@Sleeping Beauty from my experience, definitely start with the gut. As @Asklipia notes, start with good food, something like the Perfect Health Diet, then slowly add pre and probiotics as tolerated. After a long period of VLC paleo, just changing to the PHD has made a huge difference to me in a few months and I am starting to become much more tolerant of the pre and probiotics which caused me so much trouble in the beginning.
Regarding supplementation in general and methylation in particular, I have found some benefit from experimenting with these prior to the dietary change, though I note the reservations of @Vegas that the shutdown of these pathways may be protective and ramping them up artificially may be counterproductive. A crisis a couple of weeks ago made me realise that the dietary changes had induced a lot of metabolic changes which made my supplementation regimen untenable so I stopped everything while I tried to work out what was now helpful and what was not.
This in itself reinforces the notion of starting with the gut - supplement needs might be very different once changes start happening in the microbiota (and will probably continue to change, so be flexible!).
I haven't worked everything out yet but several things are obvious. My neurotransmitter balance has changed so that supplementation to boost acetylcholine (eg choline bitartrate and acetylcarnitine) is now counterproductive.
My need for digestive enzymes has almost disappeared, going from a very high dose (6 x Creon 40,000 pancreatic enzymes capsules per meal [the number refers to lipase units]) to maybe 1 per meal (could probably stop but after so many problems in the past haven't yet had the courage).
Methylation supplements need to be redefined. I definitely felt worse for stopping these so have been experimenting to find a new balance. My unquenchable need for methylfolate has moderated considerably, but even more interestingly, my response to carnitine has changed dramatically.
Previously L-carnitine fumarate did nothing for me but I did respond to Acetyl-carnitine. With the benefit of hindsight, I think the latter was purely the result of a boost to acetylcholine, rather than any change to mitochondrial function. Certainly my energy levels didn't really improve and OAT tests continued to show abnormalities in fatty acid metabolism characteristic of a lack of carnitine and the Kreb's cycle remained stuffed.
This time around I had to stop acetyl-carnitine so cautiously tried LCF again. Now I am very sensitive to it. I am hoping this means that intractable blockages in mitochondrial function might slowly be lifting.
When I get more uBiome results I'll report on changes in gut flora that have accompanied these events.
With best wishes
Alice
Regarding supplementation in general and methylation in particular, I have found some benefit from experimenting with these prior to the dietary change, though I note the reservations of @Vegas that the shutdown of these pathways may be protective and ramping them up artificially may be counterproductive. A crisis a couple of weeks ago made me realise that the dietary changes had induced a lot of metabolic changes which made my supplementation regimen untenable so I stopped everything while I tried to work out what was now helpful and what was not.
This in itself reinforces the notion of starting with the gut - supplement needs might be very different once changes start happening in the microbiota (and will probably continue to change, so be flexible!).
I haven't worked everything out yet but several things are obvious. My neurotransmitter balance has changed so that supplementation to boost acetylcholine (eg choline bitartrate and acetylcarnitine) is now counterproductive.
My need for digestive enzymes has almost disappeared, going from a very high dose (6 x Creon 40,000 pancreatic enzymes capsules per meal [the number refers to lipase units]) to maybe 1 per meal (could probably stop but after so many problems in the past haven't yet had the courage).
Methylation supplements need to be redefined. I definitely felt worse for stopping these so have been experimenting to find a new balance. My unquenchable need for methylfolate has moderated considerably, but even more interestingly, my response to carnitine has changed dramatically.
Previously L-carnitine fumarate did nothing for me but I did respond to Acetyl-carnitine. With the benefit of hindsight, I think the latter was purely the result of a boost to acetylcholine, rather than any change to mitochondrial function. Certainly my energy levels didn't really improve and OAT tests continued to show abnormalities in fatty acid metabolism characteristic of a lack of carnitine and the Kreb's cycle remained stuffed.
This time around I had to stop acetyl-carnitine so cautiously tried LCF again. Now I am very sensitive to it. I am hoping this means that intractable blockages in mitochondrial function might slowly be lifting.
When I get more uBiome results I'll report on changes in gut flora that have accompanied these events.
With best wishes
Alice