Wasn’t always generic I’d guess
Yep, the specificity is actually pretty low for specifically the prediabetes cutoff on HbA1c in the US. I think the idea was to get more people alarmed earlier at the risk of false positives.
You could also be an “exercise nonresponder” btw.
Take a look at the sales of metformin in the millions
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Seems to fit well with increasing t2dm/prediabetes incidence. If anything I remember some Indian metformin getting recalled due to carcinogens and these people are generally running relatively slim profit margins. A geri psych fellow once told me 1 in 10 times the cause of poor response to psych meds is actually because the medication is generic and made outside of the US despite FDA “bioequivalence”. Yet the insurance companies will often deny paying for branded to test that theory.
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Yes, I’ve definitely had patients tell me that the generics aren’t working as well. Never sure if it’s placebo or real effect.
The carcinogen problem with medications is certainly concerning. I remember a huge recall of zantac and I think something else was also recalled lately for the same issue.
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Could be placebo…if you happen to be in contact with their PCP, an easy way to test that theory for chronic outpatient is just to prescribe them CGM for t2d and then mix a small amount of branded samples and their generics randomly - they might still see the difference in pills so it’s not perfect. For HTN, they can get portable BP monitors to do similarly but I wish they were continuous/real time - I’m still waiting on those wristwatch ones that can be calibrated with purported high accuracy. They’ve already been approved in EU apparently.
All good points.
We know what we know and we think we know what we think we know:).
In creating your stack, did you add one at a time? I have tried to simplify what I take into 3 categories. I subjectively feel better, I objectively have data supporting its use, and I have weighed risks and benefits and although have no subjective and or objective data, still choose to take it. Many flaws to this approach, but my template for now.
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For the most part. Might help to describe the process. It starts with building a systems model of aging in biology, particularly biochemistry and genetics heavy in fundamental metabolic pathways. Then you make hypotheses to see on what already works for all organisms and follow down what genes are preserved in humans and what combinations already work in mammals. With current advances in software, I can run many experiments in silico to test a broad range of compounds, predicted protein-protein interactions, and then cluster compounds network-level effects. If you manually curate that you probably would have already honed in on AMPK, SIRT, IGF-1, mTOR, and TP53 - along with the other pathways as large nodes to target, then you can compare with what is currently strongly recommended by consensus because chances are your model is wrong.
Now that I have this list of compounds (including natural ones) or interventions (including exercise) then you hypothesize what would happen and how you would measure that effect, preferably non-invasively. Check the literature. For diet, I basically did a “broad spectrum micronutrient” treatment, but I made sure to avoid any possible contaminants that may affect my results. So I didn’t go one at a time with vitamins, minerals, dietary factors, nutraceuticals, sleep, and exercise dosing. It just doesn’t make sense. However, I do manually keep a list of compounds (or similar compounds that have broader literature) I have in estimated quantities, including foods, herbs, spices. Most of you already know about grapefruit and drug interactions.
After doing a broad spectrum micronutrient and broad dietary nutraceutical experiment, I measure results as comprehensively as possible. (The most relevant, relatively cost effective ones for most people here are VO2max, HRV, vitals, visceral fat/DEXA or fat calipers/waist to hip ratio if that’s not available, CBC with diff/CMP/TSH/CRP/fasting IGF-1/lipids/HbA1c - there are more tests I use but I’ll just mention the ones that aren’t that expensive)
Then I add drugs one by one. Before taking anything, I look for drug-drug interactions first, consult different clinical experts (especially pharmacogenetics can change a lot of things), clinical support systems, etc etc. Take it, measure expected responses, note potential symptoms, increase dose, measure again, note potential symptoms, and repeat until desired effect, then crossover of n=1. If it works as I think it does, it stays.
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I came across your regimen as of June and noticed your daily consumption of spermidine. I would like to be taking 15 mg/day of spermidine but it is rather expensive. May I ask your source?
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Natto/5-10 yr old cheddar, approx 20 mg/day Spermidine. These are two super dense Spermidine whole foods, and you get additional nutritional benefits.
Some mushrooms are also high, but more exotic, less available, and expensive.
I dumped my (as you say expensive) Spermidine supplement.
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CTStan review the following posting;
Also if you look on another posting I up-load several months back a copy of a document showing/listing spermidin amounts per food.
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I bought the aged cheddar, and Amazon sold me a big jar of dried wild mushrooms. I even got some spermidine powder when it was on sale. For a while I was eating the cheese fairly often. I found ways to prepare the mushrooms, and I mixed the powder into a protein shake along with creatine and Ca-AKG. But the powder is running out and despite my good intentions, I realized I’m far more regular when I have daily capsules. It is just so much easier to take three overpriced Doublewood capsules and settle for 12 mg. I was hoping for a thrifty source of capsules but I guess there is no such. I’ll look for the German powder. Thanks.
CTStan, here is a link to the document.
I use this one.
Manual calibration for BP and I check it once a month and it appears to remain reasonably accurate.
Takes BP every 5 minutes.
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Very reasonable cost.
FWIW
I looked at the “CardiacSense” watch, list price in the UK*, cost is over 825.00 GBP. I do not think may consumers will purchase at 825.00 GBP
- The UK distributer site posted a price, others distributer did not post a price.
The other reason I bought the Aupalla was that from what I could see, it was the only providing HRV data without having to take out a monthly subscription.
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@tongMD - I love this whole approach!
Create a model (of the current understanding) based on the systems and pathways that effect aging recognizing the genetic differnces that can alter the process.
You just summerized about 100 years of what we understand about aging and showed by adding software advances, that hopefully accelerate our prediction process that is light years ahead of what we have been doing. One of our biggest problems in medicine is everything is slow! Slow to share data, slow to come to conclusions without decades of RCT and slow to address integrate most of what you just typed out in 4 paragraphs.
Let me know when you create an app to input data that can generate some reasonable options beyond what most of us have to do…and just guess!
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Welcome to the forum and thanks for the detailed overview of your regimen, supplements, medications.
I love the in-depth analysis for potential drug/drug interactions, etc. Ideally it would be something we all could do.
I just wanted to pull out links to all the sited and resources you referenced:
NIH-Library of Integrated Network-Based Cellular Signatures
https://lincsproject.org
Universal Natural Product Database
https://bioinf-applied.charite.de/supernatural_new/index.php
Kyoto Encyclopedia of Genes and Genomics
On a related issue, I’ll see if I can get Matt Kaeberlein and Mitchell Lee to share the outcomes of outcomes of testing of the combinations of the more common supplements and rapamycin, SGLT2 inhibitors, Acarbose, etc. that people here are using - to see if the combinations are synergistic or counterproductive. This type of information is probably something they’ll get as part of their research, and would likely have little or no commercial value by itself - so I’m hoping they will be predisposed towards releasing this basic information for us.
See: Ora Biomedical: Matt Kaeberlein's New Longevity Biotech Company
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From my understanding, Dr. K didn’t want to test acarbose in dogs because it would decrease compliance due to GI toxicities, rather than worrying about potential drug-drug interactions of acarbose with rapamycin. I suspect he currently believes it would be close to additive but I’m not sure.
As for his newest startup - it’s an interesting concept and I look forward to it - there will be a lot of great outcomes from novel or optimized methods involving high throughput screening as a field. I’m more focused on what I can apply directly as of now or in the near future with the best odds, information, and models available.
The main risk I worry about for my situation with acarbose is possible hypoglycemia (primarily mitigated by an accurate enough CGM with a hypoglycemia alarm) with any herbs or foods that affect AMPK activation directly or indirectly, on top of intermittent fasting and intense exercise. So far, no hypoglycemia.
I will also note I’m going on a bit of a departure from the literature with acarbose (partly from a few suspicions that it won’t necessarily pan out in real-world humans), so it could end up being no additional effects if the effect is not because of postprandial glucose levels. I’m not taking acarbose all the time and I’m not taking it with rapamycin together - just high carb meals prn (if I’m at a restaurant due to social reasons and end up eating a high carb meal very occasionally a few times a month) and I take only 25 mg acarbose separate from other compounds (about 12-20 hrs apart) beyond any potential dietary nutraceuticals. Very little is absorbed systemically and all of that is excreted quickly in urine. Most acarbose is eliminated in the feces. The remaining metabolites take a bit longer, but I think at the 12 hr mark it’s probably insignificant if those metabolites (or any related effects from acarbose) even have activity. I’d probably be more concerned about any potential acarbose drug interactions that are significant if it’s closer to the first few hours after ingestion.
I would note there are dietary sources of alpha-glucosidase inhibitors that I take. An obvious one is an anthocyanin from steamed sweet potatoes (traditional Okinawan diet staple) that is stabilized after steaming to inactivate peroxidase.
My pure speculative guess is multiple natural alpha-glucosidase inhibitors taken in food form already indirectly naturally tested in a population that appear to have a high average life expectancy partly based on mild calorie restriction (mTOR inhibition, but acts differently) and indirect intermittent fasting (via light evening meal or skipping dinner) is the better choice. I suspect using only acarbose as the single alpha-glucosidase inhibitor will run into problems when it comes to real-world translational results.
Not to mention, there’s a suggestive additive effect with rapamycin - it appears to be very low-hanging fruit so far when tested in mammals.
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