Effect of Vitamin C Supplementation in Patients With Primary Hypothyroidism

NCT05733078 | Unknown Phase 2

• 1 other identifier: UAEU_CMHS_IM_DOH_2023/56
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Thyroid disease affects almost a quarter of a billion individuals worldwide and more than 50% of them being not aware of this condition. The commonest thyroid disease is iodine deficiency related thyroid dysfunction with nearly 2 billion people around the globe at risk with insufficient iodine intake. Autoimmune thyroid disorders are commonest cause of thyroid dysfunction in iodine sufficient parts of the world. Sub-optimally or untreated hypothyroidism can lead to cognitive decline, dyslipidemia, hypertension, infertility as well as cardiovascular and neuromuscular problems. The prevalence of hypothyroidism can vary in general population with up-to 5.3% people with overt hypothyroidism based on studies from the West, with estimated 10% of the population having subclinical hypothyroidism globally. In the gulf region however, there are no national studies that provide insight into exact prevalence of hypothyroidism, however some cross-sectional screening studies indicate frequency of hypothyroidism to be as high as 5-10%. Levothyroxine is a synthetic hormone with structure similar to naturally occurring thyroxine, and it is used as replacement monotherapy of hypothyroidism. It is mainly absorbed via small intestine. The optimal daily levothyroxine dosage requirement is 1.6 microgram/kg body weight/day, which can normalize TSH in most patients, however many studies indicate that nearly half the patient on replacement therapy may not attain a normal TSH and require further doses, possibly due to interference or malabsorption. Multiple dose change and repeated diagnostic procedures in these patients can not only increased health costs but increased of ensuing complications secondary to sub-optimally controlled hypothyroidism. Instead of increasing levothyroxine doses and getting variable response, recent study have shown improvement in thyroid function by adding on vitamin C alongside levothyroxine dose, albeit only in a specific subset of patient having gastritis. The effect of Vitamin C on improving levothyroxine also been shown to be effective over a short period in a non-randomized, non-controlled setting. Our study aims to investigate whether addition of vitamin C to levothyroxine can improve the biochemical and clinical thyroid status in a randomized controlled setting.

Conditions

Hypothyroidism; Primary Hypothyroidism; Vitamin C Deficiency

Outcome Measures

Primary Outcomes (3)

• Change in Thyroid function (TSH)

  The primary outcome will be assessing the change in TSH levels in mIU/ml before and after supplementation the same levothyroxine dose with and without intervention (1 gram of effervescent vitamin C).

  24 weeks

• Change in Thyroid function (T4)

  The primary outcome will be assessing the change in T4 levels in pmol/L before and after supplementation the same levothyroxine dose with and without intervention (1 gram of effervescent vitamin C).

  24 weeks

• Change in Thyroid function (T3)

  The primary outcome will be assessing the change in T3 levels in pmol/L before and after supplementation the same levothyroxine dose with and without intervention (1 gram of effervescent vitamin C).

  24 weeks

Secondary Outcomes (1)

• Change in clinical status

  24 weeks

Study Arms (2)

Control / Crossover

PLACEBO COMPARATOR

The patients in control group will have a oral rehydration effervescent tablet to take with their usual dose of Levothyroxine for 12 weeks, with thyroid function tests assessed at 6 and 12 weeks. Crossover: After first 12 weeks, the control group will then be provided vitamin C (intervention) effervescent tablets to use 1 gram daily with their usual dose of Levothyroxine for 12 weeks, with thyroid function tests assessed at 6 and 12 weeks to see if there is any difference on biochemical testing or clinical scores.

Drug: Oral Rehydration Salt Formulations

Intervention

EXPERIMENTAL

The patient in test group will be provided vitamin C effervescent tablets to use 1 gram daily with their usual dose of Levothyroxine for 12 weeks, with thyroid function tests assessed at 6 and 12 weeks. The patients who wish to continue at the end of 12 weeks will be provided another 12 weeks supply of vitamin C effervescent tablets to use 1 gram daily with their usual dose of Levothyroxine for with thyroid function tests and clinical score assessed at the end of week 24.

Drug: Vitamin C

Interventions

Vitamin C DRUG

The patient in test group will be provided vitamin C effervescent tablets to use 1 gram daily with their usual dose of Levothyroxine for 12 weeks, with thyroid function tests assessed at 6 and 12 weeks. The patients who wish to continue at the end of 12 weeks will be provided another 12 weeks supply of vitamin C effervescent tablets to use 1 gram daily with their usual dose of Levothyroxine for with thyroid function tests and clinical score assessed at the end of week 24.

Intervention

Oral Rehydration Salt Formulations DRUG

The patients in control group will have a oral rehydration effervescent tablet to take with their usual dose of Levothyroxine for 12 weeks, with thyroid function tests assessed at 6 and 12 weeks. The control group will then be provided vitamin C (intervention) effervescent tablets to use 1 gram daily with their usual dose of Levothyroxine for 12 weeks, with thyroid function tests assessed at 6 and 12 weeks to see if there is any difference on biochemical testing or clinical scores.

Also known as: Vitamin C

Control / Crossover

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18; both male or female
• Diagnosed to have Primary hypothyroidism \> 6 months.
• Under follow up in Endocrine clinic in Tawam hospital during the 6 months
• No evidence of secondary hypothyroidism (no pituitary problems/surgery or thyroid surgery/ablation)
• TSH \> 4 despite being on \> 1.6 ug/kg/day of Levothyroxine for more than 8 weeks

You may not qualify if:

• Presence of coeliac disease
• Presence of selenium or iodine deficiency
• Gastric/intestinal resection surgery or confirmed malabsorption syndromes
• Known mental health issues affecting compliance
• Patient unable to consent.
• Overt biochemical hypothyroidism with TSH \> 20 or T4 \< 6

Sponsors & Collaborators

• Dr Adnan Agha: lead

Study Sites (1)

Internal Medicine, College of Medicine and Health Sciences

Al Ain City, Abu Dhabi Emirate, 15551, United Arab Emirates

RECRUITING

Related Publications (4)

• de Benoist B, McLean E, Andersson M, Rogers L. Iodine deficiency in 2007: global progress since 2003. Food Nutr Bull. 2008 Sep;29(3):195-202. doi: 10.1177/156482650802900305.

  PMID: 18947032 BACKGROUND

• Jubiz W, Ramirez M. Effect of vitamin C on the absorption of levothyroxine in patients with hypothyroidism and gastritis. J Clin Endocrinol Metab. 2014 Jun;99(6):E1031-4. doi: 10.1210/jc.2013-4360. Epub 2014 Mar 6.

  PMID: 24601693 BACKGROUND

• Virili C, Antonelli A, Santaguida MG, Benvenga S, Centanni M. Gastrointestinal Malabsorption of Thyroxine. Endocr Rev. 2019 Feb 1;40(1):118-136. doi: 10.1210/er.2018-00168.

  PMID: 30476027 BACKGROUND

• Agha A, Afandi B, Yasin J, Sharma C, Alshaer MH, Alshamsi MAS, Yaaqeib DE, Alblooshi BKE, AlKaabi J. Vitamin C supplementation in patients with hypothyroidism requiring high-dose levothyroxine: a proof-of-concept pilot study. Front Endocrinol (Lausanne). 2025 Oct 23;16:1679835. doi: 10.3389/fendo.2025.1679835. eCollection 2025.

  PMID: 41210509 DERIVED

MeSH Terms

Conditions

Hypothyroidism; Ascorbic Acid Deficiency

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Adnan Agha

  United Arab Emirates University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adnan Agha, FRCP

CONTACT

+971562790723; adnanagha@uaeu.ac.ae

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University

Model Details: Randomization of patients: The patient will be randomized into control(placebo) and test (Vit C tablet) groups using the randomization code. The patients in treatment group will be provided vitamin C effervescent tablets to use 1 gram daily with their usual dose of Levothyroxine for 12 weeks. In the control group the patients will be given oral rehydration effervescent tablet as placebo with their usual dose of Levothyroxine for 12 weeks. The patient in test group will be provided vitamin C effervescent tablets to use 1 gram daily with their usual dose of Levothyroxine for 12 weeks, with thyroid function tests assessed at 6 and 12 weeks. The patients who wish to continue at the end of 12 weeks will be provided another 12 weeks supply of vitamin C effervescent tablets to use 1 gram daily with their usual dose of Levothyroxine for with thyroid function tests and clinical score assessed at the end of week 24.

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 17, 2023
• Study Start: November 1, 2023
• Primary Completion: March 1, 2024
• Study Completion: June 1, 2024
• Last Updated: January 11, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

AE (1)