This article was great! Definitely where I've found myself in the last few years of my experiments with chronic fatigue/hypothyroid/estrogen dominance. May I humbly suggest an add on to this energy metabolism? But I feel melatonin is also an overlooked antioxidant that we're discovering plays a HUGE role in the body's ability to repair itself from the damage of everyday living and even in cancer prevention. I say this because it was what ended up being the "cure" to my own energy disorder.
I had a nominal recovery from my chronic fatigue with vitamins and supplements back in 2016, and from reading articles on the internet I thought at first I was dealiing with copper toxicity, before finding the Weston A Price Foundation and diving headlong into their approach and saw good things at the outset, so I stopped taking most all of my vitamins and supplements in the effort to get everything from my diet and food. Needless to say it was a disaster and all of my progress evaporated in less than two years (not saying that Weston A Price isn't useful! I still follow a majority of their principles and advice with great success, but it's not the whole picture is what I'm saying), followed by me trying to reintroduce everything I had been taking and that had worked in the past, but now to no avail. To say I was beside myself in despair after having success and then losing it and not able to get it back was an understatement. I couldn't give up though and so I kept experimenting, reading the forums of other chronic fatigue sufferers. I knew the thyroid was involved, but it wasn't the whole story. I took everything; iodine, selenium, iron, tyrosine, zinc, magnesium, etc (I still do take these supplementsto be clear ). Finally, in a fit of desperation I turned to DHEA and pregnenolone when the forum said it was helpful for chronic fatigue sufferers. It was an absolute disaster, BUT it was the catalyst for finding out what was really wrong. Both of those hormones increased my estrogen in a very bad way, so I had the clue that it was hormones that were the main problem and what was dysregulated, specifically my sex hormones. It was when I was looking for a natural aromatase inhibitor that I found melatonin as an answer.
Now to go into my family history. My mom has PCOS and lost most of her hair from high testosterone and developed diabetes because of it. I had none of my mom's symptoms however and was never diagnosed with PCOS, but the more I looked into it the more it seemed that I had inherited some of its defects because in 2015 a study from China found a polymorphism or defect in the melatonin receptors in the reproductive area of women with PCOS. This seemed confirmed later in a 2019 study from Iran when they gave PCOS women 10mg of melatonin and it resolved their issues. The findings now are that we have 4x the amount of melatonin in our reproductive sites than in our blood and they found this deficiency by measuring the follicular fluid of these women. What is so crazy is that the first time I recovered I was taking 2mg of melatonin in a blend, so I didn't know it was what was having the impact and it was one of the first supplements I stopped since I didn't know if it was necessary or not. Needless to say, after reading those studies I ran out and bought 5mg of melatonin and IMMEDIATELY all of my vitamins and supplements that had worked in the past worked again like before. It was incredible!
That's why I'm writing this because I feel it fits into your framework of lifestyle/ environmental factors turning certain genes or receptors on and off and what a critical role melatonin in particular has in repairing and regulating energy in the body. Another study showed that if a woman's melatonin status is compromised during pregnancy it is passed to her children who then also manifest endocrine disorders later.
Even if you don't have the genetic defect like I do, they know that the melatonin receptors can be calcified and become defective that way, which explains the importance of vitamin K2 that you've discussed in the past Chris. :-)
The other big piece in my recovery story was getting my dopamine status back up and getting it regulated correctly. A new finding shows there's a polymorphism in dopamine regulation in bruxism (clenching and grinding of the teeth). My dad has that and I do too. It would make sense that these two dysregulations in both melatonin and dopamine could be a perfect storm for fatigue disorders since melatonin and dopamine act as each other's counter balance/ shift manager in circadian rhythms/ energy outputs. However, it seems melatonin is the master repairer in this relationship as it protects dopamine neurons even though it opposes dopamine production directly.
Anyway, sorry for the long story, but I felt I had to offer this insight as the research into melatonin is truly groundbreaking and its very essential role in energy recovery and maintenance. All of the vitamins and supplements you listed in your article haS been the backbone of my recovery, but none of them worked until I put in the true base of melatonin in place, in my case. :-) Like you said, it may look different for everyone as we all have unique factors in our genetic make up, but there are still some constants and I think melatonin may be one of them as it seems our lifestyle/environment is damaging the formation of its receptors in the body, particularly reproductively.
I hope this helps others in their journey and yours too. ❤
Great article on what should be the most central topic in nutrition.
I get to teach prsctitioners on a regular basis and, regardless of the exact topic/focus, I will invariably find myself speaking about of influence of energy availability. The patterns here:
- practitioners immediately 'get it' as to how pervasive energy metabolism is in every single condition we work with
- they struggle to integrate this way of thinking into how they assess, plan treatment, etc. ("Do we then focus on energy first and then on dealing with inflammatory problems?" "So this is actually more important than dystegulatiom of the HPAA/stress response?" etc)
For anyone who connects with these ideas but also resonates with those example questions, I would propose considering a simple equation (one that brings it together) and then to reread this article. The equation is that of relative energy availability, ie. quantifying how much every availability we have vs. how much our system wants. Energy availability = energy production (mitochondria) + energy signalling (thyroid/insulin/etc) - energy theft (inflammation). Energy desired = physical and cognitive workload + predicted demands (reflexive computation at the brain stem/PAG, based on prior experience) - indications of physical adaption (cortisol). If there is no gap between the two, there is no mobilization (stress response). If there is a gap, either because availability is low or perceived needs are high, there is a mobilization response (aka sympathetic stress response).
This is, of course, just one model to bring these important contributing factors together in a way that avoids having to choose which 'anglr' to apply when making assessments and one that applies to all and makes evidence, while also explaining why we need to tend to multiple zones in some individuals while others will respond really well from support in just one zone (if that happened to be their one limiting factor). There are other models that are just as valid but I hope that this is intuitive and outlines how we never need to worry about whether we use an 'emrgey first' stretrgy or another approach that has proved to be successful some of the time, as they are all connected. In all individuals, all of the time.
So dropping this in here in the hope that it will allow people to take these important ideas laid out in the article and immediately translate them into use on the frontline. Because energy metabolism governs everything!
Thank you Chris. This is so good and so helpful. “idiosyncratic genetic impairments in energy metabolism that are rare as individual diagnosable diseases are likely to be common as heterozygous partial biochemical impairments. My suspicion is that it is very common to have one or a few “carrier status” mutations that do not lead to disease, but do form idiosyncratic bottlenecks in energy metabolism.” This is definitely my experience. Also “ A high-energy, low-entropy state allows us to maximally contract our muscles when contraction is needed, and fully relax our muscles when it is not. A low-energy, high-entropy state mixes these together and results in fatigue and muscle tension, or the rigidity, tremors, and slow movements of Parkinsonism.” I’ve been having issues with not being able to get to sleep and not entering deep sleep with one of the symptoms being leg tremors/restless legs and a mild recurrence of allergies. Finally yesterday I was able to put a stop to it with riboflavin. I guess it’s just something I’ve got to take religiously. And though sometimes it seems that high dose thiamine would be a good choice for me it always results in symptoms of riboflavin deficiency when I try it. “using imagination for sufficient hope instead of excessive worry” has been a discipline I’ve had to learn. The discipline of expecting good things instead of worrying about what bad thing might be around the corner. I imagine it as being in a room full of rats but remembering to leave the door cracked for the cat to get in. Gonna do some more reading on the ACAD enzyme you mentioned.
I have been looking at Sequencing.com and Nebulagenomics also. I have run my 23andMe and Ancestry dot com and FTDNA results through Promethease and seen a few interesting things on Strategene (note these DNA results providers can be inaccurate so not used for diagnosis, just for further research). I think I have a metabolic smoking gun somewhere though, that will turn up on whole exome or whole genome sequencing eventually. I've been using DNA for genealogy for quite a few years and there are quite a few early deaths on my dad's side including suicides. A deep dive into the family tree can be instructive.
Yes, of course! Energy metabolism trumps everything! I believe this is why the carnivore diet fixes nearly everything for nearly everyone! It did for me. Except for a few seasonal allergies here and there... for which I'll try your riboflavin trick asap as it is still May! For some of my carnivore years the allergies have been better than others (sometimes nonexistent), but I haven't been eating eggs this year and it's worse... and I'm homozygous MTHFR C677 on a high fat diet so ... riboflavin is not a bad idea.
This is a great comprehensive overview. I’m interested if you’ve looked at Morley Robbins theories around iron and iron deficiency. Also, your thoughts on mitochondrial function and nutritional support for improving it.
Could psoriasis be caused by a retinyl esters toxicity?
In 1947, the New Enlgland Journal of Medicine published a study in which 11 severe psoriasis patient were put on a diet low in vitamin A and carotene: 7 complete clearing of lesions, 2 marked improvement, 1 slight improvement, 1 no improvement.
Another study shows that psoriasis patients have slightly low retinol-binding protein (RBP) and high dehydroretinol, along with other vitamin A related abnormalities.
Amazing!! This article is well thought out. Chris is many leagues above most of the nutrition gurus in the space at the moment, thank you for your work. W/ regards to energy metabolism, the most recent change I have made in my health has been vitamin B1 megadosing for my IBS. It has massively reduced bloating, gas, indigestion and as a side effect has improved my energy levels! I'm not sure of the effects on my blood sugar though which would be interesting. Thanks to Eliot Overton for making me aware of this as well.
Hey- so much great information! There’s so much testing here. When people work with you, can you narrow down which tests are most relevant? Or, do you still suggest doing everything listed above?
Definitely food for thought (pun unintended)... Interesting to see a kind of grand unified theory for wellness, based on energy metabolism. However, your earlier remarks in the article suggested another important dimension, that of entropy. The article does not appear to address directly the question of entropy reduction.
This might be the point where a novice like me might ask questions about inflammation, for example, or even psychoneuroendocrinoimmunology. There may be a grand unified theory, but it appears to this layperson to lie in the interaction among several critical systems. I'd appreciate your thoughts. Thanks!
Great article. Just signed up on the 101 course, I actually got the cliff notes last year. Just wondering if you've looked into how caffeine can affect micronutrients absorption, specifically vitamin D? I drink a few cups of black and green tea throughout the day, sometimes with meals. Really appreciate your research, and can't wait to get my lessons from the 101 course!
Hi Chris,it’s me again lol.sorry if wrong place to post but I’m unsure of best place to ask this question. How is the book coming along?yes it’s that question again ,sorry to keep snapping at your heels but don’t you think it’s about time you completed as it’s ,correct me if I’m wrong about 4 years overdue?
It’s not to say I don’t appreciate all the freebies you give,they are very much appreciated but it’s just I was hoping to read what I know will be a work of art before I pop my clogs lol,which I’m hoping will be a lot later than sooner,73 now and counting 😀.
Had a bit D test the other day,came back at 155🧐🧐.I immediately stopped supplementing 4000 iu daily to zero.? Triclycerides were 0.7 and other panels in range except urea just out,I’ve increased water ,always a poor water drinker?
I do thankyou once again for your responses which are always on the money.
This article was great! Definitely where I've found myself in the last few years of my experiments with chronic fatigue/hypothyroid/estrogen dominance. May I humbly suggest an add on to this energy metabolism? But I feel melatonin is also an overlooked antioxidant that we're discovering plays a HUGE role in the body's ability to repair itself from the damage of everyday living and even in cancer prevention. I say this because it was what ended up being the "cure" to my own energy disorder.
I had a nominal recovery from my chronic fatigue with vitamins and supplements back in 2016, and from reading articles on the internet I thought at first I was dealiing with copper toxicity, before finding the Weston A Price Foundation and diving headlong into their approach and saw good things at the outset, so I stopped taking most all of my vitamins and supplements in the effort to get everything from my diet and food. Needless to say it was a disaster and all of my progress evaporated in less than two years (not saying that Weston A Price isn't useful! I still follow a majority of their principles and advice with great success, but it's not the whole picture is what I'm saying), followed by me trying to reintroduce everything I had been taking and that had worked in the past, but now to no avail. To say I was beside myself in despair after having success and then losing it and not able to get it back was an understatement. I couldn't give up though and so I kept experimenting, reading the forums of other chronic fatigue sufferers. I knew the thyroid was involved, but it wasn't the whole story. I took everything; iodine, selenium, iron, tyrosine, zinc, magnesium, etc (I still do take these supplementsto be clear ). Finally, in a fit of desperation I turned to DHEA and pregnenolone when the forum said it was helpful for chronic fatigue sufferers. It was an absolute disaster, BUT it was the catalyst for finding out what was really wrong. Both of those hormones increased my estrogen in a very bad way, so I had the clue that it was hormones that were the main problem and what was dysregulated, specifically my sex hormones. It was when I was looking for a natural aromatase inhibitor that I found melatonin as an answer.
Now to go into my family history. My mom has PCOS and lost most of her hair from high testosterone and developed diabetes because of it. I had none of my mom's symptoms however and was never diagnosed with PCOS, but the more I looked into it the more it seemed that I had inherited some of its defects because in 2015 a study from China found a polymorphism or defect in the melatonin receptors in the reproductive area of women with PCOS. This seemed confirmed later in a 2019 study from Iran when they gave PCOS women 10mg of melatonin and it resolved their issues. The findings now are that we have 4x the amount of melatonin in our reproductive sites than in our blood and they found this deficiency by measuring the follicular fluid of these women. What is so crazy is that the first time I recovered I was taking 2mg of melatonin in a blend, so I didn't know it was what was having the impact and it was one of the first supplements I stopped since I didn't know if it was necessary or not. Needless to say, after reading those studies I ran out and bought 5mg of melatonin and IMMEDIATELY all of my vitamins and supplements that had worked in the past worked again like before. It was incredible!
That's why I'm writing this because I feel it fits into your framework of lifestyle/ environmental factors turning certain genes or receptors on and off and what a critical role melatonin in particular has in repairing and regulating energy in the body. Another study showed that if a woman's melatonin status is compromised during pregnancy it is passed to her children who then also manifest endocrine disorders later.
Even if you don't have the genetic defect like I do, they know that the melatonin receptors can be calcified and become defective that way, which explains the importance of vitamin K2 that you've discussed in the past Chris. :-)
The other big piece in my recovery story was getting my dopamine status back up and getting it regulated correctly. A new finding shows there's a polymorphism in dopamine regulation in bruxism (clenching and grinding of the teeth). My dad has that and I do too. It would make sense that these two dysregulations in both melatonin and dopamine could be a perfect storm for fatigue disorders since melatonin and dopamine act as each other's counter balance/ shift manager in circadian rhythms/ energy outputs. However, it seems melatonin is the master repairer in this relationship as it protects dopamine neurons even though it opposes dopamine production directly.
Anyway, sorry for the long story, but I felt I had to offer this insight as the research into melatonin is truly groundbreaking and its very essential role in energy recovery and maintenance. All of the vitamins and supplements you listed in your article haS been the backbone of my recovery, but none of them worked until I put in the true base of melatonin in place, in my case. :-) Like you said, it may look different for everyone as we all have unique factors in our genetic make up, but there are still some constants and I think melatonin may be one of them as it seems our lifestyle/environment is damaging the formation of its receptors in the body, particularly reproductively.
I hope this helps others in their journey and yours too. ❤
Great article on what should be the most central topic in nutrition.
I get to teach prsctitioners on a regular basis and, regardless of the exact topic/focus, I will invariably find myself speaking about of influence of energy availability. The patterns here:
- practitioners immediately 'get it' as to how pervasive energy metabolism is in every single condition we work with
- they struggle to integrate this way of thinking into how they assess, plan treatment, etc. ("Do we then focus on energy first and then on dealing with inflammatory problems?" "So this is actually more important than dystegulatiom of the HPAA/stress response?" etc)
For anyone who connects with these ideas but also resonates with those example questions, I would propose considering a simple equation (one that brings it together) and then to reread this article. The equation is that of relative energy availability, ie. quantifying how much every availability we have vs. how much our system wants. Energy availability = energy production (mitochondria) + energy signalling (thyroid/insulin/etc) - energy theft (inflammation). Energy desired = physical and cognitive workload + predicted demands (reflexive computation at the brain stem/PAG, based on prior experience) - indications of physical adaption (cortisol). If there is no gap between the two, there is no mobilization (stress response). If there is a gap, either because availability is low or perceived needs are high, there is a mobilization response (aka sympathetic stress response).
This is, of course, just one model to bring these important contributing factors together in a way that avoids having to choose which 'anglr' to apply when making assessments and one that applies to all and makes evidence, while also explaining why we need to tend to multiple zones in some individuals while others will respond really well from support in just one zone (if that happened to be their one limiting factor). There are other models that are just as valid but I hope that this is intuitive and outlines how we never need to worry about whether we use an 'emrgey first' stretrgy or another approach that has proved to be successful some of the time, as they are all connected. In all individuals, all of the time.
So dropping this in here in the hope that it will allow people to take these important ideas laid out in the article and immediately translate them into use on the frontline. Because energy metabolism governs everything!
Thank you Chris. This is so good and so helpful. “idiosyncratic genetic impairments in energy metabolism that are rare as individual diagnosable diseases are likely to be common as heterozygous partial biochemical impairments. My suspicion is that it is very common to have one or a few “carrier status” mutations that do not lead to disease, but do form idiosyncratic bottlenecks in energy metabolism.” This is definitely my experience. Also “ A high-energy, low-entropy state allows us to maximally contract our muscles when contraction is needed, and fully relax our muscles when it is not. A low-energy, high-entropy state mixes these together and results in fatigue and muscle tension, or the rigidity, tremors, and slow movements of Parkinsonism.” I’ve been having issues with not being able to get to sleep and not entering deep sleep with one of the symptoms being leg tremors/restless legs and a mild recurrence of allergies. Finally yesterday I was able to put a stop to it with riboflavin. I guess it’s just something I’ve got to take religiously. And though sometimes it seems that high dose thiamine would be a good choice for me it always results in symptoms of riboflavin deficiency when I try it. “using imagination for sufficient hope instead of excessive worry” has been a discipline I’ve had to learn. The discipline of expecting good things instead of worrying about what bad thing might be around the corner. I imagine it as being in a room full of rats but remembering to leave the door cracked for the cat to get in. Gonna do some more reading on the ACAD enzyme you mentioned.
Thank you, wonderful article. Yes, perfecting Energy by seeking answers through genetics and labs!
This is awesome! I feel like we are on the cutting edge. I feel privileged and keenly grateful to have access to Chris Masterjohns’s brain.
I have been looking at Sequencing.com and Nebulagenomics also. I have run my 23andMe and Ancestry dot com and FTDNA results through Promethease and seen a few interesting things on Strategene (note these DNA results providers can be inaccurate so not used for diagnosis, just for further research). I think I have a metabolic smoking gun somewhere though, that will turn up on whole exome or whole genome sequencing eventually. I've been using DNA for genealogy for quite a few years and there are quite a few early deaths on my dad's side including suicides. A deep dive into the family tree can be instructive.
Yes, of course! Energy metabolism trumps everything! I believe this is why the carnivore diet fixes nearly everything for nearly everyone! It did for me. Except for a few seasonal allergies here and there... for which I'll try your riboflavin trick asap as it is still May! For some of my carnivore years the allergies have been better than others (sometimes nonexistent), but I haven't been eating eggs this year and it's worse... and I'm homozygous MTHFR C677 on a high fat diet so ... riboflavin is not a bad idea.
This is a great comprehensive overview. I’m interested if you’ve looked at Morley Robbins theories around iron and iron deficiency. Also, your thoughts on mitochondrial function and nutritional support for improving it.
Could psoriasis be caused by a retinyl esters toxicity?
In 1947, the New Enlgland Journal of Medicine published a study in which 11 severe psoriasis patient were put on a diet low in vitamin A and carotene: 7 complete clearing of lesions, 2 marked improvement, 1 slight improvement, 1 no improvement.
Another study shows that psoriasis patients have slightly low retinol-binding protein (RBP) and high dehydroretinol, along with other vitamin A related abnormalities.
https://www.nejm.org/doi/full/10.1056/NEJM194706192362503 (1947 study)
http://www.ncbi.nlm.nih.gov/pubmed/4096526 (vitamin A abnormalities study)
Then, why not recommend to supplement flush niacin, as a general rule for the population, to increase NAD+ through the Preiss-Handler pathway?
Amazing!! This article is well thought out. Chris is many leagues above most of the nutrition gurus in the space at the moment, thank you for your work. W/ regards to energy metabolism, the most recent change I have made in my health has been vitamin B1 megadosing for my IBS. It has massively reduced bloating, gas, indigestion and as a side effect has improved my energy levels! I'm not sure of the effects on my blood sugar though which would be interesting. Thanks to Eliot Overton for making me aware of this as well.
What is the fee for the results from the Sergey Andryukhin’s app Gene Inspector from already done Dante WGS?
Hey- so much great information! There’s so much testing here. When people work with you, can you narrow down which tests are most relevant? Or, do you still suggest doing everything listed above?
Definitely food for thought (pun unintended)... Interesting to see a kind of grand unified theory for wellness, based on energy metabolism. However, your earlier remarks in the article suggested another important dimension, that of entropy. The article does not appear to address directly the question of entropy reduction.
This might be the point where a novice like me might ask questions about inflammation, for example, or even psychoneuroendocrinoimmunology. There may be a grand unified theory, but it appears to this layperson to lie in the interaction among several critical systems. I'd appreciate your thoughts. Thanks!
Great article. Just signed up on the 101 course, I actually got the cliff notes last year. Just wondering if you've looked into how caffeine can affect micronutrients absorption, specifically vitamin D? I drink a few cups of black and green tea throughout the day, sometimes with meals. Really appreciate your research, and can't wait to get my lessons from the 101 course!
Hi Chris,it’s me again lol.sorry if wrong place to post but I’m unsure of best place to ask this question. How is the book coming along?yes it’s that question again ,sorry to keep snapping at your heels but don’t you think it’s about time you completed as it’s ,correct me if I’m wrong about 4 years overdue?
It’s not to say I don’t appreciate all the freebies you give,they are very much appreciated but it’s just I was hoping to read what I know will be a work of art before I pop my clogs lol,which I’m hoping will be a lot later than sooner,73 now and counting 😀.
Had a bit D test the other day,came back at 155🧐🧐.I immediately stopped supplementing 4000 iu daily to zero.? Triclycerides were 0.7 and other panels in range except urea just out,I’ve increased water ,always a poor water drinker?
I do thankyou once again for your responses which are always on the money.
Kind regards
Chris from England 🙏🏻❤️