~Thyroid Regulation

~Thyroid Regulation
Reprinted with permission of Life Extension®.

Millions of Americans suffer from fatigue, weight gain, depression, and cognitive impairment. Many believe that they have no choice but to accept these seemingly “age-related” declines in quality of life.

Underactive thyroid (hypothyroidism) is often overlooked or misdiagnosed and can be the underlying cause of these symptoms. Patients and their doctors often disregard these common signs of thyroid hormone deficiency, mistaking them for normal aging.1

Overactive thyroid (hyperthyroidism) afflicts fewer people than hypothyroidism, yet the symptoms can be equally devastating. Subclinical hyperthyroidism, characterized by suppressed thyroid stimulating hormone (TSH) levels accompanied by normal thyroid hormones (T4 and T3) levels,2 has been associated with increased rates of cardiovascular disease; arrhythmia in particular.3 Overt hyperthyroidism compromises bone health,4 elevates blood glucose levels,5 and often causes anxiety.6

Fortunately, a simple blood test for TSH, T3 and T4 can reveal an underlying thyroid condition and help direct treatment to improve the symptoms.1, 2

In this protocol we will discuss the function and regulation of the thyroid gland, and the systemic implications of both hypothyroidism and hyperthyroidism. We will examine the importance of proper testing and interpretation of thyroid hormone levels and reveal natural approaches for maintaining optimal thyroid hormone levels.

Role of the Thyroid The thyroid is a butterfly-shaped organ located just below the Adam’s apple in the neck. Made up of small sacs, this gland is filled with an iodine-rich protein called thyroglobulin along with the thyroid hormones thyroxine (T4) and small amounts of triiodothyronine (T3).

The primary function of these two hormones is to regulate metabolism by controlling the rate at which the body converts oxygen and calories to energy. In fact, the metabolic rate of every cell in the body is regulated by thyroid hormones, primarily T3.7

In healthy individuals the gland is imperceptible to the touch. A visibly enlarged thyroid gland is referred to as a goiter. Historically, goiter was most frequently caused by a lack of dietary iodine. 8 However, in countries where salt is iodized, goiter of iodine deficiency is rare.

Thyroid Regulation

The production of T4 and T3 in the thyroid gland is regulated by the hypothalamus and 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). This TRH then stimulates the pituitary to release thyroid stimulating hormone (TSH).9,10 When thyroid hormone levels increase, production of TSH decreases, which in turn slows the release of new hormone from the thyroid gland.

Cold temperatures can also increase TRH levels. This is thought to be an intrinsic mechanism that helps keep us warm in cold weather.11

Elevated levels of cortisol, as seen during stress and in conditions such as Cushing’s syndrome, lowers TRH, TSH and thyroid hormone levels as well.12,13

The thyroid gland needs iodine and the amino acid L-tyrosine to make T4 and T3. A diet deficient in iodine can limit how much T4 the thyroid gland can produce and lead to hypothyroidism.14

T3 is the biologically active form of thyroid hormone. The majority of T3 is produced in the peripheral tissues by conversion of T4 to T3 by a selenium-dependent enzyme. Various factors including nutrient deficiencies, drugs, and chemical toxicity may interfere with conversion of T4 to T3.15

Another related enzyme converts T4 to an inactive form of T3 called reverse T3 (rT3). Reverse T3 does not have thyroid hormone activity; instead it blocks the thyroid hormone receptors in the cell hindering action of regular T3.16

Ninety-nine percent of circulating thyroid hormones are bound to carrier proteins, rendering them metabolically inactive. The remaining “free” thyroid hormone, the majority of which is T3, binds to and activates thyroid hormone receptors, exerting biological activity.17 Very small changes in the amount of carrier proteins will affect the percentage of unbound hormones. Oral contraceptives, pregnancy, and conventional female hormone replacement therapy may increase thyroid carrier protein levels and, thereby, lower the amount of free thyroid hormone available.18

Thyroid Dysfunction

Hyperthyroidism

In hyperthyroidism, the thyroid gland produces too much thyroid hormone, which can significantly accelerate the body's metabolism. Typical symptoms of hyperthyroidism include sudden weight loss, a rapid heartbeat, sweating, nervousness or irritability. Hyperthyroidism affects about one percent of the population.19

Extreme hyperthyroidism, or thyrotoxicosis, can culminate in what’s referred to as “thyroid storm”.20 In this medical emergency, patients suffer from elevated heart rates and blood pressure, extreme exhaustion, and high fever. Thyroid storm sharply increases a patient’s risk for stroke and heart attack, and is fatal for up to 50% of patients, even with the best medical care.21


Hyperthyroidism: What you need to know

Hyperthyroidism is usually caused by Graves’ disease characterized by symptoms such as rapid heartbeat, sweating, nervousness, tremors, muscle weakness, sleep difficulties, increased appetite and sudden weight loss.22 Affected individuals can also experience thyroid storm--a potentially deadly medical emergency.23

Medical Treatment of Grave’s disease 24

  • Anti-thyroid drugs, such as methimazole or proplythiouracil, inhibit the production of T3.

  • Radioactive iodine, which causes destruction of the overactive thyroid gland.

  • Surgical removal of the thyroid gland (thyroidectomy).

  • Βeta-blockers may be used to control the high blood pressure and increased heart rate associated with hyperthyroidism.


Nutritional Support of Hyperthyroidism

  • Increased thyroid activity increases loss of L-carnitine through the urine. Individuals suffering from hyperthyroidism may, therefore, require supplemental L-carnitine.25

  • L-carnitine supplementation helped prevent or reverse muscle weakness and other symptoms in individuals suffering from hyperthyroidism. Clinical trials have shown that doses of 2,000-4,000 mg/day of L-carnitine are helpful in individuals who suffer from hyperthyroidism.26

  • Passion flower (Passiflora incarnata ) and valerian (Valeriana officinalis) are botanicals that have a calming effect on the nervous system27,28 and thus may help control the symptoms of an overactive thyroid.



Hypothyroidism

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormones, characterized by a reduction in metabolic rate. The main symptoms of hypothyroidism are fatigue, weakness, increased sensitivity to cold, constipation, unexplained weight gain, dry skin, hair loss or coarse dry hair, muscle cramps and depression. However, most symptoms take years to develop. The slower the metabolism gets, the more obvious the signs and symptoms will become. If hypothyroidism goes untreated, the signs and symptoms could become severe, such as a swollen thyroid gland (goiter), slow thought processes, or dementia. 29

Subclinical hypothyroidism, an often under-diagnosed thyroid disorder, manifests as elevated TSH, normal T4 and normal T3 levels.30 Individuals with subclinical hypothyroidism are at greater risk for developing overt hypothyroidism.31 An August 2010 study reported that 8.3% of women with no history of thyroid disease suffer from subclinical hypothyroidism.32 An article in the American Family Physician in 2005 estimated that about 20% of women over the age of 60 suffer from subclinical hypothyroidism.33

There is evidence that the standard blood TSH test reference range may cause many cases of hypothyroidism to be missed. Most physicians accept a reference range for TSH between 0.45 and 4.5 mU/L to indicate normal thyroid function. In reality, though, a TSH reading of more than 2.0 may indicate lower-than-optimal thyroid hormone levels.34

According to a study reported in Lancet, various TSH levels that fall within normal range are associated with adverse health outcomes.26

  • TSH greater than 2.0: increased 20-year risk of hypothyroidism and increased risk of thyroid autoimmune disease

  • TSH between 2.0 and 4.0: hypercholesterolemia and cholesterol levels decline in response to T4 therapy

  • TSH greater than 4.0: greater risk of heart disease


There is another and separate problem brought on by these overly broad normal ranges for TSH. People already diagnosed and being treated for hypothyroidism are often not taking correct doses of thyroid replacement hormone. A November 2010 study reported that about 37% of people being treated for hypothyroidism were taking incorrect doses, about half too much and another half too little hormone.35

Consequences of Hypothyroidism

Gastrointestinal problems: Hypothyroidism is a common cause of constipation. Constipation in hypothyroidism may result from diminished motility of the intestines. In some cases, this can lead to intestinal obstruction or abnormal enlargement of the colon.36 Hypothyroidism is also associated with decreased motility in the esophagus, which causes difficulty swallowing, heartburn, indigestion, nausea, or vomiting. Abdominal discomfort, flatulence, and bloating occur in those with small intestinal bacterial growth secondary to poor digestion.31

Depression and psychiatric disorders: Panic disorders, depression, and changes in cognition are frequently associated with thyroid disorders.37 Hypothyroidism is often misdiagnosed as depression.38 A study published in 2002 suggests that that thyroid function is especially important for bipolar patients: “Our results suggest that nearly three-quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response.” 39

Cognitive decline: Patients with low thyroid function can suffer from slowed thinking, delayed processing of information, difficulty recalling names, etc.40 Patients with subclinical hypothyroidism show signs of decreased working memory,41 and decreased speed of sensory and cognitive processing.42 An evaluation of thyroid hormones along with TSH may help avoid misdiagnosis as being depressed. 43

Cardiovascular Disease: Hypothyroidism and subclinical hypothyroidism are associated with increased levels of blood cholesterol, increased blood pressure, and increased risk of cardiovascular disease. 44 Even those with subclinical hypothyroidism were almost 3.4 times as likely to develop cardiovascular disease than those with healthy thyroid function.45

  • High blood pressure: Hypertension is relatively common among patients with hypothyroidism. In a 1983 study, 14.8% of patients with hypothyroidism had high blood pressure, compared with 5.5% of patients with normal thyroid function. 46 “Hypothyroidism has been recognized as a cause of secondary hypertension. Previous studies … have demonstrated elevated blood pressure values. Increased peripheral vascular resistance and low cardiac output has been suggested to be the possible link between hypothyroidism and diastolic hypertension.” 47

  • High cholesterol and atherosclerosis: “Overt hypothyroidism is characterized by hypercholesterolemia and a marked increase in low-density lipoproteins (LDL) and apolipoprotein B” 48 These changes accelerate atherosclerosis, which causes coronary artery disease.43 The risk of heart disease increases proportionally with increasing TSH, even in subclinical hypothyroidism.49 Hypothyroidism that is caused by autoimmune reactions is associated with stiffening of the blood vessels. 50 Thyroid hormone replacement may slow the progression of coronary heart disease by inhibiting the progression of plaques.51,52

  • Homocysteine: Treating hypothyroid patients with thyroid hormone replacement might attenuate homocysteine levels, an independent risk factor for cardiovascular disease: “A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism.” 53

  • Elevated C-reactive protein: Overt and subclinical hypothyroidism are both associated with increased levels of low-grade inflammation, as indicated by elevated C-reactive protein (CRP). A 2003 clinic study observed that CRP values increased with progressive thyroid failure and suggested it may count as an additional risk factor for the development of coronary heart disease in hypothyroid patients. 54


Metabolic Syndrome: In a study of more than 1,500 subjects, researchers found that those with metabolic syndrome had statistically significantly higher TSH levels (meaning lower thyroid hormone output) than healthy control subjects. Subclinical hypothyroidism was also correlated with elevated triglyceride levels and increased blood pressure. Slight increases in TSH may put people at higher risk for metabolic syndrome. 55

Reproductive system problems: In women, hypothyroidism is associated with menstrual irregularities and infertility.56 Proper treatment can restore a normal menstrual cycle and improve fertility. 57

Fatigue and weakness: The well known and common symptoms of hypothyroidism, such as chilliness, weight gain, paresthesia (tingling or crawling sensation in the skin) and cramps are often absent in elderly patients compared with younger patients, fatigue and weakness are common in hypothyroid patients.58

Testing Thyroid Function

Thyroid stimulating hormone (TSH) level is the most common test for screening for thyroid dysfunction. In the last decade the diagnostic strategy for using TSH measurements has changed as a result of the sensitivity improvements in these assays. It is now recognized that the TSH measurement is a more sensitive test than T4 for detecting both hypo- and hyperthyroidism. 59 As a result, some countries now promote a TSH-first strategy for diagnosing thyroid dysfunction in patients. 60

In 2008 many labs adopted the reference range for TSH, 0.45 to 4.50 μIU/mL, recommended by both the Endocrine Society and the American Medical Association. Although this range is an improvement over the previous 0.45-5.5 mIU/L, it is still considered too broad by many clinicians. 59, 60, 61

The American Association of Clinical Endocrinologists now recommends an upper limit of 3.0 mIU/L.61 The guidelines for diagnosing thyroid disease from The National Academy of Clinical Biochemistry point out that “more than 95% of normal individuals have TSH levels below 2.5 [mIU/L].. 62 This panel suggests that the upper limit of TSH should be reduced to 2.5 mIU/L.63

On the other hand, current studies also suggest that TSH values below the normal range may represent thyroid hormone excess and, in elderly patients, might be associated with an increased risk of death due to cardiovascular disease. 64, 65

Life Extension suggests an optimal level of TSH between 1.0 and 2.0 mIU/L, as some studies have noted that a TSH above 2.0 may be associated with adverse cardiovascular risk factors. 26 In addition, a TSH between 1.0 and 2.0mIU/L has been associated with the lowest subsequent incidence of abnormal thyroid function.66

However, while a measure of TSH alone is a useful screening tool in assessing thyroid function, Life Extension advocates additional testing, including Free T3 and T4 levels, to provide a more complete evaluation of the thyroid.

Note: TSH values do fluctuate with time of day, infection, and various other factors. In a 2007 survey published in the Archives of Internal Medicine, values spontaneously returned to normal in more than 50% of patients with abnormal TSH levels when the test was repeated at a later date.67 No single measurement of TSH should be considered diagnostic.

Basal Body Temperature: An alternative method for assessing thyroid status that was widely used in the past, before the development of accurate thyroid function blood tests, is the basal body temperature test. The temperature is taken when the body is at complete rest, immediately after waking and before beginning any activity. The normal basal temperature is 97.6-98.2ºF, and some alternative practitioners believe that a 5-day consecutive temperature reading below 97.6 ºF is indicative of hypothyroidism. One study showed a significant correlation between the basal body temperature and low thyroid function in whiplash patients. The authors of this study conclude that basal body temperature “seems to be a sensitive screening test, in combination with laboratory analysis, for the hypothyroidism seen after whiplash trauma.”68 However, there are many reasons for alteration of basal body temperature, a thyroid panel blood test should be taken to accurately evaluate the thyroid function.

Tests for T4 and T3: Thyroid hormones can be tested in both their free and protein-bound forms. Tests for the protein-bound forms and unbound form of T4 or T3 are generally referred to as Total T4 or Total T3 respectively; unbound forms are called Free T4 and Free T3. Each of these tests gives information about how the body is making, activating, and responding to thyroid hormone. Levels of free T3 and T4 will be below normal in clinical hypothyroidism. In subclinical hypothyroidism the TSH will be elevated while the thyroid hormone levels are still in the normal reference range.

Reverse T3: Certain individuals with apparently normal T4 and T3 hormone levels still display the classic symptoms of hypothyroidism. This may be due to an excessive production of reverseT3 (rT3). rT3 is inactive and may interfere with the action of T3 in the body. Stress and extreme exercise may play a role in lowering thyroid hormone action by suppressing production of TSH and T3 and elevating rT3 levels.69,70

Autoimmune antibodies: When evaluating the thyroid it is also important to consider that the most common cause of overt hypothyroidism in the United States is an autoimmune disorder known as Hashimoto’s thyroiditis.71 In this condition the body produces antibodies to the thyroid gland and damage the gland. Hashimoto’s thyroiditis is diagnosed by standard thyroid testing in conjunction with testing for the presence of these antibodies called antithyroglobulin antibodies (AgAb) and thyroperoxidase antibodies (TPOAb). Some people with celiac disease or sensitivity to gluten are at increased risk for developing autoimmune thyroid disease and should be evaluated.72

Elevated thyroid antibodies are often associated with chronic urticaria, also called hives. Studies report that as many as 57.4% of patients with hives have the presence of anti-thyroid antibodies.73,74 An August 2010 paper suggests that treatment with T4 improves the itching associated with urticaria, but did not advise treatment with T4 unless the patient was hypothyroid. 75

Additional testing: Sometimes biopsy or enzymatic studies are required to establish a definite diagnosis for thyroid dysfunction. Major abnormalities of the thyroid gland detected in physical exam can be further assessed by ultrasound or a procedure known as scintigraphy.

Hypothalamic pituitary axis (HPA): There is an intimate relationship between the thyroid, the adrenal glands and the sex hormones.76 If hypothyroidism is suspected, an evaluation of the adrenal glands as well as the sex hormones is suggested.


Hypothyroidism: What you need to know

  • Thyroid diseases occur about five times more frequently in women than in men. As many as 20% of women over 60 years old have subclinical hypothyroidism.77

  • If untreated, chronic hypothyroidism can result in myxedema coma, a rare, life-threatening condition. Mental dysfunction, stupor, cardiovascular collapse, and coma can develop after the worsening of chronic hypothyroidism as well.78

  • An autoimmune disease called Hashimoto’s thyroiditis is the most common cause of low thyroid function in the US. The body’s immune system mistakenly attacks the thyroid tissue impairing the ability to make hormones.79 Hypothyroidism caused by Hashimoto's disease is treated with thyroid hormone replacement agents.

  • Hashimoto’s disease usually causes hypothyroidism, but may also trigger hyperthyroid symptoms.80

  • Hyperthyroidism is usually caused by Graves’ disease, in which antibodies are produced that bind to TSH receptors in the thyroid gland, stimulating excess thyroid hormone production.20

  • The distinction between Hashimoto’s thyroiditis and Graves’ disease may not be as important as once thought. In 2009 researchers wrote that, “Hashimoto's and Graves' disease are different expressions of a basically similar autoimmune process, and the clinical appearance reflects the spectrum of the immune response in a particular patient.”81 The two diseases can overlap causing both thyroid gland stimulation and destruction simultaneously or in sequence.82 Some clinicians consider the two conditions different presentations of the same disease.83 About 4% of patients with Graves’ disease displayed some symptoms of Hashimoto’s thyroiditis during childhood.84

  • Pregnant women are especially at risk for hypothyroidism. During pregnancy, the thyroid gland produces more thyroid hormone than when a woman is not pregnant,85 and the gland may increase in size slightly.

  • Uncontrolled thyroid dysfunction during pregnancy can lead to preterm birth, mental retardation, and hemorrhage in the postpartum period. 86 It is important to work closely with a physician to monitor thyroid function during pregnancy.

  • Tests to diagnose and monitor hypothyroidism include: Thyroid Stimulating Hormone (TSH), Total T4, Total T3, Free T4 (fT4), Free T3 (fT3), Reverse T3 (rT3), Thyroid peroxidase antibody (TPOAb), Thyroglobulin antibody (TgAb)



Thyroid Hormone Replacement

The most common treatment for low thyroid hormone levels consists of thyroid hormone replacement therapy. The goal of thyroid hormone replacement is to relieve symptoms and to provide sufficient thyroid hormone to decrease elevated TSH levels to within the normal range.87

Conventional treatment almost always begins with synthetic T4 (levothyroxine) preparations like Synthroid® or Levoyxl®. Low doses are usually used at first because a rapid increase in thyroid hormone may result in cardiac damage.88

Sometimes hypothyroid symptoms persist despite T4 treatment. In a 2001 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.89 A December 2010 study compared the T3 and T4 levels of hypothyroid patients treated with T4 alone against the levels found in healthy people and reported that T4 supplementation alone did not increase T3 to the same level as found in healthy people.90 As you will read later, deficiencies in nutrients like selenium can disable the body from converting T4 to biologically active T3.

In an animal study, rats with the thyroid gland removed were treated with T4 alone. The researchers found that no single dose restored normal concentrations of TSH, T4, and T3 in the blood, tissues and organs.91 The following year the same authors reported that a combination of T4 and T3 was able to normalize hormone levels in both blood and tissues.92 Other studies have failed to demonstrate any advantage of the combination therapy, although the results do suggest the possibility of a subset of hypothyroid patients who would benefit from combination therapy.93,94

One combination option is a drug called Thyrolar, which combines synthetic T3 and T4 in a fixed 1:4 ratio. Caution should be used, however, in administering T3 to older individuals because excess T3 may cause adverse cardiac events in this population.95

Another T3 option is a drug called Cytomel®, which is a synthetic form of T3. This can be used in combination with T4.

Desiccated Thyroid: 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.

Armour thyroid is preferred by some clinicians because it may achieve results in patients that fail to respond to levothyroxine alone. Patients with hypothyroidism show greater improvements in mood and brain function if they receive treatment with Armour thyroid rather than Synthroid®.96 One argument favoring natural hormones is that other naturally occurring hormones and chemicals found in these preparations may buffer or enhance the effect of the active hormones. 87,92

Ultimately, there may not be a single correct approach to low thyroid hormone levels. Instead, the best option may be to monitor thyroid levels through regular blood testing and systematically try various protocols to see what yields the best resolution of symptoms. Some people may prefer to begin with desiccated thyroid, while others may find it preferable to begin with T4 supplementation then move to a combination T3-T4 therapy if they experience no improvement from T4 alone.

Absorption of Thyroid hormone Medications: Coffee,97 aluminum antacids,98 ferrous sulfate (iron),99 calcium carbonate,100 soy 101 and possibly grapefruit juice102 can all decrease the absorption of thyroid hormone prescriptions. Most doctors simply advise patients to take thyroid away from any food or medication.

While most people take thyroid hormone in the morning, a December 2010 paper suggests that it is more effective to take thyroid just before bed.103

Nutrients to Support Thyroid Function

Iodine: The body needs iodine to make thyroid hormone. As of the late 1990s, thirty-two European countries were still affected by iodine deficiency.104 In 2007 the WHO estimated that over 30% of the world’s population (2 billion people) has insufficient iodine intake as measured by urinary iodine excretion below 100 micrograms (mcg)/liter.105 Iodized salt has proven to be effective at preventing iodine deficiency. The Morton Salt Company began selling iodized salt in the US in 1924.106

Hypothyroidism in the unborn child, congenital hypothyroidism or cretinism, is frequently caused by iodine deficiency. In industrialized countries the incidence is about 1 case in 4,500 live births. Yet, the incidence of cretinism can increase to as much as 1 case in 20 live births in areas that have iodine deficiency.107 Because of this, iodine deficiency remains one of the leading causes of mental retardation.108

During pregnancy T4 production doubles, causing increases in daily iodine requirements.109 Iodine deficient pregnant women cannot produce the thyroid hormones that are needed for proper neurological development of their growing babies, and are at high risk of giving birth to infants with cognitive impairment and learning delay. Even moderate iodine deficiency in a pregnant woman can lower her infant’s IQ from 8 to 16 points.110, 111

People who avoid iodized salt or adhere to a salt-restricted diet may become iodine deficient.112 Vegetarians are also at risk of developing iodine deficiency, especially if they eat food grown in low iodine soil.113 Vegans that avoid sea vegetables, are also at higher risk.114

Diets both low and high in iodine are associated with hypothyroidism. This is supported by studies that have shown that both low and high urinary iodine excretion are associated with hypothyroidism.115 High intake of iodine also increases the risk of Hashimoto’s thyroiditis.116

Iodine or foods high in iodine, such as seaweed, are thought useful in treating hypothyroidism but this is probably only true for people who are iodine deficient.113, 114 In 2007 Jane Teas reported a slight increase in TSH levels in healthy postmenopausal women who consumed 5 grams/day of seaweed (Alaria esculenta).117 A 2008 trial measuring the effect of eating Kombu (Laminaria japonica) seaweed in Japanese adults found that eating 15 and 30 grams of Kombu (containing 35 and 70 mg of iodine) daily for about a week, significantly increased TSH (which reflects lower thyroid hormone output).118

The upper intake level (UL) of iodine for adults is 1.1mg per day. The safety of therapeutic doses of iodine above the established upper intake level (UL) is evident in the lack of toxicity in people living in the northern coastal regions of Japan, whose diets contain large amounts of seaweed, have been found to have iodine intakes ranging from 50,000 to 80,000 mcg (50-80 mg) of iodine per day. 119 Studies using 3.0 to 6.0mg iodine per day to effectively treat fibrocystic breast disease may reveal an important role for iodine in maintaining normal breast tissue architecture and function. 120 Iodine may also have import antioxidant functions in breast tissue and other tissues that concentrate iodine. 121

Life Extension’s review of the scientific literature suggests an iodine intake up to 1,150 mcg daily is reasonable. However, the amount of supplemental iodine needed for an individual varies widely based on the factors listed above. It is important to test thyroid function when supplementing with iodine since both low and excessively high intake can contribute to hypothyroidism.

Selenium: After iodine, selenium is probably the next most important mineral affecting thyroid function. The thyroid contains more selenium by weight than any other organ.122 Selenium is a necessary component of the enzymes that remove iodine molecules from T4 converting it into T3; without selenium there would be no activation of thyroid hormone. When patients suffering from various forms of thyroid disease were tested for selenium levels, all were found to be lower than normal healthy people.123 Some researchers suggest that selenium supplementation will improve conversion of T4 to T3.124 Selenium also plays a role in protecting the thyroid gland itself. The cells of the thyroid generate hydrogen peroxide and use it to make thyroid hormone. Selenium protects the thyroid gland from the oxidative damage caused by these reactions. Without adequate selenium, high iodine levels lead to destruction of the thyroid gland cells.125, 126

People living in areas with low soil selenium content are more likely to develop Hashimoto's disease. 127 This may be because a selenium deficiency makes the enzyme glutathione peroxidase less effective. 128 Thus selenium supplementation has been suggested for treating Hashimoto’s disease.129

In a placebo controlled study published in 2002, researchers in Germany reported on an experiment in which they gave 200 mcg of sodium selenite daily to patients with Hashimoto's disease and high levels of thyroid peroxidase antibodies. After three months, the thyroid peroxidase antibody levels of the patients taking selenium were decreased by 66.4% compared to their pre-treatment values, and antibody levels returned to normal in nine of the selenium treated patients.130 Austrian researchers reported in 2008 that they 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 suggest that selenium supplementation might be of greater benefit to patients with higher disease activity. 131

Selenium deficiency is also common in celiac disease, and this may be the tie-in to increased frequency of thyroid problems with celiac disease.132

During severe or prolonged infection, blood levels of selenium, T4, T3 and TSH decrease and the conversion of T4 to T3 slows, inducing a hypothyroid state.133 Because the enzymes that moderate this conversion require selenium, it has been hypothesized that supplementing extra selenium might prevent this decrease in T3 during illness. Supplying extra selenium may decrease mortality from infection, but it does not normalize thyroid hormone levels.134 It seems that the suppression of T3 during sickness is mediated by cytokines, in particular interleukin-6 (IL-6).135 It may be that IL-6 and other cytokines, generated by the infection, limit production of the selenium-enzymes and interfere with hormone production.

Zinc: Zinc may be helpful in patients with low T3 and may contribute to conversion of T4 to T3. In animal studies, zinc deficiency lowered T3 and free T4 concentrations by approximately 30%. Levels of total T4 were not affected by zinc deficiency.136 In a group of patients with low levels of free T3 and normal T4, but elevated rT3 and mild to moderate Zn deficiency, taking oral zinc supplements for 12 months, normalized the serum free T3 and total T3 levels, decreased the rT3 and normalized TSH levels.137.

On the other hand, like iodine, too much zinc may suppress thyroid function.138 Very high doses of zinc interfere with copper absorption and can lead to serious and potentially fatal copper deficiency. 139., 140., 141. Thus it is advised to take copper when supplementing with zinc.

Iron: Iron deficiency hinders manufacture of thyroid hormone by reducing activity of the enzyme thyroid peroxidase. In one study 15.7% of women with subclinical hypothyroidism were iron deficient, compared to only 9.8 % of the control group.142 Iron-deficiency anemia decreases, and iron supplementation improves, the beneficial effects of iodine supplementation.143 Treating iron deficient hypothyroid patients with levothyroxine (T4) along with iron improves their iron deficiency anemia more than treatment with iron alone.144

Copper: An August 2010 study revealed that copper is important for normal brain development and its deficiency leaves the hypothalamus unable to regulate thyroid hormone effectively. Copper deficient pregnant rats give birth to infant rats that produce 48% less T3 than those born from healthy mothers.145

Vitamin E: Vitamin E may reduce the oxidative stress caused by hypothyroidism. In one animal study, vitamin E was shown to protect animals from increased oxidation and thyroid cell damage.146 In another study, vitamin E reduced the amount of thyroid cell replication in animals with induced hypothyroidism.147

Vitamin D: Deficiency of vitamin D may increase risk of autoimmune thyroid disease. When adjusted for age, presence of thyroid antibodies was inversely correlated with vitamin D levels in a group of 642 participants (244 males and 398 females) in New Delhi, India.148 Moreover, other evidence suggests that vitamin D deficiency is more common among individuals with thyroid cancer or thyroid nodules, compared to the general population.149 Given the many benefits of adequate vitamin D, it makes sense to supplement if needed.

Vitamin B12: Hypothyroid patients are often vitamin B12 deficient. In a 2008 paper, Pakistani doctors reported that of 116 hypothyroid patients tested for vitamin B12, approximately 40% were deficient.150 It isn’t clear what the link between B12 deficiency and low thyroid function is, nor if thyroid function will improve with B12 supplementation.151 But, since low B12 causes serious neurologic damage, all hypothyroid patients should be tested.

DHEA and Pregnenolone: Japanese researchers reported that concentrations of DHEA, DHEA-sulfate, and pregnenolone-sulfate are significantly lower in hypothyroid patients compared to age and sex matched healthy controls.152

Turmeric (Curcuma longa) Extract: A 2002 study, using rats, found that treatment with turmeric extract reduced the impact of chemically induced hypothyroidism in terms of thyroid weight, T4, T3 and cholesterol levels. 153 Results of a similar trial on rats treated with vitamin E and curcumin, a component found in turmeric, showed that treatment prevented a decline in basal body temperature and protected the liver.154

Rhodiola rosea: Given the fact that stress can influence thyroid status, it may be beneficial for some individuals with hypothyroidism to consider adaptogenic herbs such as Rhodiola.155, 156 Adaptogenic herbs support the adrenal glands and can improve the body’s response to stress.157

Dietary Recommendations

Some foods contain goitrogenic substances that reduce the utilization of iodine. These foods include canola oil, vegetables from the Brassica family (e.g., cabbage158 and brussels sprouts159), cassava160, and millet.161 The actual content of goitrogens in these foods is relatively low, however, and cooking significantly reduces the impact of these goitrogens on thyroid function.162

Studies show conflicting information concerning the impact of soy on the thyroid. Isoflavone molecules in soy do inhibit an enzyme involved in thyroid hormone synthesis,163,164 but that has not translated into poor thyroid function in otherwise healthy individuals with adequate iodine intake.165,166,167

For those with hypothyroidism, raw goitrogenic foods and soy foods that have not undergone fermentation and/ or food processing should be consumed in moderation and discontinued if symptoms should appear.

Life Extension Recommendations

Thyroid hormone supplementation: If hormones are necessary, work with an experienced medical provider to find a hormone supplement that works best for you.

TSH Target: An ideal TSH level is between 1 and 2 mIU/L. TSH levels lower than this may increase risks and symptoms associated with hyperthyroidism. TSH levels higher than this may increase the risks and symptoms associated with hypothyroidism.

  • Iodine: Up to 1,150 mcg daily

  • Selenium: 200 - 400 mcg daily

  • Zinc: 30 - 80 mg daily

  • Copper: 1 - 2 mg daily

  • Natural Vitamin E: 400 IU alpha-tocopherol and 200 mg gamma-tocopherol

  • Vitamin C: 1,000 - 2,000 mg daily

  • Iron: Check for deficiency and correct if low

  • Vitamin B12 (as methylcobalamin): 1,000 - 2,000 mcg daily

  • DHEA: The exact dosage to be taken should be determined by blood testing and the advice of a physician. Typical dosages range from 15 - 75 mg daily taken in the morning. DHEA serum blood tests are suggested 3-6 weeks after initiating DHEA replacement therapy to optimize individual dosing.

  • Pregnenolone: Check for deficiencies and correct if low. Typical dosages are 50 - 100 mg daily. A complete hormone profile is suggested when supplementing with pregnenolone as it may affect levels of other hormones, such as progesterone, estrogen, testosterone and/or DHEA.

  • Rhodiola; standardized extract: 250 - 500 mg daily


Safety Caveats

Iodine: If you have a thyroid condition or are taking antithyroid medications, do not use without consulting your healthcare practitioner.

Zinc: Supplemental zinc can inhibit the absorption and availablility of copper. If more than 50 mg of supplemental zinc is taken daily, 2 mg of supplemental copper should also be taken to prevent deficiency. Chronic ingestion of more than 100 mg of zinc daily may be toxic.

Copper: Individuals with in-born errors of copper metabolism (e.g. Wilson’s disease) should avoid daily, chronic use of copper.

Vitamin E: If you are taking anti-coagulant or anti-platelet medications, or have a bleeding disorder, consult your healthcare provider before taking this product.

Vitamin C: Ascorbic acid is the acidic form of vitamin C, and even in tablet form, can cause gastric upset or diarrhea for some people. This can often be alleviated by consuming it with meals. Start with a low dose then gradually increase. If you have a stomach ulcer, use an antacid, buffering agent, or a buffered form of vitamin C. Calcium carbonate and magnesium oxide are effective antacids. Unbuffered ascorbic acid in the mouth may be harmful to tooth enamel.

Iron: Do not take this product unless you are truly deficient in iron. Excess iron may cause increased oxidation leading to inflammation.

DHEA: Do not use DHEA if you are at risk for or have been diagnosed as having any type of hormonal cancer, such as prostate or breast cancer.

Pregnenolone: Pregnenolone may affect levels of other hormones, such as progesterone, estrogen, testosterone and/or DHEA. Do not take this product if you have a history of seizures. Do not take this product if you have breast cancer, prostate cancer, or other hormone-sensitive diseases.

Rhodiola: Individuals with manic or bipolar disorder should not use Rhodiola. Take early in the day if Rhodiola Extract interferes with your sleep.

References below.


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