Dr Vera's Folinic Acid
Dosage
1 capsule per day, or as prescribed
Indications
Folinic acid is a metabolically active form of folic acid
* May help to maintain normal homocysteine levels.
* May act as a methyl donor in the body.
Formulations
Folinic acid (as calcium folinate) 500 mcg
Interactions
Dosages of supplemental folic acid above 500mcg per day may mask underlying
vitamin B12 deficiencies.
Contraindications
Patients with epilepsy should not take high dosages of supplemental folic acid,
as seizure activity may increase.
It is recommended to monitor or supplement B12 levels with increased dosages of
folic acid.
Folate
Folic acid occurs naturally as a complex of related substances called folates
which are found in foods such
as sprouts, beans, eggs, lentils, Brewer's yeast, organ meats and green leafy
vegetables [1]. However, food
preparation and processing can destroy almost all of the naturally occurring
folate, as it is highly sensitive
to heat, air and light [2]. Oral folates are generally available in two
supplemental forms: folic and folinic acid.
Although the most common supplemental form of the folates is folic acid, it only
makes up 10% or less of dietary
folates. The majority of folates in the diet consist of reduced folates and
methyltetrahydrofolates. Although
folic acid is generally well absorbed, evidence suggests that reduced folates
and methyltetrahydrofolates
are absorbed differently [3].
Folinic Acid
Administration of folinic acid bypasses the deconjugation and reduction steps
required for folic acid. Folinic
acid has been deemed to be a more metabolically active form of folate, which is
capable of boosting levels
of the coenzyme forms of the vitamin in circumstances where folic acid has
little to no effect. It is also
suggested that folinic acid is more readily transported through the blood brain
barrier into the central
nervous system and has a longer half-life in the body than folic acid [3]. Human
absorption kinetic studies
of orally administered folinic acid have demonstrated a bioavailability of 92%
[4]. Following an oral dose of
folinic acid, the majority of folates are metabolized to 5-MTHF directly during
absorption in the intestine,
bypassing the need for deconjugation and subsequent reduction in the liver [3].
Blood Brain Barrier
Cerebral folate deficiency is associated with developmental delay, seizures and
autism [5] and also
psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia
[6]. Despite normal folate levels
in serum and red blood cells, analysis of CSF reveals extremely low levels of
5-MTHF, indicating disturbed or
defective folate transport across the blood-brain barrier. Oral folinic acid
supplementation has shown great
success in correcting CSF abnormalities leading to clinical improvements in its
associated manifestations.
Folinic acid may directly cross the blood brain barrier since reduced folates
are actively transported into the
brain, whereas folic acid is poorly transported to the brain and rapidly cleared
from the CNS [7].
Autism
A recent study attempting to improve baseline plasma methionine/cysteine/glutathione
levels and
increase antioxidant and methylation capacity, gave 20 autistic children
supplements of 800 mg of folinic
acid b.i.d. and 1000 mg betaine (trimethylglycine) b.i.d. for a period of 3
weeks. Folinic acid is converted to
5, 10-methyleneTHF which supports purine and thymidylate synthesis and also
methionine synthesis and
betaine provides a folate-independent pathway for methionine regeneration. After
only 3 weeks, a highly
significant increase in plasma methionine, cysteine, and glutathione levels were
associated with almost
2-fold increase in the ratio of reduced to oxidized glutathione (GSH/GSSG).
These results would suggest that
supplementation with folinic acid and betaine had a strong positive impact on
antioxidant capacity in the autistic children [8].
Depression
Patients with major depressive disorder often demonstrate lower serum and red
blood cell folate
concentrations. Lower serum folate concentrations have been closely associated
with greater severity of
depression [3]. Some evidence also suggests that low folate levels can result in
a poorer response to selective
serotonin reuptake inhibitors (SSRIs) [9]. It has been reported that the
efficacy of conventional antidepressants
such as fluoxetine (Prozac) is significantly enhanced by the addition of daily
folate [10, 11].
Other uses
Therapeutically, folinic acid can reduce homocysteine levels and the occurrence
of neural tube defects, may
play a role in cervical dysplasia and protecting against neoplasia in ulcerative
colitis. Folic acid deficiency is
considered to be one of the most common nutritional deficiencies [3]. Folinic
acid has largely been reserved
for the use of methotrexate rescue and as an adjunct to some chemotherapy drugs.
Folinic acid has several advantages over folic acid which might, under some
circumstances, offer a therapeutic
advantage. It bypasses several steps in the conversion of folic acid to 5-MTHF;
is more readily transported
into the CNS than folic acid; has a longer half-life in the body; and it appears
to be a more metabolically
active form of folate, capable of boosting levels of the coenzyme forms of the
vitamin in circumstances
where folic acid has little or no effect [3].
References
1. Osiecki H, The Nutrient Bible. 7th ed. 2006, Brisbane, Australia: Bio
Concepts Publishing.
2. Braun L and Cohen M, Herbs and Natural Supplements: An evidence based guide.
2005, NSW: Elsevier Australia.
3. Kelly GS, Folates: Supplemental Forms and Therapeutic Applications. Alt Med
Rev, 1998. 3(3): p. 208-220.
4. McGuire BW, et al., Pharmacokinetics of leucovorin calcium after intravenous,
intramuscular and oral administration. Clin Pharm, 1988. 7: p. 52-58.
5. Moretti P et al, Cerebral folate deficiency with developmental delay, autism
and response to folinic acid. Neurology, 2005. 64: p. 1088-1090.
6. Ramaekers VT et al, Psychomotor retardation, spastic paraplegia, cerebellar
ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in
cerebrospinal fluid: a novel neurometabolic condition
responding to folinic acid substitution. Neuropaediatrics, 2002. 33: p. 301-308.
7. Levitt M, et al., Transport characteristics of folates in cerebrospinal
fluid; a study utilizing doubly labeled 5-methyltetrahydrofolate and
5-formyltetrahydrofolate. J Clin Invest, 1971. 50: p. 1301-1308.
8. James SJ. Fall DAN!TM 2003 Conference. 2003. Portland, Oregon USA.
9. Alpert JE and Fava M, Nutrition and depression: the role of folate. Nutr Rev,
1997. 55: p. 145-149.
10. Lake JH, Textbook of Integrative Mental Health Care. 2007, New York, USA:
Thieme Medical Publications.
11. Gilbody S, Lightfoot T, and Sheldon T, Is low folate a risk factor for
depression? A meta-analysis and exploration of heterogeneity. J Epidemiol
Community Health, 2007. 61: p. 631-637.
