Jenny, like you my symptoms fluctuate. I think if a supplement makes you feel a certain way, then that is the way the supplement makes you feel even if it doesnt do it all the time, because sometimes other things are blocking it.
There is a tendency to think of only the methylation supplements as having any importance in the protocol but that would be a mistake. All kinds of things up and down regulate enzyme activity. Heres a list of some of the things that will affect the activity of methyl cycle:
Methylation (SAMe) Feedback mechanism (Too much, Too little)
Radical oxygen species (oxidants)
Anti-oxidants
Inflammatory cytokines
Chemicals/Toxins/Medicines (ethanol,)
Hormones (sex hormones, adrenal hormones, insulin, IGF, etc)
Neurotransmitters (dopamine, etc)
Blood sugar/glucogen
Presence of cofactors (zinc, iron, copper, etc.)
Heavy metals (Hg, PB, Al)
Nitric oxide
Heat
ph
etc. (Science has identified very few of the substances that regulate genes)
Take a second look at Fredd's protocol or my own supplement list. Notice that they also provide many things that regulate methyl cycle enzymes. In particular:
High anti-oxidant supplementation.
DHA (fish oil), DHEA, Vitamin K, and nettle all significantly inhibit inflammatory cytokines (according to
www.lef.org)
ph balance maintenance.
I think you could drive yourself crazy worrying about what will UPregulate this or DOWNregulate that. In general I think of it in terms of NORMOregulating and ABNORMOregulating. The oxidants, chemicals, and inflammatory cytokines ABNORMOregulate and the anti-oxidants, hormones, and inflammatory cytokine inhibiting supplements NORMOregulate. (You have to generalize to get anywhere. Then you test. Then you fine tune only if you HAVE to).
I should make it clear that I do not choose supplements based on what they make me feel. I am extremely loyal to a supplement if it makes sense that I need it it is a basic nutrient, it has been proven to help others with my symptom, I know a bit about how it works and it strikes me as being an important piece of the puzzle. If so, I put it in play and look for the next puzzle piece because I know it can take many pieces to solve a puzzle. Freddd found the critical puzzle piece for methe knowledge that there were active forms of B vitamins and that some people could not make active forms out of inactive onesthe idea of just using active B supplements for everything so one neednt actually know which enzymes are broken to fix the problem. This is a profound concept!
When I said that I know how various supplements make me feel I listed some examples and I dont think any were methylation supplements. I started taking DHEA before I found Freddds website and DHEA was the one supplement that made the drastic change for me. In only about 10 minutes it quenches panic/depression and normalizes blood pressure (drops mine over 30 points and keeps it there for 12 hours). It is a potent TNF-alpha inhibitor so for all I know that is how it regulates my enzymes back into functionality. But what is regulated this way can be unregulated. And so some other chemical can come along and cast me adrift again. I do not know if I would have this problem if I actually took methylation supplements in the high doses that Freddd does. I have many things on my to investigate list.
I got onto WrongDiagnosis because I was a vegetarian and that topic was B12. A vegetarian has to pay attention to B12. I read Fredds list of possible B12 deficiency symptoms and recognized many symptoms I had experienced on the list. It was a revelation to find there was a single other person in the world who ever felt like insects were crawling all over them when they were not, for instance. I cannot tell if Freddds protocol banishes this symptom for me because it is a rare symptom. But Freddd;s protocol saved my life nonetheless.
Here is what I can tell of the methylation cycle and why its important:
(1) It normalized my high homocysteine. Every 3 points above normal (6.3) is linked to a 35% higher rate of strokes. Strokes run in my family and I had two TIAs myself at age 49.
(2) I now have normal levels of carnitine (further evidence my methyl cycle is working). I do not know what my carnitine levels were before. I just care that I am methylating because DNA needs to be methylated to prevent cancer and methylated estrogen is actually being PATENTED to TREAT cancer!
(3) When I am not methylating I have a terrible weakness and pain in my wrists which goes away when I am methylating. (I am also trying to pay attention to see if abnormally severe back pain can be tied to methylation status (for one of my doctors had attributed it to low Vitamin D but that was not it. I do have this banished almost 100% but not by Vitamin D)).
(4) I have an insect bite allergy and when I am methylating properly insect bites itch for about 10 minutes and then never again, nor do they swell. (Everyone notices this btw). (Please don't assume this will take care of anaphylactic shock allergies).
So (1) can tell me exactly how I am doing whether I am controlling my methyl cycle optimally. But (3) and (4) can be my instantaneous rule of thumb guide. As you can see the effects I can actually feel are not major (I am already using DHEA to clear up the lion's share of my symptoms). Proper methylation avoids cancer, strokes, and heart disease. Ill take that!
I strongly believe you cant control what you cant measure. If you can find a way to measure it, it seems to me you can find a way to control it. Homocysteine is the control IMHO (its relatively cheap and we know what the optimal value should be (6.3). Unlike measures of B12 and folate, homocysteine is an organic acid test which means its results are always useful.
Lastly I think having the guts to try a full protocol all at once so it has a chance to work helps a lot. I doubt if it can be effective any other way.
I took an ESR test and was normal so conclude no CFS. I would have guessed otherwise at one time, but no more. I have had a lifelong wide array of disparate symptoms to which I have never affixed names. Many are on Freddd;s list of possible B12 deficiency symptoms. But many are not. And, yes, fatigue is one of them, but I;m anemic, slubclinically hypothyroid, and have adrenal issues. I think that is plenty of reasons for fatigue.