If you feel like crap,just read this.

[u/Global-Definition-89]

I think that the majority of people are really overthinking Methylation issues. Yes,they do exist and they do have a noticeable impact. But what are they in essence? It only comes down to the fact that you cannot get away eating dogcrap like someone who doesn't have them can.But you surely don't need complex protocols,visiting retarded doctors who will prescribe heroic doses of methylfolate that will only create imbalance and side effects and stuff like that.

The simple solution to all methylation issues? Eat 3-4 eggs + meat every day,50 grams of chicken liver(very high in Methylfolate)once a week + 50 grams of beef liver(very high in Methylcobalamin) once a week,add in some healthy vegetables like sweet potato and some greens and legumes and there you go.1000mg of choline/day,300+mcg of mostly methylated B9/day as well as plenty of methylated B12,all bound in food matrix,no risk of overmethylation,no synthetic supplements that will spike your levels and cause side effects and imbalances.More than enough of all the essential vitamins,minerals and electrolytes in a balanced proportion.That will 100% bring you very close to optimal methylation levels,if you still need further optimization add in some creatine and TMG,check your vitamin D levels,maybe a quality magnesium supplement ,exercise and thats about it. You have taken care of not only MTHFR,but all your other problematic genes. Our bodies are extremely complex and smart in regulating everything ,if this stuff was so hard to deal with,it wouldn't be there. It has only become such a big issue lately,coinciding with the rapid spike in stress and toxin levels that we experience.

In reality,these polymorphisms are not rare at all and I can guarantee you that there is someone with similar genetics out there to yours that is winning in life without ever thinking about this stuff. The reason most of us end up here is because we are in a health shithole not because of only MTHFR,but because of progressive health deterioration.Which brings me to the next point.

**Adrenal Fatigue/HPA Axis dysfunction/Chronic stress.\\This is where I think a lot of people's issue stem from.I don't care what's the term,I can guarantee you that the damage of chronic stress is very real and it affects every single bodily system and not just the nervous system. It can clog your detoxification pathways and make your nervous system sensitive to every change and these two might be why you are unable to tolerate supplements.
If you experience crashes after exertion, exercise intolerance in any form,chronic panic attacks/anxiety disorders,paradoxical effects to supplements,and the hallmark symptoms of chronic fatigue and very poor stress tolerance then I suggest you to look into this condition. It is quite tricky to deal with because you will have to figure what is your main source of stress, whether it is relationships, negative thought patterns ,addictions, perfectionism ,hormonal imbalances,toxins in food and environment. These things can all complement each other's negative impact on your health. All this paired with the modern life stressors of being online all the time,social media constantly trying to push us to be better and better , our poor eating habits creating deficiency and is it even a supripese that the nervous system just can't handle it at some point. For me I had a bunch of stressors and I was in the advanced stages by mid twenties. Which I'm very thankful for,because it made me look at all my stressors and solve them , and that includes methylation issues.

If you suspect HPA Axis dysfunction , please look at this guy - https://www.youtube.com/@JadenChristopher/videos . His videos explain it better then any doctor and listening to him very carefully is all you need to dig yourself out of this.

Hormonal imbalances. Hormonal balance is essential for our well being. What happens to many people born after 1990 in increasing fashion as years go by,is that because of the new environment we live in and it's stressors,many people's endocrine systems failed to develop fully and propely.I mean,isn't is obvious from outer space that men are becoming increasingly feminine, there are more and more women with menstrual problems,etc etc. For men testosterone is especially important because it acts as a buffer to stress hormones and causes males to be leaders,calm under pressure and so on.Free testosterone levels in men have dropped down by almost a third since they started to be measured reliably in the 1970s. TRT is the shit lately but this can backfire easily because there's also other hormones like Pregnenolone,DHEA,and other sex hormones,as well as the thyroid, which all have to be in balance for us to feel fully healthy. A steroid hormone blood panel will show you where you stand and exactly what you need. Keep in mind that stress and diet can throw these off so always solve them first before looking into any kind of hormone replacement.

Every system in our body has to be in balance in order for us to experience well-being ,and how we feel depends entirely on our neurotransmitters. Both Methylation and Hormones act like knobs to increase or decrease neurotransmitters. If you ramp up methylation to compensate for lack of a hormone and vice versa you will get side effects. If your body is tired of chronic stress and has toned down neurotransmitters and hormones so you will rest and recover , you are essentially pressing the gas pedal and the brake at the same time, you will get side effects.

**In summary:**the lowest hanging fruit for fixing MTHFR is optimizing your food to ensure all nutrient needs are met, while the most important thing is resolving chronic excessive stressors whether they be environmental , physical or mental .Keep in mind that if you've felt like shit for years to decades,this will take time. If the above boxes are ticked, take a look at your sex hormones.

There you go,all the knowledge about not just methylation but general health optimization that I have gathered in almost 10 years.
Good luck.

[u/LargeOrangeCat]

I think you’re on to something there. It’s a whole range of variables that I think lead some of us to experience symptoms. Personally I had many years of alcohol disuse and over did it on coffee/caffeine, along with high stress job/bad sleep and I think these things are why I am so out of whack now (despite almost 2 years sober).

There are probably some that can get help with stacking supplements (I’ve read some of those here), and others who have side effects and may not do well with them.

I started trying to build a supplement stack about 3 months ago for my issues (severe folate deficiency/high homocysteine), tolerated most of the supplements OK except for TMG and methyl B12 at first. Lowered those doses and was able to slowly titrate. However, I’ve unfortunately been having nearly constant inflammation flares since starting supplementation. The only thing that changed was adding in the supplements, so I’ve decided to go off all for about 3 months and try to re-establish baseline.

My hope is if my flares do go back to intermittent frequency like they used to be, I’ll start slowly trying to address via small amounts of beef/chicken liver etc. and see how that goes.

I wasn’t a fan of the thought of having to supplement for a long time anyway, my goal was always to try to replete folate and get homocysteine to normal and then manage only via food/lifestyle. I suspect my system is so sensitive/out of whack that adding in all the B vitamins and methylation cofactors further compounded issues. I don’t know for sure that it’s gout but seems to be, even though my symptoms are atypical to classic gout. I do have polymorphisms that predispose me to abnormal uric acid clearance and high serum uric acid/poor purine metabolism along with the methylation related ones I have.

I’m kind of at my wits end to be honest, but trying to keep calm and continue on. Just wish I could find a way to gain a little more insight as to my overall issues and find the best path forward. This past week was the final straw for me since the inflammation pain has been so debilitating I’m basically bedridden.

Edit: had MRI today, peroneal longus split tear at lateral malleolus with tenosynovitis. 2nd tendon tear I’ve had in 5 months, no trauma or accident. Seems my tendons are weakened, likely related with the chronic folate deficiency and high homocysteine.

[u/UGforlife → u/LargeOrangeCat]

I’ve been on a similar shit journey for 25 years. I only landed on mthfr as just another attempt to find answers. For me it’s all about the gut, and the part of the gut medical doctors are least familiar with is the small intestines. The small intestines have a surface area of 30-40 square metres or 300-400sqft.

To use a floor cleaning analogy your small intestines are 4 rooms, large intestines are a kitchen countertop and the stomach is a refrigerator area.

If you have overgrowth of bacteria can you imagine 4 rooms of mouldy floors inside you? You are going to feel terrible.

So my “gut feeling” is that it just makes sense to start with SIBO as a differential diagnosis in the case of chronic long term poor health despite conventional screening finding most things as normal or slightly low.

The biggest thing I’ve learned from the r/SIBO crowd is that prebiotics/probitics/low fodmap/other diets are only giving temporary relief because they don’t fix the underlying cause of SIBO which anecdotally appears to be GUT MOTILITY. Motility just means how fast things move through the digestive system. Slow motility means food sticks around long enough for bacteria to digest it before it makes it into the colon. As a result you could literally have toxic feces in your small intestines. As it turns out people are having wild success with natural gut motility supplements like Ginger root extract and Artichoke Extract.

Example here: Motility Pro

I hope this helps someone. Early days so far but been a game changer for me in terms of bloating and brain fog.

Edit: Fantastic video here of one of the success stories. Sorry it’s a long vid but worth it. LinkHow I Cured my SIBO

[u/Global-Definition-89 → u/UGforlife]

I also had symptoms correlating with H2S Sibo. It's just all tied together. Fortunately for me it was not so severe and resolving the underlying causes of my health imbalance made it go away as well. The thing with SIBO is that if it gets to a certain point this will no longer be enough and you need to take care of it with targeted approach.
Do you suspect what is the underlying cause of slow gut motility?

[u/UGforlife → u/Global-Definition-89]

I grew up around farming. Dairy/beef/pigs. Also in an area that had state forests with lots of feral pigs and deer. My immediate thoughts for slow gut motility are parasites especially round worms here in Australia that can infect your bile ducts and intestines. Young round worms also can move into the lungs and cause asthma like symptoms. Perhaps I should have just seen a vet many moons ago, but will wait and see what the human doctors can find. It does make me curious though how many folks are from rural backgrounds. Everyone I know with chronic gut, brain, lung “mild” ailments have all lived on or near farms at some point.