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You are able to cancel your order with no penalty! You must cancel your order before it ships.

We try our best to ship items as fast as we can. Once your order is received, it is “picked” and “packed” within 24 hours and sent out for shipping. Tracking numbers will be updated 1-2 days after your order has been SHIPPED and you will receive an email confirming your order is on its way along with a tracking number. If you click on the tracking number, you should be taken to the shipping website where you can sign up to receive delivery status updates. 

Shipping times vary depending on where you live, but generally most orders arrive within 2-5 business days. *It is important to note that due to Covid-19, there may be a 24–48-hour additional delay in shipping.

Absolutely! Please send your question to team@healthy-brain.ai. We do receive a large number of emails, so kindly give us 1-2 business days to respond.

This an acronym for “methylene terrahydrofolate reductase”. This is an especially important enzyme in vitamin B9 (folate) metabolism. Basically, the MTHFR enzyme has a significant influence on how well the body processes, makes, and utilizes several different forms of folate.

Another word for vitamin B9. Both “folate” and “B9” are generic vitamin category terms as they include a variety a different folate forms in the body that have different functions. So they refer to a family of closely related B9 vitamins more than any one B9 form per se. 

A-MTHFR’s most important job is to make a specialized form of B9 called “L-methyl folate” (AKA “LMF” or “5-MTHF”). As it produces each molecule of LMF, it also helps to keep other less specialized upstream forms of folate from building up in an unhealthy way.  When MTHFR functions properly and is able to produce LMF in a consistent way, it also helps to support the normal functioning of other chemical reactions that are critically dependent on LMF, including keeping toxic metabolites in check (homocysteine) and supporting neurotransmitter production (Ex: serotonin and dopamine). 

A-It’s a specialized bioactive folate form that the body produces from simpler ingested folate forms. It is also the main natural folate form found in blood. “Bioactive” means that it is a vitamin that can perform one or more key biological functions. From a brain health perspective, LMF is a critically important  micronutrient given that it is the only form of folate (B9) that can pass into brain tissue from the bloodstream. All other forms of folate are not able to access brain tissue. This is due to the fact that the brain is normally protected by something called the blood brain barrier (BBB). The BBB is a natural filter that surrounds the brain, creating an nearly impenetrable boundary/barrier between brain tissue and the fluid that surrounds the brain (CSF) vs the blood and other tissues outside of the brain. When it comes to folate, even though there are several versions of folate in the body, only one-LMF-can use specific folate transporters to pass into brain tissue through the blood brain barrier. It’s like having the right key for a lock. After LMF gets into the CSF through the blood brain barrier, it is is then taken up by brain cells and used to help make key neurotransmitters like dopamine, norepinephrine, and serotonin. This unique and specialized brain support function is one of the main reasons that LMF has garnered lots of attention in clinical and brain research settings over the past two decades. 

Folic acid (FA) is a synthetic form of folate (B9) that is a commonly consumed folate source in many industrialized countries including the US. It has also been a regular if not main source of folate for many people in the US after the FDA required that it be added to all enriched grain products in 1998. As the science of how folic acid is processed in the body has rapidly advanced in recent years, updated research suggests that while it still likely has some cost-effective health value as an inexpensive folate source for some groups of people, it’s no longer regarded (particularly in the MTHFR research and medical communities) as an ideal “one-size-fits-all” folate suited source for everybody.  It’s main advantages include: a very low cost and the fact that it can be easily added to nearly all commercially-available processed foods, cereals, breads, and most inexpensive supermarket-stocked over-the-counter multivitamins. It is also credited with helping to reduce the overall rate of neural tube defects when taken by pregnant women. While folic acid has several potential advantages, it is still a synthetic form of folate that is not found  in nature. So before it can be used by any cells of the body it has to first get metabolized and converted to biologically usable folate forms that the body can recognize and respond to. This set of extra processing steps can create some folic acid drawbacks for many people. One of Folic acid’s main drawbacks  is the fact more than 50% of people have an genetic susceptibility that can interfere with their ability to efficiently use folic acid.  In fact, published studies report that a significant percentage of the general population (up to 60% in the US) has a genetically-caused impairment (an MTHFR enzyme defect) in folate metabolism that reduces their ability to process and utilize folic acid. This common MTHFR-related metabolic defect has been shown to result in: (a) an unhealthy and potentially toxic accumulation of unmetabolized folic acid (UMFA) in the blood combined with (b) an insufficient production of a bio-active folate form (LMF) that is essential for normal neuronal and vascular tissues.  Given these adverse health concerns, folic acid can end up having an unfavorable risk/benefit profile for many people, particularly those who have some underlying genetic defects (MTHFR mutations) and/or who are are on certain medications that impair folic acid metabolism (Ex: Depakote, Lamictal etc). In short, for people who have susceptibilities in their ability to metabolize folic acid, it’s better to avoid or at least greatly minimize the consumption of foods/vitamin products that contain folic acid.

Higher UMFA levels have been linked to several adverse health outcomes/problems in multiple published scientific studies including:  • Impaired immune function through the reduction of both NK cells and NK cell activity  • Reduced transport of bioactive folate (LMF) into brain tissue from folic acid binding to and blocking LMF transport receptors  • Increased cognitive symptoms in some elderly patients  • Increased levels of neurotoxic inflammatory biomarkers (ex: IL8, TNF-alpha) associated with cognitive dysfunction

In several ways: (1) LMF is the only known folate form that can pass through an intact blood brain barrier into the cerebral spinal fluid where it is then taken up by neurons. (2) It is a key cofactor for the production of neurotransmitters like Dopamine and Serotonin. (3) It enhances neurotransmitter synthesis by supporting the production of SAMe and BH4. (4) It helps to reduce/regulate levels of homocysteine (Hcy) which is important since increased Hcy is neurotoxic. (5) Clinical studies show that LMF can help to reduce depression and cognitive symptoms.  

The body has several standard  enzymatic steps for converting synthetic Folic acid into natural bioactive folate forms and eventually into LMF, the most specialized folate form that is used by brain cells. There are 4 main steps to get from Folic acid to LMF. Those are depicted here in a simple flow chart: FA->->->->LMF    Health problems can develop when one or more of these 4 enzymatic steps is slowed or impeded. This metabolic slowing can result in reduced levels of downstream folates like L methyl folate (LMF) and a build-up of upstream folates like Folic acid (AKA “UMFA”). 

While folic acid (FA) is inexpensive and plentiful (it’s in most foods that people in the US consume each day), it’s also not a natural B9 form. It’s synthetic, so it’s not known in nature. Therefore the body’s cells don’t have any pre-existing way to use it directly. They have to first convert it to a natural folate form that the body’s cells can recognize. So, tradeoff is that while Folic acid is very cheap, available in most processed foods, and something that quickly accumulates in the blood, the body can’t immediately utilize this absorbed FA so it has some extra work to do to get it converted to a B9 form that is biologically useful. One could say Folic acid a “high maintenance” form of folate.

While folic acid (FA) is inexpensive and plentiful (it’s in most foods that people in the US consume each day), it’s also not a natural B9 form. It’s synthetic, so it’s not known in nature. Therefore the body’s cells don’t have any pre-existing way to use it directly. They have to first convert it to a natural folate form that the body’s cells can recognize. So, tradeoff is that while Folic acid is very cheap, available in most processed foods, and something that quickly accumulates in the blood, the body can’t immediately utilize this absorbed FA so it has some extra work to do to get it converted to a B9 form that is biologically useful. One could say Folic acid a “high maintenance” form of folate.

These are common genetic mutations that increase one’s susceptibility for developing: various B vitamin insufficiencies; increased neurotoxic biomarkers such as elevated homocysteine; imbalances in folate (B9) metabolism; cardiovascular disease; and various neuropsychiatric conditions.

An estimated 50-60% of US residents have at least one MTHFR mutation.

Yes. In two different psychiatric clinical settings in which we (CS; MKS) screened for MTHFR mutations in all referred patients over a several year period, we observed frequencies of 91% (OBH) and 94% (CCI). Increased rates of MTHFR mutations in persons being treated for psychiatric conditions has also been reported in the literature.

Yes. In published dementia studies, MTHFR mutations have been observed in 89-93% of subjects. 

Having MTHFR mutations increase the risk for developing several B vitamin insufficiencies/deficiencies (Ex: B2, B6, B9, B12 especially).

Several MTHFR mutation variants appear to increase the risk for having/developing increased homocysteine levels in the blood and brain tissue. Elevated homocysteine is a potentially modifiable neurotoxic marker that increases risk for depression, dementia, increased loss of neurons, injury to the blood brain barrier, and accelerated brain atrophy (shrinkage). Elevated homocysteine levels are also associated with elevations in other potentially neurotoxic biomarkers such as: homocysteic acid (HCA), thiolactone (HTL), and S-adenosyl homocysteine (SAH).

This risk relationship is well established in 20+ years of published scientific studies: MTHFR mutations lead to lower Bs, which secondarily lead to elevations in homocysteine (HCY).

Low B vitamin levels have been linked to memory loss, cognitive decline, dementia, Alzheimer’s dementia, and vascular dementia.

Elevated homocysteine has been associated with various kinds of psychiatric symptoms/conditions including depression, psychosis, anxiety, ADHD, autism, and bipolar symptoms. 

Low B vitamins (B9, B12 etc) are associated with reduced levels of  neurotransmitters in the brain (in cerebral spinal fluid studies).

Low levels of B12 and B9 have been linked to increased brain atrophy.

In prospective brain MRI studies, elevated homocysteine levels have been consistently linked to increased rates of brain atrophy in a graded positive association fashion (the higher homocysteine, the greater the atrophy). The homocysteine level with the lowest atrophy risk was assessed as < 8.

Yes. In the 60% of the US population is estimated to have at least one allele of the two most common clinically-significant MTHFR mutations-1298C and/or 677T, these 5 mutation combinations tend to occur 99% of the time:  C677T  TT (677 homozygote.. means two 677 mutations) C677T+ A1298C (677+1298 double heterozygote.. means one mutation of each)  A1298C  CC (1298 homozygote.. means two 1298 mutations) C677T  T (677 heterozygote…means one 677 mutation) A1298C  C (1298 heterozygote…means one 1298 mutation) These 5 MTHFR mutation variants have also been found to confer different relative/predictive risks for developing other associated health conditions (psychiatric, cognitive, cardiovascular etc).  It’s too complicated to try to summarize all of the main risks here, but in general the adverse health risk gradient is believed to be the highest for C677T  TT and the lowest for A1298C  C, following roughly the first (highest risk) to last (lowest risk) sequence of these 5 mutations as listed just above.  The relative risk for having lower B vitamins and/or elevated homocysteine appears to more or less follow this same mutation gradient according to available studies and our clinical findings. 

Yes. Clinical studies have demonstrated multiple kinds of benefits from B vitamin combinations in terms of several improved brain health outcomes including: reduced depression symptoms, improved cognitive performance, reduced rate of cognitive decline, and reduced brain shrinkage on serial MRI tests.

Yes. Studies indicate that several kinds of B vitamin regimens have been successfully used to reduce elevated homocysteine levels.  B vitamin regimens are actually the most common strategy for treating elevated homocysteine. That said, the lack of access to baseline lab screening is often a barrier to using some of these newer evidence-based approaches.

In many cases, yes. However, some primary care providers are less familiar with the published research findings on MTHFR mutations, homocysteine, and B vitamin insufficiencies. Therefore, some providers may be less comfortable ordering these kinds of labs, especially as they relate to risks for cognitive decline, depression, and brain atrophy outcomes. On the other hand, most  primary care providers are much more willing to draw a fasting homocysteine, B12, folate, and sometimes also an MTHFR mutation lab, after a stroke, heart attack, blood clot, or new diagnosis of dementia. So access to these labs will often vary depending on the provider and medical risk context. 

Yes, including a recent placebo-controlled double-blinded study in subjects who had at least one MTHFR deficiency and clinical evidence for depression at baseline. B vitamins demonstrated efficacy  for reducing depression symptoms and homocysteine level by 6 weeks.

Yes. Published studies have shown that B vitamins can be used to reduce the rate of cognitive decline and homocysteine level at the same time.

A-B vitamins have also been used to improve cognitive performance in correlation with reductions in baseline homocysteine level.

A-B vitamins have also been used to reduce both homocysteine levels and the rate of brain atrophy (shrinkage) as assessed by prospective MRI brain scans.

Aa) improving brain health outcomes, (b) reducing neurodegenerative risk, and/or (c) addressing modifiable  risk factors for people who have underlying MTHFR mutations, low Bs, and/or elevated homocysteine levels? 38. Yes, there are multiple published micronutrient/B vitamin studies that have looked at several different outcomes in relation to each of these three key brain health goals.