Adding L-Carnitine and Selenium to Methimazole in Graves' Disease: A Prospective Randomized Trial on Thyroid Markers and Quality of Life.

2025-08-20
Nutrients 17(16)
- Mattia Rossi
- Letizia Meomartino
- Marco Zavattaro
- Gloria Selvatico
- Ruth Rossetto Giaccherino
- Loredana Pagano

PubMed: 40871722
DOI: 10.3390/nu17162693

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 60
Population: 60 consecutive patients with newly diagnosed overt Graves' Disease
Methods: Multicenter prospective randomized trial; participants received either standard treatment with MMI alone or MMI plus combined LCT/Se supplement
Duration: up to 24 months
Funding: Unclear

Rigorous Journal

Background: The therapeutic response in Graves' Disease (GD) remains largely unpredictable. Patients often experience persistent symptoms that are poorly correlated with thyroid hormone levels, an undefined treatment duration, and the need for long-term or definitive therapies. Based on the nuclear antagonistic properties of L-carnitine (LCT) on thyroid hormone action and the immunomodulatory role of selenium (Se), we aimed to assess the impact of adding a combined LCT and Se supplement to standard methimazole (MMI) therapy on the biochemical profile and quality of life (QoL) of patients with overt GD. Methods: This multicenter prospective randomized trial enrolled 60 consecutive patients with newly diagnosed overt GD. Participants were randomized to receive either standard treatment with MMI alone (Control Group) or MMI plus the combined LCT/Se supplement (Intervention Group). TSH, fT3, fT4, and TSH-receptor antibodies (TRAb) levels were evaluated every two months for up to 24 months or until spontaneous remission or definitive therapy. At each visit, patients completed a symptom questionnaire addressing the frequency of typical thyrotoxic symptoms. Results: No significant differences were observed between groups in the trend or time-to-normalization of TSH, fT3, and fT4 levels. However, the Intervention Group reached TRAb negativity significantly earlier (HR = 2.35 (1.14-4.81), p = 0.016), with a synergistic interaction with MMI therapy. MMI requirements were consistently lower in the Intervention Group, both in average dosage (p = 0.013) and cumulative dose (p = 0.020). The rate of spontaneous remission was significantly higher (OR = 11.22 (3.35-46.11), p < 0.001). Overall symptom burden did not differ significantly between groups; however, the supplement exerted an independent effect in reducing the severity of tremor, irritability, mood lability, heat intolerance, and exertional dyspnea. Conclusions: Our findings suggest the clinical benefits of adding combined LCT and Se supplementation to MMI in the treatment of overt GD, including shorter disease duration, lower cumulative MMI exposure and earlier TRAb normality, that could positively influence TRAb-related prognostic outcomes.

Research Insights

L-Carnitine→Increased Spontaneous Remission Rate
The rate of spontaneous remission was significantly higher (OR = 11.22 (3.35-46.11), p < 0.001)
Effect
Beneficial
Effect size
Large
Dose
not stated
L-Carnitine→Reduced Exertional Dyspnea
the supplement exerted an independent effect in reducing the severity of exertional dyspnea
Effect
Beneficial
Effect size
Small
Dose
not stated
L-Carnitine→Reduced Heat Intolerance
the supplement exerted an independent effect in reducing the severity of heat intolerance
Effect
Beneficial
Effect size
Small
Dose
not stated
L-Carnitine→Reduced Irritability
the supplement exerted an independent effect in reducing the severity of irritability
Effect
Beneficial
Effect size
Small
Dose
not stated
L-Carnitine→Reduced Medication Requirement
MMI requirements were consistently lower in the Intervention Group, both in average dosage (p = 0.013) and cumulative dose (p = 0.020)
Effect
Beneficial
Effect size
Moderate
Dose
not stated
L-Carnitine→Reduced Mood Lability
the supplement exerted an independent effect in reducing the severity of mood lability
Effect
Beneficial
Effect size
Small
Dose
not stated
L-Carnitine→Reduced TRAb Level
the Intervention Group reached TRAb negativity significantly earlier (HR = 2.35 (1.14-4.81), p = 0.016)
Effect
Beneficial
Effect size
Moderate
Dose
not stated
L-Carnitine→Reduced Tremor
the supplement exerted an independent effect in reducing the severity of tremor
Effect
Beneficial
Effect size
Small
Dose
not stated
Selenium→Increased Spontaneous Remission Rate
The rate of spontaneous remission was significantly higher (OR = 11.22 (3.35-46.11), p < 0.001)
Effect
Beneficial
Effect size
Large
Dose
not stated
Selenium→Reduced Exertional Dyspnea
the supplement exerted an independent effect in reducing the severity of exertional dyspnea
Effect
Beneficial
Effect size
Small
Dose
not stated
Selenium→Reduced Heat Intolerance
the supplement exerted an independent effect in reducing the severity of heat intolerance
Effect
Beneficial
Effect size
Small
Dose
not stated
Selenium→Reduced Irritability
the supplement exerted an independent effect in reducing the severity of irritability
Effect
Beneficial
Effect size
Small
Dose
not stated
Selenium→Reduced Medication Requirement
MMI requirements were consistently lower in the Intervention Group, both in average dosage (p = 0.013) and cumulative dose (p = 0.020)
Effect
Beneficial
Effect size
Moderate
Dose
not stated
Selenium→Reduced Mood Lability
the supplement exerted an independent effect in reducing the severity of mood lability
Effect
Beneficial
Effect size
Small
Dose
not stated
Selenium→Reduced TRAb Level
the Intervention Group reached TRAb negativity significantly earlier (HR = 2.35 (1.14-4.81), p = 0.016)
Effect
Beneficial
Effect size
Moderate
Dose
not stated
Selenium→Reduced Tremor
the supplement exerted an independent effect in reducing the severity of tremor
Effect
Beneficial
Effect size
Small
Dose
not stated