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Levothyroxine (Synthroid) Supplement Interactions

Answer:

Levothyroxine (Synthroid, Levoxyl), liothyronine (Cytomel), and other thyroid hormone drugs for hypothyroidism (underactive thyroid), can be affected by taking supplements and can affect your ability to absorb certain vitamins and minerals. Care must be taken with regard to using these supplements, which include calcium, iron, and soy (including soy protein powders and soy isoflavones -- found in some menopause supplements) (which can affect absorption of thyroid hormone drugs), alpha-lipoic acid (which may lower levels of thyroid hormone T3 and increase levels of TSH) and L-carnitine and acetyl-l-carnitine (which can inhibit the activity of thyroid hormones -- and may help people with hyperthyroidism, or overactive thyroid).

Antacids containing aluminum hydroxide and magnesium hydroxide  (such as Maalox) should be taken at least four hours before or after taking levothyroxine, as they may delay or prevent the absorption of the drug (Synthroid Prescribing Information 2017).

There is some evidence that kelp supplements (such as tablets and capsules) can increase levels of TSH (thyroid-stimulating hormone).

Although often promoted for thyroid health, iodine supplements will not help your thyroid work better, and may even cause problems, unless you have an iodine deficiency.

Preliminary evidence suggests ashwagandha may increase thyroid hormone levels, and so should be used with caution in people taking thyroid hormones, or people with hyperthyroidism.

Be aware that high doses of biotin (as found in some B-complexes or supplements for hair and nails) may interfere with certain thyroid laboratory tests.

Resveratrol has been shown to increase TSH levels and cause thyroid enlargement in animals, although it's not known whether it effects thyroid function in people. 

Long term exposure to high or even moderate amounts of lithium can affect thyroid function.

Also, be aware that some thyroid-boosting supplements, including herbal supplements, have been found to contain thyroid hormones at significant levels, which are not listed and may be due to drug spiking. See the details in our Warnings section.

Certain foods and drinks may also interfere with absorption or bioavailability of levothyroxine. Soybean flour, cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of levothyroxine from the gastrointestinal tract; grapefruit juice may delay the absorption and reduce its bioavailability (Synthroid Prescribing Information 2017). There is also some evidence that coffee may bind to and reduce the absorption of levothyroxine; the evidence suggests it may be best to wait one hour after taking this medication before drinking coffee (Benvenga, Thyroid 2008; American Thyroid Association). [Note: It is not known which compound/s in coffee are responsible for this effect. Therefore, it is possible (but not proven) that decaffeinated coffee may also reduce absorption (Wegrzyn, J Acad Nutr Diet 2016).] Green tea may also interfere with thyroid hormones, so it may be best to consume green tea, as well as green tea supplements, at least one hour apart from thyroid medication.

Cruciferous vegetables such as broccoli, brussels sprouts and cabbage contain compounds that can interfere with thyroid function. However, these compounds are typically found in only very small amounts in these vegetables, and they appear to be deactivated upon cooking (McMillan, Hum Toxicol 1986; Felker, Nutr Rev 2016). See our Answer about supplements and thyroid function for details.

Many reviews have investigated a possible association between fluoride exposure and thyroid dysfunction (including risk of hypothyroidism). However, best available evidence suggests that fluoride intake from drinking water does not have an adverse effect on the thyroid gland or its function. There is no evidence that fluoride intake from other sources such as toothpaste (which is less than the amount from drinking water) affects thyroid function.

Although it is recommended that levothyroxine be taken on an empty stomach about 30 to 60 minutes before breakfast, and, as noted above, at least 60 minutes before drinking coffee, some people find it difficult to consistently take this medication in the morning. Interestingly, some studies have shown that taking levothyroxine in the evening (at least one hour after dinner) can be just as effective in controlling hypothyroidism as taking it in the morning (Pang, Clin Endocrinol (Oxf)2020; Mello, Front Med (Lausanne) 2022), although people who wish to try this should still consult with their physician before making this change.

Certain drugs, such as levothyroxine, may prevent the metabolism, and thus increase blood levels, of cannabidiol (CBD). Levothyroxine can inhibit cytochrome p450 enzyme CYP3A4, which metabolizes CBD in the body. A small study found that children taking CBD who were also taking levothyroxine had higher blood levels of CBD compared to those taking the same dose of CBD but without levothyroxine. Other experts have cautioned that, theoretically, co-administration of CBD and levothyroxine may increase blood levels and, consequently, the effects of levothyroxine, leading to symptoms of hyperthyroidism, although this interaction has not been reported in humans.

About generic versions of levothyroxine:
The reason why it's particularly important to consider possible supplement interactions when taking thyroid medication is that it has a "narrow therapeutic index." This means that drug levels must be maintained within a relatively narrow range to be effective and not cause side effects. For this same reason, switching from a branded thyroid medication to a generic, or from one generic to another, can be problematic if the two drugs are not closely bioequivalent or are formulated differently -- causing one to release its active ingredient at a different rate than the other under certain circumstances, such as when taken with food or without food.

Due to historic concerns with generic versions of thyroid medication, the FDA tightened the bioequivalency requirements on generics in 2007. Nevertheless, many physicians have continued to prescribe the branded versions. In a study funded by the FDA to validate the equivalency of generic drugs, researchers reviewed the medical records of thousands of people newly started on generic (Mylan, Sandoz, or Lannett) or branded (primarily Synthroid or Levoxyl) levothyroxine for mild hypothyroidism between 2008 and 2017. They found similar attainment of normal thyroid status regardless of whether generic or brand-name medicine had been administered (Britto, JAMA Network Open 2020). While this is encouraging, it should be noted that the study did not evaluate the effects of switching from branded to generic (or generic to branded) products, nor did it include patients with moderate or severe hypothyroidism. In addition, there have been recalls of generic thyroid medication found to be subpotent or superpotent.

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