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Researchers from the University of Turin published the results of a prospective, randomized, and controlled trial evaluating the use of L-carnitine and selenium when combined with standard therapy for Graves’ disease, an autoimmune disorder that affects the thyroid gland. This study follows a previously published pilot study, which found that 500 mg of L-carnitine in combination with 83 mcg selenium (as selenomethionine) taken daily for one month could improve quality of life and symptoms associated with subclinical hyperthyroidism, defined as positive antibodies and a TSH between 0.1-0.4 mIU/L, without modifying thyroid hormone or antibody levels. This earlier study was uncontrolled, however, but justified the subsequent controlled trial.
The same dose of L-carnitine and selenium was used in the intervention group of this trial, while participants in both the intervention and control groups also received standard therapy (methimazole and beta blockers). Participants were eligible if they had received their first diagnosis of overt Graves’ disease, with several exclusion criteria, such as pregnancy and Graves orbitopathy at enrollment. The trial included 60 adult participants (mean age approximately 49) who had clinical follow-up with labs every 2 months for up to 2 years, with some withdrawing early due to spontaneous remission, indication for definitive therapy (e.g., thyroidectomy or radioiodine), or an intolerance to the treatment. There were some limitations to the study, such as a lack of blinding and the use of a non-validated symptom questionnaire
During the study, people receiving L-carnitine and selenium were significantly more likely to experience a spontaneous remission (63% vs. 13%) even after multivariate adjustment, though remission was not a primary outcome of the study. As was observed in the pilot study, this trial also found no significant differences in the indices of thyroid function (e.g., TSH, fT3, fT4). And while no significant difference was observed in TSH–receptor antibodies (TRAb) over time, the intervention group reached TRAb negativity (TRAb < 3.5 UI/L) significantly earlier (HR 2.35), with a synergistic interaction with methimazole reported. Specifically, a lower average and a lower cumulative dose of methimazole were used in the intervention group. No difference in the need for definitive therapy was observed. Lastly, while no significant difference was observed in the overall symptom score between groups, specific hyperthyroid symptoms were significantly lower in the intervention group, including irritability, tremor, mood lability, heat intolerance, and exertional dyspnea.
The lack of a difference in thyroid indices is consistent with previous findings, which suggest that L-carnitine has a peripheral action, rather than directly inhibiting the thyroid gland or influencing hypothalamic–pituitary feedback. Though most of the relevant studies were conducted in the 1960s, in vitro data do suggest that L-carnitine inhibits thyroid hormone uptake into the cell and nucleus. Interestingly, L-carnitine urinary excretion has been reported to be increased among people with hyperthyroidism (but mitigated by anti-thyroid medication), and decreased among people with hypothyroidism. Supplementation has also been reported to improve symptoms of fatigue among people with hypothyroidism already being treated with levothyroxine. Case reports point to a benefit for its use in thyroid storm when combined with methimazole, and an early trial found that a dose of at least 2 g per day could reverse and prevent symptoms of intentionally induced hyperthyroidism among women given a fixed TSH-suppressive dose.
Results with selenium have been more mixed; for example, in a small study that enrolled newly diagnosed participants with Graves’ disease, no difference in any study parameters was observed between those receiving selenium (160 mcg/day) and methimazole vs. only methimazole. Yet (as reviewed here), selenoproteins are involved in the metabolism of thyroid hormones and can also scavenge reactive oxygen species (ROS), protecting against oxidative damage and inflammation. Graves’ disease is characterized by an excess of ROS, with a 2023 review finding that 9 of 11 clinical trials observed a shorter time to normal thyroid function when supplementing with selenium. The largest of these (still fairly small, n=159) was a randomized and controlled clinical trial published in the New England Journal of Medicine, and found that a dose of 100 mcg twice per day improved quality of life, reduced eye involvement, and slowed disease progression among participants with mild Graves' orbitopathy (compared to pentoxifylline or placebo). Another randomized and controlled clinical trial found benefit when combined with vitamin D (with all participants receiving methimazole) among people with Graves’ disease with insufficient/marginal status of these two nutrients. Lastly, a systematic review and meta-analysis published in Thyroid in 2016 found that selenium significantly reduced thyroid autoantibodies in people with chronic autoimmune thyroiditis.
The authors of the 2025 study from the University of Turin suggest that the combination of L-carnitine and selenium may have a synergistic effect, and that L-carnitine may also have an immunomodulatory role, and its actions are not limited to peripheral thyroid hormone antagonism. They also point out that the symptoms that improved in the intervention group were the ones independent of the conventional medications. Hopefully, larger studies with longer duration are able to flesh out the benefits of these nutrients in more detail.
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