The most read article on MTHFR.Net is ‘Methylfolate Side Effects‘.
Avoiding side effects caused by methylfolate is ideal.
It’s time I address it.
How do we reduce the likelihood of methylfolate side effects?
Before I spell some of the common causes of side effects induced by methylfolate, I should clearly state this is not all of them. I also do not know all the reasons why methylfolate causes side effects. The body is complicated. That said, the reasons outlined below are the very common causes of side effects caused by methylfolate. It is also understood how to prevent many people from experiencing side effects from methylfolate – and I share these below for you.
A note on supplementation:
Many people think that once a supplement is recommended, it is needed to take every day, sometimes multiple times a day and forever.
A supplement is defined as ‘something that completes or enhances something else when added to it’.
This means that a supplement enhances your biochemistry and physiology – and once complete – stop. If you continue to supplement beyond completing or enhancing your biochemistry, you are going to push it beyond where it needs to be.
This is a COMMON MISTAKE made by patients AND doctors worldwide.
Exercise makes you feel good. Breathing makes you feel good. Drinking water makes you feel good.
If you exercise too hard, you get sore and hard to do anything for the next few days.
If you breathe too quickly or forcefully, you can get light-headed and faint.
If you drink too much water, you can get a stomach ache, cramp, lose electrolytes and – if an excessive amount all at once – die.
Listening to this podcast will help answer questions about ‘How much to take?‘ (opens in new window so you can listen to it and read at the same time because I know you like to multitask 😉 )
Now on to the recommendations…
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:
- 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:
- 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.
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.
Optimal Adrenal is a blend of adaptogens that I designed for those experiencing lack of clarity and stress. It is also effective for those easily startled, panicked or pissed off. It may be taken any time of day but most effectively in the morning and afternoon.
Effects are typically felt quite immediately with these recommendations. Some degree of improvement is seen within one week for most people. All? No. Most. Some people have very tough blockages which require a lot of massaging and slooow headway – one nutrient at a time. One intervention at a time.
Introduce one nutrient or one change at a time – every few days – so you are assured it is either helping, doing nothing or hindering. If you add many things or change many things at once, it becomes frustrating trying to pinpoint what is going on.
It is important to prepare your cells and other biochemical pathways before stimulating them with methylfolate and methylcobalamin.
Following the lifestyle, dietary and environmental recommendations in the MTHFR Protocol post is a very important first step.
The next step is to begin with some basics – and these basics are as explained above:
- B vitamins (no B12 and no methylfolate)
- multivitamin/multimineral (no B12 and no methylfolate – plus no Iron or Copper)
- reducing stress by supporting lifestyle, diet and adrenals
Implementing these things may significantly improve your ability to tolerate methylfolate and methylcobalamin.
This is definitely a big start in the right direction and should help many people.
ALREADY TAKING METHYLFOLATE AND FEEL GREAT?
Excellent! However, it may be a ‘honeymoon’ period and in a few days or weeks, side effects may appear.
Discuss this article with your doctor and make appropriate changes to your protocol.
Just think of a bell-shaped curve.
Before you started taking methylfolate, you felt terrible. You began taking it and started to feel good. Day after day goes by and you continue to improve. In time if the above things are not corrected, you will begin to slide down the other side of the bell-shaped curve.
My whole point of this article is to prevent this from happening!
My goal is to keep you feel amazing!
I’ve made people go down the ‘other side’ by not pulsing methylfolate and by not preparing their biochemistry for it. It is much harder getting them back where they were than it is preventing them from getting side effects in the first place.
Do heed this warning.
I’ve seen it happen way too much – caused by me, caused by other doctors and caused by over-excited people feeling amazing and pushing their system too hard with methylfolate. Methylfolate is powerful.
Keep in control.
If you feel amazing, that could be a warning shot across the bow to actually stop taking the methylfolate for a day or two.
That is how I do it.
Remember, I am compound heterozygous MTHFR myself which means my MTHFR enzyme is reduced by about 70% in function.
Do I take methylfolate every day?
No. I take it when I feel mentally slow or use my brain heavily such as during conferences or writing long articles such as this 🙂 (but I won’t take it now because it is midnight and time to go sleep. I don’t want my adrenals to get taxed…)
Want to get more in depth and learn more nuances and see how it all ties together?
Get access to the recorded conference where I discuss folate, CBS, transsulfuration, oxidative stress, mitochondrial function, sulfation, detoxification and multiple genetic issues.
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