What should people with glucose-6-phosphate dehydrogenase deficiency be doing not just about glutathione, but about folate, vitamin K, fatty acids, and neurotransmitters?


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Question: What should people with glucose-6-phosphate dehydrogenase deficiency be doing not just about glutathione, but about folate, vitamin K, fatty acids, and neurotransmitters?

G6PD, glucose-6-phosphate dehydrogenase deficiency, is an inborn error of metabolism. It's the most common one in the world. About 8% globally have some impairment in this enzyme. The reason that it's important is because glucose-6-phosphate dehydrogenase is the enzyme that allows you to make NADPH, which is a specific derivative of niacin that's involved in antioxidant defense, detoxification, synthesis of neurotransmitters, and synthesis of nucleotides, which are needed for cell division because they're parts of DNA.

Someone with G6PD deficiency is vulnerable to hemolysis, or the destruction of red blood cells, because of glutathione deficiency. Glutathione reductase uses energy and NADPH, the thing that you can't make, to recycle glutathione. But it also uses riboflavin. So, one of the adaptations that someone with this impairment has to try to protect themselves is for the glutathione reductase enzyme to hog all the riboflavin so that it says, "I don't have enough of the raw material I need to make this happen, so I'm just going to make myself get way better at using what I do have." That's an adaptation to compensate for not being able to make NADPH is just to get way better at using NADPH to recycle glutathione.

Supplementing glutathione is not necessarily a bad idea. You just have to be aware that at a certain point you just can't solve every one of the dozens of problems that are happening. I think that you should measure your glutathione status. Probably the best test available, not because it's the best we could have available but because there's nothing better right now, is LabCorp's test for glutathione. If that looks low, then I would supplement with glutathione to try to bring that up to normal.

For the folate recycling, you have to consider this basically as if you had a really bad MTHFR polymorphism because G6PD is needed to make the NADPH that MTHFR uses, again, with the help of riboflavin to make the methyl group on methylfolate. You can take some methylfolate, but as I've made the point in my MTHFR protocol at chrismasterjohnphd.com/methylation, you have to take 18,000 times the RDA to compensate for the 18,000 times a day that you add a methyl group to the folate molecule using that enzyme. It's not safe to take anywhere near that much folate.

What I would do is just very strictly follow the MTHFR protocol that I have at chrismasterjohnphd.com/methylation, and that involves doubling your choline intake because you don't need NADPH to use choline to support methylation. Just as if MTHFR didn't work because of genetics and not enzyme, what you would do is you double your choline utilization for methylation because you're not good at using folate.

On recycling vitamin K, it probably just means that you need a high amount of vitamin K in your diet. I think it's probably similar as if you had a bad VKOR polymorphism. VKOR is the enzyme that recycles vitamin K using NADPH that you got from this pathway that's not working right when you have G6PD deficiency.

In terms of all this stuff that you are not good at synthesizing, like cholesterol, fatty acids, nucleotides, and neurotransmitters, I think the only thing that you can do for that is to try to eat a lot of these things preformed. That means eating a diet rich in relatively lean animal foods because they have a lot of preformed stuff, like cholesterol, in them and mainly in the flesh, not the fat. With plants, you want to eat mostly fibrous vegetables because they are highly cellular and rich in nutrients that you can’t make.

You don't want to go extremely low-fat, but if you eat a diet fairly rich in animal foods, you're going to get a lot of the specific fatty acids that you can't make. A high-fat diet is mostly giving you just a bunch of fat that you could have made yourself.

This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/08/ask-anything-nutrition-feb-23-2019

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