Controlling the symptoms of a thyroid disorder can be a frustrating experience. More and more people are now looking at reverse T3 tests to uncover additional clues… although doctors will rarely order them. Read on to learn what reverse T3 can reveal about your health and how to naturally fix high or low levels.

What is Reverse T3?

Reverse T3 (also known as rT3 or reverse triiodothyronine) is a metabolite of T4, an important thyroid hormone [1].

Your thyroid gland primarily produces two hormones: T4 (thyroxine) and T3 (triiodothyronine) [2].

Usually, your body converts T4 into T3. Afterward, T3 goes on to have a variety of biological effects, like increasing heart rate, breathing rate, and metabolism [2].

Your body may sometimes convert T4 into rT3 instead. This rT3 has little biological activity and is considered an inactive compound [1].

Why do we care about rT3?

Levels of rT3 increase during times of serious illness or starvation. Certain drugs like amiodarone can also elevate its levels. On the other hand, people with hypothyroidism (low thyroid hormone) may have lower rT3 levels [1].

However, it’s unclear how useful it is to measure rT3. Knowledge of rT3 levels usually does not affect your doctor’s decision-making. As a result, tests for rT3 are not routinely performed [3].

Thyroid Hormones Overview

To fully understand what rT3 is, it’s helpful to first talk about the different thyroid hormones found inside your body.

TSH (short for thyroid-stimulating hormone) is a hormone released from the pituitary gland. It does exactly what its name implies–it stimulates the thyroid gland to produce hormones [2].

T4 is the most abundant thyroid hormone found in your body. But it has very little biological activity on its own. T4 must be converted into T3 to play out the roles we normally associate with thyroid hormones [2].

T3 mainly increases metabolism, which is typically linked to thyroid hormones in general. Your thyroid gland produces some T3, but most of your T3 comes from the conversion of T4 [2].

D2 is the enzyme that converts T4 into T3. It works by removing an iodine molecule from T4. In fact, T4 is named so because it contains 4 iodine atoms. Once an iodine is removed, T4 becomes T3 [4].

D3 is the enzyme that converts T4 into rT3. D3 also removes an iodine molecule from T4, but at a different location than D2 [4].

There is a third enzyme called D1 that is able to convert T4 into both T3 or rT3. However, scientists have yet to unravel the exact role and relevance of D1 [4].

Reverse T3 Test

If you have a thyroid disorder, you’re probably accustomed to routine lab tests. These tests usually look at TSH, T4, and T3 levels to help adjust thyroid medication dosing [5].

Doing an rT3 test is an additional option, often considered to be an alternative approach. Similar to other thyroid tests, you have to give a blood sample for an rT3 test [3].

Lab analysis takes some time to finish – usually about 4-7 days [6].

Results are reported as a number, usually in units of ng/dL.

Normal Levels

The normal range of rT3 is [6]:

  • 6-12 months old – 8.1 to 52.8 ng/dL
  • 1-15 years old – 8.3 to 22.9 ng/dL
  • 16 years or older – 10 to 24 ng/dL

rT3 levels may naturally increase with age [7, 3].

It’s also important to note that rT3 levels outside of the normal range are not necessarily bad.

For example, people in critical condition can have high levels. This is a result of the body reducing the amount of T4 that is converted into T3, which leads to more conversion into rT3. This process helps slow metabolism and preserve energy during illness [8].

Is rT3 Testing Useful?

Many practitioners and patients are ultimately faced with the same dilemma: how useful is rT3 testing? Is it worth the hassle? The opinions are still divided.

The general expert consensus is that rT3 tests have little clinical benefit. Currently, the information revealed by rT3 tests does not factor into clinical decision-making [3, 5, 8].

Research is continually discovering new details about rT3. It could be a useful diagnostic tool in the future.

For example, rT3 may be helpful in low T3 syndrome and pre-existing hypothyroidism in critically ill patients [9].

In both conditions, T3 and T4 are reduced. Patients with low T3 syndrome have elevated rT3, while critically ill patients with hypothyroidism usually do not [9].

However, a study of 246 patients found that rT3 levels do not reliably differentiate the two conditions [9, 3].

Alternative Medicine Perspective

While most doctors don’t routinely test rT3 levels, there are still some that do. The majority of rT3 tests in the U.S. is ordered by a small subset of alternative medicine practitioners [3].

Many alternative practitioners will look at rT3 to understand why their patients suffer from thyroid symptoms–even when all their other thyroid labs are normal or even after they’ve been treated with conventional medications (such as levothyroxine).

One of the common beliefs is that a subset of unspecific factors can increase rT3. These span all the following:

The subsequent rise rT3 is thought to trigger hypothyroid symptoms, including fatigue and weight gain [3].

According to the research, stress, weight loss, liver diseases, iron deficiency, and low ferritin can elevate rT3 [3, 10].

However, there is currently no evidence to suggest that elevated rT3 levels can cause thyroid symptoms. It’s true that high rT3 has been linked to various diseases, including chronic fatigue and depression. But the cause and effect are far from clear [3].

What’s more, symptoms of many diseases linked to high rT3 overlap. For example, iron deficiency and stress can both cause fatigue, gut issues, and mood imbalances. Liver disease can lead to anemia and sex hormone imbalances. Extreme weight loss can cause heart palpitations. The list goes on [11, 12, 13].

All in all, it’s unlikely that high rT3 is causing many of the symptoms talked about in various health blogs. Rather, the key may lie in addressing the underlying condition. rT3 may alter the main disease symptoms, but it probably doesn’t trigger them.

To go along with this, the belief that rT3 competes against T3 – referred to as rT3 dominance – is widespread in the alternative medicine community [3].

Reverse T3 Dominance: Fact or Fiction?

The idea behind rT3 dominance is that rT3 competes with T3 at binding sites. High levels of rT3 cause less T3 to bind to receptors. This means that even normal levels of T3 can result in hypothyroid symptoms [3].

Alternative medicine practitioners will test for rT3 and diagnose rT3 dominance based on an rT3/T3 ratio [3].

Treatment usually includes supplements that are believed to promote the conversion of T4 to T3 rather than rT3 [3].

However, there are a few problems with this practice.

The major issue is the idea that rT3 blocks T3. It is true that rT3 is able to bind to the same receptors that T3 does. But, studies show T3 has a binding affinity that is 100x stronger than rT3 [14, 3].

On top of that, the concentration of T3 in the body is much higher than rT3 [14, 3].

Bottom line: The idea of reverse T3 dominance is currently not supported by strong scientific evidence.

High Reverse T3

Causes

Low T3 Syndrome

Low T3 syndrome is a condition that causes abnormal levels of T3 and T4. It is also known as euthyroid sick syndrome or non-thyroidal illness syndrome.

Unlike other thyroid disorders, this condition is not caused by noticeable thyroid gland changes. Instead, low T3 syndrome is mostly due to more subtle alterations in thyroid hormone enzymes, transporters, and receptors [15, 8].

One important change is a decrease in D1 and an increase in D3, which reduces T4 conversion into T3. While it’s not fully understood how this happens, inflammation likely plays a big part [15].

Low T3 syndrome usually leads to [15]:

  • Low T3
  • High rT3
  • Low to normal T4
  • Normal TSH

However, thyroid hormone level changes can vary greatly, depending on the root cause of the syndrome [15].

Causes of Low T3 Syndrome

A common cause of low T3 syndrome is critical illness. Almost all patients in the intensive care unit have some form of thyroid hormone imbalance. It is also associated with many chronic illnesses [15, 8].

All the following conditions can cause low T3 syndrome, leading to high rT3 levels:

Bottom Line

Low T3 syndrome disrupts the normal balance of thyroid hormones, often resulting in high rT3 levels.

Low T3 syndrome sometimes serves a purpose: it’s the body’s natural energy-conserving response to severe injury. But it may become dysfunctional in other cases – such as in chronic fatigue and depression [30, 16].

Over time, low T3 syndrome can impair consciousness, heart function, recovery, and overall health [8, 16, 28].

Iron Deficiency

Iron deficiency and low ferritin may increase rT3 levels, according to two Iranian studies on adolescent girls. In one of the studies, restoring normal iron levels brought rT3 back down to normal. Therapy included both iron and iodine [31, 32].

Additional clinical studies are lacking, but animal research confirmed this observation. In rats, iron deficiency increased rT3 while decreasing T3 and T4 [33].

Aging

As you grow older, your rT3 levels may naturally rise [7].

Multiple studies have found that elderly people have slightly elevated rT3 levels [7, 34].

It’s not exactly clear why this happens, but we have a few good ideas.

Kidney and liver function diminishes with age. It could be that the elderly metabolize and clear out rT3 more slowly [3, 34].

Also, illness and malnutrition are more common in the elderly. These factors are linked to higher rT3 levels as well [3, 34].

Fetal Development

Thyroid hormones play a crucial role in fetal development [35, 36].

Interestingly, rT3 levels in the fetus are relatively high while T3 is usually low [35, 36].

This occurs because the concentration of D3 (the enzyme that converts T4 into rT3) is also very high in the fetus and the placenta [35, 36].

Why does this happen?

It’s believed that high D3 levels help protect developing infants from excess thyroid hormones [35, 36].

This is important because a considerable amount of T4 and T3 is transferred from the mother to the fetus. High levels of D3 are needed to inactivate excess T4 into rT3, to ensure proper development [35, 36].

The mother’s rT3 levels should not affected by this process. However, pregnancy can increase the body’s demand for thyroid hormones, often leading to hypothyroidism [35].

Medications

Certain medications may increase rT3, including:

  • Levothyroxine (Synthroid), a synthetic form of T4 [37]
  • Amiodarone, used to treat irregular heartbeat [38]
  • Dopamine, used to maintain blood pressure during severe illness [39, 40]
  • Cimetidine (Tagamet), used for heartburn [41]
  • Dexamethasone, an anti-inflammatory [42]
  • Enflurane or halothane, used for anesthesia [43]
  • Propranolol (Inderal), used for high blood pressure and irregular heartbeat [44]
  • Propylthiouracil, a drug used to treat high levels of thyroid hormones (hyperthyroidism) [45]

Liver Disease

The liver is responsible for converting T4 to T3. Specifically, liver cirrhosis has been linked to high rT3, low T3, and low T4 levels. The more severe liver damage, the more these values will drift from the normal range. Other chronic liver diseases, such as fatty liver and hepatitis, were not associated with high rT3 [10, 46].

Other

Some other causes of high reverse T3 include:

  • Hyperthyroidism in the elderly [47]
  • Hypothyroidism in children [48]
  • Anorexia [49]
  • Heat exposure, such as excessive sauna use [50]
  • Kidney failure [51]
  • Cancer including brain, breast, lung, colon, and liver cancers [52, 53, 54, 55, 56]
  • Genetic defects of the thyroid [57, 58, 59]

Health Effects

Reverse T3 is generally considered to have little biological activity, but it is linked to several health effects. As mentioned earlier, it can probably alter the symptoms of an already existing disease.

For example, one older study found that higher rT3 levels are associated with worse depression symptoms [60].

Another study suggests there is an association with worse glucose tolerance in kidney failure [51].

High rT3 levels may also be linked to an increased risk of dying within a year of having a heart attack [61].

But it’s not all bad.

The body naturally favors rT3 conversion during times of severe illness or injury. This is believed to be a protective mechanism to conserve energy and prevent protein breakdown [8, 15].

Additionally, animal and cell studies discovered that rT3 helps with brain development in early childhood. More specifically, it organizes the actin filaments of astrocytes, a type of cell that supports neurons [62, 63].

Weight Gain

Thyroid hormones are known to play an important role in metabolism and weight control [64].

The conversion of T4 into rT3 helps slow metabolism, but it’s unknown if rT3 itself affects body weight. There is no scientific evidence to say one way or the other [64].

Here’s what we do know: low levels of T3 are associated with weight gain. Theoretically, if the body is converting more T4 into rT3, then less T3 is being made [64].

But in these cases higher rT3 is more of a symptom rather than a cause. Effects on weight are much more likely due to levels of T3 and the activity of thyroid enzymes [65].

Low Reverse T3

Causes

Hypothyroidism

Hypothyroidism is when the thyroid gland does not produce enough T4 and T3 [5, 66].

Common causes include Hashimoto’s disease, iodine deficiency, and pregnancy [5, 66].

People with this condition often have lower levels of rT3. And this makes sense, rT3 is made from T4 and people with hypothyroidism have low levels of T4 [5, 66].

Treatment of hypothyroidism usually involves levothyroxine, a synthetic version of T4. This potentially can restore rT3 to normal levels as well [5, 66].

Hyperparathyroidism

Hyperparathyroidism is characterized by high levels of parathyroid hormone. It is usually caused by problems in the parathyroid glands [67].

This increase in parathyroid hormone can drastically raise calcium levels and a decrease phosphate [67].

One study has found that hyperparathyroidism can also lower levels of rT3 [67].

Interestingly, hypothyroidism may cancel out this effect. People with both disorders can have normal rT3 levels [9].

Medications

Some drugs can decrease rT3, including:

  • Bexarotene (Targretin), a drug used to treat cancer [68]
  • Salsalate, an NSAID used to treat pain and arthritis [69]
  • Rifampicin, an antibiotic [70]

Health Effects

Currently, low levels of rT3 are not known to cause any health effects [3].

However, low rT3 is often the result of reduced levels of T4. Low T4 can cause hypothyroid symptoms [5].

How to Fix High Reverse T3

The production of rT3 is often due to bodily processes that we don’t have much control over. But, there are a few natural ways to possibly change rT3 levels.

For instance, rT3 levels will increase if you don’t take in enough calories. One study found that fasting increases rT3 by 58%. They also found that a calorie-restricted diet of 800 kcal was enough to not impact rT3 levels [71].

Check your iron and ferritin levels. Iron deficiency and low ferritin have been linked to high rT3. If your levels are low, we recommend you first educate yourself about all the ways you can increase iron and ferritin. Then talk to your healthcare provider about the best treatment strategy [33].

Maintaining normal blood glucose levels is important as well. Studies have found that patients with poorly controlled diabetes (HbA1c >12%) have greater levels of rT3 [22, 23].

Exercise and a low-carb diet can help normalize blood glucose levels, which may lower rT3 [72, 73].

Reducing or quitting smoking may also help reduce rT3 levels [74].

You should also avoid soy (and its isoflavones). Soy protein increased rT3 levels in a study of 400 people given over 3 months, possibly by blocking the enzyme that makes T3 (D2). After 6 months of high soy intake, rT3 levels did normalize. For many people, soy is simply not worth the risk [75].

Reduce stress and balance your circadian rhythm. High stress–especially physical exertion–and a lack of sleep are both linked to high rT3 levels [76, 77].

Certain supplements may decrease rT3 levels, including:

Limitations and Caveats

There are relatively few clinical trials that have studied rT3, likely because testing is uncommon.

Research is still exploring the potential effects of rT3, especially its role in cells of the nervous system [62].

We also still do not fully understand the role of deiodinases, the enzymes that convert T4 into T3 or rT3 [81].

Resources

Did you know that you can analyze your thyroid lab test results with Lab Test Analyzer? It gives you natural recommendations and tells you if your values are in the range you need for optimal health.

LabTestAnalyzer is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thank you for your support.

Takeaway

Reverse T3 is an inactive metabolite of T4.

It’s unclear how useful rT3 testing is. Currently, clinical decisions rarely factor in rT3 levels.

High rT3 is linked to worse symptoms of depression, increased chance of dying after a heart attack, and glucose intolerance. Although high rT3 helps the body conserve energy faced with severe illness, it’s often dysfunctional in those with chronic fatigue syndrome and depression.

If your levels are high, several natural fixes may help. These include supplemental zinc, selenium, and N-acetylcysteine. Make sure to keep your blood glucose in check. Additionally, avoid fasting–it can increase rT3.

About the Author

Mathew Eng, PharmD

PharmD

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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