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Jun 16, 2023Liked by Chris Masterjohn, PhD

10 mg/day of biotin stopped the chronic, dull aching pain in my colon and salivary gland that had plagued me since I cut back on oxalates in April 2022.

I believe I unintentionally sabotaged my attempt to keep a maintenance level dose of oxalate in my diet. I decided to eat oatmeal with every meal which should have provided roughly 80 mg of oxalate per day. However, I was also drinking a cup of milk with each meal. The calcium likely bound enough of the oxalate to kickoff a period of dumping that lasted for a year, causing declining kidney function and what I believe is a salivary stone.

While I would not recommend people experiment on themselves, I wish we had some data on whether high-dose biotin and folate obviates the need to reduce oxalates gradually, maintaining just enough oxalate in the diet to prevent damage from dumping. I imagine it would.

Safely speeding up the oxalate removal process would be a huge quality of life improvement for people that suffer from high oxalates, given that Sally K. Norton says this can take a decade or more.

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Yes I hope we have much to learn and I hope we can learn more soon!

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Thanks so much for continuing to learn and write about this, Chris! 😁

I am currently on a low-fat (no added oils; only flaxseed and hemp hearts), whole foods vegan diet, low in beta carotene (primarily consisting of legumes, whole grains, bananas, strawberries, apples, dates, raisins, cabbage, cauliflower, mushrooms, blackstrap molasses), and transitioned to eating this way not long after my “oxalate dumping” response to both egg consumption and biotin supplementation, which I posted about under your earlier article on the subject.

What is weird to me is that while I think you’re right about B12 and folate reducing this reaction, vitamin A seems to be part of the underlying issue in my case (overloading the aldehyde dehydrogenase enzyme?)...because now that I am eating a ZERO retinol diet, biotin supplementation no longer triggers the dramatic “oxalate dumping” symptoms, even though I am not consuming B12 and my folate intake hasn’t increased all that much.

Since I clearly have enough B12 stored in my body to get me through this brief period of veganism, and since I was consuming plenty of B12 when eating eggs and beef every day, B12 deficiency shouldn’t have been a concern.

Likewise, folate is a nutrient I consume at well over 100% of the RDA, sometimes reaching 300%, due to my high legume intake.

So I suspect the retinol in the eggs (and occasional dairy) I was consuming at the time may have interfered with the B12 and/or folate somehow, even at such a relatively low dose.

My feeling is that I am still converting excess stored carotenoids and retinyl esters into retinaldehyde and then retinoic acid for removal from my body as quickly as my body dares, and whatever form of vitamin A is in eggs (multiple forms I guess?) caused a glut somewhere, leading to a transitory suppression of B12 and folate due to chronic hypervitaminosis A:

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2230.2006.02144.x

https://pubmed.ncbi.nlm.nih.gov/22098008/

Whether or not this idea is correct, my body doesn’t tolerate retinol. My CFS/POTS was much worsened when I was consuming eggs. It kinda stinks I’m still this sensitive to retinol at 4.5 years (minus 3 months of egg consumption) of consuming under 3% of the RDA for RAE, but at least I enjoy banana smoothies more than omelettes. 🙃

I will continue the vegan diet a while longer to limit purines and fats (another thing it seems my body isn’t keen on; perhaps because my microbiome is sensitive), but will start to supplement B12, and then try the biotin supplement again a few times to see if I still tolerate it. I am taking supplemental calcium and iron.

While I haven’t been tested to determine any genetic challenges I might have, I know I do not tolerate methylated B vitamin supplements (anxiety and insomnia results) or a super high-choline diet (350 mg to 600 mg choline from plants is what I typically get and do well on), so I figure I’m an over-methylator.

Anyway, thanks again for writing about this, Chris! 😁 It is extremely helpful.

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I think you hit the nail on the head with aldehyde dehydrogenase, but I am skeptical you are constantly draining the carotenoids like that.

I think, rather, you probably have a defect in aldehyde dehydrogenase that is the common denominator both to your intolerance of retinol and oxalate.

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Jun 16, 2023Liked by Chris Masterjohn, PhD

I’m not taking folate or biotin, but I have been on a carnivore diet for over three years (years prior to that it was nutrient-dense-focused Paleo and keto), which provides a lot of B vitamins. Last year I started getting oxalate crystals coming through my skin. A year later I’m still getting crystals coming through. In previous iterations of my paleo diet I had eaten a lot of oxalate foods.

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This is a very interesting phenomenon, which I keep hearing over and over, and which I have experienced myself. Sally Norton has seen it with many of her clients. People who switch to a low oxalate diet often have a worsening of symptoms at the 2-3 year mark. The theory is that it takes a few years for the body's metabolism and/or renal function to recover to a point where the body is finally ready to start dumping the oxalate stores.

The same thing has been seen in primary hyperoxaluria patients post liver transplant (which is the equivalent to dietary hyperoxaluria patients going on a low oxalate diet). Check out figure 2 in this paper: https://academic.oup.com/ndt/article/16/2/348/1849702

Notice how the plasma oxalate concentration peaks at 3 years.

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Dec 16, 2023Liked by Chris Masterjohn, PhD

I stopped eating a high oxalate diet, was eatinf sweet potatoes every day not knowing any better and it took 3 years or so before I noticed dumping which came in sharp shard like feelings in BM's and stuff in my eyes. I was going through fairly severe health issues, severe insomnia, etc... the dumping came after I started recovering and sleeping better. Also, I think possibly after I added electrolytes that contained potassium and magnesium citrate???

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Jun 16, 2023Liked by Chris Masterjohn, PhD

I figured that my body was doing its self-healing thing, and that eventually the oxalate crystals would all be exuded. It’s nice to know that might be on the downhill side of this as I am at 37 months and carnivore. Thanks!

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Super interesting.

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I tried taking biotin in 1000, 500, and 250mcg and each time I felt absolutely horrible, like a horrendous flu. A better way to describe it is as though I felt like I had been poisoned for a day or two. I’m willing to suffer a bit to get these damn Oxalates out so figured I’d try that route but it was too much for me. I still get episodes of dumping occasionally and I deal with it as it’s not too bad like it used to be where I could barely function (like with extra biotin) but the rest of the time I feel pretty darn good now. Ever since I jumped on high dose thiamine, life seems to be worth living now.

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Is the thiamin helping you tolerate the biotin or is it just solving a different problem?

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Jun 18, 2023Liked by Chris Masterjohn, PhD

The latter and thanks for asking. I’ve been on the thiamine for about 4 months now. Just recently tried biotin again about 3 weeks ago and it was rough. Can’t figure out why exactly or what it’s doing but it feels like an Oxalate dump on steroids. I don’t recall cloudy urine (which is typical for me when dumping) but I did have sandy stools. Hope that helps.

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Very interesting, thanks.

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What dose of thiamine are you using and can you describe your experience before and after starting it?

I tried 50mg of allithiamine late last year and I can't say I noticed any benefit but after my success with biotin I'm willing to revisit.

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Jun 19, 2023·edited Jun 19, 2023Liked by Chris Masterjohn, PhD

I’m up to 500mg of HCL twice a day and I take it with other cofactors involved in the citric acid cycle and oxidative phosphorylation. I seem to do best there for right now but many others usually need to go quite a bit higher. TTFD which is the derivative in allihiamine is too strong for me as is benfotiamine so I’ve settled on HCL for now. Different forms seem to affect people differently (I know, shocker). I’ve been battling depression for quite some time and I then after taking some antibiotics for another issue, I started getting really fatigued to where I couldn’t do anything. I’ve been on this health journey for about a decade and have fixed a plethora of other diseases and issues I used to have using better nutrition and lifestyle practices but the depression was the only one I couldn’t overcome for some reason until I started addressing Oxalates and taking thiamine and it gave me crazy energy that I haven’t had before. Now I’m all good minus the occasional Oxalate dumping and tampering with different vitamins and supplements that can sometimes cause insomnia.

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I’m not taking any thiamin right now.

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Look like you may have been quoting someone else’s question elsewhere in the thread rather than asking me that.

Thank you for sharing.

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My most recent oxalate dumping started when I downed a bowl of delicious blackeyed peas. It caught me off guard because I've been feeling pretty good for months, ie. no more migraines. It started with tingling in my feet and back, I started feeling "funny" and itchy, uh oh. In my experience and that of many others it seems dumping starts at some point, when the "something missing" shows up in supplement or dietary form and body has the energy currency to get it out of storage and down the drain. Ie. it may be months after starting a new regimen, like in my case I'm doing the RnB protocol per Greg Russell-Jones PhD about 4 months in (Facebook Group Understanding B12 Deficiency for more info). The way to mitigate dumping according to the group and my own experience is dilution, more hydration, potassium and magnesium, and more hydration. I'm taking large doses of one thing: Riboflavin. About 100mg per day in divided doses. Everything else is cheapo Winco Men's Under50 multivitamin, half a Jarrow B-Right, some bone minerals, one drop of topical active B12. But...I've been adding moderately more leafy greens, then the blackeyed peas...boom. I've felt "things" from extra K and molybdenum supps and the blackeyed peas dump felt similar, like little prickles in different old injuries, needle like sensations here and there, warmth and aching in my neck or an ankle. Stings, burns. Then it gets to be a bit much and a Dead Sea Salt bath (potassium and mag chloride and a bit of sulfate) is in order.

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Very interesting and thank you for sharing!

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Jun 19, 2023Liked by Chris Masterjohn, PhD

The premise in a nutshell is “fix B2 first” increase FMN and FAD by minerals (if missing) potassium iodide, a selenite or selenate supp, a molybdate supp. Then slowly increasing B2, then adding a lowish dose b complex or more thiamine etc. Watching iron levels and thyroid. This is fundamental cellular energy production. The mineral forms seem to matter. Even RDA amounts of the “something missing” can cause strong side effects so you go slow. The Winco multi has the right forms and I definitely felt it when I went to a whole one. Other people use topical forms or oral drops etc. This goes a long way to increasing energy and utilization of food, help toleration of more foods, increase melatonin in brain and gut, etc. Can be destabilizing to mood, up or down, so it’s important to make slow adjustments so the brain can adapt. Just like titrations up or down in a drug. It affects neurotransmitter and adrenaline and cortisol levels and receptors have to adjust to the changes.

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Jun 19, 2023Liked by Chris Masterjohn, PhD

We’ve been eating soaked and cooked beans daily with breakfast for awhile. But blackeyed peas are in a different category. A staple in my grandmas house. Still eating the same batch every morning with breakfast, just upped the bone minerals and potassium foods and much more comfortable reaction-wise.

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Cool. Why are you focusing on B2 first?

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Jun 28, 2023Liked by Chris Masterjohn, PhD

Obviously there are going to be exceptions to every protocol, so I am interested in those as well. Some have reported they needed extra Pantothenic acid or biotin or thiamine before being able to add higher doses of B12 down the road. The ultimate goal of high dose B12 is remyelination and repair of the nervous system. But he emphasizes the developmental delay or neurological damage can't be repaired without getting B2 working well.

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The majority cohort of clients that Greg Russell-Jones has worked with to date fall largely into the autism spectrum and chronic fatigue from what I understand. Many many moms with babies with feeding problems, super food intolerant, people down to just a few foods, etc. Honestly I think over the years he was working on the reasons why B12 supplementation is ineffective, and he determined that nearly everyone he saw exhibited a normal or elevated pool of serum B12 (much of which was inactive due to riboflavin that was not being activated due to low iodine status, low selenium, or low molybdate. Once the process of activating riboflavin into FAD and FMN was improved, it could turn on many many processes including recycling B12, activating B6 enzymes, helping with iron retention in people with chronically low iron status. I know a person who was until recently a non supplementing vegetarian with extreme fatigue, disordered eating, IBS and a high TSH ;drop that down to the "normal range" which also resulted in a characteristic fall in "normal" serum iron and B12 as they started getting used up to make new cells. It revealed the low iron status and low B12 status. It was low all along, it just wasn't obvious in the labs until a month later. This spring they started with half a Winco Men's Under 50 multi and a couple of liver capsules, plus eating meat most days. Added 25 mg of riboflavin and it's like the lights turned on and they started becoming more social, doing light yard work, etc. Now is the continued slog for them to replete iron, the other Bs, and keep eating and getting stronger.

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Interesting. I can relate to some of that with B2.

I think autism and CFS are very heterogeneous and I doubt the B12 is always at the center of the story, hence the diversity you report.

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I can tell that B12 may not be at the center of my story either, but if it’s getting short shrift in terms of functional deficiency in my body due to inefficiencies elsewhere, the outcome is no bueno. I just re read some of your stuff on glycine because I seem to fluctuate so easily in the methylation department and want to get that dialed in better.

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Please forgive me if I missed this in a previous post but...are you not using the Genova ION panel anymore? If not, is there a particular reason? Thank you.

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No, It’s linked directly above in the comprehensive screening.

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I wonder if excessive amounts of biotin are counterproductive due to an excessive accumulation of biotin metabolites, as suggested in this paper: "Plasma Levels of Biotin Metabolites Are Elevated in Hemodialysis Patients with Cramps".

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It would help if you link to the study rather than just posting the title.

I haven’t looked at it, but with the success of high dose biotin in biotinidase and HCS deficiency patients I kind of doubt it.

Elevated biotin metabolites could be a sign of biotinidase deficiency.

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https://www.jstage.jst.go.jp/article/tjem/239/4/239_263/_article

Yeah, part of the theory would be that oxalate-toxic patients have impaired renal function. (My creatinine peaked at 1.4)

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They say in the abstract that supplementing biotin alleviated the cramps. This shows the biotin metabolites are not causing the cramps because biotin supplementation would increase them, not decrease them. Their data are clearly consistent with the cramps being worse in patients with impaired biotinidase, the metabolites being a marker for that, and the available biotin being the factor preventing the cramps.

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I suspect the muscle spasms I had that responded so dramatically to biotin were caused by low glycogen levels secondary to impaired gluconeogenesis secondary to oxalate toxicity. I suspect the biotin simply knocked off some of the oxalate that had been blocking the biotin-depedent enzymes responsible for gluconeogenesis. But maybe you are right that oxalate is not just being displaced but actually degraded. Dang, I hope you are right about that. Would a folic acid supplement work as well as THF in promoting the second step of the degradation pathway?

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That seems plausible, but the principle is insufficient to explain the four cases where high doses provoked dumping symptoms.

I would think if your gluconeogenesis were impaired your blood sugar would be low.

If you have the nutrients needed for recycling, any form of folate should be adequate.

The drawback of folic acid is it could overwhelm DHFR.

Foilinic acid would be a natural form that is less subject to overwhelming DHFR and is not subject to the methyl trap.

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I haven't measured my blood glucose in a year or so, but it has never been low. Is it possible that the body prioritizes blood sugar at the expense of muscle glycogen synthesis?

I'm basing my theory regarding the muscle spasms on the fact that one day I decided to go low carb, and the spasms suddenly returned, despite being on the same dose of biotin. The spasms quickly resolved the next day when I went back on carbs. Also, before starting biotin, for months I tried increasing and decreasing the amount of sodium, calcium, potassium, and magnesium in my diet and nothing helped in the slightest.

I guess my main question would be, what is the overall quantity of biotin-dependent enzymes in the human body? If one were to suddenly displace all of the oxalate that might be bound to these enzymes, perhaps by taking a megadose of biotin, could that increase free and/or plasma oxalate to a degree that might cause dumping symptoms?

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Well, your last questions I basically the great unknown. I’ve never seen a paper showing the oxalate stays stuck to the enzyme in a suicide inhibitor fashion, and my hypothesis is it is just being converted to formate.

In any case, muscle glycogen is depleted with exercise and liver glycogen is depleted with fasting or low carb. Low carb will not deplete muscle glycogen directly but it will prevent it from refilling after exercise.

The blood sugar will certainly take priority, but it is not very plausible that muscle glycogen depletion causes spasms. If this were the case low carb would cause spasms in everyone.

I find it more likely you have an issue with fat or BCAA metabolism.

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Another important point is that it is not at all possible for biotin to displace oxalate on the enzymes because biotin does not bind to the oxalate-binding part of the enzyme. I covered here where they bind and the papers I cite have diagrams showing the binding locations.

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Yes, very important point.

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Chris, do ALDH1&2 actually need 10-formyl-THF to break down the formyl group or do they also break down formate directly? Thank you for your answer

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I believe they act directly on formate.

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Hey, Chris! I cannot find any info on ALDH1 & ALDH2 needing iron? What exactly are you referring to when you say that iron is important there?

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Thank you ! So - I take it there are articles which are unrestricted - available beyond the initial 24-48 hours ? There are some really helpful articles that would help a lot of people. I always encourage people to become a Masterpass member.

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Jan 12·edited Jan 12Author

The ones marked "free" are free.

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Hello Chris ! can you please tell me if the entire article is FREE to share ? I see it says the word FREE on top of the title . I want to share the entire article but hesitate to do it since I know most of these articles are only available to the public for 24-48 hours. Thank you so much

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Easiest way to check that is to copy and paste the URL into a different browser in which you are not logged in and see if you can read it. For example I stay logged in with Chrome so in Safari or Firefox a free article will be free to me and a paid article will not.

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If oxalate is converted in the human body to formate, and if formate can also be converted to oxalate, then should somebody who is trying to maintain a low oxalate diet be concerned about the use of formic acid as a food preservative? And its unregulated use by beekeepers? And should one factor in the natural formate content of foods like apples, which are otherwise low in oxalate, when estimating total oxalate load?

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That's an interesting idea. I would think that if formate utilization is maintained efficient as described, the equilibrium would strongly favor its utilization or detoxification, since it's accumulation would be poisonous and cause blindness (as in methanol toxicity), though given how preferable it would be to have oxalate accumulate, I would think if formate utilization were fundamentally impaired and oxalate levels were low, it could very much and would very much desirably be converted to oxalate.

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Chris, so we need biotin, folate , maganese and THF?

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If my model is correct those are some of the big players.

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What are the amounts to be used? Of biotin / maganese and folate? tHF

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I would use the targets in the Cliff Notes and the Vitamins and Minerals 101 lessons, unless you have data-driven or experientially determined needs for higher doses.

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