Karel1
#41
“My lithium value was low <0.1 mmol/L. Reference range is 0.5-1.0. This came as a surprise as I had been taking 15 Mg Li-Asp per week.”.
Lithiumcarbonate is used for various diagnoses; dependent on renal function and other medication 3x300mg or 3x400mg daily are necessary to get lithium values of 0,8-1,2 mmol/l that are both safe and therapeutic for many people. (Li2CO3)
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DrT
#42
Too much lithium can be harmful to kidney function.
One must be very careful with supplementation. I’m sure there are bioavailability differences between LiCO3 and Li-Asp.
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Is there any reason I can not or should not go overseas, maybe to Vitalia City, and do a small clinical trial of Klotho on Alzheimer’s patients?
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I like that idea. Seems like it would be a worthwhile project. There needs to be contract research organizations (CROs) in Vitalia to do this type of thing across a broad number of potential therapeutic / longevity interventions. Everyone interested in doing this shouldn’t have to start from scratch getting clinical space and hiring the people experienced in doing clinical trials, even in a small/limited scope scenario.
Really, what we need is an SRI-like organization (smaller, and more focused, obviously) based in Vitalia that just focuses on longevity compound clinical trials / testing.
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I got around to listening to the podcast this weekend. Fascinating!
We have a couple of users here - have they experienced any cognitive enhancement from taking klotho?
Those who have done extensive reading (especially @DrT), are you aware of any downsides or side effects? None were mentioned in the podcast that I can recall, just appeared that an “excessive” dose didn’t help.
I was concerned at the statement that a klotho level that was 30% lower than the mean level was associated with 30% mortality over five years. That is a compelling reason to get tested, and, if the results show you are low klotho, to begin injecting now without waiting for human studies.
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DrT
#46
Just off the top of my head: if klotho increases kidney clearance of phosphate, then one obvious danger is phosphate depletion. This can lead to cardiac arrhythmia which is very serious. As with all supplementation: MORE IS NOT NECESSARILY BETTER!
Be careful people!
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Listen further in to the podcast. it works differently in primates than in mice. In primates anything over a typical youthful dose did not work. The smaller doses worked at about 1/3 to 1/5 the amount needed to match a youthful level. Use too much and it doesn’t harm but doesn’t work. They also seemed to indicated that monthly injections would likely be what is needed, not daily.
The podcast also mentioned that rapamycin increases Klotho. Could that be it’s main mechanism of action?
I’d like to hear of any research on how to increase klotho to a therapeutic level without injecting it. klotho patch?
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They said the cognitive benefits of Klotho on the monkeys lasted about three weeks. But I’m not sure I would necessarily conclude that the protective effect of Klotho against cancer and cardiovascular mortality also lasted three weeks per shot.
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Interesting podcast. It sounds like something will come of all of this someday. For now, exercise remains the magic bullet.
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DrT
#51
But if peptides are made using bacterial fermentation the impurities will be different.
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Dubal is another great discovery. You might also check out her recent discussion with retired neuroscientist Mark Mattson on his YouTube Channel Brain Ponderings. Also, an older talk by Tamara Isakova on Youtube. A take-away from the Isakova talk was that alpha Klotho concentration in plasma was positively associated with kidney health (eGFR in this case), which is another reason for ensuring optimum kidney function. A take-away from Dubal and Mattson talk (could have been Attia) was that exercise was a robust promotor of Klotho, even better than the favorable gene than some carry. There is another talk, about 8 months ago, by Saul Villeda which discusses platelet factor 4. And going back to the 2020 plasma exchange paper from the Conboy lab, it seems that neutral blood exchange in mice, replacing 50% of plasma with saline and albumin increased PF4 but how much is not known. Sufficient physical activity into older age seems like a must as it appears to have broad positive effects on body and brain function.
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I believe the experts (Dubal, Isakova for example) indicate that Klotho is not easy to measure, so would be surprised if there was a test on the market. But according to a talk I saw by Tamar Isakova Klotho is proportional to kidney function as measure by eGFR. So do what you can to keep kidney function optimized, eGFR up around 90 to 100 as you age. And chronic exercise is a great booster of klotho according to Dena Dubal, on the order of 30%.
Just listened to the podcast. Very interesting!
I am interested enough to spend some time researching this further.
Hopefully we see more testing on this. For now I am happy to learn that some of the things I am already doing (taking rapamycin, Vit D and exercise) have a positive impact on Klotho levels.
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Researching pio - lots of anti aging and klotho upregulating information online. Low dose - 15 mg every day or two…
“we found that pioglitazone treatment in aging also increased renal klotho expression by more than 60%”
from: https://www.kisupplements.org/article/S2157-1716(15)31196-5/fulltext
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59vw
#57
The KL dose in rhesus macaques was 10 ug/kg which is logs above the homeopathic dose DrT and others are using here (human dose of 700 ug for a 70 kg person). I think more dosing studies need to be done in humans before people start injecting themselves with Klotho. It’s tempting but my guess is DrT and others are taking big risks with a dose that is likely not biologically significant. Not recommending anyone inject themselves with a higher dose, seems like that would be extremely dangerous with unknown purity. I’m willing to be convinced otherwise but this just sounds really bad.
Free access paper here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432271/pdf/43587_2023_Article_441.pdf
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"which is logs above the homeopathic dose DrT and others are using " - the only caveat is that Dr Dubal is suggesting dosing every 2-3 weeks and Dr T is dosing daily - therefore Dr T dose x 21.
Even if you only want to try a small increase in Klotho from 700 pcg/ml to 1000 pcg/ml. (300 pcg/ml increase). Then at the very least ( assuming 100%pure and 100% bioavailability - which is not possible,) 70kg person- 6 litres of blood// 300pcg/ml x 6000ml = 1800000 pcg or 1.8ug total dose would be needed for a transitory increase .
Dr Dubal also mentioned that 1ug/kg dose was similar in effect to the 10ug/kg dose in the rhesus. Also the 0.4ug/kg dose effectively doubled Klotho levels in Rhesus monkeys
therefore rhesus dose x 0.324 = human equivalent dose (HED) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/ “A simple guide for dose conversion between animals and humans” (the paper also recommends starting at 1/10th of the calculated HED to prevent side effects)
0.4ug/kg x 0.324 x 1/10th = 0.01296 ug/kg x 70 kg = 0.9072 ug starting dose -and up to 9ug equivalent dose - every 2-3 weeks
Just food for thought
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DrT
#59
I really don’t understand where you get the idea that I dose Klotho daily. From my earlier post:
“Eventually I get to a solution of 2ng/ml. I inject 0.2ml once per week.”
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I did the klotho test from Longevity Labs in TX, and while I have the rs9536314(GG) bad SNP for it, I was above range for all age groups. I do take Rapa, Vit D and exercise (gym and zone2) - which research suggests raises klotho levels. Goes to show, whether you have a “bad” SNP, it doesn’t mean it is expresssing and/or lifestyle factors can overcome the bad SNPs. So now, I have bucky labs klotho I bought awhile back, waiting on these results, I guess I’ll keep in freezer for now 
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