Orthomolecular Interventions
Vitamin A
Vitamin A and hypothyroidism
Lack of vitamin A is linked to (Sworczak & Wiśniewski, 2011):
- decreased uptake of iodine by the thyroid
- restricted hormone production and release
- enlargement of the thyroid gland
- higher levels of TSH secretion
- vitamin A deficiency can lead to reduced binding and uptake of T3 by tissues, as well as decreased hepatic conversion of T4 to T3 (The Relationship between Thyroid Disorders and Vitamin A.: A Narrative Minireview – PMC, n.d.
- In animals, vitamin A deficiency leads to an enlarged thyroid, reduces the thyroid’s iodine uptake, hampers the production of thyroglobulin and the joining of iodotyrosine residues to create thyroid hormone, and lowers the levels of T3 and T4 within the thyroid. (Zimmermann et al., 2004)
- TSH hyperstimulation, indicated by higher levels of TSH, thyroglobulin, and thyroid volume, has been shown to decrease with vitamin A treatment. (Zimmermann et al., 2004)
- There is a significant relationship between the size of a goiter and the severity of vitamin A deficiency. Treatment with just vitamin A resulted in lower TSH levels and smaller goiter size, while the levels of thyroid hormones in the blood remained unchanged. (Sworczak & Wiśniewski, 2011)
- Multiple studies have shown that a lack of vitamin A raises the risk of developing goiter. Among adults in Senegal and children in Ethiopia, there was a significant negative relationship between worsening goiter severity and levels of serum retinol. (Zimmermann et al., 2004)
- Vitamin A supplementation helps the body use iodine more effectively. (Zimmermann et al., 2004)
- Evidence strongly supports the combined fortification and supplementation of iodine and vitamin A in areas where both deficiencies exist. (Zimmermann et al., 2004)
Vitamin A deficiency is common
- 75% of adults in the US do not achieve the 3,000 IU/day recommendation for vitamin A intake (Gröber & Holick, 2022).
- 34% of adults in the US consume less than the EAR (Estimated Average Requirement) for vitamin A (Sestili & Fimognari, 2020).
- Hospitalized patients have been shown to have significantly lower levels of vitamin A when compared to convalescent persons (Tepasse et al., 2021).
- Vitamin A deficiency is one of the top micronutrient deficiencies, especially in countries with low protein and meat consumption (Iddir et al., 2020).
Dietary beta carotene needs to be converted to vitamin A (retinol)
- Conversion has been shown to be impaired in 24–57% of people with associated genetic variations (Sestili & Fimognari, 2020).
- Decreased conversion of beta carotene to retinol may have clinical consequences, especially for vegans (Sestili & Fimognari, 2020).
- Vitamin A levels decrease during various infections due to decreased absorption and urinary losses ((Sestili & Fimognari, 2020; Iddir et al., 2020).
Signs of vitamin A deficiency (Office of Dietary Supplements – Vitamin A and Carotenoids, n.d.)
- dry eyes
- night blindness
Vitamin D
Key actions of vitamin D in regards to hypothyroidism:
- anti-inflammatory
- anti-autoimmune
Vitamin D and immunity
- Vitamin D is recognized as a natural modulator of the immune system. When its vitamin D receptors are activated, vitamin D controls calcium metabolism, cell growth, proliferation, apoptosis, and various immune functions. (Agmon-Levin et al., 2013)
- Vitamin D has a significant role in modulating Th1, Th2, and Th17 cells, and in regulating the secretion of cytokines such as IFN-γ, IL-4, and IL-17 [44–47]. (Wang et al., 2015)
- Thyroid autoimmunity, which involves elevated levels of thyroid autoantibodies such as anti-thyroid peroxidase) and anti-thyroglobulin), is linked to vitamin D deficiency (Mirhosseini et al., 2017)
Vitamin D and TSH regulation
- TSH levels are strongly linked to vitamin D levels. In winter, when vitamin D production is minimal and its levels are at their lowest, thyroid cells respond less to TSH, causing a decrease in thyroid hormones (T4) and an increase in serum TSH levels (Mirhosseini et al., 2017).
Vitamin D deficiency common
- In Canada, one out of ten people has a thyroid disorder, with half of these cases remaining undiagnosed. Additionally, one-third of Canadians are deficient in vitamin D (25(OH)D levels below 50 nmol/L), and fewer than 10% have vitamin D levels above 100 nmol/L. (Mirhosseini et al., 2017)
Vitamin D deficiency and hypothyroidism
- In a study by Mirhosseini et al., 2017 individuals with hypothyroidism were three times more likely, and those with subclinical hypothyroidism nearly twice as likely to have vitamin D deficiency compared to healthy individuals (Mirhosseini et al., 2017)
Vitamin D deficiency and autoimmune
- A deficiency in vitamin D has been linked to a higher risk of developing hypothyroidism and autoimmune thyroid diseases. (Mirhosseini et al., 2017)
- Low vitamin D levels have been linked to the presence of antithyroid antibodies and abnormal thyroid function tests (Agmon-Levin et al., 2013)
25(OH)D and hypothyroidism
- Mansournia and colleagues conducted a study with 41 hypothyroid patients and 45 healthy controls, finding an inverse relationship between 25(OH)D levels and the risk of hypothyroidism (Kmieć & Sworczak, 2015).
25(OH)D and thyroid autoimmunity
- 25-hydroxyvitamin D (25(OH)D), is the main circulating form of vitamin D in the blood and is considered the best indicator of vitamin D status in the body.
Low I25(OH)D and thyroid autoimmunity
- It has been shown that as 25(OH)D levels decrease thyroid peroxidase antibody prevalence increases (Kmieć & Sworczak, 2015)(Camurdan et al. 2012).
- Low serum 25(OH)D levels increase the likelihood of developing autoimmune thyroid disease . Vitamin D deficiency is commonly seen in thyroid disorders, and low serum 25-hydroxyvitamin D (25(OH)D) levels are linked to the development of both Hashimoto’s thyroiditis and Grave’s disease. (Mirhosseini et al., 2017)
- A recent meta-analysis of 20 case–control studies revealed that individuals with autoimmune thyroid disease had lower serum 25(OH)D levels compared to healthy controls. (Mirhosseini et al., 2017)
25(OH)D sufficiency and hypothyroidism
- Enhancing serum 25(OH)D levels also significantly influenced inflammation by reducing hs-CRP levels, which could explain why improving 25(OH)D status benefits thyroid function. (Mirhosseini et al., 2017)
- Maintaining proper thyroid function necessitates maintaining physiological levels of serum 25(OH)D, typically between 100–130 nmol/L. It is recommended that these levels be sustained over a significant duration, such as 2–3 years, to achieve the goal of preventing or treating chronic diseases. (Mirhosseini et al., 2017)
- • Keeping serum 25(OH)D levels above 125 nmol/L lowered the risk of elevated TSH and alleviated symptoms associated with low thyroid function, such as brain fog, weight gain, low mood, unrefreshing sleep, and low energy. (Mirhosseini et al., 2017)
- Of participants in a health and wellness program that provided vitamin D supplementation, who attained serum 25(OH)D levels above 100 nmol/L, only 8.8% remained at risk for autoimmune thyroid disease, one year later (Mirhosseini et al., 2017).
25(OH)D sufficiency decreases risk of thyroid autoimmunity
- A study by Mirhosseini et al., 2017, showed that:
- 25(OH)D levels greater than or equal to 125 nmol/L – significantly reduced risks for elevated levels of anti-thyroid peroxidase, anti-thyroglobulin antibodies, and inflammation (hs-CRP), as well as a 60% lower chance of low thyroid hormone levels (FT4) and a 14% lower chance of low FT3 levels
- 25(OH)D levels less than125 nmol/L were associated with 115% higher risk of elevated anti-TG antibodies, 118% higher risk of anti-thyroid peroxidase antibodies, and a 107% higher risk of elevated TSH.
Causes of vitamin D deficiency
- limited sun exposure
- strict vegan diet (most sources of vitamin D are animal-based)
- darker skin (the pigment melanin reduces the vitamin D production by the skin)
- digestive tract and kidney issues
- obesity (vitamin D is sequestered by fat cells)
Measuring vitamin D
The best indicator of vitamin D status is serum 25(OH)D, also known as 25-hydroxyvitamin D. 25(OH)D reflects the amount of vitamin D in the body that is produced by the skin and obtained from food and supplements.
Vitamin D levels and health status
Institute of Medicine, Food and Nutrition Board. (2010)
Serum (ng/ml) and Health status
<20 deficient
20–39 generally considered adequate
40–50 adequate
50–60 proposed optimum health level
200 potentially toxic
Iodine
Key actions of iodine in the context of hypothyroidism:
- component of thyroid hormones
- (T4, T3) anti-inflammatory
- anti-proliferative – protects against inappropriate thyroid growth and cancer (Boretti & Banik, 2022)
- anti-microbial (infections with certain bacteria or viruses can trigger or exacerbate autoimmune responses) (Bhattacharyya & Kumar, 2024)
Iodine deficiency is common
- Approximately one-third of the global population faces the risk of iodine deficiency (10 Signs and Symptoms of Iodine Deficiency, 2017).
- The amount of iodine in food is determined by the amount of iodine in the soil. Some regions of the world have iodine-deficient soils.
- A key source of iodine is through fortification of table salt. However, governments and institutions promote reduced salt intake for various health reasons.
- iodine needs are increased during pregnancy and lactation (10 Signs and Symptoms of Iodine Deficiency, 2017).
- Iodine deficiency or excess in children can lead to long-term thyroid problems even when stores are replenished (Chung, 2014).
Iodine deficiency and hypothyroidism
- Symptoms of iodine deficiency are the same as symptoms of hypothyroidism (See Introduction for symptoms)
Iodine deficiency and goitre
- Goitre is a medical condition characterized by the abnormal enlargement of the thyroid gland. Goitre is primarily caused by iodine deficiency.
- Iodine levels have been shown to be lower in nodular thyroid tissue (Bellisola et al., 1998).
- How goitre forms (Bellisola et al., 1998):
- With insufficient iodine, T4 levels drop, signalling the pituitary gland to release TSH.
- TSH tells the thyroid to make more T4, but with iodine deficiency it is unable create more T4.
- Thyroid cells then grow and multiply to better “trap” what little iodine is available in the blood supply.
Iodine excess and autoimmune thyroid
- Elevated iodine intake has been associated with hypothyroidism and autoimmune thyroid (both Hashimoto’s and Grave’s disease) (Chung, 2014).
- The autoimmune reaction is due to increased iodine in the context of low antioxidant capacity (Kalarani & Veerabathiran, 2022):
- Iodide is converted to iodine in the process of making T4.
- The process is facilitated by hydrogen peroxide – which, in excess causes oxidative stress, damaging thyroid cells.
- The immune system responds to the damage by attacking thyroid cells and enzymes (autoimmune reaction).
Iodine, selenium and autoimmune thyroid
- Increased iodine intake promotes increased hydrogen peroxide activity.
- Glutathione peroxidase protects against hydrogen peroxide-induced oxidative stress and resulting cellular damage.
- Selenium is a key component of glutathione peroxidase,
- Insufficient selenium in the context of increased iodine is a key driver of autoimmune thyroid activity (Kalarani & Veerabathiran, 2022; Vasiliu et al., 2020).
Iodine and existing autoimmune thyroid
- Elevated iodine in people with existing autoimmune antibodies increases risk of thyroid dysfunction (Chung, 2014).
- This outcome is to be expected:
- The presence of autoimmune antibodies indicates a state of low glutathione peroxidase – as glutathione peroxidase protects against the oxidative stress and cellular damage that causes thyroid autoimmune activity.
- If glutathione peroxidase is low, adding more iodine without supporting increased glutathione peroxidase would cause additional damage to thyroid cells.
- Supporting glutathione peroxidase production and addressing oxidative stress are strongly recommended if supplementing iodine in the context of autoimmune activity.
Iron
Causes of Iron Deficiencies
Chronic blood losses due to:
- prolonged or heavy menstrual bleeding (Munro et al., 2023) parasitic infestations
- frequent blood donation
- regular intense exercise (Iron, 2014)
Decreased iron absorption due to:
- Celiac disease
- gastritis
- Helicobacter pylori infection
- Inflammatory bowel diseases (IBD)
- gastric bypass surgery
Other causes of iron deficiency:
- vegetarian or vegan diet with inadequate sources of iron (Iron, 2014)
- chronic kidney disease (CKD)
- pregnancy (due to increased need)
- chronic inflammation
Deficiency of iron can be identified by (10 Signs and Symptoms of Iron Deficiency, 2020):
- unusual tiredness
- pale skin, inner eyelids, gums, or nails
- cracks at the corners of the mouth
- mouth ulcers
- swollen, pale or smooth tongue
- shortness of breath
- headaches
- dizziness, lightheadedness
- heart palpitations
- dry or damaged skin or hair
Iron deficiency and hypothyroidism
Iron deficiency can result in (Szklarz et al., 2022)
- decreased:
- TRH stimulation of TSH
- thyroperoxidase activity
- deodinase activity
- serum T4 and T3 (Eftekhari et al., 2006)
- binding of T3 to its nuclear receptor
- increased:
- reverse T3 (Szklarz et al., 2022)
Selenium
Key actions of selenium in the context of hypothyroidism:
Selenium is a component of the selenoproteins (selenium-containing proteins):
- thyroperoxidase (assembly of T4 molecule)
- deiodinase enzymes (conversion of T4 to T3, and degradation of reverse T3)
- glutathione peroxidase (protection against oxidative stress)
Selenium also:
- is a component of the antioxidant molecule thioredoxin (important for thyroid protection)
- recycles coenzyme Q10 (Srivastava et al., 2021)
- supports the antioxidant actions of coenzyme Q10 (Srivastava et al., 2021) and vitamin E (Keflie & Biesalski, 2021)
Selenium deficiency is common
- Inadequate intake of selenium is widespread in many parts of the world (Gröber & Holick, 2022), including in Western countries (Iddir et al., 2020).
- Issues with liver function can contribute to decreased production of selenoproteins (Erol et al., 2021).
- Selenium levels are known to be lower in people with obesity (Bermano et al., 2021).
Selenium deficiency and hypothyroidism
- Selenium deficiency is known to result in:
- decreased production of selenoproteins (Gröber & Holick, 2022)
- decreased activity of glutathione peroxidase (Berger et al., 2001)
- impaired conversion of T4 to T3 (Berger et al., 1996)
- Severe and long-term selenium deficiency disrupts thyroid hormone production resulting in destruction of thyroid follicles, which are then replaced by fibrous tissue (Mahmoodianfard et al., 2015).
Tyrosine
Tyrosine is a dietary amino acid that also functions as a neurotransmitter. The body can also make tyrosine from the amino acid phenylalanine.
Key actions of tyrosine in the context of hypothyroidism:
- Tyrosine is a precursor molecule required for the production of thyroid hormones.
- T4 is composed of tyrosine and four iodine molecules.
Causes of tyrosine deficiency:
- a low-protein diet
- poor protein digestion and absorption
- chronic stress – which increases tyrosine utilization for the formation of stress neurotransmitters (dopamine, norepinephrine, epinephrine)
Zinc
Key actions of zinc in the context of hypothyroidism:
- acts as a cofactor for deiodinase enzymes (convert T4 into T3) (Beserra et al., 2021)
- is required for the synthesis of thyrotropin-releasing hormone (TRH) and TSH (Beserra et al., 2021)
- has a role in the binding of T3 to the thyroid hormone receptor (Severo et al., 2019)
- is needed for thyroid transcription factor 2 – which turns on genes that make proteins involved in the production of T4 and T3 (Wróblewski et al., 2023)
- increases the activity of the thryoid-protective antioxidant molecules glutathione and catalase (Jarosz et al., 2017)
- modulates immune system function to prevent autoimmune activity and chronic inflammation (Wessels et al., 2017)
Causes of zinc deficiency:
- poor dietary intake
- inflammatory bowel disease
- gastrointestinal tract surgery
- celiac disease (due to decreased absorption)
- vegetarianism or veganism (due to high amounts of zinc-binding phytates in grains and legumes) (Zinc, 2014)
- pregnancy and lactation (due to increased needs)
Zinc deficiency and hypothyroidism
- Zinc deficiency can lower levels of TSH, T4, and T3 in the blood. People with hypothyroidism often have low zinc levels in their blood (Fröhlich & Wahl., 2019).
- Thyroid hormones are essential for the absorption of zinc, and hence hypothyroidism can result in acquired zinc deficiency (Betsy et al., 2013).
