Folate Therapy Directly Linked to Positive CFD Outcomes

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Folate Therapy Directly Linked to Positive CFD Outcomes

Cerebral folate deficiency (CFD) is a condition associated with low levels of a vital, transportable
form of folate called 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF) while folate
levels are normal in other body (non-nervous) systems.

Symptoms of CFD usually reveal themselves at around four to six months of age, and while they
may seem typical for infants, they are marked and intense in the presence of CFD.

      • Irritability,
      • unrest, and
      • sleep disturbances–

Leading to

      • delayed development,
      • deceleration of head growth,
      • decreased muscle tone and coordination.

In one-third of children, CFD also ushers in problems with voluntary movement, spasticity, speech
difficulties, and epilepsy. This sounds like an onslaught of bad news; however, the situation is not
bleak. Folate treatment, like administering a methylfolate supplement, can result in significant
improvement of clinical symptoms and a return of 5-MTHF levels in the CSF to normal. Normal
levels lead to vast health improvements.

The conversion of folic acid into a bodily useful folate is complex. First, the folic or folinic acid
must be absorbed as folate, and the next key step in the conversion is transporting the folate
through the blood. Two folate transporters come from the intestine. Defects in the genes of
those transporters are associated with systemic methylfolate deficiency.

When folates are absorbed in the gut with the help of an essential chemical reducer called
MTHFR (the “R” is for “reductase”), the folates are then converted to the main transportable
form, 5-MTHF. Then, 5-MTHF crosses the blood brain barrier. What it all comes down to, very
simply, is that people with CFD aren’t able to reduce and transport vital folates in the nervous
system, and that causes very real problems, even when the other systems of the body have
plenty of 5-MTHF.

Low CSF (reminder:“cerebrospinal fluid”) folate levels were first reported in 1981, with CFD
subsequently defined as “any neurological syndrome associated with a low CSF 5-MTHF, in the
presence of normal folate metabolism outside the nervous system” (Pope, 2019). A variety of
causes of CFD have been described, as indicated below, along with the clinical symptoms that
typically accompany those causes.

Folate Therapy Directly Linked to Positive CFD OutcomesFolate Therapy Directly Linked to Positive CFD Outcomes

Folate Therapy Directly Linked to Positive CFD Outcomes

Although prolonged CFD can clearly result in a range of clinical symptoms, the clinical outcomes
are encouraging, showing that CFD is also a potentially treatable condition. The treatment, in
these cases, is folate therapy, preferably with metabolically active forms of folate. Already
converted from folic acid to a usable form of methylfolate, 5-MTHF is efficient, well absorbed in
the intestine and could also prevent the potential negative effects of unconverted folic acid in the

Oral folates have been used extensively to treat CFD, most successfully when started extremely
early, and recent studies have suggested that administering folate either via intramuscular or
intravenous routes may even improve CFD clinical outcomes even further. Since these
treatments have resulted in such positive outcomes, a case could be made for screening the
cerebrospinal fluid of patients with unexplained neurological disorders. If screening showed low
5-MTHF in the CSF, it is altogether possible that folate therapy could be a step toward relief and
improved health in those patients, as well.

Pope S, Artuch R, Heales S, Rahman S. Cerebral folate deficiency: Analytical tests and
differential diagnosis. J Inherit Metab Dis. 2019;1–18. 12092

    Written By,
    - Jamie Hope



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