Folate, folic acid and 5-methyltetrahydrofolate are not the same thing.
Folate, an essential micronutrient, is a critical cofactor in one-carbon metabolism. Low folate status may be caused by low dietary intake, poor absorption of ingested folate and alteration of folate metabolism due to genetic defects or drug interactions. Folate deficiency has been linked with an increased risk of neural tube defects, cardiovascular disease, cancer and cognitive dysfunction. Naturally occurring 5-MTHF has important advantages over synthetic folic acid - it is well absorbed even when gastrointestinal pH is altered and its bioavailability is not affected by metabolic defects.
Neuroinflammation in fibromyalgia and CRPS is multifactorial
Littlejohn1 notes that chronic pain has been associated with lipopolysaccharide (LPS)–stimulated proinflammatory cytokines (particularly IFN-γ and TNF); however, he does not pursue this line of thought to connect it to relevant literature showing clear evidence of gastrointestinal dysbiosis and increased intestinal permeability in patients with fibromyalgia and complex regional pain syndrome (CRPS). The gastrointestinal tract is the most abundant source of LPS, systemic absorption of which is increased by SIBO and increased intestinal permeability. In 1999, Pimentel et al.2 showed that oral administration of antibiotics led to alleviation of pain and other clinical measures of fibromyalgia. In 2004, Pimentel et al.3 showed that among 42 fibromyalgia patients, all (100%) showed laboratory evidence of SIBO, severity of which correlated positively with severity of fibromyalgia. In that same year, Wallace and Hallegua4 showed that eradication of SIBO with antimicrobial therapy led to clinical improvements in fibromyalgia patients in direct proportion to antimicrobial efficacy. In 2008, Goebel et al.5 documented that patients with fibromyalgia and CRPS have intestinal hyperpermeability; mucosal “leakiness” was highest in
High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.
Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions. We suggest that high folic acid consumption reduces MTHFR protein and activity levels, creating a pseudo-MTHFR deficiency. This deficiency results in hepatocyte degeneration, suggesting a 2-hit mechanism whereby mutant hepatocytes cannot accommodate the lipid disturbances and altered membrane integrity arising from changes in phospholipid/lipid metabolism. These preliminary findings may have clinical implications for individuals consuming high-dose folic acid supplements, particularly those who are MTHFR deficient.