New Attia podcast on Klotho

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.

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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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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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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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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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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No risk of causing an embolism?

How do you define “low dose” here?