Nutraceuticals in Thyroidology: A Review of in Vitro, and in Vivo Animal Studies

Benvenga, Salvatore; Ferrari, Silvia; Elia, Giusy; Ragusa, Francesca; Patrizio, Armando; Paparo, Sabrina Rosaria; Camastra, Stefania; Bonofiglio, Daniela; Antonelli, Alessandro; Fallahi, Poupak

doi:10.3390/nu12051337

Cited by 22 publications

(17 citation statements)

References 98 publications

(144 reference statements)

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“…The frequency of hypothyroidism is higher in women, especially over 60 years, and it can be diagnosed measuring serum TSH and free T4 values ( 2 ). Hypothyroidism can be caused by different conditions ( 6 – 9 ): 1) A low iodine intake in countries with severe iodine deficiency; 2) autoimmune thyroiditis that is the most common cause in iodine sufficient countries; 3) thyroidectomy; 4) radioiodine treatment for hyperthyroidism. Drugs, such as tyrosine kinase inhibitors, and immune checkpoint inhibitors, are a novel cause of primary hypothyroidism ( 10 , 11 ).…”

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confidence: 99%

The Stability of TSH, and Thyroid Hormones, in Patients Treated With Tablet, or Liquid Levo-Thyroxine

et al. 2021

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Approximately, 5% of the population is affected by hypothyroidism, mainly women and persons aged more than 60 years. After the diagnosis of hypothyroidism the usual therapy is tablet levothyroxine (L-T4), with a monitoring of the thyroid-stimulating hormone (TSH) level in primary hypothyroidism every 6–8 weeks and L-T4 is adjusted as necessary to reach an euthyroid state. Once TSH is stabilized in the normal range, it is recommended to conduct annual testing in the treated subjects to warrant suitable replacement. More recently advances regarding L-T4 treatment are the introduction of new oral formulations: the liquid solution, and soft gel capsule. The soft gel capsule permits a quick dissolution in the acid gastric pH. The liquid preparation does not require an acid gastric environment. Many pharmacokinetic studies demonstrated a more rapid absorption for the liquid L-T4, or capsule, than with tablet. Many studies have shown that the liquid, or capsule, formulations can overcome the interaction with foods, drugs or malabsorptive conditions, that are able to impair the tablet L-T4 absorption. Lately studies have suggested that liquid L-T4 can permit to maintain more efficiently normal TSH levels in hypothyroid patients in the long-term follow-up, than tablet L-T4, both in patients with malabsorptive states, and in those without malabsorption. Further large, prospective, longitudinal studies are needed to evaluate the stability of TSH, in hypothyroid patients treated with different L-T4 formulations.

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Section: Introductionmentioning

confidence: 99%

The Stability of TSH, and Thyroid Hormones, in Patients Treated With Tablet, or Liquid Levo-Thyroxine

et al. 2021

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“…The frequency of hypothyroidism is higher in women, especially over 60 years, and its diagnosis can be done by measuring thyroid-stimulating hormone (TSH) and T4 levels by blood tests ( 1 ). Hypothyroidism is commonly caused by a low iodine intake in countries with severe iodine deficiency, and autoimmune thyroiditis, or treatment with radioiodine, or thyroidectomy, in developed countries ( 5 – 8 ). Drugs, such as tyrosine kinase inhibitors, are a novel cause of primary hypothyroidism ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

L-T4 Therapy in Enteric Malabsorptive Disorders

et al. 2021

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Levothyroxine (L-T4) absorption can be impaired by various causes: a) L-T4 ingestion during breakfast, or with food; b) conditions of reduced gastric acidity; c) intestinal procedures and diseases such as bariatric surgery, lactose intolerance (LI), celiac disease (CD), inflammatory bowel disease; d) drugs that alter L-T4 absorption, increasing the gastric pH, or preventing the dissolution of tablets. The development of new oral formulations, i.e. the liquid preparation and the soft gel capsule, represents the most recent advance regarding L-T4 therapy. Treating hypothyroidism with L-T4 tablets can lead to an improper control of thyroid-stimulating hormone (TSH) in ~10%–15% of patients. The improperly elevated TSH is usually managed by increasing the L-T4 daily dose, and revaluating TSH upon 2-6 months. The increase of the L-T4 dosage may cause iatrogenic hyperthyroidism, especially when the underlying disorders are cured. Liquid L-T4 can be administered in patients unable to swallow capsules or tablets, and this is one of its major benefits. Liquid L-T4 can: 1- overcome food and beverages interference; 2- bypass the malabsorption associated with an increased gastric pH; 3- circumvent the issue of malabsorption in patients who underwent bariatric surgery; 4-maintain TSH values under control better than L-T4 tablets in hypothyroid patients with typical or atypical CD, or in patients with LI. Few clinical studies evaluated soft gel L-T4 with encouraging findings in patients with gastric- or coffee-related malabsorption, or hypothyroid patients without malabsorption. Additional research is necessary to investigate liquid L-T4, or soft gel capsule, in other conditions of altered L-T4 absorption.

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“…On the basis of this background, and taking into account that: (i) C cells interact with follicular cells by being hyperplastic when TSH is high ( 30 ); (ii) no objective morphometric analysis has been conducted in previous studies on Cd-induced C cells damage ( 3 , 26 , 28 , 29 ); (iii) no data are available regarding the effects of MI alone, Se alone and the association of MI with Se on the Cd-induced C cells damage; and (iv) many naturally occurring nutraceuticals, including MI and Se, are being increasingly used in the clinical pratice ( 31 ), we intended to demonstrate the protecting role of Se and MI on the murine C cells of thyroid gland exposed to Cd. Their protective effects were compared with those by resveratrol, another naturally anti-oxidant with beneficial effects ( 31 – 33 ) that had not been tested in our previous study on Cd-induced toxicity in testis ( 34 ) and kidney ( 35 ).…”

Section: Introductionmentioning

confidence: 99%

The Association of Myo-Inositol and Selenium Contrasts Cadmium-Induced Thyroid C Cell Hyperplasia and Hypertrophy in Mice

et al. 2021

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Previous studies have demonstrated that, in addition to inducing structural changes in thyroid follicles, cadmium (Cd) increased the number of C cells. We examined the effects of myo-inositol (MI), seleno-L-methionine (Se), MI + Se, and resveratrol on C cells of mice exposed to cadmium chloride (Cd Cl2), as no data are currently available on the possible protective effects of these molecules. In contrast, we have previously shown this protective effect against CdCl2 on the thyroid follicles of mice. Ninety-eight C57 BL/6J adult male mice were divided into 14 groups of seven mice each: (i) 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); (ii) Se (0.2 mg/kg/day per os); (iii) Se (0.4 mg/kg/day per os); (iv) MI (360 mg/kg/day per os); (v) Se (0.2 mg/kg/day) + MI; (vi) Se (0.4 mg/kg/day) + MI; (vii) resveratrol (20 mg/kg); (viii) CdCl2 (2 mg/kg/day i.p.) + vehicle; (ix) CdCl2 + Se (0.2 mg/kg/day); (x) CdCl2 + Se (0.4 mg/kg/day); (xi) CdCl2 + MI; (xii) CdCl2 + Se (0.2 mg/kg/day) + MI; (xiii) CdCl2 + Se (0.4 mg/kg/day) + MI; (xiv) CdCl2 + resveratrol (20 mg/kg). After 14 days, thyroids were processed for histological, immunohistochemical, and morphometric evaluation. Compared to vehicle, Cd significantly decreased follicle mean diameter, increased CT-positive cells number, area and cytoplasmic density, and caused the disappearance of TUNEL-positive C cells, namely, the disappearance of C cells undergoing apoptosis. Se at either 0.2 or 0.4 mg/kg/day failed to significantly increase follicular mean diameter, mildly decreased CT-positive cells number, area and cytoplasmic density, and was ineffective on TUNEL-positive C cells. Instead, MI alone increased significantly follicular mean diameter and TUNEL-positive cells number, and decreased significantly CT-positive cells number, area and cytoplasmic density. MI + Se 0.2 mg/kg/day or MI + Se 0.4 mg/kg/day administration improved all five indices more markedly. Indeed, follicular mean diameter and TUNEL-positive cells number increased significantly, while CT-positive cells number, area and cytoplasmic density decreased significantly. Thus, all five indices overlapped those observed in vehicle-treated mice. Resveratrol improved significantly all the considered parameters, with a magnitude comparable to that of MI alone. In conclusion, the association Myo + Se is effective in protecting the mouse thyroid from the Cd-induced hyperplasia and hypertrophy of C cells. This benefit adds to that exerted by Myo + Se on thyrocytes and testis.

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Nutraceuticals in Thyroidology: A Review of in Vitro, and in Vivo Animal Studies

Cited by 22 publications

References 98 publications

The Stability of TSH, and Thyroid Hormones, in Patients Treated With Tablet, or Liquid Levo-Thyroxine

The Stability of TSH, and Thyroid Hormones, in Patients Treated With Tablet, or Liquid Levo-Thyroxine

L-T4 Therapy in Enteric Malabsorptive Disorders

The Association of Myo-Inositol and Selenium Contrasts Cadmium-Induced Thyroid C Cell Hyperplasia and Hypertrophy in Mice

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