In search of biochemical correlates of fasting intolerance, and of paradoxical postprandial ketogenesis, lactate suppression, and protein-cured glucose intolerance.
I sent this out, and when I got home I tested the beer for lactate. So, I rewrote this section:
==========
I was a drinking an IPA, which is not sour, so should not have more than trace lactate. The lactate meter (NovaBiomedical Lactate Plus) does not clearly state its isomeric specificity, but it should be isomer-specific and not detect bacterial lactate. Bacterial lactate is D-lactate. While D-lactate is made by humans as a detoxification product of methylglyoxal, circulating lactate is mostly L-lactate, which is what is made from glycolysis.
Therefore, this is almost certainly an effect of the alcohol.
===========
It now reads like this:
=========
I was a drinking an IPA, which is not sour, so should not have more than trace lactate. The lactate meter (NovaBiomedical Lactate Plus) does not clearly state its isomeric specificity, so it is not clear if it would pick up bacterial lactate.
I tested my beer with the lactate meter (same beer as I used on February 3) and it clocked in at 0.6 mmol/L. The average human has almost 5 liters of blood, 3 liters of which is plasma. 18 ounces of beer is 0.53 liters, which means there were 0.32 millimoles of “lactate” in the beer I drank. If 100% of that entered my bloodstream at once, and was not taken up by any cells or metabolized in any way — which is completely implausible — it would be distributed through 3 liters of plasma and would raise my plasma “lactate” by 0.11 mmol/L.
The beer rose my lactate 26.3 times more than this.
Therefore, this is definitely not an effect of any “lactate” in the beer and is almost certainly an an effect of the alcohol.
Is there any chance you are also manganese deficient as it’s also a cofactor for pyruvate carboxylase? Biotin has been helping me tolerate fat better and has given increased energy but there is still something missing as I just can’t build muscle. I have been working very part time at a not too physically demanding job and have developed myofascial pain syndrome behind my right shoulder blade from repetitive motion. The muscle pain is so intense at times that I can’t sleep. The only thing that stops it is ridiculously high doses of vitamin C 5-10 000 mg a day. Vitamin C is also involved in fat metabolism. I could never take vitamin C before because I would immediately have symptoms of copper deficiency. This is no longer the case since doing the high dose vitamin A. But something is still off because my skin and hair become very dry when using the vitamin C and fatty acids don’t seem to be the solution. Anyways, I’m glad to be using vitamin C for the pain instead of opiates. I will keep following your journey since although there are differences there is also sometimes some overlap. I appreciate your courage and interest in experimenting.
Hi Chris - Fantastic detail & open mind. Some of the ‘opposite - of - expected’ occur in me ... high cortisol. High cortisol drives up glucose & flattens ketones during fasting (I’m zero carb OMAD 50 year old 12 % fat woman with 60 min hard workout and 60 min rapid walking each day plus mindfulness, horizon-watching, forest-bathing, but also Type-A INTJ by nature). Example, despite fasting and zero carb life, ketones drop & I feel awful. But if I take herbals that lower cortisol, suddenly I’ve got ketones, and have the fasting energy others talk about. Cortisol is a son of a b*tch that I think has been making everything harder for me. (I’m also celiac. Hashimotos, mthfr, cpet gene allele). - MarySue IRL :)
Did you think of trying these experiments with biotin sparing amino acids like aspartate with/without protein? Anyway please stop self-annihilating experiments(I am selfish. please for our good) and if at all please do only biotin rich experiments. Most importantly thank you for all the information you provide.
I have a few thoughts as an outsider with far less expertise than you. Have you considered any of your issues being related to autoimmune issues in the modern sense of leaky gut? I say this because many of your symptoms are also found in people with autoimmune/ gut issues and while you are aware of foods that have triggered some of your past issues, it seems like you still comsume plant foods now that can contribute to autoimmune issues. How do you know those foods are not causing issues or at the very least are not confounders? You don't need obvious symptoms to have gut/ leaky gut/ autoimmune issues. Have you ever measured any leaky gut biomarkers? I would worry about certain foods (wheat, potatoes etc) causing issues in your situation and your investigation. At the very least it could throw everything off. So could your issues be related to autoimmune/ leaky gut/ gut issues rather than a specific biochemical issue or another issue? I would suggest that anyone who is not having perfect bowel movements or perfect digestion has at least some degree of unresolved gut issues. And that's just based off noticeable signs, not unnoticeable ones. Also, have you considered the fact that maybe you need additional nutrients despite no deficiencies? I say this because I personally have found myself needing certain nutrients despite no sign of deficiency. I discussed this in my response to Dave. So even with biomarkers/ genetics that don't indicate deficiencies, maybe you still need (or if not need, could use) more of a certain nutrient. Many are helped by supplements that they don't *need* according to biomarkers and genetics. I would also question whether the standards/ ranges for nutrient adequacy/ deficency are even accurate as research their based on has limitations. And isn't it true that nutrient adequacy/ deficiencies would be based on the individual? So one level of a nutritent may be good for one person but not another.
Chris, I am curious about the subject you brought up about reactive hypoglycemia, as I struggle with that as well. It seems strange the body would react as if the blood sugar is much lower than it is. Do you have any thoughts on why this is? Maybe this question is more suitable for an AMA, if so let me know.
I too seem to have the paradoxical rise in lactate the longer I fast. The past 2 mornings my waking fasting lactate was lower than my fasting lactate taken later in the morning (yesterday: 7:00am 1.9mmol/l; 11:50am 3.2mmol/l. Today: 7:00am 1.1mmol/l; 9:30am 3.6mmol/l; then 10min after mixed bfast 3.1mmol/l). This pattern is consistent. Does this pattern point to a genetic issue? Or could it be a nutrient deficiency(s)?
My waking fasting lactate is higher than 1.0 more often than not on my Nova lactate meter whether or not I've had any alcohol within the past few days. Most of the reasons for elevated lactate you listed in a different article seem unlikely to me. I've tried high dose thiamine, but that seemed to raise fasting lactate. Waking urine PH is usually ~5.5, but goes up to ~6.5 after a meal. My glucose and ketone readings seem pretty normal.
Do you have any initial suggestions for diet/supplements to address my high fasting lactate and paradoxical rise in lactate the longer I fast? Or is this not enough info to provide a suggestion?
I'm on the BioOpt waitlist, but just seeing if there's something obvious I could try to address this in the meantime.
Very interesting to see the bodyweight impact on your symptom presence/severity! Might you be able to estimate your bodyfat percentage when you were between 153 and 159 lb?
Chris - Right in line with what I said before, look at Chris Palmer's lactate spike comments at 1:30-1:35 of this Tim Ferris interview. All stress-related and true-er in fit exercisers like you and me. https://youtu.be/JVl1X0fb1uA
UPDATE LOG
I sent this out, and when I got home I tested the beer for lactate. So, I rewrote this section:
==========
I was a drinking an IPA, which is not sour, so should not have more than trace lactate. The lactate meter (NovaBiomedical Lactate Plus) does not clearly state its isomeric specificity, but it should be isomer-specific and not detect bacterial lactate. Bacterial lactate is D-lactate. While D-lactate is made by humans as a detoxification product of methylglyoxal, circulating lactate is mostly L-lactate, which is what is made from glycolysis.
Therefore, this is almost certainly an effect of the alcohol.
===========
It now reads like this:
=========
I was a drinking an IPA, which is not sour, so should not have more than trace lactate. The lactate meter (NovaBiomedical Lactate Plus) does not clearly state its isomeric specificity, so it is not clear if it would pick up bacterial lactate.
I tested my beer with the lactate meter (same beer as I used on February 3) and it clocked in at 0.6 mmol/L. The average human has almost 5 liters of blood, 3 liters of which is plasma. 18 ounces of beer is 0.53 liters, which means there were 0.32 millimoles of “lactate” in the beer I drank. If 100% of that entered my bloodstream at once, and was not taken up by any cells or metabolized in any way — which is completely implausible — it would be distributed through 3 liters of plasma and would raise my plasma “lactate” by 0.11 mmol/L.
The beer rose my lactate 26.3 times more than this.
Therefore, this is definitely not an effect of any “lactate” in the beer and is almost certainly an an effect of the alcohol.
========
Is there any chance you are also manganese deficient as it’s also a cofactor for pyruvate carboxylase? Biotin has been helping me tolerate fat better and has given increased energy but there is still something missing as I just can’t build muscle. I have been working very part time at a not too physically demanding job and have developed myofascial pain syndrome behind my right shoulder blade from repetitive motion. The muscle pain is so intense at times that I can’t sleep. The only thing that stops it is ridiculously high doses of vitamin C 5-10 000 mg a day. Vitamin C is also involved in fat metabolism. I could never take vitamin C before because I would immediately have symptoms of copper deficiency. This is no longer the case since doing the high dose vitamin A. But something is still off because my skin and hair become very dry when using the vitamin C and fatty acids don’t seem to be the solution. Anyways, I’m glad to be using vitamin C for the pain instead of opiates. I will keep following your journey since although there are differences there is also sometimes some overlap. I appreciate your courage and interest in experimenting.
How’s the book coming along Chris?
Hi Chris - Fantastic detail & open mind. Some of the ‘opposite - of - expected’ occur in me ... high cortisol. High cortisol drives up glucose & flattens ketones during fasting (I’m zero carb OMAD 50 year old 12 % fat woman with 60 min hard workout and 60 min rapid walking each day plus mindfulness, horizon-watching, forest-bathing, but also Type-A INTJ by nature). Example, despite fasting and zero carb life, ketones drop & I feel awful. But if I take herbals that lower cortisol, suddenly I’ve got ketones, and have the fasting energy others talk about. Cortisol is a son of a b*tch that I think has been making everything harder for me. (I’m also celiac. Hashimotos, mthfr, cpet gene allele). - MarySue IRL :)
Did you think of trying these experiments with biotin sparing amino acids like aspartate with/without protein? Anyway please stop self-annihilating experiments(I am selfish. please for our good) and if at all please do only biotin rich experiments. Most importantly thank you for all the information you provide.
I have a few thoughts as an outsider with far less expertise than you. Have you considered any of your issues being related to autoimmune issues in the modern sense of leaky gut? I say this because many of your symptoms are also found in people with autoimmune/ gut issues and while you are aware of foods that have triggered some of your past issues, it seems like you still comsume plant foods now that can contribute to autoimmune issues. How do you know those foods are not causing issues or at the very least are not confounders? You don't need obvious symptoms to have gut/ leaky gut/ autoimmune issues. Have you ever measured any leaky gut biomarkers? I would worry about certain foods (wheat, potatoes etc) causing issues in your situation and your investigation. At the very least it could throw everything off. So could your issues be related to autoimmune/ leaky gut/ gut issues rather than a specific biochemical issue or another issue? I would suggest that anyone who is not having perfect bowel movements or perfect digestion has at least some degree of unresolved gut issues. And that's just based off noticeable signs, not unnoticeable ones. Also, have you considered the fact that maybe you need additional nutrients despite no deficiencies? I say this because I personally have found myself needing certain nutrients despite no sign of deficiency. I discussed this in my response to Dave. So even with biomarkers/ genetics that don't indicate deficiencies, maybe you still need (or if not need, could use) more of a certain nutrient. Many are helped by supplements that they don't *need* according to biomarkers and genetics. I would also question whether the standards/ ranges for nutrient adequacy/ deficency are even accurate as research their based on has limitations. And isn't it true that nutrient adequacy/ deficiencies would be based on the individual? So one level of a nutritent may be good for one person but not another.
Chris, I am curious about the subject you brought up about reactive hypoglycemia, as I struggle with that as well. It seems strange the body would react as if the blood sugar is much lower than it is. Do you have any thoughts on why this is? Maybe this question is more suitable for an AMA, if so let me know.
Hi Dr. CMJ and community,
I too seem to have the paradoxical rise in lactate the longer I fast. The past 2 mornings my waking fasting lactate was lower than my fasting lactate taken later in the morning (yesterday: 7:00am 1.9mmol/l; 11:50am 3.2mmol/l. Today: 7:00am 1.1mmol/l; 9:30am 3.6mmol/l; then 10min after mixed bfast 3.1mmol/l). This pattern is consistent. Does this pattern point to a genetic issue? Or could it be a nutrient deficiency(s)?
My waking fasting lactate is higher than 1.0 more often than not on my Nova lactate meter whether or not I've had any alcohol within the past few days. Most of the reasons for elevated lactate you listed in a different article seem unlikely to me. I've tried high dose thiamine, but that seemed to raise fasting lactate. Waking urine PH is usually ~5.5, but goes up to ~6.5 after a meal. My glucose and ketone readings seem pretty normal.
Do you have any initial suggestions for diet/supplements to address my high fasting lactate and paradoxical rise in lactate the longer I fast? Or is this not enough info to provide a suggestion?
I'm on the BioOpt waitlist, but just seeing if there's something obvious I could try to address this in the meantime.
Very interesting to see the bodyweight impact on your symptom presence/severity! Might you be able to estimate your bodyfat percentage when you were between 153 and 159 lb?
Chris - Right in line with what I said before, look at Chris Palmer's lactate spike comments at 1:30-1:35 of this Tim Ferris interview. All stress-related and true-er in fit exercisers like you and me. https://youtu.be/JVl1X0fb1uA