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T3 & Physiological Instability

July 27, 2000

On June 11, 2000, I replied to a question from a physician about a presumed problem with patients taking plain T3. Weve posted the question and answer here because over the past six months, I’ve received many e-mails asking the same question the physician asked. The e-mails appear to be prompted by a physician advising patients on the Internet that plain T3 causes “physiologically inconsistent responses.” As a remedy for this supposed problem, the physician recommends one of two solutions: (1) take timed-release T3 instead of plain T3, or (2) take plain T3 after eating. I dont believe there is any point to these supposed “solutions.” First, taking T3 after eating interferes with its absorption from the GI tract. One could get the same effect by reducing the amount taken on an empty stomach. But even that supposed solution is pointless in that it addresses a problem that doesn’t exist. I say this because I dont believe plain T3 causes clinically relevant inconsistent physiological responses. I explain below in my reply to the physician.

Dear Dr. Lowe: I am a physician practicing nutritional, holistic, and preventive medicine. I have a question related to your recommending the use of Cytomel instead of compounded timed-release T3. Ive been usingtimed-release T3 for about a year, and I feel my results have been pretty good. Some of my patients have recently requested that I treat them according to your protocol. They want me to switch from the timed-release T3 to plain T3. My understanding is that plain T3 has such a short half life in the body. And because of that, its hard to get consistent physiologic responses unless patients take the hormone several times per day. My understanding is that even then, results are variable. Please advise me of your experience with this. Thank you.

Dear Doctor: For many years, Ive heard physicians express a precaution that plain T3 causes inconsistent physiologic responses. In particular, Ive heard that plain T3 causes cardiac arrhythmias. Ive long had a particular interest in these precautions. After hearing the precautions, I began meticulously comparing the effects on patients of different thyroid hormone preparations. Ive compared the effects, on the one hand, by careful clinical observations. Ive also done so, however, by extremely systematic monitoring of patients, including serial EKGS and, when needed, cardiac consultations. From these comparisons, I can say
emphatically that among my patients, Ive seen no evidence of inconsistent physiologic responses to plain T3.

Ive found that some patients have markedly improved or recovered with the use of timed-release T3. I assume that most of these patients were hypothyroid.

However, Ive also found that many patients either dont benefit with timed-released T3, or they improve only slightly. When we switch these patients toplain T3, most have markedly improved or completely recovered. (Of course, the
use of thyroid hormone isnt the only component of our patients regimen. We require that all patients engage in a more comprehensive regimen of metabolic rehab. So, when I refer to a patient improving under our care,invariably, the patient has also engaged in other metabolism-regulation methods. Such methods include diet modifications, nutritional supplementation, and exercise to tolerance.)

I suspect that the reason most patients dont haveinconsistent physiological responses to pain T3 is a “buffering effect” of the “genomic” actions of T3. Most effects of T3 on the body are not a result of direct actions of the hormone on cells. Instead, most effects of T3 result from the actions of the hormone on genes in cell nuclei. These genomic actions of T3 appear to serve as a “buffer.” By this I mean that most cells are protected from a direct, abrupt effect of T3. The physiologic effects of T3 are highly indirect. The effects result from changes in protein synthesis due to T3-induced alterations in gene transcription. When a patient takes T3, the hormone must first enter the cells and then enter their nuclei. Next, the hormone must bind to T3-receptors on different genes.

The binding of T3 to T3-receptors on genes alters the genes transcriptional activity. Transcription of some genes is activated; that of others is inhibited. The resulting increase in messenger RNA from the activation of genes may also be enhanced by post-transcriptional actions of T3. For example, T3 may increase the survival time of some messenger RNAs. The increase or decrease in gene transcription (resulting
from the transcription-regulating effects of T3/T3-receptor binding on genes) changes the numbers of proteins synthesized by cells. The change in concentrations of the proteins then alters physiology. For instance, the concentration of the apoenzyme component of various enzymes is increased. The increase in the concentration of the enzymes then alters the rate of different biochemical reactions, and this is reflected in changed physiology.

Some patients report that they perceive rapid effects after consuming plain T3. If these effects are real, its unlikely that they are induced through the genomic route. Some genomic effects of T3 in isolated laboratory media may occur within minutes after cell nuclei are exposed to T3. But this observation doesnt translate into physiological and clinical effects in humans taking T3 by mouth. Most physiologic and clinical effects of swallowed T3 have much longer latenciessome effects may take days, weeks, or even months.

There are a few known exceptions to this rule of “genomic buffering.” Most functions of heart and liver cells, like those of other tissue cells, are altered by T3 acting through heart cell genes. But the heart and liver respond in some ways directly to T3. Presumably, this rapid effect occurs following T3 binding to T3-receptors outside cell nuclei, such as on the plasma membrane. As a result, some patients may experience a mild increase in heart rate or force of contraction within a couple of hours after taking their single daily dose of plain T3.

Fibromyalgia patients may be especially perceptive of these transient changes in heart function because of a generally heightened sensitivity to body sensations. In my experience, however, this quick response of the heart to T3 is clinically
irrelevant except in one group of patientsthose with severely compromised cardiac function or underlying cardiac abnormalities. (I hastily add that while we must take great care to ensure the safety of such patients, the judicious use of T3 may be critical to some of these patients improving their cardiovascular status. As I described on pages 885 and 886 of The Metabolic Treatment of Fibromyalgia, T3 is being used as a form of treatment for patients with some cardiac abnormalities.)

Rarely, a patient reports that she has a detectable response to plain T3 within minutes after ingesting it. My impression is that most of these patients expect T3 to produce an almost instantaneous effect. I say this because of my questioning of
these patients. I find that most dont understand that time-consuming genomic actions mediate the majority of the physiological effects of T3. Its possible, of course, that some patients have a rapid allergic reaction to some non-hormonal
component of the tablets that contain T3. Also, perhaps a few patients experience some nebulous “energy” effect after ingesting T3 but before absorbing it. Other than these possible exceptions, no physiological effects from T3 should occur until after the T3 passes from the GI tract into the blood.

As I explained in Chapter 5.4 of The Metabolic Treatment of Fibromyalgia, circulating blood levels of T3 reach a peak 2-to-4 hours after a patient ingests it. Absorption is not immediate. After absorption, some non-genomic effects may occur after an hour or two. As I said, though, my observations and objective testing compel me to reach two conclusions: (1) that few if any patients have “inconsistent physiological responses” other than a mild increase in heart rate or force of contraction, and (2) except for the rare patient, these cardiac effects are clinically unimportant.

I hope my answers are of some value to you.
Best regards,
Dr. John C. Lowe


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