Increasing mitochondrial energy production using 4 labtests, by Chris Masterjohn - I got out of ME and resolved low ATP

[Lolinda]

A PhD's Secret Weapon: The Four Biomarkers Every Expert Should, But Doesn’t, Analyze

text version:
https://chrismasterjohnphd.substack.com/p/how-to-interpret-ketone-ratios-and

Chris Masterjohn presents in this video / article that one needs to measure two ratios:
lactate : pyruvate
beta hydroxy butyrate : acetoacetate

These tests aren't impossible at all to get, see the lab list below.
Using these two ratios, one can pinpoint problems in energy metabolism and then fix or improve them:

• if the first ratio is high, then excess electrons from food breakdown are loaded in the cytosol onto pyruvate, producing much lactate.
• If the second ratio is high, then the electrons are transported into the mitochondria by a well functioning malate aspartate shuttle, and excess electrons from food breakdown are loaded there on acetoacetate, producing much beta hydroxy butyrate.
• If none of the ratios are elevated, then all the electrons from food breakdown are absorbed by a well functioning respiratory chain in the mitochondria, producing nice ATP.

Please look into my next post below, which has a diagram explaining all this biochemistry. Each of the components may have a defect.

The nutritional interventions to fix them are always different. We all know people here on Phoenixrising who report significant improvements in energy or even resolution of CFS / ME by things such as diets or variousest vitamins or minerals, sometimes in extremely high doses at other times in low doses, or who had success taking variousest substances/diets that influence energy metabolism somehow. Scroll down for example in the long post of CFS/ME improvement stories by @Hip , who mentions (after some antiviral treatments) high dose biotin, q10, mitochondrial vitamin cocktails, keto, .... I am one of them. I have rescued myself from full blown diagnosed ME using the ketogenic diet (which heavily influences energy metabolism as explained in Masterjohn's video but not shown in the diagram below) and I have increased my ATP by 48% (measured at IMD Berlin, Germany, before and after) using B6 and folate (In spite of having had no deficiency, according to ordinary lab tests). Then, all these people reporting such successes tell other people to try. But then for these other people It often doesn't work or they even get worse. In Masterjohn's framework, the different types of issues need different treatments:

To say it very clearly: I did not get out of ME using the method by Chris Masterjohn. I did it on my own, much before his October 2023 publication of this. However, his framework explains why I succeeded: why I needed the ketogenic diet and why certain vitamins helped and others not. My goal is now to use his theory to find further interventions so I can live without keto while keeping all the happy energy I currently have, which I had never before in my life.

How to access the full version:
The video posted in YouTube was originally the full version. I accessed it during the first 48 hours in which it was free. Now it is only the first part of the video that is accessible. If you pay him those little 12 bucks (if I remember correctly) for a month's access, then you can read the text version. Honestly, this is so little money for such useful information that I wish to respect his copyright for his hard work. I am not his employee and I do not gain any financial or other advantage from posting this information here. It is just pretty much my own story and I see and understand now what I did ... and I hope it helps you.

 

[linusbert]

so why not take all together and fix all combinations at once?
b1, b6, b7, b2, cu, coq

 

[godlovesatrier]

Tbh I would say I've fixed my mitos but that doesn't fix my ME. Taking solgar q10 and 1000mg liquid pomegrenate extract increases mitophagy and fuels mitos. But it just leads to an over extension of the immune system (for me anyway) and I think probably others too.

It is an amazing combo tho taken sparingly.

 

[Lolinda]

so why not take all together and fix all combinations at once?
b1, b6, b7, b2, cu, coq

that would be cool: solving all problems by simply taking a multivitamin . I like your comment a lot, because 1. It is cool just like your avatar photo weightlifting the cat and 2. it gives good opportunity to explain important things.

The short answer:
YES, I know several people, including myself, who got a bit more energy by taking a multivitamin that has the nutrients you mentioned and others.
And NO, because bigger blocks In energy metabolism that would seriously diminish anyone's energy 1. need sometimes extremely high doses (e.g. 10 or 100x the RDA) of one but not the other nutrient to overcome a very specific blockade, 2. taking the wrong one can seriously deteriorate the patient, detailed examples and metabolic reasonings given in the article, 3. there are highly effective interventions not contained in any multivitamin, and not shown in the diagram but elaborated in the article, such as the ketogenic diet

As a more detailed answer,
here I provide you my own example, explained in the terms of Masterjohn's biochemistry, so you see what his article is really about:

To start with, please kindly read this description and map it onto the following diagram:

Using these two ratios, one can pinpoint problems in energy metabolism and then fix or improve them:
if the first ratio is high, then excess electrons from food breakdown are loaded in the cytosol onto pyruvate, producing much lactate. If the second ratio is high, then the electrons are transported into the mitochondria by a well functioning malate aspartate shuttle, and excess electrons from food breakdown are loaded on acetoacetate, producing much beta hydroxy butyrate. If none of the ratios are elevated, then all the electrons from food breakdown are absorbed by a well functioning respiratory chain in the mitochondria, producing a lot of nice ATP. Now, each of these components may have a defect. And the nutritional interventions to fix them are always different.

This image is not taken from Masterjohns article, but I searched a lot just for posting you this answer (Hope you appreciate ) and finally found it in the paper:
https://www.mdpi.com/2072-6643/14/17/3605
EV1 lactate and EV2 OH-butyrate are my additions, based on Masterjohn's article:
EV1 lactate = emergency valve 1: In the cytosol, if there are too many electrons from glycolysis, and their ordinary further transport into the mitochondria via de malate aspartate shuttle is blocked, then they are taken from NADH and loaded onto pyruvate to form lactate and leave the cell
EV2 OH-butyrate = emergency valve 2: In the mitochondria, if there are too many electrons (either arriving from the cytosol via the malate aspartate shuttle or arriving from burning fatty acids as fuel in the mitochondria), and their further transport via the electron transport chain (=respiratory chain In the mitochondria, producing ATP) is blocked, then they are taken from NADH (reverting it to NAD+) and loaded onto acetoacetate to form beta hydroxy butyrate and leave the cell.

Both emergency valves are very important because the NADH:NAD+ ratio in the cytosol and in the mitochondria must be kept in a narrow range, because many other metabolic processes are dependent on this ratio.

Now, if you look at all the above, then it is clear that measuring the two ratios recommended by Masterjohn,
lactate : pyruvate
beta hydroxyutyrate : acetoacetate
you essentially measure how much "emergency activity" happens in the cytosol or the mitochondria, thus indicating how much the respective subsequent pathways are blocked and cannot accept all the electrons that should fuel in the end ATP production in the mitochondria.

A concrete example how to use this theory practically:
if the lactate to pyruvate ratio is elevated but the beta hydroxy butyrate to acetoacetate ratio is not, then we know that the emergency valve 1 is used, while the emergency valve 2 is not used. so the block is between the cytosol and the mitochondria, in the malate aspartate shuttle (yellow circle in Masterjohn's diagram)

Of course, the first thing is to put in the vitamins you see in Masterjohn's colorful diagram (my first post) in the yellow circle. it's a good idea to start low and see if some good things happen
But what if not? There are different possibilities:
One is that simply nothing happens. Then you may e.g. further increase the amount of the vitamins pushing the malate aspartate shuttle but maybe you still do not get more energy, and your measurements of the two ratios do not improve.
For example you have a genetic or toxic block in one of the enzymes In the malate aspetate shuttle.
Now, you see from this diagram that when burning fat for fuel (= ketogenic diet, that is what I do), then this circumvents the entire malate aspartate shuttle. yupee!! I get electrons from burning fatty acids in the mitochondria and if the respiratory chain in the very end functions well, then a lot of nice ATP pops out (which is meanwhile the case in me, measured at IMD Berlin)

 

[linusbert]

thanks for kind words.
thats not voluntarely, the cat demands to be on the highest point, so i need to raise him to the ceiling.

everyone always comes back to keto or carb/insulin less diet.
i tried that, it gave me a big push towards my first crash.
i need frequent meals like every 2h and it must be the bad foods which push insulin, carb rich. so i am on that diet now, eating 300g carbs per day, well at least its wholericebread now, but still pushing insulin output.

the longer the fast the worse it gets, it seams like my body is not able to get enough energy from fat. i think in fasting it burns the glycogen stores down, then goes to protein and somehow fat doesnt work.
but glucose doesnt seam to fix the issue too because i am still sick. just better with that diet.

so what pathway do i need to feed now?
also i had done a pyruvate lactate ratio once, it was weird. 2 month later i was diabetic, then it became really weird.

non-diabetic urin:
pyruvat 4.72 (0.9 - 6.6)
laktat 9,16 (6.3-40.7)
1,94 ratio

it was when diabetic:
blood:
pyruvat 2.3 mg/l (ref 3.6-5.9)
lactate 231 mg/l (ref 57-220)
ratio 100

btw copper deficient and not fixable by copper.

 

[GreenEdge]

everyone always comes back to keto or carb/insulin less diet.

Maybe you should too???

There's no known genetic difference between individuals that effects fat metabolism. Bile salts required for fat metabolism are made in your liver and stored in your gallbladder.

• Even if no gallbladder, your liver can still produce bile acid to digest fat.
• Fatty liver disease may be associated with changes in bile acid metabolism. However, fatty liver disease can be reversed in as little as 2 weeks on a keto or carb/insulin less diet. A diseased liver is the first organ to heal on that diet.

 

[Omgitsremy89]

@linusbert I am in the same boat as you, basically chained to a High carb diet and having to top of glycogen stores ever 2-3 hours or I will begin having what I call cortisol storms.

During these, it feels like my adrenals are pushing hard, which feels nice, my BP is more resilient and I tend to have more energy and less pain. However, I will literally goes days without sleep. And eventually I know my adrenals will crash if I continue on a low carb diet.

I know some people who had the same blood sugar issues (which may also be fat malabsorption) have reported symptom relief after going keto, I just dont have the guts to commit to the diet long enough for my metabolism to become fat adapted. It just seems like a risk if adrenal fatigue is behind the symptoms. Especially hearing anecdotes like your own.

How long did you commit to keto before crashing?

Thank you for the detailed run down @Lolinda.

When I do eventually take the keto plunge, I will most likely run these tests and make sure Im taking everything that helps fat digestion and Fatty acid transport. So far my plan is to take Carnitine, taurine, glycine, choline, b1, 2, 5 7 and maybe oxbile / lipase and some bitters!!

 

[linusbert]

Maybe you should too???

There's no known genetic difference between individuals that effects fat metabolism. Bile salts required for fat metabolism are made in your liver and stored in your gallbladder.

did you read what i wrote? i crashed under that diet!

sorry but this is just factually wrong and dangerous what you write!
there is a lot of genetic fatty acid oxidation disorders as well as any other substance in the body. usually running under the metabolic myopathy and metabolism disorders.

 

[linusbert]

During these, it feels like my adrenals are pushing hard, which feels nice, my BP is more resilient and I tend to have more energy and less pain. However, I will literally goes days without sleep. And eventually I know my adrenals will crash if I continue on a low carb diet.

I know some people who had the same blood sugar issues (which may also be fat malabsorption) have reported symptom relief after going keto, I just dont have the guts to commit to the diet long enough for my metabolism to become fat adapted. It just seems like a risk if adrenal fatigue is behind the symptoms. Especially hearing anecdotes like your own.

How long did you commit to keto before crashing?

for me its different, i get muscle cramping and weakness and some very very bad feeling of sick.

for roughly a year, i didnt do keto, i did zero sugar, low carb, high fat like 70% and everything cooked "myself" (means my lovely girlfriend did it) with best organic ingredients you can buy in germany. usually it was good chunk of fatty meat with fats and salad and vegetables and salad.
and i had a rough decline, at first it was just weakness... and muscle stiffness (for example i did photography, but the camera became heavier and heavier over time and my shoulder muscles where it was strapped stiffed), weird low blood pressure and heartrate, feeling of sickness... i looked really sick (which is weirdly funny, because i was more physically able back then but today i look much healthier despite not beeing in good shape) on the day of the crash the first time the cramping began.. and is the main problem since then, but the others can come too.

keto isnt a solution for everybody, actually i recommend listening to the chris masterjohn video the thread opener did link to initially. he explains it pretty well. some have fatty acid disorders and oxidation chain disorders, by going keto you can fix one and burden the other pathway. he had a patient which got bedbound under this.
so this is highly individual and no fits-all cure exists. what cures some can make others very sick. so careful. listen to your body, if it goes downhill you shouldnt continue. and forget all these "herx" and it "first gets worse before it gets better" crap. sometimes it can, but usually its a sign your body is broken. for example at first you drink alcohol and get worse, over time the body adapts and you can drink more alcohol without sideeffects. so is chronic alcohol good for your body, because it got first worse and then better?...
so there really isnt a diet for everyone, some can repair with meat only, some with vegetables and grains only, some go better with a mix.

 

[Lolinda]

Hi everybody! I am happy to see all your participation in this thread! Let's create something practically useful for all:

I suggest to collect a list of laboratories all over the world. So far I know:

LAB LIST
(Labs that test for all 4 markers: lactate, pyruvate, beta hydroxybutyrate, acetoacetate)

• All the world: Great plains Lab in the USA (I think they got renamed to Mosaic) accepts urine samples from all over the world. These markers can be measured from urine, though a bit less valid. I have sent in once from Europe
• Europe: generally, my impression is that the biggest hospitals in Europe do have a mitochondrial metabolic unit which has a lab that offers these markers
• Germany: Labor Limbach. It is this test package (unfortunately they do not list the metabolites tested, but I was told it is the right thing that has all the 4 and even further tests. You can check further below at Switzerland Viollier, because Viollier sends blood to Limbach, and Viollier exactly lists what you get tested at Limbach): https://lv.limbachgruppe.com/onlinelvz/11_de#/detailView/6395
• Switzerland: Viollier (sending to Labor Limbach in Germany). Click on "Analyses individuelles" at the bottom to see the 4 tests contained: https://www.viollier.ch/fr/analysis/14100
• USA: I think Masterjohn mentioned Quest (please someone confirm and provide a link to the test package. I didn't pay much attention to USA testing)

-> please send me private messages if you have additions, and I will add here. PM would be best, because public posts would just congest this thread with dispersed information.


LAB LIST ATP

• IMD Berlin in Germany tests for ATP in white blood cells and accept blood from other countries (I don't know how representative that test is for the entire body, but I did the test before and after optimizing my energy production and saw a nice increase from deficient to good values while feeling a surge in energy that stayed with me)

Then, I suggest that anybody who wishes to do so, posts in public their own analysis for their own case, so we all can comment and contribute to each other:

YOU POST YOUR OWN ANALYSIS AS A FIRST STEP

• Lab values (including the 4 markers) and some medical history (@linusbert did it nicely, and I think from the only 2 markers he provided, already something can be concluded)
• Your own analysis, based on Masterjohn's theory:
  • Precisely where do you conclude to have bottlenecks in energy production
  • What do you think could be good ideas to supplement or change nutrition in order to fix/circumvent bottlenecks
  • Open questions, requests for comments from others

LIST OF DOCTORS FOR MITO / ENERGY PRODUCTION

• ...

-> please send me PM so I can insert here (insert with or without your name as the source as you wish) and with comments if you made experiences with them or not yet.

The above will enable all of us to help each other. We are all not medical doctors and do not give medical advice. But doctors for mitochondrial issues are rare. And I had only unusably bad ones. For example, at the time when I did not yet read all the science and I had ME so bad that I was unable to walk up a stair slowly, a doctor who specializes on adult metabolic issues and rare diseases helped me nothing, and then I resolved ME using the ketogenic diet but still had some issues and I was literally told "if you treat yourself we cannot help you.". (Fuck off you bastard!!!!). Before that, when gliding into CFS and then ME, I heard from other doctors the false and harmful stupidity that if I don't have an elevated lactate then I cannot have a mitochondrial disease (they didn't even think of measuring anything else, let alone thinking about ratios). So let's be as nice and as helpful to each other as we would wish our doctors to be, let's put in the hard work of analysis, and let's not indulge in excuses, because Masterjohn already gave us the right theory.

I would say I've fixed my mitos but that doesn't fix my ME

That's an important remark: fixing mitos / fixing the 4 markers / more ATP does not equal resolving all ME in everybody. But better having the mitos fixed than not and I am so so so happy to be out of ME myself and wish you all the same

 

[sb4]

I had a great planes oganic acids urine test done years ago. Think I was low carb / possibly keto at the time so that no doubt influences the results.

3-Hydroxybutyric = 277 (ref < 1.9) [High]
Acetoacetic = 370 (ref <10) [High]
BHB/AcAc = 0.75

Lactic = 8 (ref 0.74-19)
Pyruvic = 2 (ref 0.28-6.7)
Lactate/Pyruvate = 4

I would have to assume that BHB and AcAc are so high because of low carb, unless it is an energy blockage.

What are Masterjohns recomended ratios?

 

[Rufous McKinney]

Let's create something practically useful for everybody:

appreciating your efforts here, to do that........

 

[godlovesatrier]

@sb4 do you have a 16s? This shows your butyrate to be high. Which is a good thing I'd wager, butyrate is often super low in pwme.

Can't comment on the others but several of these markers show up in biomesight testing, so I just wondered if you had any info. For me high butyrate correlates with massive improvements in health, but it may not be that way for everyone I appreciate.

 

[sb4]

@godlovesatrier I don't know what a 16s is. What is it?

 

[godlovesatrier]

It's a rna based analysis of faecal matter to understand the composition of bacteria in the gut.

https://www.healthrising.org/blog/2023/02/10/gut-biomarker-chronic-fatigue-syndrome-pt-1/ this is a good article to read and explains the NIH study that got released in Feb 2023 with the gut findings.

 

[sb4]

From Masterjohns video the urine ratios are:
Urine Lactate/Pyruvate: normal range 5-10 [mine 4]
Urine BHB/AcAc: normal range 0.2-6 [mine 0.75]

These values are for in light ketosis so will vary a bit depending on diet.

 

[Mitomystery]

From Masterjohns video the urine ratios are:
Urine Lactate/Pyruvate: normal range 5-10 [mine 4]
Urine BHB/AcAc: normal range 0.2-6 [mine 0.75]

These values are for in light ketosis so will vary a bit depending on diet.

My Lacate is 4.6/ Pyruvate 1.0 = 4.6 ratio and BHB is 1.4/ acac1.7 = 0.82

Does this mean my BHB/AcAC is the problem?

 

[sb4]

My Lacate is 4.6/ Pyruvate 1.0 = 4.6 ratio and BHB is 1.4/ acac1.7 = 0.82

Does this mean my BHB/AcAC is the problem?

Your stats look quite a lot like mine. Where you low carb at the time?

I don't know much about the theory but your BHB/AcAc is in masterjohns normal range. Your Lactate to Pyruvate is low which he treats with high dose Thiamine.

I have had some limited success with thiamine but it's by no means a solution for me or even something I take regularly. Others have had better success with it though so its worth a shot.

 

[CFS_RPH]

A PhD's Secret Weapon: The Four Biomarkers Every Expert Should, But Doesn’t, Analyze

text version:
https://chrismasterjohnphd.substack.com/p/how-to-interpret-ketone-ratios-and

Chris Masterjohn presents in this video / article that one needs to measure two ratios:
lactate : pyruvate
beta hydroxy butyrate : acetoacetate

These tests aren't impossible at all to get, see the lab list below.
Using these two ratios, one can pinpoint problems in energy metabolism and then fix or improve them:

• if the first ratio is high, then excess electrons from food breakdown are loaded in the cytosol onto pyruvate, producing much lactate.
• If the second ratio is high, then the electrons are transported into the mitochondria by a well functioning malate aspartate shuttle, and excess electrons from food breakdown are loaded there on acetoacetate, producing much beta hydroxy butyrate.
• If none of the ratios are elevated, then all the electrons from food breakdown are absorbed by a well functioning respiratory chain in the mitochondria, producing nice ATP.

Please look into my next post below, which has a diagram explaining all this biochemistry. Each of the components may have a defect.

The nutritional interventions to fix them are always different. We all know people here on Phoenixrising who report significant improvements in energy or even resolution of CFS / ME by things such as diets or variousest vitamins or minerals, sometimes in extremely high doses at other times in low doses, or who had success taking variousest substances/diets that influence energy metabolism somehow. Scroll down for example in the long post of CFS/ME improvement stories by @Hip , who mentions (after some antiviral treatments) high dose biotin, q10, mitochondrial vitamin cocktails, keto, .... I am one of them. I have rescued myself from full blown diagnosed ME using the ketogenic diet (which heavily influences energy metabolism as explained in Masterjohn's video but not shown in the diagram below) and I have increased my ATP by 48% (measured at IMD Berlin, Germany, before and after) using B6 and folate (In spite of having had no deficiency, according to ordinary lab tests). Then, all these people reporting such successes tell other people to try. But then for these other people It often doesn't work or they even get worse. In Masterjohn's framework, the different types of issues need different treatments:

View attachment 52769

To say it very clearly: I did not get out of ME using the method by Chris Masterjohn. I did it on my own, much before his October 2023 publication of this. However, his framework explains why I succeeded: why I needed the ketogenic diet and why certain vitamins helped and others not. My goal is now to use his theory to find further interventions so I can live without keto while keeping all the happy energy I currently have, which I had never before in my life.

How to access the full version:
The video posted in YouTube was originally the full version. I accessed it during the first 48 hours in which it was free. Now it is only the first part of the video that is accessible. If you pay him those little 12 bucks (if I remember correctly) for a month's access, then you can read the text version. Honestly, this is so little money for such useful information that I wish to respect his copyright for his hard work. I am not his employee and I do not gain any financial or other advantage from posting this information here. It is just pretty much my own story and I see and understand now what I did ... and I hope it helps you.

Wow this is very interesting information. So my wife has severe ME/CFS and we recently had her lactate and pyruvate done.

Lactate: 10.4 mg/dL
Pyruvate 0.2 mg/dL
L/P Ratio: 52
we have not yet tested for the BHB/AcAc levels but based on this her ratio is extremely high. She takes alot of B vitamins already and actually has elevated B12 (1026. Range 200-910 pg/mL)

Based on the research from Chris how would you interpret this?

Thank you so much!