Books and Websites
Could it be B-12? - This book explains the importance of B-12 and its functions in keeping the body in good health - and why this deficiency is so frequently overlooked by modern medical practicioners. Of particular interest to me was the chapter on the impact of general anesthesia or dental work on the body's B-12 reserves. (Spoiler alert: nitrous oxide is hugely destructive.)Note that this book does not address the impact of the genetic variants which impact 40% of the US population, impairing our capacity to absorb the inactive form of B-12, cyanocobalamin, which is the standard B-12 in supplements and enriched foods absorption, and it barely mentions adenosylcobalamin, which is essential to the production of energy in every cell in the body. See also the author's website, B-12 Awareness.
For more information on the methylation cycle and the MTHFR genetic variant, see these websites:
Glutathione and the Methylation Cycle by Rich Van Konynenburg Ph.D. Rich's ground-breaking exploration of the involvement of impaired methylation cycle in ME/CFS remains, for me, the gold standard of understanding of this topic. This page lists numerous papers by him and links to an absolutely brilliant lecture in which he explains the methylation cycle in clear and lucid detail. Unfortunately, to my knowledge, Rich was not aware of the role of the COMT genetic variant and adenosylcobalamin deficiency in this illness, but if you want to truly understand the methylation cycle, this is the place to start, IMHO.
About Methylation And The Methionine Cycle - This is a very detailed discussion of the methylation cycle, but the author completely misses the significance of adenosylcobalamin.
TBD
For more information on adenosylcobalamin, its role in the Krebs cycle (which produces ATP, the "fuel" of the cells), and the COMT genetic variant, see these websites:
4 Must Know Facts About Adenosylcobalamin
The Super Form of B-12
What is the COMT Gene and How Does It Affect Your Health?
Dr. Gregory Russell-Jones' B-12 Discussion
Dr. Schweikart's Adenosylcobalamin Discussion
Phoenix Rising Forums
Note: you may need to create a free account on Phoenix Rising Forums and log in so you can see the Message numbers (#) at the bottom of each user comment. These notes identify each message by number to make it easier for you to find the message in question.
If you are unfamiliar with the methylation cycle and/or how the MTHFR genetic variants impact this vital function, you may want to start with The Stages of Methylation and Healing, which gives an overview of the methylation cycle.
Below you'll find a number of forum posts that I feel are relevant to understanding the health impacts of adenosylcobalamin deficiency and related conditions, along with potential ways to address this, and potential adverse effects of some of these corrective actions.
B-12 The Hidden Story
This very long thread contains tons of information about the methylation cycle and methyl B-12 and methyl float deficiency. Here are two messages of particular interest:Message #2901 discusses four supplements needed to overcome 4-way deadlock of the Krebs cycle (often referred to as "methyl block" or "methyl trap". These supplements are AdoCbl (adenosylcobalamin) and LCF (L-carnitine fumarate) in addition to the more widely known methyl folate and MeCbl (methylcobalamin).
Message #2902 suggests magnesium theronate for sleep.
Large Amounts of MFolate and Potassium
Message #23 discusses the recycling of adenosylcobalamin in normal functioning and mentions factors (nitrous oxide, cyanide as in cyanocobalamin) that destroy the active forms of B-12. In other words, in normal functioning, B12 is mostly recycled, not used up, but if B-12 reserves are exhausted, glutathione production drops, making it difficult for the body to recover its B-12 reserves. This directly impacts the Krebs cycle and mitochondrial production of ATP.
Message #30 discusses anger/anxiety when starting AdoCbl (adenosylcobalamin) if taking carnitine and suggests microdose of carnitine and/or TMG dose. Mentions L-carnitine fumarate as a cause of anxiety/anger, but I believe this is a transient startup effect. Also mentions the COMT genetic variant and associates this with extreme anger or anxiety when increasing methylation.
(This has happened to me three times; extreme anger when I started methylcobalamin and methyl folate a decade ago, and intense anxiety when I started adenosylcobalamin in July 2020 and again when I started l-carnitine fumarate a week later.)
Message #31 says anxiety-anger activation happens with ATP startup; carnitine can produce very large hyper reactions most often. TMG can take the ATP edge off.
Plausibility of NAC inducing B-12 Deficiency or Methyl Trap
Message #2 explains how blood tests can show normal or high B-12 levels despite B-12 deficiency because low glutathione prevents proper B-12 utilization. Adverse effects when starting NAC are transient, not permanent.Message #4 discusses the effects of "methylfolate trap" which is addressed by NAC. NAC may have nasty start-up effects but is beneficial long-term in improving glutathione production. This message also mentions the "methyl trap" theory of Yasko/Konynenburg/Fredd, which is not the same as the "methylfolate trap" discussed in this thread.
Carnitine or NAC for those with CBS+, NOS+, COMT+, SUOX+ ??
This thread discusses various aspects of the methylation cycle, B-12 deficiency, and transient adverse effects of NAC startup, and discusses various genetic variants which can impact methylation cycle function. I think there's a lot of good info in this thread, and a number of things that correlate with my own experience.Message #4: NAC detox is a "methyl trap." The use of L-carnitine fumarate is better for people with FMS/ME/CFS.
Message #6: NAC reaction: headache.
Message #9: The responder believes Fredd's hypothesis that ME-CFS is caused by an underlying long-term and drastic B-12 deficiency. (I think he's right.)
Message #12: discussion of L-carnitine fumarate, AdoCbl (adenosylcobalamin), TMG (trimethylglycine), mitochondria, ATP (adenosine triphosphate), Krebs cycle. Also: it can take a year or more for mitochondria to restore; years for other functions affecting neurological & bone growth.
Message #13: NAC, hypotension, nitric oxide increase. (Hypotension, or orthostatic intolerance, has been a hallmark of my illness, especially in recent years. Treatment with the drug Mestinon proved to be both dangerous and ineffective.)
Message #16: Contains a list of basic cofactors from Fredd. Mentions his levels of healing post.
Message #18: Discussion of adverse effects and the inefficiency of folic acid. Also has a link to the "levels of healing" post.
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