I am surprised that there are no different normal values for L:P with and without keto. Just think about it: L:P goes up if too many electrons arrive from glycolysis than what can be accepted by the later stages of electron transport (malate aspartate shuttle, ...). Now, reduce glycolysis to a tiny fraction of normal by eating a ketogenic diet and this should not influence L:P ratio?? and think about it: keto is a treatment for issues that feature an elevated L:P ratio. So it should change it!!
@Chris: I beg you to answer this! :-) I think this would give folks more confidence in what you present bc this seems totally lacking any logic that the same normal values should do....
You may be right, but I know of no evidence this is true, and this does not seem obvious at all to me. There is no particular reason keto should decrease the downstream metabolism of pyruvate more than it decreases glycolysis. In fact even mild elevations of ketones directly suppress glucose levels without stimulating insulin.
I have found a study that shows: The LP ratio stays indeed pretty much the same on different ketogenic diets and normal diet. (There is a tiny decrease in L:P on average on keto compared to non-keto)
.Metabolic effects of three ketogenic diets in the treatment of severe epilepsy
this study is not as perfect as I would have liked it to be, because they show the L:P averages of different patient groups and not the averages of the same group under different ketogenic or "normal" diets. Also, I would have liked the study in normal people and not epileptic patients. Also, knowing about the average values isn't precisely a statement on what the normal range should be. With all these limitations, I think the study pretty much settles the question that indeed, L:P does not change whether keto or "normal" diet. So as you write it, pyruvate and lactate decrease similarly, largely keeping their ratio.
PS Big like that you, such a famous guy, responded to my tiny question!!
This was fascinating. I was trying to get into your new program. I will have my doctor run these tests all together many of them I have run in the past. I am struggling with long covid as well and rely on various supplements just to function especially to help with inflammation, but I have told all my doctors that I am sure most of the answer can be found in energy production. I have antibodies to the GAD 65 receptor and have been diagnosed with a neuromuscular issue. I also have issues with heme. In addition I have a history of multiple floxing and high normal glucose while not consuming alcohol, sugars or high carbs.
Will you be potentially working with someone to use AI to generate programs to feed the results from these tests to help identify potential solutions as you outlined in the ven diagrams?
Thanks so much for your unbelievable productivity. I have been over 25 years and still trying to figure out what my metabolic issues are.
Hi, this is a fascinating and very useful article, however it leaves important questions open:
Can the L:P ratio (lactate:pyruvate) and the BHB:AcAc ratio be used in order to further optimize energy/performance/health when they are within the normal range?
Does oxalate interfere with the malate-asparate shuttle by reducing the production of oxaloacetate from pyruvate carboxylase or reducing the conversion of oxaloacetate to malate by malate dehydrogenase? Or both?
I'm currently investigating whether the headaches I wake up with are caused by oxalate clearing while sleeping. My hypothesis is that at night the body decides to detoxify oxalates. This ties up pyruvate carboxylase from generating oxaloacetate which slows down the citric acid cycle, leading to a rise in lactate and ketones.
I'm considering experimenting with supplementing either oxaloacetate before bed, or a cheaper precursor such as aspartate or glutamate, to see if keeping the citric acid cycle going during the overnight fast prevents the headaches. But first I plan on testing morning ketone levels to see if they are markedly elevated on days in which I wake up with a headache.
So Do you have a date when the Vitamins book will be completed? It's been years. My comments about this seem to be overlooked. Disappointed, frankly I'm not sure I still want it...
I can't wait. I plan on buying one for each of my family members. I want them to have a good resource to go to without having me randomly pepper in, "consider eating this food to get nutrient x". It's too hard and it doesn't stick in their mind when they haven't prioritised it. Something comprehensive like your book that they can reach for whenever they want to is far more useful.
I am surprised that there are no different normal values for L:P with and without keto. Just think about it: L:P goes up if too many electrons arrive from glycolysis than what can be accepted by the later stages of electron transport (malate aspartate shuttle, ...). Now, reduce glycolysis to a tiny fraction of normal by eating a ketogenic diet and this should not influence L:P ratio?? and think about it: keto is a treatment for issues that feature an elevated L:P ratio. So it should change it!!
@Chris: I beg you to answer this! :-) I think this would give folks more confidence in what you present bc this seems totally lacking any logic that the same normal values should do....
You may be right, but I know of no evidence this is true, and this does not seem obvious at all to me. There is no particular reason keto should decrease the downstream metabolism of pyruvate more than it decreases glycolysis. In fact even mild elevations of ketones directly suppress glucose levels without stimulating insulin.
I have found a study that shows: The LP ratio stays indeed pretty much the same on different ketogenic diets and normal diet. (There is a tiny decrease in L:P on average on keto compared to non-keto)
.Metabolic effects of three ketogenic diets in the treatment of severe epilepsy
(1989)
https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-8749.1989.tb03973.x
this study is not as perfect as I would have liked it to be, because they show the L:P averages of different patient groups and not the averages of the same group under different ketogenic or "normal" diets. Also, I would have liked the study in normal people and not epileptic patients. Also, knowing about the average values isn't precisely a statement on what the normal range should be. With all these limitations, I think the study pretty much settles the question that indeed, L:P does not change whether keto or "normal" diet. So as you write it, pyruvate and lactate decrease similarly, largely keeping their ratio.
PS Big like that you, such a famous guy, responded to my tiny question!!
Cheers from your happy reader:
Linda
This was fascinating. I was trying to get into your new program. I will have my doctor run these tests all together many of them I have run in the past. I am struggling with long covid as well and rely on various supplements just to function especially to help with inflammation, but I have told all my doctors that I am sure most of the answer can be found in energy production. I have antibodies to the GAD 65 receptor and have been diagnosed with a neuromuscular issue. I also have issues with heme. In addition I have a history of multiple floxing and high normal glucose while not consuming alcohol, sugars or high carbs.
Will you be potentially working with someone to use AI to generate programs to feed the results from these tests to help identify potential solutions as you outlined in the ven diagrams?
Thanks so much for your unbelievable productivity. I have been over 25 years and still trying to figure out what my metabolic issues are.
Hi, this is a fascinating and very useful article, however it leaves important questions open:
Can the L:P ratio (lactate:pyruvate) and the BHB:AcAc ratio be used in order to further optimize energy/performance/health when they are within the normal range?
And how to do that?
in detail: https://chrismasterjohnphd.substack.com/p/submit-questions-now-for-the-fall/comment/51562128
Does oxalate interfere with the malate-asparate shuttle by reducing the production of oxaloacetate from pyruvate carboxylase or reducing the conversion of oxaloacetate to malate by malate dehydrogenase? Or both?
I'm currently investigating whether the headaches I wake up with are caused by oxalate clearing while sleeping. My hypothesis is that at night the body decides to detoxify oxalates. This ties up pyruvate carboxylase from generating oxaloacetate which slows down the citric acid cycle, leading to a rise in lactate and ketones.
The headache may be caused directly by a lack of ATP or by a rapid fall in lactate as the citric acid cycle resumes normal function. The latter possibility I learned from Brad Marshall's blog post found here: https://fireinabottle.net/lactate-and-the-lipoic-acid-flu-an-hypothesis-and-n1/.
I'm considering experimenting with supplementing either oxaloacetate before bed, or a cheaper precursor such as aspartate or glutamate, to see if keeping the citric acid cycle going during the overnight fast prevents the headaches. But first I plan on testing morning ketone levels to see if they are markedly elevated on days in which I wake up with a headache.
So Do you have a date when the Vitamins book will be completed? It's been years. My comments about this seem to be overlooked. Disappointed, frankly I'm not sure I still want it...
You can get a refund at any time. It will be finished.
I can't wait. I plan on buying one for each of my family members. I want them to have a good resource to go to without having me randomly pepper in, "consider eating this food to get nutrient x". It's too hard and it doesn't stick in their mind when they haven't prioritised it. Something comprehensive like your book that they can reach for whenever they want to is far more useful.
Chris said it will appear at the end of the year. But Vitamin & Mineral 101 is still good and detail