TGA Therapeutic Goods Administration : Folate and folic acid for use in listed medicines

This factsheet has been created for sponsors who wish to list folate products on the ARTG. It is intended to provide general information on the most commonly used folates and answer the most frequently asked questions.

Folate, or vitamin B9, is an essential vitamin required by the human body for normal growth and development as it plays a critical role in the synthesis of DNA and RNA, and in the metabolism of certain amino acids.

The term 'folate' is actually a generic name for a group of related compounds with similar nutritional properties. The three most commonly used forms are folic acid, calcium folinate and levomefolate salts. All three forms can be incorporated into the body's metabolic pathways and may provide sources of the same biologically active form of folate - a compound known as 5-methyltetrahydrofolate (5-MTHF) or levomefolic acid.

The relationship between these forms of folate is summarised in the diagram below. Specifically, it demonstrates the point at which these ingredients enter the metabolic pathway.

Supplement		Metabolic Pathway
Folic acid	→	Dihydrofolate (DHF)
		↓
Folinic acid (folinate salts)	→	Tetrahydrofolate (THF)
		↓
		5,10-Methylenetetrahydrofolate (5-10 MTHF)
		↓
Levomefolic acid (levomefolate salts)	→ (=)	5-Methyltetrahydrofolate (L-5-MTHF or levomefolate)

Folates in Listed Medicines

There are four folate sources currently permitted for use in listed medicines via the Permissible Ingredients Determination (the Determination). These are folic acid, calcium folinate, levomefolate glucosamine, and levomefolate calcium.

These ingredients are most commonly used in preparations indicated for reducing the risk of having a child with spina bifida and/or neural tube defects. These indications are restricted representations and a sponsor must have an advertising exemption for the claim, or have a product that meets the requirements of the folic acid advertising exemption (see FAQs below). When a sponsor wishes to make these indications, products must contain a dose equivalent to 400-500 micrograms of folic acid and include the following statements on the label:

• (NEUR) 'Warning: Do not exceed the stated dose except on medical advice. If you have had a baby with a neural tube defect/spina bifida - seek specific medical advice (or words to that effect)'; and
• (VIT) 'Vitamins can only be of assistance if the dietary vitamin intake is inadequate.' or 'Vitamin supplements should not replace a balanced diet'.

Frequently asked questions

Show more information about If the ingredient in my product is calcium folinate or a levomefolate salt, can I use the Coded (Standard) Indications NEUR1, NEUR2, FOLIC1, FOLIC2 and VIT2 for my product?Show more information about If the ingredient in my product is calcium folinate or a levomefolate salt, does the Advertising Exemption of 15 May 2015: 'Folic acid (minimum recommended daily dosage of 400 micrograms)' apply to my product?Show more information about If the ingredient in my tablet or capsule is calcium folinate or a levomefolate salt, do I need to comply with the requirements of section 9 of the Therapeutic Goods Order No. 78 - Standard for Tablets and Capsules (TGO 78)?