Average Reading Time: 3 minutes and 21 seconds
MTHFR (methylenetetrahydrofolate reductase) is an enzyme that converts folic acid into its active form, 5-MTHF (levomefolic acid). Certain mutations of the MTHFR gene adversely affect this process.
Two mutations in specific, occurring on position 677 and position 1298 of the gene, are considered to be of clinical significance. (1,2)
Briefly, the heterozygous (inherited from one parent) mutation of MTHFR 677CT has been linked to a reduction in MTHFR activity and, therefore, folic acid conversion by 20-40%. The homozygous (inherited from both parents) MTHFR 677TT can reduce this conversion by 40-70%.
The heterozygous mutation of MTHFR 1298AC has a minimal effect on enzyme activity on its own, but in someone who also has the 677CT mutation, it has been shown to reduce activity by 40-50%. (3-6) These are serious limitations in the body’s ability to break down folic acid.
While the prevalence of these mutations varies by ethnicity and geographic location, meta-reviews of the scientific data are revealing. Approximately 35% of the US population are likely to have the 677CT mutation, 13% are likely to have the 677TT, and 17% are likely to have the 677CT and 1298AC mutations. (7,8)
That’s 65% of folks in the United States who are predisposed to have trouble maintaining healthy folate levels through supplementation or natural food sources.
MTHFR Health Concerns
Chronic folate deficiency is known to hide the presence of a severe vitamin B12 deficiency during blood screenings, which is only compounded in individuals with a reduced ability to convert folic acid. Severely low levels of B12 can also lead to a toxic build-up of un-metabolized folic acid in the body, creating a downward spiral of nutritional insufficiency. (9-12)
Clearly, these two critical vitamins are meant to work together, and insufficient conversion to their biologically available forms is linked to some major long-term health problems, including:
- Megaloblastic anemia (11)
- Elevated homocysteine levels (4, 13, 14)
- Elevated risk for heart disease (2)
- Endothelial cell dysfunction (13)
- Cognitive impairment (14)
- Dementia (12)
- Depression (12)
- Peripheral neuropathy (11)
- Preeclampsia (15)
- And More (11)
The Best Forms of Folate & Vitamin B12
5-MTHF is the most biologically active form of folate. It is the form of folate naturally present in food, and the form into which the body must convert all other forms of folate in order to use them. (16) In this same way, methylcobalamin is considered the best supplemental form of B12, as it does not need to be metabolically converted before the body can use it, unlike cyanocobalamin.
Despite some research showing that folic acid and 5-MTHF have equivalent bioavailability, 5-MTHF is often the preferred form to replenish folate. This is due, primarily, to the presence of digestive or metabolic variabilities that can affect the conversion of folic acid to 5-MTHF. (17-19)
Furthermore, studies have shown that 5-MTHF increased plasma folate more effectively than folic acid irrespective of genetic differences in metabolism. (16, 20)
Vitamin B12 and 5-MTHF are More Potent Together
Vitamin B12 supports healthy methylation through its roles in the synthesis of methionine from homocysteine and the synthesis of S-adenosylmethionine (SAMe) – a naturally-occurring compound found in almost every tissue and fluid in the body (21) and well-known mood support supplement.
Methylation is a biochemical process and epigenetic signaling tool involved in almost every single function of the body. Compromised methylation has been clearly linked to autoimmune conditions. (22)
Under-methylated homocysteine is linked to a swarm of health concerns. As an example of its importance in homocysteine metabolism, one study showed that the combination of B12 and folate (5-MTHF) had a greater impact (7%) on homocysteine processing than did folate alone. (23)
Like folate, red blood cells require vitamin B12 for proliferation and manufacturing. (24) B12 is essential for neurological health, and chronic insufficiency can affect the spinal cord, peripheral nerves, the optic nerve and the brain. (9)
Research also backs a role for methylcobalamin supplementation in the following: (25,26)
- Melatonin secretion
- Enhancing light sensitivity
- Normalizing circadian rhythms
- Improving sleep-wake cycles
Oral Delivery Just as Effective as B12 Shots
B12 from food sources is delivered into the bloodstream only when the stomach is producing sufficient amounts of Hydrochloric acid (HCI). Many people have digestive concerns that can affect their HCI levels and, as a result, B12 shots were considered a superior treatment for years.
New research shows that oral supplementation with methylcobalamin is just as effective and carries the added benefits of lower cost and ease of administration. (27, 28) Hooray!!! No more shots!
New and Improved Formula – LifeSpa’s B-12 Boost is the most biologically active form of the water-soluble B vitamin, folate. It is the preferred form of folate supplementation due to an array of conditions that can limit conversion or absorption of folic acid. Data indicates that supplementing with 5-MTHF increases plasma folate more effectively than folic acid. MecobalActive™, which is found in the B-12 Boost formula, is a highly pure form of methylcobalamin that does not use any harmful solvents during manufacturing.