My Keto Experience

[serg1942]

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.

Hi @nerd,

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(...) "

https://www.researchgate.net/public...mmunity_via_direct_lysine_methylation_of_IRF3

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!

Sergio

 

[nerd]

I hope you don't mind me asking some questions about the biochemistry you have laid out.

Your questions are welcome.

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?

No, that's not the main reason. My methylation cycle is well managed with B12, SAMe, TMG, lecithin, as far as I can tell from my symptoms. The reason is that L-Carnitine is required for the transport of long-chain fatty acids and if your keto diet doesn't solely rely on MCT, which would be unhealthy I think, you'd also need more L-Carnitine because of the much higher intake of fats in the ketogenic diet. This allows for L-Carnitine to be depleted faster. The supplements can counteract this.

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?:

I must have made copy-paste mistake when copying the doi reference to the post. The doi (10.1073/pnas.2436556100) is completely off-topic to the place it's mentioned. But I must have had a reference for the statement, though I'm not sure if I can rediscover it.

I think we can agree that the ATPase-driven oligomerization of RIG-I can be triggered by dsRNA and this causes IFN-I activation (10.1038/embor.2013.102). But what role do lysine and methylation play in this?

Maybe I meant the methylation of lysine residues in histone (H3K4me3). HDAC6 inhibitors promote the methylation of lysine residues of histone H3 by the inhibition of its demethylase (10.1124/mol.110.067702). HDAC6 is also linked to the RIG-I activation (10.1016/j.ebiom.2016.06.015). A recent study establishes the evidence on the lysine methylation-regulated deacetylation of histone H3 (10.1093/nar/gkab154). BHB is not an HDAC6 inhibitor though (10.5698/1535-7597-14.6.355). It might have been a mistake to not check if or not all HDACs are affected. Sodium butyrate isn't an HDAC6 inhibitor either. SAHA (Vorinostat) is a pan-HDAC inhibitor, though, so it should do the job.

What I probably didn't mean is the HDAC3 inhibition of BHB and the RIG-I-overactivated downstream inhibition of IFNB1 inducing IFN-β (10.1007/s13238-020-00751-5; 10.1039/c7ib00146k).

Another narrative I might have targeted is not to take lysine without sufficient methylation support since the methylated form can not be acetylated and the excess of lysine acetylation would be the problem. Lysine acetylation participates in RIG-I activation and its oligomerization (10.1016/j.ebiom.2016.06.015). In this case, my writing was inaccurate because how I wrote it, it seems like lysine supplementation could help in this context. The competitive aspect continues in the remaining paragraph, so I think this is what I really meant.

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?

Exactly, I think this is what I meant, similar to the lysine acetylation preservation by methylation. There is one study that suggests this mechanism (10.1101/2020.11.20.392290).

Then, having both lysine and proper SAMe and methyltranferases, where will our immune system be in terms of EBV control?

I guess in a susceptible state to environmental factors that influence methylation and acetylation. I also discuss the controversy in this post on reactivation therapy.

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?

I try to stay open-minded to all new theories, but I'm quite sure that it is triggered by pathogens and predisposed by genes or pre-existing immune dysregulations from other pathogens or vaccines. Many pathogens share their mechanisms, so it doesn't have to be one in particular. It might be more useful to look for virally-mediated proteins than to look for viral antibodies or complete viral proteins via PCR.

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?

I gave a short overview of my understanding of the methylation blockage in this comment. I think the pathology of CFS/ME involves a methylation (group) overdemand and one methylation problem that can result from this, like mast cell instability, is the insufficient resupply of methyl group donors. The complete dysbalance in the methylation cycle, which is tied to the NAD+ cycle, also comes with substrate and feedback inhibition of its metabolites, e.g. via SAH. The choline cycle and TMG are tied to this as well. If you have further questions on the methylation, please feel free to ask them in the referenced post.

Please excuse the interrogatory.

This isn't interrogatory. The shorter the better. This is just my style.

Ok, please be benevolent with me, as I just once had some basic understanding of immunology and biochemistry, but not anymore!

I'm no expert either. I'm just good in reading into certain topics. Maybe a year ago, my pathology modeling knowledge was better, now it's biochemistry and metabolic modeling. But it fades quickly, as you can see. I don't know if it's because of CFS/ME or if it's like that for everyone.

I hope you continue improving!

Thank you! I wish this for you and everyone in this awesome community. I guess we need to educate ourselves and hypothesize ourselves because (almost) no one else will. Even active researchers will depend on our feedback among all the theories that are out there. But we can't do it with the same degree of quality that we would invest into it when we'd published our work. I think an "almost accurate" but consensus-driven approach allows for more progress than an "perfectly accurate" approach from a a single researcher who hasn't the means and funds or energy to evaluate every (sub-)theory.

And without a complete overview, it's getting nowhere, as we can see in the decades of CFS/ME research. They aren't productive enough because they waste their resources on trials like Rituximab of the functional disease and not the determining of the causality. This is the work style of HIV and cancer research where sufficient funds are available. But as Ronald Davis and the OMF try to explain, you have to adapt to the limited funds that are available.

 

[serg1942]

Hi @nerd ,

Thank you so much for your detailed response! I will read it carefully when my mitos allow and will add some more questions regarding the ketosis in ME/CFS, if you don't mind.

In the meanwhile, may I ask how are you doing on the keto diet? Are you still on it? If so, are you still noticing improvement?

Thank you!
Sergio

 

[nerd]

In the meanwhile, may I ask how are you doing on the keto diet? Are you still on it? If so, are you still noticing improvement?

Sorry that I forgot to respond. I'm still on the ketogenic diet. It seems like some of the improvements disappeared along with my keto rash. Maybe it was the bacterial infection, after all, that regulated my immune system and helped kind of. Or maybe it's just the heat that I can't handle well. The keto diet certainly didn't help with preventing PEM, that's very clear to me. Air hunger isn't affected either, as bad as usual.

I think my brain fog baseline has improved. My low neuromuscular tone has not improved. Peripheral neuropathy seems to have improved, though, consistent with sugar-free and low-carb diet, in that I barely notice any tremors anymore. No polyuria either. I haven't checked my creatinine levels in my urine yet, but I gauge that they have become lower as well.

The muscle function and exhaustibility itself have changed, that's all I can say for now until I can verify if I can also rebuild muscle. But I think most dominantly it is my adrenal function that has improved and this might also be due to the glycolysis and how it causes polyuria and creatininuria, thereby exhausting the adrenal glands. So I stand up earlier, even when I feel wracked, my circadian rhythm has improved. I don't think it's improved muscle function itself that makes me feel like I have to stand and walk. Maybe it's just my hyperactivity kicking in again, which basically disappeared with CFS/ME. I think I can stand better, but the tonus in the spine hasn't improved, so it's still a challenge to keep my back upright.

Two side effects have emerged. First, there occasionally is some severe pain left of my spine. I think this only happens when my smooth muscle tone occasionally improves, for whatever reason, and so I feel the pain from my scoliosis. Second, I have nausea very frequently. But this might also be due to the other drugs and supplements that I use, like Ivermectin and Quercetin, all trying to boost apoptosis, which typically triggers nausea. None of the "immune boosters" that I took previous to this kind of therapy have ever triggered nausea. It's not the kind of nausea where you don't have any appetite. I have appetite, I'm hungry, but it's kind of a mild burning in my whole stomach area, maybe similar to what I remember from choline infusions, but with nausea at the same time.

I have begun using Valaciclovir along with Ivermectin, and soon, I intend to try Low-dose Naltrexon, Low-dose Phenytoin, Ketotifen (there's a shortage until August, unfortunately), and an H2 antihistamine (in case the nausea is caused by mast cells of the stomach). I also want to begin the reactivation therapy as soon as I have a complete analysis of all the drugs since the ketogenic diet + 500mg Valaciclovir daily + a normal dose of liposomal Quercetin is just a mild reactivation therapy that might need years for sufficient latent viral elimination. And there is still the unsolved question of how to handle miRNAs which will be released during reactivation therapy, no matter how severe the abortive infections are in my case. Moreover, I will have to determine which virostatic provides the best balance of efficacy in the nervous system while being safe. One risk for these drugs are seizures, after all, and Phenytoin could reduce this risk hopefully, just as neuroinflammation.

 

[Jenny TipsforME]

I’ve just started keto this week. How have your experiences been around sleep? @nerd @livinglighter and co

I find while I do sleep it’s deeper but I’m waking up really early and don’t get back to sleep. I’m wondering if this is the Dawn Effect? If it’s harder to stay in ketosis early in the morning due to cortisol etc would that give a hypoglycaemic reaction? I’m finding sleeping tablets are counterproductive because they trigger acid, which is a louder problem on increased fat. Also I am going to sleep more easily, so that doesn’t seem like the right thing, I’m just not getting back to sleep if I wake at 3 or 4am+.

I’m feeling really really tired, but it is tiredness rather than ME symptom exacerbation. I seemed to go into ketosis easily, judging by the urine test, but I was already low sugar/carbs. I feel like it’s definitely worth giving keto a good go for a few reasons I’m too tired to explain right now.

NB I’m not well enough to read long answers

 

[Murph]

keto update from me:

I've been on it and off it over the last 2 years and I'm increasingly convinced it is making a big positive difference for me. PEM threshold way higher. I can do things I can't do when off keto. e.g. I started lifting some weights again, weights that had just been sitting in a corner collecitn dust, but I grabbed them spontaneously a few days after getting back on keto.

A few notes

• My blood sugar control seems to be a bit screwy. I'm no good on regular carbs these days. It could be that aspect which is being improved by keto.
• You can lose weight pretty easily on keto: in fact the challenge is willing yourself to eat enough to not end up in calorie deficit.
• Also, managing the digestion is a challenge - you need to eat a lot of fat, but need fiber to balance that.
• I seem to need b-vitamin supplements to reap the benefit.

if you're wondering what to try in the next few months, and open to trying a diet, I can recommend giving keto a shot. it's cheap (you were going to be buying food anyway, you just buy something higher in fat) very widely tried and probably pretty safe for almost everyone. It doesn't work for everyone but maybe you'll be in a subset like me!

 

[Jenny TipsforME]

In the autumn I felt like keto had quite a big positive impact. At the moment it’s not having such a good effect physically (which might mean it was coincidental before). BUT I do find it consistently improves my cognitive clarity/stamina which has greatly improved my quality of life. My brain seems to prefer running off ketones. Also I don’t get worse POTS symptoms after eating, which was quite a big problem for me.

@Murph I still find it difficult not to gain weight on keto. I think my calorie needs are just really low and as soon as you’re adding extra fat that’s not very much food quantity at all. I’m a short, middle aged woman who can’t exercise and uses a wheelchair so I must have one of the lowest calorie needs around! I generally get around this by only having a token amount of food at lunch, just enough so my stomach isn’t empty to take medication.

I’ve got a somewhat lighthearted recent blog post on keto
https://tipsforme.wordpress.com/202...-could-be-a-high-tension-competitive-tv-show/

 

[Murph]

In the autumn I felt like keto had quite a big positive impact. At the moment it’s not having such a good effect physically (which might mean it was coincidental before). BUT I do find it consistently improves my cognitive clarity/stamina which has greatly improved my quality of life. My brain seems to prefer running off ketones. Also I don’t get worse POTS symptoms after eating, which was quite a big problem for me.

@Murph I still find it difficult not to gain weight on keto. I think my calorie needs are just really low and as soon as you’re adding extra fat that’s not very much food quantity at all. I’m a short, middle aged woman who can’t exercise and uses a wheelchair so I must have one of the lowest calorie needs around! I generally get around this by only having a token amount of food at lunch, just enough so my stomach isn’t empty to take medication.

I’ve got a somewhat lighthearted recent blog post on keto
https://tipsforme.wordpress.com/202...-could-be-a-high-tension-competitive-tv-show/

Wow, amazing how you've got AI to write that blogpost for you! I've been on low fodmap for years, I think that's why I find keto kind of easy, I'm already restricting lots of sugars and carbs, so taking them all out isn't so hard.

(ps I think cauliflower is high fodmap?)

 

[*GG*]

i just eat coconut oil, I used to be able to buy online at a great price, but I find something with a little taste in the store now. I bake a lot of chicken and like the skin crispy, so I pour it into a container, and am now eating that fat. I used to give it away, good in soup etc..

Been on an off Keto the last 3 plus years, typically this time of year, after the holidays. Doesn't seem like I'm dropping the weight this spring, 1 month on now, lost about 3lbs only, think I used to be able to drop a couple pounds a week to start. Not sure if I already plateaued off, but I'm going to stick to it for at least another month. I might try carnivore

I put on 20lbs in the last half year, so would like to drop that much weight, and perhaps more! But taking things day by day. I was told with Keto you want to get 70% of your calories from fat, so that's how it's different from Atkins, which has also helped me in the past!

GG

 

[GreenEdge]

Why Is MCT Oil Good for the Keto Diet?
Compared to short-chain and long-chain triglycerides (or LCTs), MCTs (also sometimes called “MCFAs” for medium-chain fatty acids) are more easily converted to ketones because the body has to do less work breaking apart their carbon bonds.

Coconut oil naturally contains MCTs, namely: 42% lauric acid, 7% caprylic acid, and 5% capric acid (1)

Pure MCT oil does not solidify in the fridge. This is not to be confused with coconut oil – which will solidify upon refrigeration. MCT oil will maintain it's liquid form if you put it the fridge.

 

[Jenny TipsforME]

What I can’t work out is d-ribose and keto. It’s not straightforward and I’ve read conflicting information.

I think it was perhaps indirectly pushing me out of keto but I find it really helpful.

 

[livinglighter]

I’ve begun my keto journey now. It wasn’t easy. At first I depended on carbs a lot for energy. My overall condition has changed quite a bit and I don’t need carbs to manage like I did before.

What I done was found lots of keto food replacements and tried out different recipes until I found things I enjoyed eating.

It’s early days but I’m trying to eat very low carb and sugar for the rest of my life.

 

[Murph]

Another keto update from me.

I got on keto a few weeks ago, and unlike last time, there was no upside in energy. i was flummoxed because i was eating right, was definitely in ketosis, taking all my usual supplements that help and still felt terrible.
Then i remembered it had been ages since I did any potassium supplementation so I got straight onto that and boom.

Within a day of tipping LiteSalt in my drink, everything was a million times better. I feel kind of spectacular! here's hoping it lasts (and hoping I don't overcorrect and end up with some sort of potassium poisoning!)

so I guess the tip for anyone reading this in future is to test keto with potassium vs just keto if you're already trying keto!