Ketogenic diet

[leokitten]

In the beginning of my problems I highly suspected that SIBO was the underlying problem for all my symptoms, probably because I felt that there is a very strong connection between what I eat and how I feel, and the fact that starving bacteria(all meat diet) for a day or two would kinda like push a reset button, so to speak. I wouldn't feel normal, but much much better. Then I would begin eating normally and get back to the same place again. To some extent this is still true, although it doesn't work as well anymore.

All in all, I feel that at least for me, there are two components when it comes to GI tract: feeding or not feeding bacteria (limiting carbs and fibers) and general GI hypersensitivity, which is not directly related to bacteria (e.g. sensitivity to seasonings, honey, dairy, wheat, etc). It's not really the overgrown bacteria in the small intestine (SIBO) or wheat or dairy that is the real problem, but the way GI tract and immune system copes with it. I suspect that it's not even the microbiome that is at fault, but the gut cells are somehow malfunctioning. Although, I have to say that SCD(specific carb diet) was very helpful in the beginning, I suspect because of it's modulating ability on the diversity of gut microbiome(source: SIBO conference, L. Weinstock), but it wasn't a cure by any means. I think scientists may be paying too much attention on microbiome and not enough on the gut integrity and what's going on there and why.

Sorry I went a bit off-topic.

What you wrote in the first paragraph is basically my own experience and that of others. @Trish's theory that it could be SIBO is a valid one, but you cannot prove that it isn't cellular metabolic impairments that are suggested by a number of high quality ME research studies. There are no high quality research studies suggesting SIBO is a major cause of ME symptoms.

Based on what you've written be careful that your body is not fooling you. I don't think you can prove whether you have SIBO and whether it is the underlying cause of your symptoms. It could be that you do have ME cellular metabolic dysfunction/impairment, and by changing your diet to different macro proportions you are circumventing this and finally your cells have enough energy to function better, and then you feel better.

I think, in general, one needs to second guess when they have gut issues that it has to be some bacterial/fungal/microbiome issue etc. It could the above and the cells in your body do not have the energy they need to run properly, including all of the cells comprising your gut and gut immune system. When tissues do not generate enough energy to work correctly then obviously you are going to have problems.

 

[leokitten]

It says here on MitoAction to avoid fasting (my bolding).

Diet The Ketogenic diet (used sometimes for those with seizure disorders) can be a stressor for those with mitochondrial disease. This diet increases cellular utilization of thebeta oxidation pathway. This diet can be helpful for those with a pyruvate dehydrogenase disorder. Avoid diet deficiencies of any kind. It is important for patients to have a balanced diet including pyridoxine (B6), ferrodoxin, iron, copper, riboflavin (B2), zinc, and selenium as well as other vitamins and/or minerals. Avoid fasting! A state of hyperglycemia can also be toxic and lead to problems similar to those of diabetics. Hyperglycemiacan cause increased superoxide production (oxygen free radical) in the endothelium, which can lead to a vascular endotheliopathy (vessel wall dysfunction and metabolic derangement). Some foods like peas, beans, legumes, and almonds have substances in them that can be toxic to the mitochondria.

PWME do not have genetic mitochondrial diseases. No researcher, no doctor, no patient, no one knows exactly the cellular energy impairments we actually have, and how different or not they are to congenital disorders. I wouldn't go so far to make that extrapolation.

We have no idea. Most PWME do not recover significantly or go into remission spontaneously, I think the figure we constantly see is 5%. So many people try interventions on their own. They reduce the risk somewhat by trying interventions that have some scientific evidence that support it. But in the end it's all a shot in the dark, trial or error approach with all the risks that come with it.

There are a lot of PWME that will tell you, from their own experiences, that fasting significantly improves symptoms and that fasting doesn't cause a rebound worsening or payback. And it's like clockwork, we can essentially prove that the fast is the cause of symptom improvement because it happens every single time right away. When we stop fasting and, for many of us, go back to eating a normal healthy diet with standard macros, our symptoms gradually get worse, PEM ensues, and most of us crash.

 

[Pechius]

What you wrote in the first paragraph is basically my own experience and that of others. @Trish's theory that it could be SIBO is a valid one, but you cannot prove that it isn't cellular metabolic impairments that are suggested by a number of high quality ME research studies. There are no high quality research studies suggesting SIBO is a major cause of ME symptoms.

Based on what you've written be careful that your body is not fooling you. I don't think you can prove whether you have SIBO and whether it is the underlying cause of your symptoms. It could be that you do have ME cellular metabolic dysfunction/impairment, and by changing your diet to different macro proportions you are circumventing this and finally your cells have enough energy to function better, and then you feel better.

I think, in general, one needs to second guess when they have gut issues that it has to be some bacterial/fungal/microbiome issue etc. It could the above and the cells in your body do not have the energy they need to run properly, including all of the cells comprising your gut and gut immune system. When tissues do not generate enough energy to work correctly then obviously you are going to have problems.

Absolutely. I'm not discounting the possibilities that you have mentioned and they're always in the back of my mind. I wasn't very clear in my post that I don't think that SIBO or the microbiome is the underlying problem. That was my wishful thinking 3-4 years ago. I think at that time I just couldn't accept ME/CFS diagnosis and the uncertainty that comes with it so had to latch on to something. I'm open to all the possibilities now..

 

[leokitten]

Yup. The trouble is that in ME/CFS many more enzymes and metabolic pathways are busted; it’s not an isolated problem with PDH. Especially in women with ME fat oxidation isn’t working well either (Naviaux comments on this in the supplement to his metabolomics paper) so eating a fat-based diet makes little sense.

I wouldn't make such a blanket statement. Naviaux doesn't know for sure. His paper studied 45 subjects (n = 22 men and 23 women), that's a very, very small study. I know that Fluge/Mella also found some evidence in a much larger cohort but I think we are mixing up the scientific findings and ketogenic diet here.

Both found evidence of reduced mitochondrial fatty acid oxidation in female patients in serum and skeletal muscle cells I believe. Ketone bodies are not fatty acids. Only your liver cells use fatty acid oxidation to make ketone bodies. Naviaux and Fluge/Mella did not study liver cells and if they were affected. They also did not study whether there was impaired ketone oxidation.

As a scientist who also does metabolomics research (in cancer) I can tell you that the field is still quite new and the techniques are still lacking in interlab and interassay reproducibility. So currently for these techniques the need for very large cohorts is paramount. In the experiments I'm doing we typically have more than 1000 patients.

Naviaux would tell you he doesn't know for sure. If a woman with ME truly has fatty acid oxidation pathway impairment in her liver then when trialing a ketogenic diet it most likely won't work and won't work right away.

 

[leokitten]

Only popped back onto this thread because I was just re-reading Fluge and Mellas research from 2016;

"We hypothesized that ME/CFS is associated with defective oxidative metabolism involving PDH, leading to increased utilization of ketogenic amino acids to fuel the TCA cycle."

https://insight.jci.org/articles/view/89376

eta: doesn't this mean we are already using more ketogenic amino acids than healthies?

Probably no. I would say a possible theory is that due to the fact that we keep eating carbohydrates like normal and we have a healthy supply of glucose in the blood our bodies do not utilize ketosis in any significant way. If this theory is true, it seems that our cells do not get any signal that they aren't making enough ATP from the glucose mitochondrial pathway.

 

[Sid]

I wouldn't make such a blanket statement. Naviaux doesn't know for sure. His paper studied 45 subjects (n = 22 men and 23 women), that's a very, very small study. As a scientist who also does metabolomics research (in cancer) I can tell you that the field is still quite new and the techniques are still lacking in interlab and interassay reproducibility. So currently for these techniques the need for very large cohorts is paramount. In the experiments I'm doing we typically have more than 1000 patients.

Some women might have fatty acid oxidation impairment but many other might not. I would avoid suggesting to people that they shouldn't do something just because you think so. Naviaux would tell you he doesn't know for sure. If a woman with ME truly has fatty acid oxidation pathway impairment then when trialing a ketogenic diet it most likely won't work and won't work right away.

I agree there are severe limitations to his study but if I recall correctly the Norwegians also found that the only useable substrate in women was protein.

My impression is that those who do badly with fasting will be less likely to do well with keto since keto is a modified fast. Some feel better with fasting as you point out so it makes sense to try keto.

I used to be able to do IF; now I cannot fast at all. My energy drops to literally zero. I know many women who have this sort of response.

 

[leokitten]

I agree there are severe limitations to his study but if I recall correctly the Norwegians also found that the only useable substrate in women was protein.

My impression is that those who do badly with fasting will be less likely to do well with keto since keto is a modified fast. Some feel better with fasting as you point out so it makes sense to try keto.

I used to be able to do IF; now I cannot fast at all. My energy drops to literally zero. I know many women who have this sort of response.

Sorry @Sid I accidentally hit post before I was done. Please re-read my post as it changed.

 

[leokitten]

I agree there are severe limitations to his study but if I recall correctly the Norwegians also found that the only useable substrate in women was protein.

My impression is that those who do badly with fasting will be less likely to do well with keto since keto is a modified fast. Some feel better with fasting as you point out so it makes sense to try keto.

I used to be able to do IF; now I cannot fast at all. My energy drops to literally zero. I know many women who have this sort of response.

I totally agree. But this post gives a more fair and balanced assessment of the situation, some women will do better with ketogenic and IF intervention, some won't. We can't say that all woman will do badly because honestly we don't know.

 

[Sid]

I totally agree. But this post gives a more fair and balanced assessment of the situation, some women will do better with ketogenic and IF intervention, some won't. We can't say that all woman will do badly because honestly we don't know.

Indeed.

I will just add that since we have no studies, anecdotally I was doing keto on and off for 10 years (2003-2013) before healthy kids on reddit and such used it to shave off those troublesome 10 lbs and in that time ‘met’ hundreds, maybe thousands of people with various disorders trying it. One woman with ME/CFS benefitted (couldn’t walk around the block previously), a few men. Some got miraculously better initially and relapsed severely as time passed.

As keto has been around for a very long time (100 years ago it was used to stave off death in type I diabetics before discovery of insulin, still used in refractory epilepsy, lots of studies on this now), if it side-stepped the metabolic derangement(s) of ME/CFS we would know about it and everyone would be using it. There is nothing new here, it’s just that every generation reinvents the wheel since no effective treatments are available.

 

[Mij]

@leokitten I'm absolutely not trying to discount what you are saying or trying to scare people not to try this diet.

If some here are not feeling benefits from fasting then at least they can consider that a mitochondrial deficit might be a factor. That's all.

 

[leokitten]

Indeed.

I will just add that since we have no studies, anecdotally I was doing keto on and off for 10 years (2003-2013) before healthy kids on reddit and such used it to shave off those troublesome 10 lbs and in that time ‘met’ hundreds, maybe thousands of people with various disorders trying it. One woman with ME/CFS benefitted (couldn’t walk around the block previously), a few men. Some got miraculously better initially and relapsed severely as time passed.

As keto has been around for a very long time (100 years ago it was used to stave off death in type I diabetics before discovery of insulin, still used in refractory epilepsy, lots of studies on this now), if it side-stepped the metabolic derangement(s) of ME/CFS we would know about it and everyone would be using it. There is nothing new here, it’s just that every generation reinvents the wheel since no effective treatments are available.

@Sid the thing is that ME researchers are, I believe, finding more and more evidence that comes to the conclusion that this is a heterogeneous disorder. That the causes, triggers, and possibly even drivers of the disease are different between patients and though we all end up in pretty much the same place the treatments that will work will vary between patients.

So it completely makes sense that circumventing metabolic impairments works really well in a subgroup and not in another. That's why it's important for people to catalog our experiences when such an intervention works really well. That's also why we cannot make blanket statements that something definitely won't work. There likely will never be a treatment that "we would know about it and everyone would be using it".

Quoting from Ian Lipkin in the recent article from Simon McGrath in ME Research Review:

The heart of ME/CFS? Lipkin’s Collaborative probes the impact of exertion

"He believes that in ME/CFS, as with cancer, a group of similar-looking patients will prove to have different causes or triggers for their illness but will share a final common pathway: “ME/CFS”. As with cancer, he expects they will find the specific cause of ME/CFS for some groups of patients quite quickly – the low-hanging fruit.

On the other hand, Lipkin believes it may prove much harder to find causes for ME/CFS in other patients – the fruit higher up the tree.

Lipkin is aiming for precision medicine, where doctors try to establish each patient’s exact problem so that it can be treated in the most effective way. If for example, the microbiome is abnormal, there are already plausible treatments available, such as probiotics, antibiotics or antivirals that could have a profound impact on illness. Other patients may have abnormalities in immune system or mitochondrial function that will require the development of specific drugs or genetic therapies."

Now look I'm not a fan of Ian Lipkin at all, I think he has a chronic problem of throwing out pretty bombastic statements to give patients hope, like saying "We will solve ME/CFS in the next 3-5 years" which was back in 2015. I believe he cares more about his personal research interests, getting funding, and putting out publications in research areas that are hot topics currently (e.g. microbiome research). It's funny at the end of 2015 he said we'll solve it in 3-5 years, and now in the above article in mid 2018 he's now saying "he also said he was very hopeful that there would be real progress for patients within five years." Oh brother please stop...

But besides that I do believe these statements above about heterogeneity are probably correct, and they aren't just his there have been other high-profile ME researchers who've said the same thing.

Taking from this, and I've thought about it a good deal and do not want to be negative, but if this disease is so heterogeneous and requiring precision medicine approaches to treatments then, pardon my bluntness, this is going to suck and get ready to wait for a very long time. The industry is only really doing precision medicine in cancer and this mostly because the disease is one of the most prevalent diseases humans get combined with one of the most horrendous and lethal.

There are $$billions$$ of dollars of research going into cancer, not $15 million for ME/CFS like in the U.S.. Precision medicine is very expensive, requires way more research, and many more treatments/drugs have to go through the clinical trial and FDA approval process. There isn't just one or a few targets anymore. If people think we are going to have new FDA-approved drugs or other therapies within the next 10 years I have a lot of doubts. If they repurpose existing FDA-approved drugs that might shorten the time, but I think many ME physicians have tried many of these and the results are not enough.

"Patients may have abnormalities in immune system or mitochondrial function that will require the development of specific drugs or genetic therapies." This is going to take 20 years or more unless they seriously start spending $100s of millions of dollars now.

Lipkin mentions probiotics, antibiotics, antivirals for subgroups, but we've tried all these interventions, we've seen the evidence anecdotal and clinical, if they do work they only work in a few, and when they do work most only have improvements but not remission. They cannot go back to a life full of free will. ME effectively robs you of free will. That cannot be said of the majority of other diseases that have FDA-approved treatments, people with other, even very serious illnesses can get back to a fairly normal life when they get treatment.

I would be ecstatic if they have a diagnostic test for this disease within 10 years. That's all I can realistically hope for.

 

[Tom Kindlon]

 

[Sasha]

I read about this this morning on the BBC site and there seem to be a lot of caveats about it, which is what you'd expect from an observational study of diet.

But I do think it's important to look at long-term data - that is, over years and decades. One-year follow-up is nothing, for a diet. In practice, though, I doubt we'll ever see very clear studies - it's hard to keep control of people's diets for long periods.

 

[leokitten]

Update:

It's been just over two weeks now since I recovered from the crash I had after starting the ketogenic diet (see earlier in this thread). I had transitioned and was on the ketogenic diet for two full weeks before that crash. These two weeks I had more activity than the two weeks before the crash, both mental and physical. I'm working a lot more (although still from home to save energy) and had more days when I went on walks and errands.

I felt better these two weeks than the first two weeks of the diet. The same symptom remissions and significant improvements I listed have continued. The only symptoms blips I had these two weeks were:

1. During a couple of long walks it was really sunny and I forgot my sunglasses. Due to the diet I do not have photosensitivity anymore to warn me, so when I got home the ME "hungover like" deep eyeball pain I've described came back, it lasted the rest of the day and disappeared by the next morning. For all my subsequent walks I took sunglasses and never got the symptoms again.
2. This past Tuesday, I started getting blip of the isolated fatigue symptom I described, which was my only symptom warning sign before the previous crash. To explain in more detail, it's a fraction of the level of crushing ME fatigue I would feel before the diet, but it is still noticeable. After a day or so of it persisting, I started another 48-hr intermittent fast (IF). Within like three hours the symptom quickly vanished. I find this very intriguing, wondering what is happening with my body.

For the first week of this second two week period, I experimented with not tracking my macros with my keto app, just to take it easier after that crash and to see how well I could manage in my head knowing pretty well the food I have at home. Having the glucose+ketone meter to give me accurate feedback on how well I am doing makes this more feasible. I was able to keep a pretty consistent GKI = 2 during this time. As a side observation, I found I feel equally as good on a GKI = 2 versus something lower, so now I have more information going forward.

I wonder does anyone else who improves on IF also find that it is a PEM reliever or even shielder?

 

[Hutan]

"The Lancet Public Health: Moderate carbohydrate intake may be best for health"

I'm not sure that it tells us very much that is really useful for our specific situations.
It's to be expected that the people with a moderate carbohydrate intake were doing the best out of a general population sample.

A high carbohydrate intake suggests that a person either doesn't know what a balanced diet looks like and/or can't afford expensive protein rich foods or lives in an institution that is saving money by feeding them mostly cheap carbohydrates. So, as well as the dietary problems, there are probably plenty of other factors pushing them towards poorer health. To be fair, the study did try to remove the impact of some factors like education but the article noted the likelihood of 'residual confounders'.

Writing in a linked Comment, Dr Andrew Mente and Dr Salim Yusuf from McMaster University, Hamilton, Canada say, "Such differences in risk associated with extreme differences in intake of a nutrient are plausible, but observational studies cannot completely exclude residual confounders when the apparent differences are so modest.

At the other end of the carbohydrate spectrum, it's not very easy to just fall into a habit of low carbohydrate intake. I expect most people eating this way are doing it deliberately because they either already have poor health and are trying to fix it, or are really body conscious, work out a lot, and perhaps even take body building supplements that stress their bodies. So again, there are probably other factors contributing to poorer health outcomes in the long term.

However, our data suggests that animal-based low carbohydrate diets, which are prevalent in North America and Europe, might be associated with shorter overall life span and should be discouraged. Instead, if one chooses to follow a low carbohydrate diet, then exchanging carbohydrates for more plant-based fats and proteins might actually promote healthy ageing in the long term

I guess that's a good, although pretty obvious, point - you have to make sure that you are getting enough fibre and other plant nutrients if you are following a low carbohydrate diet. This study found that a plant rich low carbohydrate diet actually increased longevity relative to a moderate diet, but they acknowledged that the number of people following that diet was small and that further research was needed before drawing solid conclusions.

Although carbohydrates are technically not an essential nutrient (unlike protein and fats), a certain amount is probably required to meet short-term energy demands during physical activity and to maintain fat and protein intakes within their respective sweet spots. On the basis of these principles, moderate intake of carbohydrate (eg, roughly 50% of energy) is likely to be more appropriate for the general population than are very low or very high intakes.

An issue is that we are not the general population, so what is best for most people might not be what is best for us (or some of us).

 

[Sasha]

I see that there are claims that the ketogenic diet also helps with migraines.

Does anyone here have experience of that?

 

[Keela Too]

I see that there are claims that the ketogenic diet also helps with migraines.

Does anyone here have experience of that?

My migraines go in waves of clusters, so difficult to say really - but now you mention it, I do seem to have had fewer since starting Low Carb in April.

Note: I’m not always fully keto I think, but I usually fast 16hrs of each 24, and have cut out all bread, rice, pasta, potatoes [whaaaaaa], cereals and only take tiny portions of root veg. I no longer track every morsel.

 

[Mij]

One thing I noticed when I ate a gluten free diet (no bread, pasta, less carbs etc) is that I no longer experienced sick type headaches. They weren't migraines (no aura) but very similar to migraine sickness.

I do the 14-16hr fast overnight almost every day, but when I have the odd "popcorn night" I feel awful the next day.

 

[adambeyoncelowe]

I've had a short break from low-carb when I was on holiday, and I got migraines every day. They've gone again now.

 

[Sasha]

One thing I noticed when I ate a gluten free diet (no bread, pasta, less carbs etc) is that I no longer experienced sick type headaches. They weren't migraines (no aura) but very similar to migraine sickness.

I do the 14-16hr fast overnight almost every day, but when I have the odd "popcorn night" I feel awful the next day.

Apparently migraines without auras (same here) are the most common type of migraine:

https://www.webmd.com/migraines-headaches/what-is-a-migraine-without-aura#1