Help please!

[Foxten]

Hi!

First post here, and would really appreciate some guidance in helping my daughter. Will try and keep the history brief!

Long term history of food, animal and pollen allergies. The last three to four years has been a constant struggle for her health wise, catching every virus she encounters. In that time she has also battled terrible anxiety and now depression. She does not handle stress well and gets angry very easily. She is always exhausted. Wide awake at bed time and struggles through the day. No diagnosis at this point, doctors seem to think the sleep/exhaustion is all part of her anxiety and depression. Had nitrous oxide a few times last year for dental work and I do feel concerned that this has contributed, although she did seem to recover well from it at the time. She is a long way from the bright, happy, healthy and confident person she was before all this began.

I discovered an article on undermethylators a while back, and it seems to fit her. We tried Folinic Acid because she does not consume a lot of folate foods. That ended with her in pain and very low mood wise (overmethylating?) I decided to run the raw DNA results we had from Ancestry through Nutra hacker. I know it is not the most reliable source and that is why I am here hoping someone will be able to help me work out which way to go. I have been trialling vitamins and we were doing ok until recently with B2, P5P and hydroxy B12. But the B2 and B12 together seemed to mess with her bowels. I added in a mineral supplement (without iron and copper), in case she needed iodine as there is a strong family history of hypothyroidism, it also has some potassium in it. She only took that and P5P while away for three weeks. Her energy levels have improved, but we also saw a return of the anxiety she seemed to be getting on top of.

Her results from nutrahacker:
Homozygous - MTRR (rs1802059), VDR (1544410), VDR (rs731236), SOD2 (rs4880 ), GSTP1 (rs1695), NAT2 (rs1208) and NAT2 (rs 1801280)
Heterozygoes - CYP1A2 (rs 762551), COMT (rs4633), COMT (rs4680), MAO-A (rs6323), CBS (rs 1801181 and rs234706), MTHFR (rs1801131 and rs2066470), MTR (rs1805087) MTRR (rs1801394) and SHMT1 (rs1979277)

It seems like so many, and I can't work out what is being expressed and making a difference and what isn't! I think she needs more folate, but am hesitant to give her that as she reacted poorly when she tried it. I am only using 1/4 to a 1/3 of each tablet/capsule/lozenge to try and avoid depleting other nutrients.

If anyone can help me at all, I would really be grateful. She needs a break! Thank You.

 

[Countrygirl]

Hi @ Foxten I'm sure many of will be able to help you here. For me it is the middle of the night and I waiting for my zopiclobe to kick in so will have to return to morrow. There is a mass of info that can help you and hopefully members were will be able discuss the topics you have mentioned.

@Hip may be able to give some good advice for starters.

I hope to return later tomorrow.

Welcome to the forums and I hope your situation improves asap.

 

[Foxten]

Back again after doing some more reading and thinking.... would I be right in thinking that B12 is something we need to add back in, considering she has both MTR and MTRR SNPs?

Thank You @Countrygirl. It really would be wonderful to see her feeling back to her old self, or closer to it!

 

[Diwi9]

@Foxten - I don't really have input regarding methylation...but there are others on here who know a lot (@caledonia comes to mind).

Because of your daughter's allergy problems, it might be worthwhile to look into Mast Cell Activation Syndrome (MCAS). Many people on the forums have problems with MCAS and it has been widely discussed. There are treatments.

I hope you find some help here. It is always heartbreaking to hear about children with this horrible disease...but wonderful to know when a child is so loved that a parent comes here to help. There is a private sub-forum on PR for parents, I believe you need to request permission to join from a moderator.

 

[Foxten]

Hi @Diwi9. Thanks for the MCAS suggestion. I am wondering about things like that. What I have found, is her usual spring time allergies have not been as severe this year, perhaps due to helping out her methylation. I don't know how people here feel about the under and over methylator tags. But She certainly seemed to be under according to the high histamine levels. But since beginning supplements, her allergies seem to be a lot milder.

 

[Hip]

she has also battled terrible anxiety and now depression.

If your daughter has generalized anxiety disorder (which is common in ME/CFS), then the supplements listed on this thread may help:

Completely eliminated my severe anxiety symptoms with three supplements!

You doctor can also prescribe SSRI drugs for anxiety (which work for depression also), but these are sometimes not well tolerated by ME/CFS patients.


I also have comorbid depression with my ME/CFS; it comes and goes on its own accord, and for me I found it hard to treat. But I have had some success with high dose inositol 15 grams daily, Spanish saffron 100 mg, and low dose amitriptyline (¼ of a 10 mg tablet).

I also find that if I don't take B12 sublinguals regularly, I get more depression. Folinic acid 200 mcg daily (but not methylfolate) may possibly help, but I am not sure.


My latest discovery is that hydrogen rich water helps combat the emotional sensitivity of ME/CFS (such sensitivity can make you more vulnerable to stress, I find). Hydrogen rich water also has some mild antidepressant effects for me.

Hydrogen rich water is just ordinary water with some hydrogen gas (H2) dissolved in it (much like sparkling mineral water has CO2 dissolved in it). You can buy tablets or sticks that dissolve in water to make hydrogen rich water, but they are at present a little expensive. Hydrogen rich water has ben shown to stimulate the release of ghrelin, a hormone which acts on the hypothalamus (a brain area linked to emotions and the stress response).

 

[frederic83]

But I have had some success with high dose inositol 15 grams daily,

This one also helped me with depression (high dose), but I don't have to take it daily otherwise I loose the effect.

 

[sregan]

@Foxten How old is your daughter? I can relate and had some success treating my daughter some of this might apply click here

Have you given her a lot (quantity or duration) of MB12 or MFolate? How long have you been working with her?

 

[Foxten]

Thank You all for you replies.

@sregan - she is 11. We've been trialling a few things over the last couple of months. With varying levels of change. After looking at the MTR and MTRR info I have changed it up again recently. She is only taking Hydroxy B12 at the moment, and is doing a lot better after a short amount of time. So I'm thinking her biggest issue lies with that. Especially considering she has had four rounds of Nitrous Oxide before we found out about all this. And even though she has recovered well from it, her energy levels always seem to suffer. I am not sure if she needs methyl B12 though, considering she has both Homozygous and Heterozygoes issues with those two. But there is a definite change. Energy levels are improving, mood is improving and motivation is improving.

 

[Learner1]

The suggestion to look into MCAS is a good one. My doctor has been managing mine with lots of methylating nutrients plus lots of B5, vitamin C, curcumin, boswellia, and quercetin.

Best if you look at the entire methylation process. Once you start methylating, things can back up as they can't get out of the body.

You need adequate fiber (vegetables, ideally) and water, as well as B12 and mokybdenum to help with removal.

Then, working backwards, adequate amino acids - glycine, cysteine, and glutamine. Need to be careful and not have too much glutamine. Glycine can be taken before bed to promote sleep, and many of us take NAC, n-acetyl-cysteine. And adequate B6.

For the methionine cycle, methyl B12, b6, B2, magnesium, and may be potassium are needed.

And once those are in place, folate. Not folic acid, as many of us can't use it, but folinic acid or 5-MTHF.

Checking out gut health with a DNA stool test would be useful, too.

And phosphatidyl serine or Seriphos before bed may help reregulate cortisol patterns. There are several other natural strategies, too.

It would be best to work with a functional medicine doctor, and even better if you do a comprehensive nutrient test, like a Genova Diagnostics NutrEval FMV with Amino Acids and Vitamin D test to guide your decision-making, rather than randomly trying things that people on the internet tell you they use- we all have different genes and environmental factors.

Sounds like you're starting to make progress... and it should be a solvable, though complex problem.

Best wishes...

 

[sregan]

Thank You all for you replies.

@sregan - she is 11. We've been trialling a few things over the last couple of months. With varying levels of change. After looking at the MTR and MTRR info I have changed it up again recently. She is only taking Hydroxy B12 at the moment, and is doing a lot better after a short amount of time. So I'm thinking her biggest issue lies with that. Especially considering she has had four rounds of Nitrous Oxide before we found out about all this. And even though she has recovered well from it, her energy levels always seem to suffer. I am not sure if she needs methyl B12 though, considering she has both Homozygous and Heterozygoes issues with those two. But there is a definite change. Energy levels are improving, mood is improving and motivation is improving.

My daughter and I also have MTR and MTRR mutations and feel I need extra B12 because of it. One of those mutations means you don't recycle B12 that well and the other means you use it up very quickly. It's a double whammy. Wondering if the Hetero COMT is anything to worry about. If it is I believe D3 will speed up COMT to some extent and can overcome the mutations. My suggestion is to get her minerals up. Most likely depleted from methylation are (in order) Potassium, then Zinc and Magnesium.

per Freddd

“Vit D appears to be the most commonly limiting of the usual vitamins with zinc and magnesium the most limiting of the common mineral supplements.”

In the trace category Copper, Manganese, Molybdenum, Boron and Selenium might be all supplemented in small doses per day. Extra care when using Selenium and Copper (Copper taken always with Zinc.)

Freddd was taking 60mg of Zinc per day with 15-30mg of copper (You daughter probably doesn't need that much copper). You should adjust for her weight.

“ I cut back [zinc] to 35-40mg daily. I'm about 2 months into copper usage now, somewhat improved and not getting worse.”

“I'm taking [copper] 7.5mg twice a day with food. It doesn't seen to upset my stomach”

Vitamin D did wonderful things for my daughter (for a while) as did a b-complex with active B's and methylfolate. I had her talking MB12 with that B-complex but I think the MFolate in it was too much for the amount of B12 she was taking and it stopped helping her after about 2 months of working very well.

Right now she's stable on Mirtazapine and I'm trying to get her minerals up just as I suggested for you.

 

[frozenborderline]

If your daughter has generalized anxiety disorder (which is common in ME/CFS), then the supplements listed on this thread may help:

Completely eliminated my severe anxiety symptoms with three supplements!

You doctor can also prescribe SSRI drugs for anxiety (which work for depression also), but these are sometimes not well tolerated by ME/CFS patients.


I also have comorbid depression with my ME/CFS; it comes and goes on its own accord, and for me I found it hard to treat. But I have had some success with high dose inositol 15 grams daily, Spanish saffron 100 mg, and low dose amitriptyline (¼ of a 10 mg tablet).

I also find that if I don't take B12 sublinguals regularly, I get more depression. Folinic acid 200 mcg daily (but not methylfolate) may possibly help, but I am not sure.


My latest discovery is that hydrogen rich water helps combat the emotional sensitivity of ME/CFS (such sensitivity can make you more vulnerable to stress, I find). Hydrogen rich water also has some mild antidepressant effects for me.

Hydrogen rich water is just ordinary water with some hydrogen gas (H2) dissolved in it (much like sparkling mineral water has CO2 dissolved in it). You can buy tablets or sticks that dissolve in water to make hydrogen rich water, but they are at present a little expensive. Hydrogen rich water has ben shown to stimulate the release of ghrelin, a hormone which acts on the hypothalamus (a brain area linked to emotions and the stress response).

I’ve been reading the longecity threads on hydrogen. SEemd actually very promising. I’m almost tempted to mix hydrogen and oxygen gas at the ratio used in infarct studies and use that. Producing hydrogen water by electrolysis also seems plausible. But all this is out of reach while this I’ll, so I’m trying to look into the most legit hydrogen water products on the market. Frankly it just seems like an area where scams would be rife. I don’t wanna waste money. It’s harder to fake the taste and effect of thiamine, for example, than a few ppm of hydrogen. Are there any brands of tablets or waters that have been independently tested ? How about devices?

 

[Hip]

I opted to make my own hydrogen rich water (HRW), which can be done pretty cheaply. I outlined my method in this post and video on Longecity (that method evolved out of all the experimentation that was done on this thread).

With my method, the cost of making 1 large bottle of hydrogen rich water is a few cents.

I also developed a method of measuring the concentration of H2 dissolved in my water, and my method consistently produces concentration of around 5 ppm, which is a good concentration.


I have not really searched through all the hydrogen rich water products on the market. There are more available now than when first got interested in HRW. Because you need high pressures to create high concentrations of HRW, the best production methods will have a pressure bottle in which you place tablets to create H2 gas.


In terms of the benefits of HRW, it did not seem to help my ME/CFS symptoms overall, even when drinking it regularly several times daily. However, intriguingly, I find HRW does help the emotional sensitivity / stress sensitivity symptom of ME/CFS quite noticeably. Helps my anhedonia a little bit too.

So when I am having one of those days where my mind feels more sensitive to stress or social discord, I will make some HRW and after drinking it, it does seem to usefully strengthen emotional resilience.


Although hydrogen rich water and the H2 it contains is touted to be a potent gaseous antioxidant in the body, studies indicate that one of the main mechanisms of action of HRW is its stimulation of the ghrelin hormone in the stomach. So it may be that ghrelin is producing many of the benefits of HRW.

Ghrelin directly stimulates the hypothalamus, which is a main emotion-processing center in the brain. Then in turn, the hypothalamus will activate the whole HPA-axis, which is thought to be hypoactive in ME/CFS, so this is probably a good thing.

This mechanism likley explains why HRW strengthens my emotional and stress resilience:

Hydrogen rich water > stimulates ghrelin > stimulates hypothalamus > activates HPA-axis > improves stress resilience.



Some info on measuring the strength of hydrogen rich water in this post.

 

[frozenborderline]

@Hip is there any reason why it would be harmful to just be more sloppy, mix malic acid and magnesium directly in the water, and then sniff the gas?

 

[Hip]

@Hip is there any reason why it would be harmful to just be more sloppy, mix malic acid and magnesium directly in the water, and then sniff the gas?

It's not clear if H2 gas breathed in via the lungs would have the same effect as H2 dissolved in water and drunk. It may be the ghrelin released in the stomach when the water is drunk that accounts for most of the benefits of hydrogen rich water.

This paper says:

The possibility that most of the benefits observed with HW in experimental studies are mediated by ghrelin merits consideration. Ghrelin is well known to function as an appetite stimulant and secretagogue for growth hormone, but it influences physiological function throughout the body via interaction with the widely express GHS-R1a receptor.

Rodent and, to a more limited extent, clinical studies establish that ghrelin has versatile neuroprotective and cognitive enhancing activity, favorably impacts vascular health, exerts anti-inflammatory activity useful in autoimmune disorders, and is markedly hepatoprotective.

This paper says:

Our findings demonstrate that the neuroprotective effects of oral hydrogen water, which produces negligible levels of H2 in the brain, result from gastric induction of the neuroprotective peptide hormone ghrelin and the subsequent activation of ghrelin receptors.

In addition, we have shown an obligate role for β1-adrenergic receptors in hydrogen water-induced ghrelin up-regulation in plasma, consistent with previous reports that adrenergic stimulation regulates ghrelin release in vitro and in vivo.

The second paper also found:

We employed three different methods to prepare hydrogen water (see Methods), which resulted in H2 concentration of 0.04–0.8 mM, and we observed that the effects of hydrogen water on ghrelin induction and protection of dopamine neurons were dose-independent over this range.

So this study found that the amount of ghrelin released from drinking hydrogen rich water did not depend on the H2 concentration in the water, at least in the range of H2 concentrations they used in the study, which was concentrations from 0.04 mM to 0.8 mM (this corresponds to H2 concentrations in the water of 0.08 ppm to 1.6 ppm).

Which suggests that even the cheapest and simplest methods of hydrogen rich water production will be just as good; ie, you don't necessarily need high ppm.

The above comes from a discussion on Longecity.

 

[frozenborderline]

It's not clear if H2 gas breathed in via the lungs would have the same effect as H2 dissolved in water and drunk. It may be the ghrelin released in the stomach when the water is drunk that accounts for most of the benefits of hydrogen rich water.

This paper says:


This paper says:


The second paper also found:

So this study found that the amount of ghrelin released from drinking hydrogen rich water did not depend on the H2 concentration in the water, at least in the range of H2 concentrations they used in the study, which was concentrations from 0.04 mM to 0.8 mM (this corresponds to H2 concentrations in the water of 0.08 ppm to 1.6 ppm).

Which suggests that even the cheapest and simplest methods of hydrogen rich water production will be just as good; ie, you don't necessarily need high ppm.

The above comes from a discussion on Longecity.

what is your source for the magnesium sticks, test tubes and stoppers? Do you have any concerns about the magnesium sticks having any contaminants?

 

[Hip]

what is your source for the magnesium sticks, test tubes and stoppers? Do you have any concerns about the magnesium sticks having any contaminants?

I use 99.99% pure magnesium rods bought from China on eBay. These are very pure, but in any case, because the test tube containing the magnesium rod and citric acid is isolated from the drinking water in my 1 liter plastic bottle (the test tube is closed with stopper with a tiny pinhole to let the H2 gas escape), the reactants do not get into the water.