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Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways

jimells

Senior Member
Messages
2,009
Location
northern Maine
Well this is interesting. My gut can't or won't absorb carbohydrates. The gut bacteria sure love them carbs, and have a wild drunken party if I eat more than a tiny amount of any kind of carbohydrates. At least that seems to be what is going on.

I've wondered if *not* absorbing carbs is a protective reaction, like our other "sickness behaviors", by keeping all that glucose out of the body to start with. So far, my weight has changed little over the course of the illness (now celebrating its 12th birthday, uggh). My sensitivity to carbs correlates with the overall severity of my illness.

Like others have reported, my non-fasting glucose usually tests high-normal. I used to attribute that to the stress of travel and dealing with mostly useless doctors. Now it seems maybe this is typical for our illness? Some researcher must've looked at this by now, I should think, but maybe not.
 

Sidereal

Senior Member
Messages
4,856
After my severe ME crash my fasting blood glucose went up to 100-110 having previously always been normal when I had mild ME.

I suspect those with normal BG have high pyruvate because they can't get from pyruvate to acetyl CoA. Those people would not know that their glucose utilisation is busted because no one measures pyruvate routinely in patients.
 

Mary

Moderator Resource
Messages
17,376
Location
Southern California
@JaimeS - wow - thank you so much for all your hard work, and beautiful pictures! I especially love the bucket brigade :D

I've just given it a cursory read - I don't have a biology or chemistry background but was able to get some general ideas. I'm going to look it over some more when I have more energy.

Several years ago I took calcium pyruvate and it helped my energy for 3 or 4 days, and then stopped. I've just recently ordered it again. Overall I'm doing better than I was those many years ago so perhaps the calcium pyruvate will make more of a difference this time - we are ongoing lab experiments!

Anyways, I really appreciate what you did so much - and you make it entertaining too, not an easy feat! :thumbsup:
 

Vasha

Senior Member
Messages
119
Wow-I missed quite a bit of discussion!:)

Can someone explain to me the difference between a ketogenic diet and a paleo diet? I know ketogenic diets are meant to induce ketosis, but I am not sure what that entails, practically speaking.

I'll try to add a little detail to @Kyla's overview . . .
Paleo tends to be lower-carb (though there are many, many versions of diets that people call "Paleo" and some pretty pretty high in sugar to me, as I think it was Kyla pointed out) through its emphasis on whole, ancestral foods.

Ketogenic diets, however, are specific diets that shift the body into ketosis-a state where it relies on ketone bodies produced in the liver rather than glucose. (This is not the same as the similar-seeming ketoacidosis-the dangerous state diabetics risk getting into.) It's the same metabolic shift that happens in starvation that allows the body to burn its stored fat, but ketogenic diets are of course not starvation diets (though people do use them to lose weight). They create a state of nutritional ketosis.

A pretty good explanation of how ketosis works as a part of metabolism is here (there are two parts). It's by an MD who used ketosis for losing weight and now for performance.

Nutritional ketosis only happens when a diet is very high in fat, proportionally (usually about 80% of calories). As @Kyla pointed out, ketogenic diets have been used for many decades to help control intractable eplieptic seizures (though I don't think anyone knows just why they work). They were used as a first-line therapy in the early 20th century, and then fell to later-tier therapies, usually for severely affected children, once there were anti-seizure medicines.

The ketogenic diet has again become an earlier-line therapy for epilepsy in some hospitals, and is currently a subject of interest among some researchers for a variety of neurological diseases. It's been or is being looked at in Alzheimer's disease (in an attempt to slow progression), ALS (same), progressive MS (same), and Parkinson's, off the top of my head. (These are mostly small studies, not much replication yet.)

As @Sidereal touched on, ketosis is also used by some healthy people who believe it increases their performance. And the familiar Atkins diet is one form that been used a lot by people trying to lose weight. (The "induction phase" is ketogenic.) @jeff_w linked to this helpful Reddit forum that shares a lot of info-the forum is mostly people working on losing weight, etc.

As @Sidereal and @Gondwanaland also suggested, I don't think this is anything to undertake lightly, and likely wouldn't work for everyone. Traditional therapeutic ketogenic diets have been very hard to start (commencing with a several-day fast to get the body into ketosis), and go up to a 4:1 ratio of fat to other calories. They are very low carb--even limiting vegetables--and require lots of electrolyte replacement and probably some other supplementation. They've also been hard to do, because they required weighing food, etc.

However, for a long time now, there have been more doable versions. "Modified Atkins" is one (as i understand it, it's basically the early phase of the Atkins diet, longer term). Another is using copious amounts of medium-chain triglycerides, found in, e.g., coconut oil and, umm :rolleyes: MCT oil :)). With the MCT oil version, the idea is that the MCT oil is very easily used. It allows the diet to contain more vegetables and other carbs.

I'm exploring this, but am not an expert. Again, it's an intense undertaking, and may be more difficult on a sick body than a healthy one. But because I have a lot of neurological symptoms, it is something I'm interested in trying for myself.

Re Paleo: I'll also say that I read a lot on the Autoimmune Paleo Approach Sarah Ballantyne came up with last year, and I think she covered a lot of bases for anyone who may have autoimmune features. Her book is great (also with excellent diagrams :)) - an interesting mix between a bio textbook and a dietary approach. It is not ketogenic, or even super low carb (though it is lower-carb), but based on cutting out things that many people react to or that enhance inflammation. It focuses on fats, proteins, and lots and lots of vegetables for micronutrients. It doesn't rely on specific calorie counts, etc., which again I find in its favor. After all, humans vary a lot in what works for them, within reason. Again, it's all unproven, but I found it plausible, and have considered it strongly, too.

Hope that helps a bit! I have to go again for awhile, but am happy to share sources if helpful to anyone...just PM me. :) I'll try not to be too slow . . .

Vasha
 
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Vasha

Senior Member
Messages
119
@Vasha - thanks so much for your kind words, first of all

@alex3619 informed me that this idea is a pretty old one, actually, and it's been poked and prodded-at for awhile.

He recommended alanine for CFS.

Just because it's an 'older' idea doesn't make it more/less valid, just commenting that it's been around for awhile as a thought. :)-J

Definitely. Older can be good, if it hasn't been debunked. Tagging @alex3619, in case he has anything more to say on diets.

Vasha
 

Sidereal

Senior Member
Messages
4,856
If you think about it, a ketogenic diet makes no sense for ME/CFS. A true ketogenic diet is a very low carb, protein restricted diet composed of mostly fat. Protein is the most usable macronutrient in ME but on this diet you gotta restrict it since excess protein is antiketogenic.

Fat oxidation isn't working too well in ME/CFS as evidenced by high rates of overweight and obesity in this disease. Many here cannot fast at all and are on the verge of collapse if they miss a meal. Ketosis mimics fasting (starvation) metabolism. Only the healthiest people can essentially fast long term and feel decent.

You need some glucose for the brain even when in ketosis; ketones can't fuel the brain entirely. To get glucose you need your gluconeogenesis to be working which for many here it isn't. This process requires cortisol which many here are low on.

And then there is the issue of mass extinction of commensal species in the gut which feed on polysaccharides (ie carbs). This will severely worsen the disease process.

Being sick with this sucks but please don't make yourselves worse. I went from mild to severe ME in ketosis and I know of hundreds of other cases of "adrenal fatigue" developing on this diet.
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
Traditional therapeutic ketogenic diets have been very hard to start (commencing with a several-day fast to get the body into ketosis), and go up to a 4:1 ratio of fat to other calories. They are very low carb--even limiting vegetables--and require lots of electrolyte replacement and probably some other supplementation. They've also been hard to do, because they required weighing food, etc.

I would not do this as an ME patient. I tried Atkins when I was well and it made me quite ill.

Part of the problem is that, no matter what, you have to take care with what enters into your body. High-fat diets are okay, if you're eating fats that sit well with you and are nutritionally rich, such as olive oil and coconut oil. I am not against saturated fats, either, which are much-maligned so far as I'm concerned - I say, if you can handle them, eat them!

I guess my point is that it is quite possible to follow a strict regimen and be very, very unhealthy. I was following a written diet for Atkins when I did it as a late teens / early twenty-something, and it was a nightmare. But looking back, what they had me eating was nonsense: enormous amounts of cauliflower and broccoli, raw, but an enormous amount of processed meat like hot dogs as my main protein source. What was I thinking?!

Everyone should take a nutrition class from a decent nutritionist before they call themselves a grown-up.

-J
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
Fat oxidation isn't working too well in ME/CFS as evidenced by high rates of overweight and obesity in this disease.

My mom's lipase is so poor she can't consume anything fatty at all - and by that I mean anything with more than a gram or two of fat at a time. Needless to say, she's slender. I'm not as bad, but trending the same way - fish oil in the morning makes me feel pretty good for a day or two, but by the third day it makes me nauseated. High fat foods have always made me ill, but in my case I'm sick if I have more than 600 calories or 20-g of fat in a meal. I've lost 21 pounds since becoming ill, though primarily by cutting out wheat, dairy, and aspartame, and taking a mega-dose of Vitamin D (it was low). This is by way of agreeing with you, but showing how it can work in the opposite direction.

I think I could take some fatty acid supplements without harming myself, so long as they weren't at mega-doses.

At one time, before giving up dairy, I was on whey protein. It was amazing. That was when I was sicker, so I was more likely to notice something helpful, but the lift in my energy levels were astounding. When I cut out dairy, I cut out whey, but I'm not sure I was right to do so. Whey only has traces of lactose, and I'm beginning to feel like that was the culprit. Like, I'm not 'lactose intolerant' because I don't have enough lactase; I'm 'lactose intolerant' because lactose splits into glucose and galactose, and I don't process glucose as I should.

No idea if that's the case, but it's a thought. Perhaps I should try going back and see how I do. Plant proteins just really weren't the same...

-J
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
I've been on a modified GAPS diet for 3+ years. I calculated my current intake this month on the calorie counter site I used to get a handle on my intake for the American Gut project last year. I wish I'd kept a record at that time, but the results may well have been pretty similar. I was eating a couple zucchini daily, plus a large carrot juice initially. Currently, I'm eating about 1 kg carrots (!) daily, which accounts for my carbs. I found the transition to relying on fats rather than carbs left me with very little energy initially. But I think my body adapted within a few weeks. My fat now is 3-4 Tb beef fat, 1 Tb ghee most days, 2-3 Tb mixed seed/nut spread.
Fat - 58.1%
Pro - 12.4%
Carb - 29.5%

http://www.caloriecount.com/
 

Vasha

Senior Member
Messages
119
....And then there is the issue of mass extinction of commensal species in the gut which feed on polysaccharides (ie carbs). This will severely worsen the disease process.

Being sick with this sucks but please don't make yourselves worse. I went from mild to severe ME in ketosis and I know of hundreds of other cases of "adrenal fatigue" developing on this diet.
@Sidereal, yes, gut issues that could arise without enough cabrohydrates are a big question for me. I certainly agree that the gut is looking crucially important and that messing it up could really set a person back.

As far as your experience, oh my I'm so sorry to hear that! It certainly signals great caution, and thank you for sharing it.If I may ask (and no need to answer of course!) were you on a ketogenic diet, or in ketosis for another reason (e.g., not being able to eat enough)?

I would not do this as an ME patient. I tried Atkins when I was well and it made me quite ill.
I wonder if this is a sign for people who would not react well. I also did Atkins when well--on a lark, which I had to be talked into, because I am generally an "everything in moderation" sort of person, and Atkins sounded so extreme to me--with friends. I felt very energetic on it, after a week or two of feeling awful in transition. Indeed, I would say that the muscle fatigue I felt then is the only other time I've felt muscle fatigue that seemed similar to ME. Once I adjusted, it was terrific, and I've never had more energy. But again, it's a risk for anyone who's ill,

Part of the problem is that, no matter what, you have to take care with what enters into your body. High-fat diets are okay, if you're eating fats that sit well with you and are nutritionally rich, such as olive oil and coconut oil. I am not against saturated fats, either, which are much-maligned so far as I'm concerned - I say, if you can handle them, eat them!

I guess my point is that it is quite possible to follow a strict regimen and be very, very unhealthy. I was following a written diet for Atkins when I did it as a late teens / early twenty-something, and it was a nightmare. But looking back, what they had me eating was nonsense: enormous amounts of cauliflower and broccoli, raw, but an enormous amount of processed meat like hot dogs as my main protein source. What was I thinking?!

Everyone should take a nutrition class from a decent nutritionist before they call themselves a grown-up.

-J

Yes; I think this is so important. I really don't think there is any one diet that applies to everyone, but the quality of the food probably does matter to everyone. Processed fats and sugars (and additives) are so much more likely to be hard on a body. So many diets--whatever their original worth--spawn industries of snack foods and desserts that "comply" but are really processed and artificial.

The only caveat I would add about nutrition class is that nutrition is so complicated, so poorly understood overall, and so besieged by various lobbies that it's really difficult to figure out. I've dived into a lot of research in the last year or two, and basically found that it is unsettled and prone to grand statements (carbs are bad! Fat is bad! Fat is good! etc) that must be too simplistic. But there are a few takeaways I came up with:
1. Nothing is likely to be right for everyone
2. Processed foods, and sugar, have a lot to be said against them [<I think this is hard for us, because preparing whole-food-based, fresh meals can just be impossible in terms of both energy reserves and money.]
3. The whole-foods/ancestral diet approach (done with real whole foods, and variety) may have something going for it, not because of the story behind it, but because it can be very nutrient dense (macro and micro). Again, I think this is a real commitment, but is promising. (Besides Dr. Kaufman, I see a functional medicine MD who focuses on nutrition and the like, and she advocates nutrient-dense and gut-healing foods.)
4. A lot of what I found out was really counter-intuitive to me. For example, the idea that foods that are easiest to digest, and easiest on your gut, are fats and proteins.

My mom's lipase is so poor she can't consume anything fatty at all - and by that I mean anything with more than a gram or two of fat at a time. Needless to say, she's slender. I'm not as bad, but trending the same way - fish oil in the morning makes me feel pretty good for a day or two, but by the third day it makes me nauseated. High fat foods have always made me ill, but in my case I'm sick if I have more than 600 calories or 20-g of fat in a meal. I've lost 21 pounds since becoming ill, though primarily by cutting out wheat, dairy, and aspartame, and taking a mega-dose of Vitamin D (it was low). This is by way of agreeing with you, but showing how it can work in the opposite direction.
-J

This sounds familiar to me, too. I have always been relatively thin (BMI 19-20) and when I got the most sick, I could not tolerate fat at all. Really at all. I was obviously burning it, because I lost basically all my body fat (40 lbs) plus some.

--
*I do want to be really, really clear that I am not advocating a ketogenic diet for anyone* I think I was clear, but just in case. :) When people's systems are as fragile and ill as they are in ME/CFS, great caution is always warranted. And @Sidereal and others' experiences definitely illustrate this.

I did want to say that newer ketogenic diets are not as strict as the old 4:1 ratio; it seems that the neurological benefits accrue on less-strict diets. (But they are still limiting, obviously.) They are fat-intensive, adequate protein, low carbs (i.e., lots of above-ground vegetables, only limited starchy vegetables, and a few fruits (basically berries)).

I became interested in it for another reason entirely from what we've been taking about on this thread: the use in neurological diseases. The brain needs fatty acids, and all cells, including neurons, need cholesterol to build cell membranes and such. I've had so much trouble with neurological issues that bathing the brain in fat seemed a plausible thing to consider. (<That's a bit casual obviously-it seemed plausible after reading up on studies of ketogenic diets in various neurological and neuroimmune diseases.)

Not sure what I will do, and NOT advocating for others. Just in case. :)

Vasha
 
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Vasha

Senior Member
Messages
119
I've been on a modified GAPS diet for 3+ years. I calculated my current intake this month on the calorie counter site I used to get a handle on my intake for the American Gut project last year. I wish I'd kept a record at that time, but the results may well have been pretty similar. I was eating a couple zucchini daily, plus a large carrot juice initially. Currently, I'm eating about 1 kg carrots (!) daily, which accounts for my carbs. I found the transition to relying on fats rather than carbs left me with very little energy initially. But I think my body adapted within a few weeks. My fat now is 3-4 Tb beef fat, 1 Tb ghee most days, 2-3 Tb mixed seed/nut spread.
Fat - 58.1%
Pro - 12.4%
Carb - 29.5%

http://www.caloriecount.com/
Hi @ahmo, I was going to mention GAPS and forgot. Have you done well on it?

Vasha

P.S. is there a reason for the carrots, specifically?
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
GAPS has been fabulous for me. First, it got me off gluten, dairy. After 6 months I had to go on a severely limited form, minus histamines (fermented food, avocado...) and high thiol (eggs, garlic, onion, green veg). Later more losses, when I took out seeds and nuts for autoimmune purposes. I've been able to put seeds and nuts back in, but no green veg, as they block folate for me. Also now able to tolerate 1-2 Tb yogurt plus sauerkraut.

I make 3 litres bone broth every 3 days, render fat every 2-3 months, cook a roast in the bone broth every couple weeks..this makes my life very simple. The high carrot intake, as well as fairly high seeds/nuts (omega-6s) has been the antioxidant I've needed to combat peroxynitrite. When things were more out of control, I needed even higher amount of carrots, as well as additional antioxidant supps. I'm still hoping my need for carrots comes down, but if this is as good as it gets, it's good enough for me.;)
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
I make 3 litres bone broth every 3 days, render fat every 2-3 months, cook a roast in the bone broth every couple weeks..this makes my life very simple. The high carrot intake, as well as fairly high seeds/nuts (omega-6s) has been the antioxidant I've needed to combat peroxynitrite.

Carrots! One day I had a carrot juice prepared fresh and it was like... I couldn't BELIEVE the increase in my well-being. It absolutely floored me. Then I thought, "if only I could afford a professional juicer and five pounds of organic carrots a day...." But now I'm growing them. :)

Ahmo, I really want to do a series of blog posts on cooking. Do you have the energy to send me instructions for how to do something that has helped you, like the bone broth, or rendering fat? Those old-timey cookery things seem to have been lost on my generation entirely. When I say to others that I have bought bone broth, they make a face... even people of my mom's generation, actually...

My abs look pretty damn good, but I suspect that's from all the nights I spend wracked with sobs because I can't eat anything fun. I would take a selfie to show you, but this isn't Facebook and I'm not your misguided teenage niece.

HAHAHAOMG:rofl::rofl::rofl:

-J
 

JaimeS

Senior Member
Messages
3,408
Location
Silicon Valley, CA
So guys, with this knowledge, assuming we're making two pills, hydrophobic (fatty) and hydrophilic (water soluble), what is in your ideal ME supplement?

Fatty, I'd say:
Vitamin A
Vitamin D
CoQ10
Omega-3s and 6s
Vitex agnus castus

Non-fatty, I'd say:
Benfotiamine, B12, B6, FMN
Pyruvate (does it exist as a supplement?)
Digestive enzymes (lipase, protease)
Trace minerals (Cu, Se, Zn, Mn, Ca)
Vitamin C

Anyone want to add or remove anything? Yes, I know we're all unique snowflakes, but for the sake of argument. Since I know a small-time pill manufacturer, this could actually be made.

-J
 

Vasha

Senior Member
Messages
119
So guys, with this knowledge, assuming we're making two pills, hydrophobic (fatty) and hydrophilic (water soluble), what is in your ideal ME supplement?

Looks really good @JaimeS! I'm also struck by how much this list looks like the basic building blocks for the business of the body: making cells, running respiration, neurological signaling...

I am not familiar with "Vitex agnus castus," though? Wikipedia tells me that it's thought to be an anaphrodisiac. o_O I assume you chose it for some other reason.;)

Vasha