www.drlowe.com--T3--Fibromyalgia, Hypothyroidism, Thyroid Hormone Resistance

bookcovr.jpg (3834 bytes)

The Metabolic Treatment
of Fibromyalgia
by Dr. John C. Lowe
Readers' Comments

T3
[Q&As are placed in reverse chronological order. In other words,
the latest Q&As come first. Earlier ones are further down the page.]

Latest Updates to drlowe.com

Also see: "Doctor Says No Patient Needs to Take T3,
and T3 Can Be Dangerous." Reply by Dr. John C. Lowe

Also: The Endocrinology Specialty's Presumption that T3 is dangerous

February 4, 2008
Question: In your book The Metabolic Treatment of Fibromyalgia, you seem to demolish Dr. Dennis Wilson’s theories. What you say makes sense to me. But what about the fact that lots of doctors, mine included, say they get patients well by using T3 as Dr. Wilson teaches. How do you reconcile on the one hand him being wrong about so much, and on the other hand patients getting well with his treatment?

Dr. Lowe: It is nothing new for people to succeed at practical matters despite not understanding why. An example from another field is Adolf Hitler’s economic successes before world war II. (I hasten to add that in using this example, I make no association whatever between Dr. Wilson’s beliefs or teachings and Hitler’s hideous crimes against humanity. I use the example because it’s about the issue of some people succeeding at something and maybe not knowing why.)

Historian John Toland (who lost relatives in the holocaust) wrote, “Hitler’s achievements in the first four years [of his regime] had truly been considerable and impressive. Like Roosevelt, he had paved the way to social security and old-age benefits. And, like Roosevelt, he had intuitively divined that the professional economists, whose thinking was hobbled by accepted theory, had little understanding of the depression. Both leaders, consequently, had defied tradition to expand production and curb unemployment.”[1,p.403]

Toland then quotes economist J. Kenneth Gallbraith: “That a nation oppressed by economic fear would respond to Hitler as Americans did to FDR is not surprising.” Toland inserted, “Perhaps [Hitler] understood economics too little to know what he was doing.” Then he quotes Gallbraith again: “But in economics it is a great thing not to understand what causes you to insist on the right course.”

Perhaps that’s true in economics. But I can’t agree that in medicine it’s a great thing not to understand why a clinician does the right thing and helps patients. I believe that Dr. Wilson failing to know why his therapy helps some patients is a not so great a thing. The T3 therapy he recommends does indeed help many patients. Based on his book,[4,p.17] however, he is mistaken about why the therapy helps them.

For example, as I wrote in The Metabolic Treatment of Fibromyalgia,[2,pp.844-6] he claims that T3 increases body temperature, and the increased temperature activates enzymes that enable patients to get well. It’s true that in a research lab, raising the temperature of a petri dish may increase the activity of some enzymes in it. But inside the human body, the range of temperature changes is generally too small to markedly change the activity of enzymes.

Dr. Wilson has it backward: T3 doesn’t Increase enzyme activity by raising the body temperature; instead, it’s the other way around: T3 increases gene transcription for enzymes (such as sodium-potassium-ATPase), and the resulting increased enzyme activity raises the body temperature. The enzymes do this by cleaving phosphates off ATP molecules. The cleaving releases the energy that was maintaining the phosphate bonds. About half the energy is used to fuel chemical reactions. The other half is released as body heat.

This may seem trifling, and indeed, the issue of which comes first, increased temperature or enzyme activity, may only be an academic concern. But other issues I believe Dr. Wilson gets wrong have practical implications. For example, I don’t believe sustained-release T3 is the best use of T3. The reason? The longer T3 stays in the small intestine, the greater the chance that calcium and other agents in food will bind some of the T3. The binding will then carry the T3 out in the patient’s stool, reducing the amount that reaches his blood.

Moreover, Dr. Wilson’s idea that the enzyme that converts T4 to T3 gets “stuck”[3,p.2] is entirely without scientific substantiation.[2,p.280] In fact, the relevant research literature shows this notion to be close to the outer realm of possibilities. Directing treatment at a “stuck” enzyme is to therapeutically shot way off target. In contrast, treatment intelligently directed at a target that is truly instrumental in causing a patient’s symptoms is far more likely to benefit the patient.

As may be with Hitler’s economic successes, Dr. Wilson’s treatment protocol enables some patients to get well, although I believe he doesn’t know why. Too of many of the mechanisms he proposes are refuted by the research literature. Therefore, I believe that what I wrote of the success of his treatment and the mechanisms by which it does so is consistent. Nonetheless, I appreciate you bringing the seeming inconsistency to my attention.

Reference
1. Toland, J.: Adolt Hitler. NY, Ballantine Books, 1976.
2. Lowe, J.C.: The Metabolic Treatment of Fibromyalgia. Boulder, McDowell Publishing Co.,
2000.
3. Wilson’s Syndrome Patient Instruction Sheet. Publisher nor date designated.
4. Wilson, E.D.: Wilson’s Syndrome. Orlando, Cornerstone Publishing Co., 1991.

November 9, 2005

Question: I am a 41-year-old woman who lives on the east coast. About a year ago, my doctor tested me by your protocol and lab tests. When he and I did a telephone consultation with you, he agreed to put me on Cytomel. I now take 100 mcg per day. I'm doing your protocol as you describe it in Your Guide to Metabolic Health. I take vitamin supplements daily and exercise at least three times a week. Since I started the protocol and Cytomel, I've regained my life. I have no more pain, no migraines, no swelling, no tingling, no insomnia, and I'm no longer cold all the time. The list of improvements goes on and on. For example, I've lost 65 lbs. I feel great. I suffered for 10 years of my life without a correct diagnosis, so needless to say, I don't want to go back.

The problem I'm facing is that my TSH is very low and my T3 is high. On occasion, I feel that my heart is pounding or I feel anxious. Other than these symptoms every once in a while, I don't feel overstimulated. But because of these symptoms and the lab results, my doctor wants to take me totally off T3 and send me to a local endocrinologist. I've inquired at the endocrinologist's office and learned that he doesn't believe in using Cytomel or your protocol. What can I do? There must be other options than just taking the Cytomel away completely. I feel good now and live an active lifestyle. I don't want that taken away. Please help. I'm desperate not to go back to the way I was before.

Dr. Lowe: The improvements you describe are typical of what we hear from patients using high-enough doses of Cytomel. Because of your improvements, and because your symptoms of possible overstimulation are occasional, taking you completely off Cytomel seems to me radically improper.

For someone taking 100 mcg of T3, we expect your pattern of lab results—a low TSH and high T3. However, your TSH and T3 levels are irrelevant to whether you're overstimulated or not. Two studies we just completed confirm other researchers findings: these tests are not reliable gauges of a patient's metabolic status. Many patients taking T3 have TSH and T3 levels like yours but still have severely low metabolic rates. Their metabolic rates become normal only when they increase their dosages further. Their metabolic rates become normal and they have no detectable overstimulation.

In some cases such as yours, the patient's Cytomel dose may need to be reduced. But symptoms such as occasional heart pounding and anxiety are usually not due to a patient's Cytomel dose. I say this because when Cytomel is solely responsible, symptoms of overstimulation are consistent, not occasional.

However, it's important to consider whether a patient's Cytomel dose is high enough to sensitize her to other stimulating chemicals. (Examples are caffeine in coffee, theobromine and theophylline in chocolate, and ephedrine in cold medicines.) If the Cytomel has excessively sensitized her to such chemicals, then when she consumes them in foods or medicines, she'll experiences transient symptoms of overstimulation. She'll be overstimulated for a few hours, but then the symptoms will disappear. The Cytomel will have also excessively sensitized her to her own adrenaline and noradrenaline. Because of this, emotional arousal or intense exercise might also cause temporary symptoms of overstimulation.

The proper solution to occasional symptoms of overstimulation is to find the causes and correct them. The patient's may have to reduce her Cytomel dosage low enough to relieve excess sensitivity to stimulating chemicals. And she may have to reduce her intake of such chemicals. In general, though, the proper approach is not to take the patient completely off Cytomel—not when it has relieved her troubling and disabling symptoms.

Most endocrinologists subscribe to the practice guidelines of the American Association of Clinical Endocrinologists. When a patient such as you sees one of these endocrinologists, he’s likely to take her off T3 and switch her to T4-replacement. As many patients have told us, when an endocrinologist switched them to T4-replacement, they became ill and dysfunctional again. These reports are consistent with studies that show the ineffectiveness and potential harm of T4-replacement. The studies show that T4-replacement leaves many patients suffering chronically from hypothyroid symptoms[1][2][3][4][5][6][7] and gaining weight they can't lose through dieting and exercise.[8] The patients are also likely to use more drugs and develop one or more of several potentially-fatal diseases.[9]

Potential harm from T4-replacement has thus been scientifically documented. In view of the risks, you must consider for yourself whether you'll permit your therapy to be changed from Cytomel to T4-replacement. If you decide not to permit it, you can seek out an alternative doctor who understands how ineffective and harmful T4-replacement is for many patients. Alternative doctors are generally more cooperative than conventional doctors, and most of them take the time to learn the cause of troubling symptoms. Because of this, you should be able to find one who'll help you ferret out and correct what's causing your occasional symptoms of overstimulation.

References

1. Walsh, J.P., Shiels, L., Mun Lim, E.E., et al.: Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism. J. Clin. Endocrinol. Metab., 88(10):4543-4550, 2003.

2. Sawka, A.M., Gerstein, H.C., Marriott, M.J., et al.: Does a combination regimen of thyroxine (T4) and 3,5,3'-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial. J. Clin. Endocrinol. Metab., 88(10):4551-4555, 2003.

3. Clyde, P.W., Harari, A.E., Getka, E.J., and Shakir, K.M.M.: Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. J.A.M.A., 290:2952-2958, 2003.

4. Cassio, A., Cacciari, E., Cicgnani, A., et al.: Treatment of congenital hypothyroidism: thyroxine alone or thyroxine plus triiodothyronine? Pediatrics, 111(5):1055-1060, 2003.

5. Bunevicius, R., Kazanavicius, G., Zalinkevicius, R., and Prange, A.J. Jr.: Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N. Engl. J. Med., 11:340(6):424-429, 1999.

6. Bunevicius, R. and Prange, A.J.: Mental improvement after replacement therapy with thyroxine plus triiodothyronine: relationship to cause of hypothyroidism. Int. J. Neuropsychopharmacol., 3(2):167-174, 2000 (June).

7. Bunevicius, R., Jakubonien, N., Jurkevicius, R., Cernicat, J., Lasas, L., and Prange, A.J. Jr.: Thyroxine vs thyroxine plus triiodothyronine in treatment of hypothyroidism after thyroidectomy for Graves' disease. Endocrine, 18(2):129-133, 2002.

8. Tigas, S., Idiculla, J., Beckett, G., and Toft, A.: Is excessive weight gain after ablative treatment of hyperthyroidism due to inadequate thyroid hormone therapy? Thyroid, 10(12):1107-1111, 2000.

9. Saravanan, P., Chau, W.F., Roberts, N., et al.: Psychological well-being in patients on ‘adequate' doses of L-thyroxine: results of a large, controlled community-based questionnaire study. Clin. Endocrinol. (Oxf.), 57(5):577-585, 2002.

January 9, 2004

Question: I am a doctor in Australia who uses T4/T3 combinations. I’m aware of four subtypes of T3 receptors, but I cannot find any literature on any T4 receptors. Are there any? If not, then why do we need T4 supplementation rather than just T3 alone? Would appreciate some journal references.

Dr. Lowe: In my book The Metabolic Treatment of Fibromyalgia, I refer to thyroid hormone receptors as "T3-receptors." I do so because evidence suggests that it is T3 and not T4 that binds to thyroid hormone receptors on genes within the nuclei of cells. In laboratory tests, T4 does bind to thyroid hormone receptors, but with far lower affinity than does T3.

It is debatable, however, whether T4 binds to thyroid hormone receptors in our bodies and exerts metabolic effects. Most thyroid researchers today argue that T4 is a storage form of T3. We believe that T4 exerts metabolic effects only after the enzyme 5'-deiodinase removes the fourth iodine atom from the T4 molecule. Removing the iodine atom, of course, converts T4 to T3.

PubMed (US National Libraries of Medicine) lists many review papers on thyroid hormone receptors. If you go to PubMed and type in the key words "thyroid hormone receptor and review," some 17 pages of abstracts will come up. You can then read the abstracts and find articles that you're interested in. If you have a medical library close to you, it will probably carry some journals that contain the articles.

If you don't have a copy of The Metabolic Treatment of Fibromyalgia, I recommend it. In the book, I describe and explain the function of thyroid hormone receptors. I also provide massive documentation for the safety and effectiveness of T3 and T4/T3 therapies as alternatives to the generally ineffective T4-replacement. You may find the documentation of value if you have occasion to defend you're practice of T4/T3 therapy.

You asked, if we don't have T4 receptors, "then why do we need T4 supplementation rather than just T3 alone?" With rare exception, we don't.

No one can rationally defend T4 supplementation on scientific grounds. I say this because the widespread use of T4 supplementation is not based on scientific studies that show it to be safer or more effective than the use of T3 alone. Instead, its widespread use is the result of a financial venture between the endocrinology specialty and corporations that profit from sales of the most commonly prescribed brands of T4.

Our long clinical experience shows that in general, patients respond far better to T3 alone than they do to T4 alone. Moreover, our safety monitoring of patients shows that the responsible use of T3 alone is as safe as the use of T4 or T4/T3. By "responsible use," of course, I mean employing the same precautions that are appropriate to the use of any thyroid hormone product.

September 24, 2002

Questions: My rheumatologist treats me for my fibromyalgia with amitriptyline, brand name Elavil. I haven’t gotten any better from using this drug for a year. At my last visit with him, I asked him to prescribe T3 so that I can see if your type of treatment helps. He went ballistic! He told me T3 will give me osteoporosis and might make me have a heart attack. He said he never prescribes dangerous drugs and he’s not going to start by submitting to patients’ requests for T3. He said others have also asked for it. If T3 is so dangerous, why do you have your patients use it?

Dr. Lowe: First, let me clarify an important point: Our treatment protocol does not consist solely of patients using T3. Only two groups of our patients use T3. One group is patients who appear to have thyroid hormone resistance. The other group is hypothyroid patients who fail to benefit from desiccated thyroid. Our other patients use desiccated thyroid as part of their metabolic rehabilitation regimen. (We don’t, of course, waste time any more trying T4 alone; it’s too seldom of any use.)

Now, to address your rheumatologist’s assertion that T3 is dangerous, and his implication that amitriptyline is not. I think the best way to reply to him is to quote publications that are available to him. In the USA, when patients get their prescriptions filled for T3 (usually the brand Cytomel), the pharmacist usually gives them a leaflet on the product. The leaflet contains the following statement:

This statement makes a fact perfectly clear: When used sensibly, T3 is extraordinarily safe among prescribed drugs. When I say extraordinarily safe, I’m comparing T3 with drugs such as the amitriptyline which your rheumatologist prescribes for you. Below is a list of potential harmful effects of amitriptyline. This list comes from the Physician’s Desk Reference, 53rd edition, Medical Economics Company, Inc., Montvale, 1999, page 3418.

Some patients took amitriptyline at the same time as monoamine oxidase inhibitors. Some of them had crises of extremely high fever. Some had severe convulsions. Others died.

Patients with cardiovascular disease have had a range of harmful effects from taking amitriptyline. Some had irregular heartbeats, extremely rapid heart rate, and abnormalities of their EKGs. Some had heart attacks and strokes. Patients had altered impulse conduction between the chambers of the heart and heart block. Others had low blood pressure, orthostatic hypotension (which many fibromyalgia patients already have), fainting, and palpitations. Other patients had high blood pressure.

Amitriptyline enhances some patients’ response to alcohol, barbiturates, and other central nervous system depressants. If a patient taking amitriptyline drinks excess alcohol, "potentiation may increase the danger inherent in any suicide attempt or overdosage."

In pregnant women, amitriptyline crosses the placenta to the fetus. The children of some mothers who took the drug during pregnancy had harmful central nervous system effects, limb deformities, and delays in development.

The patient using amitriptyline may go into a coma. She may have tremors, trouble coordinating her muscles during movement, confusion, disorientation, delusions, hallucinations, and seizures. She may develop a peripheral nerve disorder with numbness, tingling, and other abnormal sensations in the hands, feet, arms, and legs. She may have abnormal involuntary movements such turning of the head one side. Her speech may be impaired, and she may have problems using language properly. Her ability to concentrate may diminish, and she may become restless, excited, and anxious. She may have insomnia, nightmares, and be drowsy, dizzy, weak, and fatigued. She may have headaches and ringing in the ears.

The patient may also have skin rashes, eruptions of itching skin wheals, sensitivity to light, and edema of her face and tongue. The drug may suppress her bone marrow. Her white blood cell and platelet count may drop, and her eosinophil count may rise. Her skin may hemorrhage, and she may develop hepatitis and jaundice. She may be nauseated and have epigastric distress, vomiting, and anorexia. She mouth may be dry and inflamed. She may have odd tastes and lose her sense of taste. The parotid glands in her mouth may swell, and her tongue may turn black. She may also have diarrhea. Her blood sugar levels may become abnormal, and she might suffer liver failure.

The male’s testicles and breasts may swell, and he may become impotent. The female’s breasts may swell and her nipples discharge a milky fluid.

The patient may gain weight and her hair begin falling out. She may urinate and perspire too much. On the other hand, she may retain urine, and her urinary tract may dilate. She may be constipated, and her bowel may become obstructed from paralysis of the bowel wall.

The pressure in her eyes may rise. Her pupils may dilate and her vision blur, and the ability of her eyes to adjust to distance may diminish.

Some patients have developed a lupus-like syndrome with arthritis with positive tests for ANA and rheumatoid factor.

As you can see, T3 has no reported adverse effects. By contrast, amitriptyline has 88 reported potential harmful effects—not the least of which is death. Let me understate the circumstance as politely as I can: Your rheumatologist seems confused about the relative risks of using T3 and amitriptyline. If so, perhaps your sharing this question and answer with him will clear up his confusion.

April 13, 2002

Question: My doctor has begun using your T3 protocol and is getting good results. Thanks for developing the protocol. I get the idea from Internet news groups that more doctors are now using your protocol. Is this true, and do you have any idea how many doctors are using your T3 protocol?

Dr. Lowe: Thank you for writing and letting me know that your doctor is now prescribing T3. I don’t know how many doctors are prescribing T3. I do know, however, that over the last several years, many doctors have begun prescribing it in the United States, Canada, and the United Kingdom. This is good news for patients: As steadily more doctors begin using T3 and seeing good results, the unfounded bad name given T3—mainly by conventional endocrinologists—will be rectified. Contrary to the false belief of most conventional endocrinologists, T3 is harmless when used properly, and it dramatically improves many people’s health.

You mentioned our "T3 protocol." It’s important to understand that this term is not an accurate designation of our protocol. Many people mistakenly believe that our protocol solely involves the use of T3. They do so, I suspect, for a particular reason: About a third of our fibromyalgia patients have thyroid hormone resistance, and these patients improve or recover only with the use of T3—although they must use T3 within the context of a comprehensive program of metabolic rehab. How this information translates in some people’s minds into our protocol solely involving T3 is beyond me.

Most of our fibromyalgia patients have either primary or central hypothyroidism. These patients improve or recover with the use of desiccated thyroid (such as Armour)—but, again, only when they use desiccated thyroid within the context of a comprehensive program of metabolic rehab.

I’ll be grateful if you’ll relate this to your doctor so that he’ll have an accurate understanding of what our protocol involves. Thank you again for writing, and best of luck with your treatment.

January 30, 2002

Question: I’m a physician who has just begun using T3 in my practice. One thing I’m concerned about is the short half-life of T3. Shouldn’t patients divide their daily dose up and take part of it at least twice each day, or instead use sustained-release T3? It seems that this would allow the effects of T3 to continue through the day rather than stop midway or in the evening?

Dr. Lowe: The short time that T3 is in the circulating blood isn’t the limit of its beneficial effects on the body. When T3 binds to T3-receptors on genes, the binding regulates the transcription of mRNAs, and the mRNAs are later translated into proteins. The transcription and translation initiated by the binding of T3 to T3-receptors occur in waves, and these waves far outlast the T3 that started them at the chromosomes. Moreover, the newly synthesized proteins themselves far outlast the transcription and translation. As a result, a single dose of T3 will be long gone from the patient's system before he or she experiences most of the benefits of that dose—a molecular and metabolic yield that may smoothly spread out over one to three days. The "rocky road" (inconsistent physiological responses) that some physicians fear with single daily doses of T3 simply isn't a feature of this dose schedule.

August 7, 2001

Question: During nine months of being very sick, I went through several doctors. Then I read your contribution about T3 in Mary Shomon's book, Living Well With Hypothyroidism. Soon after, I found a doctor who agreed to try your treatment. It worked. We started off with 25 mcg of Cytomel and worked our way up until I felt normal. The effective dosage was 125 mcg. I now take 125mcg of T3 in a time-released capsule (75 mcg in the morning and 75 mcg at night). I have been feeling great! However, my doctor is now afraid that we're masking another problem, and he's dropping my dose way down. I wanted your advice since it was truly you who was able to end my being sick. Obviously, I don't want to mask another problem, but I don’t want to go back to the way I was before. I couldn't do anything from work to working out. Please let me know your thoughts on this matter. I greatly appreciate your help.

Dr. Lowe: Congratulations on recovering with the use of T3. I hope your doctor will continue to cooperate and treat you with the dosage of T3 that has proven effective for you. Your having done so leaves me without an idea what your doctor is referring to as another problem masked by the T3.

Your doctor is correct, but only in trifling way. Logically, when someone gets well with the use of T3, we can't conclude that the T3 has relieved a thyroid hormone deficiency or thyroid hormone resistance. With most patients, we only presume that thyroid hormone deficiency or resistance is the mechanism that was causing the health problems that T3 relieved; and we only presume that T3 has corrected a deficiency or overridden resistance. It is within the realm of possibility—but the realm's outermost hinterland—that the T3 may be compensating for some other problem that was causing the patient's symptoms.

Most patients, though, are pragmatic; their main concern is getting and staying well—not remote theoretical possibilities. They are likely to ask, "If my use of T3 isn't harming me, what difference does it make if the T3 is compensating for some other problem?" Again, I'm afraid, the answer is theoretical: T3 could be compensating for some stealthy, progressive, disease-causing process that might eventually make the patient ill or kill her. If so, then the responsible and humane course of action would be to learn what the problem is and properly deal with it; to merely compensate for it with the use of T3 would been irresponsible and inhumane.

But you wrote that before beginning the use of T3, you "went through several doctors." I assume that these doctors did diagnostic testing to rule out other health problems and found nothing. If this is true, it seems unlikely that further diagnostic work will unearth problems the T3 could be effectively compensating for. If so, to me, it seems imprudent for you to become ill again (by reducing her T3 dosage) just for a theoretical possibility that T3 may be compensating for another health problem. Besides, I can't think of an underlying condition that T3 might be compensating for that your doctor should be concerned with.

Your doctor and you might also consider another possibility. If you do have some other health problem that T3 is effectively compensating for, T3 might be the proper treatment for that health problem. The T3, by compensating for the other health problem, might in fact prevent the other problem from causing you harm over the long haul.

March 12, 2001

Question: My doctor will only prescribe Synthroid for my hypothyroidism. This medication doesn’t seem to work for me because I still have all my hypothyroid symptoms. I asked him to let me also use Cytomel. He refused and said that Cytomel is extremely dangerous. What is so dangerous about Cytomel?

Dr. Lowe: When used properly, Cytomel is not dangerous. Your doctor is misinformed.

Synthroid contains the form of thyroid hormone called T4. Many hypothyroid patients, such as you, benefit little or none from its use, despite the brand they use. Cytomel contains the more metabolically active form of thyroid hormone called T3. T3 is effective for many patients who failed to benefit from the use of T4.

Your doctor’s false belief about the use of T3 isn’t unusual. Many doctors believe that T3 is dangerous. When pharmacists fill prescriptions for Cytomel, however, they often give patients a leaflet that makes the safety of T3 perfectly clear. Verbatim, the leaflet reads: "NO COMMON SIDE EFFECTS HAVE BEEN REPORTED with the proper use of this medicine." (Medi-Span, Inc.: Database Version 97.2. Data © 1997.) When used with reasonable precaution, T3 is perfectly safe.

Doctors commonly prescribe a variety of drugs to control hypothyroid symptoms that continue despite patients’ use of T4. In stark contrast to T3, most of these drugs have long lists of potentially harmful effects. The safety of T3 use starkly contrasts with the risks of using the other drugs. Since this fact is well documented in the medical literature, I find it baffling that so many doctors falsely believe just the opposite.

November 19, 2000

Question: This past week, I talked with my endocrinologist about letting me use T3. She has read information I gave her from your website and commented that it is interesting. However, she is wary of patients using T3 and advised me against using it. I am wondering why you aren’t uneasy about recommending T3 when my endocrinologist is?

Dr. Lowe: I am comfortable advising physicians on the use of T3 because of my knowledge of the hormone and my experience (both clinical and experimental) with its use. Moreover, my book The Metabolic Treatment of Fibromyalgia is a comprehensive text on thyroidology and contains more scientific information on the use of T3 than any other book ever written. In contrast, most conventional endocrinologists have little to no knowledge of T3. Also, they have little to no clinical experience with its use. Therefore, for them to represent their opinions about T3 as expert advice is a pretense and raises ethical questions.

Conventional endocrinologists' lack of knowledge about T3 results from conduct that is clearly unscientific—that is, overall, they accepted without question mandates passed down to them by old guard thyroid specialists, much as loyal military personnel obediently and unquestioningly comply with orders from higher command. The particular mandate of conventional thyroid specialists I refer to here is this: "The only thyroid hormone preparation a doctor should ever prescribe is T4 (thyroxine)."

To the discredit of both conventional endocrinologists and the thyroid specialists whose edicts the obey, this mandate is not scientifically based. Instead, it’s based on a powerful marketing campaign of a major pharmaceutical company. This marketing campaign, not science, is precisely why most doctors robotically write "Synthroid" on their prescription pads when they learn that a patient is hypothyroid. Conventional doctors, including endocrinologists, have allowed their minds to be utterly subjugated by this marketing campaign. As a result, they’ve deprived themselves of clinical experience with any thyroid preparation other than T4.

So, the wariness of conventional doctors, including endocrinologists, about the use of T3 is born of ignorance. Thus, as a whole, they are the least qualified doctors from whom to seek expert advice about T3. In the past several years, many unconventional doctors have acquired extensive experience with the use of T3. These doctors include many family physicians, physiatrists, psychiatrists, nutritional and holistic doctors, and naturopathic physicians. For expert advice about T3, it seems prudent to bypass endocrinologists and to look to these more knowledgeable and experienced doctors.

November 10, 2000

Question: I have fibromyalgia and normal thyroid test results. I am on a very good diet and exercise regularly, as you advise patients to do. Based on your work, my doctor is treating me with T3. But rather than the plain T3 you recommend, he is treating me with timed-released T3. He is convinced that timed-release T3 is the best way since he believes that Cytomel (plain T3) is "a very bumpy road." My question is this: Can a fibromyalgia patient with normal thyroid test results recover taking 125 mcg of timed-release T3? Thank you for your time and consideration.

Dr. Lowe: It is possible that a fibromyalgia patient with normal thyroid test results can recover with the use of timed-release T3. However, the likelihood of recovery is far less than with the use of plain T3. Your normal thyroid test results suggest that your fibromyalgia symptoms are the result of partial cellular resistance to thyroid hormone. For most patients with thyroid hormone resistance, timed-release T3 doesn’t work well, if it works at all.

This past year, several Internet doctors, who give advice on thyroid hormone therapy, sired a false belief about the effects of plain T3 on the body—that it causes "physiological instability." These doctors must have a large audience. I say this because I’ve heard (through e-mails, letters, and phone calls) echoes of their false belief in almost every conceivable variation of words. Your doctor’s belief about plain T3 being "a very bumpy road" is an especially creative and graphic variation of the false belief.

Let me explain the error in the Internet doctors’ thinking. Within a couple of hours after a patient ingests a single daily dose of plain T3, the blood level of T3 peaks. The Internet doctors infer that because the blood level of T3 peaks, the metabolic reactions of body tissues also peak, resulting physiological instability. Their inference is wrong.

The origin of the doctors’ erroneous thinking may be the reaction of the heart to T3 in some individuals. In some patients who take a single daily dose of plain T3, the heart rate slightly speeds up for a short time. The speed up results from a direct effect of the T3 on heart cells. Avoiding this increase in heart rate in patients with fragile heart conditions is prudent. However, in the vast majority of patients, the increased heart rate is transient and harmless. This is especially true for patients who take heart-protective nutrients and engage in regular cardiovascular exercise. (I have written more on drlowe.com about the effects of T3 on heart function.)

In contrast to the heart in some individuals, most other body tissues don’t react to plain T3 with a metabolic surge. Certainly, plain T3 doesn’t cause physiological instability. Recently, I explained the biological systems that buffer the physiological effects of plain T3, preventing physiological instability. I encourage your physician and you to read this explanation. I hope the explanation will make one thing clear: that overall, only two reactions of the body to plain T3 might, by a stretch, be interpreted as physiological instability: (1) the short-lived peak in the blood T3 level, and (2) a slight speed up of the heart rate. In most patients, neither of these is of any clinical importance.

My research group has spent the past ten years studying fibromyalgia caused by thyroid hormone resistance. We have laboratory proof that about one third of the fibromyalgia patients we’ve evaluated and treated have thyroid hormone resistance. Our treatment results have forced us to a firm conclusion: For most fibromyalgia patients with thyroid hormone resistance, using plain T3 (as part of comprehensive metabolic rehab) is the only route to recovery. With the proper use of plain T3, 75% to 85% of these patients permanently recover. It will be tragic indeed if, despite our research findings, some resistance patients are blocked from taking this route to recovery by a well-intended but false idea that plain T3 is "a very bumpy road" to travel.

July 5, 2000

Question: I was on a fibromyalgia discussion group last night. The subject of discussion was patients who have thyroid hormone resistance. Someone posted that you believe plain T3, taken once a day, is more effective than sustained-release T3 for these patients. This seems contrary to the belief of Dr. Dennis Wilson. If you believe this, why would plain T3 be more effective?

Dr. Lowe: Whoever posted the statement was right. In my experience, for thyroid hormone resistance patients, sustained-release T3 is a poor alternative to plain T3 taken once per day. We don’t have enough evidence to know why plain T3 is more effective.

It is possible, however, that some patients have resistance due to mutations in the c-erbA-beta gene. Such mutations would result in a patient having mutant T3-receptors that have a low binding affinity for T3. (We’ve had gene sequencing on a few of our patients to identify mutations in the gene, but the results were negative. However, we’d have to test many more patients before concluding that mutations in the gene aren’t generally involved.) Lab studies have shown that mutant, low affinity T3-receptors properly regulate gene transcription only after they're exposed to saturation amounts of T3. Under normal conditions, T3-receptors aren’t saturated, and the use of sustained-release T3 isn’t likely to provide saturation. Saturation isn’t likely to occur with sustained-release T3 because the T3 enters cells only in small amounts over an extended time. As a result, it’s not likely that large enough amounts of T3 will reach the receptors at one time to saturate them. But plain T3 in single doses enters cells in larger amounts. These larger amounts may provide the saturation needed to provoke transcription regulation by mutant T3-receptors. If so, these saturation amounts of T3 may induce waves of transcription that on the clinical level relieve symptoms of hypometabolism.

February 1, 1998

Question: Is there any indication for using a divided dose of T3 in a patient whose resting heart rate is already 100? What heart rate would be considered overstimulation if resting is 100? My before lab values showed a normal TSH with a low T4 and free T3. Thanks.

Dr. Lowe: If your resting heart rate is 100, I believe it is important to determine why before beginning thyroid hormone. Some conditions that cause a high resting heart rate contraindicate taking thyroid hormone. If you have one of these conditions, taking thyroid hormone in divided dosages is not likely to avert adverse effects.

There are several conditions that contraindicate the use of thyroid hormone until they are properly dealt with. One is an adrenal tumor called a pheochromocytoma. The tumor secretes epinephrine (adrenaline) and norepinephrine (noradrenaline). This type of tumor is usually benign. But the increased amounts of these hormones can overstimulate some body tissues, such as the heart. The hormones do this by binding to proteins (called beta-adrenergic receptors) on the cells of the tissues. Taking thyroid hormone increases the population of these receptors on the heart muscle. The increase in the amounts of epinephrine and norepinephrine (because of the tumor) reaching the heart, and binding to the increased population of beta-receptors (because of the thyroid hormone) will speed the heart rate even more. Speeding the heart rate in someone with severe cardiovascular deconditioning can be dangerous. The danger is possible impaired blood flow through the coronary arteries due to fat accumulation. The likelihood of this is high if fat metabolism has been impaired by too little thyroid hormone regulation. As the heart rate speeds up, the increased oxygen demand of the heart may cause ischemia (insufficient blood supply). Ischemia can damage the heart muscle. And in extreme cases, myocardial ischemia is lethal.

Another condition that can predispose one to heart muscle ischemia is severe cardiovascular deconditioning. This is common among fibromyalgia patients. Deconditioning of the heart muscle can reduce the volume of blood pumped out of the heart into the circulation with each contraction. The volume of blood pumped out may be too small to meet the oxygen demand of body tissues. If so, various regulatory mechanisms will speed the rate of heart contractions. (The increased speed of contractions increases the blood entering the circulation, and this gets more oxygen to the tissues.) The speed of contractions will increase until the demand of tissues for oxygen is met. Someone with a small heart in relation to the body mass will have an even faster heart rate naturally. If this heart-speeding process is occurring, and the individual takes thyroid hormone, the heart rate is likely to accelerate even more. And again, ischemia is a risk if the coronary arteries are partially occluded.

Of course, these two conditions don't exhaust the possibilities. I use them just to illustrate my point—that it is important to determine why your resting heart rate is so rapid before beginning thyroid hormone.

I should also mention that if a patient is taking an antidepressant that prevents the reuptake of serotonin, this alone may account for tachycardia (a heart rate of 100bpm or greater). This isn't a rare reaction in patients. In addition, in some patients the increase in serotonin in the heart causes the coronary arteries to constrict. This is most likely the basis for the increase in the incidence of ischemic heart disease and heart attacks among people using these antidepressants over a prolonged time.

Incidentally, one possible cause of your normal TSH and low T4 and free T3 is hypothalamic hypothyroidism. In this condition, the TSH released from the pituitary gland may have a faulty molecular structure. If so, the TSH, though normal in amount, wouldn't stimulate your thyroid gland to release enough T4 and T3. A laboratory can test your TSH for "bio-activity." If this is the problem, the solution to your low hormone levels is to take exogenous thyroid hormone—but only after learning why your resting heart rate is so rapid.

December 24, 1997

Question: Dr. Smith recently referred one of his patients back to his primary care physician for a prescription for T3. The physician adamantly refused, saying that T3 was old hat, unstable, and caused strokes. Is there anything in the literature about any relationship between T3 and strokes?

Dr. Lowe: The physician should call a pharmacy and request the leaflet given to patients when they pick up a Cytomel (T3) prescription. The physician would learn, as the patient leaflet on Cytomel explains, "POSSIBLE SIDE EFFECTS: NO COMMON SIDE EFFECTS HAVE BEEN REPORTED with proper use of this medication." Other than Nystatin, he probably will find that no other drug he might prescribe is as free from adverse effects as T3.

I don't know what he means by "old hat." As medications go, T4 has been around a lot longer, and desiccated thyroid even longer. As for stability, T3 is certainly as stable as T4 and desiccated thyroid. Synthroid (the most prescribed form of thyroid hormone) is not more stable than Cytomel. At this time, Synthroid users are being reimbursed millions of dollars, partly because of significant variability in the potency of the product.

And ". . . caused strokes"? If anything, the use of T3 may help prevent strokes. I scanned MEDLINE for studies on "T3" and "strokes" published between 1966 and 1997. These key words were mentioned in 43 publications. Most publications reported the beneficial effects of T3 on cardiovascular function. The word "stroke" was most often used in regard to the "stroke work in cardiac contractility" (a physiological description)—not in the sense of cerebrovascular accidents (strokes). I'll mention just a few representative publications. These suggest that it is urgent for the physician you mention—for his patients' welfare—to quickly update his knowledge.

In one study, a researcher found that T3 levels were significantly lower in 42 of 65 stroke patients. [Liang, D.S.: Stroke and thyroid hormones. Chinese Journal of Neurology & Psychiatry, 24(6):352-354, 384, Dec., 1991] It is certainly possible that the low levels of T3 were partly responsible for the strokes. It is well-known that low thyroid hormone levels result in high blood fat levels, and high blood fat levels predispose patients to heart attacks and strokes. By lowering blood fat levels, the use of T3 is likely to help prevent, rather than cause, strokes in some of the above-mentioned physician's patients.

The use of T3 is even beneficial in patients with the most frail heart conditions. Researchers in one study reported, "Triiodothyronine [T3] administration in patients undergoing cardiopulmonary bypass surgery is safe, may lessen the need for pharmacological (vasodilator) therapy, but may increase heart rate." [Vavouranakis, I., et al.: Triiodothyronine administration in coronary artery bypass surgery: effect on hemodynamics. Journal of Cardiovascular Surgery, 35(5):383-389, Oct., 1994]

In rabbits recovering from post-ischemic heart damage, T3 enhanced recovery without adverse effects such as excessively forceful heart contractions. [Wechsler, A.S., et al.: Effects of triiodothyronine on stunned myocardium. Journal of Cardiac Surgery, 8(2 Suppl):338-341, Mar., 1993]

In another study, researchers induced severe ischemic heart injury in rats. T3 was administered to some but not other damaged rats. They wrote, "We conclude that administration of T3 in a severe left ventricular injury model significantly augments rapid ventricular recovery." [Salter, D.R., et al.: Acute severe post-ischemic myocardial depression reversed by triiodothyronine. Annals of Thoracic Surgery, 54(2):301-305, Aug., 1992]

As I said, these are only a few representative publications. I could cite many other studies that show the opposite from what the above-mentioned physician believes. Every physician has an ethical responsibility to stay abreast of the scientific evidence related to any medical issue he or she renders judgment on. I would urge this physician to live up to this responsibility and use MEDLINE to read the relevant studies. He will learn that rather than causing strokes, T3 is more likely to prevent them. If he doesn't do this, and correct his beliefs about T3, he himself may be responsible for causing in some of his patients the very harm he fears T3 will do.

December 17, 1997

Question: I've been told that you are about to participate in some studies to test the effectiveness for fibromyalgia of the Wilson's syndrome protocol. The point, it seems, would be to see if cycling with timed-release T3—with the eventual goal of "getting off" T3—would alleviate fibromyalgia symptoms without the side effects usually seen with full-strength, one-time-a-day doses of Cytomel. If this is true, why then does your protocol seem to specify only one full dose of non-timed-release Cytomel? And also, if a person can get off the T3, do you believe the cycling will "cure" the resistance?

Dr. Lowe: This is the first I've heard of my presumed participation in a study of Dr. Dennis Wilson's treatment protocol. I would decline to participate for several reasons.

First, the belief that timed-released T3 is of any advantage over plain T3 (such as Cytomel) is simply false. My understanding of the processing and action of T3 in the body leaves me without a plausible explanation of how timed-release T3 might be superior. Some physicians have told me that timed-released T3 ". . . avoids the cardiac arrhythmias caused by plain T3." My response is that I've done hundreds of series of ECGs on patients taking plain T3, but I've never seen such arrhythmias. (See "Important Issues") The argument that the use of timed-release T3 avoids arrhythmias is a theoretical notion without objective substantiation (there are no studies that show this!).

Second, I don't believe that "cycling" is a valid concept. Over the years, I've monitored scores of fibromyalgia patients who reduced their dosages after improving with the use of T3 (within the context of our entire protocol). Invariably, their symptoms and signs soon became as intense as before they had improved. When they increased their dosages again, they improved again. And once more, when they again reduced their dosages, their symptoms and signs intensified. In many cases, the patient's status worsened after a minor dosage decrease, and improved after a minor increase. The blinded controlled studies we have conducted of fibromyalgia patients taking T3 have involved "cross-overs." This means that without the researchers or patients knowing when, the patients were switched from T3 to placebos and back again. The studies showed clearly that in general, when patients were taking T3, their status improved, and when taking placebos, their status worsened.

These clinical and experimental findings argue against that idea of "cycling" enabling patients to maintain improvement after stopping their use of T3. With increases and decreases in dosage, the only thing that has cycled in our patients is their fibromyalgia status. So, do I believe that "cycling" will "cure" cellular resistance to thyroid hormone? Unequivocally, no!

Third, the leaflet on Cytomel pharmacies give patients when they fill their prescriptions states, "POSSIBLE SIDE EFFECTS: NO COMMON SIDE EFFECTS HAVE BEEN REPORTED with proper use of this medication." This information is accurate—when plain, full-strength, one-time-per-day doses of T3 are used properly, there are no adverse effects. The only adverse effects occur when a patient takes a dosage that for her is excessive. With Cytomel, if overstimulation occurs, it can be stopped with one or two small doses of propranolol. Or the patient can simply reduce her dosage of Cytomel the next time she takes it. I want to emphasize, however, that when our protocol is used properly, there is no overstimulation to be avoided by using timed-release T3. The protocol has safeguards against adverse effects.

And finally, why do I specify that the typical patient use one full dose of non-timed-release Cytomel for life? Because extensive testing has shown that this is safe, effective, and most economical—when used within the context of our entire protocol.