peroxynitrite more involved than realized ?

[Kathevans]

@alicec You say that, "Messing about with the upper digestive tract results in more fat than usual reaching the colon," and that that increases Oxalate uptake. Do you mean by gastric bypass? I've never had that, but I do have fat malabsorption going on, and high cholesterol. I wonder if I work on that it would help the Oxalate issues.

 

[Violeta]

[

@alicec You say that, "Messing about with the upper digestive tract results in more fat than usual reaching the colon," and that that increases Oxalate uptake. Do you mean by gastric bypass? I've never had that, but I do have fat malabsorption going on, and high cholesterol. I wonder if I work on that it would help the Oxalate issues.

Yes, I got out my liver tonic this morning and am going to work on that, too. I'm not sure if that same issue of fat malabsorption is what causes the high oxalates (would alkalinity of bile neutralize oxalates) or if it is because of lack of bicarbonates from something wrong with the pancreas. If the chyme leaving the stomach doesn't contain enough HCl, secretin isn't secreted, and then I forget the exact terms, but it affects the secretion of the alkaline pancreatic fluid, leaving the small intestines acidic instead of alkaline. That affects the digestive enzyme action in the pancreas, too which might also affect digestion of fats by lipase. I should end the sentence with a ??? because I don't have time right now to check thoroughly for validity, so if anyone needs to make a correction in what I said, please do so.

 

[Kathevans]

@Violeta Oh, excellent! I'm going to try to understand that! I do drink lemon juice with each meal, but haven't been able to tolerate Betaine. Maybe I need some pancreatic enzymes... Just thinkin'...

 

[JaimeS]

@alicec @JaimeS @Sidereal @adreno @alex3619
@Violeta is asking such interesting questions above, and I am curious about the answers... any ideas?

@Gondwanaland , I'd have to know a lot more about oxalates first... and that's for another day.

-J

 

[alicec]

Do you mean by gastric bypass? I've never had that, but I do have fat malabsorption going on, and high cholesterol. I wonder if I work on that it would help the Oxalate issues.

I was replying to a specific question about gastric bypass. Fat malabsorption from whatever cause does seem to exacerbate oxalate issues and is talked about a lot on the low-ox site since apparently it is common in autistic children.

Measures to address this would be very wise. I would endorse high doses of pancreatic enzymes - something I have found to be incredibly helpful for many years. It is only recently that my pancreas seems to be getting the correct signals and I have been able to virtually eliminate them.

 

[Gondwanaland]

I would endorse high doses of pancreatic enzymes

Do you mind sharing which ones you take? I am going to order from the cmpdg pharmacy soon and would like to have an idea of which ones and how much to throw in from the locally available ones ( Bromelain, Pancreatin, Amilase, Tripsin, Papain, Lipase, Protease).

 

[Violeta]

Gondawanaland, I like your disclaimer, and since I usually don't read word for word and will read parts of words, at first I thought it said, "Disclaimer: I am a patient and not a medical professional, and what I say reflects confusions from self experimentation."

I might add that to my signature!

 

[alicec]

Do you mind sharing which ones you take? I am going to order from the cmpdg pharmacy soon and would like to have an idea of which ones and how much to throw in from the locally available ones ( Bromelain, Pancreatin, Amilase, Tripsin, Papain, Lipase, Protease).

I take Creon 40,000, a prescription only product from Abbott. All pancreatic enzyme preparations consist of lipase (fat digesting), amylase (carb digesting) and protease (protein digesting) in similar proportions, but there may be variable amounts of the mixture in each tablet/capsule. Creon denotes its strength in the number in the title - ie Creon 40,000 contains 40,000 lipase units per capsule.This is the strongest preparation and there are other Creons with lesser doses - the lowest is Creon 5,000 - ie 5,000 lipase units per capsule.

There are a number of pancreatic enzyme products available without prescription from places like iherb. These contain maybe 5-10,000 lipase units per pill.

The advantages of the Creon product is that it comes in much higher doses for those with serious digestive problems, it is dispersed in many tiny enteric coated balls (enclosed in a single capsule) which get better distributed through food than does a single tablet, and at least in Australia, it is cheaper because I can buy it on our pharmaceutical benefit scheme.

Please note for people which might have chemical sensitivity, there is something in the outer capsule (? plasticisers) that cause almost instant headache in me. It is easy though to open the capsule and consume the little enteric-coated balls directly.

As to how much to take - trial and error is the ultimate test but a good guide is the elastase marker on a CDSA. Mine was less than 10% of average and I needed 7 of the 40,000 preparation per meal for several years. Gradually I could get it down to maybe 4 per meal but since the adventures of the gut strategy I now have 1 or 2 per meal, sometimes none. My pancreatic elastase is now low normal.

 

[Gondwanaland]

Thanks for the detailed info, Alice.

All pancreatic enzyme preparations consist of lipase (fat digesting), amylase (carb digesting) and protease (protein digesting) in similar proportions

So there is no need to add trypsin and pancreatin? My concern is that the enzyme supplementation might turn my pancreas "lazy" and getting used to produce even less than the usual. But since you reported a decreased need of enzyme supps, so it seems the pancreas welcomes the little help.

I am not sure how to empirically evaluate my digestion "potency" since those tests you mentioned aren't available here where I live. I suppose that the fact that my LDL went up and HDL went down means that I would benefit from some lipase? DH and I have been on Gamma E for several months, then we stopped for like a month, and last week I was going to restart the supplementation for both of us, so last Sat we took each one capsule at dinner and then we were feeling equally awful, tired and depressed the whole Sunday. It could only be Gamma E, and that was a first that it oxidized us rather than anti-oxidize

 

[alicec]

So there is no need to add trypsin and pancreatin?

Pancreatin is just another name for pancreatic enzymes. If you found something that also contained trypsin that wouldn't be a problem but the pancreatin alone should be sufficient.

Yes evaluating digestive function can be difficult. There are immediately obvious things like flatulence and bloating that should disappear. In the longer term my food sensitivities disappeared, I'm sure at least partially because of the enzymes. There were less tangible apparent improvements that it is hard to say for sure were due to the enzymes but nothing else had made much difference up till then so I imagine the enzymes played a role.

 

[Kathevans]

Thank you @alicec I haven't had the CDSA for about 5 years, and I think my oxalate problems have taken root--though I see there may well have been a genetic proclivity--since my treatment for SIBO two years ago, and the very high 'healthy' oxalate diet I put myself on.

 

[MyOwnOpus]

Hi Mimi -

Have you found dr. Brewer helpful to you? I just saw him for the first time last week. I'm unsure of what to.think.

 

[ahmo]

@MyOwnOpus You will send a message directly to Mimi by putting @ sign in front of name, which will then prompt the avatar and name as you type: @Mimi

 

[sb4]

I recently read an interesting post on another forum about peroxynitrites role in peripheral neuropathy and it got me thinking if this could explain the small fibre neuropathy present in some POTS patients.

The post basically showed that when you stop ONOO from forming, you stop peripheral neuropathy, and when you increase ONOO you increase neuropathy. It seems to work by the ONOO reacting with the tyrosine side chains of the microtubules. It does this easier on nerves that are poorly myeliated (SFN?).

The post goes on to say that progesterone, pregnenolone, and gama-tocopherol should have a protective effect via stabilizing and myelinating the tubules, and binding with ONOO. This is interesting as I noticed improvement in some POTS symptoms when using DHEA and Pregnenolone, however it had some bad effects on libido and other issues causing me to stop.

It also says how things like methylene blue can cause worsening neuropathy by increasing ONOO (MB increases super oxide formation causing more NO to turn into ONOO). Interestingly enough I was on MB when a drastic worsening of my POTS occurred.

What do you think @Learner1 ?

 

[Violeta]

I recently read an interesting post on another forum about peroxynitrites role in peripheral neuropathy and it got me thinking if this could explain the small fibre neuropathy present in some POTS patients.

The post basically showed that when you stop ONOO from forming, you stop peripheral neuropathy, and when you increase ONOO you increase neuropathy. It seems to work by the ONOO reacting with the tyrosine side chains of the microtubules. It does this easier on nerves that are poorly myeliated (SFN?).

The post goes on to say that progesterone, pregnenolone, and gama-tocopherol should have a protective effect via stabilizing and myelinating the tubules, and binding with ONOO. This is interesting as I noticed improvement in some POTS symptoms when using DHEA and Pregnenolone, however it had some bad effects on libido and other issues causing me to stop.

It also says how things like methylene blue can cause worsening neuropathy by increasing ONOO (MB increases super oxide formation causing more NO to turn into ONOO). Interestingly enough I was on MB when a drastic worsening of my POTS occurred.

What do you think @Learner1 ?

Have you tried gamma tocopheral? That might spare you the hormonal effect.

 

[sb4]

Have you tried gamma tocopheral? That might spare you the hormonal effect.

I have not, but might in the future. Problem is, I'm doing a lot ATM.

 

[Violeta]

I have not, but might in the future. Problem is, I'm doing a lot ATM.

I know what you mean. Thank you for the information, though. I have postherpetic neuralgia, I am going to try vitamin e for that. I see other antioxidants such as quercetin, luteolin, and ginkgo can help, too. Thank you for pointing in this direction.

 

[Violeta]

I know what you mean. Thank you for the information, though. I have postherpetic neuralgia, I am going to try vitamin e for that. I see other antioxidants such as quercetin, luteolin, and ginkgo can help, too. Thank you for pointing in this direction.

Now I am seeing that ROS scavengers are a better idea than antioxidants.

 

[Learner1]

I recently read an interesting post on another forum about peroxynitrites role in peripheral neuropathy and it got me thinking if this could explain the small fibre neuropathy present in some POTS patients.

The post basically showed that when you stop ONOO from forming, you stop peripheral neuropathy, and when you increase ONOO you increase neuropathy.

That makes sense.

It seems to work by the ONOO reacting with the tyrosine side chains of the microtubules. It does this easier on nerves that are poorly myeliated (SFN?).

I think there's more to it than that. This articke is about diabetic neuropathy and ONOO, but I believe the well-described mechanisms in it are the same, just the trigger (hyperglycemia) is different for the diabetics... oxidative and nitrosative stress are well-documented in ME/CFS:

https://www.hindawi.com/journals/jdr/2017/1673081/

The post goes on to say that progesterone, pregnenolone, and gama-tocopherol should have a protective effect via stabilizing and myelinating the tubules, and binding with ONOO. This is interesting as I noticed improvement in some POTS symptoms when using DHEA and Pregnenolone, however it had some bad effects on libido and other issues causing me to stop.

Interesting. I don't know, though all hormones are derived from cholesterol, so perhaps there's a rationale.

I will say, one of the very first things my doctors did was to balance all my hormones with a DUTCH test (dried urine test of comprehensive hormones) so I could function. We keep my DHEA level at what a 20 year old woman's would be. Pregnenolone was tricky - more than a tiny bit shot my estradiol level through the roof. And I take small amounts of testosterone and estriol, with a hefty dose of progesterone. (I had surgical menopause due to uterine cancer, which is why I need so many hormones, but we are careful to stay in the not-cancer promoting ranges... More is not better, as you've found...)

It also says how things like methylene blue can cause worsening neuropathy by increasing ONOO (MB increases super oxide formation causing more NO to turn into ONOO). Interestingly enough I was on MB when a drastic worsening of my POTS occurred.

What do you think @Learner1 ?

I think increasing superoxide if you already have an ONOO problem should be avoided.

I think, as the article I linked to describes, that taking a higher but balanced amount of antioxidants, particularly glutathione (and its precursors like folate, B12, B6, B2, magnesium, glycine and NAC), alpha lipoic acid, and vitamin C, and flavonoids, like resveratrol would be most helpful, along with phospholipid replenishment like NT Factor and phosphatidyl choline would be helpful, especially if levels were monitored with lab tests to ensure nutrients were properly balanced.

More is not better, as they can become pro-oxidants if they are in excess. In my experience, I tend to be depleted in glutathione, ALA and vitamin C, so we pay atttention to those as they change more often while I'm on more stable but high doses of A and mixed E.

From the article:

Antioxidants diminish or delay the oxidation of other molecules by inhibiting the initiation or propagation of oxidizing chain reactions, thus reducing its capacity to damage. Antioxidants may act as radical scavengers, peroxide decomposers, hydrogen donors, electron donors, singlet oxygen quenchers, enzyme inhibitors, or metal-chelating agents [111]. Their effect depends on concentration [112], polarity, and the medium [113], and also the presence of other antioxidants [114].

In fact, antioxidants may act from directly scavenging free radicals to increasing antioxidative defenses.

There are several types of antioxidants in cells: dietary antioxidants (vitamins A, C, and E), endogenous antioxidant enzymes (superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase (GPx), glutathione S-transferase (GST), and peroxiredoxins), and antioxidant molecules (glutathione (GSH), coenzyme Q, ferritin, bilirubin, uric acid, lipoic acid, melatonin, carotenoids, and flavonoids).

Under physiological conditions, these molecules and enzymes work synergistically and together with each other to protect the cells [115]. The SOD dismutates the O2•− to form H2O2 upon which acts as the catalase or the GPx to produce water. The GST converts the reactive electrophilic species to form easily excretable hydrophilic products as a result of the conjugation with GSH.

Vitamins C and E and the alpha-lipoic acid are involved in the elimination of the products of lipoperoxidation (LPO) [116]. As well, the flavonoids are capable of eliminating FR [117].

Some specialized proteins have regulator functions of the redox signaling with an antioxidant effect, like the peroxiredoxins (Pxr), thioredoxins (Trx), and glutaredoxins (Grx), with intracellular effects on the ROS and RNS [118]. The members of these families of proteins are ubiquitously expressed in all organisms, tissues, types of cells, and organelles. Some of these proteins can also move between cellular compartments and the extracellular space [119].

The stoichiometric number of antioxidants that capture FR by an antioxidant molecule and the effectiveness of FR scavenging can be evaluated by performing in vitro tests. The biological functions of antioxidants have been widely evaluated for their effects on the expression of antioxidant enzymes. For example, γ-tocopherol is a relatively mild ROS scavenger when compared to α-tocopherol. However, the oxidized product, γ-tocopheryl-quinone, reacts readily with the thiols to release the nuclear factor (Nrf-2) resulting in the expression of antioxidant enzymes such as hemooxygenase-1 [120].

There are several existing strategies with the use of different antioxidants to manage DPN. The choice of antioxidant depends on its chemical structure and concentration, the type of DPN, and stage of the illness, its severity, and the prevalence and primary causes from which it originated [121]. The antioxidants have different mechanisms and action sites through which they exert their biochemical effects and improve nerve dysfunction produced by oxidative stress in DPN.

Measuring NO and nitrotyrosine levels would be a good place to start, along with a flavonoid rich diet and a good zupplement protocol based on a Genova Diagnostics NutrEval test.

 

[frozenborderline]

I recently read an interesting post on another forum about peroxynitrites role in peripheral neuropathy and it got me thinking if this could explain the small fibre neuropathy present in some POTS patients.

The post basically showed that when you stop ONOO from forming, you stop peripheral neuropathy, and when you increase ONOO you increase neuropathy. It seems to work by the ONOO reacting with the tyrosine side chains of the microtubules. It does this easier on nerves that are poorly myeliated (SFN?).

The post goes on to say that progesterone, pregnenolone, and gama-tocopherol should have a protective effect via stabilizing and myelinating the tubules, and binding with ONOO. This is interesting as I noticed improvement in some POTS symptoms when using DHEA and Pregnenolone, however it had some bad effects on libido and other issues causing me to stop.

It also says how things like methylene blue can cause worsening neuropathy by increasing ONOO (MB increases super oxide formation causing more NO to turn into ONOO). Interestingly enough I was on MB when a drastic worsening of my POTS occurred.

What do you think @Learner1 ?

Hmm, that's concerning about the methylene blue. I had been advised to try methylene blue by people on that same forum you are talking about (i'm pretty sure). It's often considered something that would help with oxidative metabolism in general, but i guess what you are saying is that in the wrong conditions it could hurt and exacerbate the problem?


As far as pregnenolone goes, I've tried a couple different brands, including health natura's which was supposed to be very pure, and had bad, adrenergic symptoms from it. A friend thinks these are due to trace amounts of the phytoestrogen diosgenin, which it's made from.
I have gotten fairly positive effects from progesterone, specifically progestE. It's not a life-saver or lazarus like improvement, it's just helping with pain and fatigue some--helping me weather more difficult episodes. Frankly I think i take it too often, without taking any androgen-improving product, but i haven't grown breasts yet, haha.
I have DHEA and plan to introduce that to balance it as soon as I get a friend to help me with the volumetric dosing (I really tend to not have the cognitive energy to weigh out supplements precisely and organize thing"