Improving Thyroid Hormone Conversion
According to the British Thyroid Foundation, 1 in 20 people in the UK suffer from thyroid disorders.
However, Thyroid UK believes that the incidence is much higher due to undiagnosed hypothyroidism. This blog discusses how thyroid hormone conversion can become compromised and examine some of the causes that lead to low active thyroid levels. Finally, we will offer some solutions to help improve thyroid hormone conversion.
Basic Thyroid Physiology
The thyroid is a vitally important hormonal gland and considered the thermostat of the body. It plays a major role in the metabolism, growth and maturation of the human body, helping to regulate many body functions by constantly releasing a steady amount of hormones into the bloodstream. Every cell in the body depends upon thyroid hormones for regulation of its metabolism.
Hypothalamic–pituitary–thyroid axis
The process of thyroid hormone synthesis and secretion is regulated by a negative feedback loop and this process depends upon:
the hypothalamus – a region of the brain responsible for monitoring messages from the nervous and endocrine systems
the pituitary gland – often called the master gland because it controls a number of hormone glands in your body, including the thyroid and adrenals, the ovaries and testes
the thyroid gland – butterfly-shaped organ located in the base of your neck. It stores and produces hormones that affect the function of virtually every organ in our body
When the hypothalamus senses low circulating levels of thyroid hormone (triiodothyronine T3 and thyroxine T4, it responds by releasing thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary to produce thyroid-stimulating hormone (TSH).
TSH, which talks directly to the thyroid gland itself causes iodine to enter the thyroid, and turns on an enzyme called thyroid peroxidase (TPO). Thyroid cells combine iodine and the amino acid tyrosine to make:
T3 = bioactive hormone – named for its three molecules of iodine
T4 = prohormone – named for its four molecules of iodin
This feedback loop continues until levels in the blood return to normal.
Approximately 100μg of thyroid hormones are secreted from the gland each day mostly in the form of T4 with about 10% as T3.(1)
80% of T4 undergoes peripheral conversion to the more active T3, which is approximately 5 times more biologically active than T4.
T4 is converted into the more active T3 by the deiodinase system (D1, D2, D3) mainly in the liver, gut, brain, skeletal muscle and the thyroid gland itself.
T4 circulates through to the liver where 60% of it is converted into T3 through the glucuronidation and sulphation pathways during phase II of detoxification.(2) Another 20% is converted into reverse T3 (rT3) which is permanently inactive. rT3 is essentially the opposite of T3, specifically designed to balance out levels of T3 in the body. The final 20% is converted into T3 sulphate and T3 acetic acid which can then be further metabolised by healthy gut bacteria to produce more active T3.(3)
TSH is Normal!
Frequently people experience common hypothyroid symptoms but lab results are normal. Symptoms normally present as fatigue, brain fog and memory issues, cold hands and feet, hair loss, depression, constipation, difficulty sleeping and muscle weakness or joint pain and more. This common problem may be caused by poor thyroid hormone conversion and is explained below:
How is T4 Converted to T3?
Reactions that catalyse the conversion of thyroid hormones are triggered by enzymes called deiodinases which come in 3 forms:
deodinase type I (D1) converts inactive T4 to active T3 throughout the body. D1 can be suppressed and down-regulated in response to stress, liver dysfunction, insulin resistance, inflammation, gut dysbiosis, etc.
deodinase type II (D2) is 1,000 times more efficient at converting T4 to T3 than D1 in the rest of the body. D2 also has an opposite response from that of D1 to physiologic and emotional stress etc. D2 is stimulated and up-regulated in response to such conditions.
deodinase type III (D3) converts T4 to rT3 and competes with D1. rT3 is up-regulated during chronic physiologic stress and illness.
Deiodinase enzymes are essential control points of cellular thyroid activity that determine intracellular activation and deactivation of thyroid hormones. Most of the “deiodination” occurs in the liver, kidney and thyroid gland.
So let’s now look into some of the causes that lead to a low peripheral T3 level.
Stress
Chronic physical, psychological or environmental stress results in decreased D1 activity(4) and an increase in D3 activity(5) decreasing thyroid activity by converting T4 into rT3 instead of T3. rT3 is inactive and it functions to slow the body down which is necessary in times of stress or trauma for the body to heal. Conversely, D2 is stimulated, which results in increased T4 to T3 conversion in the pituitary and reduced production of TSH.
Therefore, stress management and adrenal support is vital when supporting the thyroid. You may be interested in our blog on the science of stress and resilience.
Insulin Resistance/Diabetes
It has been shown in a number of studies that insulin resistance, diabetes, or metabolic syndrome have associated significant reduction in T4 to T3 conversion, an intracellular deficiency of T3, and an increased conversion of T4 to rT3, further reducing intracellular T3 levels.(6)(7)
Iron/Selenium/Zinc deficiency
Iron deficiency has been shown to significantly reduce T4 to T3 conversion, increase rT3 levels, and block the thermogenic (metabolism boosting) properties of thyroid hormone.(8)(9)
Selenium is a fundamental component of various seleno-proteins, molecules essential to the body’s ability to create and use thyroid hormones. It plays a role in maintaining thyroid health since it works together with iodine and is required to produce T3. Low levels of selenium inhibit conversion of thyroid hormones into the form that is required by the cells and can result in increased rT3.(10)
Zinc plays a role in the functioning of the immune system and it may play a role in thyroid hormone metabolism in low T3 patients and in part contribute to conversion of T4 to T3.(11)(12) In addition a deficiency in zinc(13) can also drive up rT3 levels.
Furthermore, it is interesting to note that researchers have found that the nutritional zinc status in obese and diabetic subjects is altered: low zinc concentrations in plasma and erythrocytes with high urinary zinc excretion has been reported in obese children and adolescents.(14)
Chronic Illness/Inflammation
The inflammatory cytokines IL-1, Il-6, C-reactive protein (CRP), and TNF-alpha will significantly decrease D1 activity and reduce tissue T3 levels. Studies have shown that these inflammatory cytokines affect thyroid hormone conversion, reducing T4 conversion to T3 and also increasing rT3. This leads to reduced T3 and therefore increased incidence of under-active thyroid conditions.
Gut Dysbiosis
Another factor that can affect thyroid hormone conversion is poor gut health, also known as dysbiosis. Gut imbalances include: small intestinal bacterial overgrowth, reflux/GORD, yeast overgrowth, history of chronic antibiotic use and inflammatory bowel disease.
One role of the gut bacteria is to assist in converting inactive T4 into T3. As mentioned earlier approximately 20% of T4 is converted to T3 in the digestive tract, in the forms of T3 sulphate (T3S) and triidothyroacetic acid (T3AC). The conversion of T3S and T3AC into active T3 requires an enzyme called intestinal sulphatase, and intestinal sulphatase comes from beneficial gut bacteria.
Lipopolysaccharides (LPS) are present in the cell walls of gram-negative bacteria. Under normal circumstances they protect the cell membrane. However, when gram-negative bacteria die, the LPS is released and can cause a number of problems including high amounts of inflammation and negatively affect thyroid metabolism(15) in several ways:
reduce thyroid hormone levels
decrease TSH
promote autoimmune thyroid disease (Hashimoto’s). LPS can impact deiodinase activity inhibiting the amount of T3 in circulation
increase amounts of rT3
Inflammation in the gut also reduces T3 by raising cortisol. Cortisol decreases active T3 levels while increasing levels of rT3.(16)
Liver Health
A sluggish liver can impact thyroid health adversely by affecting conversion of T4 to T3.(17) This will result in lower T3 levels. A sluggish liver could be due to liver disease, an infection like hepatitis C, alcoholism, nutrient deficiencies, methylation and glutathione problems, etc.(18)(19)
How to Improve Thyroid Hormone Conversion
Before beginning to work on improving thyroid conversion, it is imperative that you tackle the underlying cause. Lowering rT3 levels and increasing T3 levels is not straightforward. There are so many variables and other factors that may hamper progress. For example, if high levels of rT3 are secondary to insulin resistance and diabetes, and you don’t make changes to your diet, any nutritional supplement additions may not make a difference.
Liver Detoxification and Function
In the liver D1 is involved in converting T4 into T3 and rT3 is also broken down there, consequently liver support is essential.
There are 2 metabolic pathways in the liver that can have an impact on thyroid hormones. One of these is the glucuronidation pathway. Glucuronidation is often involved in the xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, oestrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. It has also been shown to degrade rT3. This pathway is supported by B vitamins, magnesium, and curcumin.
The second is sulphation. Sulphation involves binding things partially broken down in the liver with sulphur containing compounds. It is one of the major detoxification pathways for neurotransmitters, toxins, and hormones. Vitamin B6 and magnesium are important for sulphur amino acid metabolism, as are foods containing sulphur such as: eggs, meat, poultry, nuts and legumes.
Another important factor is lipid peroxidation and supporting antioxidant status in the liver. Some studies have confirmed increased oxidative stress in hypothyroid states. It seems that thyroid hormones have a strong impact on oxidative stress and the antioxidant system.(20) For more information see our blog: Glutathione – The Master Antioxidant.
Adrenal Support
A few pointers are:
avoid or minimise stimulant drinks
stabilise blood sugar (via a moderate or low-carb diet)
practice stress management and relaxation techniques
make pleasure a regular part of your life
Improve Gut and Liver Health
Below are some pointers to help improve gut and liver health:
Eat plenty of fermentable fibre – Bacterial metabolites are potent endocrine modulators. When you consume fermentable fibres, your gut bacteria ferment these fibres and produce beneficial short-chain fatty acids (SCFAs).
Eat anti-inflammatory foods rich in beneficial bacteria – It has been found that beneficial microbiota will actually release anti-inflammatory messages and dampen the inflammatory response. Foods recommended are fermented foods such as cultured vegetables, coconut water kefir, and probiotic beverages as the primary system of delivery for good bacteria.
Leafy greens and Cruciferous vegetables – Green vegetables of all kinds provide anti-inflammatory and antioxidant properties. Cruciferous vegetables such as cauliflower, cabbage, kale, broccoli and Brussels sprouts are a rich source of sulphur-containing phytochemicals called glucosinolates which offer antioxidant and anti-inflammatory properties and also support detoxification of carcinogens and other xenobiotics.
Key Takeaways
The thyroid is a vitally important hormonal gland and considered the thermostat of the body.
Every cell in the body depends upon thyroid hormones for regulation of its metabolism
The thyroid gland produces a number of hormones including T4 (a prohormone) and T3 which is the only thyroid hormone actually used by the body’s cells. T4 is converted to T3 in the liver, gut, brain, skeletal muscle and the thyroid gland itself. Some T4 is converted to reverse T3, an inactive form
Reactions that catalyse the conversion of thyroid hormones are triggered by enzymes called deiodinases which come in 3 forms:
Deodinase type I (D1) converts inactive T4 to active T3 throughout the body.
Deodinase type II (D2) is 1,000 times more efficient at converting T4 to T3 than D1 in the rest of the body.
Deodinase type III (D3) converts T4 to rT3 and competes with D1. rT3 is up-regulated during chronic physiologic stress and illness.
Most of the “deiodination” occurs in the liver, kidney and thyroid gland.
Stress and illness can increase conversion of T4 to inactive rT3.
Insulin resistance/diabetes has been associated with a significant reduction in T4 to T3 conversion and an increased conversion of T4 to rT3.
Iron deficiency has been shown to significantly reduce T4 to T3 conversion and increase rT3 levels.
Low levels of selenium inhibit conversion of thyroid hormones into the form that is required by the cells and can result in increased rT3.
A deficiency in zinc can drive up rT3 levels.
Chronic illness and inflammation may reduce tissue T3 levels, by reducing T4 to T3 conversion increasing rT3.
Gut dysbiosis can affect thyroid hormone conversion. Approximately 20% of T4 is converted to T3 in the digestive tract so it is essential that gut microbiota is healthy for this conversion to take place.
A sluggish liver can impact thyroid health adversely by affecting conversion of T4 to T3.
Thyroid conversion may be improved by working on supporting the adrenal glands, optimising gut and liver health, balancing blood sugar and ensuring adequate intake of cofactors important for conversion such as selenium, iron and zinc.
(I did post about that possibility the other day.)
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