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Uremic Metabolites: Kidney Function Biomarkers 

Conquer Aging Or Die Trying!
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Papers referenced in the video:
Predicting Age by Mining Electronic Medical Records with Deep Learning Characterizes Differences between Chronological and Physiological Age
www.ncbi.nlm.n...
Age-related changes in clinical parameters and their associations with common complex diseases
pubmed.ncbi.nl...
Variation in serum creatinine level is correlated to risk of type 2 diabetes
www.ncbi.nlm.n...
Age and cystatin C in healthy adults: a collaborative study
pubmed.ncbi.nl...
Cystatin C and long-term mortality among subjects with normal creatinine-based estimated glomerular filtration rates: NHANES III (Third National Health and Nutrition Examination Survey)
pubmed.ncbi.nl...
Metagenomic and metabolomic remodeling in nonagenarians and centenarians and its association with genetic and socioeconomic factors
pubmed.ncbi.nl...
The Intestinal Microbiota and Metabolites in the Gut-Kidney-Heart Axis of Chronic Kidney Disease
pubmed.ncbi.nl...
Characteristics of Colon-Derived Uremic Solutes
www.ncbi.nlm.n...

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21 окт 2024

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Комментарии : 72   
@PaulBeauchemin
@PaulBeauchemin Год назад
My eGfr was in the 40’s for 5 years with high creatinine. About 3.5 years ago I started 6 mg of weekly rapamycin. Test two months later showed eGfr in the 80’s where it as stayed (and corespondent lowere creatinine). Most dramatic results I’ve gotten with any changes I’ve tested
@jamesgilmore8192
@jamesgilmore8192 Год назад
That is interesting Paul. It's possible rapamycin could limit muscle breakdown, thereby lowering creatinine, which would give an improved eGFR, without kidney function actually improving. That's the problem with creatinine eGFR, its quite dependant on what's happening to creatinine production (amount of muscle mass, recent exercise etc). Have you had your Cystatin C measured before and after, perhaps it could add more information?
@barrie888
@barrie888 Год назад
Hcw here, great review Sir
@MMPRECISIONPAINTING
@MMPRECISIONPAINTING Год назад
Hi Michael. Your videos are awesome! I was curious as to how you go about calculating your B.M.R. and your daily caloric expenditure. Do you use a wearable device or calculate some other way? I have a job where my activity level varies significantly from one day to the next. I have an oura ring, but have tested it against a polar h10 chest, and the chest strap always calculates double or triple the calories burned vs the oura ring. I'm trying to caloricaly restrict by a certain percentage, but with no way to get an accurate caloric expenditure it makes it difficult to do so accurately. Just wondering what you do, or would suggest in this situation?
@jamesgilmore8192
@jamesgilmore8192 Год назад
MM - Doing it at home, you probably need to go on changes in daily scale weight, and if you want to get more detailed aim for a %BF over a week or month using callipers and circumferences etc. Daily caloric expenditure is a problem that is unresolved even in the research community to the accuracy you would want.
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
Hi @MMPRECISIONPAINTING, I didn't calculate my BMR, but instead, have weighed myself daily for many years in conjunction with diet tracking to find the calorie intake that maintains body weight. Then, a small daily calorie cut below that every day with the goal of getting lean/staying lean.
@MMPRECISIONPAINTING
@MMPRECISIONPAINTING Год назад
@@conqueragingordietrying123 Thank you for the info.
@jamesgilmore8192
@jamesgilmore8192 Год назад
@@MMPRECISIONPAINTING The only other thing that comes to mind is using the average HR across the day (or week) of your chest strap and trying to triangulate that with tracked calories and scale measurement.
@SH-jg5zq
@SH-jg5zq Год назад
Thank you 🙏🙏🙏
@abdelilahbenahmed4350
@abdelilahbenahmed4350 Год назад
Thx Prof LUSTGARTEN for this outstanding video about the aging kidney. In this video we see, in particular, that Trigonelline is among the uremic metabolites that accumulate in the presence of poor kidney function. On the other hand, we know that lots of older people in some countries , in North Africa, Iran and India for instance, often consume relatively large quantities of fenugreek ( very high in Trigonelline) . Trigonelline is also present in barley, cantaloupe, corn, onions, peas, soybeans, and tomatoes, oats, potatoes. Do you think lowering our trigonelline intake to a reasonable level could impact positively our renal function ? In your case, and in addition your intake of one tablespoon of flaxseed, what are the other nutritional or lifestyle interventions that helped you improve significatly your kidney function ?
@jamesgilmore8192
@jamesgilmore8192 Год назад
Just adding that trigonelline is also sometimes used as a coffee biomarker.
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
Thanks Abdelilah, this is a great point. Even if we eat lots of trigonelline, with good kidney function, we'd pee it out. With sub-optimal kidney function, it would accumulate in blood. A similar story is true for TMAO (intake via fish vs accumulation systemically because of poor kidney function). Flaxseeds are still significantly correlated with lower creatinine (and a higher eGFR), but whether that's causation is unknown. I recently increased their intake further, so it will be interesting to see if creatinine levels are reduced for tomorrow's blood test. There are a few foods that are significantly correlated with creatinine, including salt, so I stick to the low end of my intake range to potentially limit any adverse effects on kidney function.
@petermilian4455
@petermilian4455 Год назад
Could you do a video (or pin a comment) that describes your routine for increasing the accuracy / consistency of your test results? What day of the week / time you get tested, what you do or do not do in the 1-2 days prior to the test, what you do the day of the test etc.? A big part of how fascinating your data is to me is the effort you (appear to) put in prior to testing to reduce noise in your biomarker testing data.
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
Hi @petermilian4455 and thanks-I can detail some of that here. The last workout is on a Friday before a Monday test, with as much recovery as possible for the 2 days prior. Since I track diet, I try to eat exactly the same intake both in terms of foods, macros and micros for the day before each test. The exception to the rule is if I'm doing a specific experiment (i.e. supplements that weren't in previous tests), or increasing a particular nutrient test-over-test. Also, prior to each test, I fast for ~17h-there's no specific reason for that duration, but I used that amount a few years ago, and to be consistent, have aimed for that amount since. On the morning of the test, I drink 20 oz of water after waking up, and approximately 2h before the test, which standardizes hydration status.
@petermilian4455
@petermilian4455 Год назад
@@conqueragingordietrying123 Thanks for the detailed response. Is there any reason in particular you chose 20 oz of water for the morning before your tests or would more / less be fine as long as whatever quantity you choose is consistent?
@javadivawithdog
@javadivawithdog Год назад
But patient age is in the equation for eGFR. If no thing else changes, the eGFR will decrease every year as a function of the equation alone.
@jamesgilmore8192
@jamesgilmore8192 Год назад
That's a fair point, and the factor is 0.993^age, which is weak, but over time would lower eGFR. The cystatin C equation is slightly better at 0.996^age. They are both murky equations in the context of longevity optimisation lets be honest, but they have been validated against other ways to measure GFR. To keep them constant over a 10 year timeframe means you are doing well.
@Battery-kf4vu
@Battery-kf4vu Год назад
Hi Michael. I noticed your TMAO was cut in half between the 2 tests. Do you have an idea on what caused that?
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
Hey @Battery-kf4vu, my best guess would be a reduction for TMA-producing gut bacteria, as my sardine intake wass not lower, test-over test. But I don't have gut microbiome data that goes with this test, to know for sure. It could be normal test-to-test variability, too, as I'm still in the early stages of metabolomic tracking.
@darkhorseman8263
@darkhorseman8263 Год назад
The body produces TMAO to maintain blood flow during high osmotic pressure. People with low levels of tmao have lower survival from heart attacks. TMAO is beneficial. Dont believe outdated science. The body will produce less of it if your blood pressure lowers, though. This could be indicative of better blood flow. Fish and whales produce it to maintain blood flow during dives. Helps bloodflow during high pressure. One of the reasons Fish is superior to other meat is its large TMAO content.
@jamesgilmore8192
@jamesgilmore8192 Год назад
@@darkhorseman8263 Do you have some literature we could look at? I haven't been following TMAO for a while
@Battery-kf4vu
@Battery-kf4vu Год назад
@@conqueragingordietrying123 Could it be due to what you took to try and increase your NAD? I doubt it but just wondering.
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
@@Battery-kf4vu That's definitely possible-NAD was 59uM, 2x higher than my baseline, and included niacin+tryptophan supplementation. I feel a difference with niacin on my GI system, and not in a good way, so higher PCS could reflect that.
@Blurns
@Blurns Год назад
All I've learned from this is that I may live longer if I steal a kidney from someone half my age.
@vedransimic86
@vedransimic86 Год назад
Great you covered the creatinine as I was wondering about the discrepancy between the outcomes due to muscle mass and those regarding impaired kidney function. So I guess cystatin C is a better marker of kidney function than creatinine. If you would have to choose: would you say that Uremic Metabolites are a better marker than cystatin C?
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
I wouldn't say better, but complimentary. For example, if cystatin C is low but uremic metabolites are high, it wouldn't suggest poor kidney function (initially), but gut microbiome dysbiosis. But, elevated uremic metabolites over time may lead to decreased kidney function, so both measures are useful.
@vedransimic86
@vedransimic86 Год назад
@@conqueragingordietrying123 Ah, okay! I like your nuanced answer, but if you would have to choose between the two, which one would you give the preference?
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
@@vedransimic86 Hmm, probably the uremic metabolites, as they'd be the first to change before potentially seing poor kidney function, as detected via creatinine or cystatin C
@vedransimic86
@vedransimic86 Год назад
@@conqueragingordietrying123 Okay, perfect! Then I wil consider those. Thanks!
@jamesgilmore8192
@jamesgilmore8192 Год назад
Mike -- I thought p-Cresol sulfate was fairly conclusively shown to be produced by fermentation of undigested tyrosine in the large intestine, which is quite specific. Maybe you need to sleuth out any tyrosine changes in that month and reorganise the intake to not overwhelm the small intestine.
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
Definitely, thanks @jamesgilmore8192. the major change prior to this test was the combination of niacin + tryptophan, but I'm not sure (yet) how that affects gut tyrosine use.
@jamesgilmore8192
@jamesgilmore8192 Год назад
​@@conqueragingordietrying123 Its very possible tryptophan could reduce the rate of tyrosine absorption because of the side chain differences, but time will tell as you get some more measurements. Heres a couple of refs (these are the best i could find, not in humans, maybe you can find better): Absorption of Amino Acids from the Small Intestine of Domestic Fowl Local and Systemic Effects of Phenylalanine on Intestinal Transport of Tyrosine and Tryptophan You'll need to make the leap from the specific cases studied here to your case through the general chemical structure, so weak reasoning...
@freemarketswork
@freemarketswork Год назад
Many things can increase p-cresol, including industrial toxins and mold toxins.
@jamesgilmore8192
@jamesgilmore8192 Год назад
@@freemarketswork Did you have any papers on that? I couldn't find any.
@Thomas-wz2nu
@Thomas-wz2nu Год назад
How about your vid on hypothyroidism? I read that this on levothyroxin are more likely to get cancer. Causation or correlation ?
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
Hi @Thomas-wz2nu, a thyroid video is definitely on the to-do list. Can you please post the link for L-thyroxine with caners?
@Thomas-wz2nu
@Thomas-wz2nu Год назад
@@conqueragingordietrying123 Retrospective so perhaps just correlation
@jhouck4828
@jhouck4828 Год назад
What about using creatine and kidney function
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
Explained in the video
@jhouck4828
@jhouck4828 Год назад
​@@conqueragingordietrying123I still didn't see it,thanks
@jamesgilmore8192
@jamesgilmore8192 Год назад
@@jhouck4828 creatine and creatinine are different. creatine isn't used for kidney function.
@bottlenecks
@bottlenecks Год назад
The first time I checked my TMAO levels, they were off the charts at 102.4 uM. (Not sure what that unit "uM" is.) Then I stopped L-Carnitine supplementation, and tested again 2 months later, and TMAO was down to 5.3 uM. Also, fish eaters have higher TMAO presumably? So I wouldn't expect to get a useful figure by blindly adding up all these metabolites.
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
I'd expect circulating levels of TMAO to depend on kidney function-even with a high intake of precursors (or TMAO itself, from fish), the kidney should filter it out to physiologically -relevant levels. If kidney function is suboptimal m they won't. The metabolites in the list are well known to accumulate in the presence of CKD.
@jamesgilmore8192
@jamesgilmore8192 Год назад
@@conqueragingordietrying123 and bottlenecks. Total amounts are useful here, especially with some of these metabolites being substantially influenced by the microbiome, which is basically a black box still on an individual level. Some of the production mechanisms for specific metabolites are well understood, such as your example of carnitine ->TMA->TMAO, and for those yes maybe you need to exclude them if you've been supplementing.
@jamesgilmore8192
@jamesgilmore8192 Год назад
I believe the units are micro moles per litre, but someone correct me if I'm wrong.
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
@@jamesgilmore8192 Yep, uM
@jamesgilmore8192
@jamesgilmore8192 Год назад
@@conqueragingordietrying123 Mike it's possible there could be competitive inhibition of excretion if there are too many uremic metabolites at too high a concentration. I cant find any studies on normal people and metabolites specifically, but we know it can happen for drugs in circulation, and sometimes specifically in CKD also. If you reduced the one or two of those high uremic metabolites, I wouldn't be surprised to see the total of the other metabolites decrease as well.
@seekfactsnotfiction9056
@seekfactsnotfiction9056 Год назад
I started taking 1g of Creatine Monohydrate (from Sun Warrior brand) in my smoothie along with 15g of Dymatize whey protein (only half scoop) after 7 to 9 weeks of use, my urine sample shows high creatinine and protein with infection! I was even referred to see a specialist! Was that because of using whey protein and Creatine?! Even though I was taking way less than recommended dose or this is a coincidence?
@jimjam1719
@jimjam1719 7 месяцев назад
yes, more for the creatine, that's why i don't take it, even though "they" say we have extensive studies (so many years long) on it for being safe, every time i took it, i had high creatinine/protein levels, as soon as i cleaned off of it, the levels went to a very good normal, however, "they" say that that is to be expected, but my question is, if you keep having higher levels from taking it, what is it doing to the kidneys over the long haul? "they" also say that if your kidneys are already in bad shape in the first place, you shouldn't take creatine, so, that goes back to my question, why is that if creatine is so good for you? i think creatine is not good for them, besides, i get minor sharp pains in the kidney area of my body when i take creatine (whether it be 1-2mgs or recommended 5mgs per day), so i stopped taking it some years back. i still take whey protein but not excessively, even too much protein can harm kidneys, how much is too much?, depends on the person. protein is necessary though, how much is for the individual circumstances to decide.
@reforesters
@reforesters Год назад
I also did an IOLLO test. And I was alarmed to find that my kidney function tests (specifically p-cresol sulfate and dimethylarginine) were high and increased my "biological age" by more than 18 years. Interestingly, your values for both of these markers are even higher than mine. So, I'm curious if that pushed up your "biological age" on their estimator. I had around the same time had a cystatin-C test done (.8) indicating my kidney function was fine. I supplement with creatine, so my eGFR is never very meaningful. I'm curious what might be going on here. Ideas what might be driving up those two values? Given the variability in these numbers, does it really make sense, in your opinion, to include those in a biological age calculator?
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
I've had this discussion with iollo's CEO-until their biological age algorithm is published, I wouldn't place any value on it. That said, it's not good that my PCS and dimethylarginine (SDMA +ADMA) are relatively high. It's probably a gut microbiome issue, as PCS is initially derived from gut bacterial metabolism. It's possible that the metabolites change more quickly than established markers (Cystatin C), and with a long enough time with elevated uremic metabolites, eGFR starts to decline...
@reforesters
@reforesters Год назад
@@conqueragingordietrying123 Thanks. Yeah. It's an interesting problem, having so many metrics to draw from. I suppose you really need to do these tests at least a half dozen times, given the variability, for it drive a new strategy. Otherwise, an elevated marker could be just a quick meaningless blip based on foods of the prior days. Don't you think? I'm curious if the research they are using to determine correlations between metabolite level and age are based on sound science.
@jamesgilmore8192
@jamesgilmore8192 Год назад
18 years, that's quite a change in biological age. Perhaps you are a kidney ageotype at least on PCS and DMA? Regardless, it would be good for Iollo to publish normal ranges for metabolites and any trends with age as they gather more data. Its a nontrivial task to reweight omics variables into a "biological age", hopefully they use something reasonable.
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
@@reforesters Definitely on multiple testing, but i use that approach for all other tests, too, not just iollo. For now, probably not on the biological age metric, but they did mention publishing their algorithm at some point, which had a high correlation with chronological age, in the Horvath/Levine category (0.94).
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
@@jamesgilmore8192 iollo has "normal ranges", but despite my great respect for their company, I think that's premature and to be taken with a grain of salt, as there's a paucity of studies that used direct metabolite quantification (i.e. targeted metabolomics), as opposed to relative values (i.e. untargeted metabolomics). But knowing how the metabolites change during aging nd with health/disease is more instructive, imo, for now.
@osamaabdelfattah5469
@osamaabdelfattah5469 Год назад
Have you checked your egfr?
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
Yes, of course, there are videos on the channel documenting that-93 on the last test, 96 average since 2015.
@greensmoothieparty
@greensmoothieparty Год назад
Your TMAO was also reduced by half between the two tests and to a more optimal result.
@darkhorseman8263
@darkhorseman8263 Год назад
TMAO actually increases rates of survival after heart attacks. It's beneficial. Whales produce lots of it to help their blood vessels maintain flow during high osmotic pressures during dives. Eating lots of fish increases lifespan. Fish contains large amounts of tmao. Dont follow outdated science and hysteria. The newest studies tell a very different tale of TMAO. Yes, levels can be higher in heart attack victims, but that is just the body creating it to try to maintain blood flow. Those with lower levels have lower survival rates.
@conqueragingordietrying123
@conqueragingordietrying123 Год назад
Yep, that's good news, but PCS increased by a lot more. I prefer looking at net effects rather than individual metabolites...
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