What is an undermethylated depressive supposed to eat?

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I am A1298c ++. I have had lifelong OCD, anxiety and depression. Folate makes me feel worse. I know that William Walsh recommends avoiding folates since they are a serotonin reuptake promoter, not inhibitor. I now know not to supplement with methylfolate, but am also concerned about too much folate in my diet. Is there a specific amount that I should be shooting for? Should I be supplementing Niacin?

I am currently on a high dose of an SSRI, so I can't use Sam-e etc. I don't know if the reuptake inhibition of 100s of mg of ssri is strong enough to deal with the folate in your diet. I am not 100% sure what I should be eating. I know that I should avoid things with folic acid and enriched flour (which can be difficult). I know that I need vegetables etc, but don't want to overdo it with the folate.

Part of it is OCD, but I get to the point where I don't know what to eat. Don't eat too much meat, especially beef as it can cause cancer. Be plant based, but don't consume too much folate. This is without even getting into histamine foods, etc. They also say that certain foods increase/decrease testosterone, etc and help depression aren't right for undermethylated depressives.

I know that everyone is different, but is there a rough guide for what I should be eating and avoiding?

I am also very active and need to consume 2000 calories a day.

Thank you in advance
 

drmullin30

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Folate makes me feel worse
Hi @anxiousguy I totally empathize with your condition as I am also homozygous for MTHFR 1298 and I also have MAO, and COMT SNPs like yours as well as many of the others that you have including BMHT and CBS, MTR, MTRR and VDR. It is this constellation of SNPs that cause your mental illness.

I also have many SNPS in the serotonin pathway so I have chronic low serotonin and I have suffered with severe panic and OCD for most of my life until I started using nutrigenomics to treat myself including supplementing L-5-methyl folate. I now take a high dose of L-5-methyl folate every day and it is essential to my mental health. L-5-methyl folate is implicated directly in serotonin synthesis through the MTHFR 1298 B4 biopterin pathway so folate is needed for serotonin production. I humbly suggest you reconsider your stance on methylofalate is it's likely essential for you given your SNPs. This is the case for me anyway.

I have always felt that Walsh was somehow off base about folate and wonder if he doesn't confuse L-5-methylfolate with folic acid. Folic acid is definitely bad for those of us with low serotonin. I can't tolerate even trace amounts of synthetic folic acid or I get full blown panic attacks. So make sure you have a good understanding of the many different molecular forms of B9 as well as the other b-vitamins as they all have very different effects. For my low serotonin I also use 5-htp, B6 and tryptophan to help increase my serotonin synthesis.

I also used to take high dose SSRI. Roughly 15 years ago I was taking 40 mg of citalopram per day just to keep the panic at bay. I will say unequivocally that it did nothing for my health and may have done damage to my neurology and getting off of it was one of the worst experiences of my life. SSRI withdrawal is pure torture but the side effects and health problems caused by the drug made it absolutely necessary. I haven't touched a pharmaceutical product in over ten years since I got off the citalopram. That industry does not have your health or best interests at heart and is entirely driven by corporate profit. You should be aware that SSRIs may be high in oxalates, sulfites or bromine and many other potentially harmful substances. Bromine and oxalates can cause thyroid problems (happened to me) and oxalates are a major issue for some including me. More on this later when I talk diet.

There are many reasons why the folate makes you feel worse. One is the COMT ++ SNP you have that makes you sensitive to too many methyl groups that come from supplements like SAMe, and methyl folate. I can't handle any SAMe supplementation either or I get panicky.

Another reason may be the need for vitamin b12. Folate and b12 must always be taken together as well as riboflavin (B2) and pyridoxine (B6) in order for it to work. In fact, for folate to work properly the entire methylation cycle needs to be functioning.

You have MTR and MTRR SNPS so you might consider supplementing with methyl b12 but you could start with hydroxy b12 as this is great to control the COMT issue. I used methyl folate and hydroxocobalamin together with great success several years ago to reduce my anxiety while I slowly introduced and raised my methylcobalamin (mb12) intake.

NAC is also very good for anxiety if it is driven by glutamate excess. Glutamate is the most excitatory neurotransmitter and can be toxic when in excess and cause severe anxiety. I have GAD1 SNPs that suppress the conversion of glutamine to GABA in my body so that also adds to my problem with anxiety. Folate and detoxification will increase glutamate so this is another treatment conflict I had to deal with. I'm on the advanced methylation or Freddd's protocol now so I don't take NAC anymore and I don't need it as I'm converting glutamate to GABA well now because my methylation cycle is working. Mercury toxicity will also increase glutamate and aggravate your CBS SNP if it's active. B6 is vital for the conversion of glutamate to GABA.

Do you know if you have glutamate driven anxiety? If you do have issues with excess glutamate, I used Kava Kava for years to help with this and it was a revelation for my anxiety. Now that I'm on the advanced methylation protocol though I don't need that anymore either.

As @GreenEdge mentioned TMG, it is also helpful for the BMHT SNPs that you and I have and I have taken TMG with success for years and it doesn't seem to trigger the COMT SNP.

Yet another reason folate can cause problems is that folate will likely cause neurological methylation start-up and detoxification symptoms which includes anxiety as neurons heal and come back online and heavy metals are eliminated.

Your CBS SNP may mean you have problems with your Trans-sulfuration pathway which will cause major problems for detoxification and liver function and may cause problems with glutamate as it does for me. You may be high in sulfites which are also anxiety inducing so you could consider a sulfite free diet and investigate whether you need to supplement molybdenum or alpha-lipoic acid to correct sulfuration issues if you have them. You can test your sulfite load with urine test strips to see if you have high sulfites. B12 and molybdenum help the conversion of sulfite to sulfate which is vital for anxiety control and methylation.

I also use diet to treat my condition and it has been crucial to my success. I eat a grain free, (I'm celiac), dairy free, sulfite free, sugar free, alcohol free, low oxalate ketogenic paleo diet. I don't eat any processed food whatsoever because of my myriad sensitivities and there are a limited number of supplement manufactures I can use due to contamination or additives. I cook all my own food and use as much organic as possible.

If I were you I would reconsider my stance on beef and meat. The cancer studies done on red meat were very flawed as they didn't distinguish between processed red meat and unprocessed red meat. Undermethylators need lots of high quality protein, iron, zinc and bioavailable b-vitamins which beef and red meet provide much better than any other food source. I also eat 200-300 grams of grass fed organic beef liver every week. Certainly processed red meat like hotdogs, bacon, salami and bologna are carcinogens but plain meat is a very good food for me anyway and I eat a lot of meat. Many members of this forum are trying carnivore or Lion diets with success. Meat doesn't contain antinutrients like grains, legumes or some vegetables so some find it is better for those with autoimmune issues.

Along with diet, if I were you I would determine ASAP if you have a problem with oxalates. I have learned in the last year that oxalates have been a major driver of anxiety and depression for me all my life ( I really wish I had figured this one out sooner). I have SNPs that impair my ability to detox oxalates and I have SNPs that encourage endogenous oxalate production under certain conditions. Oxalate crystals can contain heavy metals such as mercury, cadmium and lead and can deposit in joints and tissues including the brain and amygdala and cause symptoms. Since I have gone low oxalate my mental health has improved dramatically and I have been able to reduce the dose of many supplements. This is a quote from the sulfation article linked below:
"The WHO (World Health Organization) and the AMA (American Medical Association) probably made the biggest medical mistake in world history by discounting the seriousness of oxalate overload because it impairs sulfation and sulfation is the key to life."

OK here are some good resources to help you and I've attached a PDF book by Amy Yasko that's been very helpful for me to understand my genetics and epigenetics.

http://heartfixer.com/AMRI-Nutrigenomics.htm - great explanations of SNPS and their impacts
https://sallyknorton.com/ - great resource on oxalates
https://mthfrsupport.com/2018/03/understanding-sulfation-and-oxalate/ - details problems caused by oxalates for people with methylation issues
https://acu-cell.com/ - great resource for deficiency and toxicity symptoms of major nutrients as well as interactions between them

I hope you find this helpful and please don't hesitate to contact me directly if you want.
 

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Thank you for the responses.

@GreenEdge Can I take TMG and NAC with 300mg of zoloft? Would the TMG do what folate does and promote reuptake instead of inhibition?

@drmullin30
I've tried folates and they always make me feel bad. I noticed that when I started eating lots of leafy greens and avocados, that it would make my mental health problems worse. When I was given Deplin by a psychiatrist, it literally made me suicidally depressed. I've tried small amounts of L5MTH etc and it always seems to have that effect on me.

It is partly an OCD thing, but I get very confused as to what I can eat. Avoid sugar, gluten, high sulfate foods, high histamine foods, dairy, etc. Don't eat too much meat either. I NEED to eat calories since I am very active, but it is hard when I can't have anything. IT seems like undermethylated depressed patients need protein, and I love protein! There are so many contradictions and paradoxes.

Thank you
 

drmullin30

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when I started eating lots of leafy greens and avocados, that it would make my mental health problems worse.
These foods are also really high in oxalates so you should definitely look into that.

I've also updated my post above so make sure you've re-read it.

I also had major problems with anxiety and depression when I first started taking folate but I realized that it was all start-up and detoxification. Unfortunately, the path to health sometimes goes through a worsening of symptoms but in my case it was well worth it. I suspect you have other treatment conflicts within your SNPs against folate as well that need to be considered. Do you have a 23 and me report or similar?

When you take folate, what other b-vitamins are you taking with it?

Have you tried folic acid or folinic acid in addition to methyl folate? Did you have side effects?
 
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GreenEdge

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DogLover

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I have always felt that Walsh was somehow off base about folate and wonder if he doesn't confuse L-5-methylfolate with folic acid.
I've also wondered this.

I can't tolerate even trace amounts of synthetic folic acid or I get full blown panic attacks.
If you don't mind, I have a few questions about this:
1. How fast those symptoms occur after ingesting folic acid? Is it something that happens within a few hours or does it take a few days?
2. How long do symptoms last?
3. Are there any hidden sources of folic acid? It is my understanding that actual folic acid is mostly present as an artificial additive in processed foods.

Do you know if you have glutamate driven anxiety?
Is there a way to test for this? NAC? Kava kava? How quickly would they respond? Hour? Day? Week?

Along with diet, if I were you I would determine ASAP if you have a problem with oxalates.
Other than an elimination diet, is there a quick and dirty way to test if oxalates are a personal driver of anxiety?

Just a bit about me: Lifelong anxiety and depression. Tapering from Effexor at 10% per month for 1.5 years, current dose at 4.78mg/day. Clean diet with absolutely no sugar, gluten or processed foods. Eating grass fed beef, too much coconut oil, all veggies, nuts and fruits. I'm currently experiencing episodes of anxiety/panic/terror that I suspect correspond to effexor tapering.
 

DogLover

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Folate makes me feel worse.
If you don't mind, could you expand upon this a bit? Is this something you notice quickly after ingesting folate? Does happen over a few days? More gradual? How long does it take for it to go away? What does it feel like?
 
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@DogLover

I noticed when I took Deplin, which is obviously a huge dose, that I became EXTREMELY depressed. Also, when I started eating lots of leafy greens and taking L5MTHF, I would notice that my mood dipped. I am assuming that that is what Walsh is referring to as far as it acting as a serotonin reuptake promoter instead of inhibitor. The problem isn't not enough serotonin, but how long..
 

drmullin30

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If you don't mind, I have a few questions about this:
1. How fast those symptoms occur after ingesting folic acid? Is it something that happens within a few hours or does it take a few days?
2. How long do symptoms last?
3. Are there any hidden sources of folic acid? It is my understanding that actual folic acid is mostly present as an artificial additive in processed foods.
The onset of symptoms is within minutes and the symptoms will last a few hours to days depending on the dose. Folic acid is found in any fortified grains or cereals which is almost all flower and anything that's fortified with b-vitamins.

Is there a way to test for this? NAC? Kava kava? How quickly would they respond? Hour? Day? Week?
I imagine you can get a neurotransmitter profile done that might detect high glutamate. Also, if you have GAD1 SNPs and anxiety it's pretty much a guarantee that you have high glutamate. High glutamate will also cause heart arrhythmias and panic attacks.

NAC will work almost instantly to calm glutamate induced anxiety as long as your cysteine and sulfites aren't already high. NAC combines with glutamate and glycine to form glutathione and helps quench the anxiety that way.

Kava Kava is more subtle as it's not entirely known how it works but it's suspected it acts like a glutamate reuptake inhibitor and it may raise GABA and serotonin. Many people have what's called reverse tolerance. E.g. you have to take it for several weeks before it starts to work. This supplement was a godsend for me when I was going through a lot of detoxification which will raise endogenous glutamate.

Other than an elimination diet, is there a quick and dirty way to test if oxalates are a personal driver of anxiety?
You can get a urine test for oxalates but it false negatives are possible if you aren't eliminating oxalates at the time of the test. Here are some websites with good info about symptoms and effects:

https://www.healthline.com/health/what-to-know-about-primary-hyperoxaluria#diagnosis
https://sallyknorton.com/tag/hyperoxaluria/
https://sallyknorton.com/symptoms/

I'm currently experiencing episodes of anxiety/panic/terror that I suspect correspond to effexor tapering.
I can empathize with this. SSRI withdrawal is brutal and panic is a symptom. I also had what are called "brain zaps" or "brain shocks".

FYI I am homozygous for MTHFR 1298 and I need to take very large doses of L-5-methylfolate to function. Without it I become severely anxious and depressed.
 

DogLover

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@anxiousguy @drmullin30

Thank you so much for your replies.

Fortunately, my symptoms are back under control. Whew! The only way I can describe the feeling is absolute terror. I wouldn't wish it on my worst enemy... not that I collect them or anything.

It seems that there can be quite a long lag time between anti-depressant withdrawal and dose reduction. My experience puts that lag at a month or more, especially if those cuts are not particularly large. I've been tapering by 10%/mo, but if a few months go by and things are good I get cocky and decide to cut a little more. It always takes a month or more for those additional cuts to cause trouble. That's a hard lesson to learn due to the lag time. I've learned to be in no hurry, if it takes another few years to get off these things, so be it.

Aside from the anti-depressants, I've had such good results over the last year that I really want to shout it from the rooftops! I found that gluten is absolutely murder on my mood. I feel SO MUCH BETTER after cutting it. The road was confusing, however, because the symptoms from gluten don't show up for about three days after ingestion and seem to last a week or two. I also was able to curtail my anxiety by treating candida, which I will admit I'm not 100% sure about as there is not easy way to test candida like bad actors in the diet. However, treatment coincides with improvement.

I will explore those links and experiment with NAC. Thanks again!
 

dannybex

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The onset of symptoms is within minutes and the symptoms will last a few hours to days depending on the dose. Folic acid is found in any fortified grains or cereals which is almost all flower and anything that's fortified with b-vitamins.
Are you aware that Dr. Russell-Jones of b12oils fame says folic is perfectly fine to use as long as one has sufficient B2?
 

drmullin30

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@dannybex I'm aware and I use his products but that hasn't been the case for me. I take at least 50 mg a day of b2 and I still can't handle any folic acid.

If you are like me and have several homozygous SNPs on genes in the folic acid conversion pathway namely, MTR, MTHFR, MTHFD and MTHFS then I'm not sure folic acid is the right form.

The MTHFS SNP in particular causes major problems with folic acid and folinic acid. The problem with this is that folic and folinic acid normally acts as a regulator of folate metabolism by inhibiting enzymes in this metabolism. In particular, it inhibits the serine hydroxymethyltransferase (SHMT) enzyme, which normally is the main enzyme that converts tetrahydrofolate to 5,10 methylenetetrahydrofolate, which in turn is the substrate for making methylfolate. So, a deficiency in MTHFS will allow folic acid and folinic acid to rise inhibiting SHMT, which will lower 5,10 methylenetetrahydrofolate, and thus will also lower production of methylfolate, which is needed by methionine synthase in the methylation cycle.

So for those of us with the MTHFS SNP, folic acid basically shuts down methylation.
 

dannybex

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I don't use folic myself, was just pointing it out. I use both folinic and more recently methylfolate, both of which help me sleep.
 

drmullin30

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@dannybex yes I've been able to lower my dose significantly in the last couple of months. I think it's partly the oils, partly the oxalate treatment program and partly the lithium I'm getting from the Concentrace supplement. All my dosages are down for all of my supplements since starting those three things this year.
 

DogLover

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@anxiousguy

I noticed that in your bio it says "Very little processed food/dairy/gluten." I cannot speak to processed food or dairy, but I know from personal experience if I eat ANY gluten it will cause horrible depressive symptoms. I've tested this three times and each time symptoms returned. I would suggest if you suspect gluten being a symptom driver, eliminate it with extreme vigilance for two weeks and assess your symptoms. Should you try this, read your labels, because there is wheat in just about everything that comes in a box, can or bag. For me, if I have a large portion of gluten, such as a cracker or slice of bread, symptoms take somewhere in the 1.5 to 2 weeks to lift.

@drmullin30

I've had a day or two to read about oxalates and came across a thing or two, if you could be so kind as to weigh in... I've read that a common driver of oxalate overload is a lack of bile and digestive enzymes. The theory goes like this: Without bile, consumed fats do not get properly broken down and end up binding to free calcium and passing them in the stool. Oxalates in the diet are normally bound to calcium rendering them harmless, but are unable due to the lack of calcium. So, the trick to removing oxalates, is to support bile production and supplement with calcium prior to consuming oxalates along with removing high oxalate foods.

Two questions:
1. Have you treated your oxalate sensitivity with calcium supplements?
2. Have you looked into your digestive system as a possible cause of oxalate sensativity?

I ask this because I'm ready to test for oxalate problems due to the fact that I showed high oxalates in an OAT I took a while back, but after cutting out everything from my diet except veggies, meat, fruit and nuts, I'm finding the prospect of cutting my non-meat choices in half a little unsettling.
 
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drmullin30

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Two questions:
1. Have you treated your oxalate sensitivity with calcium supplements?
2. Have you looked into your digestive system as a possible cause of oxalate sensativity?
Yes, I use calcium citrate to help absorb oxalate in the gut and to help prevent kidney stones. I need to supplement calcium anyway as I don't eat dairy, grains or nuts and I started having calcium deficiency symptoms years ago when I started methylation protocols before I started low oxalate.

I can tell when I'm dumping oxalates as I often need more calcium during those times (I know based on deficiency symptoms) to bind to the oxalic acid that gets dumped into my gut and bloodstream. I also try and take all of my electrolyte minerals in citrate form. Magnesium citrate, potassium citrate, zinc citrate, etc. Citric acid (citrate) dissolves oxalates so it helps rid the body of oxalate deposits. That's why I also drink at least one lemon's worth of fresh squeezed organic lemon juice every day. I also use a supplement called Chanca Piedra which breaks down oxalate crystals, kidney stones and reduces endogenous oxalate synthesis and helps deal with hyperoxaluria symptoms.

Bile, digestion and calcium absorption is definitely an issue per the theory as you mentioned. I have been taking ox bile and digestive enzymes with HCL for years to help with digestion. Taurine is also good for bile production and I supplement with that. Copper is also an important mineral for bile production so make sure you aren't copper deficient. I also use probiotics as they help break down oxalates in the gut.

I've struggled with digestion issues my whole adult life until I went low oxalate last year and things started to improve dramatically. Oxalates cause leaky gut and can make candida worse and they block absorption of important nutrients. All of which makes oxalate sensitivity and toxicity worse so it's a vicious cycle that has taken me years to break.

Hope this info is useful.
 

DogLover

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Yes, I use calcium citrate to help absorb oxalate in the gut and to help prevent kidney stones.
Can you manage oxalate with calcium supplementation alone, or do you really need to exclude them from your diet? (Eliminating nuts, sweet potatoes and leafy greens from my diet is proving difficult.)
 

drmullin30

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Can you manage oxalate with calcium supplementation alone, or do you really need to exclude them from your diet? (Eliminating nuts, sweet potatoes and leafy greens from my diet is proving difficult.)
In my case I had to eliminate them from my diet to see improvement and recovery. I've not heard, or read of anyone who has oxalate sensitivity or toxicity being able to manage with just calcium supplementation. If you look into the sheer volume of oxalates in high oxalate foods, you'll see you have to be taking huge doses of calcium to counteract that much oxalic acid and that may cause other problems due to mineral imbalances. In addition, if you have an oxalate problem, your body has been storing and depositing oxalates all throughout the body's tissues and you won't eliminate those deposits until you are consuming a low enough amount usually less than 50 mg per day.

I get it, getting down to less than 50 mg per day of oxalates is very difficult and results in a very restrictive diet which can be depressing and overwhelming. If you have a serious oxalate problem like me, my suggestion is, lots of meat. I eat a lot of meat and eggs to get my calories.

I would try it for several weeks, if you don't see results in your health that are worth the sacrifice than you can stop. In my case, it was beyond worth it. My physical and mental health have been steadily improving since I went low oxalate last year and I've been able to cut back on my supplement dosages so I'm saving money. This last year I feel like I've been aging backwards so it's been amazing.
 
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