Thiamine + Vitamin C

Usage

Thiamine + Vitamin C is prescribed for the prevention and treatment of thiamine deficiency, particularly in cases of Wernicke-Korsakoff syndrome (WKS), often associated with alcohol use disorder. It is also used in patients receiving parenteral nutrition, especially those on warfarin therapy to prevent vitamin deficiencies. Although it has been studied in sepsis and septic shock, evidence does not currently support its use for improving outcomes in these conditions. Thiamine is crucial for carbohydrate metabolism and nerve function, while vitamin C is an essential antioxidant and cofactor for various enzymes.

This combination doesn’t fall neatly into a single pharmacological classification. Thiamine is classified as a vitamin and a nutritional supplement, while vitamin C is considered a vitamin, antioxidant, and in some cases, an immunomodulator.

The mechanism of action involves distinct roles for each component. Thiamine, as thiamine pyrophosphate (TPP), is a coenzyme for crucial enzymes in carbohydrate metabolism, including transketolase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase. Vitamin C acts as an antioxidant, scavenging free radicals, and is a cofactor for enzymes involved in collagen synthesis, carnitine synthesis, and tyrosine metabolism.

Alternate Names

• Thiamine: Vitamin B1, Aneurine hydrochloride
• Vitamin C: Ascorbic acid
• The combination itself does not have a specific international nonproprietary name (INN).

Brand names vary depending on the manufacturer and formulation. Examples of brand names containing thiamine include: Thiamilate and Betaxin. Brand names containing vitamin C include: Redoxon and Cebion.

How It Works

Pharmacodynamics: Thiamine is essential for carbohydrate metabolism, particularly in the brain and nervous system. Vitamin C is an antioxidant that protects cells from damage caused by free radicals. It also plays a role in immune function and collagen synthesis.

Pharmacokinetics:

• Absorption: Thiamine is absorbed in the small intestine. Vitamin C is absorbed in the small intestine, with absorption efficiency decreasing at higher doses.
• Metabolism: Thiamine is converted to its active form, TPP, within cells. Vitamin C is metabolized in the liver.
• Elimination: Thiamine is primarily excreted in the urine. Vitamin C and its metabolites are mainly excreted renally.

Mode of Action: Thiamine, as TPP, acts as a coenzyme for several enzymes in carbohydrate metabolism. Vitamin C acts as an electron donor and participates in various enzymatic reactions.

Receptor binding, enzyme inhibition, or neurotransmitter modulation: Thiamine does not directly bind to receptors, inhibit enzymes, or modulate neurotransmitters in a classical sense. Its primary function is as a coenzyme. Vitamin C functions as a cofactor for various enzymes and contributes to the reduction of certain metal ions.

Elimination pathways: Both thiamine and vitamin C are primarily eliminated through renal excretion.

Dosage

Standard Dosage

Adults:

• Thiamine Deficiency: 5-30 mg/day orally, divided into doses. For severe deficiency (e.g., Wernicke-Korsakoff syndrome), up to 300 mg/day IV or IM may be necessary.
• Vitamin C: RDA is 90 mg/day for men and 75 mg/day for women.

Children: Dosage varies depending on age and specific requirements. Pediatric dosing guidelines should be consulted for specific recommendations.

Special Cases:

• Elderly Patients: No specific dose adjustments are generally required unless there is renal impairment.
• Patients with Renal Impairment: Thiamine dose may need to be adjusted in severe renal impairment.
• Patients with Hepatic Dysfunction: No specific dose adjustments are usually necessary.
• Patients with Comorbid Conditions: Consider individual patient needs and comorbidities.

Clinical Use Cases

While studies have investigated the use of thiamine and vitamin C in sepsis, ICU settings, and other acute conditions, there is no strong evidence to support routine use in these situations outside of addressing specific deficiencies. These are often given concurrently with hydrocortisone in certain protocols although evidence of efficacy in clinical trials is not robust.

Dosage Adjustments

Dosage adjustments may be needed based on individual patient characteristics, including renal function, presence of other medical conditions, and concomitant medications.

Side Effects

Common Side Effects

• Thiamine: Generally well-tolerated. Rare instances of allergic reactions (e.g., rash, itching, swelling) have been reported with IV administration.
• Vitamin C: High doses may cause gastrointestinal discomfort (e.g., nausea, diarrhea, abdominal cramps).

Rare but Serious Side Effects

• Thiamine: Anaphylaxis (rare).
• Vitamin C: Kidney stones (with high doses), G6PD deficiency-induced hemolysis.

Long-Term Effects

No significant long-term adverse effects are typically associated with appropriate doses of either thiamine or vitamin C.

Adverse Drug Reactions (ADR)

Anaphylaxis (rare) with thiamine. Hemolysis in individuals with G6PD deficiency with high-dose vitamin C.

Contraindications

• Thiamine: Hypersensitivity to thiamine.
• Vitamin C: History of kidney stones (high doses should be avoided), G6PD deficiency (high doses should be avoided).

Drug Interactions

• Thiamine: May interfere with the bioavailability of levodopa. Antagonists are present in tea, coffee, raw fish, and red cabbage.
• Vitamin C: Can interact with warfarin, deferoxamine, fluphenazine, chemotherapeutic agents, estrogens. May interfere with certain laboratory tests (e.g., urine glucose, occult blood).

Pregnancy and Breastfeeding

• Thiamine: Generally considered safe during pregnancy and breastfeeding at recommended doses.
• Vitamin C: Generally considered safe during pregnancy and breastfeeding at recommended doses.

Drug Profile Summary

• Mechanism of Action: Thiamine: Coenzyme for carbohydrate metabolism. Vitamin C: Antioxidant, enzyme cofactor.
• Side Effects: Generally well-tolerated at recommended doses. High doses of vitamin C may cause GI upset and, rarely, kidney stones or hemolysis in susceptible individuals.
• Contraindications: Thiamine: Hypersensitivity. Vitamin C: G6PD deficiency (high doses), history of kidney stones (high doses).
• Drug Interactions: See above.
• Pregnancy & Breastfeeding: Generally safe at recommended doses.
• Dosage: See Dosage section.
• Monitoring Parameters: Monitor for signs of thiamine deficiency (e.g., neurological symptoms) and vitamin C deficiency (e.g., fatigue, easy bruising). In patients receiving high-dose vitamin C, monitor kidney function and blood glucose levels.

Popular Combinations

Thiamine is frequently combined with other B vitamins in B-complex formulations. Vitamin C is often combined with other antioxidants or in multivitamin preparations.

Precautions

Monitor for adverse effects, especially in patients with renal or hepatic impairment. Adjust dose as necessary. Advise patients to avoid exceeding recommended dosages of vitamin C.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Thiamine + Vitamin C?

A: The recommended dosage varies depending on the indication and patient-specific factors. Standard adult dosages for thiamine deficiency are 5-30 mg/day orally. Vitamin C RDA is 90 mg/day for men and 75 mg/day for women. Higher doses of thiamine are used to treat severe deficiency (e.g., up to 300 mg/day in Wernicke-Korsakoff syndrome).

Q2: What are the common side effects of this combination?

A: Thiamine is generally well-tolerated. High-dose vitamin C can cause gastrointestinal issues like diarrhea, nausea, and abdominal cramps.

Q3: Are there any serious side effects I should be aware of?

A: Although rare, serious side effects include allergic reactions to thiamine and kidney stones with high doses of vitamin C. In patients with G6PD deficiency, high doses of vitamin C can cause hemolysis.

Q4: Can pregnant or breastfeeding women take this combination?

A: Thiamine and vitamin C are generally considered safe during pregnancy and breastfeeding when taken at recommended doses. Consult appropriate guidelines for specific recommendations.

Q5: How is thiamine deficiency diagnosed?

A: Thiamine deficiency is diagnosed based on clinical symptoms, dietary history, and laboratory tests measuring thiamine levels in blood or urine, or the activity of thiamine-dependent enzymes.

Q6: What are the indications for using thiamine + vitamin C together?

A: The primary indication is preventing or treating thiamine deficiency, especially in cases of inadequate dietary intake or increased needs. While often given together in hospital settings, especially with hydrocortisone in trials for severe sepsis or septic shock, more research is needed regarding the efficacy of this approach.

Q7: What are the signs and symptoms of thiamine deficiency?

A: Early symptoms can include fatigue, irritability, and loss of appetite. More severe deficiency can lead to beriberi (characterized by peripheral neuropathy, muscle weakness, and heart failure) or Wernicke-Korsakoff syndrome (involving confusion, ataxia, ophthalmoplegia, and memory problems).

Q8: Does vitamin C interact with any commonly prescribed medications?

A: Yes. Vitamin C can interact with warfarin, deferoxamine, and certain chemotherapeutic agents. It may also interfere with laboratory tests, such as urine glucose tests. It’s essential to consider potential interactions when prescribing this combination.

Q9: Are there any dietary sources of thiamine and vitamin C?

A: Thiamine is found in pork, beef, legumes, whole grains, and nuts. Vitamin C is abundant in citrus fruits, berries, tomatoes, and leafy green vegetables.