In the ACM data, note that methionine is on the left and trigonelline on the right.... I'd bet that higher methionine is linked with a better conversion of homocysteine into methionine. Or, it could reflect a reduced ACM risk for higher protein (and correspondingly, methionine) intakes. Nonetheless, my initial hypothesis that I don't want to convert homocysteine into methionine (because methionine restriction extends lifespan in animal models) may be wrong. For trigonelline, Vincenzo Sorrentino and I discussed that in an earlier video-trigonelline is a uremic toxin, which means that it's elevated in the presence of poor kidney function. In this case, that's likely what it reflects, but without dietary data, we can't know for sure.
Hi Mike, The models Yan et al presented didn't adjust for income and education level, two well known longevity factors. If the methionine issue is related to protein intake, it might also be related to ones ability to buy quality protein, implying the relationship is confounded. Here's the section from the paper: "Model 1 was adjusted for sex and age. Model 2 was additionally adjusted for BMI, fasting glucose, waist circumference, LDL cholesterol, high‐density lipoprotein cholesterol (HDL), cholesterol, TG, systolic blood pressure (SBP), diastolic blood pressure (DBP), having antihypertensive treatment (AHT) or not, having lipid‐lowering treatment (LLT) or not, smoking status, the prevalence of baseline T2D, and CAD. "
I had read these studies a few years ago and started eating mushrooms every day--- in particular, boleus (aka porcini). These have the highest concentration of ergothioneine, by far, of any mushroom (although they are very expensive and hard to get.) I did notice one major positive side effect. I'm not sure what it means, but it was noticeable. When I was a younger man, my veins were very prominent and full. You could see them quite easily in my arms and hands, for example--- like little balloons. As I aged, they seemed to "deflate" and lose tone and I couldn't see them anymore. After starting on the mushrooms, they went back to how they used to look ten years ago. Maybe that's meaningful? Anyway, I think it is very interesting that there is an ergothioneine transporter in the human body that is SPECIFIC to that chemical. It only does one thing: transport ergothioneine. That tells me that this chemical is essential to human life in some way we don't yet understand. Since our body can't produce it, those two facts are good enough for me to try to increase my intake.
@@jamesgilmore8192 I tried to reply to your question, but UA-cam removed my comment (which included two scientific paper references.). I don't know what rule I broke. I'll try again.
@@jamesgilmore8192 Google the following two papers. (Apparently I can't share the link to the papers here or UA-cam takes them down.). "Ergothioneine, recent developments" by Irwin K. Cheah and Barry Halliwell. Also, "The ergothioneine transporter (ETT): substrates and locations, an inventory" by Dirk Gründemann, Lea Hartmann, Svenja Flögel
Hey we’re on the same wavelength again. I’ve been taking 15mg of ergothioneine every day for 2 months to see what happens. I was so surprised to find it has mental benefits, those were the main thing I noticed. Mood is better, music sounds brighter and I’m more hopeful each day. I love ergothioneine, it’s a subtle but beneficial antidepressant for me.
Also I'd like to point out when I read the paper you referenced The association between plasma metabolites and future risk of all-cause mortality, page 809, a number of reduced risk metabolites were amino acids like Leucine, etc. which you can increase from protein powder.
Good observation Mike. Yet isoleucine has an increased HR. If we take the aminos at face value here (ignoring pathways etc) it seems to point towards eating fish and white meat over red meat as net positive. The ratio of leucine/isoleucine is higher in fish for example.
@@Childofthebong ha, I did a cost analysis of ergothioneine content in mushrooms and supplements and porcini and white button come out on top. The porcini serving is lower than white as they have more ergo.
@@jamesgilmore8192 Yes, I came to the exact same conclusion several years ago when I first came upon the ergothioneine papers. Although porcini are much more expensive than white (or almost any other) mushroom, you need a much smaller dose to get the same amount of ergothioneine. They are, however, an acquired taste--- they don't taste like what people think of when you say "mushroom."
Do you check if there is a u shaped curve, correlation between niacin supplementation and the aging marker? For example what impact has 200mg niacin on aging and NAD instead of 600mg.. Another really interesting point would be niacinamide supplementation or a combination of both niacin and nicotinamide. Niacinamide has not an effect on LDL Also you maybe missed methylation as an super important factor concerning high dose b3 Niacin is a big methyl thief and high dose b3 leads to significant undermethylation (if you are a normal or undermethylator) B3 should always be combined with the same amount of TMG as a methyl donor (Chris Masterjohn phd) Great videos❤
"Niacin is a big methyl thief" I didn't know that. I saw DMG on the right side and was wondering about methylation. I really wish I understood the glycine story better.
Great video! Bruce Ames was talking about this so long ago. He was always ahead of his time! Shiitake mushrooms have so much more ergothioneine than button mushrooms.
Thanks @jpintero6330! I can eat white button mushrooms in larger amounts, and are generally cheaper, which is why I pictured them in the video. it's ok to use a different mushroom variety, no worries!
They could all have different reasons for being unfavourable. -VitD could be supplementation and reverse causation. -dimethylglycine could be a downstream block in the metabolic pathway as there are many enzymes needed (the increased HR seems to replicate in other studies). - Mike mentioned trigonelline in the comments -- its a uremic toxin. - creatine, could be resistant uptake in the muscle, i dont think this cohort would be supplementing. Any thoughts everyone?
thanks Michael, very interesting. You should put together a stack of sine qua non metabolites to measure, implemented by IOLLO, and then marketing it.. I would sell it in Europe ;) I find it interesting that one can see damaged microchondria leaking out long chain FAs bound to carnitine... that's indeed very interesting about ergo: it is also produced by Lactobacillus reuteri, which is part of a (very) youthful microbiome. it is pretty easy to make yoghurt with them.
Hmm, I'm not sure if iollo would like that, but on the other hand, marketing a subset of their metabolites as the "Lustgarten special" may be good marketing, as you mentioned... Ah, it's not just produced by L. reuteri, other microbes degrade it, especially at higher gut pH, which is more likely to be present at older ages So plasma measurement is essential, imo
I live on medicinal mushrooms. Especially Chaga the King and Reishi the Queen of Mushrooms. I don’t however eat ground mushrooms. Mold. Fungus. No good. Health Guru.
Oh and btw, find that pretty intressting that creatine is assoc with higher all cause morality risk. Did you have any idea if supplementation of creatine increases blood-creatine? Or was it creatinine which is assoc with higher all cause mortality risk and it is just a typo? (Cant believe it right now that creatine is worse, it is well studied)
Any thoughts on the referenced paper showing higher levels of methionine being associated with lower ACM and trigonelline being associated with higher ACM? You've previosuly discussed trying to reduce methionine and increase trigonelline but this paper shows the opposite effect.
Yep, good catch @alexmiller6560. I'd bet higher methionine is linked with a better conversion of homocysteine into methionine. Or, it could reflect a reduced ACM risk for higher protein (and correspondingly, methionine) intakes. Nonetheless, my initial hypothesis that I don't want to convert homocysteine into methionine (because methionine restriction extends lifespan in animal models) may be wrong. For trigonelline, Vincenzo Sorrentino and I discussed that in an earlier video-trigonelline is a uremic toxin, which means that it's elevated in the presence of poor kidney function. In this case, that's likely what it reflects, but without dietary data, we can't know for sure.
Great data ! One thing caught my eye though : Trigonelline (coffee, chickpeas ) is pretty far on the right side.. even though it s supposed to be associated with extended lifespan ? what s your take on this ?
That's right, good catch, @jbosson82! James Gilmore also caught that in the comments. Vincenzo Sorrentino and I discussed that in an earlier video-trigonelline is a uremic toxin, which means that it's elevated in the presence of poor kidney function. In this case, that's likely what it reflects, but without dietary data, we can't know for sure.
@@conqueragingordietrying123 Super intetesting ! Does that mean that trigonelline is a defense mechanism from a distressed kidney, and that its benefits might be related to a support to the kidney function ?
Mushrooms are rich in nicotinamide, so I reduced their intake for a test without a major dent on homocysteine (nicotinamide can raise homocysteine), so Ive increased them to their usual levels (~250g/d average) since...
That's right, good catch, James! Vincenzo Sorrentino and I discussed that in an earlier video-trigonelline is a uremic toxin, which means that it's elevated in the presence of poor kidney function. In this case, that's likely what it reflects, but without dietary data, we can't know for sure.
Definitely on beta-carotene, but note that the acylcarnitines are not homogeneous in terms of all-cause mortality risk: some are inversely, others positively associated...
@@soulnight1606 Only by a small amount, to keep beta-carotene at 50 mg/d, not less. I've been doing that because I've been increasing collards, which also have beta-carotene, to increase Vitamin K, which is a net positive in terms of correlations with 26 biomarkers.
only the versions with an attached short chain fatty acid. The long chain fatty acids are negative for ACM. IMHO this reflects the health of the mitochondria, at least an important aspect of it: the transport of long chain fatty acids. They get bound to carnitine, in order to get transported across the inner membrane of the mitochondria, but fail to do so. hence they accumulate, and even leak out of the cell, or the cell dies altogether
I saw that, too-good question. These are associations-stronger data is in RCTs, where creatine has a lot of positive data behind it Beyond that, I'd carefully track biomarkers to see if creatine is a net positive (or not) for you...
@@conqueragingordietrying123 With the study being done on plasma, you are only capturing the transport medium of creatine. That leaves increased intake (nutrition/supplement), increased production (liver, kidney, pancreas), reduced uptake (muscles/brain), and maybe increased cellular breakdown as possibilities. As Mike mentioned these are only associations and getting at the mechanistic cause is more challenging.
Creatine increased my blood creatinine levels dramatically, as well as my cystatin C. Maybe it is not bad for the kidneys, but I won't take my chances.
In the ACM data, note that methionine is on the left and trigonelline on the right....
I'd bet that higher methionine is linked with a better conversion of homocysteine into methionine. Or, it could reflect a reduced ACM risk for higher protein (and correspondingly, methionine) intakes. Nonetheless, my initial hypothesis that I don't want to convert homocysteine into methionine (because methionine restriction extends lifespan in animal models) may be wrong.
For trigonelline, Vincenzo Sorrentino and I discussed that in an earlier video-trigonelline is a uremic toxin, which means that it's elevated in the presence of poor kidney function. In this case, that's likely what it reflects, but without dietary data, we can't know for sure.
Hi Mike, The models Yan et al presented didn't adjust for income and education level, two well known longevity factors. If the methionine issue is related to protein intake, it might also be related to ones ability to buy quality protein, implying the relationship is confounded.
Here's the section from the paper: "Model 1 was adjusted for sex and age. Model 2 was additionally adjusted for BMI, fasting glucose, waist circumference, LDL cholesterol, high‐density lipoprotein cholesterol (HDL), cholesterol, TG, systolic blood pressure (SBP), diastolic blood pressure (DBP), having antihypertensive treatment (AHT) or not, having lipid‐lowering treatment (LLT) or not, smoking status, the prevalence of baseline T2D, and CAD. "
Actually I had pretty much that exact question. I was also wondering about hits on DMG and glycine derivatives.
there is another version of methionine on the right
The excitement in the mice community is palpable. Yet another step closer to immortality.
I had read these studies a few years ago and started eating mushrooms every day--- in particular, boleus (aka porcini). These have the highest concentration of ergothioneine, by far, of any mushroom (although they are very expensive and hard to get.) I did notice one major positive side effect. I'm not sure what it means, but it was noticeable. When I was a younger man, my veins were very prominent and full. You could see them quite easily in my arms and hands, for example--- like little balloons. As I aged, they seemed to "deflate" and lose tone and I couldn't see them anymore. After starting on the mushrooms, they went back to how they used to look ten years ago. Maybe that's meaningful? Anyway, I think it is very interesting that there is an ergothioneine transporter in the human body that is SPECIFIC to that chemical. It only does one thing: transport ergothioneine. That tells me that this chemical is essential to human life in some way we don't yet understand. Since our body can't produce it, those two facts are good enough for me to try to increase my intake.
Interesting comment thankyou. Did you have a reference for the recpetor?
@@jamesgilmore8192 Redox Biol. 2021 Jun; 42: 101868.
Jan 26. doi: 10.1016/j.redox.2021.101868
PMCID: PMC8113028
PMID: 33558182
Ergothioneine, recent developments
Irwin K. Cheaha, and Barry Halliwell
@@jamesgilmore8192 I tried to reply to your question, but UA-cam removed my comment (which included two scientific paper references.). I don't know what rule I broke. I'll try again.
@@jamesgilmore8192 Google the following two papers. (Apparently I can't share the link to the papers here or UA-cam takes them down.). "Ergothioneine, recent developments" by Irwin K. Cheah and Barry Halliwell. Also, "The ergothioneine transporter (ETT): substrates and locations, an inventory"
by Dirk Gründemann, Lea Hartmann, Svenja Flögel
@@CyrilAndPriscillayt doesn't like links, all you need to do is post the title and we can search it.
Thank you Michael! Spectacular presentation, as usual!
Thanks @CyrilAndPriscilla!
Hey we’re on the same wavelength again. I’ve been taking 15mg of ergothioneine every day for 2 months to see what happens. I was so surprised to find it has mental benefits, those were the main thing I noticed. Mood is better, music sounds brighter and I’m more hopeful each day. I love ergothioneine, it’s a subtle but beneficial antidepressant for me.
yep, therefor French people have overall a good mood, thanks to their camembert and mushroom consumption :)
Also I'd like to point out when I read the paper you referenced The association between plasma metabolites and future risk of all-cause mortality, page 809, a number of reduced risk metabolites were amino acids like Leucine, etc. which you can increase from protein powder.
Good observation Mike. Yet isoleucine has an increased HR. If we take the aminos at face value here (ignoring pathways etc) it seems to point towards eating fish and white meat over red meat as net positive. The ratio of leucine/isoleucine is higher in fish for example.
💪💪💪👍Thank you Mike!
It will certainly be interesting to see if iollo measured ergothioneine levels respond to mushroom intake later this year.
Definitely!
Test it with porcini
@@Childofthebong ha, I did a cost analysis of ergothioneine content in mushrooms and supplements and porcini and white button come out on top. The porcini serving is lower than white as they have more ergo.
@@jamesgilmore8192 Yes, I came to the exact same conclusion several years ago when I first came upon the ergothioneine papers. Although porcini are much more expensive than white (or almost any other) mushroom, you need a much smaller dose to get the same amount of ergothioneine. They are, however, an acquired taste--- they don't taste like what people think of when you say "mushroom."
Do you check if there is a u shaped curve, correlation between niacin supplementation and the aging marker? For example what impact has 200mg niacin on aging and NAD instead of 600mg..
Another really interesting point would be niacinamide supplementation or a combination of both niacin and nicotinamide. Niacinamide has not an effect on LDL
Also you maybe missed methylation as an super important factor concerning high dose b3
Niacin is a big methyl thief and high dose b3 leads to significant undermethylation (if you are a normal or undermethylator)
B3 should always be combined with the same amount of TMG as a methyl donor (Chris Masterjohn phd)
Great videos❤
"Niacin is a big methyl thief" I didn't know that. I saw DMG on the right side and was wondering about methylation. I really wish I understood the glycine story better.
interesting content as usual Sit, tks
Another gem!
Great video! Bruce Ames was talking about this so long ago. He was always ahead of his time! Shiitake mushrooms have so much more ergothioneine than button mushrooms.
Thanks @jpintero6330! I can eat white button mushrooms in larger amounts, and are generally cheaper, which is why I pictured them in the video. it's ok to use a different mushroom variety, no worries!
And oyster mushrooms have more ergothioneine than shiitake mushrooms have, according to Dr. Michael Greger.
Porcinis are even higher!
@@ChillFantasticFive That's good, but they're too hard to find. I can always get oyster and shiitake mushrooms.
@@jamesherried9269 i get a freeze dried mix from costco and powderize myself or rehydrate. Mix has porcinis and 2 others. Combo is probably good too
How can we interpret the fact that creatine, trigonelline, dimethylglycine and vitamin D3 appear on the *right*-hand side of the chart? 🤔😐
They could all have different reasons for being unfavourable.
-VitD could be supplementation and reverse causation.
-dimethylglycine could be a downstream block in the metabolic pathway as there are many enzymes needed (the increased HR seems to replicate in other studies).
- Mike mentioned trigonelline in the comments -- its a uremic toxin.
- creatine, could be resistant uptake in the muscle, i dont think this cohort would be supplementing.
Any thoughts everyone?
Hmm yeah, I wonder what dosages they were doing there, it was probably in excessive amounts. If not then I question alot :O
Honestly based video and nice thumbnail
thanks Michael, very interesting.
You should put together a stack of sine qua non metabolites to measure, implemented by IOLLO, and then marketing it.. I would sell it in Europe ;)
I find it interesting that one can see damaged microchondria leaking out long chain FAs bound to carnitine... that's indeed very interesting
about ergo: it is also produced by Lactobacillus reuteri, which is part of a (very) youthful microbiome. it is pretty easy to make yoghurt with them.
Hmm, I'm not sure if iollo would like that, but on the other hand, marketing a subset of their metabolites as the "Lustgarten special" may be good marketing, as you mentioned...
Ah, it's not just produced by L. reuteri, other microbes degrade it, especially at higher gut pH, which is more likely to be present at older ages
So plasma measurement is essential, imo
I used an ergothionine supplement for a month and noticed no effects whatsoever.
nice piperine on the list, now i can excuse it for being in a bunch of my extracts 😂
Piperine is an interesting one-I'm thinking about giving it its own video
Piperine is very influential in nutrient absorption. I wonder if that is the reason it is on the list or if there is a secondary reason.
Excellent.
Keep in mind those animals are always growing, they never go "adult"
I live on medicinal mushrooms. Especially Chaga the King and Reishi the Queen of Mushrooms. I don’t however eat ground mushrooms. Mold. Fungus. No good. Health Guru.
Oh and btw, find that pretty intressting that creatine is assoc with higher all cause morality risk.
Did you have any idea if supplementation of creatine increases blood-creatine? Or was it creatinine which is assoc with higher all cause mortality risk and it is just a typo? (Cant believe it right now that creatine is worse, it is well studied)
From your graph Beta-Carotene was almost equal to erothioneine and far easier to find food for.
Not a fan of mushrooms? Beta-carotene is a big one, too
Any thoughts on the referenced paper showing higher levels of methionine being associated with lower ACM and trigonelline being associated with higher ACM? You've previosuly discussed trying to reduce methionine and increase trigonelline but this paper shows the opposite effect.
Yep, good catch @alexmiller6560. I'd bet higher methionine is linked with a better conversion of homocysteine into methionine. Or, it could reflect a reduced ACM risk for higher protein (and correspondingly, methionine) intakes. Nonetheless, my initial hypothesis that I don't want to convert homocysteine into methionine (because methionine restriction extends lifespan in animal models) may be wrong.
For trigonelline, Vincenzo Sorrentino and I discussed that in an earlier video-trigonelline is a uremic toxin, which means that it's elevated in the presence of poor kidney function. In this case, that's likely what it reflects, but without dietary data, we can't know for sure.
Great data ! One thing caught my eye though : Trigonelline (coffee, chickpeas ) is pretty far on the right side.. even though it s supposed to be associated with extended lifespan ? what s your take on this ?
That's right, good catch, @jbosson82! James Gilmore also caught that in the comments.
Vincenzo Sorrentino and I discussed that in an earlier video-trigonelline is a uremic toxin, which means that it's elevated in the presence of poor kidney function. In this case, that's likely what it reflects, but without dietary data, we can't know for sure.
@@conqueragingordietrying123 Super intetesting ! Does that mean that trigonelline is a defense mechanism from a distressed kidney, and that its benefits might be related to a support to the kidney function ?
Didn't you tell us in an earlier video that mishrooms worsend some of your blood markers? If, what kind of mushrooms did you ate before?
Mushrooms are rich in nicotinamide, so I reduced their intake for a test without a major dent on homocysteine (nicotinamide can raise homocysteine), so Ive increased them to their usual levels (~250g/d average) since...
Trigonelline is on the right and methionine on the left...
Yep, good catch @Battery-kf4vu (a few others saw it, too!). Please see the pinned comment...
Trigonelline has an increased ACM at least in this study.
That's right, good catch, James!
Vincenzo Sorrentino and I discussed that in an earlier video-trigonelline is a uremic toxin, which means that it's elevated in the presence of poor kidney function. In this case, that's likely what it reflects, but without dietary data, we can't know for sure.
@@conqueragingordietrying123 That seems plausible for this cohort.
@@conqueragingordietrying123 seems likely here. But yes nutritional and the adjustments undertaken by the authors could be another factor
d3 and creatine seems to be on wrong side . myths busted ?
These are associations, but they're definitely the opposite of expected...
Seems like beta carotene and carnitine, carnosine are also some good markers of longevity. And probably via natural means?
Definitely on beta-carotene, but note that the acylcarnitines are not homogeneous in terms of all-cause mortality risk: some are inversely, others positively associated...
@conqueragingordietrying1797 where you not trying to reduce your carrot intake?
@@soulnight1606 Only by a small amount, to keep beta-carotene at 50 mg/d, not less. I've been doing that because I've been increasing collards, which also have beta-carotene, to increase Vitamin K, which is a net positive in terms of correlations with 26 biomarkers.
only the versions with an attached short chain fatty acid. The long chain fatty acids are negative for ACM. IMHO this reflects the health of the mitochondria, at least an important aspect of it: the transport of long chain fatty acids.
They get bound to carnitine, in order to get transported across the inner membrane of the mitochondria, but fail to do so. hence they accumulate, and even leak out of the cell, or the cell dies altogether
@@monnoo8221 what versions of beta carotene have short chain fatty acids attached and which have long chain fatty acids?
I take creatine daily, because I rarely eat meat. I noticed that creatine is associated with an increased ACM risk. Do I need to stop using creatine?
I saw that, too-good question. These are associations-stronger data is in RCTs, where creatine has a lot of positive data behind it
Beyond that, I'd carefully track biomarkers to see if creatine is a net positive (or not) for you...
@@conqueragingordietrying123 With the study being done on plasma, you are only capturing the transport medium of creatine. That leaves increased intake (nutrition/supplement), increased production (liver, kidney, pancreas), reduced uptake (muscles/brain), and maybe increased cellular breakdown as possibilities. As Mike mentioned these are only associations and getting at the mechanistic cause is more challenging.
Thank you! I can't wait for your new book to come out. Do you have any idea when it will be completed? @@conqueragingordietrying123
Creatine increased my blood creatinine levels dramatically, as well as my cystatin C. Maybe it is not bad for the kidneys, but I won't take my chances.
It might be the foods it is in. Animal protein is associated with lower lifespan in some studies.
poggers