Losing Progress, Looking for Next Step

[johnymous]

I've been dealing with health issues the past 6-7 years and while making some serious headway, I've recently started to backslide and am not quite sure of my next step. I'm starting to feel like I'm entering the final phase of my ability to manage symptoms and looking for a helping hand in finding some direction.

There's a lot to say, but I'll try to keep it brief for anyone kind enough to read:

~2012: Eating typical American diet. Having cyclic episodes of extreme tension such that I couldn't function. Like panic attacks without the mental aspect. (now believe to be histamine related). Having difficulty getting through work. Unable to relax ever. 195 lbs. Lots of symptoms hanging around for years seem to be coming to a peak such that I could barely make it through my day at work (desk job).

~2013: stumbled upon the "elimination diet" and felt the best I'd ever felt in my life. Radical dietary change. Alternating between periods of extreme fatigue and mental sluggishness to extreme energy and near manic mental states. 175 lbs, weight loss attributable to healthy dietary change IMO.

~2014: daily life much better, but still sink into periods of either extreme fatigue or extreme tension. Tension states tend to "peak" in episodes lasting anywhere between 1-4 hours where I am completely dysfunctional and my whole body feels like it's about to cramp. 160 pounds, weight loss no longer easily explained by diet.

~2015: Daily life declining, have eliminated certain other foods to improve energy levels, still having periods of extreme tension. Bowel movements only ever 3-4 days, weight drops to 145lbs. I started seeing Integrative doctors. Intolerance to exercise starts developing. 24-72 hours following weight lifting and my body feels like a hot swampy mess of acids and fatigue. Best description I can offer, unfortunately.

~2016: After some nutritional therapy (magnesium, VitD, B12, amino acids, lithium orotate, others) I crept back up to 165ish pounds over ~8 months. Diet was limited to only peanut butter, chicken, sweet peas, cauliflower, and green beans at this point. Felt incredible despite limited diet. Was treated for viral infection, parasite, and fungal overgrowth. Had no issues with any. No issue with B12 at this point either.

~2018: Very slow decline back to 150 pounds. States of tension becoming the new normal. Foods limited to chicken, sweet peas, and green beans only. Supplements include GABA, Reduced Glutathione, Magnesium, Tri-Salts, Vitamin D, and occasional digestive enzymes. Enzymes start shifting me towards tense states.

~2019: Took 1 x B12/Methylfolate/P5P capsule by Jarrow Formulas and my entire body felt like it was on fire. I couldn't sleep for 72 hours, couldn't relax, couldn't think, was one of the most intense episodes of my life. Feel anxious just thinking about it. Down to ~145 pounds, only relief comes from skipping meals. I started seeing another doctor in my (new) area.

~2020: Treated for manganism via Liposomal EDTA. Treated with minocycline for walking pneumonia, though treatment made me tense again. Fluconazole was recommended to be taken every couple of days with antibiotic therapy. 1st day after taking fluconazole was great, the following day was pure misery. Took metronidazole and symptoms were much improved. Any B12 supplementation immediately worsens symptoms.

Quick 8 Month summary:
Taking metronidazole, liposomal EDTA, lithium orotate, Vitamin D, magnesium citrate, tri-salts, hydrolyzed collagen, melatonin at night, NAC, reduced glutathione, GABA, and Vitamin A, spore probiotics at lunch. Weight creeping back up. Was able to work out again, fairly strenuously, was sleeping well, couldn't skip a daily dose of metronidazole, or would start losing weight again. Bowle movements become 2-3 daily, quality of life much improved. I would start feeling really good again and do something silly like go for a run. I would almost immediately trigger a backslide where I was again faced with burning GI, weight loss, and tension.

Last 3 months:
I started realizing that my tension episodes were very similar to what I was reading from people posting about Mast Cell Activation Syndrome(MCAS). I started realizing that poor responses to B12 were very similar to what I was reading by people posting about Methylation issues. I started realizing that skipping meat dramatically reduced my histamine-related symptoms. I felt calm, burning GI would disappear and started putting on weight. Crept back up to 155 pounds. Realized that burning symptoms in GI, arms, legs, feet, etc. were greatly reduced with OTC antihistamines. Stopped taking metronidazole and antihistamines seemed to offer the same benefit of reducing burning symptoms, constipation, and weight loss.

Last 30 days:
Any meat sets my symptoms off tremendously. Have been almost-vegan for the past 3 weeks or so, though have eaten meat with 3-4 meals following cognitive issues. Seems like nothing can stop the momentum of histamine/tense state. Weight continues to drop, states of tension becoming the normal again, can't exercise—even to walk my dog in the evening. Have started treatment for possible mercury toxicity with an activated silica product (IMD by quicksilver), though tests were inconclusive. I feel like my doc has kind of ran out of ideas and isn't very attentive anymore.

New Supps:
Taking ~175mg SAM-e in the evening seems to improve sleep and mood.
B12 Intolerance seems to be better, but still problematic. Taking 10mg DAO with meals. Taking 60mg Allegra (fexofenadine) 2x daily. IMD (for metal detox)

Notes:

The last month I've read a lot about the methylation cycle and dynamics of histamine/mast cell activation. I feel both offer a much better vocabulary for explaining my symptoms but I've still not had any great epiphanies. I do think that my Tense/Tired states might be expressions of under/over methylation.

The only relief I can be guaranteed is by skipping meals. Over the last 5-6 years, my momentum has been a reduction in caloric intake, a reduction in daily meal count, an increase in tension, and a loss of weight. When I can't bear things, I skip a meal and things level out briefly.

I feel like I've been coming up with a lot of "hacks" without addressing some underlying issue. I'm not in the "danger red" zone of malnutrition yet, but my reduction in meat and necessary skipping of meals again is pushing me in that direction faster than I'd like.

I'm looking for some new avenues to explore the possible underlying causes. I've got a lots of recent test data, including SNP analysis where there are some possible red flags.

I'm in the WNC area, but would also love to find a practitioner that specializes in methylation and/or histamine related issues to consult with. Any advice, similar experiences, or random thoughts will be greatly appreciated. I've started to feel like I'm circling the drain lately and none of my old tricks seem to be working. I'm currently with an Integrative Doc that's 8/10 IMO, but I feel like their blinders are on looking for what they're expecting to find. Feeling like it's time for a fresh set of eyes.

On my radar is to get a Genova Methylation panel ran, as well as a blood histamine to confirm that my burning/tense states are actually reflective of elevated histamine levels.

Thank You

I'm already feeling apologetic for the length of this post, so I'll stop here. I'm more than happy to provide elaboration to anyone that's kind enough to have a discussion with me.

 

[Judee]

Any meat sets my symptoms off tremendously.

This seems to fit with something another member said in his recent blog post here: https://forums.phoenixrising.me/blo...cfs-a-complex-fungal-intolerance-part-4.2671/

 

[johnymous]

This seems to fit with something another member said in his recent blog post here: https://forums.phoenixrising.me/blo...cfs-a-complex-fungal-intolerance-part-4.2671/

Thanks for the thought though, oddly enough, any type of anti candida treatment really makes things worse. I used to find benefit from several anti candida therapies, but now it makes things much worse. Also, a diet heavy in meat used to be my strongest refuge.

 

[andyguitar]

When I can't bear things, I skip a meal and things level out briefly.

Skipping meals will alter your blood sugar levels. Have you been tested to see if everything is normal with your blood sugar levels?

 

[johnymous]

Skipping meals will alter your blood sugar levels. Have you been tested to see if everything is normal with your blood sugar levels?

I have, several times, though never in a continuous rate like someone might using finger pricks or etc.

Tests always resulted in normal ranges

 

[Seadragon]

Have you been thoroughly investigated for food allergies eg Coeliac?

Also have you had tests done for stomach ulcers (H.Pylori) and possible issues with the gall bladder?

I can definitely relate to your description of post exertional malaise (PEM) feeling like "a hot swampy mess of acids and fatigue". I experience that also but do not have the same diet related issues as you.

 

[johnymous]

Have you been thoroughly investigated for food allergies eg Coeliac?

Also have you had tests done for stomach ulcers (H.Pylori) and possible issues with the gall bladder?

I can definitely relate to your description of post exertional malaise (PEM) feeling like "a hot swampy mess of acids and fatigue". I experience that also but do not have the same diet related issues as you.

Neg for celiac on multiple occasions, need for h pylori within past several months, had a Ultras sound of the gallbladder a year or so ago and was normal.

Re: PEM ( didn't know it was a thing, thanks for the heads up) it seems to become an issue when i hit low points. I think it's definitely reflective of something deeper, I'm just not sure what. I have histamine-like reactions to exercise also, which happens immediately after more aerobic stuff, out there PEM follows a weight lifting workout mostly.

I thought it might be nutritional, but copious amounts of amino acids pre or post workout don't seem to make a difference in way or another.

 

[Wishful]

oddly enough, any type of anti candida treatment really makes things worse. I used to find benefit from several anti candida therapies, but now it makes things much worse.

I don't think it's odd. They made me feel worse too, and did nothing to reduce any symptoms. Candida might be a problem for some people, but others have more problems with the treatments.

I too had a problem with meats for a couple of years. Later, I could tolerate a bit of beef, while a sixth of that amount of pork would trigger symptoms, and even a bite of chicken was too much. I eventually figured out that carnitine was involved, and possibly the problem was with palmitic acid specifically. A bit of supplemental carnitine with my meal prevented the flare-up of symptoms. Your problem sounds different, but if you are more sensitive to some meats than others, and carnitine wasn't one of the amino acids you'd been taking, you might give it a try. After taking carnitine with meals for several months, my problem with meats went away. It's still a mystery why it happened, and why it went away.

 

[johnymous]

After taking carnitine with meals for several months, my problem with meats went away. It's still a mystery why it happened, and why it went away.

That's so odd.

I haven't tried carnitine before, and have also eaten mostly chicken and i can't really say how i do with other meats. Ive tried some pork lately, and it seems to effect me just the same.

 

[Pyrrhus]

What you describe is probably quite familiar to many people on this forum. The common thread behind many of your observations is nerve inflammation. Many people have a hard time understanding how their gastrointestinal issues could be caused by nerve inflammation, but remember that the muscles that pump food through the intestines are controlled by autonomic nerves.

When these autonomic nerves are inflamed, they may not provide sufficient stimulation to the gastrointestinal muscles, resulting in constipation/gastroparesis. This constipation/gastroparesis can then lead to small intestine bacterial/fungal overgrowth (SIBO), increased stomach acid, gastroesophageal reflux, larygopharyngeal reflux, post-nasal drip (upper airway cough syndrome), and reflux-initiated spontaneous vomiting.

There is no magic pill to stop nerve inflammation, unless you can identify the cause of the nerve inflammation. One thing that seems to help with nerve inflammation is to make sure that you are taking a balanced ratio of calcium to magnesium, along with a steady supply of electrolytes. Nerves need a stable concentration of electrolytes and minerals to function properly. For me personally, I take two glasses of an electrolyte mix (Vitalyte) per day. I also take 160mg of magnesium citrate and 400mg of calcium citrate per day. (For a calcium-to-magnesium ratio of 2.5, which is roughly the ratio of calcium's RDA ~1000mg to magnesium's RDA ~320-420mg. Your ideal ratio may vary.)

Since chronic nerve inflammation can lead to a reduced methylation capacity in the inflamed nerves, one can take steps to boost the methylation capacity in the inflamed nerves. The first step to boosting methylation capacity is usually to take B vitamins. However, if the methylation capacity is reduced greatly, one may find that they can not tolerate even low doses of the two B vitamins methyl-folate and hydroxo-B12. In this case, you may start with a B-vitamin complex like "B Minus" from the company Seeking Health, which does not contain the two problematic B vitamins. Once you can tolerate this B-vitamin complex, you can then slowly work in some methyl-folate. Once you can tolerate the methyl-folate, you can then, very slowly, work in small doses of hydroxo-B12. This is the strategy that worked for me, although your results may vary. It took almost two years, but I can now tolerate 250 micrograms of hydroxo-B12 per week, with nothing more than a slight headache lasting 1-2 days after each hydroxo-B12 dose. I also take a very low daily dose of potassium (100mg potassium gluconate) to reduce the side-effects of the B vitamins. (Higher doses of potassium can be dangerous.)

Besides B vitamins, there are other supplements that can boost methylation capacity. One of those is creatine. You only need a low daily dose (500mg) of creatine monohydrate, taken with food and liquids, to see an effect. I mention creatine because creatine also has the effect of speeding up digestion, which is a nice side-effect. Be sure to take the creatine with a little food and liquids, in order to avoid any increased stomach acid or nausea.

By the way, some ME patients report that they can not tolerate red meat, but have no problem with poultry or fish.

Hope this helps.

EDIT: Clarified that 2.5 is only a rough ratio.

 

[Wishful]

I agree that it was odd. I did figure out that I could tolerate ~180 gms of beef, ~30 gms of pork, and pretty much zero chicken. Then while reading a research paper I looked up 'carnitine', saw a list of foods that contained it, and noticed that pork had about 1/6th the amount that beef had, and chicken had nearly none. That was a strong enough coincidence to convince me to buy some carnitine and some BBQ chicken. I ate half the chicken and a tsp of carnitine...and didn't get the expected worsening of symptoms. It worked with pork and larger portions of beef too.

I know that carnitine is vital for transferring fatty acids into mitochondria, but I haven't figured out why having extra fatty acids in cytoplasm that aren't passing into mitochondria would cause problems.

I just checked for new papers on carnitine function. It seems a bit more complex now: "Other roles for carnitine include buffering of the acyl coenzyme A (CoA)-CoA ratio, branched-chain amino acid metabolism, removal of excess acyl groups, and peroxisomal fatty acid oxidation." How an I supposed to figure out which role was involved with my increased symptoms? The problem went away, so I can't test any theories about it. I did post about it here, and also sent my observations to the OMF, in the hopes that some expert would make a connection..and hopefully make a breakthrough in understanding ME.


Lesson learned: paying attention to how many gms of which variety of meat (or other food) that makes your symptoms change can lead to a treatment (and even cure!). Science sometimes depends on small--but repeatable--differences.

 

[Wishful]

One thing that seems to help with nerve inflammation is to make sure that you are taking a balanced ratio of calcium to magnesium,

Does the ratio really matter? I think the body is quite good at doing its own balancing. Take too much of one nutrient, and the body excretes the excess. So, if you took too much Mg for the Ca, the extra Mg would be excreted. Yes, there are probably people with malfunctioning balancing networks, so they would need to be more careful of intake ratios, but that should be rare.

 

[Pyrrhus]

Does the ratio really matter? I think the body is quite good at doing its own balancing. Take too much of one nutrient, and the body excretes the excess. So, if you took too much Mg for the Ca, the extra Mg would be excreted. Yes, there are probably people with malfunctioning balancing networks, so they would need to be more careful of intake ratios, but that should be rare.

A very good point, thanks. A healthy person should, in theory, be able to balance electrolytes/minerals without any supplementation whatsoever. But people with ME often have hypothalamic dysfunction, which can impair the normal balancing of electrolytes and minerals. Furthermore, inflamed nerves may be more susceptible to otherwise minor swings in mineral balance.

 

[Wishful]

Furthermore, inflamed nerves may be more susceptible to otherwise minor swings in mineral balance.

In that case, you can't state a 'proper' ratio, since it varies with the individual, and maybe time of day, other foods, and various other factors. It would be up to the individual to experiment to find out what supplements work for them at what dosage at what time of day.

 

[Pyrrhus]

In that case, you can't state a 'proper' ratio, since it varies with the individual, and maybe time of day, other foods, and various other factors. It would be up to the individual to experiment to find out what supplements work for them at what dosage at what time of day.

Exactly, thanks for pointing that out. The ratio of of 2.5 is only a starting point, based on the ratio of calcium's RDA (~1000mg) to magnesium's RDA (~320-420mg). I will edit my post to make this clearer.

 

[Wishful]

I can agree with starting points. Personally, I'd start with only one supplement--whichever seemed more likely to be a factor--and see if it had any effect (good or bad). Then I'd try the other one to see if it had any effect. Then, if anything worked, I could try optimizing.

 

[johnymous]

However, if the methylation capacity is reduced greatly, one may find that they can not tolerate even low doses of the two B vitamins methyl-folate and hydroxo-B12. In this case, you may start with a B-vitamin complex like "B Minus" from the company Seeking Health, which does not contain the two problematic B vitamins. Once you can tolerate this B-vitamin complex, you can then slowly work in some methyl-folate. Once you can tolerate the methyl-folate, you can then, very slowly, work in small doses of hydroxo-B12. This is the strategy that worked for me

Besides B vitamins, there are other supplements that can boost methylation capacity. One of those is creatine.

EDIT: Clarified that 2.5 is only a rough ratio.

I completely agree that nerve issues are likely a factor. Any therapy targeting autonomic nerve health such as Yoga, deep breathing, etc. has offered some benefits—transient in most cases, unfortunately.

I can't yet tolerate B12, though it seems I can tolerate it better than 6 months ago. My last attempt was roughly 50mcg hydroxy/adenosyl and I noted a vast improvement in sleep quality for the first night, then slowly started having histamine reactions. Perhaps a response to excess toxins being kicked into my system?

It's very helpful to read your description regarding the order in which you added supplements. My own naivety regarding B vitamins has led to my fear of anything with a "B" in it. I took a methylB12/THF/p5p supplement last year and was up for 72 hours straight. It was probably the single most miserable episode I've ever had.

I might give the B-Minus supplement a try, and then see what working in some methy-folate will do. I don't think I have issues with excess methyl groups, at least not so much to shy away from some low-dose self-experimentation. I seem to tolerate SAM-e well enough.

You wouldn't happen to know of a decent resource offering an overview (in simplified format) of the approach for getting one's methylation up to snuff again? I've been digging through several resources—learning a lot—but I am still having a bit of trouble determining an order of operations.

Thanks for taking the time to comment, it was very helpful!

 

[Wishful]

My own naivety regarding B vitamins has led to my fear of anything with a "B" in it.

You're not the only one. I've had bad reactions to B2, B3, and B12. The latter two triggered strong suicidal moods. Then there are all those claims that "(supplement or herbal remedy) is good for you!"...yet for me they trigger severe ME symptoms. We're all different and need to experiment to see what works for us as individuals.

 

[Pyrrhus]

My last attempt was roughly 50mcg hydroxy/adenosyl and I noted a vast improvement in sleep quality for the first night, then slowly started having histamine reactions. Perhaps a response to excess toxins being kicked into my system?

I don't think anyone can state with certainty why these reactions occur. The best we know is that there appears to be a localized B-vitamin deficiency in inflamed nerves (not a body-wide deficiency) and that correcting this deficiency can cause temporary neuro-inflammatory symptoms. Mast cells may play a role in this inflammation, but this doesn't necessarily have anything to do with histamine. (Mast cells can be activated by other means, not just by histamine.) I doubt toxins would play any role here.

You wouldn't happen to know of a decent resource offering an overview (in simplified format) of the approach for getting one's methylation up to snuff again? I've been digging through several resources—learning a lot—but I am still having a bit of trouble determining an order of operations.

Unfortunately, I don't. There are a number of websites out there that present a simplified view of boosting methylation capacity, but these websites tend to be a subtle mix of fact and hypothesis:

• Ben Lynch is one of the big names that has presented hypotheses implying that reduced methylation capacity is the cause of some disease, and that genetics may play a big role. His hypotheses are based on the scientifically-accepted "methylfolate trap", but his hypotheses are untested, and they may confuse cause and effect.
• Amy Yasko has similarly adapted the "methylfolate trap" to develop hypotheses regarding autism spectrum disorder. There is published evidence that patients with autism spectrum disorder may have a B-vitamin deficiency in the brain, but not in the body, which would imply reduced methylation capacity in the brain. However, Amy Yasko's hypotheses remain untested, and may confuse cause and effect.
• Rich Van Konynenburg and @Freddd have adapted the "methylfolate trap" for ME/CFS, and their hypotheses and treatments are widely discussed here on Phoenix Rising.

So, in terms of order of operations, I can only offer my humble opinion. I feel that correcting electrolytes and minerals are most important and that correcting B vitamins should come next. Theoretically, that is all you would need to do to escape the "methylfolate trap", but there is always more you can try if you wish:

• You can try N-acetyl-cysteine (NAC) to boost the critical antioxidant glutathione in the inflamed nerves. Inflamed nerves tend to be low in glutathione, which may aggravate the inflammation. Glutathione appears to be required in order to import B12 into the cell, so cells that are low in glutathione may have a hard time utilizing B12. Furthermore, a reduced methylation capacity theoretically slows the production of glutathione, so a reduced methylation capacity may worsen low glutathione levels. Unfortunately, there are a number of misconceptions floating around that NAC is "bad for methylation", but I don't see any scientific basis for these. At first, you should expect a large unpleasant reaction from NAC, but if you start low and go slow you should be able to tolerate daily NAC after a couple of weeks. For some people, Glycine supplements may be more effective in boosting glutathione.
• As I mentioned before, you can try a low dose of creatine. Creatine, in the form of phospho-creatine, is a vital energy buffer in cells, especially muscle cells and nerve cells. A large portion of the body's methylation capacity is spent on synthesizing creatine, so if you supplement with creatine you are effectively freeing up a large portion of the body's methylation capacity for other uses. As with NAC, you might expect a large unpleasant reaction at first, but if you start low and go slow you should be able to tolerate low-dose creatine after a couple of weeks. As with B-vitamins, low-dose potassium can alleviate this reaction somewhat. Remember to take the creatine with food and liquids to avoid gastrointestinal upset.
• You can also try supplementing with choline. Choline is important for neurological health in the form of phosphatidyl-choline and acetyl-choline. Just as with creatine, a large portion of the body's methylation capacity is spent on synthesizing choline, so if you supplement with choline you are effectively freeing up a large portion of the body's methylation capacity for other uses. As with the other mentioned supplements, you might expect an unpleasant reaction at first, but if you start low and go slow you should be able to tolerate choline after a couple of weeks. And as with B-vitamins, low-dose potassium might alleviate this reaction somewhat. Choline supplements come in a number of different forms, including phosphatidyl-choline, citicoline, and glycero-phospho-choline.

Of course, remember that everyone reacts differently to supplements, so be sure to share your experiences with any of the above supplements here on PR, so we can all learn more.

Hope this helps.

 

[Float]

@johnymous did you consider post prandial hypotension?
If blood pressure goes low its very fatiguing.
If you get orthostatic hypotension on top of that, then the body compensates via sympathetic activation which feels like pure tension.
On top of that, post exercise everybody gets hypotension (its a healthy response) but if BP is already low then it makes it ridiculously low.
brain starved of enough nutrients incl oxygen via hypontesion, and will cause more fatigue until its recovered.
subset of MECFS get orthostatic hypotension.
Good luck