As a medical researcher I'm sure you've been meticulous in documenting every change in your protocol
Not necessarily. Sometimes it's just too much effort, or I get impatient, or I'm too brain fogged to know what to do next, etc
When you say LOTS I'm guessing you take far more than provided in SeekingHealth Trace Minerals and Pure Encapsulations B-Complex as per FREDDD? If you don't mind me asking how much do you take? How do you know if you're deficient in something? Trial and error? It amazes me that certain people can feel when they're lacking something
Several years ago I stopped taking a B complex and started taking the individual components separately. This was mainly because I wanted to vary B6 and then B1 and biotin to deal with oxalate problems, as well as experimenting with the Freddd protocol.
Later I experimented with different forms of B2. In all of this I never noticed the sensitivity that many have to B vitamins, nor did I find that B1 and B2 influenced my need for folate, as Freddd has observed.
I did take quite high doses of B6 and biotin for a while (200 and 10 mg respectively) but once I had oxalates under better control, I cut these back. Roughly I've settled on doses of around 50 mg for B1,2,3,5,6, 1 mg biotin and varying amounts of folate and B12. I thought I had B vitamins pretty well covered.
For several years I took
this trace mineral preparation daily, with additional 25 mg zinc and 200 ug selenium. Also I used a fair bit of magnesium, both topical and oral.
I thought I had minerals pretty well covered.
More than 12 months ago several things started changing. I became sensitive to oral magnesium and stopped taking it (topical was ok) and the Freddd protocol became a lot less effective.
I began casting around trying to work out the latter particularly since this had been a very helpful intervention for me. It really felt like something else was becoming limiting and I began to think about depletion of nutrients.
The magnesium problem made me think about mineral imbalances and as a result of correspondence from another thread, I was persuaded to increase boron.
This did have a magical effect (I regained the benefit of B12 and folate) for a while but this eventually petered out. I tried increasing other minerals with not much effect. Eventually trying calcium and boron together helped considerably and I began to think that my problem with magnesium actually reflected an inability to supply sufficient calcium. Sure enough, once I was supplementing calcium, I could tolerate the magnesium again.
Somewhere around this time Freddd started writing about
refeeding syndrome and this tied in with what I had been thinking about nutrient depletion.
It was around this time too that I became increasingly sensitive to B12 and carnitine. Stopping made me worse and I eventually settled on moderate amounts of folate and methylB12 as something I could tolerate and at least gain some benefit from. I kept up the increased boron (3 x 3 mg daily) and calcium (3 x 175 mg daily) even though it didn't seem to be as effective as once.
But things never felt right - I always felt I was missing something, but what?
At various times I have tried increased trace minerals, especially copper and molybdenum, with some transitory beneficial effect, but nothing dramatic.
My sensitivity to B12 and carnitine wasn't improving, I always felt like I needed more B12 but couldn't tolerate it and my brain fog and blurred vision were steadily getting worse.
About a month ago I had a breakthrough which I am still working through.
I began to think about biotin again, noticing that my nails, skin and hair were deteriorating a bit. Maybe I should go back to higher doses.
To cut what is already a long story short, adding more biotin opened the floodgates. This had now become my most limiting nutrient.
Currently I am taking 50 mg daily in divided doses. This has allowed the B12/folate to give me considerable benefit again, but then I quickly ran into the depletion problem again. Now I couldn't supply enough minerals, especially copper and molybdenum again, but also calcium.
I have been taking 3 x 3 mg copper (as chelate), 1 mg molybdenum and 3 x 700 mg calcium daily. These made the most difference but I have added in 75 mg zinc (to balance copper), 10 mg manganese and 200 ug chromium, and continued the 3 x 3 mg boron.
I only anticipate taking these huge amounts for a relatively short time - trying to replenish stores - and do intend to cut back - not sure when.
I don't think I have any overt signs of mineral deficiencies and indeed the beneficial response is always the same - namely a considerable improvement in brain fog and blurred vision, plus some improved mood and energy. I think the minerals and B vitamins, especially biotin (but also B2 and B6 deduced from experiments with sublingual forms) are simply allowing folate and B12 to work better.
The symptoms which trouble me are really partial methylation block caused by my body"s inability to get various nutrients to where they are needed. Other people might experience different symptoms depending on their own layers of need, and have difficulty supplying a different set of nutrients.
Unfortunately trial and error is the only way to work it out.
I feel confident that if I can overcome the nutrient depletion by very large doses for a while, my sensitivity to B12 and carnitine is likely to settle down and I might gain even more benefits.
I'm not at that point yet.
Can AKG revert back to glutamate?
It can be converted to glutamate by two different types of enzymes, glutamate dehydrogenase and transaminases, using various other amino acids, eg alanine or aspartate.
The first enzyme, which is theoretically reversible, actually runs in the opposite direction under conditions in eukaryote cells - ie it converts glutamate to AKG.
Transaminase reactions where amine groups from one amino acid are transferred to AKG, thus forming glutamate, happen all the time and are an important part of nitrogen metabolism. They are reversible.
Whether AKG supplementation would somehow increase the neurotransmitter glutamate is a much more difficult question to answer - probably impossible.. I did a quick google - found one
study - which concluded that glutamate from the alanine transaminase reaction does not constitute the major intracellular pool of glutamate.
I think you would just have to try AKG and see what happened.