hypothyroidism reported, significantly more often than people without this condition, that they had the following symptoms: dry skin (28%), poor memory (24%), slow thinking (22%), muscle weakness (22%), fatigue (18%), muscle cramps (17%), cold intolerance (15%), constipation (8%), and hoarseness (7%). This and other similar studies should lay to rest any controversy over the potentially debilitating effects of subclinical hypothyroidism and the need for prompt and proper treatment.

1. Carnaris GJ et al. The Colorado Thyroid Disease Prevalence Study. Arch Int Med 2000;160:526-34.

A Capsule History of the Thyroid

Galen, the famed physician of ancient Rome, was one of the first people in the Western world to describe the thyroid gland.6 It took another 1700 years, however, for scientists to understand the thyroid’s function. In 1888, at a meeting of the Clinical Society of London, a paper was presented that finally described the deleterious effects of a nonfunctioning thyroid gland on the human body and mind.

With this new knowledge, it wasn’t long before physicians began to use thyroid extracts from animals to treat their hypothyroid patients. The first reported case was described in the British Medical Journal of October 10, 1891.6 The patient was a 46-year-old woman in Newcastle, England, with a severe case of hypothyroidism. Her physician injected her with a glycerin extract of sheep thyroid gland and reported rapid and significant improvement in her symptoms. It’s interesting to note that this one case of a single patient, with no randomized, controlled study to back it up, highlighted a specific and extremely effective therapy for hypothyroidism that was soon taken up by almost the entire medical community in the Western world. (That was a much simpler time.)

Thyroid injections proved to be painful and unpleasant, however, and by 1892, doctors were using desiccated thyroid gland (i.e., a dried and powdered form), generally from cows, sheep, or pigs, to treat the disorder. An examination of the medical literature from the 1920s to the 1970s shows that whole natural thyroid proved, by the tests of both science and time, to be a safe and effective treatment for a number of related conditions, including menstrual irregularities,7 hypercholesterolemia, and symptomatic atherosclerosis.8

The use of whole natural thyroid was accepted and practiced by physicians for over 80 years, yet by 1975, most medical students were no longer taught about this therapy. It is now a rare mainstream doctor who even knows about the previous widespread use of whole thyroid, and there are practically no doctors, aside from those with an interest in integrative medicine, who even realize that whole thyroid preparations are still available for their patients.

Synthetic Thyroid—Pros and Cons

What caused the drastic change in the treatment of hypothyroidism, leading to the rapid decline in the use of whole natural thyroid? It was the commercial introduction, in 1950, of synthetic thyroxine, which is chemically identical to natural thyroxine (which had been discovered in 1916). By the 1970s, almost all the leading medical journals had jumped on the synthetic T4 bandwagon (the best known brand name is Synthroid®) and were touting its supposedly consistent potency and stability. Like natural T4, synthetic T4 has a long half-life in the body—it can be given once a day and is then slowly converted to the more biologically active T3.

While the efficacy of synthetic T4 for people who suffer from hypothyroidism can’t be disputed, it is not the safe and stable medication that many in the medical establishment make it out to be. Between 1991 and 1997, there were ten recalls of synthetic T4, involving over 100 million tablets.9 In nine of these recalls, the tablets had been found to be subpotent, or they were losing their potency before their expiration date; in the tenth recall, the tablets were found to be too potent. For patients, such unreliability means that the synthetic T4 they receive could be either too strong or not strong enough to treat their condition properly.

T4 Alone May Not Be Adequate

Beyond the reliability problem, new research is leading some physicians (even those in mainstream medicine) to question the wisdom of using only synthetic T4 for their patients with subclinical hypothyroidism. A study published in The New England Journal of Medicine in 1999 examined the effects of giving T4 along with small amounts of T3 to hypothyroid patients.10 The authors concluded, “In patients with hypothyroidism, partial substitution of T3 for T4 may improve mood and neuropsychological function; this finding suggests a specific effect of the T3 normally secreted by the thyroid gland.”

Even with studies such as this, however, most doctors continue to use T4 alone, based in part on the findings of an earlier study showing that people who received both T4 and T3 had a higher frequency of troublesome side effects, including palpitations, irritability, and tremors.11

Another study, reported in the journal Endocrinology in 1996, also gave credence to the idea that more than just T4 is needed to optimize thyroid hormone levels in patients with hypothyroidism.12 In this study, done on hypothyroid rats, the researchers demonstrated that there was no single dose of either T4 or T3 that normalized thyroid hormone concentrations in all tissues simultaneously. It was only through the administration of both T4 and T3 that tissue concentrations of thyroid hormones were normalized.

Whole Natural Thyroid—As Nature Intended

In a perfect world, a large-scale, head-to-head study between synthetic T4 and whole natural thyroid would be done to see which one proved safer and more effective for the millions of people affected by hypothyroidism, whether clinical or subclinical. Until that time comes, it’s good for those of us who believe in the innate wisdom of nature to know that whole natural thyroid, which contains all the hormones found in our own thyroid glands, is available to help ensure our good health.

Arginine Benefits

Arginine’s Cornucopia of Benefits

Some people just get better breaks than others: they’re beautiful, smart, healthy, rich, and famous. And some amino acids are endowed with more biological benefits than others. In this arena, arginine is the champ. We’ve seen how it spawns the neurotransmitter nitric oxide, which plays such a vital role in cardiovascular health, kidney health, and other aspects of our well-being, such as having sex (speaking of which, it is well known that arginine also increases sperm count and sperm motility). Increased nitric oxide production due to supplementation with arginine is also responsible for an improvement in insulin sensitivity in diabetics.11 It is important to state that there is a cautionary note with regard to diabetics taking arginine and that for a number of reasons, supplementary arginine should not be taken except under the guidance of a medical professional.

In the central nervous system, nitric oxide is essential for learning processes that take place in the cerebellum, the part of the brain that is responsible for the regulation and coordination of complex voluntary muscular movements as well as the maintenance of posture and balance. Without the arginine needed to produce the nitric oxide our brains demand, we would become stumblebums, falling down and breaking our hips, or worse.

There is also evidence that nitric oxide enhances cognitive functions throughout the brain and that it may be necessary for long-term potentiation, the mechanism involved in long-term memory. It is even thought to be an important factor in our sense of smell and our ability to identify different scents.

ARGININE STIMULATES THE RELEASE OF GROWTH HORMONE
We’ve seen that arginine also plays a key role in stimulating the release of growth hormone by the pituitary gland. After adolescence and young adulthood, natural production of growth hormone declines dramatically as we age. That’s a pity, because, although we no longer need it to grow any taller, its very lack in the concentrations characteristic of our youth may be associated with many of the “inevitable” processes of aging.

For example, the healing of wounds, whether of flesh or bone, takes ever longer as we age, but there is strong evidence that growth hormone accelerates the healing process. And speaking of flesh, we would all probably like to see more of ours as muscle and less of it as fat – a goal that was easily achievable through exercise when our bodies were still young. As we age, however, it becomes ever more difficult – eventually almost impossible – to build muscle mass, or even maintain it. But here too, growth hormone, via arginine supplementation, can help us do much better in maintaining and even improving our strength and muscle-to-fat ratio than Mother Nature, in one of her stingier moods, provided for.

Even the “container” that keeps us from leaking all over the place – our skin – benefits from increased levels of growth hormone, which stimulates the production of elastin. This protein is the principal component of the elastic fibers that keep our skin, and even our arteries, well-toned and springy. The arteries also benefit from growth hormone’s tendency to counteract atherosclerosis. And as if that weren’t enough, nitric oxide does too. If arginine had a motto, it could be, “With me you get GH and NO. If one doesn’t help you, the other will.”

ARGININE BOOSTS IMMUNE FUNCTION
In a recent meta-analysis of 12 randomized, controlled studies, it was shown that critically ill patients who were being fed enterally (i.e., directly into their intestines) fared significantly better when the enteral “feeds” (yes, that’s what they call them) were supplemented with an immunonutritional mixture of arginine, omega-3 fatty acids, and nucleotides (the building blocks of nucleic acids).12

The meta-analysis encompassed a total of 1482 patients. Surprisingly, the immune feeds had no effect on mortality, but it was found that the patients who received them had a one-third-lower rate of infection than those on standard feeds, and they spent 2.6 fewer days on ventilators and 2.9 fewer days in the hospital, on average.

One cannot say what proportion of these effects was due to the arginine, but its inclusion in the formulation to begin with speaks to the recognition of its immune-enhancing properties. These properties may be due in part to the large-scale production of nitric oxide in white blood cells when the body is under attack by invading bacteria or parasites, toward which the NO acts in its traditional chemical role of poison.

All in all, one would have to be pretty jaded not to be impressed by the abundance of ways in which arginine, a simple organic compound with the formula C6H14N4O2, has staked its claim to being the most versatile of the amino acids and one of the most important nutrients in the natural world. So extraordinary is this molecule – with a proverbial Niagara of benefits for health, memory, well-being, sexual and physical enhancement, immune boosting, and more – that no red-blooded man or woman should be without it.

Caution:
Do not take any arginine product if you have diabetes,
because growth hormone can sometimes block the
effects of insulin. And do not take arginine if you have
cancer, because it is possible that growth hormone can
increase the rate of growth of all tissues, including those
that are cancerous. Finally, do not take arginine
if you have ocular or brain herpes, because
it can increase replication of the virus if
the latter is activated.

DMAE

I think this is an important article for those of us you just run out of gas during the day and lose our thoughts right in middle of them. You might want to talk with your Doctor about DMAE Supplementation

DMAE

Reprinted from Life Enhancement, Issue #25
ver hear the expression “the lights are on but nobody’s home”? Ever have a conversation with someone and you felt like they were in the Fifty Percent Club – they were only half present, the other half being who-knows-where?

On the other hand, you’ve probably also had the experience of meeting a person who seemed to be fully there, fully present. That’s presence of mind. When you are in that state yourself, it’s a state of excellence. It’s not a feeling, it’s a high level of responsiveness to your environment.

Some of the published studies on the naturally-occurring nutrient DMAE (dimethylaminoethanol) call this state vigilance and they have elaborate operational definitions and methods of testing for it. In these studies DMAE has been shown to support the vigilance mechanisms. We asked what vigilance really means and we looked at the testing methods. We found that it boils down to this elusive excellence we’re calling presence of mind.

Brain Function Maintenance
DMAE is normally present in small amounts in our brains. When supplemental amounts are used, the brain-function support effects are remarkable. DMAE is a naturally-occurring nutrient found in seafood such as anchovies and sardines.1 Perhaps this explains why fish has often been called brain food.

Throughout the scientific literature, DMAE has been reported as helping to elevate mood, improve memory and learning, heighten intelligence, increase physical energy and, in laboratory animals, extend the life span. It is used by many people for its mild, safe, stimulant effect, and yet DMAE also makes it easier for most people to get to sleep and to have more lucid dreams.2 Many people report less fatigue in the day and sounder sleep at night, as well as needing less sleep when taking DMAE.

The stimulant effect of DMAE is significantly different from that produced by coffee, amphetamines, or other stimulant drugs: DMAE does not have a drug-like quick pick-up and quick come-down. People who take DMAE have reported that after three to four weeks they feel a mild stimulation continually, without side effects. Also, when DMAE is discontinued, no depression or letdown occurs.

Nootropic “Essence”
DMAE may be thought of as a nootropic substance. More than 20 years ago the concept of a nootropic emerged from studying the unusual pharmacology of certain drugs, especially piracetam (which, upon confirmation, was extended to clinical applications). What is it that characterizes the essence of the nootropic effect?

1) The direct functional activation of the higher integrative brain mechanisms that help maintain normal, healthy cortical vigilance;

2) a telencephalic functional selectivity; and

3) a particular efficiency in restoring deficient higher nervous system activity.3

What is especially interesting is that the nootropic concept doesn’t deal with subcortical events such as those involving the reticular or limbic systems. It deals with cortical events, meaning those that have a direct impact on consciousness.

Although the neurochemistry of nootropic mechanisms is not clearly understood, we do know that nootropic activity enhances certain characteristics of membranes, such as their stability, permeability, strength, stress resistance, and assimilability. It is also thought that serotonin mechanisms are involved.

Simply put, the goal of the search for nootropic essence is that of finding and exploiting more selective nootropic agents. DMAE, with its ability to help maintain brain functions, thus perhaps supports cognitive efficiency. It may compensate for various neuropsychologic deficits ranging from cognitive processes to aging itself.

Orphan Drug
Riker Laboratories developed a prescription drug called Deaner (also called Deanol). This substance is the p-acetamidobenzoate salt of DMAE and has very similar effects. Riker marketed its DMAE-like product for learning problems, underachievement, shortened attention span, hyperactivity, reading and speech difficulties, impaired motor coordination, and behavior problems in children. This drug is no longer available in the U.S. due to the “vigilance” of the FDA, which demanded that Riker retest Deaner’s efficacy, in accordance with new and, purportedly, higher FDA standards. Riker apparently decided that they could not afford the tens of millions of dollars that would be required to maintain its right to continue selling the product. Thus Deaner has become an “orphan drug.”

Mechanisms
DMAE probably works by accelerating the brain’s synthesis and turnover of the neurotransmitter acetylcholine, which in turn plays a key role in maintaining mental ability as well as supporting healthy memory in aging adults. It has also been suggested that DMAE may work, in part, by inhibiting choline metabolism in peripheral tissues, causing free choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors.5,6

Mood and Vigilance
In a French double-blind, crossover study designed to measure the impact of DMAE on vigilance and mood, four subjects categorized as anxiety ridden, and four subjects used as controls, were given 1200 mg/day of DMAE for five days. The subjects then had their EEG and inter-hemispheric coherence measured. In the subjects given DMAE, a significant and progressive synchronization of the two hemispheres was noted. This synchronization was correlated with improved neuromotor control, enhancement of behavioral tasks, increased verbal memory, and better control in anxious and rhythmic reactivity.7

Learning, Behavior, and IQ
DMAE has proven to be a valuable and safe alternative for certain learning and behavior problems such as Attention Deficit Disorder (ADD) and hyperkinesia (usually the providence of children but also known to affect adults). Unfortunately, amphetamine or amphetamine-like drugs are often used to deal with these problems. In one study, consisting of 25 girls and 83 boys, conducted by Dr. Carl Pfeiffer of the Brain-Bio Center in Princeton, New Jersey, DMAE was found to result in enhanced behavior in 2/3 of the boys and 3/4 of the girls. Hyperactivity was greatly lessened as attention span was lengthened, irritability was decreased, scholastic ability improved, and, in some cases, IQ was elevated.8

Similar results were found when 500 mg of DMAE was given to 74 children with learning problems, including many who were hyperactive. These subjects were screened for neurological or psychiatric illnesses beforehand. DMAE was given in a double-blind fashion for 3 months. Testing was done before and after treatment for behavior, reaction time, and a series of standard psychometric parameters. Not only was there significant improvement overall but DMAE was shown to improve performance in children with learning and behavior disorders.9

Fatigue, Depression, Confusion
In one of Dr. Pfeiffer’s earliest studies on 100 subjects, he demonstrated that DMAE can help alleviate chronic fatigue and mild depression through its effects on physical energy and motivation. He also noted personality improvements and help with insomnia.10 It is important to note that the subjects did not develop any dependency on DMAE, as often occurs with many drugs used for fatigue and insomnia.

In another study, doses of 400 to 800 mg were given daily to 52 patients with a variety of different central nervous system problems, the result of which was significant diminishment of their conditions.11

Life Span
Richard Hochschild has studied the influence of DMAE on the mean and maximum life spans of fruit flies and mice.12-14 He found that in mice of a strain that normally lives a shorter period than most species, DMAE extended the mean life span by 30% and the maximum life span by up to 27%. The same was not found to be the case in longer living strains of mice, however. But, in another study, 40% of a long-lived strain had survived to the end of the study versus only 10% of untreated mice.

Free-Radical Scavenger
In a study using rats, DMAE has been found to diminish the level of water-insoluble, cross-linked, protein fractions that normally increase with age in brain cortical tissue and liver. This cross-linking of proteins is believed to be caused by hydroxyl free radicals during several metabolic processes. DMAE actually caused the reversal of this phenomenon in old rats. The RNA in the brain cortex of these rats ultimately reached the level of young adult members of the species.

Other studies have shown that DMAE decreases the accumulation of age pigment (lipofuscin) in the brain and heart muscle of a variety of lab animals.16-18 At least one study shows that this may be the result of enhanced levels of antioxidant enzymes in the brain.19

Motor Mechanisms
Tardive dyskinesia is a movement disorder thought to arise from dopamine receptor supersensitivity brought on by long-term neuroleptic-induced receptor blockade. In a succession of studies, DMAE has been found to exercise a favorable effect on the chronic dyskinesias following prolonged use of neuroleptics. It also proved helpful with other extrapyramidal manifestations and on motor restlessness (akathisia).20

The Dose-Response Curve
In memory research, scientists often do what is known as a dose-response study. Memory is tested at several different dosage levels and the results are then plotted on a graph. As the dosage increases, memory improves – but only up to a point: as you increase the dosage further, you find memory dropping off.

DMAE is no exception to this rule. DMAE improves retention test performance but, as with most substances that support memory function, after the optimum dose is reached, performance declines.

When combined with certain drugs or nutrients, the optimum dose levels may be much lower. When DMAE is combined with cholinergic drugs, there is a striking reduction in the optimal dose for enhanced retention.21

Precautions: Overdosage can produce insomnia, dull headaches, or tenseness in muscles (especially those of the jaws, neck, and legs). These side effects disappear if the dosage is lowered slightly. No serious adverse effects have ever been reported with DMAE. Patients with certain types of epilepsy should be closely monitored by a physician. DMAE should not be used by people who are manic because it can deepen the depressive phase.

References

Honegger C, Honegger R. Occurrence and quantitative determination of 2-dimethyl-aminoethanol in animal tissue extracts. Nature. 1959;184:550-552.
Sergio W. Use of DMAE (2-dimethylaminoethanol) in the induction of lucid dreams. Med Hypotheses. 1988;26:255-257.
Giurgea CE. The nootropic concept and its prospective implications. Drug Dev Res. 1982;2:441-446.
Anderson K, Anderson L. Orphan Drugs. Los Angeles, CA: The Body Press, 1987:69.
Haubrich DR, Gerber NH, Pflueger AB. DEANOL affects choline metabolism in peripheral tissues of mice. Neuropsychopharmacol. J. Neurochem. 1981;37:476-482.
Millington WR, McCall AL, Wurtman RJ. DEANOL acetamidobenzoate inhibits the blood brain barrier transport of choline. Ann Neurol. 1978;4:302-306.
Caille E.-J. Study concerning the bisorcate demanol effects upon quantified EEG, cortical vigilance and mood. Comparative double-blind, cross-over balanced design versus pirisudanol. Psychol Med. 1986;18:2069-2086.
Pfeiffer CC, et al. Stimulant effect of 2-dimethyl-l-aminoethanol: possible precursor of brain acetylcholine. Science. 1957;126:610-611.
Lewis JA, Young R. Deanol and methylphenidate in minimal brain dysfunction. Clin Pharmacol Ther. 1975;17:534-540.
Pfeiffer CC. Parasympathetic neurohumors. Possible precursors and effect on behavior. International Review of Neurobiology. 1959:195-244.
Destram H. Presse Medical. 1961;69:1999.
Hochschild R. Effect of dimethylaminoethyl p chlorophenoxyacetate on the life span
of male Swiss Webster albino mice. Exp Geront. 1973;8:177-183.Also 1971;6:133 and
1973;8:177.
Ibid.
Ibid.
Zs-Nagy I, Nagy K. On the role of cross-linking of cellular proteins in aging. Mech Ageing Dev. 1980;14:245-251.
Nandi K. J Gerontol. 1968;23:82.
Riga S, Riga D. Brain Research. 1974;72:265.
Dylewski DP, et al. Neurobiol Aging 1983;4:89.
Roy D et al. Experimental Gerontol. 1983;18:185.
Lambert PA, Wolff PH, De Maximy B, Ghenim A. Dimethylaminoethanol in the treatment of late dyskinesia induced by neuroleptic drugs. Ann Med Psychol. 1978;136:625-629.
Flood JF, Smith GE, Cherkin A. Memory retention: Potentiation of cholinergic drug combinations in mice. Neurobiol. Aging 1983;4:37-43.
Saccar CL. Drug therapy in the treatment of minimal brain dysfunction. Am J Hosp Pharm. 1978;35:544-552. Week “Natural Testosterone Replacement”

Understaning Male HRT

Ok let’s begin with an article by Life Enhancements. It is the best information in one place I could find to get everyone on the same page. I will talk about what happened with my therapy; and how the things you read about in the article had dramatic effects on me. But first I think everyone has to have a baseline of why HRT. One quick note,, I am not an MD. so the thoughts I will give you are from the patient perspective not that of an MD providing it. SO HERE WE GO:
THE CRITICAL IMPORTANCE OF FREE TESTOSTERONE

Testosterone is much more than a sex hormone. There are testosterone receptor sites in cells throughout the body, most notably in the brain and heart. Youthful protein synthesis for maintaining muscle mass and bone formation requires testosterone. Testosterone improves oxygen uptake throughout the body, helps control blood sugar, regulates cholesterol, and maintains immune surveillance. The body requires testosterone to maintain youthful cardiac output and neurological function. Testosterone is also a critical hormone in the maintenance of healthy bone density, muscle mass, and red blood cell production.
Of critical concern to psychiatrists are studies showing that men with depression have lower levels of testosterone than do control subjects. For some men, elevating free testosterone levels could prove to be an effective antidepressant therapy. There is a basis for free testosterone levels being measured in men with depression and for replacement therapy being initiated if free testosterone levels are low normal or below normal.
Testosterone is one of the most misunderstood hormones. Body builders tarnished the reputation of testosterone by putting large amounts of synthetic testosterone drugs into their young bodies. Synthetic testosterone abuse can produce detrimental effects, but this has nothing to do with the benefits a man over age 40 can enjoy by properly restoring his natural testosterone to a youthful level.
Conventional doctors have not recommended testosterone replacement therapy because of an erroneous concern that testosterone causes prostate cancer. As we will later show, fear of prostate cancer is not a scientifically valid reason to avoid testosterone modulation therapy.
Another concern that skeptical physicians have about prescribing testosterone replacement therapy is that some poorly conducted studies showed it to be ineffective in the long-term treatment of aging. These studies indicate anti-aging benefits when testosterone is given, but the effects often wear off. What physicians fail to appreciate is that exogenously administered testosterone can convert to estrogen in the body. The higher estrogen levels may negate the benefits of the exogenously administered testosterone. The solution to the estrogen-overload problem is to block the conversion of testosterone to estrogen in the body.
Numerous studies show that maintaining youthful levels of free testosterone can enable the aging man to restore strength, stamina, cognition, heart function, sexuality, and outlook on life, that is, to alleviate depression. A study in Drugs and Aging (1999) suggested that androgen therapy can result in polycythemia (increased numbers of red blood cells) causing an increase in blood viscosity and risk of clotting. For many aging men, however, borderline anemia is a greater concern than red blood cell overproduction. When men are deprived of testosterone during prostate cancer therapy, anemia frequently manifests. Studies have not shown cases in which polycythemia developed in men taking enough testosterone to restore physiological youthful ranges. In other words, too much testosterone could cause problems, but replacing testosterone to that of a healthy 21-year-old should not produce the side effects that some doctors are unduly concerned about. As you will read in the section entitled “Testosterone and the Heart,” it appears that testosterone replacement therapy provides significant beneficial effects against cardiovascular disease.

Why Testosterone Levels Decline

Testosterone production begins in the brain. When the hypothalamus detects a deficiency of testosterone in the blood, it secretes a hormone called gonadotrophin-releasing hormone to the pituitary gland. This prompts the pituitary to secrete luteinizing hormone (LH), which then prompts the Leydig cells in the testes to produce testosterone.
In some men, the testes lose their ability to produce testosterone, no matter how much LH is being produced. This type of testosterone deficiency is diagnosed when blood tests show high levels of LH and low levels of testosterone. In other words, the pituitary gland is telling the testes (by secreting LH) to produce testosterone, but the testes have lost their functional ability. So the pituitary gland vainly continues to secrete LH because there is not enough testosterone in the blood to provide a feedback mechanism that would tell the pituitary to shut down. In other cases, the hypothalamus, or pituitary gland, fails to produce sufficient amounts of LH, thus preventing healthy testes from secreting testosterone. Blood testing can determine whether sufficient amounts of LH are being secreted by the pituitary gland and help determine the appropriate therapeutic approach. If serum (blood) testosterone levels are very low, it is important to diagnose the cause, but no matter what the underlying problem, therapies exist today to safely restore testosterone to youthful levels in any man (who does not already have prostate cancer).
As indicated earlier, a major problem that aging men face is not low production of testosterone, but excessive conversion of testosterone to estrogen. Specific therapies to suppress excess estrogen and boost free testosterone back to youthful physiological levels will be discussed later.

The Effects of Testosterone on Libido

Sexual stimulation and erection begin in the brain when neuronal testosterone-receptor sites are prompted to ignite a cascade of biochemical events that involve testosterone-receptor sites in the nerves, blood vessels, and muscles. Free testosterone promotes sexual desire and then facilitates performance, sensation, and the ultimate degree of fulfillment.
Without adequate levels of free testosterone, the quality of a man’s sex life is adversely affected and the genitals atrophy. When free testosterone is restored, positive changes can be expected in the structure and function of the sex organs. (It should be noted that sexual dysfunction can be caused by other factors unrelated to hormone imbalance. An example of such a factor is arteriosclerotic blockage of the penile arteries.)
The genital-pelvic region is packed with testosterone receptors that are ultra-sensitive to free testosterone-induced sexual stimulation. Clinical studies using testosterone injections, creams, or patches have often failed to provide a long-lasting, libido-enhancing effect in aging men. We now know why. The testosterone can be converted to estrogen. The estrogen is then taken up by testosterone receptor sites in cells throughout the body. When an estrogen molecule occupies a testosterone receptor site on a cell membrane, it blocks the ability of serum testosterone to induce a healthy hormonal signal. It does not matter how much serum free testosterone is available if excess estrogen is competing for the same cellular receptor sites.
Estrogen can also increase the production of SHBG, which binds the active free testosterone into an inactive “bound testosterone.” Bound testosterone cannot be picked up by testosterone receptors on cell membranes. For testosterone to produce long-lasting, libido-enhancing effects, it must be kept in the “free” form (not bound to SHBG) in the bloodstream. It is also necessary to suppress excess estrogen because this hormone can compete for testosterone receptor sites in the sex centers of the brain and the genitals.
Restoring youthful hormone balance can have a significant impact on male sexuality.
Testosterone and the Heart
Normal aging results in the gradual weakening of the heart, even in the absence of significant coronary artery disease. If nothing else kills the elderly male, his heart just stops beating at some point.
Testosterone is a muscle-building hormone, and there are many testosterone-receptor sites in the heart. The weakening of the heart muscle can sometimes be attributed to testosterone deficiency.
Testosterone is not only responsible for maintaining heart muscle protein synthesis, it is also a promoter of coronary artery dilation and helps to maintain healthy cholesterol levels.
There are an ever-increasing number of studies indicating an association between high testosterone and low cardiovascular disease rates in men. In the majority of patients, symptoms and EKG measurements improve when low testosterone levels are corrected. One study showed that blood flow to the heart improved 68.8% in those receiving testosterone therapy. In China, doctors are successfully treating angina with testosterone therapy.
The following list represents the negative effects of low testosterone on cardiovascular disease:
• Cholesterol, fibrinogen, triglycerides, and insulin levels increase
• Coronary artery elasticity diminishes
• Blood pressure rises
• Human growth hormone (HGH) declines (weakening the heart muscle)
• Abdominal fat increases (increasing the risk of heart attack)
Those with cardiovascular disease should have their blood tested for free testosterone and estrogen. Some men (with full cooperation from their physicians) may be able to stop taking expensive drugs to stimulate cardiac output, lower cholesterol, and keep blood pressure under control if they correct a testosterone deficit or a testosterone-estrogen imbalance. A compelling study of 1100 men showed that those with serum dehydroepiandrosterone-sulfate (DHEA-S) in the lowest quarter < 1.6 mcg/mL) were significantly more likely to incur symptoms of heart disease (295), and in a review of several studies, other authors have confirmed this association (296). Dehydroepiandro-sterone (DHEA) is produced by the adrenal gland and is a precursor hormone for the manufacture of testosterone (see the DHEA Replacement Therapy protocol).
Despite numerous studies substantiating the beneficial effects of testosterone therapy in treating heart disease, conventional cardiologists continue to overlook the important role this hormone plays in keeping their cardiac patients alive.

Testosterone and the Prostate Gland

Many doctors will tell you that testosterone causes prostate disease. The published scientific literature indicates otherwise.
As readers of Life Extension Magazine learned in late 1997, estrogen has been identified as a primary culprit in the development of benign prostatic hyperplasia (BPH). Estrogen has been shown to bind to SHBG in the prostate gland and cause the proliferation of epithelial cells in the prostate. This is corroborated by the fact that as men develop benign prostate enlargement, their levels of free testosterone plummet, although their estrogen levels remain the same or are rising. As previously discussed, aging men tend to convert their testosterone into estrogen. The published evidence shows that higher serum levels of testosterone are not a risk factor for developing benign prostate disease .
The major concern that has kept men from restoring their testosterone to youthful levels is the fear of prostate cancer. The theory is that since most prostate cancer cell lines need testosterone to proliferate, it is better not to replace the testosterone that is lost with aging. The problem with this theory is that most men who develop prostate cancer have low levels of testosterone, and the majority of published studies show that serum testosterone levels do not affect one’s risk for contracting prostate cancer.
Because there is such a strong perception that any augmentation of testosterone can increase the risk of prostate cancer, we did a MEDLINE search on all the published studies relating to serum testosterone and prostate cancer. The abstracts at the end of this protocol provide quotations from the published literature as it relates to the issue of whether testosterone causes prostate disease. Of the 27 MEDLINE studies found, five studies indicated that men with higher testosterone levels had a greater incidence of prostate cancer, whereas 21 studies showed that testosterone was not a risk factor and one study was considered neutral. Before starting a testosterone replacement program, men should have a serum PSA test and a digital rectal exam to rule out prostate cancer. Nothing is risk free. A small minority of men with low testosterone and prostate cancer will not have an elevated PSA or palpable lesion detectable by digital rectal exam. If these men use supplemental testosterone, they risk an acute flare-up in their disease state. That is why PSA monitoring is so important every 30-45 days during the first 6 months of any type of testosterone augmentation therapy. If an underlying prostate cancer is detected because of testosterone therapy, it is usually treatable by nonsurgical means.
Please remember that testosterone does not cause acute prostate cancer, but if you have existing prostate cancer and do not know it, testosterone administration is likely to boost PSA sharply and provide your doctor with a quick diagnosis of prostate cancer (and an opportunity for very early treatment). We acknowledge that some aging men will not want to take this risk.
As stated above, the MEDLINE score was 21 to 5 against the theory that testosterone plays a role in the development of prostate cancer. None of these studies took into account the prostate cancer prevention effects for men who take lycopene, selenium, and vitamins A and E, nor did they factor in possible prostate disease preventives such as saw palmetto, nettle, soy, and pygeum.

In the book, Maximize Your Vitality & Potency, a persuasive case is made that testosterone and DHEA actually protect against the development of both benign and malignant prostate disease. Dr. Wright also points out that natural therapies, such as saw palmetto, nettle, and pygeum, provide a considerable degree of protection against the alleged negative effects that higher levels of testosterone might have on the prostate gland.
We eagerly await the results of more studies, but the fear of developing prostate cancer in the future should not be a reason to deprive your body today of the life-saving and life-enhancing benefits of restoring a youthful hormone balance.
Once a man has prostate cancer, testosterone therapy cannot be recommended because most prostate cancer cells use testosterone as a growth promoter. Regrettably, this denies prostate cancer patients the wonderful benefits of testosterone therapy. Men with severe BPH should approach testosterone replacement cautiously. It would be prudent for those with BPH who are taking testosterone replacement therapy to also use the drug Proscar (finasteride) to inhibit 5-alpha-reductase levels, thereby suppressing the formation of dihydrotestosterone (DHT) . DHT is 10 times more potent than testosterone in promoting prostate growth, and suppressing DHT is a proven therapy in treating benign prostate enlargement. Saw palmetto extract suppresses some DHT in the prostate gland, but its effectiveness in alleviating symptoms of BPH probably has more to do with
• Its blocking of alpha-adrenergic receptor sites on the sphincter muscle surrounding the urethra. (This is how the drug Hytrin works.)
• Its inhibition of estrogen binding to prostate cells (such as nettle)
• Its inhibition of the enzyme 3-ketosteroid (which causes the binding of DHT to prostate cells)
• Its anti-inflammatory effect on the prostate
Note: Men with severe BPH may also consider using the drug Arimidex (0.5 mg twice a week) to suppress excess levels of estrogen. Estrogen can worsen BPH and supplemental testosterone can elevate estrogen if an aromatase-inhibiting drug such as Arimidex is not used.
It is unfortunate that many people still think that restoring testosterone to youthful levels will increase the risk of prostate disease. This misconception has kept many men from availing themselves of this life-enhancing and life-saving hormone.
Although it is clear that excess estrogen causes benign prostate enlargement, the evidence for excess estrogen’s role in the development of prostate cancer is uncertain. Some studies show that elevated estrogen is associated with increased prostate cancer risk, while other studies contradict this finding. For more information on testosterone, estrogen, and the prostate gland, refer to the February 1999 issue of Life Extension Magazine .

Testosterone and Depression
A consistent finding in the scientific literature is that testosterone replacement therapy produces an increased feeling of well-being. Published studies show that low testosterone correlates with symptoms of depression and other psychological disorders (94-97, 272).
A common side effect of prescription antidepressant drugs is the suppression of libido. Those with depression either accept this drug-induced reduction in quality of life, or get off the antidepressant drugs so they can at least have a somewhat normal sex life. If more psychiatrists tested their patients’ blood for free testosterone and prescribed natural testosterone therapies to those with low free testosterone, the need for libido-suppressing antidepressant drugs could be reduced or eliminated. As previously described, tes-tosterone replacement often enhances libido, the opposite effect of most prescription antidepressants.
One study showed that patients with major depression experienced improvement that was equal to that achieved with standard antidepressant drugs (97).
Androderm is one of several natural testosterone-replacement therapies that can be prescribed by doctors. A 12-month clinical trial using this FDA-approved drug resulted in a statistically significant reduction in the depression score (6.9 before versus 3.9 after). Also noted were highly significant decreases in fatigue: from 79% before the patch to only 10% after 12 months (218).
According to Jonathan Wright, M.D., co-author of Maximize Your Vitality & Potency, the following effects have been reported in response to low testosterone levels (305):
• Loss of ability to concentrate
• Moodiness and emotionality
• Touchiness and irritability
• Great timidity
• Feeling weak
• Inner unrest
• Memory failure
• Reduced intellectual agility
• Passive attitudes
• General tiredness
• Reduced interest in surroundings
• Hypochondria
The above feelings can all be clinical symptoms of depression, and testosterone replacement therapy has been shown to alleviate these conditions. Testosterone thus has exciting therapeutic potential in the treatment of depression in men.

Testosterone and Mental Decline
Evidence indicates that low levels of testosterone may contribute to memory impairment and increase the vulnerability of the brain to Alzheimer’s and related disorders. Beta-amyloid, a peptide that may accumulate in certain regions of the aging brain, is implicated in the development of Alzheimer’s disease. Researchers have found that testosterone exerts neuroprotective benefits from the effects of toxic beta-amyloid. An article published in Brain Research describes a study in which cultured neurons were exposed to beta-amyloid in the presence of testosterone. The resulting toxicity from beta-amyloid was significantly reduced by testosterone through a rapid estrogen-independent mechanism.
Other researchers have explored the mechanism by which testosterone may exert its protective effect in Alzheimer’s disease. Their research in animals shows that testosterone decreases the secretion of harmful beta-amyloid and increases the secretion of the non-amyloidogenic APP fragment, sbetaAPPalpha, indicating that testosterone supplementation in elderly men may be beneficial in the treatment of Alzheimer’s.
Another published study examined the neuroprotective effects of estradiol, testosterone, epi-testosterone, and methyl-testosterone in neurons induced to undergo apoptosis by serum deprivation. Physiologic concentrations of testosterone were found to be neuroprotective, similar to estradiol. Methyl-testosterone showed an effect that was delayed in time, suggesting that a metabolite may be the active agent. Epi-testosterone showed a slight neuroprotective effect but not through the androgen receptor. The authors concluded that androgens may be of therapeutic value against Alzheimer’s disease in aging males.
Researchers in Oxford, England found that lower levels of testosterone were present in men with Alz-heimer’s as opposed to controls. These results were independent of confounding factors such as age, body mass index, education, smoking, alcohol abuse, and endocrine therapy. The authors recommended further studies to determine whether low levels of total tes-tosterone precede or follow the onset of Alzheimer’s disease.

Testosterone and Aging
We know that many of the degenerative diseases of aging in men, such as Type-II diabetes, osteoporosis, and cardiovascular disease, are related to a testosterone deficiency. We also know that common characteristics of middle age and older age, such as depression, abdominal fat deposition, muscle atrophy, low energy, and cognitive decline, are also associated with less than optimal levels of free testosterone (58, 219).
A consistent pattern that deals with fundamental aging shows that low testosterone causes excess production of a dangerous hormone called cortisol. Some antiaging experts call cortisol a “death hormone” because of the multiple degenerative effects that it produces. Some of these effects are immune dysfunction, brain cell injury, and arterial wall damage.
A group of scientists conducted two double-blind studies in which they administered supplemental testosterone to groups of aging men and observed the typical responses of lower levels of cholesterol, glucose, and triglycerides, reductions in blood pressure, and decreased abdominal fat mass. The scientists showed that excess cortisol suppressed testosterone and growth hormone production and that the administration of testosterone acted as a “shield” against the overproduction of cortisol in the adrenal gland. Another study published in 1999 on testosterone and atherosclerosis in men showed a statistically significant correlation between low testosterone and excess serum insulin. It was noted that an elevated estradiol to testosterone ratio is connected with insulin resistance.
It is important to point out that testosterone is an anabolic (or protein building) hormone while cortisol is a catabolic hormone that breaks down proteins in the body. Normal aging consists of a progressive decrease in free testosterone with a marked increase in cortisol. As men age past 40, cortisol begins to dominate, and the catabolic effects associated with growing older begin to dominate.
These findings have significant implications in the battle to maintain youthful hormone balance for the purpose of staving off normal aging and its associated degenerative diseases.
THE TESTOSTERONE DOCTOR
Eugene Shippen, M.D. (co-author of The Testosterone Syndrome, 1998) provided extensive evidence documenting the pathology of the testosterone deficiency syndrome in men. Some excerpts follow from a lecture presented by Dr. Shippen at the American Academy for Anti-Aging Medicine Conference in December 1998:
• First, testosterone is not just a “sex hormone.” It should be seen as a “total body hormone,” affecting every cell in the body. The changes seen in aging, such as the loss of lean body mass, the decline in energy, strength, and stamina, unexplained depression, and decrease in sexual sensation and performance, are all directly related to testosterone deficiency. Degenerative diseases such as heart disease, stroke, diabetes, arthritis, osteoporosis, and hypertension are all directly or indirectly linked to testosterone decline. Secondly, testosterone also functions as a pro-hormone. Local tissue conversion to estrogens, dihydrotestosterone (DHT), or other active metabolites plays an important part in cellular physiology.
• Excess estrogen seems to be the culprit in prostate enlargement. Low testosterone levels are in fact associated with more aggressive prostate cancer. While fear of prostate cancer keeps many men from testosterone replacement, it is in fact testosterone deficiency that leads to the pathology that favors the development of prostate cancer.
• Testosterone improves cellular bioenergetics. It acts as a cellular energizer. Since testosterone increases the metabolic rate and aerobic metabolism, it also dramatically improves glucose metabolism and lowers insulin resistance.
• Another myth is that testosterone is bad for the heart. Actually, low testosterone correlates with heart disease more reliably than does high cholesterol (19, 231). Testosterone is the most powerful cardiovascular protector for men. Testosterone strengthens the heart muscle (232); there are more testosterone receptors in the heart than in any other muscle. Testosterone lowers LDL cholesterol and total cholesterol (69, 81, 111) and improves every cardiac risk factor. It has been shown to improve or eliminate arrhythmia and angina (9, 106, 113-115, 233, 266). Testosterone replacement is the most underutilized important treatment for heart disease.
• Testosterone shines as a blood thinner, preventing blood clots (32). Testosterone also helps prevent colon cancer (235, 236).
• Previous research on testosterone used the wrong form of replacement. Injections result in initial excess of testosterone, with conversion of excess to estrogens. Likewise, total testosterone is often measured instead of free testosterone, the bioavailable form. Some studies do not last long enough to show improvement. For instance, it may take six months to a year before the genital tissue fully recovers from atrophy caused by testosterone deficiency, and potency is restored.
• Physicians urgently need to be educated about the benefits of testosterone and the delicate balance between androgens (testosterone) and estrogens. Each individual has his or her own pattern of hormone balance; this indicates that hormone replacement should be individualized and carefully monitored.

OBESITY AND HORMONE IMBALANCE
A consistent finding in the scientific literature is that obese men have low testosterone and very high estrogen levels. Central or visceral obesity (“pot belly”) is recognized as a risk factor for cardiovascular disease and Type-II diabetes. Research has shed light on subtle hormone imbalances of borderline character in obese men that often fall within the normal laboratory reference range. Boosting tes-tosterone levels seems to decrease the abdominal fat mass, reverse glucose intolerance, and reduce lipoprotein abnormalities in the serum. Further analysis has also disclosed a regulatory role for testosterone in counteracting visceral fat accumulation. Epidemiological data demonstrate that relatively low tes-tosterone levels are a risk factor for development of visceral obesity.
One study showed that serum estrone and estradiol were elevated twofold in one group of morbidly obese men. Fat cells synthesize the aromatase enzyme, causing male hormones to convert to estrogens (278). Fat tissues, especially in the abdomen, have been shown to literally “aromatize” testosterone and its precursor hormones into potent estrogens (80, 237-242).
Eating high-fat foods may reduce free testosterone levels according to one study that measured serum levels of sex steroid hormones after ingestion of different types of food. High-protein and high-carbohydrate meals had no effect on serum hormone levels, but a fat-containing meal reduced free testosterone levels for 4 hours (243).
Obese men have testosterone deficiency caused by the production of excess aromatase enzyme in fat cells and also from the fat they consume in their diet. The resulting hormone imbalance (too much estrogen and not enough free testosterone) in obese men partially explains why so many are impotent and have a wide range of premature degenerative diseases (45).

FACTORS CAUSING THE ESTROGEN- TESTOSTERONE IMBALANCE IN MEN

If your blood tests reveal high estrogen and low tes-tosterone, here are the common factors involved:

Excess “Aromatase” Enzyme
As men age, they produce larger quantities of an enzyme called aromatase. The aromatase enzyme converts testosterone into estrogen in the body. Inhibiting the aromatase enzyme results in a significant decline in estrogen levels while often boosting free testosterone to youthful levels. Therefore, an agent designated as an “aromatase inhibitor” may be of special value to aging men who have excess estrogen.

Liver Enzymatic Activity
A healthy liver eliminates surplus estrogen and sex hormone-binding globulin. Aging, alcohol, and certain drugs impair liver function and can be a major cause of hormone imbalance in aging men. Heavy alcohol intake increases estrogen in men and women.

Obesity
Fat cells create aromatase enzyme and especially contribute to the buildup of abdominal fat. Low testosterone allows the formation of abdominal fat, which then causes more aromatase enzyme formation and thus even lower levels of testosterone and higher estrogen (by aromatizing testosterone into estrogen). It is especially important for overweight men to consider hormone modulation therapy.

Zinc Deficiency
Zinc is a natural aromatase enzyme inhibitor (247). Since most Life Extension Foundation members consume adequate amounts of zinc (30-90 mg a day), elevated estrogen in Foundation members is often caused by factors other than zinc deficiency.

Lifestyle Changes
Lifestyle changes (such as reducing alcohol intake) can produce a dramatic improvement in the estrogen-testosterone balance, but many people need to use aromatase-inhibiting agents to lower estrogen and to improve their liver function to remove excess SHBG. Aromatase converts testosterone into estrogen and can indirectly increase SHBG. SHBG binds to free testosterone and prevents it from exerting its biochemical effects in the body.

CORRECTING A HORMONE IMBALANCE

A male hormone imbalance can be detected through use of the proper blood tests and can be corrected using available drugs and nutrients. The following represents a step-by-step program to safely restore youthful hormone balance in aging men:

Step 1: Blood Testing
The following initial blood tests are recommended for any man over age 40:
• Complete blood count and chemistry profile to include liver-kidney function, glucose, minerals, lipids, and thyroid (TSH)
Free and Total Testosterone
• Estradiol (estrogen)
• DHT (dihydrotestosterone)
• DHEA
• PSA
• Homocysteine
• Luteinizing hormone (LH) (optional)
• Sex Hormone Binding Globulin (SHBG) (optional)

Step 2: Interpretation of Free Testosterone,
Estrogen, and Total Testosterone Blood Test Results

One can easily determine if they need testosterone replacement or estrogen suppression by adhering to the following guidelines:

Free Testosterone
Free testosterone blood levels should be at the high-normal of the reference range. We define high-normal range as the upper one third of the reference range. Under no circumstances should free or total testosterone be above the high end of the normal range.
What too often happens is that a standard laboratory “reference range” deceives a man (and his physician) into believing that proper hormone balance exists because the results of a free testosterone test fall within the “normal” range. The following charts show a wide range of so-called “normal” ranges of testosterone for men of various ages. While these normal ranges may reflect population “averages,” the objective for most men over age 40 is to be in the upper one-third tes-tosterone range of the 21- to 29-year-old group. Based on the following reference range chart from LabCorp, this means that optimal free testosterone levels should be between 21-26.5 nanogram/dL in aging men.

Testosterone from LabCorp
20-29 years 9.3-26.5 picogram/mL
30-39 years 8.7-25.1 picogram/mL
40-49 years 6.8-21.5 picogram/mL
50-59 years 7.2-24.0 picogram/mL
60+ years 6.6-18.1 picogram/mL

An example of how this chart can be deceptive would be if a 50-year-old man presented symptoms of testosterone deficiency (depression, low energy, abdominal obesity, angina, etc.), but his blood test revealed his free testosterone to be 9 picogram/mL. His doctor might tell him he is fine because he falls within the normal “reference range.” The reality may be that to achieve optimal benefits, testosterone levels should be between 21-26.5 picogram/mL. That means a man could have less than half the amount of testosterone needed to overcome symptoms of a tes-tosterone deficiency, but his doctor will not prescribe testosterone replacement because the man falls within the “average” parameters. That is why it is so important to differentiate between “average” and “optimal.” Average 50-year-old men often have the symptoms of having too little testosterone. Yet since so many 50-year-old men have lower than desired testosterone levels, this is considered to be “normal” when it comes to standard laboratory reference ranges.
The Life Extension Foundation would like to point out that there is disagreement between clinicians and laboratories on the best method for measuring tes-tosterone status. There are different schools of thought as to which form of testosterone should be measured and which analytical procedure provides the most accurate assessment of metabolic activity.
To illistrate this point, the reference values for measuring free testosterone from Quest Diagnostics follow:
Adult Male (20-60+ years):
1.0-2.7% 50-210 pg/mL
Optimal Range: 150-210 pg/mL
for aging men without
prostate cancer.

We believe that direct testing for free testosterone is the best way to test for testosterone activity, as free testosterone is active testosterone and consists of only 1-2% of total testosterone. Total testosterone can be good for general testing. The four main methods presently used for analyzing free testosterone are:
• Direct, Free Testosterone by Direct Analog/Radioimmunoassay (RIA)
• Testosterone Free by Ultrafiltration (UF)
• Testosterone Free by Equilibrium Tracer Dialysis (ETD)
• Testosterone Free and Weakly Bound by Radioasssay (FWRA)
The latter three test methods are older, more complicated methods that are technically demanding. The direct RIA test has a number of commercial test kits available, and they are better used in today’s automated equipment, making this test less tedious and requiring a smaller (less) sample. These advantages have convinced many laboratories and clinics to prefer direct RIA testing for free testosterone. The Life Extension Foundation agrees with this assessment, and therefore uses and recommends the direct free testosterone test with the above-mentioned reference levels.
Consequently, if your doctor tests your free tes-tosterone, be sure you know the analytical method used. If your test results have a reference range as follows, you have probably been tested with one of the other test methods:

Male Reference Range Test Type
66-417 nanogram/dL FWRA
12.3-63% %FWRA
5-21 nanogram/dL UF or ETD
50-210 picogram/mL UF or ETD
1.0-2.7% % of free by UF or ETD

No matter what test method is used to determine your free testosterone status, the optimal level (where you want to be) is in the upper one-third of normal for a 20-29 year old male.

Estrogen
Estrogen (measured as estradiol) should be in the mid- to lower-normal range. If estradiol levels are in the upper one-third of the normal reference range, or above the normal reference range, this excessive level of estrogen should be reduced. Labcorp lists a reference range of between 3-70 picogram/mL for estradiol while Quest states a reference range of between 10-50. For optimal health, estradiol should be in the range of 10-30 picogram/mL for a man of any age.
The fact that most aging men have too much estrogen does not mean it is acceptable for a man to have low estrogen. Estrogen is used by men to maintain bone density, and abnormally low estrogen levels may increase the risk for prostate cancer and osteoporosis. The objective is to achieve hormone balance, not to create sky-high testosterone levels without enough estrogen. The problem is that, if we do nothing, most men will have too much estrogen and far too little testosterone.

Total Testosterone
Some men have their total testosterone measured. Standard reference ranges are between 241-827 nanograms/dL for most laboratories. Many older men are below 241. Optimal levels of total testosterone for most men are between 500-827 nanograms/dL. If your levels are lower than 500 nanograms/dL or even a little higher and you still have symptoms, you should check your free testosterone by the Direct (RIA) method.
For other hormone tests, the following are considered to be optimal:
Where You Want to Be Comment
PSA Under 2.6 ng/mL
(optimal range) Standard reference range is up to 4, but if your level is persistently 2.6 or above, have a blood test to measure the percentage of free vs. bound PSA and a digital rectal exam to help rule out prostate cancer.
DHEA 400-560 mcg/dL
(optimal range) For older men, standard DHEA ranges are very low. It is important for men without prostate cancer to restore them to the youthful range (400-560).
DHT 20-50 nanogram/dL
(optimal range) Reference range is 30-85. DHT is 10 times more androgenic than testosterone and has been implicated in prostate problems and hair loss.
Luteinizing hormone (LH) Age 20-70: 1.5-9.3 mIU/mL 70+: 3.1-34.6 mIU/mL
(standard reference ranges)
Under 9.3 mIU/mL
(optimal range) If these levels are high, it is an indication of testicular testosterone production deficiency. LH tells the testes to produce testosterone. If there is too little testosterone present, the pituitary gland secretes more LH in a futile effort to stimulate testicular testosterone production. Testosterone replacement therapy should suppress excess LH levels. Low LH can also be a sign of estrogen overload, since too much estrogen can suppress LH activity. This could mean using an estrogen blocker like Arimidex could solve a testosterone deficiency problem.
Sex Hormone Binding
Under 30 nanomoles/L
(optimal range) Reference range is 13-71 nanomole/L. Excessive binding inactivates testosterone (297).

Referring to Table 1, there are five possible reasons why free testosterone levels may be low-normal (below the upper third of the highest number of the reference range):
• Too much testosterone is being converted to estradiol by excess aromatase enzyme and/or the liver is failing to adequately detoxify surplus estrogen. Excess aromatase enzyme and/or liver dysfunction is likely the cause if estradiol levels are over 30.
• emember, aromatase converts testosterone into estradiol, which can cause estrogen overload and testosterone deficiency.
• Too much free testosterone is being bound by SHBG (sex hormone binding globulin). This would be especially apparent if total testosterone levels were in the high normal range, while free testosterone was below the upper one-third range.
• The pituitary gland fails to secrete adequate amounts of luteinizing hormone (LH) to stimulate testicular production of testosterone. Total testosterone in this case would be in the bottom one-third to one-half range. (On LabCorp’s scale, this would be a number below 241-500 ng/dL.)
• The testes have lost their ability to produce testosterone, despite adequate amounts of the testicular-stimulating luteinizing hormone. In this case, LH would be above normal, and total testosterone would in very low normal or below normal ranges.
• Inadequate amounts of DHEA are being produced in the body. (DHEA is a precursor hormone to tes-tosterone and estrogen) (250).

Step 3: What to Do When Results Are Less Than Optimal
1. If estradiol levels are high (above 30), total testosterone is mid- to high-normal, and free testosterone levels are low or low-normal (at the bottom one third of the highest number on the reference range), you should:
• Make sure you are getting 80 mg a day of zinc. (Zinc functions as an aromatase inhibitor for some men.)
• Consume 400 mg of indole-3-carbinol to help neutralize dangerous estrogen metabolites. Cruciferous vegetables, such as broccoli and cauliflower, can also stimulate the liver to metabolize and excrete excess estrogen.
• Reduce or eliminate alcohol consumption to enable your liver to better remove excess estrogens (refer to the Liver Degenerative Disease protocol to learn about ways to restore healthy liver function).
• Review all drugs you are regularly taking to see if they may be interfering with healthy liver function. Common drugs that affect liver function are the NSAIDs: ibuprofen, acetaminophen, aspirin, the “statin” class of cholesterol-lowering drugs, some heart and blood pressure medications, and some antidepressants. It is interesting to note that drugs being prescribed to treat the symptoms of testosterone deficiency such as the statins and certain antidepressants may actually aggravate a testosterone deficit, thus making the cholesterol problem or depression worse.
• Lose weight. Fat cells, especially in the abdominal region, produce the aromatase enzyme, which converts testosterone into estrogen (242).
• Take a combination supplement providing a flavonoid called chrysin (1000 mg) along with piperine (10 mg) to enable the chrysin to be absorbed into the blood stream. Chrysin has been shown to be a mild aromatase inhibitor. This combination of chrysin and peperine can be found in a product called Super MiraForte.
• If all of the above fail to increase free testosterone and lower excess estradiol, ask your doctor to prescribe the potent aromatase inhibiting drug Arimidex (anastrozole) in the very low dose of 0.5 mg twice a week. Arimidex is prescribed to breast cancer patients at the dose of 1-10 mg a day. Even at the higher dose prescribed to cancer patients, side effects are rare. In the minute dose of 0.5 mg twice a week, a man will see an immediate drop in estradiol levels and should experience a rise in free testosterone to the optimal range.
2. If free testosterone levels are in the lower two thirds of the highest number in the reference range, but total testosterone is high-normal, and estradiol levels are not over 30, you should
• Consider following some of the recommendations in the previous section to inhibit aromatase because many of the same factors are involved in excess SHBG activity.
• Take 320 mg a day of the super-critical extract of saw palmetto and 240 mg a day of the methanolic extract of nettle (Urtica dioica). Nettle may specifically inhibit SHGB (42-44, 251, 252), while saw palmetto may reduce the effects of excess estrogen by blocking the nuclear estrogen receptor sites in prostate cells, which in turn activate the cell-stimulating effects of testosterone and dihydrotes-tosterone. Saw palmetto also has the effect of blocking the oxidation of testosterone to androstenedione, a potent androgen that has been implicated in the development of prostate disease (253).
3. If total testosterone is in the lower third of the reference range or below normal, and free testosterone is low, and estradiol levels are under 30, you should
• Initiate therapy with the testosterone patch, pellet, or cream. Do not use testosterone injections or tablets.
or
• See if your luteinizing hormone (LH) is below normal. If LH is low, your doctor can prescribe an individual dose of chorionic gonadotropin (HCG) hormone for injection. Chorionic gonadotropic hormone functions similarly to LH and can re-start testicular production of testosterone. Your doctor can instruct you about how to use tiny 30-gauge needles to give yourself injections 2-3 times a week.
After 1 month on chorionic gonadotropic hormone, a blood test can determine whether total testosterone levels are significantly increasing. You may also see your testicles growing larger.
Before initiating testosterone replacement therapy, have a PSA blood test and a digital rectal exam to rule out detectable prostate cancer. Once total testosterone levels are restored to a high-normal range, monitor blood levels of estradiol, free testosterone, and PSA every 30-45 days for the first 6 months to make sure the exogenous testosterone you are using is following a healthy metabolic pathway and not causing a flare-up of an underlying prostate cancer. The objective is to raise your levels of free testosterone to the upper third of the reference range, but to not increase estradiol levels beyond 30.
Excess estrogen (estradiol) blocks the production and effect of testosterone throughout the body, dampens sexuality, and increases the risk of prostate and cardiovascular disease. Once you have established the proper ratio of free testosterone (upper third of the highest number in the reference range) and estradiol (not more than 30), make sure your blood is tested every 30-45 days for the first 5 months. Test every 6 months thereafter for free testosterone, estradiol, and PSA. For men in their 40s-50s, correcting the excess level of estradiol is often all that has to be done.