@Chris. All I understand so far is that DCA metabolism is dependent on two things - age (the younger, the faster the clearence - as with a wast majority of the drugs) and the genotype (it appears that there are 3 or 4 variatons of the enzyme GST). DCA metabolism happens in the liver where gama S transferase does its job and breaks the molecule down in other simple compounds. Naturally, with age, the function of the liver gets "slower" or less active, that's why the clearence slows down a bit.
Till this moment, I have read a lot of papers that discuss the dosing and toxicity of DCA. What I can say - there are a lot of other toxic substances used as drugs these days. It's almost impossible to find new stuff which is 100% safe.
Take for example Rituximab, while it had promise and maybe even HAS promise for further studies on ME/CFS, it's worth noting that even substance affects the immunity, makes you more prone to infections, can cause liver,renal,cardiac,allergic reactions etc. However, with proper care and scheduling this all can be controlled to some levels.
Back to DCA. Okay, let's talk about what makes dosing a little bit difficult:
- AFAIK, the safe dose of DCA is something between 12,5 mg/kg - 6,5 mg/kg. This is confirmed by dozens toxicology studies done in the previous decades. This substance has been observed from all sides. Stacpoole has researched its safety for like 30 years, I believe. He has a study in which children took DCA for years and nothing bad happened to them (one kid had mild peripheral neuropathy which went off and never came back after a break).
The doses were 25 mg/kg daily. I don't recall if a specific dosing schedule was used. Keep in mind, these were children, so the safe dose for adults is probably lower due to slower clearence.
-Many people tend to take the recommended amount so far (400 - 500 mg daily). Doses like this are considered low and the effect is really slow if you take it like this. However, keep in mind that if you take DCA with Alpha-lipoic acid - the effects are combined and potentiated, so you don't really need to overdo the intake. Give it time. No one knows why some experience DCA's effect on their ME/CFS in a couple of days and why some experience it in a couple of weeks. Heck, there are people who don't experience any improvement at all. Their disease could be an other subtype of ME/CFS which is not mainly related to metabolism/mitochondrial "ice age - low ATP production".
You can take a larger dose than 400-500 mg daily, this is your risk, DCA is not an official supplement or drug yet. Who know's if it will be - this would need more studies targeted towards its safety. If you decide to do more than half a gram to see if it's for you, if it helps you achieve the effects faster - consider doing schedules. So far there are two ways to schedule:
A) 5 days on DCA, 2 days off DCA. Repeat. This is an old way which IMHO is more suitable for someone with ME/CFS.
B) 14 days on DCA, 7 days off DCA. Repeat. I imagine if one with ME/CFS takes a break for a week, this could provide a bounce-back to previous symptoms. However, who knows how it could really be ?
- Take Vitamin B1! This is a must, people. There have been some guesses that the main reason why DCA could cause adverse reactions is the fact that somehow thiamine is depleted faster when someone takes DCA. So take additional thiamine / benfotiamine (you need less of the latter, but more expensive).
Idk what the doses should be - maybe somewhat between 100 - 250 mg of thiamine.
-Some people say that L-Carnitine could help. I don't know a lot about it. My guess is that Carnitine helps transform DCA or energy substrate to the mitochondria and hence it could reduce the needed intake of DCA/ALA as well as adverse reactions.
-Finally, some people get adverse reactions, some don't. If you've got some kind of nerve damage from MS, if you've got a nutritional deficiency or other more serious underlying untreated diseases - the numbing of the tongue etc. is much likely to happen.
Who knows. Maybe careful intake of 400 - 500 mg DCA daily, 5 days on, 2 days off, with Alpha-lipoic and B1 could be all it takes to avoid anything unpleasant at all. That's a big question. That's why this deserves more attention and discussion in the future.