Bile Acids: The Next Frontier In Longevity?

[@kamanashisroy]

We are talking a lot of Bile acid, but there is no mention of egg (that contains choline and cholesterol ). How does egg fits into here ? Plus we could discuss how fiber may augment this bile acid secration .

[@peterz53]

Thanks Michael!! Very interesting. Lots of questions. But one thing that stands out for me is making sure that my liver is high functioning as well as gut.

[@darkhorseman8263]

I've read studies, in the past, that seem to indicate this. Bile Acids and Digestive Enzymes that aid in nutrient extraction improve ageing dynamics. Things like TUDCA. Was thinking of adding something to a probiotic that boosts them, and boosts the processing of phytates and lectins. Processing Phytates would help unlock more nutrients, but might also boost toxic heavy metal exposure, so I could never decide if it was wise to do.

[@conqueragingordietrying123]

Note that TUDCA wasn't on the list for BAs that were higher in centenarians... I'm not sure (yet) about the optimal approach for altering their blood levels. It's a bit complicated for now-for example, high levels of BA in poop is associated with poor outcomes (cancer).

[@bobmciver6437]

The life extension research on glycine seems to fit nicely in with your presentation.

[@olyav5819]

Thanks! Something new to look for. :)

[@conqueragingordietrying123]

Thanks Olya!

[@richardprice9730]

Just brilliant on Bile acids great intuive take I would agree .

[@rudyhenderson5002]

Great subject, presentation and analysis. Thanks!!

[@sabincioflec8413]

I'd argue that bile has an antimicrobial role and it helps make the gut healthy by keeping the microbiome in check. Also omega 3 helps a lot for longevity and overall antiinflamatory effects

[@conqueragingordietrying123]

100% true, there is data that supports an antimicrobial role for BAs. That info will probably be in a future video!

[@BR-hi6yt]

There are zero bacteria that produce methane in our gut, bacteria cannot make methane! They are archaea, not bacteria, and archaea have a very tough outer membrane. They arose out of hot deep sea vents. Surprising how many do not know about the archaea in our guts (and ruminants)

[@monnoo8221]

there is whole lot more about it: "The Role of Bile Acids in the Human Body and in the Development of Diseases. Molecules. 2022 Jun; 27(11): 3401." ...a truly amazing story

[@serbianboss3294]

Digestive bitters are the answer. I use them all the time. They will increase bile production, but also stomach acid and digestive enzymes. For glycine gelatin is the best.

[@rajbista1478]

Excellent info.

[@thomastoadally]

Thanks Michael! Excellent video, I am excited with your report on bile acids. As usual you are spot on to gain longevity. I will be waiting for your later report, when the test results are available. Thanks again! Take care of yourself please!

[@drrutledgemd]

Associations between Dietary Patterns and Bile Acids-Results from a Cross-Sectional Study in Vegans and Omnivores 2019 Serum B.A.s >> in vegetarians (FYI) In serum, primary and glycine-conjugated bile acids were higher in vegans than in omnivores (p ≤ 0.01). Conversely, Fecal bile acids (bad) higher in consumption of meat dairy & eggs

[@conqueragingordietrying123]

Yes, good stuff, thanks for that!

[@stafjustice9899]

Thanks you very much for this wonderful piece! It's becoming clearer that methionine restrictions induced both bile acid as well as as choline elevation.. So eating mainly whole plant based protein seems to be the key... For me that will mean more nuts and seeds, and few times fish or fowl...especially the Guinea hen... ( more protein, less fat and less methionine?)

[@conqueragingordietrying123]

I'm not sure that eating more plant-based protein is the top intervention-the MR data would argue against that. Maybe you mean more plant-based protein when compared with animal protein? If so, that may reduce dietary methionine content, which may be good for longevity in people. I'm looking into interventions that optimize the blood BA profile towards that seen in these longevity interventions-I'll have more on that in future videos!

[@timh-c7186]

@@conqueragingordietrying123 Hi Michael....isn't that what glycine achieves? That is, balancing the methionine/glycine ratio...which largely negates methionine, if I understand correctly.

[@conqueragingordietrying123]

@@timh-c7186 Hey Tim H-C, glycine is a minor player in the video, the main focus are the bile acids.

[@kamanashisroy]

@@conqueragingordietrying123 I saw a video that glycine binds with bile acid, Glycocholic acid etc .

[@conqueragingordietrying123]

@@kamanashisroy Glycine binds with cholate to make glycocholate, yes.

[@jackbuaer3828]

Hi Michael: I just saw a commercial product that attempts to do what you do. It's a blood test tracking product that defines an optimal target for biomarkers. I found it by googling optimal homocysteine levels. I think the product is directed towards health care practitioners, not consumers. The company is called optimaldx. Their work / philosophy seems similar to yours. Anyway, for folks looking for optimal range info for biomarkers that you have not yet covered, ODX might have it covered in their blog. The blog appears to be freely accessible. I have no affiliation with them and have not used their product. I googled their albumin page to see how they lined up against your target. They came in at 4.5 -5. Maybe they will update that to 4.5 -4.8 if they view one of your recent videos that covered the topic.

[@StaffanOlsson-sw6tx]

The gut is getting more and more attention. To name a few > Fecal transplantats, bile acids, the importance of the gut-brain axis.

[@conqueragingordietrying123]

Yes, it is getting more attention, but note that I've been talking about the effect of the microbiome's effect on aging since 2016: www.amazon.com/dp/B01G48A88A

[@darkhorseman8263]

Try mixing Icariin and Triphala (indian herb mix) It's good if it ends up in blood circulation, but it's better for probiotic bacteria; so bioavailability doesn't matter. Reverts them to a more youthful profile.

[@KJ-um1gq]

Ultimately, all roads lead back to CR

[@ivanandersson]

Totally unique and amazing information presented here on Michael’s channel - so much to learn and digest. However, probably difficult for a “mere mortal” to fix everything with food. Here is my core longevity supplement stack for a 55-year-old person and above, made easy (and somewhat affordable): 1 NAD precursor + TMG (first thing in the morning - metabolic health) 2 Butyrate+ insoluble fibers e.g. inulin (30 min before main meal -microbiome gut health) 3 Metformin (500mg with your main meal - mTOR regulation, etc.) 4 NAC+Glycine (in the evening -handle TMAO issues etc.) 5 Melatonin 1,5mg+niacin 500mg (flush)+curcumin (before sleep - circadian rhythm and gut-brain axis) Everything else of supplements is icing on the cake (vitamins, minerals, hormones, etc.). Then there are the issues of food, training, fasting, pollution, light, etc.

[@conqueragingordietrying123]

Hi Ivan, while food, fitness, and sleep are the top priority (for me), that doesn't mean I'm anti-supplements, but instead, targeted supplementation and regular blood testing to see if they actually work, or not.

[@newdata]

think in the same video above , NR is negative for longevity

[@張阿道]

I can imagine blood BAs being included in the big picture biomarkers, but which ones?

[@conqueragingordietrying123]

Yes, maybe eventually, I'm still trying to sort that out...

[@elliottrubenstein1746]

Interesting. Bile supplements?

[@conqueragingordietrying123]

Figuring out how to optimize blood bile acids is definitely on the to-do list. I'm not sure if supplements are ideal-RCTs are needed.

[@jaimemarun2841]

Can intermittent fasting increase the bile production?

[@conqueragingordietrying123]

I'm not sure, but figuring out interventions that optimize blood BAs is on the to-do list!

[@sooooooooDark]

ever tried adding barberries for berberine? they apparently have ~1.25% berberine content, which then would require 40g barberries for 500mg berberine (of course can go higher if u feel like thats not enough) apparently its also 1-5 times better absorbed with sodium caprate (sorry limited knowledge) and since its somehow related to capric acid which is found in the coconut butter u do its suggestible that u may can combine that into that coconut meal (side note: i find barberries go very well with yoghurt, and since u do that stuff too worth consider adding them in there)

[@jamesa54321]

I have an interesting 'condition' known as Gilbert Syndrome which is associated with lower CVD and cancer - you may have heard of it: it involves chronically elevated serum bilirubin due to lack of an enzyme. There are some theories out there as to how it works, but I wonder if bile is involved. My dad eats crap doesnt exercise apart from walk, and has mostly eated within a 4-6hr window lifelong, has yellowish eyes and nails, but seems healthier and leaner than most other men his age and has had no health conditions at 75 besides cataracts - it annoys my Mum a great deal.... For both of us it seems to make strenuous exercise unpleasant, and give us occasional issues with dyspepsia. It's a strange one....

[@KJ-um1gq]

In China, bear bile is a highly coveted supplement. Short of like Ox bile here. I take TUDCA sometimes. Huge impact not only on digestion, but also on overall well-being for me.

[@generalb4005]

So I’ve been taking Tudca and swear by this supplement. Keeps my digestion smooth. No longer suffer from bloating/insulin sensitivity and I’m losing weight. I’ve also cut down on processed foods and condiments that contain high levels of msg/modified food starch etc due to concerns of glutamate toxicity. Sulforaphane is in my stack so that’s boosting my glutathione levels which sounds like it also enhances my glycine and glutamate levels naturally didn’t know that prior to this video. I’ve recently purchased Glycine due to my long term water fasts. I wanted to make sure I boasted those glycine levels plus I wanted to make sure I was balancing out my glutamate levels since I’m sure a lot of it is still stored in my fat stores. Learned something new that in addition to all the other known benefits of glycine that it also is part of the bile acid process. Didn’t know before this video. I definitely think there’s a link between glutamate toxicity and chronic diseases/aging. Fasting, ketones, glutathione, bile acids, sulphuraphane, glycine, vitamin d, drinking close to 1 liter of water a day, and reducing synthetic forms of msg/modified food starch collectively appear to be helping me look and feel better significantly.

[@davidegiacomonigro313]

Hi Mike, may I ask you if supplementation of Cholic acid does have any impact on HDL and not HDL cholesterol? Thank you once again for your very interesting videos

[@conqueragingordietrying123]

Hi Davide, unfortunately, I haven't come across that data. Even though the BA story is interesting, I'm still investigating further!

[@davidegiacomonigro313]

@@conqueragingordietrying123 Thank you Mike for the reply

[@KoiRun50]

Does that mean that the liver and microbiome of the longer lived are fat adapted (able to digest fat efficiently)? And how does higher levels of bile acids in the blood relate to the risk of developing gallstones?

[@conqueragingordietrying123]

I can see how that's the easy interpretation, but too high of a fat intake won't optimize gut microbiome composition, which impacts levels of secondary bile acids. So there's a balance between fat intake, fiber, and other factors. The BA story may be dose-responsive, with too much linked to gallstones, and too little, a shortened lifespan. This is a developing story, I'll have more on it in future videos...

[@KoiRun50]

Perhaps nuts are a good substitute for fat from meats as they are lower in methionine. I wonder if longer lived people ate relatively more nuts.

[@conqueragingordietrying123]

@@KoiRun50 My initial reading of the literature is that a high soluble-fiber diet may optimize BA blood levels. I need to read more into this, so don't hold me to this initial hypothesis!

[@KoiRun50]

@@Finnfreya1 Where do they obtain most of their calories from? Proteins or carbs. I have a feeling these centenarians don’t eat much of anything at all.

[@Battery-kf4vu]

@@Finnfreya1 The Italians centenarians you've known didn't take olive oil?

[@riccardofabris1260]

Very interesting, thanks. I already knew several data on bile acids, however udca supplementation seems to have no significant impact on longevity, isn't it?

[@conqueragingordietrying123]

Thanks Riccardo-is there published data for UDCA on longevity? Also, I'd bet the maximum benefit for the BA story in terms of longevity wouldn't be for 1 or 2 BAs, but higher for multiple BAs.

[@Earwaxfire909]

Great work. Thank you! Are there genetics related to bile acids?

[@conqueragingordietrying123]

Thanks Earwaxfire909. I'm not sure, but that's a definite possibility.

[@bob-ss4wx]

Michael; in the previous video I believe you showed that high SHBG (Sex Hormone Binding Globulin) was number 2 in shortening lifespan. Have any plans to do a video on this?

[@conqueragingordietrying123]

Hey Bob, it's definitely on my to-do list. It's not yet at the top, though--unfortunately most people haven't measured their SHBG levels, so it won't have mass appeal. That said, I'll likely do a short video with age-related changes with aging and all-cause mortality data.

[@dirkh0]

Could it be, that these acids are a sign of proper organ functions? Eating bitter food like dandelion might also work instead of supplementing acids.

[@conqueragingordietrying123]

Yes, definitely-it could implicate a role for the liver on longevity. or, more specifically, specific liver functions and their impact on longevity. I'm not sure about dandelion.

[@dirkh0]

@@conqueragingordietrying123 I drink wormwood tea and dandelion tea regularly (5-6 times a week).

[@zacharyswain7034]

willl you start supplementing with bile acids?

[@conqueragingordietrying123]

Not yet-I'm looking into interventions that optimize them in blood, then I'd need to see what my blood levels are.

[@powerpuffherk]

But could there not be a general trend of more bile acids with ageing? Then it would not be a marker for longevity ...

[@conqueragingordietrying123]

They're higher in blood in the centenarians...

[@ddutton4716]

Does intake of bile acid resins reduce lifespan? Does the removal of the gall bladder result in lower lifespan? Great channel.

[@conqueragingordietrying123]

Thanks D Dutton. I haven't seen data that supplementing with bile acids reduces lifespan, but it is certainly possible. The gall bladder is the storage site for (primary) bile acids, whereas the liver and gut produce them, so I'd bet that lifespan won't be less (at least in terms of the bile acid story) without a gall bladder.

[@ddutton4716]

@@conqueragingordietrying123 I am sure you meant "...with bile acid binders reduces..." Regards.

[@conqueragingordietrying123]

@@ddutton4716 Nope-binders suggests a reduction in BAs. In contrast, in the video many BAs in blood were higher in long-lived people and in longevity animal models.

[@drrutledgemd]

"Pathologically" Increased serum bile acid level is associated with high-risk coronary ... Bile acid have different types, recent human studies have revealed the association between serum total bile acid level and cardiovascular diseases

[@conqueragingordietrying123]

Yep, thanks for that, there is likely a U-shaped association for BAs with longevity, with too little and too much being bad.

[@drrutledgemd]

@@conqueragingordietrying123 Sir; Right, the studies you referenced probably excluded obvious ill patients. Thus as you suggest it is unlikely to be a simple linear model but only improving health within a specific range and obviously not in patients with elevations secondary to some other pathology. A fine point that the general public might miss and choose a more is always better philosophy. PS: Great work. Take a breath. ;-)

[@johnnielsen5493]

Does anyone have an idea about whether bile salts could have a somewhat similar effect?

[@wahidrashidzada2446]

Hi Michael.Thank you for another great video. I wanted to mention Homocystiene levels and B12 supplementation. In prior videos you had talked about these topics. From what I understand is that Homocystiene gets converted to methionine, so if you have high levels of Homocystiene then methionine would also be high. Do you think that keeping Homocystiene levels low in the 5 range with B12 supplementation and increase protein intake, as you mentioned and had the lowest all cause mortality would also keep your bile acids high in an indirect method? Or are we talking about just methionine restriction in diet makes bile acids go up. or Maybe both?

[@conqueragingordietrying123]

Thanks Wahid. if methionine is high, I'd expect lower BAs, at least based on the mouse data in the video. So low homocysteine-->low methionine-->potentially more BAs.

[@TheReminderChannnel]

Would betaine hcl “fall” under bile acids?

[@conqueragingordietrying123]

Nope

[@TheReminderChannnel]

@@conqueragingordietrying123 thank you 🙏

[@Battery-kf4vu]

Great content as usual Michael! I take it glycine intake would increase glycine conjugated bile acid, perhaps it is part of the reasons that it increases lifespan? Concerning the 3 studies included in the meta-analysis on glycine, were the 3 using the same amount of glycine? Did they do an average to get to the 4-6% life extension figure? I take glycine powder, but I wonder how much would be too much? Could it lead to fibrosis or could it have other side effects?

[@conqueragingordietrying123]

Thanks Battery9876. Superficially, having more dietary glycine would be expected to result in more glycine-conjugated BAs, but, you'd need to measure them in blood to see if that's true. The same glycine content was used in all 3 studies, and the 4-6% is indeed the average extension. In terms of how much is too much, if you track blood biomarkers over many tests and glycine intake (but also, the rest of the diet), that's 1 way to evaluate how much glycine may be optimal.

[@Battery-kf4vu]

@@conqueragingordietrying123 Thanks Michael. I'd be curious to know if different dosages of glycine would have had a bigger effect on lifespan.

[@pramuanchutham7355]

Does NAC extend life, by forming Glutathione with Glycine and Glutamine?

[@johntaylor7952]

So would it follow then that people who have had their gall bladder removed have a shortened lifespan? Has this ever been studied? Tx, Michael, jt

[@conqueragingordietrying123]

Hey John, I haven't looked into it, but if anyone else has, hopefully they reply here!

[@stephmanusina3384]

I'm a 74 year old male with a congenital portosystemic shunt. My bile acids are 5 to 10 time normal (postprandial). The shunt is rerouting enterohepatic circulation away from returning to the liver hepatocytes and into systemic plasma. I think the thing you are seeing in your mouse models is aberrant bile acid signaling, i.e., FXR TGR5, and SHP, altering the micro biome. For me the high BA's is a curse. In people with normal livers, who knows. Do more research on Bile Acid Signaling. I think that is where your answer is.

[@conqueragingordietrying123]

Hi Steph Manusina, you make a great point, and I'll cover this in a future video. The published data supports the hypothesis that BAs, or at least some specific longevity-related BAs have a U-shaped association with health, with too little and too much being bad.

[@monnoo8221]

thank you very much for bringing this up, very very interesting... and what I understood from the review "The Role of Bile Acids in the Human Body and in the Development of Diseases. Molecules. 2022 Jun; 27(11): 3401." the BAs are not very well understood, due to their extremely complex role, integrating and effecting practically everything. What I understand, they can be a double edged sword, anti inflammatory and vaso-dilatative, but also negatively affecting the lung tissues and reducing mitochondrial proliferation in the heart. i am excited because i will receive the results of my own test next week, measuring the BA the first time in my life. I think the transposition of the question "is lifespan extended" into higher levels as compared to offsprings 30y younger does not catch the point (completely). After all, the centenarian could be dying just because the BA are so high. They also have to compared against controls...And that is not available. The substituting crucial questions are "does a higher BA level at age 65 predict longevity?" and "has the offspring of centenarians higher BA levels than their age matched controls?"

[@newdata]

milk thistle maybe affect bile acids as well

[@conqueragingordietrying123]

Are there published studies?

[@newdata]

@@conqueragingordietrying123 These data indicate that milk thistle may in part mediate its hepatoprotective effect in humans by stimulating the efflux of hepatotoxic bile acids by bile salt export pump (BSEP) and by inhibiting the metabolic pathways, specifically glucuronidation, that would inactivate beneficial bile acids. ...from research gate

[@factchecker9358]

How about doing the same review with egcg?

[@conqueragingordietrying123]

I'm not sure if there's ECGC data from the ITP, but a review of ITP interventions on longevity is something I can do!

[@Fanaz10]

Would it be possible to make some kind of methionine inhibitor to have the benefits of MR diet without dropping the meat?

[@conqueragingordietrying123]

We probably don't have to be vegan to be on a MR diet-see this video: kzbin.info/www/bejne/m4KzdayYmJJ9Z9U

[@thinkgrowhealthy2137]

Wow! So, are bile acids amino acids like glycine?

[@conqueragingordietrying123]

No, but glycine can be conjugated to bile acids. For example lithocholate sulfate vs glyco-lithocholate sulfate.

[@thinkgrowhealthy2137]

@@conqueragingordietrying123 I am not familiar with these. Maybe this is a topic for another video?

[@monnoo8221]

about NR: it is wrong t supplement as part of free access feeding. It interferes with circadian rhythm, and should always be taken, given only in the morning. Else, comparing NR in the blood among age cohorts is questionable (stupid?)... it is targeting intra-cellular processes of cells with a nucleus... It never could be expected to leak out of the cells, and should be expected to be tightly regulated. After all the whole reasoning based on comparing the old ones with the younger is crap. Maybe the bile acids need to be low for increasing the yet to come span of life, and high bile acids indicate a short remaining period??? You would have to know whether the now-old ones had a high bile acid level when they were 60... And regarding the metabolism the same: elevated bile acids are a spill over of a high turnover of fat and cholesterol, indicating that they are eating fat-rich, low carb, with lots of lemons...

[@rollok4979]

Based!

[@sooooooooDark]

yea in the food videos of the food bloggers around the world lots of indigenous groups add the bile of slaughtered animals into their dishes (and i mean it...feels like every tribe anywhere does it).... they mightve been onto something with their traditions/customs indeed before they had lab science, i wonder how they figured that one out, not exactly intuitive thing to grasp 🤔probably someone with very strong bodily awareness figured it

[@conqueragingordietrying123]

They probably followed how animals do it, as I've seen them go straight for the guts (literally) when eating.

[@BR-hi6yt]

Very good video - thx. btw Patreon starting at $3.50 is too much for me, I have a lot of deserving YTs and they would all add up out of hand.

[@conqueragingordietrying123]

Thanks Martin, and no worries

[@brandon53081]

Aren't egg whites & bone broth high in glycine?

[@stellarblur]

Collagen and bone broth yeah