The “CardiacSense” watch?
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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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I would like your thoughts on time-restricted feeding
As a child, I never wanted to eat breakfast and couldn’t figure out why everyone was force-feeding me. As I grew up I adopted the social norm of having breakfast. After I retired I needed to lose some weight, so along with exercise, I did a keto diet until I reached my own goal of 175 lbs. Then I just did time-restricted feeding. I do ~ 18/6, not because I have a strong belief that it is optimal, I just don’t feel hungry before 1 PM. My first meal is at noon because that is convenient for me. The plan is working so far and I eat a somewhat South Beach Diet, again by natural choice and not by plan. I do not count calories and I eat until I am full.
So, do you think I should force myself to eat earlier in the day as some proponents of time-restricted feeding advocate?
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I don’t eat too late (last meal >3 hrs before bed) because there is suggestive evidence of “fasting while sleeping” on glymphatic processes that may offset or delay dementia (fun fact - Alzheimer’s used to be my white whale).
It also consistently affects my sleep (actigraphy & subjective feelings), so I almost never do that anyways.
I’m shooting in the dark with timing and IF in the first place - it’s weak evidence in human trials compared to say traditional Mediterranean diet (see Cochrane review) and it’s speculative. I first got the general idea from traditional Okinawans eating more earlier in the day and little towards the end (or skipping dinner) - before IF went sort of more mainstream and they seem to have better sleep. My IF 16/8 probably does not result in significant weight loss, all else equal.
I’m assuming getting to a fasted sleep state quicker is generally better. It takes ~6 hrs to digest your food but there are ways to transition slightly quicker that I do personally - i.e. light dog walks after last meal, less fat in last meal. (I don’t do intense exercise right after eating or taking things like metformin - it’s too sharp of a transition)
I occasionally shift a bit to 11am-7pm in terms of occasional (~2-3x a month) social functions where eating is involved, but otherwise consistent timing.
One of the reasons why I refrain from taking things like metformin, berberine, and/or acarbose all the time is I worry about hypoglycemic responses which can depend a lot on individuals and I don’t like relying on subjective feelings based on my experience of talking with diabetic patients who ended up with a CGM.
Review of the proposed mechanisms (I suggest reading it entirely and going through all the references):
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Thank you for taking the time to share your experience.
Both the keto diet and time-restricted feeding raise my morning blood glucose levels while lowering my HEMOGLOBIN A1c levels.
Do you think perhaps A1c level may be a better marker than fasting glucose level for those on keto or time-restricted eating protocols?
I personally use a CGM with relatively high accuracy as my primary data source for glucose changes and computation of autocorrelation functions (there are some issues, but minimized). I do take HbA1c regularly for reference and fasting glucose comes with the lab bundle.
In diabetes screening, HbA1c and fpg are both used. Fpg is not great because stress can easily throw that out of whack, so I wouldn’t rely on that over 2 hr oral glucose test.
There are pitfalls with HbA1c in various clinical scenarios (ie in my case, when I donate blood it is falsely lowered) but it’s a better index of averaged glycemic exposure since RBC live for ~120d.
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@desertshores - Charles, this is simplistic, but Dr. Fung does a good job in breaking down the studies of fasting and time restricted eating. He has benefited from the popularized fad component, but I still think has some basic values that apply. Also, Dr Longo out of USC longevity center, does a nice job of breaking down many of the studies on fasting and time restricted eating with most interesting being benefits of cancer prevention and fasting before chemo treatments to enhance normal cell protection from chemo and higher sensitivity of cancer cells to chemo. He is the inventor of the Prolon diet or fasting mimicking diet that promotes benefits of fasting without the loss in muscle mass.
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I think this belongs here: