Humans cannot handle over 300 micrograms of this – but many supplements contain many times that amount…
These men locked themselves up for two years – here’s why
These men were isolated for two years conducting an incredible experiment that led to a breakthrough in age research.
And now, a new method has been discovered that does NOT require the hardships they endured…
Well, it’s just one easy thing that I just did with my wife Jodi.
And you could do it today – it only takes minutes!
I just created a short, 5-minute video that shows you how to live decades longer – with much more sexual power than ever before (lifespan and sexual ability are tied together in men) – and you can learn this TODAY
Check your supplement labels: Is this one of the ingredients?
Today’s newsletter spells out a major problem with a bad supplement that is not only in vitamins but also a lot of “fortified” foods.
Let me start at the beginning.
So even though synthetic molecules are identical to their natural counterparts, folic acid has no natural counterpart.
Folic acid is in multivitamins, B vitamin supplements, and added some foods
Manufacturers prefer this particular folate subtype over freely-available natural forms – not because of stability, but merely on account of its easier chemical synthesis.
Folic acid is simply the cheapest form.
And they justify using that form of vitamin B because some of it is converted into the natural forms within the body.
While this is certainly true, this is not the entire story.
Dihydrofolate reductase – that is the enzyme responsible for this conversion – but dihydrobiopterin reductase can also work.
However, since we haven’t evolved to consume unnatural folic acid at all, we don’t have enzymes to properly deal with it.
Folic acid is the only folate that needs to be reduced twice before it can be used: first into the natural dihydrofolate and then again into tetrahydrofolate.
Since folic acid is unnatural, our bodies had no need to evolve an enzyme to catalyze the first step…
And maybe that is why this first step occurs about 100 times slower than the other, natural one.
Humans cannot handle over 300·μg of folic acid at any given time before it spills over into the bloodstream unconverted.
Now, because of chemical synthesis and food fortification, folic acid is found inside humans for the first time in history.
“Circulating unmetabolized folic acid implies that the body’s capacity to convert folic acid to the metabolically active 5-methyltetrahydrofolate (5-MTFH) has been overwhelmed and that folic acid has passively diffused intact into the circulation. This may have adverse effects…”
Even though folic acid is listed under “vitamins” in food nutrition charts, its only non-precursor function is inhibiting folate-dependent enzymes and brain folate uptake.
Unmetabolized folic acid is consistently linked with reduced brain function, most likely on account of these antagonistic functions.
Although certainly bad, plasma “unmetabolized folic acid” isn’t the whole story:
Only the (6S) forms of folates are active in enzymes that require them…
Yet when folic acid is consumed, the unnatural (6R) enantiomer is also formed:
Although our natural enzymes always produce the proper (6S) enantiomers, high doses of folic acid lead to side reactions.
And, just like unmetabolized folic acid, (6R)-folates inhibit enzymes that strictly require the (6S) forms.
Perhaps more importantly: These (6R) derivatives also inhibit brain uptake of the natural (6S)-folates made by plants.
If prolonged, cerebral folate deficiency can lead to demyelination and seizures.
We need the natural (6S)-tetrahydrofolate for DNA synthesis.
The only safe vitamin B9 supplements are those with (6S) stereochemistry.
Both Metafolin® and Quatrefolic® contain (6S) 5-MTFH and are easily available.
Another option is to eat plants for natural (6S)-folates.
And plants leaves also contain vitamin K and Magnesium.
But it’s best to avoid folic acid from B supplements and refined foods.
All of this is well supported by evidence:
This study compared concentrations of unmetabolized folic acid against a cognitive test in hundreds of subjects.
They gave the subjects the Digit-Symbol Substitution Test (DSST) – it measures attention, learning, memory, and information processing speed.
They found that unmetabolized folic acid in the bloodstream is negatively correlated with test scores for intelligence.
“In the subgroup with low vitamin B 12 status, the mean DSST score for the subjects with detectable circulating unmetabolized folic acid was almost 5 points lower than that of the unexposed subjects…”
As you can see, the effect was more prominent in the low B12 groups.
The enzyme methionine synthase requires cobalamin (vitamin B12) and also (6S)-5-MTHF to convert the more dangerous homocysteine into the safer methionine.
This study implies that unmetabolized folic acid inhibits the enzyme methionine synthase, increasing dangerous homocysteine levels.
Of course, we still need natural folate.
Not surprisingly, this study found the reverse in participants who had more 5-MTHF.
They had an increase in test scores.
We need high amounts of natural folates for proper brain function…
But unnatural folates inhibit natural ones on many levels.
“Results for the 5-MTHF concentration, on the other hand, showed a significant positive association between that exposure and the DSST score.”
All other studies comparing folic acid blood levels or intake have shown the same thing.
These are very consistent observations.
This is also biochemically plausible. Studies done by chemists and pharmacologists have shown that it makes sense for folic acid to inhibit brain folate uptake.
Since folate-dependent enzymes are required for the synthesis of brain DNA, brain myelin, and brain methionine, these findings are not surprising.
As good as these studies were, they all have one limitation.
None of those studies determined the stereochemistry of the folates.
This study below shows that you can expect a significant amount of (6R)-5-MTFH from taking folic acid – and this is the wrong form and also an enzyme inhibitor.
Inactive (6R)-folates cannot be differentiated from the active (6S)-ones under most analytic techniques…
Therefore, many researchers erroneously take them to be active (6S)-folates.
This is because only (6S)-folates are presumed to occur after taking folic acid…
But the 2004 study below proves that assumption is quite wrong:
This study was the only one to actually measure the stereochemistry of the folates that result from consuming folic acid.
Folates are relevant to cardiologists because their deficiency raises homocysteine – an assumed risk factor for cardiovascular disease.
In the study, they gave patients either folic acid or dl-methyl-tetrahydrofolate, the easier-to-produce form having equal amounts of the (6S)- and (6R)-methylfolates.
Upon ingestion, folic acid will either remain unmetabolized or become: (6S)-folates, (6R)-folates, or a mixture of both.
Since it is commonly assumed that all folic acid is transformed by dihydrofolate reductase in the body, it had always been assumed that all folic acid metabolites are (6S)-folates.
Not only was that assumption wrong, but, actually, more (6R)-folates are actually produced:
This is hard to reconcile with our natural enzyme system.
Dihydrofolate reductase has been shown to yield exclusively the (6S)-product.
You’d almost be forced to assume that non-enzymatic side reactions are taking place.
And moreover, the amount of active (6S)-folates produced via folic acid ingestion is surprisingly low – almost negligible:
Not only has folic acid been consistently associated with cognitive decline when found in the blood unmetabolized… this form barely yields any active vitamin when it actually is metabolized.
This is unnecessarily dangerous.
Folic acid can inhibit enzymes and lower brain folate uptake while yielding little potential benefit.
The only folate supplements worth buying are exclusively (6S)-folates. Again, you can get those in Metafolin® or Quatrefolic®.
[We are not affiliated with any supplement company.]
Although simply eating green plants and avoiding the unnatural folate forms should be just as good.
Have you tried the New Super Vitamin C?
It’s much more powerful and safe than regular Vitamin C…
- There are so many different vitamin C variations and some of them can be toxic. You will discover the exact amounts and techniques here, including how much vitamin C is too much.
- This new form of Super C stays in your system for days instead of minutes. During that time, germs will just bounce off you. Imagine NEVER having to worry about getting a cold, running a fever, or coughing… And having a virtually steel-hard constitution that NEVER gets sick anymore.
- This new form of Super C produces healthy collagen, the glue that holds cells together and keeps gums healthy. Your dentist will be amazed by your strong and plaque-free teeth.
- Discover how to fix a sore throat or a cold, or even the flu, within a few hours rather than days. This new form of vitamin C works better than any other remedy on the market – because it stays in your system until every trace of disease is neutralized and gone.
- Some vitamin C products contain toxic, harmful ingredients that are cleverly hidden. With this simple vitamin guide, there won’t be any more guessing – you will know exactly what vitamins are safe and which ones have nasty additives and fillers.
Morris, M. "Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors." The American journal of clinical nutrition (2010)
Obeid, R. "Concentrations of unmetabolized folic acid and primary folate forms in plasma after folic acid treatment in older adults." Metabolism-Clinical and Experimental (2011)
Xin, W. "Differential stereospecificities and affinities of folate receptor isoforms for folate compounds and antifolates." Biochemical pharmacology (1992)
Selhub, J. "Excessive folic acid intake and relation to adverse health outcome." Biochimie (2016)
[*] Although the enzyme dihydrobiopterin reductase synthesizes (6R)-tetrahydropiopterins exclusively, these are actually of the same stereochemistry as the (6S)-tetrahydro- folates. The reason they are given different letters is an artifact of the Cahn–Ingold system, which designates stereochemistry based on the priority of connecting bonds. The #6 carbon of biopterins have different priorities as the #6 carbon of folates, and hence get a different number. Under any other system used to designate sterochemistry—such as the d/l and +/− nomenclatures—the natural (6S)-biopterins recieve the same symbol as the natural (6R)-folates.