What Does the Thyroid Do?

The thyroid is an organ in the neck responsible for regulating metabolism by controlling the rate of oxygen and calorie conversion to energy. The metabolic rate of every cell in the body is controlled by thyroid hormones, particularly T3. The thyroid produces the hormones T3 and T4 in response to stimulation by thyroid stimulating hormone (TSH), which is produced in the pituitary gland. The thyroid requires iodine and L-tyrosine to synthesize T3 and T4.

Hypothyroidism is a condition where the thyroid does not produce enough thyroid hormone, significantly slowing metabolism. Hypothyroidism has detrimental effects on the body. Fortunately, thyroid function tests (eg, TSH, T3, and T4) can help identify an underlying thyroid condition as well as help direct proper treatment and improve symptoms.

Nutrients such as iodine and selenium help support thyroid function.

What are Signs and Symptoms of Hypothyroidism?

• Fatigue
• Weakness
• Sensitivity to cold
• Constipation
• Unexplained weight gain
• Dry skin and hair (and/or hair loss)
• Muscle cramps
• Depression
• If left untreated, hypothyroidism can lead to goiter, cardiovascular disease, and dementia.

What are Conventional Medical Treatments for Hypothyroidism?

• Thyroid hormone replacement therapy
• Desiccated thyroid extract

Which Nutrients Support Thyroid Health?

• Iodine. Iodine is required to synthesize thyroid hormone. Iodine deficiency is a leading cause of mental retardation due to its significance in thyroid activity. Many table salts have added iodine, and certain foods such as seaweed contain high concentrations of iodine.
• Selenium. Selenium is a necessary component of the enzyme that converts T4 to T3. Patients with various thyroid disorders were shown to have lower selenium levels.
• Zinc. Zinc may contribute to the conversion of T4 to T3. In a group of patients with abnormal thyroid hormone levels, zinc supplementation normalized the levels.
• Iron. Iron deficiency hampers the production of thyroid hormone. One study showed subjects with subclinical hypothyroidism were more likely to be iron deficient than the control group.
• Vitamin E. Several preclinical studies indicate vitamin E may help reduce oxidative stress caused by hypothyroidism.
• Ashwagandha extract. Ashwagandha extracts have been used for centuries in Ayurvedic medicine to alleviate stress. A small study indicated that the extract also improved thyroid function and thyroid-related hormone levels.
• Korean ginseng. Korean ginseng extract has shown promise in multiple clinical trials for a variety of conditions. In a trial of subjects with congestive heart failure and low T3 and T4, intravenous ginseng extract increased levels of both hormones.
• Vitamin A. Vitamin A (a family of related retinoic acids including retinol and beta-carotene) is important for thyroid health, and deficiencies are associated with thyroid dysfunction.
• Other natural interventions for thyroid health and function include guggul extract, vitamin D, vitamin B12, and turmeric.

The thyroid is a small gland located at the base of the neck that produces thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3). Thyroid hormones exert considerable influence over most aspects of human physiology. Hypothyroidism, or underactive thyroid, is a condition in which the thyroid gland does not produce normal amounts of these hormones. Because thyroid hormones affect so many parts of the body, hypothyroidism can have serious and varied consequences.^1,2

An estimated 20 million Americans have some form of thyroid disease, and nearly 60% of those with thyroid issues are unaware of their condition.³ While people of all races and ages can develop thyroid issues, women are more likely than men to have thyroid problems: one in eight women will develop a thyroid problem during her lifetime.² Stress, unhealthy diet, and even normal aging can compromise healthy thyroid function. Hypothyroidism affects an estimated 4.6% of the world population.⁴

Hypothyroidism can cause fatigue, depression, weight gain, cognitive deficits, and several other concerns.⁵ Hashimoto’s thyroiditis, a condition in which the immune system attacks the thyroid and causes low thyroid function over time, is the most common cause of hypothyroidism in regions where iodine deficiency is uncommon.

Subclinical hypothyroidism is a term that describes mild hypothyroidism in which some lab values are abnormal but thyroid hormone production is within normal limits. While this condition does not typically cause major health problems, it may undermine quality of life in some people.⁴ For a long time, treatment of subclinical hypothyroidism with thyroid hormone replacement was standard care, even in people without symptoms; however, current evidence does not support this strategy.⁶ In most cases, subclinical hypothyroidism identified on a blood test should only be treated if the affected person has symptoms likely related to thyroid dysfunction or if there are other indications for treatment, such as if the affected person is trying to get pregnant. Subclinical hypothyroidism often resolves on its own, but in some cases it progresses to overt hypothyroidism.

In this protocol, you will learn how the thyroid gland works and what happens when there is too little thyroid hormone activity in your body. You will also learn how simple blood tests can assess thyroid function, and what treatments are available for hypothyroidism. In addition, you will discover several integrative interventions and dietary and lifestyle changes that can support healthy thyroid function.

Thyroid hormone production is regulated by two specific brain regions: the hypothalamus and the pituitary gland. To ensure stable levels of thyroid hormones, the hypothalamus monitors circulating thyroid hormone levels and responds to low levels by releasing thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary to release thyroid stimulating hormone (TSH), which in turn stimulates the thyroid gland to increase triiodothyronine (T3) and thyroxine (T4) secretion. When thyroid hormone levels increase, pituitary production of TSH decreases, which slows the release of hormones from the thyroid gland.¹ This interconnected system is known as the hypothalamic-pituitary-thyroid (HPT) axis.

On a blood test, elevated TSH levels are highly suggestive of hypothyroidism. This is because the pituitary releases excessive TSH into the bloodstream in attempt to stimulate sufficient T3 and T4 production. On the other hand, low TSH levels generally indicate hyperthyroidism, or an overactive thyroid gland. This occurs when the thyroid is making too much T3 and T4, which causes the pituitary gland to stop releasing TSH into the blood.⁷ In rare cases, abnormal TSH levels are a reflection of problems with the pituitary gland rather than the thyroid.

The Primary Thyroid Hormones: T4 and T3

Thyroxine, or T4, is produced solely by the thyroid gland and is the more common thyroid hormone in the blood, but triiodothyronine, or T3, is the more biologically active thyroid hormone. T3 is formed by the removal of one of T4’s four iodine atoms. This process is mediated by selenium-dependent enzymes.⁸

T4 is found in the body in two forms: bound and free. Free T4 is not bound to any proteins and is able to enter into body tissues. Bound T4 is attached to proteins that render it biologically inactive. Approximately 99% of T4 in the body is in the bound form.⁹ Very small changes in the amount of carrier proteins will affect the percentage of unbound hormones.

High blood levels of T4 typically indicate hyperthyroidism and low levels are associated with hypothyroidism. However, pregnancy and oral contraceptive use can elevate thyroid hormone levels, while severe illness and certain medications can lower T4 levels.⁷ Elevated levels of cortisol, as seen during times of stress and in conditions such as Cushing’s syndrome, lower TRH, TSH, and thyroid hormone levels.^10,11 Cold temperatures increase TRH levels, which is thought to be an intrinsic mechanism that helps keep the body warm in cold weather.¹²

The thyroid gland needs iodine and the amino acid L-tyrosine to make T4 and T3. A diet deficient in iodine can lead to hypothyroidism.¹³

Hypothyroidism

Hypothyroidism can be overt, in which the thyroid gland does not make enough thyroid hormones, or subclinical, in which the thyroid requires excessive stimulation to make normal amounts of thyroid hormone. Approximately one of every 300 people in the United States has overt hypothyroidism, and about one of every 23 has subclinical hypothyroidism, though not all cases are symptomatic.⁴ Hypothyroidism can be caused by Hashimoto’s thyroiditis, thyroiditis (inflammation of the thyroid), certain medications, thyroid surgery, or radiation treatment of the thyroid region. Women are more likely to develop this condition, but risk increases in both genders in people over age 60.¹⁴

Hypothyroidism is generally characterized by a reduced metabolic rate. The main symptoms are^14,15:

• fatigue
• weakness
• increased sensitivity to cold
• constipation
• unexplained weight gain
• dry skin
• hair loss or coarse, dry hair
• muscle cramps
• depression

People with hypothyroidism may also have an increased risk of bleeding and some forms of anemia.^16,17

Most hypothyroid-related symptoms take years to develop. The slower one’s metabolism gets, the more obvious the signs and symptoms become. If hypothyroidism goes untreated, severe symptoms such as a swollen thyroid gland (goiter) or slow thought processes may develop. Untreated chronic hypothyroidism can even result in a rare life-threatening condition called myxedema coma.

Subclinical Hypothyroidism

Subclinical hypothyroidism, or mild thyroid dysfunction, is a far more common condition than overt hypothyroidism. Subclinical hypothyroidism manifests as mildly elevated TSH levels (often defined as levels above 4.5 µIU/mL) and normal T4 and T3 levels. Individuals with subclinical hypothyroidism may be at greater risk for developing overt hypothyroidism, although the condition resolves on its own in about half of cases.¹⁸

Most people with subclinical hypothyroidism have mild or no symptoms. In contrast, those with overt hypothyroidism have abnormal TSH and thyroid hormone levels and often have pronounced symptoms.¹⁹

Risk factors for progression from subclinical to overt hypothyroidism include female gender, advanced age, having a goiter, and a high iodine intake. Nearly 70% of people with subclinical hypothyroidism have no symptoms, but others experience fatigue, dry skin, cognitive decline, and muscle weakness.^18,20

There are two main classifications of hypothyroidism: primary and secondary. Primary hypothyroidism arises when the thyroid gland does not make enough thyroid hormone despite normal release of TSH. This leads to low levels of circulating thyroid hormones and subsequent increases in TSH levels. Secondary hypothyroidism occurs when not enough TSH is being produced in the pituitary gland, which is much less common and is usually associated with a central nervous system problem.²¹ The focus of this protocol is primary hypothyroidism.

Chronic Autoimmune Thyroiditis (Hashimoto’s Thyroiditis)

Chronic autoimmune thyroiditis, commonly called Hashimoto’s thyroiditis, is by far the most common cause of hypothyroidism in areas where iodine deficiency is not prevalent, such as the United States. In this condition, the immune system mistakenly attacks thyroid tissue. Hashimoto’s thyroiditis is characterized by production of antibodies, such as thyroid peroxidase and antithyroglobulin antibodies, which cause the immune system to attack the thyroid and impair its ability to make hormones.²² Some patients with Hashimoto’s thyroiditis experience an initial period of hyperthyroidism, typically lasting one to two months, prior to a drop in thyroid hormone production. This phase of the disease is referred to as Hashimoto’s thyrotoxicosis, or hashitoxicosis.²³

Healthcare-Associated Hypothyroidism (Iatrogenic Hypothyroidism)

Hypothyroidism may arise as a consequence of medical treatment, either directly or indirectly. For instance, thyroid removal (thyroidectomy) due to cancer or persistent autoimmune thyroid disease is a cause of hypothyroidism. Similarly, treatment with radioactive iodine for thyroid conditions can lead to hypothyroidism. Radiation treatment to the neck or upper chest region can lead to hypothyroidism, whether it was initially intended to treat a thyroid condition or something else.^24,25 Some drugs used for non-thyroid conditions may also lead to hypothyroidism. These include high-dose lithium carbonate, amiodarone, interferon alpha, interleukin-2 (IL-2), and some immunotherapies and targeted therapies for cancer, among others.^26,27

Environmental and Infectious Causes

Exposure to some environmental toxins may disrupt thyroid function and lead to hypothyroidism. For instance, exposure to flame retardants called polybrominated diphenyl ethers (PBDEs) was linked to hypothyroidism in an observational study of Canadian women.²⁸ A variety of infections, predominately of bacterial origin, can lead to thyroid inflammation and associated thyroid dysfunction.²⁹

Other Diseases

Sometimes, diseases not directly related to the thyroid but which cause systemic problems may lead to thyroid dysfunction. Blood cancers,³⁰ iron overload (hemochromatosis),³¹ and scleroderma³² are examples of systemic diseases that may cause hypothyroidism. Hypothyroidism due to non-thyroid diseases may be a consequence of the disease itself or a side effect of treatment for the disease; for example, children or adolescents treated for leukemia may develop treatment-related hypothyroidism later in life.³⁰

Pregnancy

Pregnancy considerably increases the metabolic demands on women’s bodies, and thyroid function needs to adjust to accommodate these demands. Sometimes, women develop thyroid dysfunction (either hypo- or hyperthyroidism) during pregnancy or after giving birth.³³ Thyroid function usually returns to normal shortly after the woman gives birth unless she has a condition that can cause prolonged thyroid issues, such as iodine deficiency or autoimmune thyroid disease.

Iodine Deficiency or Excess

Iodine plays an important role in thyroid physiology. Too much or too little of this trace element can cause hypothyroidism. In the United States, iodine deficiency is uncommon. Excessive intake may occur due to overconsumption of iodine-rich foods like seaweed, or excessive supplementation (the upper limit for daily iodine intake in adults recommended by the Food and Nutrition Board in the United States is 1,100 mcg daily). People with underlying thyroid disorders may be more susceptible to thyroid dysfunction due to iodine excess.³⁴

Several tests are available to assess different aspects of thyroid health³⁵:

• Thyroid stimulating hormone (TSH) to evaluate overall thyroid function;
• Total thyroxine (T4) to measure the total amount of T4 being produced by the thyroid;
• Free thyroxine (T4), a measure of the amount of bioavailable T4 not bound to transport proteins;
• Free triiodothyronine (T3) to measure the amount of unbound T3 available;
• Reverse T3 to measure the non-functioning form of T3;
• Thyroglobulin antibodies that can attack proteins involved in thyroid hormone production;
• Thyroid peroxidase antibodies that can attack an enzyme involved in thyroid hormone production

Thyroid Stimulating Hormone (TSH)

Measuring TSH levels in the blood is the most common test of thyroid function. The normal range for TSH in healthy individuals is 0.45–4.5 µIU/mL.³⁶ In general, TSH levels above 4.5 µIU/mL suggest hypothyroidism, and levels below 0.45 µIU/mL represent thyroid hormone excess; however, TSH levels typically increase with age. A longitudinal cohort study following 908 healthy people for 13 years found serum TSH levels increased with age, with the largest increases observed in those who had lower TSH levels at the start of the study. Researchers concluded that this increase was not the result of disease, but rather age-related changes in TSH bioactivity.³⁷ A large cohort study involving over 150,000 healthy people over age 18 also demonstrated that TSH levels increased with age. The authors concluded that TSH reference ranges should be age-specific, including an age group of those over 70 years of age.³⁸ Accordingly, the American Thyroid Association recommends a TSH target level of 4–6 µIU/mL in people older than 70.³⁹

TSH production can also fluctuate with time of day, infection, and various other factors. In a survey of nearly 350,000 people published in the Archives of Internal Medicine, abnormal TSH levels spontaneously returned to normal in more than 50% of patients when the test was repeated at a later date.⁴⁰ No single measurement of TSH should be considered diagnostic, and repeated testing may be necessary to guide treatment decisions.

Note: Life Extension suggests that an optimal level of TSH for otherwise healthy people who wish to lose weight may be 1 – 2 µIU/mL. Individuals should consult with their health care provider regarding what levels are appropriate for them.

Tests for T4 and T3

Thyroid hormones can be tested in both their free and protein-bound forms. Tests for the protein-bound forms of T4 and T3 are generally referred to as total T4 and total T3, respectively; unbound forms are called free T4 and free T3. Each of these tests provides information about how the body is making, activating, and responding to thyroid hormones. The normal range for free T4 is 0.82–1.77 ng/dL,⁴¹ and for total T4 is 4.5–12.0 µg/dL.⁴² The normal range for free T3 is 2.0–4.4 pg/mL⁴³ and for total T3 is 71–180 ng/dL.⁴⁴

The feedback mechanisms by which the body regulates thyroid hormone levels are very sensitive, such that small changes in T4 levels lead to relatively large changes in TSH. Therefore, TSH is generally considered an excellent indicator of thyroid health in most people whose hypothalamus and pituitary gland are functioning normally.

Because T4 is converted to T3, and changes in levels of binding proteins do not affect free T4 levels, free T4 is typically the hormone measured in a clinical setting.⁷ While T3 testing can help diagnose or determine the severity of hyperthyroidism, it is generally not as useful in someone with hypothyroidism as it is typically the last measure to become abnormal.³⁵

Note: Life Extension suggests the following T3 and T4 levels may be optimal for otherwise healthy people attempting to lose weight. Individuals should consult with their health care provider regarding what levels are appropriate for them.

• Free thyroxine (T4): 1.46 – 1.77 ng/dL
• Free triiodothyronine (T3): 3.4 – 4.2 pg/mL
• Total thyroxine (T4):
• Men: 8.5 – 10.5 µg/dL
• Women (< 60 years): 9 – 11 µg/dL
• Women (> 60 years): 8.5 – 10.7 µg/dL

Reverse T3

T4 can also be converted into an inactive form of T3 called reverse T3 (rT3), which does not have thyroid hormone activity.⁴⁵ Certain individuals with apparently normal T4 and T3 hormone levels may still have some symptoms of hypothyroidism. This may be due to an excessive production of rT3, which may interfere with T3’s activity in the body. Stress and extreme exercise may lower thyroid hormone action by suppressing production of TSH and T3 and elevating rT3 levels.^10,46 In general, rT3 levels are elevated during times of critical llness.⁴⁷ In hypothyroid states, rT3 levels may be low due to a reduced production of T4.⁴⁸ The reference range for rT3 is 9.2–24.1 ng/dL.⁴⁹

Autoimmune Antibodies

The body’s immune system uses antibodies to attack foreign particles, such as bacteria and viruses, but in autoimmune disorders, dysfunctional antibodies are produced that attack healthy tissues, cells, or biomolecules. In people with autoimmune thyroid conditions, antibodies interfere with normal thyroid cell function, resulting in either stimulation or suppression of thyroid activity. Antibodies against thyroid peroxidase (an enzyme involved in thyroid hormone production) and thyroglobulin (a protein in the thyroid gland from which thyroid hormone is produced) are relatively common antibodies that can compromise thyroid function.³⁵ Thyroid peroxidase antibodies (also called thyroid microsomal antibodies) are normally found at levels of 34 IU/mL or less. In a person with hypothyroidism, the presence of elevated thyroid peroxidase antibodies suggests Hashimoto’s thyroiditis, the most common cause of overt hypothyroidism in the United States.⁵⁰ Interestingly, celiac disease or sensitivity to gluten appear to correlate with increased risk of developing autoimmune thyroid disease.^51,52

Elevated thyroid antibodies are often associated with chronic urticaria, or hives. Studies report that roughly 30–57% of patients with chronic urticaria also have anti-thyroid antibodies.^53,54 Some evidence suggests that treatment with T4 may improve the itching associated with urticaria, but is not recommend unless the patient has hypothyroidism.^55,56

Basal Body Temperature

Measuring basal body temperature can sometimes provide some insight into thyroid function, although it should only be used in conjunction with standard thyroid blood testing. Body temperature testing in the context of suspected thyroid issues was common before the development of accurate thyroid function blood tests.

Basal body temperature is taken when the body is at complete rest, immediately after waking, and before beginning any activity. Normal basal temperature is roughly 97.6–98.6º F, and some integrative practitioners suggest that a five-day consecutive temperature reading below 97.6º F may suggest hypothyroidism.

In a large longitudinal study of over 35,000 people whose temperatures were taken during routine medical visits, there was a correlation between TSH levels and body temperature. Hypothyroidism was linked to lower body temperatures.⁵⁷ Nevertheless, there are many reasons for alteration of basal body temperature, so a thyroid panel blood test should be taken to more accurately evaluate thyroid function.

Additional Testing

Sometimes additional testing, such as biopsy or enzymatic studies, is required to establish a definite diagnosis of hypothyroidism. Major abnormalities of the thyroid gland detected in a physical exam can be further assessed by other procedures, including ultrasound or scintigraphy.

Ultrasound may be used to more closely examine thyroid nodules (or lumps in the neck region) to determine if they are cancerous. Scintigraphy is a scan that can be used to look at the size and shape of the thyroid gland, as well as its position in the body. A small amount of radioactive iodine is used in this procedure to detect nodules and determine the cause of any thyroid issues.

The radioactive iodine uptake test may also be useful in diagnosing thyroid issues. As the thyroid takes iodine from the bloodstream to produce T4, this action can be clinically measured by having a patient swallow a small amount of radioactive iodine. This allows the doctor to track where the iodine is going and measure thyroid function by determining how much radioactivity is taken up by the thyroid gland. The test is performed by taking a pill containing radioactive iodine. The thyroid is then scanned by a computer after several hours and usually again after a full day to assess the thyroid’s uptake of the radioactive iodine. A low level of radioactivity uptake is seen in those with hypothyroidism.³⁵

Complications of hypothyroidism include goiter, depression and other mental disorders, heart problems, infertility and pregnancy complications, and nerve damage. In rare cases, long-term untreated hypothyroidism can lead to a life-threatening condition known as myxedema coma, which is triggered by severe stress, sedative use, or infection. Myxedema coma is indicated by intense cold intolerance and drowsiness, followed by lethargy and unconsciousness.⁵⁸

Fatigue and Weakness

Fatigue is a near-universal symptom of low thyroid hormone levels, and many hypothyroid patients report fatigue, weakness, and decreasing quality of life. A decrease in thyroid hormone production and a disruption in the hypothalamic-pituitary-thyroid (HPT) axis reduces energy production and metabolism, which results in tiredness.⁵⁹

Gastrointestinal Manifestations

Thyroid function and gut health are interrelated. The thyroid hormone T4 is converted to T3 in many tissues, including those of the gastrointestinal tract.⁶⁰ Inflammation in the gut may inhibit this process. In addition, the intestinal microbiome plays a key role in immune function. When potential infectious agents penetrate the intestinal lining, the immune system may respond by producing antibodies, triggering an inflammatory response that may in some cases contribute to the development of Hashimoto’s thyroiditis.⁶¹

Hypothyroidism is a common cause of constipation, which may result from diminished motility of the intestines. In some cases, this can lead to intestinal obstruction or an enlarged colon.⁶² This decreased gastric motility is also associated with small intestinal bacterial overgrowth, which may occur in nearly half of people who have hypothyroidism.⁶³ Hypothyroidism is also associated with decreased motility in the esophagus, which can cause difficulty swallowing, heartburn, indigestion, nausea, and vomiting. Other gastrointestinal manifestations of thyroid disease include abdominal discomfort, flatulence, and bloating.

Depression and Psychiatric Disorders

Changes in thyroid hormone levels can alter brain function, and thyroid dysfunction was long ago linked to mental disorders. Panic disorders, depression, and changes in cognition are frequently associated with thyroid disorders.^64-66 In fact, hypothyroidism is often misdiagnosed as depression.⁶⁷ Also, thyroid hormone replacement has been shown to enhance responsiveness to antidepressant drugs.⁶⁸

Cognitive Dysfunction

Thyroid hormones play a key role in brain function and neuronal metabolism. Patients with low thyroid function can suffer from a range of impaired cognitive functions, such as slowed thinking, decreased attentiveness, language difficulties, confusion, difficulty recalling names, and even hallucinations.⁶⁹ Cognitive deficits from hypothyroidism are often reversible with treatment.^59,70,71

Cardiovascular Manifestations

Proper thyroid function is necessary for optimal cardiovascular health because thyroid hormones influence heartbeat, blood pressure, and cholesterol levels. Hypothyroidism is associated with increased cholesterol levels and increased risk of cardiovascular disease.⁷² Abnormal thyroid hormone levels can affect the strength and speed of heart contractions and the physiology of the vascular system.⁷³

High cholesterol and atherosclerosis. Thyroid hormones aid in metabolizing cholesterol and synthesizing fatty acids in the liver. Hypothyroidism is characterized by hypercholesterolemia and an increase in low-density lipoproteins (LDL) and apolipoprotein B.⁷⁴ In one retrospective study involving 568 individuals, elevated TSH levels were associated with increased total cholesterol levels, independently of thyroid hormone levels.⁷⁵ These changes in lipid metabolism accelerate atherosclerosis, and hypothyroidism has been found to increase the risk of coronary artery disease in proportion to the degree of TSH elevation.⁷⁶ In addition, autoimmune-induced hypothyroidism has been associated with increased stiffness of the blood vessel walls.⁷⁷ Thyroid hormone replacement may slow the progression of coronary heart disease by inhibiting the progression of atherosclerotic plaques.^78,79

Homocysteine dysregulation. High blood levels of homocysteine, an amino acid derived from methionine, is an independent risk factor for heart disease.⁸⁰ In one study, fasting and post-meal homocysteine levels were higher in 40 people with hypothyroidism compared with a control group. TSH was the strongest predictor of homocysteine levels, and thyroid hormone replacement decreased fasting but not post-meal homocysteine levels.⁸¹ A meta-analysis of 17 studies found that plasma homocysteine levels were elevated in patients with hypothyroidism compared with healthy subjects, and homocysteine levels decreased with T4 replacement in patients with subclinical and overt hypothyroidism.⁸²

Elevated C-reactive protein. C-reactive protein (CRP) is a marker of inflammation that circulates in the blood throughout the body. Elevated CRP is associated with increased risk of cardiovascular disease.⁸³ Hypothyroidism is associated with elevated CRP, and CRP levels have been shown to increase with progressive thyroid failure.⁸⁴ One study found higher CRP levels and more pronounced carotid artery stiffness in people with hypothyroidism compared with those whose thyroid function was normal. This study also found that baseline CRP levels and carotid artery stiffness were correlated, and thyroid hormone replacement was independently associated with lower baseline CRP.⁸⁵

Metabolic Syndrome

Metabolic syndrome is a group of metabolic conditions that are risk factors for heart disease and type 2 diabetes, including abdominal obesity, high triglycerides, low high-density lipoprotein (HDL) cholesterol, abnormal blood glucose levels, and high blood pressure. Research suggests hypothyroidism is associated with metabolic syndrome, and people with metabolic syndrome are at greater risk of developing hypothyroidism.^86-92 Hypothyroidism is associated with insulin resistance, and severity of insulin resistance seems to increase with severity of hypothyroidism.⁹³

Chronic Kidney Disease

Chronic kidney disease (CKD) is associated with both overt and subclinical thyroid dysfunction.^94,95 In a cross-sectional population-based study of over 29,000 people without previous thyroid problems, those with higher TSH levels had lower glomerular filtration rate, which is a measure of kidney function. Individuals with TSH levels in the highest third of the reference range had a 31% increased risk of advanced kidney disease compared with those whose TSH levels were in the lowest third.⁹⁶ Importantly, appropriate treatment of thyroid disease may mitigate CKD progression in some cases.⁹⁷

Reproductive System Manifestations

Thyroid hormones regulate many aspects of ovarian function and reproductive health.⁹⁸ Thyroid problems are the most common endocrine disorder affecting women of reproductive age.⁹⁹ Low levels of thyroid hormones can interfere with ovulation, which may cause menstrual irregularities and infertility.^100,101 Proper treatment can restore a normal menstrual cycle and improve fertility.¹⁰² Hypothyroidism is also linked to miscarriage, premature delivery, low birth weight, fetal distress during labor, and gestation-induced hypertension. In males, hypothyroidism is associated with erectile dysfunction and problems with sperm motility.¹⁰³

The goal of thyroid hormone replacement is to replicate normal thyroid function in people whose thyroid is not producing adequate levels of thyroid hormones. This can usually be accomplished with medications that contain thyroid hormones (ie, replacement therapy).¹⁰⁴ Thyroid hormone replacement therapy aims to relieve symptoms and decrease elevated TSH to normal levels.¹⁰⁵

Levothyroxine (T4)

Thyroid replacement usually begins with synthetic T4 (levothyroxine) preparations, such as Synthroid or Levoxyl, which work like natural T4. Low doses are usually used at first as a rapid increase in thyroid hormone levels may result in cardiac damage.¹⁰⁶

Sometimes hypothyroid symptoms persist despite T4 treatment. In one study, T4 therapy was no more effective than placebo in improving cognitive function and psychological well-being in patients with symptoms of hypothyroidism, despite improvement in free T3 levels.¹⁰⁷ Another study compared T3 and T4 levels in hypothyroid patients treated with T4 alone against levels found in healthy people. In this study, T4 supplementation alone did not increase T3 to the same level as in healthy people.¹⁰⁸

Combination T4 and T3

While T4 therapy is the standard treatment for hypothyroidism, combination therapy with synthetic T4 and T3 may be useful in some cases. Although the scientific evidence does not show a clear advantage of combination therapy versus T4 alone, some individuals may respond better to combination therapy.^109-112 Importantly, excess T3 may cause adverse cardiac events in older individuals.¹¹³

One combination option is the drug Thyrolar (Liotrix), which combines synthetic T4 and T3 in a fixed 4:1 ratio. Another synthetic T3 option is liothyronine (Cytomel), which can be used in combination with a T4 drug.

Desiccated Thyroid Extract

Armour Thyroid, Nature-Throid, and Westhroid are prescription medications that contain desiccated porcine thyroid gland. Natural thyroid extracts have been used since 1892 and were approved by the Food and Drug Administration in 1939. Armour Thyroid and most other natural glandular preparations are made to standards approved by the United States Pharmacopoeia. Desiccated thyroid contains T4, T3, and another hormone known as calcitonin, which helps regulate calcium and phosphate levels in the blood.

In a double-blind controlled study, 70 people with hypothyroidism were randomized to receive either desiccated thyroid extract or levothyroxine for 16 weeks. Each group then switched treatment arms for 16 weeks. Approximately half of the participants preferred the desiccated thyroid extract, while 19% preferred the levothyroxine. Desiccated thyroid extract use was also associated with greater weight loss. Both treatments normalized thyroid blood tests and there was no difference in symptom relief between treatment groups.¹¹⁴

Armour thyroid is preferred by some clinicians because it may achieve results in patients who fail to respond to levothyroxine alone. Some patients with hypothyroidism show greater improvements in mood and brain function if treated with Armour Thyroid rather than Synthroid.¹¹⁵

Note that some health conditions and the use of certain medications may interfere with desiccated thyroid extract. In particular, people with adrenal insufficiency, clotting disorders, diabetes, heart disease, and thyrotoxicosis should speak with a health care provider before beginning this medication.¹¹⁶

Ultimately, there may not be a single optimal way to normalize low thyroid hormone levels. The best treatment option may be to monitor thyroid levels through regular blood testing and adjust replacement therapy protocols to see what works best. Some people may prefer to begin with desiccated thyroid, while others may find it preferable to begin with T4 supplementation and then move to a combination T3-T4 therapy if they experience no improvements. It is important to work with a physician to determine which approach is best for you.

Treating Subclinical Hypothyroidism

Previously, the recommended treatment for subclinical hypothyroidism was T4 replacement therapy, with clinical management based on TSH levels, age, and presence of any other health conditions. However, elevated TSH levels may be more common in older people, which may lead to overtreatment in this population group. Recent research suggests untreated subclinical hypothyroidism in older adults without symptoms is not necessarily harmful in all cases, and there may be a lack of benefit from treatment in this age group.¹¹⁷ A double-blind, randomized, placebo-controlled study involving 737 adults over age 65 with subclinical hypothyroidism found that levothyroxine treatment at a starting dose of 50 mcg, adjusted according to TSH levels, did not improve hypothyroid symptoms, tiredness, or quality of life measures.¹¹⁸ In another randomized, double-blind, placebo-controlled trial in 185 people over age 65 with subclinical hypothyroidism, 96 were treated with levothyroxine (T4) therapy and the rest were given placebo for 18 months. There were no differences in carotid plaque thickness or atherosclerosis progression between the placebo and treatment groups.¹¹⁹

Guidelines issued in 2019 by a consortium of North American and European researchers and physicians made a strong recommendation against the treatment of subclinical hypothyroidism with thyroid hormone replacement in otherwise healthy adults. The guidelines, which were based on a review of the available evidence that included 21 clinical trials with data on over 21,000 participants, recommended against treatment unless the patient has overt hypothyroidism, subclinical hypothyroidism with TSH levels greater than 20 µlU/mL, is pregnant or trying to become pregnant, or presents other considerations strongly indicating treatment.¹²⁰ In elderly patients (those over age 85) with TSH levels up to 10 µlU/mL, limited evidence supports no treatment.¹¹⁹

Treating aging people with thyroid hormone replacement when they are asymptomatic is not recommended, as it does not improve clinical symptoms such as depression, fatigue, body mass index, cardiovascular health, and quality of life. Subclinical hypothyroidism identified by blood testing should be monitored for progression and the presence of any symptoms, but not necessarily treated in most cases.¹²⁰

In fact, mild subclinical hypothyroidism may have an anti-aging benefit, perhaps due to its influence on metabolic rate. A recent population-based cohort study involving over 7,000 participants examined the influence of thyroid function on cardiovascular disease and mortality. Researchers found that after age 50, those with low-normal thyroid function had a longer life expectancy (by 3.5 years) and longer expected survival free of cardiovascular disease (by 3.1 years) than those with high-normal thyroid function.¹²¹ However, this theory needs to be studied further. As of early 2020, the American Thyroid Association recommends a TSH target level of 4–6 µIU/mL in people older than 70 years.³⁹

Dietary Considerations

Because the body needs iodine to make thyroid hormone, and iodine is relatively uncommon in the standard American diet, people who avoid iodized salt or adhere to a salt-restricted diet may become iodine deficient.¹³¹ Vegetarians are also at risk of developing iodine deficiency, especially if they eat food grown in low-iodine soil.¹³² Vegans who avoid sea vegetables are also at higher risk.¹³³

On the other hand, excessive iodine intake may increase risk of Hashimoto’s thyroiditis.¹³⁴ Iodine or foods high in iodine, such as seaweed, are thought to be useful in treating hypothyroidism, but this is likely only true for people who are iodine deficient.^133,134 The upper intake level of iodine for adults is 1,100 mcg per day. However, iodine ingestion at moderately higher levels is generally well tolerated in people without sensitivities or underlying thyroid issues.¹³⁵ Anyone supplementing with high doses of iodine should periodically have a thyroid panel blood test to ensure their thyroid activity remains in a healthy range.¹³⁶

Some foods contain goitrogenic substances that may reduce the utilization of iodine. These include cabbage,¹³⁷ Brussels sprouts, and other cruciferous vegetables,¹³⁸ as well as cassava,¹³⁹ millet,¹⁴⁰ and soybeans.¹⁴¹ The actual content of goitrogens in these foods is relatively low, however, and cooking significantly reduces their impact on thyroid function.¹⁴² It is unlikely that typical servings or supplements of cruciferous vegetables will have a measurable effect on thyroid function.¹⁴³ For those with hypothyroidism, it may be advisable to consume raw, goitrogenic foods in moderation. Some doctors also recommend avoiding caffeine and gluten and limiting sugar, alcohol, and dairy to help control symptoms, although more studies are needed to validate these approaches.¹⁴⁴

There has historically been some concern that soy and soy-containing foods may suppress thyroid function, but a 2019 meta-analysis of data from 18 studies concluded that soy consumption is not likely to impact thyroid function in most people. The analysis found that, while soy supplementation slightly increased TSH levels, free T4 and free T3 levels did not differ between soy-supplemented and control groups. However, there was some evidence that increases in TSH levels were slightly greater among people with subclinical hypothyroidism at baseline.¹⁴⁵ The evidence available as of the time of this writing suggests moderate soy consumption through dietary intake or supplementation is unlikely to compromise thyroid function in people without thyroid dysfunction to begin with. People who have thyroid dysfunction should monitor their thyroid hormone levels periodically if they consume significant amounts of soy foods or supplements.

Exercise

Regular physical activity can improve muscle tone, maintain cardiovascular health, and support healthy energy levels. Exercise has been shown to improve insulin sensitivity in people with hypothyroidism,¹⁴⁶ and is important for preventing atherosclerosis and other complications of hypothyroidism.¹⁴⁷ In one clinical trial, 10 women with subclinical hypothyroidism were assigned to engage in one hour of aerobic exercise three times per week for 16 weeks, and 10 similar women were assigned to remain sedentary. Those who exercised experienced improvements in exercise capacity, general health, and emotional health, as well as increases in mental and physical aspects of quality of life.¹⁴⁸ Nevertheless, individuals suffering from hypothyroidism often experience reduced exercise capacity that does not necessarily resolve with thyroid hormone replacement therapy¹⁴⁹ and have been found to exercise less than their healthy counterparts.¹⁵⁰

Research suggests thyroid disease is associated with changes in cardiovascular physiology and the effects of exercise. One study with 108 participants reported that arterial stiffness and TSH levels decrease after exercise, but in those with subclinical hypothyroidism, the effect of exercise on arterial stiffness was reduced and the effect on TSH levels was greater.¹⁵¹ Studies have also reported a slower rise in heart rate during the transition from rest to physical activity in subjects with subclinical hypothyroidism.¹⁵² Because people with hypothyroidism may adapt to cardiorespiratory conditioning less efficiently than those with normal thyroid function, they should remain aware of their exercise tolerance and modulate accordingly.¹⁵³

Stop Smoking

Cigarette smoking is believed to impact thyroid function and may play a role in the development of autoimmune hyperthyroidism (Graves’ disease), but evidence of a link between smoking and hypothyroidism is inconsistent, with some evidence suggesting a possible protective effect of smoking on Hashimoto’s thyroiditis.¹⁵⁴ Nevertheless, because smoking is clearly associated with the metabolic and cardiovascular complications of hypothyroidism, as well as myriad other health problems, it is best for those with overt and subclinical hypothyroidism to avoid smoking.

Manage Stress

Stress may exacerbate thyroid dysfunction, and relaxation techniques may be a useful means of helping control symptoms of mild thyroid conditions. Stress appears to alter the regulation of the hypothalamic-pituitary-thyroid (HPT) axis.¹⁵⁵

Stress and the immune system may interact in such a way that stress exacerbates the onset and/or progression of immune-mediated thyroid diseases.¹⁵⁶ In a controlled clinical trial, an eight-week stress management program reduced anti-thyroid antibody levels compared to usual care in women with Hashimoto’s thyroiditis. In addition, women in the stress management program reported lower levels of stress, anxiety, and depression.¹⁵⁷ Although a link between severe stress and the onset of autoimmune hyperthyroidism (Graves’ disease) is better documented, at least one case of Hashimoto’s thyrotoxicosis followed by temporary hypothyroidism after a period of stress has been reported.¹⁵⁸ More information is available in Life Extension’s Stress Management protocol.

Iodine

The body needs the trace element iodine to make thyroid hormone and for optimal immune function. While present naturally in seaweed, dairy products, grain products, and eggs, more than 70 countries have programs in which iodine is added to salt to increase consumption and reduce the risk of iodine deficiency.¹⁵⁹ Iodized salt has been sold in the United States since 1924, and it has proven effective at reducing iodine deficiency in areas where it was previously common, including the Great Lakes, Appalachian, and Northwestern areas. However, approximately 30% of the global population is still at risk of iodine deficiency.¹⁶⁰

Iodine deficiency in pregnant women is associated with miscarriage, stillbirth, preterm delivery, and congenital deformities in the infant.¹⁶⁰ During pregnancy, T4 production nearly doubles, causing increases in daily iodine requirements.¹⁶¹ Iodine-deficient pregnant women cannot sufficiently produce the thyroid hormones needed for proper neurological development of their growing babies. Infants born to women with iodine deficiency may have growth, hearing, or speech problems, or they may suffer from intellectual difficulties. In severe cases, underactive thyroid can cause hypothyroidism in the unborn child, or cretinism, which is characterized by brain damage, mental abnormalities, and growth problems. Worldwide, congenital hypothyroidism due to iodine deficiency during pregnancy is the most common preventable cause of mental disabilities.¹⁶⁰

Severe iodine deficiency is associated with goiter and hypothyroidism, as thyroid hormones cannot be adequately produced due to low levels of iodine. In cases of mild-to-moderate iodine deficiency, increased activity of the thyroid gland may maintain thyroid function for a time, but long-term thyroid stimulation may increase the risk of goiter and hyperthyroidism.¹³

It is important to test thyroid function when supplementing with iodine, as both low and excessively high intake can contribute to thyroid dysfunction.¹³⁵

Inositol

Inositol, a sugar that plays an important role in cell membrane physiology, is found in plant foods such as legumes, whole grains, and vegetables.²⁴⁰ It is also synthesized in the body from glucose 6-phosphate and acts as a secondary messenger in numerous cellular processes. Some clinical evidence suggests people with impaired thyroid function need more inositol than healthy subjects. In thyroid cells, TSH dose dependently stimulates inositol formation so inositol can regulate the entry of iodine into these cells—a process crucial for thyroid hormone biosynthesis.²⁴¹

In a clinical trial, 168 participants (mean age ~41 years) who had subclinical hypothyroidism due to Hashimoto’s thyroiditis were randomized to receive a combination of 600 mg inositol with 83 mcg selenium or selenium alone once daily for six months. Mean TSH levels at baseline were 4.22 µIU/mL; after treatment, TSH levels in the participants who received the combination had declined to 3.26 µIU/mL, whereas those who received only selenium had no significant changes. At baseline, participants had elevated serum thyroid peroxidase antibodies and/or thyroglobulin antibody levels. Change in levels of these antibodies was a secondary outcome measure in the study. After treatment, anti-thyroid peroxidase antibodies were lower in both groups, but anti-thyroglobulin antibodies were only lower in participants who received the combination of inositol and selenium. Free serum T4, another secondary outcome measure, increased significantly only in the combination group.²⁴²

In another clinical trial, 21 participants (mean age 48 years) with newly diagnosed Hashimoto’s thyroiditis with a normal functioning thyroid received 600 mg inositol and 83 mcg selenium twice daily to see if it could prevent the occurrence of overt hypothyroidism over the course of six months. After treatment, TSH and antithyroid antibodies were significantly lower compared with baseline and a potential marker of an aggressive thyroid inflammatory response decreased as well. Further studies are warranted to see if these effects can be extended into a large population.²⁴³

Also noteworthy, a pilot study published in 2022 found that the benefits of vitamin D on the thyroid may be more pronounced if inositol is also taken. Women with Hashimoto’s thyroiditis were separated into groups to receive either 2 grams of inositol, 4,000 IUs (100 mcg) vitamin D, or both daily for six months. After treatment, those that took both had lower antibodies for thyroid peroxidase and thyroglobulin than women who took just vitamin D. In addition, only in the group that received both vitamin D and inositol were there reductions in TSH levels and increased thyroid secretory capacity compared with baseline.²⁴⁴

Selenium

Selenium, an essential micronutrient found in Brazil nuts, cereals, mushrooms, and some fish (eg, tuna, halibut, and sardines), is a potent antioxidant that helps regulate thyroid hormone production and immune function.¹⁶² The thyroid contains more selenium by weight than any other organ,¹⁶³ and selenium is a necessary component of the enzymes that convert T4 into T3. Some evidence suggests selenium supplementation may help support efficient conversion of T4 into T3.¹⁶⁴

Selenium also plays a role in protecting the thyroid gland from oxidative stress. The cells of the thyroid generate hydrogen peroxide during the process of making thyroid hormone. Selenium protects the thyroid gland from the oxidative damage caused by these reactions. Without adequate selenium, high iodine levels can destroy thyroid gland cells.^165,166

In a randomized, double-blind, placebo-controlled trial, 230 pregnant women received 60 mcg per day of selenium from 12 weeks gestation until time of delivery. The women given selenium who were also positive for thyroglobulin antibodies at the beginning of the study exhibited small declines in TSH levels. Selenium supplementation was also associated with greater declines in free T4 levels than placebo at 35 weeks.¹⁶² A cross-sectional observational study of over 6,100 subjects from two Chinese counties (one with low and the other with adequate levels of selenium in the soil) found that the prevalence of thyroid disorders was lower in the adequate-selenium county, and low selenium status was associated with thyroid disease.¹⁶⁷

A recent literature review regarding selenium’s role in promoting thyroid health found that selenium supplementation in those with autoimmune thyroiditis reduced antibody levels, improved presentation of the thyroid on ultrasound, and improved patient quality of life.¹⁶⁸ In a placebo-controlled study, German researchers gave 200 mcg of sodium selenite daily to patients with Hashimoto's thyroiditis and high levels of thyroid peroxidase antibodies. After three months, the thyroid peroxidase antibody levels of the patients taking selenium decreased by 36% from their pre-treatment values. Quality of life and antibody levels improved more in selenium-treated patients than in placebo-treated patients.¹⁶⁹ However, Austrian researchers were unable to duplicate the results of the earlier study when they did not limit the study population to those with high levels of thyroid peroxidase antibodies. They suggested that selenium supplementation might be of greater benefit to patients with higher disease activity.¹⁷⁰

Vitamin A

Vitamin A is a fat-soluble vitamin necessary for several human cellular processes. Vitamin A refers to a family of structurally related retinoic acids, including retinol, retinal, retinyl esters (including retinyl palmitate), and beta-carotene (a precursor of vitamin A).¹⁷¹ Vitamin A, found in liver, fish oil, green leafy vegetables, milk, and eggs, plays a central role in immune function, vision, and reproduction.¹⁷²

Vitamin A is important for healthy thyroid function, and vitamin A deficiency is associated with thyroid dysfunction.^173,174 Vitamin A deficiency may change the structure of the thyroid gland and disrupt the delicate and critical signaling network of the hypothalamic-pituitary-thyroid (HPT) axis.^175,176 Conversely, inadequate thyroid function can impair the conversion of beta-carotene into the biologically active vitamin A.¹⁷⁷

In 84 healthy premenopausal women in Iran, supplementation with 25,000 IU of retinyl palmitate daily reduced TSH blood levels. The authors suggested vitamin A supplementation may reduce the risk of subclinical hypothyroidism in this population.¹⁷⁸ It should be noted, however, that long-term supplementation with high doses of pre-formed vitamin A is not generally recommended. The vitamin A precursor, beta-carotene, is better suited for daily supplementation.

L-Tyrosine

This non-essential amino acid plays an important role in thyroid hormone synthesis. Thyroxine (T4) is produced in the thyroid via iodination of tyrosine. Thus, theoretically, tyrosine insufficiency could undermine adequate thyroid hormone production. However, tyrosine deficiency is rare because it is found in the diet and because the body can make tyrosine from another common amino acid, phenylalanine. Although mechanistic data support the notion that tyrosine supplementation may support thyroid function, no well-designed clinical trials have shown supplementation with L-tyrosine to be an effective treatment for hypothyroidism.^1,179 Nevertheless, the nutrient is generally well-tolerated and readily available in many thyroid health formulas.

Ashwagandha Extract

Ashwagandha (Withania somnifera), also called winter cherry or Indian ginseng, is one of the most important herbs in traditional Ayurvedic medicine.¹⁸⁰ Extracts of ashwagandha have been used for centuries in the Ayurvedic system as an adaptogen to alleviate physical and mental stress.¹⁸¹ Extracts of ashwagandha have been prepared from the leaves, berries, and roots of the plant. Among the important chemical compounds found in ashwagandha are oligosaccharides and withanolide glycosides.^182-184

Research indicates ashwagandha extract may promote optimal thyroid health. In one randomized controlled trial, 50 subjects with high TSH levels received either 600 mg ashwagandha or placebo for eight weeks. Those in the treatment group experienced normalized serum thyroid indices, including T3, T4, and TSH levels.¹⁸⁵ Researchers studying the effects of ashwagandha extract on bipolar disorder also collected data on thyroid function. In this study, three individuals were treated for eight weeks with 500 mg per day of a standardized ashwagandha extract. All three ashwagandha-treated patients experienced decreases in TSH and increases in T4 levels of 7%, 12%, and 24% compared with baseline, indicating improved thyroid function. The researchers concluded that, although further study is necessary, ashwagandha may be useful in treating subclinical hypothyroidism.¹⁸¹

Korean Ginseng Extract

Korean ginseng (Panax ginseng, family Araliaceae) is a native perennial plant of Asia and North America that is an integral part of traditional Asian medicine. It has been in use for thousands of years and may have implications for diabetes, pulmonary disease, fatigue, and immune function.^186-189 Korean ginseng contains a wide range of bioactive components, including at least 112 saponins, most of which are glycosides of triterpenoid aglycones. The class of saponins called ginsenosides are believed to be important bioactive compounds in Korean ginseng.¹⁹⁰

Research suggests Korean ginseng can reduce concentrations of rT3. In a placebo-controlled trial in 54 adults with congestive heart failure and abnormally low levels of T3 and T4, administration of intravenous ginseng extract resulted in increased T3 and T4 levels as well as reduced rT3 levels two weeks after infusion.¹⁹¹ Korean ginseng has also been shown to improve symptoms of cold hands and feet, which are sometimes associated with suboptimal thyroid function. In a randomized, double-blind, placebo-controlled trial, 80 women with cold hypersensitivity of the hands and feet were given 500 mg Korean ginseng daily for eight weeks. At the end of the trial, subjects had substantially higher skin temperature in both their hands and feet.¹⁹²

Hypothyroidism affects fertility, sexual health, and menstrual cycle regularity. In a double-blind, placebo-controlled, crossover trial of 32 menopausal women, 3 grams of Korean red ginseng per day improved sexual function and sexual arousal (a common complaint in those with thyroid dysfunction) compared with placebo.¹⁹³ In hypothyroid rats, Panax ginseng improved reproductive hormone levels, including luteinizing hormone, follicle stimulating hormone, estradiol, prolactin, and progesterone. The mechanism of action was proposed to be scavenging free radicals.¹⁹⁴ Findings from another study involving hypothyroid rats suggested ginseng extract may improve cellular metabolism and energy production.¹⁹⁵

An enzymatically fermented ginseng extract has been developed that provides a highly bioavailable ginsenoside metabolite. Compared with non-fermented ginseng, the fermented preparation resulted in 15.5 times greater absorption over 24 hours and a 27-fold higher peak concentration in blood, which was reached in roughly a quarter of the time (3.3 hours vs. 12.0 hours).¹⁹⁶ Several studies have demonstrated that ginsenoside metabolites may have higher biological activity than unmetabolized ginsenosides, which are believed to be less bioavailable. Orally consumed unmetabolized ginsenosides are inefficiently metabolized by stomach acid and liver enzymes, but fermented ginseng may provide greater bioavailability of key ginseng compounds.^196-198

Guggul Extract

Guggul, the gum resin of the mukul myrrh tree (Commiphora mukul or Commiphora wightii), has been used in traditional Ayurvedic medicine to treat tumors, obesity, lipid disorders, low metabolism, and other conditions.¹⁹⁹ Evidence suggests guggul is a potent anti-inflammatory agent that also supports cardiovascular health.²⁰⁰ Guggulsterones are thought to be the most important bioactive compounds in guggul extract.^199,201,202

Some preclinical data suggest guggul enhances thyroid function by supporting the conversion of T4 to T3.²⁰³ A laboratory study showed an extract of Commiphora mukul significantly increased iodine uptake, T3 resin uptake, protein-bound iodine, and free T4 levels in thyroid tissue.²⁰⁴ Rats given guggulsterone derived from Commiphora mukul exhibited an increase in thyroid gland activity, as evidenced by increased iodine uptake and enhanced thyroid enzyme function.²⁰⁵ An extract of Commiphora mukul reversed experimentally-induced hypothyroidism in mice.²⁰³ This effect appears to have been mediated through enhanced production of T3 and a reduction in hepatic oxidative stress.^203,206

Zinc

Zinc, an essential mineral that plays a role in immune functioning, cellular metabolism, and wound healing, is found in red meat, poultry, beans, and nuts.²⁰⁷ Zinc, copper, and selenium are necessary for production of thyroid hormones, and deficiencies of these minerals may result in hypothyroidism. On the other hand, thyroid hormones are required for zinc absorption, and hypothyroidism may result in zinc deficiency.²⁰⁸ Zinc plays complex roles in regulating various aspects of thyroid hormone synthesis and metabolism, including the conversion of T4 to T3.²⁰⁹

In a randomized, double-blind, placebo-controlled trial, 68 women with hypothyroidism received either 30 mg zinc and 200 mcg selenium, zinc and placebo, selenium and placebo, or placebo alone for 12 weeks. Free T3 increased in both groups taking zinc, which suggests zinc alone or with selenium may promote proper thyroid function.²¹⁰ In a group of patients with low levels of free T3 and normal T4, but elevated rT3 and mild-to-moderate zinc deficiency, oral zinc supplementation for 12 months normalized serum free T3 and total T3 levels, decreased rT3 levels, and normalized TSH levels.²¹¹

Note: Chronic, very high doses of zinc interfere with copper absorption and can lead to serious and potentially fatal copper deficiency.^212-214 Thus it is advised to take copper when supplementing with high-dose zinc.

Iron

Iron, an essential mineral commonly found in foods such as lean meats, seafood, nuts, and beans, is a necessary component of hemoglobin, which carries oxygen from the lungs to the rest of the body, and plays a role in growth, metabolism, and development.²¹⁵ Iron deficiency hinders manufacture of thyroid hormone by reducing the activity of the enzyme thyroid peroxidase. In one study, 29.8% of women with subclinical hypothyroidism were iron deficient compared with 9.8% of the control group.²¹⁶ In a cross-sectional study of over 220 Nepalese children, anemic and iron-deficient children were more likely to have thyroid issues, including hypothyroidism.²¹⁷ In another study of over 3,000 women of childbearing age in China, there was a clear association between iron deficiency and low serum T4 levels in both pregnant and non-pregnant women.²¹⁸

Iron-deficiency anemia decreases, and iron supplementation improves, the beneficial effects of iodine supplementation.¹⁶⁶ Treating 51 iron-deficient hypothyroid patients with levothyroxine along with iron improved their iron-deficiency anemia more than treatment with iron alone.²¹⁹

Vitamin E

Vitamin E, a fat-soluble compound with natural antioxidant properties, plays a role in immune function, gene expression, and cellular metabolism.²²⁰ Vitamin E may reduce oxidative stress caused by hypothyroidism. Much of the research involves work with animal models. In one study, vitamin E protected animals from increased oxidation and thyroid cell damage.²²¹ In another study, vitamin E reduced the amount of thyroid cell replication in animals with induced hypothyroidism.²²² In yet another controlled animal trial, levothyroxine replacement therapy paired with vitamin E supplementation helped restore the cognitive decline seen in hypothyroidism via a decrease in oxidative stress.²²³

Vitamin D

Vitamin D is a fat-soluble vitamin that helps support bone growth and remodeling, enhance calcium absorption, promote immunity, and reduce inflammation. It is found in fatty fish and fish liver oil, and is produced naturally with exposure to sunlight.²²⁴ Vitamin D deficiency is associated with autoimmune thyroid disease, including Hashimoto’s thyroiditis. In addition, impaired vitamin D signaling pathways have been indicated in thyroid cancer.²²⁵

A correlational study found serum vitamin D and calcium levels were significantly lower in 30 hypothyroid patients than in 30 healthy controls.²²⁶ In a randomized, double-blind, placebo-controlled trial with over 200 hypothyroid participants, TSH levels decreased in those taking 50,000 IU/week vitamin D for 12 weeks.²²⁷ When adjusted for age, the presence of thyroid antibodies associated with Hashimoto’s thyroiditis was inversely correlated with vitamin D levels in a group of 642 participants (244 males and 398 females) in a study in New Delhi, India.²²⁸ Moreover, other evidence suggests vitamin D deficiency is more common among individuals with thyroid cancer or thyroid nodules compared with the general population.²²⁹ More long-term, randomized, controlled trials are necessary to determine the therapeutic role vitamin D may play in thyroid disease.

Vitamin B12

Vitamin B12 aids in red blood cell formation, DNA synthesis, and neurological functions. B12 can be found in a variety of dietary sources, including fish, meat, eggs, and milk.²³⁰ Hypothyroid patients are often vitamin B12 deficient. In one study, 190 patients with thyroid antibodies were more likely to have hemoglobin, iron, and vitamin B12 deficiencies and had higher homocysteine levels compared with 190 controls.²³¹ In another study that included 116 hypothyroid patients in Pakistan, approximately 40% of participants were found to have B12 deficiency.²³² A study involving multiple sclerosis patients in Saudi Arabia noted that low B12 levels were correlated with low T3 and T4 levels.²³³ Although this evidence suggests there may be a link between B12 deficiency and low thyroid function, it is not yet known whether B12 supplementation can improve thyroid function.²³⁴

Turmeric (Curcuma longa) Extract

Turmeric, a plant related to ginger and native to Southeast Asia and India, is a revered plant traditionally used for a variety of health concerns.²³⁵ Recent research indicates turmeric may play a role in maintaining thyroid health. Turmeric contains curcumin and related compounds that have antioxidant and anti-inflammatory actions and may help regulate thyroid and other hormone production and activity.²³⁶ In one retrospective study of over 2,000 people in Pakistan, people with diets high in turmeric had fewer goiters.²³⁷

In animal research, treatment with turmeric extract reduced the impact of chemically induced hypothyroidism on thyroid weight, T4, T3, and cholesterol levels.²³⁸ Results of a similar trial on rats treated with vitamin E and curcumin showed that treatment prevented a decline in basal body temperature and protected the liver.²³⁹