Ah ok great, thank you. I have some pure powder I might try sublingually. Doing all three of the others already at the moment (plus high dose pregnenolone) so hopefully this will help.
For me, I think there are 2 things going on, though interrelated. I think my mitochondria have significant oxidative stress and resources they need get depleted.
BCAAs support cardiac and skeletal muscle mitochondrial biogenesis, prevent oxidative damage, enhance physical endurance, and are involved in catabolic processes in the mitochondria. If you push the mitochondria, BCAAs, particularly isoleucine and leucine get depleted.
The glutathione helps with the oxidative stress, as well, though it's best taken whole on a regular program of B vitamins, magnesium, and other antioxidants like C, which recycles it, and E and alpha lipoic acid, all part of Lester Packer's antioxidant network.
NAD and NADH recycle each other, with NADH actually giving up the H+ which goes through the mito membrane to create energy. Under stress, the NADH/NAD ratio rises, which is not good. For some reason, adding more NAD+ helps reverse the bad ratio which facilitates more energy production. I take NMN as it takes one more conversion to get to NAD+, and instinctively, it feels like making my body have to convert more is useful, though I did just fine with NAD+. I've also experimented with NADH, which was expensive for the dose I need and doesn't help normalize the NADH,/NAD+ ratio, and NR, which does absolutely nothing for me - it has to go through more conversions to get to NAD+ and I believe my mutations on the NMRK genes prevent me from doing it.
As for pregnenolone, for me, it went right to making estrogen, E1, and I became miserable fast. It's a little unpredictable, I've known other female patients for whom it converts to too much testosterone. I have done well with using a DUTCH test (dried urine test of comprehensive hormones) to determine which hormones I am deficient in, and I do well on a combination of small doses of DHEA, testosterone, estriol, and progesterone.
For PEM, do you mean that you do the NAD+ sublingually but in a higher dose than your normal daily routine, or you do an infusion of it?
I take 125mg of sublingual NMN every morning, with an additional 62.5mg-125mg if I've had a higher activity or am dragging in the afternoon. Sometimes I take it before I do more activity than usual. Aiming for a consistent level is best, rather than yoyoing Too much can potentially drive a nascent cancer, not something I want to tangle with. I did NAD+ infusions for 1 months, but found the unpleasant immediate side effects, expense, and difficulty of a consistent supply to make it undesirable for the 36 hour effect I got, so after improving to a point, I did continued them and continued just in the NMN I'd been taking all along. I will say 125mg of sublingual NAD+ is more subtle than the IVs, but I got more consistency out of the sublingual.
Would you mind sharing what dose of the others helps you the most?
1-3g Setria glutathione
2.4-4.8g BCAAs (2:1:1 ratio)
Four other things to consider:
Lipid replenishment with NT Factor. ME/CFS patients tend to have huge oxidative and nitrosative stress. Antioxidants help to lowe in, but they do damage mitochondrial membranes. Garth Nicolsons lipid replenishment protocol can help rebuild membranes as mitochondria recycle and pick up new material every 6-8 weeks. I use 2-3 scops daily.
Carnitine, which allows fats too be brought into mitochondria for fatty acid oxidation needs to be adequate - in many of us, it's not.
T3 (and T2) thyroid hormones work in the mitochondria. Ensuring T3 is adequate, by measuring FT3, FT4, rT3, TPO and thyroglobulin antibodies AND paying attention to hypo (or hyper) symptoms, NO MATTER WHAT TSH IS, and medicating with T4 (or, better yet, T4, as not everyone converts T4 to T4 well) if FT3 is low or one has hypo symptoms can make a big difference in function.
Adrenal function - as our bodies are stressed, and particularly get depleted in nutrients, our adrenals have trouble keeping up, so ensuring vitamin C and B5 (pantethine) is adequate for adrenals to use, then supplementing with replacement dose hydrocortisone (2-30mg daily) if your morning cortisol, 24 hour saliva or urine cortisol are low, or ACTH doesn't respond adequately on an ACTH stim test. The Clinicians Coalition guide days not to supplement hydrocortisone in 3 places, but my ME/CFS doc (a Coalition member) prescribes it as for others - but I think the more conservative docs won out on this point, to the detriment of many patients.
You're welcome.😃 Let us know how you progress... It's not instant, but trying these strategies can help, unless you have other significant issues that have not been addressed (mold or other toxicity, infections, autoimmunity, spinal issues, etc.)