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Bioactive Folate for Emotional Well-Being and Methylation Support
XaQuil® DR features Quatrefolic®, a highly bioavailable glucosamine salt of methyl folate (5-MTHF), the bioactive form of folate, in a delayed-release capsule. As a direct source of 5-MTHF, this formulation bypasses the need for MTHFR enzyme conversion to efficiently support folate-dependent biochemical processes, including methylation and the synthesis of key mood-regulating neurotransmitters.
Key Benefits and Features:
| Serving Size: 1 Capsule | Amount/Serving |
| Folate (as (6s)-5-methyletrahydrofolic acid, glucosamine salt) | 25,500 mcg DFE |
Other Ingredients: Microcrystalline cellulose, capsule (hypromellose and water), ascorbyl palmitate, and silica.
Does Not Contain: Dairy, egg, gluten, shellfish, soy, tree nuts, wheat, peanuts, fish, yeast, GMO, sesame, animal products, or corn.
Take 1 capsule daily, with or without food, or use as directed by your healthcare professional.
Consult your healthcare professional before use. Individuals taking medication should discuss potential interactions with their healthcare professional. Do not use if tamper seal is damaged.
Warning: For use under the supervision of a physician. Keep this and all medications out of the reach of children.
Storage: Keep closed in a cool, dry place out of reach of children.
Folate (vitamin B9) is a naturally occurring compound in food that plays a critical role in physiological processes, including central nervous system function, DNA synthesis, cellular division, and neurotransmitter function. Dietary folate and folic acid, a common synthetic form of vitamin B9, undergo multiple metabolic steps before entering the folate cycle, including enzymatic conversion by methylenetetrahydrofolate reductase (MTHFR) to 5-methyltetrahydrofolate (5-MTHF), the bioactive form of folate used by the body. As the primary circulating form of folate, 5-MTHF supports the conversion of homocysteine to methionine, a vital step to produce S-adenosylmethionine (SAMe), an essential methyl donor involved in methylation pathways and neurological function.
Common polymorphisms of the MTHFR gene may reduce the efficiency of folate metabolism, impairing the conversion of folic acid to 5-MTHF and potentially affecting methylation pathways or resulting in unmetabolized folic acid (UMFA) accumulation. Elevated UMFA has been investigated for its potential to mask vitamin B12 insufficiency and impact neurological and cognitive function. Supplementation with 5-MTHF bypasses the MTHFR-dependent conversion step by delivering folate in its active form, helping to support folate status regardless of MTHFR genotype and without concern for UMFA accumulation.
Quatrefolic®, a patented glucosamine salt of (6S)-5-methyltetrahydrofolate, provides stable, bioavailable 5-MTHF. Research has demonstrated that Quatrefolic effectively increases plasma folate concentrations, including among individuals with common MTHFR polymorphisms, and has a stronger absorption profile compared with 5-MTHF calcium salt.
Neurotransmitters, Homocysteine, and Methylation
Research suggests that inadequate folate status may contribute to disturbances in methylation, neurotransmitter metabolism, and elevated homocysteine levels, all of which have been associated with neurological and neuropsychiatric function.
The inability to convert dietary folate and folic acid to 5-MTHF, the only form of folate that can cross the blood-brain barrier, can negatively impact the complex balance of brain neurotransmitters, which are vital to healthy mood regulation processes. One critical role of folate in the form of 5-MTHF is supporting the regeneration of tetrahydrobiopterin (BH4), a cofactor essential for the biosynthesis of monoamine neurotransmitters involved in mood and emotional well-being, including serotonin, norepinephrine, epinephrine, and dopamine.
Folate deficiency can contribute to elevated homocysteine levels, particularly in individuals with genetic polymorphisms or other factors that affect folate metabolism. Inadequate folate availability can impair methylation efficiency, leading to reduced SAMe production and disrupting cellular signaling pathways involved in mood regulation. Elevated homocysteine has been associated with increased oxidative stress, endothelial dysfunction, and impaired vascular health, all of which may adversely affect cerebral blood flow and nutrient delivery to the brain. Collectively, these biochemical and vascular mechanisms may influence neuronal function and emotional well-being.
In a prospective 2-year study, subjects (N = 246) with mild-to-moderate hyperhomocysteinemia received 15 mg of 5-MTHF on a cyclic schedule of 1 month of treatment followed by a 2-month washout period. A significant reduction in total homocysteine (tHcy) to normal levels was observed after the first treatment cycle in 51.3% of subjects, increasing to 86.8% over the 2-year follow-up period. These findings suggest that intermittent cyclic 5-MTHF supplementation may be an effective strategy for supporting healthy homocysteine metabolism.
In a randomized, double-blind, placebo-controlled trial involving healthy postmenopausal women (N = 30), supplementation with 15 mg/day of 5-MTHF for 3 weeks was associated with decreased blood pressure, reduced homocysteine levels, and reduced insulin resistance. Follow-up findings from the same research group in a similar cohort (N = 30) demonstrated a reduction of oxidative stress markers, which correlated with a shift toward blood pressure, insulin metabolism, and homocysteine levels being in a healthy range.
Healthy Mood and Emotional Well-Being
Emerging evidence suggests that a biologically distinct subgroup of individuals with depressive symptoms may be characterized by folate deficiency, impaired methylation, and disrupted monoamine neurotransmitter metabolism.
In a case-control study in subjects (n = 223) with depressive disorder and age- and sex-matched healthy controls (n = 273), investigators evaluated plasma homocysteine, folate, vitamin B12, and key neurochemical markers to explore the biochemical correlates of depression. Individuals with depressive disorder demonstrated elevated homocysteine and monoamine oxidase (MAO) activity, along with reduced folate, vitamin B12, serotonin, GABA, norepinephrine, and epinephrine levels compared with the control group. These findings suggest that elevated homocysteine may indicate impaired neurotransmitter synthesis and altered methylation pathways.
Although optimizing folate status can support healthy homocysteine metabolism and neurotransmitter balance, more quality studies with healthy individuals are needed to conclusively link supplementation with methylfolate to improved outcomes.
Safety
Owing to concerns regarding excessive folic acid intake, several regulatory and scientific bodies have established upper limits for supplemental folic acid, typically around 1 mg/day. This conservative level is primarily attributed to the potential for high folic acid exposure to mask hematologic manifestations of vitamin B12 deficiency, potentially delaying recognition of underlying neurological issues. However, available human clinical data evaluating 5-MTHF supplementation have demonstrated a favorable safety profile, with no serious adverse effects reported at doses of 5 mg/day for 6 months and 15 mg/day for 45 days in the studied populations.
XaQuil® DR delivers 15 mg (25,500 DFE) of folate as highly bioavailable 5-MTHF in a delayed-release capsule to support healthy folate and homocysteine metabolism, methylation pathways, neural cell function, and the synthesis of neurotransmitters critical to healthy mood and emotional well-being.
