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Folinic acid (Activated B9) vs. Folic acid: Evidence based information

General, Infant and Children | September 29, 2015 | Author: The Super Pharmacist


Folinic acid (Activated B9) vs. Folic acid: Evidence based information

Folic acid and folinic acid are both forms of vitamin B9 and are classified as folates. Folates are required by the human body to perform many functions including cell division, growth, and the generation of red blood cells. Although folinic acid is pharmaceutically different to folic acid, both work in reasonably similar ways to each other. People who do not have enough folic acid or folinic acid are classified as being folate deficient, and this can cause a number of side effects such as mouth sores, stomach problems (such as nausea or abdominal pain), liver problems, or problems in regards to the generation of new blood cells.

What is the difference between folinic and folic acid?

Folinic acid (5-formyl tetrahdrofolate) is an active form in the group of vitamins known as folates. It occurs naturally in a number of different foods, whereas folic acid is a synthetic form of folate.

What role does folinic acid play in regards to both folate deficiency and supplementation?

Folinic acid (Activated B9) vs. Folic acid: Evidence based informationFolinic acid is regularly used as a supplementation to treat a number of different types of cancer, as well as an antidote to the effects of certain drugs used in chemotherapy. It can also be used in the treatment of megaloblastic anaemia when a folic acid deficiency has been observed.  When used in cancer treatments, it is often referred to as leucovorin. It is used to either enhance the anti-cancer effects of a drug called fluoruracil, or as a supplement to help prevent or lessen the side effects of methotrexate. Folic acid is also used similarly in a range of treatments for cancer. The action of methotrexate requires it to counteract and complete with folic acid within cancer cells in order to destroy them.  This also has a range of other side effects such as low blood cell counts, hair loss, mouth ulcers, and liver, lung and kidney damage. Complications and side effects as a result of taking methotrexate can be reduced through the use of leucovorin, and it has also been evidenced to allow more effective high dose chemotherapy and methotrexate efficacy under specific clinical circumstances (1). Fluorouracil is another anti-cancer drug that is regularly used, although when administered alone it only remains effective within the body for a short period of time. When supplemented with folinic acid, its action is enhanced through leucovorin improving its ability to block enzymes within the cancerous cells. As a result fluororacil can remain in the cells for longer and improve its efficacy. Leucovorin has the benefit of having almost no registered side effects of its own, although it has been evidenced to increase the side effects of fluororacil when they are administered together (2).

What role does folic acid play in regards to folate deficiency?Folinic acid (Activated B9) vs. Folic acid: Evidence based information

Folic acid supplements are commonly taken before and during pregnancy to help the development of the unborn child. It is important for the treatment of anaemia, and deficiencies in unborn babies can result in neural tube defects such as spina bifida. It can also be used in the treatment of severe Crohn’s disease. As with folinic acid, folic acid is also used as an adjuvant to a number of chemotherapy regimens. 

Are there any comparative studies of folic and folinic acid for particular conditions?

There is a limited amount of evidence regarding the comparative use of both types of folate. However, in particular areas such as the treatment of patients using a particular medication for certain cancers and rheumatoid arthritis, there is some literature available for analysis. However, very little of it is recent, with the latest systematic review of the best available evidence conducted in 2000. This work was undertaken by The Cochrane Collaboration, who assessed 7 trials that considered the supplementary effects of folic and folinic acid in reducing the mucosal, gastrointestinal and haemotologic side effects of methotrexate (3). Whilst the study found that folates in general were well evidenced to be a protective effect of supplementation in managing the side effects of low-dose Methrotrexate, all the studies were unable to differentiate between folic and folinic acid. The study did find that folinic acid was significantly more expensive than folic acid, although the outcomes associated with its use were no better or worse than those associated with the use of folic acid only (4). In response to uncertainty over the efficacy of folic and folinic acid at different dose level, The Cochrane Collaboration undertook a further systematic evidence review in 2013 and again found no discernible difference between the two supplements, and as such a clinically relevant estimate of benefit of different folate supplementations for a range of conditions remains absent (5). At present there is little available evidence regarding whether folic or folinic acid is the most clinically efficacious supplement in the treatment of a number of different illnesses. As such, the supplements tend to be used interchangeably due to the evidence that any form of folate can be effective as both an adjuvant to a wide range of cancer drugs and a supplement to meet individuals with deficiencies such as expectant mothers and individuals who are anaemic. Australia's best online pharmacy


  1. Tedeschi PM, Kathari YK, Farooqi N, Bertino JR (2014) Leucovorin rescue allows effective high-dose pralatrexate treatment and an increase in therapeutic index  in mesothelioma xenografts Cancer Chemo Pharma 74(5):1029-32
  2. Ozden S, Ogden Z, Ozyurt H, Gemici C et al (2015) Survival in gastric cancer in relation to postoperative adjuvant therapy and determinants World J Gastroenterol 28:21(4):1222-33
  3. Connors NJ, Sise ME, Nelson LS, Hoffman RS, Smith SW (2014) Methotrexate toxicity treated with continuous venovenous hemofiltration, leucovorin and glucarpidase Clin Kidney J 7(6):590-2
  4. Ortiz Z, Shea B, Suarez Almazor M et al (2000) Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis Coch Data Sys Rev CD000951
  5. Shea B, Swinden MV, Tanjong Ghogomu E et al (2013) Folic acid and folinic acid for reducing side effects in patients receiving MTX for rheumatoid arthritis Coch Data Sys Rev CD000951 doi: 10.1002/14651858.CD000951.pub2
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