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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Hi @DrT
As the narcissistic MD who offended you, albeit, I’m not narcissistic. I’d like to gain some wisdom from you.
I’m sorry if I offended you, and I think I was wrong in my approach. Please accept my apology.
I have a dear friend who had a spontaneous brain bleed (subdural hematoma) and is now left with some deficits and seizures. He is a patient, and I’m working on things to help his neurologic injury.
Alpha Klotho seems to be a possible area to pursue. I’ve put him on P21 and BPC-157 to try to drive up BDNF. I however think, that increasing Klotho and generating Platelet factor 4, which is probably the active ingredient is a sensible strategy to add to what I’m doing.
The information on human dosing is difficult to decode. I would genuinely appreciate your input and wisdom to inform me on how you are dosing klotho and your basis for this.
Thank you.
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What have you subjectively noticed in terms of effects on the brain? Have you tried to verify with any cognitive performance tests? Very interested to know.
DrT
#64
Hi Dr Fraser,
Thanks for your kind email. I understand that it must be hard to watch a friend suffer like that.
I’ve asked Rapa Admin to pass on my direct email to you so we can connect that way.
Best,
DrT
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Thank you for being so gracious.
Regards,
Grant
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Keith
#66
You may want to look at using cerebrolysin to boost BDNF instead
It’s a fair call. We know P21 and BPC-157 drive up BDNF significantly. Getting a comparison of those vs. Cerebrolysin … just doesn’t exist. Because it’s not mainstream, we simply haven’t had the funding put in to investigate.
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RobTuck
#68
There is a good chance that telmisartan is a low risk and inexpensive way to increase circulating klotho that confers other benefits. In addition to blocking the angiotensin II receptor it acts as a partial PPAR-γ agonist. PPAR-γ activation is linked to anti-inflammatory and antioxidant effects, which may contribute to upregulation of Klotho. This dual mechanism gives telmisartan an edge over other ARBs by targeting multiple pathways that are relevant to Klotho expression. Mostly animal data but the theoretical framework is good.
From: Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations - PMC
Several drugs enhance circulating Klotho levels, and some cross the blood-brain barrier to potentially act in the brain. In clinical trials, increased Klotho was noted with renin-angiotensin system inhibitors (losartan, valsartan), a statin (fluvastatin), mTOR inhibitors (rapamycin, everolimus), vitamin D and pentoxifylline. In preclinical work, antidiabetic drugs (metformin, GLP-1-based, GABA, PPAR-γ agonists) also enhanced Klotho. Several traditional medicines and/or nutraceuticals increased Klotho in rodents, including astaxanthin, curcumin, ginseng, ligustilide and resveratrol. Notably, exercise and sport activity increased Klotho. This review addresses molecular, physiological and therapeutic aspects of Klotho.
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I’m really interested in finding out if anyone has solved a number of challenges I’m having with use of alpha-klotho.
#1 What dosing regimen do you use, and why?
#2 Has anyone found a cost effective way to measure levels? The best I can find is $600 and if drawn and batched (held until they have enough others submitting samples) ~$250.
It’s a bit of a challenge as too much seems to not be harmful, but eliminates the benefit.
Also on the dosing regimen, I see people doing weekly, yet this substance has a T1/2 that is well under 24 hours.
I have been most appreciative of @DrT and his input, and would appreciate additional input from anyone else that has knowledge or a method to their dosing, logic, data, etc.
Incidentally anyone buying anything from Buckylabs can get a 15% discount using code FRASER … but I’d also subscribe as I say last Friday they had a 25% off for one day and suspect that might come up at times.
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59vw
#70
See my post (#55) above in this thread… The data doesn’t support injecting klotho at the doses currently being used.
Yet many seem to be doing this… there is a facebook page of people reporting on how they dilute and inject klotho. I’m curious if they are sensing some dramatic effect and keep doing it?
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Satchel
#71
You can’t measure Klotho accurately, currently. All research labs have in house assays that still cannot distinguish between wild type and KLVS type Klotho. Very frustrating for everyone as this would solve the dosing problem - if only you could measure levels with some level of confidence!
I would suggest that you pursue PF4 injections instead. Readily available and tested in people at ridiculously high doses (in a surgical setting) for 20+ yrs. Since it is the main mediator of Klotho - it seems like a no brainer (pun intended!)
https://www.nature.com/articles/s41586-023-06436-3
https://www.nia.nih.gov/news/blood-clotting-protein-young-mice-may-rejuvenate-older-mice-brains
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