A question for the reader, and input is welcome. The Long Covid post will be long, I will do my best to make it accessible and link everything else you may need to read for further context, but, the Endotoxin Tolerance one is ginormous, colossal. I personally hate "substack baiting" which is what I define as posting small, non-significant posts.
So choose. Either a massive, gigantic post in one single part, which will make it for a lengthy, difficult read. Or dividing into a few parts (2, 3 I don't know).
At least 2 parts. You and others decide the total number.
The material is 'meaty' and note taking/learning is more apt to take place from this reader in multiple parts. Also, allows you to edit previous posts incrementally.
Getting through one of them is a personal achievement!
I never retroactively edit posts, otherwise they would become messes, plus I prefer leaving a trail behind of unedited posts so most can tangibly track work/line of thought and changes in style.
But I would also like to give a hat tip to your new intro summary/Key conclusions in bullet points. That I think helps so much the reader to assess the significance upfront.
Many thanks for this summary of the Tryptophan story
I will keep that in mind and add the intro and key conclusions at first seems like a better way to introduce the information given the size of some of these. Thank you 👍🏻
This is actually the second version of the article 😆 the first one was too big, it has over 60 papers. Better this way.
I take tryptophan at night, before going to bed, with melatonin and magnesium. I am fucked up, I take 1 gram sometimes 1.3 to me THIS IS HIGH, but to "doctors" it isn't. I would say start small, but again most people won't need it. I take it daily.
I have massive gripes with all "bio absorption" papers, and I am starting to have massive gripes with how they classify T cells, T cell exhaustion too 😆.
Your body has a maximum cap on how many grams of amino acid it can metabolize per hour, either take creatine before or after, doesn't matter much, but taking 10 grams of Creatine within a short period, you are most likely pissing away 3-5 grams hehe.
Agree it is better this way. I like that you are thorough. It was soooo important in the begining when I did not "know" you. These days, I know everything you say is backed by plethora of evidence.
For sharing how you take Tryptophan, thank you. I am trying to optimise (everything) Im taking and it is really challenging. Why? Because, I actually do not know whether Im taking to much. With food it is different. If I eat to much or of I eat something that does not agree with me my body instantly tells me. With Vit C is pretty straight forward. But everything else...a bit of a puzzle.
I thought this might intrest you:
"OpenAI Loses Third Board Member With Exit of Presidential Candidate Will Hurd
Hurd announced a 2024 presidential campaign bid at end of JuneReid Hoffman and Neuralink’s Zilis also stepped down this year
Tryptophan and it's effects on the body are incredibly complex, it took me a long time to make sense of all of this, this is one of the reasons I tell people to take notes on paper, it helps a lot.
Reading the other kynurenine substacks can be helpful but yeah, it is complicated 😆
Would love to read more extensively about creatine and also about whey as I am not convinced about them anymore regarding training. Maybe some other effects could justify them again.
I hope you do not mind me asking you to share your views (if you wish) on (potentially) unrelated matter to
"The importance of (proper) Tryptophan…" I know your intrest in AI so...Nvidia (NVDA),announced a huge new partnership with biotech AI startup Recursion Pharmaceuticals (RXRX), which has developed a novel AI-driven platform for drug development and discovery.
Recursion will train its AI models on Nvidia’s cloud platform, which Nvidia will then license through its newly announced BioNeMo generative AI cloud service for drug discovery."
I am hoping this is not about mRNA. What are your thoughts?
I think the next post might help my readers make a little more sense of these changes.
NVidia is now hedging its bets and investing, hard, on many AI-based companies (since this is the future). Recursion is a drug-discovery company, I don't think there is any mRNA involved, can't see to find any information, to it is either actual new chemical compounds or the low hanging fruit of "drug discovery" monoclonal antibodies.
As I wrote multiple times, AI-based anything is unstoppable now.
Apperently, there is company that has a technology to inject some sort of gas into dead "things" (including deceased humans) and make robots. (I am not kidding)
You are evidently right about this, according to the current state of research. People -- particularly women and children, who take in a large amount of fructose in fruit, fruit juices, or corn syrup -- don't absorb it too well at all. The fact that women show depression more often than men is likely caused by this absorption problem. But not ingesting the stuff is no cure. Dropping a fruit juice habit, however, reportedly does help. See https://larryturner.substack.com/p/regarding-the-hfcs-structural-change for more discussion.
Wait, I started taking daily whey protein about a month ago. Mayo Clinic had good things to say about creatine except for this:
Possible interactions include:
Caffeine. Combining caffeine with creatine might decrease the efficacy of creatine. Use of creatine with a daily amount of caffeine greater than 300 milligrams might also worsen the progression of Parkinson's disease. Further research is needed.
I drink 4 cups of coffee a day. I'm not giving that up. From my cold, dead hands, etc. So should I not take creatine? My mom died from Parkinson's so I'm concerned from a hereditary standpoint.
I think that is mostly aimed at the bros, people who lift heavily, or intense exercises and make use of pre-workouts (loaded with caffeine) and take creatine shortly after.
As long as you space the two enough (3-4 hours) it will be mostly fine, I also consume a lot of caffeine have been for years, so creatine.
Hmmm, brain / cognitive function for me has been an issue over the past few months, mentioned it in the comments in prior posts so won't go reposting.
I've slowly been working in the supplements I've been off for a few months to try and pin point / work out if there was a benefit that I no longer have / explain my decline where the majority of the other variables have remained the same (exercise sleep nutrition etc).
Vitamin D supplementation (winter here in aus) prolonged fasting (3 days per month) / strict Ketogenic diet were the last few things on my list to reintroduce, however the whey protein is something I'd forgotten about / not considered since dropping it a few months ago as I'm pretty much on my protein intake goal per day through whole foods, so saw no need.
While I am a small Substack, I get a lot of comments sometimes, and emails too so you can feel free to repost it if you want.
Creatine directly affects brain function, so does magnesium (most people have poor intake it magnesium regardless of diet), NAC+glycine, but one that literally is a "brain food" in a way is Thiamine. You may want to add 50-150 (even 300 is safe) mg of thiamine or Benfothiamine (even better for cognitive function), both of these directly affect memory, cognition etc.
Another one is Choline. I have been trying it for the first time and even though my supplements are "cognitive focused" this one is making a MASSIVR difference for me. Just food or supplements for your thought 😆.
Will have to give the Thiamine a go, or maybe start back on Vegemite 😃
Guess I just want to rule out things I was taking before, to try and work out of it was a supplement, or perhaps something else going on with my brain (fog & cognitive) -
Easy example that happened just the other day, walked out of our kitchen, into the laundry, it was night so I'm thinking I'll need to turn on the light in the laundry, as I walked 1.5M to the laundry, I turned the light off (it was already on) 🤯 it's like the ability to react quickly is gone, or takes longer process. Adding up weight plates at the gym on the barbell is another little thing that was very, very easy before, but now I need to think about it.
37 y.o, no recent infections or anything that I can pin point, a noticeable change after coming off strict KETO for a month.
So what is the proper daily dose of Tryptophan for a vaccination wounded soldier? All at once dose, spread out during the day, between meals, after meals, with a little carbo, with no protein, or at night?
I take it at night with melatonin and magnesium, and I often say start with the minimal dosage available in your country, go up as you feel comfortable.
Some people don't need it, other do.
Creatine and whey would be a better supplement for most
What do mean with "comfortable" here? People start taking tryptophane, melatonin, magnesium because they have problem. Do you mean that dosage should be increased until the problem is cured? If so, what indicates that dosage is too high?
Because I am not insane to recommend people starting take a high dosage of anything, even if this would help solve their problem, acclimating the body towards higher dosage of anything is a bettet approach to me.
The dosage should be increased until the person finds the point where that is the dosage they need to by symptom free, than after sometime, slowly cut back and see if they still are symptom free, most of the time they stay on these because of the benefits.
Side effects such as headaches, drowsiness, nausea all indicate you may had a little too much at once for Melatonin and Tryptophan. Magnesium it is hard for someone to take too much since I don't recommend massive high dosages, just above average.
I need to revisit something I was reading about tryptophan yesterday but my thought about your post hovers around SSRI use. Surely that affects the tryp-kyn pathway. 🤔🤔
The serotonin hypothesis has been debunked quite a few times recently if that is what you mean. Some of the tryptophan effects are serotonin independent too.
I like to read it as a whole, otherwise i have to go back constantly to remind me again on terminology etc. It isnlike reading rhe hobbit bit by bit and then you have to refamiliarize yourself with all the names over time
Thank you for your kind words, and for telling me this, now I can reference people to your comment and it may be of help to others. My aim here is always to inform and help people, that is why I abhor paywalling.
I will need to further dig into the bone marrow angle though, but once again glad I was of help and you are now better. I hope you keep improving pray 🙏🏻 this made my week. 😁
A question for the reader, and input is welcome. The Long Covid post will be long, I will do my best to make it accessible and link everything else you may need to read for further context, but, the Endotoxin Tolerance one is ginormous, colossal. I personally hate "substack baiting" which is what I define as posting small, non-significant posts.
So choose. Either a massive, gigantic post in one single part, which will make it for a lengthy, difficult read. Or dividing into a few parts (2, 3 I don't know).
Hmmmmm….
Idk. My vote is to divide it into parts.
At least 2 parts. You and others decide the total number.
The material is 'meaty' and note taking/learning is more apt to take place from this reader in multiple parts. Also, allows you to edit previous posts incrementally.
Getting through one of them is a personal achievement!
I never retroactively edit posts, otherwise they would become messes, plus I prefer leaving a trail behind of unedited posts so most can tangibly track work/line of thought and changes in style.
Note, two parts minimum.
100% Agree!
Parts. I would agree.
But I would also like to give a hat tip to your new intro summary/Key conclusions in bullet points. That I think helps so much the reader to assess the significance upfront.
Many thanks for this summary of the Tryptophan story
I will keep that in mind and add the intro and key conclusions at first seems like a better way to introduce the information given the size of some of these. Thank you 👍🏻
parts
Noted 🫡
Divide it into parts 🙏❤
"What led me to this was a sudden lightbulb moment, as it often occurs in my weirdly wired brain, the thought is as follows." ❤....
Thank you for this soooo well researched article on Tryptophan.
And thank you for being so insightful & caring.
Do you take Trypthophan with carbs?
How often & how much you take? I was told to take Trypthophan with carbs to optimise absorbtion (otherwise to take 5HTP) at night.
In regards to Creatine, I was told to take 5gr(rounded teaspoon) before and after exercise and before sleep.
What are your thoughts?
This is actually the second version of the article 😆 the first one was too big, it has over 60 papers. Better this way.
I take tryptophan at night, before going to bed, with melatonin and magnesium. I am fucked up, I take 1 gram sometimes 1.3 to me THIS IS HIGH, but to "doctors" it isn't. I would say start small, but again most people won't need it. I take it daily.
I have massive gripes with all "bio absorption" papers, and I am starting to have massive gripes with how they classify T cells, T cell exhaustion too 😆.
Your body has a maximum cap on how many grams of amino acid it can metabolize per hour, either take creatine before or after, doesn't matter much, but taking 10 grams of Creatine within a short period, you are most likely pissing away 3-5 grams hehe.
"I have massive gripes with all "bio absorption" papers"
lol . . . I would LOVE to read about this one, even if it's just a brief aside!
Agree it is better this way. I like that you are thorough. It was soooo important in the begining when I did not "know" you. These days, I know everything you say is backed by plethora of evidence.
For sharing how you take Tryptophan, thank you. I am trying to optimise (everything) Im taking and it is really challenging. Why? Because, I actually do not know whether Im taking to much. With food it is different. If I eat to much or of I eat something that does not agree with me my body instantly tells me. With Vit C is pretty straight forward. But everything else...a bit of a puzzle.
I thought this might intrest you:
"OpenAI Loses Third Board Member With Exit of Presidential Candidate Will Hurd
Hurd announced a 2024 presidential campaign bid at end of JuneReid Hoffman and Neuralink’s Zilis also stepped down this year
Bloomberg
https://www.bloomberg.com/news/articles/2023-07-13/republican-presidential-hopeful-will-hurd-leaves-board-of-openai#xj4y7vzkg
The funniest thing I’ve read today: Here is where things get a little bit complicated.
I can assure you, my smallish brain already thought it was quite complicated enough. 🤪😆😆
Tryptophan and it's effects on the body are incredibly complex, it took me a long time to make sense of all of this, this is one of the reasons I tell people to take notes on paper, it helps a lot.
Reading the other kynurenine substacks can be helpful but yeah, it is complicated 😆
Would love to read more extensively about creatine and also about whey as I am not convinced about them anymore regarding training. Maybe some other effects could justify them again.
I might do it, just gonna take some time 🙏🏻
Dear John,
I hope you do not mind me asking you to share your views (if you wish) on (potentially) unrelated matter to
"The importance of (proper) Tryptophan…" I know your intrest in AI so...Nvidia (NVDA),announced a huge new partnership with biotech AI startup Recursion Pharmaceuticals (RXRX), which has developed a novel AI-driven platform for drug development and discovery.
Recursion will train its AI models on Nvidia’s cloud platform, which Nvidia will then license through its newly announced BioNeMo generative AI cloud service for drug discovery."
I am hoping this is not about mRNA. What are your thoughts?
I think the next post might help my readers make a little more sense of these changes.
NVidia is now hedging its bets and investing, hard, on many AI-based companies (since this is the future). Recursion is a drug-discovery company, I don't think there is any mRNA involved, can't see to find any information, to it is either actual new chemical compounds or the low hanging fruit of "drug discovery" monoclonal antibodies.
As I wrote multiple times, AI-based anything is unstoppable now.
Apperently, there is company that has a technology to inject some sort of gas into dead "things" (including deceased humans) and make robots. (I am not kidding)
Nobody knows. The ones developing foundational models will be the best bets at least for now, but nobody knows who.
Probably an outlier
Now go back to your previous post, https://hiddencomplexity.substack.com/p/the-attempt-to-control-our-food-system, and consider the direct follow-on effects of restricting dietary tryptophan in the general population during "The Covid" by driving up egg prices. Egg whites appear to be the major source of tryptophan in the typical western diet (https://en.wikipedia.org/wiki/Tryptophan)...
Just because something is a source of Tryptophan does not mean our digestive system can absorb it.
I often say there should be a distinction between normal/natural levels of nutrients and therapeutic levels.
You are evidently right about this, according to the current state of research. People -- particularly women and children, who take in a large amount of fructose in fruit, fruit juices, or corn syrup -- don't absorb it too well at all. The fact that women show depression more often than men is likely caused by this absorption problem. But not ingesting the stuff is no cure. Dropping a fruit juice habit, however, reportedly does help. See https://larryturner.substack.com/p/regarding-the-hfcs-structural-change for more discussion.
Wait, I started taking daily whey protein about a month ago. Mayo Clinic had good things to say about creatine except for this:
Possible interactions include:
Caffeine. Combining caffeine with creatine might decrease the efficacy of creatine. Use of creatine with a daily amount of caffeine greater than 300 milligrams might also worsen the progression of Parkinson's disease. Further research is needed.
I drink 4 cups of coffee a day. I'm not giving that up. From my cold, dead hands, etc. So should I not take creatine? My mom died from Parkinson's so I'm concerned from a hereditary standpoint.
I think that is mostly aimed at the bros, people who lift heavily, or intense exercises and make use of pre-workouts (loaded with caffeine) and take creatine shortly after.
As long as you space the two enough (3-4 hours) it will be mostly fine, I also consume a lot of caffeine have been for years, so creatine.
Hmmm, brain / cognitive function for me has been an issue over the past few months, mentioned it in the comments in prior posts so won't go reposting.
I've slowly been working in the supplements I've been off for a few months to try and pin point / work out if there was a benefit that I no longer have / explain my decline where the majority of the other variables have remained the same (exercise sleep nutrition etc).
Vitamin D supplementation (winter here in aus) prolonged fasting (3 days per month) / strict Ketogenic diet were the last few things on my list to reintroduce, however the whey protein is something I'd forgotten about / not considered since dropping it a few months ago as I'm pretty much on my protein intake goal per day through whole foods, so saw no need.
Will report back if any meaning results 👍
While I am a small Substack, I get a lot of comments sometimes, and emails too so you can feel free to repost it if you want.
Creatine directly affects brain function, so does magnesium (most people have poor intake it magnesium regardless of diet), NAC+glycine, but one that literally is a "brain food" in a way is Thiamine. You may want to add 50-150 (even 300 is safe) mg of thiamine or Benfothiamine (even better for cognitive function), both of these directly affect memory, cognition etc.
Another one is Choline. I have been trying it for the first time and even though my supplements are "cognitive focused" this one is making a MASSIVR difference for me. Just food or supplements for your thought 😆.
Will have to give the Thiamine a go, or maybe start back on Vegemite 😃
Guess I just want to rule out things I was taking before, to try and work out of it was a supplement, or perhaps something else going on with my brain (fog & cognitive) -
Easy example that happened just the other day, walked out of our kitchen, into the laundry, it was night so I'm thinking I'll need to turn on the light in the laundry, as I walked 1.5M to the laundry, I turned the light off (it was already on) 🤯 it's like the ability to react quickly is gone, or takes longer process. Adding up weight plates at the gym on the barbell is another little thing that was very, very easy before, but now I need to think about it.
37 y.o, no recent infections or anything that I can pin point, a noticeable change after coming off strict KETO for a month.
We'll see.
So what is the proper daily dose of Tryptophan for a vaccination wounded soldier? All at once dose, spread out during the day, between meals, after meals, with a little carbo, with no protein, or at night?
I take it at night with melatonin and magnesium, and I often say start with the minimal dosage available in your country, go up as you feel comfortable.
Some people don't need it, other do.
Creatine and whey would be a better supplement for most
What do mean with "comfortable" here? People start taking tryptophane, melatonin, magnesium because they have problem. Do you mean that dosage should be increased until the problem is cured? If so, what indicates that dosage is too high?
Because I am not insane to recommend people starting take a high dosage of anything, even if this would help solve their problem, acclimating the body towards higher dosage of anything is a bettet approach to me.
The dosage should be increased until the person finds the point where that is the dosage they need to by symptom free, than after sometime, slowly cut back and see if they still are symptom free, most of the time they stay on these because of the benefits.
Side effects such as headaches, drowsiness, nausea all indicate you may had a little too much at once for Melatonin and Tryptophan. Magnesium it is hard for someone to take too much since I don't recommend massive high dosages, just above average.
I need to revisit something I was reading about tryptophan yesterday but my thought about your post hovers around SSRI use. Surely that affects the tryp-kyn pathway. 🤔🤔
The serotonin hypothesis has been debunked quite a few times recently if that is what you mean. Some of the tryptophan effects are serotonin independent too.
I like to read it as a whole, otherwise i have to go back constantly to remind me again on terminology etc. It isnlike reading rhe hobbit bit by bit and then you have to refamiliarize yourself with all the names over time
I'd prefer the single, massive post.
Thank you for your kind words, and for telling me this, now I can reference people to your comment and it may be of help to others. My aim here is always to inform and help people, that is why I abhor paywalling.
I will need to further dig into the bone marrow angle though, but once again glad I was of help and you are now better. I hope you keep improving pray 🙏🏻 this made my week. 😁