nerd

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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.
 

Mary

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@nerd - thanks for sharing your experience! I tried keto a couple of years ago and lasted less than a week. In 2014 I discovered that branched chain amino acids reduced my PEM recovery time from 2-1/2 - 3 days down to 1 day which was huge for me. I've been taking them ever since.

So a couple of days into keto I started crashing (it was not the keto flu - crashing (or PEM) has its own distinct and very familiar exhaustion! ) Anyways, I started crashing easier, and took longer to recover - I was rapidly going back to the bad old days pre my 2014 BCAA discovery. So I stopped it, and loaded up on BCAAs and got back to where I started from.

I figured that since I was eating so few carbs on keto, my body started using more aminos, including BCAAs for fuel. So I've wanted to try keto again for various reasons, but figured if I were to do this, I'd have to increase my BCAAs by quite a bit.

Do you have any thoughts on this?
 

wabi-sabi

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So a couple of days into keto I started crashing (it was not the keto flu - crashing (or PEM) has its own distinct and very familiar exhaustion! ) Anyways, I started crashing easier, and took longer to recover
I had a similar experience with keto. I came to the conclusion that it is not a miracle cure! It was so horrible I will never do it again!

As long as I get sufficient protein, I do better when I eat more carbs.
 

nerd

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As long as I get sufficient protein, I do better when I eat more carbs.
Maybe here is the difference. I was doing bad with carbs and especially sugar anyway. I'm probably insulin insensitive due to hyperinsulinism and hypoglycemia. My neuropathy was triggered by carbs like it is with Diabetes mellitus. I think CFS/ME patients are susceptible to reduced insulin sensitivity because of the issues with glycolysis. The same pathology causes early-onset Alzheimer's. You don't want to overstimulate glycolysis. Otherwise, neuropathy happens.

I figured that since I was eating so few carbs on keto, my body started using more aminos, including BCAAs for fuel. So I've wanted to try keto again for various reasons, but figured if I were to do this, I'd have to increase my BCAAs by quite a bit.
My take on this is that it doesn't really "change" CFS/ME. It has health and immunological benefits that I think can have some positive effects with CFS/ME in the long term. And it significantly reduces the role of glycolysis from energy utilization, though this needs time. It will also take time for the insulin sensitivity to go back to normal. By not feeding into the synergistic effect of CFS/ME's glycolysis with carb intake, I also hope that it reduces the metabolic consequences on oxidation, ATP, hypoacetylation, and all the other issues, though most of them are only partially affected by ketone pathways. There is no wonder to expect.

What can go wrong? I think it's possible that you end up with Acetoacetate instead of BHB because of a low NADH/H+-NAD ratio in the liver. Acetoacetate is an inefficient energy source and can not be used by all cell types. A keto rash can also be a sign that too much acetoacetate is produced. The reverse is also possible in that you get sufficient BHB from the liver but with too low NAD-NADH/H+ ratio, which prevents the cells from using the BHB. To check for the first case, you could use a BHB supplement and see how it affects your energy. If you don't notice a difference, the cells are overoxidized. In either case, a comparison of breath acetones with blood BHB could also give a relative measure of how the balance between Acetoacetate and BHB is maintained. The glycolysis does the same thing to the cells but it is more susceptible to overoxidation because of more interactions with the NAD cycle.

It's also possible that there is a blockage in the citric acid cycle and thiamine deficiency would be a typical trigger for this. The normally increased glycolysis in CFS/ME will increase the demand for thiamine anyway. Thiamine is an essential cofactor of α-ketoglutarate dehydrogenase, which catalyzes α-ketoglutarate to Succinyl-CoA, and pyruvate dehydrogenase, which breaks down pyruvate to Acetyl-CoA, which ensures that glucose metabolites are integrated into the citric acid cycle. In the case of thiamine deficiency, BCAAs would be the only way to refuel these two CoAs. And without these CoAs, neither glucose nor ketones can fuel the energy metabolism.

And again, methylation plays a role in terms of the interaction with histone and its methylation vs. acetylation. BHB is a histone deacetylase inhibitor, and histone deacetylase is clearly associated with CFS/ME (10.1016/j.clinthera.2019.02.012). This is probably the result of the deregulation of pyruvate dehydrogenase in CFS/ME. This might be something positive.

Now, there's another thing to consider. Even if you pace, it is possible that the normalized citric acid cycle function contributes to Acetyl-CoA metabolites in the cytoplasm (outside of the mitochondria) and thereby induces histone acetyltransferase (just as glycolysis does). How is the citric acid cycle affected inside vs. outside the mitochondria? If it doesn't work with glycolysis, the problem will persist with ketosis but the elevated energy throughput might enhance the problem and you might not even notice it because it is the metabolism itself that tries to adapt to the increased energy availability. The problem exists with glycolysis all the same, but in CFS/ME, the glycolytically-mediated energy metabolism is very imbalanced and depends on the current phase.

What's more? EBV's EGR1 gene could profit from increased acetylation of h3 and enhanced histone acetyltransferase. But this again is the same concern with glycolysis.

By the way, the increased histone acetylation from Acetyl-CoA upregulates Foxo3 protein synthesis in the nucleus via SIRT3 (10.1007/s11064-018-2588-6; 10.1016/j.tem.2013.09.002), which, together with Foxo1, regulates Foxp3 (10.1084/jem.20100004), and Foxp3 is speculated to play a pathological role in CFS/ME lymphocytes. However, I still don't understand how this could exactly work in CFS/ME. Is there a dysfunctional TGF-β–driven Foxp3 induction due to Foxo3 deficiency or is there a Foxo3 or Foxo1 surplus causing the Foxp3+ oversaturation?
 

Sledgehammer

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I passed that camp a few crashes back. I'm now living in the hole up and protect myself from further injury camp.
It's good to know what does and doesn't work for some. I've been there too trying many diets with no or little effect. I'll give this a go and see what happens. Fingers crossed I doubt it'll make me feel more rotten than I already do.
 

Mary

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In the case of thiamine deficiency, BCAAs would be the only way to refuel these two CoAs. And without these CoAs, neither glucose nor ketones can fuel the energy metabolism.
Very interesting! I started taking thiamine 4 or 5 years ago, it gave me an almost immediate energy boost, followed by severe fatigue the next day. Eventually I figured out that it was causing my phosphorous to tank due to refeeding syndrome. The fatigue dissipated after drinking several glasses of kefir (high in phosphorous) and eventually I bought a phosphate supplement which I take about twice a week. I'm currently taking 300 mg thiamine a day.

@nerd - I'm afraid all the chemistry you cited is beyond me. I can't really tell what it means for me in terms of trying the keto diet, whether I should attempt it again or not. I appreciate your taking the time to write all of that, I just really can't comprehend it all unfortunately!
 

Mary

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How did you figure it out? This sounds so complicated.
It was a bit of research, experience, muscle testing and trial and error! In 2010 I started taking methylfolate. I had read several of Freddd's B12 posts and learned that you had to watch out for low potassium when starting B12 or folate, due to refeeding syndrome. Also see this post: Why is potassium supplementation needed in methylation treatmt? | Phoenix Rising ME/CFS Forums

I did develop hypokalemia (low potassium) about 2 days after starting methylfolate. My chief symptom was severe fatigue, after an initial really nice energy boost. So this was my introduction to refeeding syndrome. Fortunately I was able to deal with it because I was expecting it, and started taking potassium,(titrated up in divided doses) and the severe fatigue went away.

This article has more info: Refeeding syndrome: what it is, and how to prevent and treat it (nih.gov) It says in part:
Refeeding syndrome can be defined as the potentially fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving artificial refeeding (whether enterally or parenterally5). These shifts result from hormonal and metabolic changes and may cause serious clinical complications. The hallmark biochemical feature of refeeding syndrome is hypophosphataemia. However, the syndrome is complex and may also feature abnormal sodium and fluid balance; changes in glucose, protein, and fat metabolism; thiamine deficiency; hypokalaemia; and hypomagnesaemia.
So in 2015 or so I tried thiamine, 100 mg, and had a great energy boost, followed a day or 2 later by severe fatigue. I immediately thought of potassium but more potassium didn't do anything for me, and I just gave it up. A year or 2 later I tried thiamine again, with the same experience, only this time I wondered if it was refeeding syndrome again. And I remembered my reading that low phosphorous (hypophosphataemia) was the hallmark of refeeding syndrome. One way to find out! I read about phosphorous sources - found that dairy was high in phosphorous - I drank probably 3 glasses of kefir (a lot) and within a few hours the horrible fatigue went away, and I was able to keep taking the thiamine. I was so glad because it helped me so much! Eventually I bought a monosodium phosphate supplement and still take it around 2 x a week.

One other thing - I used muscle testing also, which indicated that thiamine was good for me, so I was determined to find out the problem so that I could keep taking it.

I tried to tell an endocrinologist about this once - actually I wanted to talk to him about phosphate diabetes which has been found in some people with ME/CFS only I never got that far. When I mentioned refeeding syndrome, he scoffed at me, said that only applied to people who are starving or who were at Auschwitz. He wouldn't listen. I'm used to solving things on my own because I've found doctors for the most part to be useless.
 
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I tried Keto with bad results, but it did significantly change my diet.
I now eat healthy oils to taste on a diet high in organic produce. I eat carbs in the morning only for energy.
Although it was suggested to me by a doctor my attempt was not closely supervised. I did read two books Mercola and the Art and Science of Low Carb Living. I lasted six weeks and it cost me a full year on my normal seasonal improve decline cycle.
I do think the keto flu and a ME crash are very similar. I had lower right abdominal pain, which I attributed to my pancreas, not gall bladder.
This included an extremely painful case of what was likely pancreatitis after a fall onto exactly that area.

That lower right abdominal pain was my first symptom as I started to get older, at around 40. I reported my experience to the recommending doctor and he refused to document the symptoms. I ended up firing the doctor with no drama, but was retaliated against by his medical organization.
 

Mary

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@Mary What an experience! Did you get any useful testing from the endocrinologist?
Nope. He only did the basic stuff which said I'm perfectly healthy, like everyone else here. I've been helped much more by my chiropractor who does muscle testing. If you'd like more info on this, please PM me as I don't want to derail this thread!
 

nerd

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It was a bit of research, experience, muscle testing and trial and error! In 2010 I started taking methylfolate. I had read several of Freddd's B12 posts and learned that you had to watch out for low potassium when starting B12 or folate, due to refeeding syndrome. Also see this post: Why is potassium supplementation needed in methylation treatmt? | Phoenix Rising ME/CFS Forums

I did develop hypokalemia (low potassium) about 2 days after starting methylfolate. My chief symptom was severe fatigue, after an initial really nice energy boost. So this was my introduction to refeeding syndrome. Fortunately I was able to deal with it because I was expecting it, and started taking potassium,(titrated up in divided doses) and the severe fatigue went away.
Last I checked, I also had this issue with intracellular electrolytes, i.e. sodium too high, potassium and phosphorus too low, magnesium normal. I just don't remember if I was taking B12 at the time. If I was taking it, then it must have been the first week.

I'm currently taking 300 mg thiamine a day.
Seems like a lot. Why so much? Even for Beriberi, the typical thiamine deficiency disease, they don't use more than 100mg daily. I'm not sure if there are potential feedback mechanisms when it is overdosed.

I had lower right abdominal pain, which I attributed to my pancreas, not gall bladder.
But the pancreas sits in the upper left abdomen. The gallbladder sits in the upper right abdomen. Both can hurt in the stomach region as well. Lower right sounds like something else. Maybe SIBO or some other GI-related thing? Sad that your physician wasn't willing to support you with this.

I tried to tell an endocrinologist about this once - actually I wanted to talk to him about phosphate diabetes which has been found in some people with ME/CFS only I never got that far. When I mentioned refeeding syndrome, he scoffed at me, said that only applied to people who are starving or who were at Auschwitz. He wouldn't listen. I'm used to solving things on my own because I've found doctors for the most part to be useless.
They just don't want to understand that we're not asking for a diagnosis for the diagnosis's sake but to improve our quality of life. Instead, they keep pushing us around. They're not even willing to accept that CFS/ME is a real disease. And no one tells them to inform themselves.
 
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But the pancreas sits in the upper left abdomen. The gallbladder sits in the upper right abdomen. Both can hurt in the stomach region as well. Lower right sounds like something else. Maybe SIBO or some other GI-related thing? Sad that your physician wasn't willing to support you with this.
This was a few years ago, I don’t recall all the sources o consulted at the time. Pancreas pain can be on the right where the ‘head’ is located. The ‘tail’ extends to the left. Thank you for your constructive feedback.

https://www.health.harvard.edu/a_to_z/acute-pancreatitis-a-to-z
 

livinglighter

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I don't understand the mechanisms, but I don't agree with carbs anymore. My body doesn't seem to know how to utilise it properly anymore. I gain weight rapidly and crash a lot when I eat carbs with each meal every day. However, the first few days on Keto is bad. Then I start to have more energy and lose weight rapidly. Then I get exhausted and begin to crash again and need carbs for energy upkeep. It's a vicious cycle. I seem to find a better balance with a small portion of carbs a day, like 1 serving of rice or a slice of bread,