What is folate, what does it do and where you find it. Why is the connection with the upper lip and tongue tie, which it has been seen more and more causing problem with breast-feeding.
What is the form that the body use?
The body uses the form folate which is transformed from the folic acid that is in supplements and in some food in the body. Folate is attached to a methyl group to make N5 or N10, methylhydrofolate (MTHF) which then is used in the liver with vitamin B12 and B6 to reduce homocysteine, make some red blood cells and much more.
Structural components of folic acid is glutamic acid, para aminobenzoic acid (PABA) and pteroic acid (pterin). Even though mammals (including humans), have all the components to make folic acid, we lack the enzyme to bond the pterin molecule to PABA to form pteric acid and therefore attach to glutamic acid. The active form of folic acid is folate, which has got multiple glutamic acid residue attached (4).
Sources of the most available form of folic acid are mushrooms, green vegetables such as spinach, Brussels sprouts, broccoli, asparagus, Romaine Lettuce turnip greens, endive salads, legumes such as lima and liver. Raw foods are usually higher in folate than cooed foods, however some foods needs to be cooked in order to get other nutrients, so maybe have half and half. If you are pregnant eating endive, and raw or cooked spinach or eat mushrooms slightly cooked, you get more of the bioavailable form of folate.
About 150 forms of folate has been found in food, but mainly in the form is N5, N10 THF.
In Lima beans the folate bioavailability (easily absorbed form) is 95% while in Romaine lettuce is about 25% (probably because of the fiber content).
Folate in foods can also be easily oxidized and therefore lost in the preparation and processing. Folate from foods also can be lost through inhibitors from foods themselves, such as conjugase inhibitors which prevents the digestion and absorption of folate.
So much that can stop folate to work and being absorbed and being used by the body. Now from food the absorption and transportation of folate is due to the health of the intestinal track mucosal brush border (so a healthy intestinal tract). There is a folate binding protein at the mucosal brush which will carry the folate to the liver to be transformed into the active one and then used.
Folate absorption and transportation also is thought to be pH, energy and sodium dependent. Folate is absorbed through the small intestine where the optimal pH is about 6 to 7 (far from the stomach pH).
It seems because of all the factor that can affect the ingestion, absorption and bioavailability of the folate, that folate is more easily absorbed in supplement forms and at empty stomach. Folate is transformed more and more time in the liver and what ever we do not use or the used one is recycled, stored and then used again. Some is also stored in the liver cells. In the blood, the folate form is monoglutamate. This is usually bound to protein, and about a third of folate is also found in free form.
So why is folate so important?
Folate is important for the metabolism of few amino acids such as serine, glycine, methionine and histidine.
What this amino acids do?
Methionine is one that is involved in the reduction of homocysteine, which is the one connected in adults with heart problems and high bad cholesterol and possible damage to the artery. This cycle is important for the maintenance of myelin and neural function depends on the methylation reactions using SAM (S-Adenosyl methionine). SAM is made by the oxidation and reduction of methionine and folate in the form of N5 methyl THF and N10 Methyl group, are essential for this reaction to occur. In the same cycle, for the homocysteine to be reduced again there is a need for methylated folate form as well as B12 and B6.
Histidine needs to be converted into glutamate to be less damaging to the body and folate in the above forms is essential for this conversion (Possible connection to allergy?)
Purine and Pyrimidine synthesis
Folate is involved in the synthesis of the above amino acid, which are essential for cell division, and DNA synthesis, hence the possible connection with spina bifida and maybe upper lip and tongue tie.
Folate also is essential for the making of the red blood cell and therefore deficiency can cause megaloblastic macrocytic anaemia (large immature erythrocytes, cells for the transportation of blood cells, this is also due to a deficiency of B12). The anaemia is the results of decreased DNA synthesis and failure of the cells to divide properly, with a continued formation of RNA. The results is high production of cytoplasmic components including haemoglobin, and the immature cells contains high amounts of haemoglobins . Haemoglobins are the cell that transports blood cells around the body. The formation of the blood transportation cells, involves the bone marrow, the kidney (secretion of erythropoietin) and the homocysteine cycle.
Low folate and B12 has been connected also to depression when the anti-depressants do not work (This is quiet true in eating disorders). If folate has been given without B12 and B6, there is a possible connection to an undetected deficiency of B12 and B6 with depression.
Post natal depression could be also the cause of low B6 and B12 and zinc as the homocysteine cycle needs zinc for the enzyme to function well as the other vitamins.
Heart diseases also have been connected to deficiency or low B12, folate and B6.
What is the possible connection with the upper lip and tongue tie and problems arising from low folate?
The reason that somebody connected the form of folic acid and folate to the above problem is to do with the genetic. In order for the folic acid to become active and have the methyl group attached, the body needs to have the right enzyme. Enzyme are made genetically, you either have it or have a bit of production or you do not have it at all.
As I mentioned above in order for the folate to be active and work in the body, it needs to be transformed with the methyl group attached. So it is similar to a lock and key process, without the methyl group the folate cannot work properly and therefore the key would not fit the lock and cannot be used. Now the enzyme that helps this function to happen is a mouthful to say, it is called 5,10-methylene tetrahydrofolate reductase (MTHFR) and the genetic code that is considered defected is C677T, Ala –> Val (1). It seems that the prevalence of the VAL/Val genotype depends on the ethnic groups. In African population is low, while in Europe and North America is about 5 to 15% and in Italy is much higher depends on the regions (1).
I have not seen any scientific evidence though, yet, connecting the upper lip and the tongue tie to the genetic defect of folic acid. However it does not mean that it is not possible. If there is a defect in the folic acid formation or some women have low enzyme activity for the transformation it can be possible. However a complete blockage of the folic acid might cause spina bifida or other muscular skeletal malformation, so not quite sure how that would work and why it would only have extra layer of thick skin on the lips and tongue and no one else. Maybe it is a thought for somebody out there to studies this factor.
What problem would the genetic polymorphism have on adults?
Now the above genetic problem might have more consequences for male and female adults in life in general if they have more stress, drink a lot and eat unhealthy as that would mean that the toxins are not eliminating enough and the homocysteine will be higher and higher and heart problem can be triggered. As well as anaemia, depression and other disorders connected to high homocysteine.
Who might need more folate, B12 and B6?
People who might need more folate, B12 and B6 are people who drink a lot, as folate is decreased with alcohol, achlorydia (low stomach acid), inflammatory bowel diseases, malignancies, when taking oral contraception, in pregnancy and during lactation. If you know that you have a possible genetic low MTHR (the enzyme that transform the methyl group), then take the active form of the folate which is now out for sell by many companies, Biocare, Solgar and others.
How would you know that you might have a problem?
Well look at the your own family history, if they had a lot of heart problems, if you drink a little and cannot cope with it much, stomach problems, family cancer, possible irritable bowel syndrome and possibly allergy, even though not scientific connection yet.
Is Folic acid or folate toxic?
There are studies that showing that even at high dosage folate it is not toxic, that is above 10 mg a day. However the normal recommendation even in pregnancy is about 400 mcg. In adults about 200 to 250 mgc a day. Vitamin C have been shown to protect folate from oxidation (free radical formation). In the presence of too much folate, it seems that zinc absorption is diminished (3).
Which food is folic acid added to?
Folic acid is added in grains and in pregnancy supplements and has been so since 1998. Now this has seen a reduction in spina bifida which is one of the consequences of deficiency in folate, however some now connects it to the possibility of tongue tie and upper lip tie but the folic acid form, even though as I mentioned above there is a need for more studies and only for some that have problems converting the active folic acid there is the need to take methyltetrahydrofolate form of folate.
Reference and Bibliography
- Cortese C. & Motti C. (2001). MTHFR gene polymorphism, homocysteine and cardiovascular disease. Public Health Nutr. Apr;4(2B):493-7.
- Girelli et al (1998). Methylenetetrahydrofolate reductase C677T mutation, plasma homocysteine, and folate in subjects from northern Italy with or without angiographically documented severe coronary atherosclerotic disease: evidence for an important genetic-environmental interaction. Jun 1;91(11):4158-63.
- Groff J. L. & Gropper S.S. (2000). Advanced Nutrition and Human Metabolism. Wadsworth Thomson learning. USA
- Knowles L. et al (2016). Treatment with Mefolinate (5-Methyltetrahydrofolate), but Not Folic Acid or Folinic Acid, Leads to Measurable 5-Methyltetrahydrofolate in Cerebrospinal Fluid in Methylenetetrahydrofolate Reductase Deficiency. JIMD Rep. Feb 23 (abstract)
