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Why some of us are sensitive to oxalates on low VA diet

#1 · December 21, 2019, 10:59 pm

Quote from bludicka on December 21, 2019, 10:59 pm
Oxalates may be one of the factors that ALDH enzymes are overhelmed and exhausted. VA toxicity alters gut microbiome, causes gut inflammation... which may also contribute to impaired metabolism of oxalates.

https://www.researchgate.net/figure/Oxalate-related-metabolic-pathways-Metabolic-pathways-and-critical-enzymes-that-catalyze_fig1_267031279

https://www.ncbi.nlm.nih.gov/pubmed/9038835

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139422/

"Oxalate-related metabolic pathways. Metabolic pathways and critical enzymes that catalyze the respective steps in conversion of various precursors to oxalate are shown. ADH-1, alcohol dehydrogenase 1; ALDH, aldehyde dehydrogenase; AOX, aldehyde oxidase; LDH, lactate dehydrogense; XO, xantine oxidase; GOX, glycine oxidase; AGAT, alanine glyoxylate aminotransferase; HAO-1, hydroxyacid oxidase 1. Modifi ed from (11, 14). "

The bulk of oxalate production comes from glyoxylate oxidation, with glycolate as the main source (40). These metabolic reactions are catalysed by several key enzymes, including alcohol dehydrogenase 1 (ADH-1), lactate dehydrogenase (LDH), hydroxyacid oxidase 1 (HAO-1), xantine oxidase (XO), alanine- glyoxylate aminotransferase (AGAT), and glyoxylate reductase (GRHPR). Malfunctions in the activities or defi cient expression of these enzymes can change the metabolic conversion of various oxalate precursors (14, 41, 42).

"NADH was a potent inhibitor of oxalate production by LDH by increasing glycolate formation from glyoxylate"(NADH is produced by ALDH)

"Aldehyde dehydrogenase (ALDH) is a key enzyme in fructose, acetaldehyde and oxalate metabolism and represents a major detoxification system for reactive carbonyls and aldehydes."

"In contrast, glyoxylate, glyoxal, and glycolate were converted to oxalate with glyoxylate > glyoxal ≫ glycolate. Although glycolaldehyde is converted to glycolate, it appears that the intracellular concentration reached was not sufficient to stimulate oxalate synthesis. Pathways describing how these 2 and 3 carbon aldehydes and acids are converted to oxalate are shown in Fig. 4. The exact role of aldehyde dehydrogenase (ALDH) and which of the isoforms may be active in reducing glycolaldehyde to glycolate and glyoxal to glyoxylate are unclear. There is evidence that ALDH isolated from human liver homogenates can reduce both glyoxal and glycolaldehyde to glyoxylate and glycolate, respectively [21]. It is of interest that glyoxal could be converted to oxalate in HepG2 cells. This dialdehyde could be expected to be converted to glycolate by the glyoxalase system after reacting with glutathione [22]. Our results suggest that some glyoxal may escape glutathionylation and instead be converted to glyoxylate by ALDH. The formation of glyoxal, a product of cellular peroxidation [23], may be accelerated in these cells when they are deprived of glucose as increased peroxidation is observed under these conditions [24]. The increase in oxalate synthesis in cells incubated with 1 mM sugar may in part be due to increased glyoxal formation. The role of peroxidation and glyoxal formation in endogenous oxalate synthesis warrants further investigation."

Oxalates may be one of the factors that ALDH enzymes are overhelmed and exhausted. VA toxicity alters gut microbiome, causes gut inflammation... which may also contribute to impaired metabolism of oxalates.

https://www.researchgate.net/figure/Oxalate-related-metabolic-pathways-Metabolic-pathways-and-critical-enzymes-that-catalyze_fig1_267031279

https://www.ncbi.nlm.nih.gov/pubmed/9038835

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139422/

"Oxalate-related metabolic pathways. Metabolic pathways and critical enzymes that catalyze the respective steps in conversion of various precursors to oxalate are shown. ADH-1, alcohol dehydrogenase 1; ALDH, aldehyde dehydrogenase; AOX, aldehyde oxidase; LDH, lactate dehydrogense; XO, xantine oxidase; GOX, glycine oxidase; AGAT, alanine glyoxylate aminotransferase; HAO-1, hydroxyacid oxidase 1. Modifi ed from (11, 14). "

The bulk of oxalate production comes from glyoxylate oxidation, with glycolate as the main source (40). These metabolic reactions are catalysed by several key enzymes, including alcohol dehydrogenase 1 (ADH-1), lactate dehydrogenase (LDH), hydroxyacid oxidase 1 (HAO-1), xantine oxidase (XO), alanine- glyoxylate aminotransferase (AGAT), and glyoxylate reductase (GRHPR). Malfunctions in the activities or defi cient expression of these enzymes can change the metabolic conversion of various oxalate precursors (14, 41, 42).

"NADH was a potent inhibitor of oxalate production by LDH by increasing glycolate formation from glyoxylate"(NADH is produced by ALDH)

"Aldehyde dehydrogenase (ALDH) is a key enzyme in fructose, acetaldehyde and oxalate metabolism and represents a major detoxification system for reactive carbonyls and aldehydes."

"In contrast, glyoxylate, glyoxal, and glycolate were converted to oxalate with glyoxylate > glyoxal ≫ glycolate. Although glycolaldehyde is converted to glycolate, it appears that the intracellular concentration reached was not sufficient to stimulate oxalate synthesis. Pathways describing how these 2 and 3 carbon aldehydes and acids are converted to oxalate are shown in Fig. 4. The exact role of aldehyde dehydrogenase (ALDH) and which of the isoforms may be active in reducing glycolaldehyde to glycolate and glyoxal to glyoxylate are unclear. There is evidence that ALDH isolated from human liver homogenates can reduce both glyoxal and glycolaldehyde to glyoxylate and glycolate, respectively []. It is of interest that glyoxal could be converted to oxalate in HepG2 cells. This dialdehyde could be expected to be converted to glycolate by the glyoxalase system after reacting with glutathione []. Our results suggest that some glyoxal may escape glutathionylation and instead be converted to glyoxylate by ALDH. The formation of glyoxal, a product of cellular peroxidation [], may be accelerated in these cells when they are deprived of glucose as increased peroxidation is observed under these conditions []. The increase in oxalate synthesis in cells incubated with 1 mM sugar may in part be due to increased glyoxal formation. The role of peroxidation and glyoxal formation in endogenous oxalate synthesis warrants further investigation."

#2 · December 22, 2019, 12:19 am

That is interesting that fructose metabolism relies on ALDH.

VA has its own specific enzymes, retinol dehydrogenase and others. On what basis are we assuming that alcohol dehydrogenase, aldehyde dehydrogenase and others are relevant to VA toxicity?

#3 · December 22, 2019, 1:09 am

Quote from tim on December 22, 2019, 12:19 am

That is interesting that fructose metabolism relies on ALDH.

VA has its own specific enzymes, retinol dehydrogenase and others. On what basis are we assuming that alcohol dehydrogenase, aldehyde dehydrogenase and others are relevant to VA toxicity?

I don't know, I only read what Grant wrote, maybe Dr. Garrett Smith has more informations in the paid forum.

But a quick search on google: https://febs.onlinelibrary.wiley.com/doi/pdf/10.1046/j.1432-1033.2002.02935.x

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3161159/

"Class I ADH (ADH1) is expressed in many epithelial tissues and at very high levels in adult liver where it serves as an important enzyme in the clearance of toxic alcohols including ethanol [62, 63]. Adh1−/− mice exhibit normal survival to adulthood and normal fertility, and when maintained on a vitamin A deficient diet during development they display a similar degree of survival compared to wild-type [14]. However, Adh1−/− mice administered a dose of retinol exhibit a marked reduction in metabolism of retinol to RA compared to wild-type, and this failure to clear retinol results in a significant increase in vitamin A toxicity as measured by a reduced LD50 value for retinol and by increased release of cytosolic liver proteins into the serum indicating hepatic cell death"

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#4 · December 22, 2019, 1:39 am

Maybe it's just a coincidence but in low oxalate group there are mostly women - maybe women eat healthier and drink more different juices high in oxalates but women produce less of the enzymes Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase 2 (ALDH2) enzymes:

http://content.time.com/time/magazine/article/0,9171,153672,00.html

"Women have far smaller quantities of the protective enzyme alcohol dehydrogenase that breaks down alcohol in the stomach."

And many women have stronger oxalate dumping symptoms before menstruation - there is a link between hormones and oxalate dumping. But also between alcohol dehydrogenase enzymes and hormones.

"An additional factor for women is hormone differences from men. Research suggests that the menstrual cycle and the use of any medication that affects the liver (because of the change in hormones) may intensify a woman’s response to alcohol. Women have been shown to develop their highest blood alcohol concentrations immediately before menstruating, and their lowest on the first day of menstruation."

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#5 · December 22, 2019, 4:08 am

Retinol dehydrogenase is alcohol dehydrogenase by another name. Retinaldehyde dehydrogenase is aldehyde dehydrogenase by another name. The ADH & ALDH families of enzymes are complex with much still to know. There seems to be substrate preferences but much substrate non specificity from what I’ve read. There is a good overview paper that I’ve stored somewhere.

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#6 · December 23, 2019, 2:07 am

This article raises another reason why putting extra demands on the alcohol and aldehyde detox pathways might lead to oxalate sensitivities. Low thiamine.

Marginally Insufficient Thiamine Intake and Oxalates

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#7 · December 28, 2019, 6:13 am

@rachel I think this is highly significant. This was posted somewhere else on this forum but can’t remember where & I watched the video link. It seems that endogenous oxalate production increases under conditions of B1 deficiency as the pathways NOT leading to oxalates require B1 so the only option is the oxalate pathway. I plan to look into this more when I have time.

The B1 deficiency book by Derrick Lonsdale is hard going but full of interesting information. It’s a vital vitamin that has rather got overlooked and so is vitamin B2. I now realise (from Garrett Smith’s work) that some of my vA toxicity symptoms that came on with vA supplementation & went as soon as I stopped vA supplements are in fact B2 deficiency symptoms. It’s turning out to be a confusing but fascinating mix of toxicity & deficiency layered on to individual genetics/biochemistry.

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#8 · December 28, 2019, 6:30 am

@jaj

Maybe I should save up for his book. It's just so expensive! I have been struggling with thiamine deficiency for a couple of years now even before I discovered VA toxicity and started a low VA diet. I thought I had it under control now but have this month experienced it again despite regular supplementation. I believe my recent low thiamine symptoms are due to insufficient B2 to activate the B1. I have started taking B2 and my low thiamine symptoms are clearing. It really is a confusing mix of toxicity and deficiency like you say!

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#9 · December 28, 2019, 6:40 am

@rachel. The book is very dry & hard going tbh. You can get the first 3 chapters free on a Kindle - well I could. I’m ploughing through the rest but the first chapters offer a good explanation. Also there are lots of other articles on Hormonesmatter but I expect you know that.

Very pleased to hear that you have found a B2 link that is helping you. I think that B2 is important for me too & B1. I’m supplementing with both now & seeing good results. We’ll get there 😀

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#10 · February 13, 2020, 10:15 am

Quote from puddleduck on February 13, 2020, 10:15 am

Quote from bludicka on December 22, 2019, 1:39 am

Maybe it's just a coincidence but in low oxalate group there are mostly women - maybe women eat healthier and drink more different juices high in oxalates but women produce less of the enzymes Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase 2 (ALDH2) enzymes:

http://content.time.com/time/magazine/article/0,9171,153672,00.html

"Women have far smaller quantities of the protective enzyme alcohol dehydrogenase that breaks down alcohol in the stomach."

And many women have stronger oxalate dumping symptoms before menstruation - there is a link between hormones and oxalate dumping. But also between alcohol dehydrogenase enzymes and hormones.

"An additional factor for women is hormone differences from men. Research suggests that the menstrual cycle and the use of any medication that affects the liver (because of the change in hormones) may intensify a woman’s response to alcohol. Women have been shown to develop their highest blood alcohol concentrations immediately before menstruating, and their lowest on the first day of menstruation."

How interesting! Maybe this is why I’ve gotten worse PMS since starting Vitamin A detox. Thank you for sharing this.

Quote from Rachel on December 23, 2019, 2:07 am

This article raises another reason why putting extra demands on the alcohol and aldehyde detox pathways might lead to oxalate sensitivities. Low thiamine.

https://www.hormonesmatter.com/marginally-insufficient-thiamine-intake-oxalates/

Thank you for the link! 🙂 I’m having trouble reading right now, but I will save it to read later.

Right now, what I comprehended was that maybe oxalate avoidance isn’t addressing the root cause of the problem? That’s good, because I can’t afford to go carnivore right now. 😝

After I reached 3.5 grams thiamin (doing Dr. Costantinit’s High Dose Thiamin Therapy), I experienced something that seemed like “oxalate dumping” (horrible kidney pain, UTI type stuff, even though I was taking D-Mannose for several days). But the next day there was a weird “cooling/soothing” sensation in the kidney area, and the gut, and the brain, which I’ll take as a good sign even though who knows what causes it.

Having kind of bad CFS “flare-up” right now though, and it made me wonder if oxalates are part of the issue.

The “cooling/soothing” sensation still happens in my brain and gut every now and then, and my body is much warmer (usually it is the opposite—my body is so chilly while my brain feels like it’s been in a sauna for 2 hours).

Quote from bludicka on December 22, 2019, 1:39 am

Maybe it's just a coincidence but in low oxalate group there are mostly women - maybe women eat healthier and drink more different juices high in oxalates but women produce less of the enzymes Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase 2 (ALDH2) enzymes:

http://content.time.com/time/magazine/article/0,9171,153672,00.html

"Women have far smaller quantities of the protective enzyme alcohol dehydrogenase that breaks down alcohol in the stomach."

And many women have stronger oxalate dumping symptoms before menstruation - there is a link between hormones and oxalate dumping. But also between alcohol dehydrogenase enzymes and hormones.

"An additional factor for women is hormone differences from men. Research suggests that the menstrual cycle and the use of any medication that affects the liver (because of the change in hormones) may intensify a woman’s response to alcohol. Women have been shown to develop their highest blood alcohol concentrations immediately before menstruating, and their lowest on the first day of menstruation."

How interesting! Maybe this is why I’ve gotten worse PMS since starting Vitamin A detox. Thank you for sharing this.

Quote from Rachel on December 23, 2019, 2:07 am

This article raises another reason why putting extra demands on the alcohol and aldehyde detox pathways might lead to oxalate sensitivities. Low thiamine.

https://www.hormonesmatter.com/marginally-insufficient-thiamine-intake-oxalates/

Thank you for the link! 🙂 I’m having trouble reading right now, but I will save it to read later.

Right now, what I comprehended was that maybe oxalate avoidance isn’t addressing the root cause of the problem? That’s good, because I can’t afford to go carnivore right now. 😝

After I reached 3.5 grams thiamin (doing Dr. Costantinit’s High Dose Thiamin Therapy), I experienced something that seemed like “oxalate dumping” (horrible kidney pain, UTI type stuff, even though I was taking D-Mannose for several days). But the next day there was a weird “cooling/soothing” sensation in the kidney area, and the gut, and the brain, which I’ll take as a good sign even though who knows what causes it.

Having kind of bad CFS “flare-up” right now though, and it made me wonder if oxalates are part of the issue.

The “cooling/soothing” sensation still happens in my brain and gut every now and then, and my body is much warmer (usually it is the opposite—my body is so chilly while my brain feels like it’s been in a sauna for 2 hours).

Rachel-2 in Colorado has reacted to this post.

Why some of us are sensitive to oxalates on low VA diet

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