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Home > Anti-aging Research > Triiodothyronine [T3]

Liothyronine/Cytomel®/Triiodothyronine [T3]

News & Research:

  • Worsening HFpEF Linked With Low T3/T4 Ratio - Medscape, 10/6/22 - "Among those whose ratio of free triiodothyronine (FT3) to free thyroxine (FT4) was in the lowest tertile, there was a significantly increased rate of a composite of urgent heart failure (HF) visits involving diuretic intensification, HF hospitalization, or cardiovascular death compared with those whose ratios were in the higher tertiles" - Note: I seen other studies to support this but I doubt if doctors are current on it. Getting a prescription that includes T3 is like trying to get a prescription for cocaine.
  • an a Commonly Prescribed Thyroid Medication Lift Depression and Dementia? - Medscape, 12/16/21 - "While the therapeutic advantages and disadvantages over replacement with pure levothyroxine [T4] or a mixture of T4 with triiodothyronine [T3] have generated a consensus in favor of levothyroxine alone, we still grapple with treated patients who complain of impaired well-being ... Despite thyroid hormone replacement's clinical use for over 100 years and levothyroxine monotherapy for about 50 years, when to use a mixture, if ever, remains contentious despite numerous comparison trials ... A recent trial sponsored by the US military perhaps offers the branch point that affects prescribing. The group studied about 75 people with established hypothyroidism that was corrected to normal TSH with medication. They also administered a variety of quality-of-life and skill measurements. Using a crossover design, they identified people who scored poorly on the quality-of-life assessment when taking levothyroxine alone, and then offered a T3-containing alternative, and saw the quality-of-life score improve. But again, measurements of well-being and a few cognitive symptoms remained mostly independent of the type of thyroid hormone that produced the therapeutic TSH"
  • Combo Thyroid Hormones as Good as Levothyroxine for Hypothyroidism - Medscape, 3/22/21 - "Patients with hypothyroidism treated with the three most common pharmacological strategies of levothyroxine (LT4) alone, LT4 in combination with triiodothyronine (T3), or desiccated thyroid extract showed no differences in thyroid symptoms or secondary outcomes in a double-blind randomized study ... Additionally, some patients treated with LT4 alone report greater improvements in symptoms with the addition of T3 ... Overall, 45% of patients indicated they preferred desiccated thyroid as their first choice of treatment, 32% preferred LT4/T3 as their first choice, and 23% preferred LT4 alone ... When Switched to Desiccated Thyroid, Many Felt 'Much Better' ... A further exploratory analysis revealed that those who experienced symptoms while taking LT4 alone reported greater alleviation of symptoms with the other two treatments ... However, with the subgroup analysis based on the scores of symptom questionnaires, we found that symptomatic patients on LT4 improved while being treated with LT4/T3 or desiccated thyroid ... Reports of improvements in switching to desiccated thyroid were notable, Hoang added. "Many patients when switched from LT4 to desiccated thyroid extract said they felt much better, [with] more energy, less mental fogginess, a better outlook, less flair of lupus symptoms, easier to lose weight, etc."" - Note:  So why is trying to get a prescription for desiccated thyroid extract or a t4/t3 combo like trying to get a prescription for cocaine?  Lotta old-timer endocrinologists think they know it all when the research doesn't back them up.
  • New Trials on T3/T4 Combination for Hypothyroidism 'Justified' - Medscape, 3/2/21 - "There was sufficient justification for new trials of our current T3 preparation based on the fact that the trials were underpowered and had other issues, such as not selecting patients with residual symptoms, short duration of the study, and once-daily dosing of T3"
  • Serum Triiodothyronine-to-thyroxine (T3/T4) Ratio Predicts Therapeutic Outcome to Biological Therapies in Elderly IBD Patients - Medscape, 2/1/21 - "Baseline T3/T4 ratio was higher in patients with mucosal healing, as compared with those without mucosal healing (P < 0.0001), regardless of the disease type or biological drug (OR 6.4 [2.9–14.3] for each T3/T4 unit increase, P < 0.0001). A cut point of 3.3 was identified as the optimal threshold of baseline T3/T4 ratio for predicting mucosal healing, providing 78% sensitivity and 89% specificity (area under the ROC curve 0.88 [0.79–0.94]; positive and negative likelihood ratios 6.8 [2.9–15.9] and 0.3 [0.1–0.5] respectively) ... T3/T4 ratio seems a reliable tool for predicting therapeutic outcome of biological therapy in elderly patients with IBD"
  • Armour Thyroid (USP) and combined thyroxine/ tri-iodothyronine as Thyroid Hormone - british-thyroid-association.org, Feb 2007 - "Thyroid contains both thyroxine (T4) and tri-iodothyronine (T3) extracted from the thyroid gland of pigs. One grain, about 60 mg, of desiccated pig thyroid extract contains about 38mcg of T4 and 9mcg of T3, a ratio of around 4 to 1. The normal concentration of these hormones in the human thyroid is, however, at a ratio of 14 to 1"
  • Can 'Normal' T4 Levels Increase AF Risk? - Medscape, 12/11/18 - "After adjustment, the relative risk for prevalent AF in the highest normal free T4 quartile group was double that of the lowest group. No similar associations were seen between the quartiles for free T3. Thyroid-stimulating hormone (TSH) results were mixed."
  • The Love-Hate Relationship With Levothyroxine - Medscape, 10/25/18 - "Some might have a preference for animal-derived, nonsynthetic, natural forms of treatment, such as desiccated thyroid extract (DTE) from bovine and porcine sources, which contain both T3 and T4 at an approximate physiologic ratio of 1:4 ... I discuss with these patients that the physiologic ratio of T3:T4 secretion by the thyroid gland in humans is approximately 1:14.[4] In contrast, the makeup of DTE is approximately 1:4; thus, there is a relatively higher proportion of T3 than T4 in animal-derived sources of thyroid hormone ... Given the potential risks for cardiac arrhythmias and worsened bone health associated with perhaps any T3 therapy, I offer two separate prescriptions for synthetic T3 and T4 as the initial step to hypothyroid individuals who strongly prefer trying T3. To best replicate the physiologic ratio of T3:T4 production, the separate prescriptions should be about 1:13-1:20 that of T3 to T4 ... T3 also has a much shorter half-life than T4; thus, twice-daily dosing may be best. For example, an individual who has been taking 112 µg of synthetic T4 once daily and wants to try incorporating T3 would be prescribed 5 µg of synthetic T3 twice daily combined with 100 µg of synthetic T4 to reach a total of 110 µg of thyroid hormone per day, which is as close to the previous weight-based dose as possible"
  • Chronic Fatigue Syndrome Linked to Low T3 Syndrome - Medscape, 3/29/18 - "Some people with the condition known as chronic fatigue syndrome (CFS) have low circulating levels of the thyroid hormone triiodothyronine (T3) and normal levels of thyroid-stimulating hormone (TSH) ... This low T3 syndrome might be in line with recent metabolomic studies that point to a hypometabolic state (Proc Natl Acad Sci U S A. 2016;113:E5472-E5480), and if confirmed, T3 and iodide supplements may be indicated as treatments, say Núñez and colleagues"
  • Chronic fatigue syndrome possibly explained by lower levels of key thyroid hormones - Science Daily, 3/20/18 - "In hypothyroidism, the body tries to encourage thyroid hormone activity by releasing more thyroid-stimulating hormone -- however, this does not happen in patients with chronic fatigue syndrome ... the researchers compared thyroid function and markers of inflammation between 98 CFS patients and 99 healthy controls. Remarkably, the CFS patients had lower serum levels of certain key thyroid hormones such as triiodothyronine (T3) and thyroxine (T4), but normal levels of thyroid-stimulating hormone ... Additional analyses indicated that CFS patients had a lower urinary iodine status and low-grade inflammation, which possibly mirrored the symptoms of patients with hypothyroidism. These CFS patients, however, had relatively higher levels of another thyroid hormone called "reverse T3" or rT3. This appeared to be due to a shift in hormone production, where the body preferred to convert T4 to rT3 instead of producing T3. The low T3 levels found in CFS patients coupled with this switchover to rT3 could mean that T3 levels are severely reduced in tissue"
  • Symptoms Persist Despite Normalized TSH With Levothyroxine - Medscape, 10/25/16 - "Despite having normal blood levels of thyroid-stimulating hormone (TSH), many patients treated for hypothyroidism with levothyroxine (L-T4) continue to have symptoms, including fatigue as well as a higher body mass index (BMI) and a greater likelihood of antidepressant and beta-blocker use, compared with healthy controls ... for the first time, we have documentation that supports the patients' complaints, demonstrating that…[this] was not only in their minds, as some have suggested ... those in the L-T4–treatment group had approximately 10% to 15% higher total and free thyroxine (T4) levels and about 5% to 10% lower serum and total triiodothyronine (T3) levels compared with the healthy controls ... And the serum T3:T4 ratios in the L-T4–treated group were approximately 15% to 20% lower than in the healthy matched controls ... Also, compared with the healthy controls, those in the L-T4 group had major differences in seven of 21 objective parameters, including BMI (P < .001), total cholesterol (P < .01), HDL cholesterol (P = .02). and LDL cholesterol (P = .03); and in use of beta-blockers (P < .0001), statins, and antidepressants ... those taking L-T4 weighed approximately 10 pounds more than healthy controls of the same height, despite consuming fewer calories ... "Endocrinologists have accepted and propagated the notion that blood T3 levels are 'normal' in hypothyroid patients treated with levothyroxine," Dr Bianco noted ... Yet there are "are a handful of relatively recent studies indicating this is not the case," of which "ours is the most recent one, confirming that serum T3 is lower in these patients."
  • To T3 or Not: Combo Therapy in Hypothyroidism - Medscape, 12/18/14 - "One theory as to why some patients may indeed continue to experience hypothyroid symptoms such as fatigue, weight gain, and "brain fog" despite achieving normal TSH levels with L-T4 monotherapy was recently proposed with the discovery of common variations in the deiodinase 2 (DIO2) gene ... The latter was found to be associated with reduced ability to convert T4 to T3, potentially leading to a lack of response to monotherapy with T4 ... I suggest Armour to patients because it's economical and it's simple ... One problem with combination therapy [with synthetic T4 and T3] is that people find it to be very hard to take three pills a day, and you only have to take one Armour ... Furthermore, the synthetic T3 is very expensive, so I'm really looking at it from a more practical point of view ... After a minimum of 4 weeks on Armour, 78% expressed a preference for Armour compared with L-T4, with no serious adverse events noted, even with 30 of the subjects aged 65 years or older ... The [different] study involved 70 patients, aged 18 to 65, who were treated for 16 weeks with either desiccated-thyroid extract or L-T4 and then crossed over for the same duration ... Patients treated with desiccated thyroid had an average weight loss of 3 lb, and there was no difference in thyroid-function blood tests between the two groups after treatment ... Regarding the theory that it could be dangerous — where are the case reports of people getting sick? You will not find a single scientific paper stating any real danger from desiccated thyroid, and as far as I'm concerned, the [medical societies] are scaring people away from this"
  • Low thyroid levels may signal heightened risk of death in hospitalized patients - Science Daily, 10/30/13 - "When older individuals have low levels of thyroid hormones, particularly T3, it reflects that the body is weak and more susceptible to the harmful effects of disease ... As a result, older individuals who have a reduced ability to synthesize T3 hormones have a higher rate of mortality, both in the short- and long-term"
  • Persistence of Mortality Risk in Patients With Acute Cardiac Diseases and Mild Thyroid Dysfunction - Am J Med Sci. 2011 Aug 26 - "A total of 1026 patients (mean age: 67.7 years) were divided into 4 groups: (1) euthyroid (EU, n = 579); (2) subclinical-like hypothyroidism (SLHYPO, n = 68); (3) subclinical-like hyperthyroidism (SLHYPER, n = 23) and (4) low-triiodothyronine syndrome (LowT3, n = 356). Follow-up started from the day of thyroid hormone evaluation (mean follow-up: 30 months). The events considered were cardiac and overall deaths ... Survival rate for cardiac death was lower in SLHYPO and in LT3 than in EU (log rank test; χ = 33.6; P < 0.001). Survival rate for overall death was lower in SLHYPO, SLHYPER and LowT3 than in EU (48.3; P < 0.001). After adjustment for several risk factors, the hazard ratio for cardiac death was higher in SLHYPO (3.65; P = 0.004) in LowT3 (1.88; P = 0.032) and in SLHYPER (4.73; P = 0.047). Hazard ratio for overall death was higher in SLHYPO (2.30; P = 0.009), in LowT3 (1.63; P = 0.017) and in SLHYPER than in EU (3.71; P = 0.004). Hazards for SLHYPO, SLHYPER and LowT3 with respect to EU were proportional over the follow-up period ... In patients with acute cardiac disease, a mildly altered thyroid status was associated with increased risk of mortality that remains constant during all the follow-up"
  • Antipsychotics Significantly Decrease Free Thyroid Hormone Concentrations - Doctor's Guide, 9/4/08 - "In patients who receive antipsychotic medication, levels of free thyroxine and free triiodothyronine show significant decreases that may affect thyroid hormone functional activity in some tissues, such as the liver"
  • Best Thyroid Treatment? - Dr. Weil, 8/29/08
  • Looking For The Fountain Of Youth? Cut Your Calories, Research Suggests - Science Daily, 7/3/08 - "While scientists do not know how calorie restriction affects the aging process in rodents, one popular hypothesis is that it slows aging by decreasing a thyroid hormone, triiodothyronine (T3), which then slows metabolism and tissue aging" - All the studies I've read seem to support the opposite:
  • T3 Supplementation Raises Patients' Response to Sertraline - Clinical Psychiatry News, 11/06 - "The sertraline-T3 cohort also was much more likely (odds ratio 2.69) to go into remission by the sixth week of treatment. At that point, 58.5% (31/53) of the T3-augmented patients but only 38% (19/50) of the placebo group was in remission"
  • Longer-lived Rodents Have Lower Levels Of Thyroid Hormone - Science Daily, 10/12/06 - "T4 levels varied significantly between all of the groups, with the shorter-lived groups having higher levels of T4 than longer-lived groups ... However, because T3, levels did not differ significantly among all the groups, further research in this area using larger sample sizes (numbers of rodents in each group) is needed"
  • Thyroid Supplementation Enhances Antidepressant Response - Medscape, 9/21/06 - "Remission occurred in 31 patients (58.5%) receiving T3 compared with 19 patients (38%) in the placebo group"
  • T3 Therapy Not Yet Ready for Psychiatric Use - Clinical Psychiatry News, 2/05 - "Today, many patients with complaints of chronic malaise or fatigue approach their physician seeking T3 therapy, but the fact is that none of the handful of well-designed randomized controlled trials done since then has been able to confirm the initial report of superior outcomes ... There is reason for concern that supraphysiologic doses of T3 in this setting could interfere with protein and fat metabolism and interact synergistically with catecholamines to increase myocardial oxygen demand, with resultant increased arrhythmia, MI, heart failure, and death"
  • Algorithm-Based Treatment Shows High Lack Of Response To Selective Serotonin Reuptake Inhibitors - Doctor's Guide, 4/17/03 - "When the clinicians added T3, they found it was effective among 10 out of 16 women patients (62.5%), but was not effective in any of the 9 male patients who received it. Although values were within the normal range, patients who responded to T3 had higher serum thyroid-stimulating hormone levels than those who did not ... The effect of T3 may be related to thyroid function even within the normal range"
  • Options for Treatment-Resistant Depression - Psychiatric Times, 7/02 - "Use of T3 may interfere with thyroid metabolism if taken chronically, so its use should generally be limited to two or three weeks. Doses of T3 between 25 mcg/day to 50 mcg/day are more effective than T4"
  • Bipolar Patients Sensitive to Thyroid Function Variations - Doctor's Guide, 1/8/02 - "They studied 65 patients in the depressed phase of bipolar I disorder to test the hypothesis that patients with lower thyroid function, even within the normal range, might have a poorer response to treatment initially ... Outcomes were relatively poor unless patients had FTI [free thyroxine index] values above the median and TSH values below the median"
  • Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature - Am J Psychiatry 2001 Oct;158(10):1617-22 - "This meta-analysis supports the efficacy of T(3) in accelerating clinical response to tricyclic antidepressants in patients with nonrefractory depression"
  • Sustained Release T3 / Time Release T3 - WilsonSyndrome.com - "When Dr. Wilson first started treating Wilson's Thyroid Syndrome, Cytomel (instant release) was all he used. When he had about 300 patients at a time on Cytomel, he would get about 6-8 beeper pages over the weekend from patients having complaints and 2-3 of those calls would be about some pretty worrisome side effects. When Dr. Wilson conceived of and started using T3 mixed with a sustained release agent (see WTS history) he would go 6 months without a page"
  • Synthroid / Armour Thyroid - WilsonSyndrome.com - "Some patients and physicians hear about the need for T3 and think they can gain the benefits of T3 by using Armour instead of Synthroid because it contains T3. But Armour thyroid doesn't contain just T3. It contains a lot of T4 as well! T4 is the very hormone we're trying to reduce in WTS in order to deplete RT3 levels"
  • Thyroid Hormones Accelerate Depressive Response to Drug Therapy - Doctor's Guide, 10/30/01 - "Five of the six studies found T3 to be significantly more effective than placebo in accelerating clinical response ... Investigators say they found that the average effect was highly significant"
  • The acute effect of calcium carbonate on the intestinal absorption of levothyroxine - Thyroid 2001 Oct;11(10):967-71 - "When 1,000 microg of levothyroxine alone was given to subjects, the maximum average total T4 absorption was 837 microg (83.7% of the dose ingested) at 120 minutes. When levothyroxine was coadministered with 2.0 g of calcium (as calcium carbonate), the maximum average T4 absorption decreased to 579 microg (57.9% of the dose ingested) at 240 minutes"
  • Use OF T3 Thyroid Hormone to Treat Depression - DrMirkin.com, 5/19/01 - "some people become depressed when they take just T4 and their depression can be cured when they take both thyroid hormones, T3 and T4"
  • Replacing T4 With Triiodothyronine Improves Cognition And Mood In Hypothyroidism - Doctor's Guide, 7/5/00 - "Substituting T3 for a portion of T4 changed the concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) as well as improving cognition and mood"
  • T3---fibromyalgia, hypothyroidism, thyroid hormone resistance - drlowe.com
  • Wilson's Thyroid Syndrome - "Conversion of T4 to T3 can also be impaired by glucocorticoids" - Maybe that is the mechanism by which cortisol causes depression, and if so, could T3 then cure the depression? - Ben
  • Adding Natural Hormone Boosts Brain Function In Hypothyroidism - Doctor's Guide, 2/11/99 - "We found there wasn't much difference between the two treatments in terms of metabolic effects or effects on various peripheral organs," Prange said. "There were big differences, however, in the mental state of the patients. If these findings hold up, they will be very important."
  • Depression Management - ContinuingEducation.com, exp. 12/31/02 - See table six, recommends 5 - 50 mcg T3, 100 mcg (.1 mg) T4
  • Liothyronine Sodium - RxList.com - "Twenty-five mcg of liothyronine [T3] is equivalent to approximately 1 gram of desiccated thyroid or thyroglobulin and 0.1 mg of L-thyroxine [T4]" - I don't know if that is correct concerning 1 gram of desiccated thyroid.  That would mean that it would take 17 of the normal 60 mg desiccated thyroid capsules to equal 25 mcg T3 and 100 mcg T4 (1000/60 = 17).  I would think that that amount would be lethal.  Maybe it should have been grains instead of grams.  Any feedback would be appreciated. - Ben

Abstracts: