I recently switched to a ketogenic diet and would like to share my experience and draw attention to some aspects that might not be common knowledge yet.
I prepared myself for the ketogenic diet. I had MCT oil, Acetyl-L-Carnitine, and the right food available. I use Fora 6 and Ketonix for keto measurement. I use Cronometer for nutrition tracking.
On day 1, I already was in ketosis. This is surprisingly fast and my only explanation for this is that my insulin defectiveness actually contributed to a faster ketosis onset. There was no typical keto flu. I felt metabolically fit but still "powerless" like you would during fasting. I intentionally waited for ketosis onset until I started taking fats so that my cholesterol doesn't rise unnecessarily.
On day 2, I felt fit and I had more power. My ketosis went into overdrive mode though (>100 ppm), like there was something overdemanding or overtriggering it. Carbs could not stop the overdrive as they should. I guess this was also due to insulin issues because I became hyperglycemic instead (2 hours post intake). Still felt good though. My kidneys got rid of all the excessive acetones.
On day 3-4, it was the first time in a long time that I felt like I was in remission. I felt completely normal during the day in terms of fatiguability and brain fog, though I still continued pacing. During the night, my symptoms changed from typical CFS/ME malaise feeling to "normal illness feeling". It basically felt like I was sweating out a cold, but I felt fit in the morning. This wasn't the case before. Before keto, I felt hungover in the morning. Furthermore, my lymph nodes were swollen again, and I still had pain occasionally.
On day 5-6, I experienced kind of a relapse. I metabolically felt like before keto. Same sleep issues. Needed 14 hours of sleep. Basically PEM. I guess just being awake for the whole days and not resting half of the days in bed kind of triggered PEM just as it used to do before keto. Keto doesn't seem to eliminate PEM, though it makes you feel like you're up to it when you're not in PEM.
Later, I also noticed that there is a burning pain in the thyroid region. And I experienced issues with my gallbladder dealing with all the fats. I should have increased fats gradually and support my gallbladder. Now, I'm going to take a premixed supplement to support gallbladder function and I'm eating more saturated fats to give the gallbladder more distinct signaling when to release bile. Moreover, I take Betain HCL+Pepsin (Doctor's Best) to support this trigger when I'm about to eat a larger portion.
In the course of nutritional tracking, I noticed how difficult it is to get sufficient potassium. So I switched to potassium salts. Without grains, the only remaining natural potassium source is an avocado but I'm no fan of it because of its environmental damage. Calcium might also be an issue if you're vegan because most of my calcium now comes from cheese. Other than that, there shouldn't be an issue with electrolytes and amino acids if you eat sufficient nuts.
Here is another observation I made. I need at least 1g of Acetyl-L-Carnitine during keto. Otherwise, my cholesterol levels increase. L-Carnitine is important for the utilization of long-chain fatty acids. Medium-chain triglycerides (MCT) can bypass the L-Carnitine-dependant breakdown.
I eat a lot of olives. Not only because I love olives but also because olives and their oil have a protective effect on lipoprotein oxidation (pmid:15168866; 10.1038/sj.ejcn.1601293).
I also try to eat a lot of eggs. Eggs are ideal sources of Lysine and Leucine. These two are the only ketogenic amino acids. Moreover, as already discussed, Leucine triggers AMPK and SIRT1 activation (10.1155/2014/239750).
In the context of the methylation trap theory, Lysine and SAMe-dependant methylation can help alleviate ATPase-driven RIG-I oligomerization (10.1073/pnas.2436556100) and its IFN-I activation. IFN-I activation can be speculated to play a role in the CFS/ME EBV-induced pathogenesis (10.1073/pnas.1913776117). Moreover, Lysine methylation can reduce ubiquitination-dependant proteasome-mediated p53 degradation, which is essential for EBV's BZLF1-mediated lytic replication and MHC class I suppression, which blocks CD8+ T cell maturation (10.1016/j.virol.2009.03.017; 10.1038/ncomms3359). However, ubiquitination plays a supportive part in the cytotoxic response during EBV's acute EBNA1- and EBNA4-driven phase (10.1073/pnas.94.23.12616). I'll write more about the link between lytic EBV, CFS/ME, and the thymus another time.
Lastly, I'd like to point out another study on ketogenesis and CD8+ T memory cell development, already posted here.
Concluding, I still feel more fit during the day. My brain fog is gone. No cognitive blackouts anymore. My muscle weakness is gone. PEM is still a thing. I still need more sleep, though I could stand up earlier, feel better, and thereby risk triggering PEM again. My connective tissue seems to have improved, but certainly not completely. I still have pleuritis and ECG abnormalities. It might still get a little bit better because they say that it takes one month until your cells are completely adapted to ketogenic energy utilization.
First, congratulations for your improvement and for putting together all this knowledge and sharing it with us! I have enjoyed reviewing the literature and trying to follow your reasoning.
I hope you don't mind me asking some questions about the biochemistry you have laid out. I will like to ask more specific things on what might be expected with a ketogenic metabolism in ME/CFS, as I am myself trying to figure out why some PWCFS respond so well to a ketogenic diet while others don't. But let me first address your first message so that I don't overwhelm you! :
I guess you assume that you might lack L-carnitine because methylation is needed to synthesize it? . What's your methylation (and adjacents) cycle status at the moment?
You say that taking enough lysine can alleviate RIG-I formation and subsequent IFN-I activation (which have been associated with viral chronic infections).
Ok, help me understand what you mean: It seems that methylation of lysine will actually lead to activation of IFN I response, what is the opposite of what you imply. What am I missing?:
"(...) Lysine methyltransferase NSD3 interacts with and directly monomethylates IRF3 in the nucleus, leading to the en- hanced IRF3 transcriptional activity and antiviral immune responses (...) is constitutively expressed and localizes to the cytoplasm under steady state; upon innate recognition of pathogens, IRF3 is phosphorylated by TBK1 and IKKε, leading to the formation of IRF3 homodimers and subsequent translocation to the nucleus, where it activates the transcription of genes encoding type I IFN(...) "
Ok, how exactly does lysine methylation reduce the degradation of p53 by BZLF1 protein mediated by ubiquitination of lysine? I guess that methylation of lysine residues might compete with ubiquitin? Could you please provide a source for this step?
Finally, you explain that methylation of lysine will reduce ubiquitination-mediated p53 degradation for EBV lytic phase of infection. But, on the other hand, we need proper lysine ubiquitination for proper MCH-I specific viral recognition by T cytotoxic cells... Then, having both lysine and proper SAMe and methyltranferases, where will our immune system be in terms of EBV control?
Aside from this, may I ask what your theory of ME/CFS pathogenesis is? I guess you think EBV plays a key role. What about the CDR state, HHV-6 or borrelia B? . What role do they play? What about a partial methylation blockage? . Could it be restored? Is it a main contributor or just a downstream epigenetic aberration, perhaps induced by the mitochondria as a defensive mechanism? Please excuse the interrogatory. I really like to know how great thinkers see the whole picture!
Ok, please be benevolent with me, as I just once had some basic understanding of immunology and biochemistry, but not anymore!
Thank you for sharing your work and congrats again for your Improvement. I hope you continue improving!