If the whole point of adding L-methylfolate, vitamin B12 and vitamin B6 is to reduce homocysteine levels in the individual, then I believe finding the lowest optimum amount of each ingredient is a necessity.
Homocysteine is also lowered by more than just L-methylfolate, methylcobalamin and pyridoxal-5-phosphate. Homocysteine is directly lowered by trimethylglycine known as betaine or TMG. Why don't these prescription medications use TMG? I don't know.
It is also known that riboflavin, vitamin B2, is required to help reduce elevated homocysteine levels in those with homozygous C677T MTHFR mutations. One may say that adding riboflavin is not needed because the homozygous C677T mutation is not significant in the population. I absolutely disagree.
Riboflavin is inexpensive and if one is going to such an expense to help lower their homocysteine levels, then why not add the most active form of riboflavin possible?
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Why take more of L-methylfolate if it is not needed? L-methylfolate can only process so much homocysteine as it approaches homocysteine metabolism from one angle.
Adding TMG is a great idea as TMG completely reduces the need for high dose L-methylfolate as TMG bypasses the genetic mutation in MTHFR and is able to lower homocysteine directly. This means, that if a formula has added TMG, then the ability to lower the amounts of L-methylfolate and active B6 is possible to do.
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Now on to the recommendations…
1. Electrolytes.
Methylfolate supports methylation.
Methylation supports cell growth and division.
What happens when a cell divides? It becomes two cells. What happens when 10 billion cells divide? They become 20 billion cells.
What is inside these cells? Magnesium and potassium – and glutathione. If any of these are deficient, then the cell does not function properly, gets sick and dies.
As the cells malfunction, you malfunction. As the cells die, you experience greater side effects and a flare of your immune system – especially if your cells die a necrotic death which is what happens when the cells are very weak. This form of cell death triggers autoimmunity. Not good.
- Solution: Take electrolytes BEFORE taking any form of methylfolate OR methylcobalamin. I formulated Optimal Electrolyte to really make a significant impact in one's potassium and magnesium levels and also support mitochondria. Optimal Electrolyte is based upon my pretty famous MTHFRade formula which has helped thousands of people. They're easy to take, taste good, mix readily in water and your picky children will be compliant with them as well.
- Who needs electrolytes? Given that a significant number of us are potassium deficient, I would venture to say everyone. I take electrolytes almost daily – usually right after I wake up – and sometimes a few times a day if I am exercising or sweating (sauna, heat). I simply feel much better while taking it.
- Key signs that you need electrolytes:
- Nausea
- Dizzy
- Frequent urination
- Drinking water and then having to go to the bathroom quite quickly
- Muscle aches/spasms
- Frequent thirst which is insatiable
- Dry skin
- Key issues increasing need for electrolytes:
- Stress
- Exercise
- Sweating
- Diet high in sodium / low in potassium (MOST of us)
- Caffeine intake
- Processed foods (due to high sodium/low potassium)
- High protein diet (GAPS and Paleo – high protein depleting magnesium and potassium – especially if not eating greens/veggies)
- How to take electrolytes: In a tall glass of water OR stainless steel OR glass water bottle, add 1 scoop of Optimal Electrolyte. Sip or drink one serving 20 minutes prior to exercise and possibly another serving during or after – depending on the duration of activity.
- If you are not active due to fatigue, simply add 1/2 to 1 serving in a tall glass of filtered water and drink over a few minute time period.
- NOTE: Fill your glass or water bottle half full. Then add the electrolytes. They fizz quite readily and may spill over if you add them to a full bottle or glass. Stir or shake the bottle lightly a few times (sealed of course!) and then fill to the top.
2. Glutathione. As methylfolate supports methylation, cells divide. As cells divide, the amount of glutathione they have reduces by…let's say 50%. If one is already deficient in glutathione – and many people with MTHFR are deficient in glutathione – then there is going to be a flare of side effects.
Foods which increase glutathione are those which contain cysteine, glutamine and glycine. However, it is not that easy. Also requires magnesium, ATP, amino acid transport across the cell membrane and also the outer mitochondrial membrane. Then these components work together to form the glutathione.
Then, once the glutathione is formed, it gets used up quickly IF there is adequate selenium. After it gets used, it is damaged and has to get repaired and this requires vitamin B2 as active riboflavin. This active form of riboflavin is FAD and needs T4 thyroid hormone to form it. Hypothyroid? Hmmm.
- Solution: Easiest way to increase glutathione levels is with liposomal glutathione. This allows the glutathione to 'slip' inside the cell with tiny liposomes. In fact, this is more effective at raising red blood cell levels of glutathione than IV glutathione – and significantly less expensive.
- Who needs glutathione? Any one living and breathing. If you have any chronic condition, it is likely you are low in glutathione.
- How to take glutathione: Start very slowly with a small amount. If you are sensitive in general to things, start with just a few drops. May mix liposomal glutathione in some juice if you like.
- Pulsing glutathione is also likely recommended. This means taking it every other day or every few days initially. As you continue to improve or feel better, you may increase the frequency or the dosage…slowly.
- If you feel worse, then stop taking it. You may need to open up your sulfite pathway with vitamin B1 (Thiamin) and molybdenum first. If you know you do not tolerate sulfites – wine, dried fruits – or sulfur-containing foods like eggs, cruciferous vegetables or your flatulence smells like sulfur, then you should also support sulfite pathway first with B1 and molybdenum before you take glutathione. Avoiding sulfur-containing foods and supplements for a few days is also recommended to help clear out the sulfite pathway. Keyword there is 'a few days' – not a few months or forever. Introduce them back slowly – but first introduce glutathione.
- NOTE on Thiamine: I recommend Vitamin B1 because sulfites somehow induce a vitamin B1 deficiency. Those with high sulfites are more prone to B1 deficiency. Yes, thiamine contains sulfur – but it also needed for so many important reactions. You can try B1 on it's own to see how you do with it – or you can try taking Molybdenum first for a few days and then take B1.
3. Superoxide Dismutase (SOD). If glutathione and electrolytes don't cut it, then superoxide dismutase, known commonly as SOD, may be deficient for various reasons. If you have SOD snps, are low in zinc, copper and/or manganese, then the likelihood you will experience side effects from methylfolate is high.
What does SOD do? SOD breaks down the very damaging reactive oxygen species called superoxide. SOD converts superoxide into hydrogen peroxide. It is then up to glutathione to clean up hydrogen peroxide (along with catalase).
Why does one get side effects from methylfolate with SOD issues? When taking methylfolate, your body produces nitric oxide from it. It is one of the results from supplementing with methylfolate. This is beneficial as nitric oxide increases blood flow. However, when SOD enzyme is not working due to SOD snps or mineral deficiencies of copper, zinc or manganese, then superoxide levels are likely high. If this is the case, then the high superoxide levels combine with the increased nitric oxide to form a very damaging pro-oxidant called peroxynitrite.
Solution: The best way to support SOD is to make sure your red blood cell levels of manganese, zinc and copper are in the normal ranges. If they are and you have a SOD snp, then you may need to supplement with SOD directly.
4. Protein or Methionine. If you not consuming adequate protein, you may not be consuming enough methionine. Methionine is THE amino acid which helps produce the body's #1 methyl donor: SAMe. If you are a vegan, vegetarian, have digestive issues, take antacids, eat like a snake (don't chew much), drink a lot of fluids (of any type) during meals, then you may be low in methionine.
What does Methionine do? As mentioned above, it is the key amino acid needed to produce your most important methyl donor known as SAMe – also known as SAM, or s-adenosylmethionine. SAMe supports over 200 absolutely critical reactions in the human body. Another key point about SAMe is that it is the 2nd most important compound in our body. Who's first? ATP which is your power source.
What happens if you increase methionine or protein intake before supporting with electrolytes and glutathione and SOD? Methionine is quite easily damaged by oxidative stress (think free radicals but this isn't entirely correct as the term oxidative stress). If methionine is ingested from the diet in those with high oxidative stress (due to low glutathione and low SOD), then side effects may occur.
Point: Reduce your oxidative stress first with the glutathione and SOD – and possibly also vitamin E and phospholipids such as phosphatidylcholine. Selenium and riboflavin are also important – but I get into those below..
Why does one get side effects from methylfolate when methionine is low? In short, because methylfolate may make your methionine levels lower over time if you are not consuming enough protein. This gets complicated quickly and I am going to refrain from getting into it here. It will just lead to confusion.
What are the side effects from giving methylfolate when methionine is low? Histamine may increase. Histamine leads to running noses, itchy, skin disorders, tight chest (asthma or just difficulty breathing).
Solution: Eat more protein. This may be partly why some people do very well with GAPS or Paleo 'diets' as they are typically more protein. If you are eating more protein and still having issues, it may be that you are not absorbing it. Work with your doctor to increase absorption of your protein. Chewing helps and so does not drinking very much during meals as this dilutes your stomach acid and digestive enzymes.
If you know you have digestive issues are not enough stomach acid, taking 1 capsule of PreGestion during meals may be useful. Also taking 1 capsule of Methionine may also be more readily available in this form rather than from food if your digestion is weak or compromised.
These four recommendations may make a significant difference in how you respond to methylfolate and methylation in general.
- Electrolytes
- Glutathione
- SOD
- Methionine
Of course, there are other factors at play – such as a generalized deficiency in various B vitamins and other minerals.
If you know or suspect that you may be deficient in various minerals or vitamins, then it is important that you replenish many of them prior to supporting with methylfolate or methylcobalamin. Why? Because if you support with these two powerful methyl donor nutrients, it can cause a 'clog' in your biochemistry. This 'clog' may occur in how your brain chemicals (neurotransmitters) get formed and/or eliminated. Obviously, this can cause some significant issues.
The easiest way to replenish vitamins and minerals – and reduce some stress at the same time – is with Optimal Start. This is a specialized formulation I developed that helps people begin to restart their biochemistry without shocking it with methylfolate, methylcobalamin, iron or copper.
If you feel you are fine in most minerals and vitamins except B vitamins, then taking B Minus would be something to consider. B Minus is without methylfolate and methylcobalamin. This helps prime a lot of biochemical pathways without stimulating methylation. Most people respond very well to this formulation.
STRESS IS WASTEFUL AND DEMANDING
The biggest result I see is by reducing people's stress and supporting their adrenals. Stress is a direct stimulator of methylation. If reducing stress, then the demand on methylation goes down. Therefore, your dependence upon nutrients such as methionine, methylfolate and methylcobalamin go down.
If one is stressed, they are using up a variety of nutrients – and their cortisol is likely low – especially if they have been stressed or anxious for some time. This leads to autoimmunity, fatigue, hypothyroidism, wasting, poor memory, hard to get out of bed in the morning, frequent urination (loss of K and retention of Na) and…
Supporting adrenals can be quite rapid if:
- eating properly
- avoiding caffeine and stimulants
- supplementing with adrenal cortex (best taken in the morning around breakfast)
- sleeping before 11 PM
- getting at least 7 hrs of rest nightly
- increasing activities which you really enjoy
- avoiding high glycemic, refined carbohydrates
- eating quality protein foods and quality healthy fats
If you are a person that is easily startled or irritated, then you are likely maladapted. This means your nervous system is geared towards reacting vs responding.
This isn't healthy – and you know this.
The way to support this is by doing the above recommendations along with taking adaptogens.
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Let's summarize what we know about lowering homocysteine:
- inactive standard form of folic acid doesn't work well at all for those with MTHFR mutations – especially the C677T mutation
- active L-methylfolate works very well in lowering homocysteine as it bypasses the genetic defect of the MTHFR C677T mutation
- TMG, also known as Betaine or Trimethylglycine, works well in lowering homocysteine safely and effectively
- Vitamin B2, known as riboflavin, is needed by homozygous C677T MTHFR mutations in order to lower homocysteine effectively.
- Vitamin B12 is needed in order to prevent a vitamin B12 deficiency and to also help lower homocysteine by donating a methyl group. This is why methylcobalamin is the preferred form of vitamin B12. If the individual takes an already methylated form of vitamin B12, the ability for it to help donate a methyl group in the reaction to lower homocysteine is immediate. Basically, methylcobalamin helps transform homocysteine to methionine. There is a less commonly known MTHRR mutation (MTRR A266G) which requires methylcobalmin in order to get homocysteine levels dropped.
- Vitamin B6, the active form, is the backbone to get L-methylfolate and vitamin B12 to actively lower homocysteine. Without vitamin B6, this reaction does not take place. That said, vitamin B6 helps lower homocysteine.
I use the hydroxy/adenosyl combo from Pure Encapsulations, a made in USA brand that works well for me. They also have an Hydroxy lozenge which should have good absorption…https://www.
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