#103

Don’t forget all the other medical problems most smokers end up with later in life. Smoking is bad on your bones. Smoking means a higher risk of Cancer and other diseases. Thats why theres a warning on the packages.

#104

I was a welder for 19 years. During the time I was working as a welder, we had 7 employees die. All had one thing in common. they all smoked. Thats a big percentage since the most ever working in the plant at any time was 26 employees and a manager and co manager.

1 Like
#105

I’d like to see ITP test Rapa + Canagliflozin

3 Likes
#106

The only supplement I have seen him “promote” are the one he takes and is not compensated for other than a company that has contributed to his research fund. Which at the rate he is raising money he will never start it. As for returning the funds? Good question. I do not question his deep dive into research papers. As for David Sinclair, as much as DS deserves all the recognition he gets, Dr Brad did give him a black eye over the issue of supplement company that DS built to sell a resveratrol supplement and sold it for over $300m that was based on faulty data. We all make mistakes. dah.

1 Like
#107

Metformin greatly reduces chances of developing long COVID from a new study.

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#108

Hi, Appreciate your posts. I am a Java programmer working for a large US Bank and would be willing to donate some of my time to assist in helping with any website work, if that is of use. Although these days programmers are mostly commoditized. LOL.

1 Like
#109

Just saw this:

Association between oral metformin use and the risk of age-related macular degeneration: A systematic review with meta-analysis

Rodent studies demonstrate that oral metformin use may reduce chronic low-grade inflammation, downregulate apoptosis and extend life span. Emerging epidemiological evidence suggests that oral metformin use may protect against development of age-related macular degeneration (AMD) in humans. In this study, we systematically reviewed the literature on the association between oral metformin use and AMD in patients with type 2 diabetes and conducted a quantitative meta-analysis to provide a summary estimate of the association. We searched 12 literature databases on 10 August 2022 and identified nine eligible studies with data on a total of 1 427 074 individuals with diabetes. We found that patients with diabetes using metformin had a significantly lower odds ratio (OR) of having or developing AMD (OR 0.63; 95% CI: 0.46–0.86; p = 0.004). Our analyses also revealed that although the findings were robust in the sensitivity analysis, the Funnel plot indicated a certain publication bias towards finding a protective effect. Results of individual studies suggested inconsistent findings, as some studies found lower risk of AMD from higher total metformin exposure, whereas other studies found a higher risk of AMD from higher total metformin exposure. Taken together, there may be a link between metformin use and lower risk of AMD, but the relationship is only studied in observational studies, various sources of bias can be speculated to influence, and careful interpretation is warranted.

https://onlinelibrary.wiley.com/doi/10.1111/aos.15655

3 Likes
#110

All the more reason for diabetics to take Metformin. I wonder if Rapamycin Diabetes counts?

1 Like
#111
2 Likes
#112

Added Metformin to my stack about two weeks ago (1,000mg extended release every night).

Just like with Rapamycin, I’m noticing no effects at all from it, good or bad. I’m starting to think my body is immune to all of this longevity stuff or something, lol.

Anyway, will keep taking it, might as well I guess.

2 Likes
#113

Hey Phil,
Might just be your age under 45 years. You are doing prevention and won’t see the improvements. It is as if you get the same day back - every day - think “Ground Hog Day” movie. .

We older guys are actually reversing functional declines, so we get back what was lost. Reverse on lost memory, reduction in stubborn fat, less inlammation and arthritis… and more.

You haven’t lost anything enough to notice it. IMHO! .

6 Likes
#114

Hey thank you for the offer! I’ll have to think about how to fit volunteers in and open to any suggestions.

IMO, programmers aren’t completely commoditized but it’s easy to feel that way with Copilot X in certain fields of programming - i.e. most front-end work seems pretty mindless and API plumbing isn’t too far off…but I’d add there are plenty of extremely highly complex tasks computationally in programming that aren’t easy to automate.

Hard to automate "knowing where to look”, asking “good” questions, and implicit knowledge etc.

4 Likes
#115

Hello all, lot of questions :slight_smile:

about this “Rapamycin Diabetes”, that metformin can help.
-Can someone share knowledge on this?
-When it happen?
-hours after intake?
-when it stops?
-Is there anyone that tested get metformin just when using rapamycin instead of every meal?

I started metformin 7 days ago, but there was so much bad changes in my body, that I’m almost certainly stopping.

Also a brief google check, on stopping metaformin, was scary to read. I couldn’t be certain if the changes in the intestine microbiome would help.

If someone has knowledge, I will appreciate

#116

Blood glucose disregulation caused by rapamycin tends to happen to people if they are dosing at higher levels, on a continual basis (i.e. daily dosing), over a longer period of time. As you can see from our survey of users - it doesn’t seem to happen very frequently with weekly dosing:

Screen Shot 2023-08-23 at 3.56.42 PM
Screen Shot 2023-08-23 at 3.56.42 PM1288×1318 81.3 KB

See full survey here: Rapamycin User Poll / Survey - Please Respond - #4 by RapAdmin
Another survey here: Rapamycin User Survey #2 - Please Respond

Some percent of people experience this type of issue (typically at moderate levels) when dosing rapamycin once per week as is typically done in longevity applications, but exactly what percent is not known - our survey suggests around 5%, but its hard to know how accurate that is. People here report it periodically, but I have not personally experienced it (Been taking rapamycin almost 4 years now).

So - you may or may not experience it, and the higher the dose, the more requently you take it, and the longer you take it for, the higher the risk.

Generally this is believed to happen because of mTORC2 inhibition - which similar to the blood glucose disregulation, only typically happens to people taking higher doses of rapamycin, frequently, over a longer period of time (e.g. weeks, or months). More reading on this issue of mTORC2 inhibition and side effects here: Evidence that mTORC2 inhibition is detrimental, by Dudley Lamming

and here: Bryan Johnson's Longevity Protocol - Your Thoughts? - #372 by RapAdmin

Some people find that Acarbose or Canagliflozin address this issue when they do experience it. You don’t have to use Metformin. Other people, if they run into this issue either decrease the frequency of dosing, or dosing level - and this reduces or eliminates the issue.

See more info here: Acarbose - Details On Another Top Anti-Aging Drug
And Here: Canagliflozina – Outro medicamento antienvelhecimento de destaque

More reading on this topic here:

While we don’t know for sure if rapamycin-induced blood glucose disregulation is harmful or not, it seems reasonable to try to avoid the situation until we know for sure.

Fasting and rapamycin: diabetes versus benevolent glucose intolerance

https://www.nature.com/articles/s41419-019-1822-8

Full paper here:

and

Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13666

4 Likes
#117

This in on my physician feed.
Metformin can deplete vitamin B-12.

Dr. Yelena Budovskaya of TruMe warned me of this 2 years ago when I told her I was taking Metformin. I never could tolerate it… so on Acarbose.

Metformin Use Tied To Increased Risk Of Vitamin B12 Deficiency, Research Suggests

HCPlive (8/24) reports, “Metformin use was associated with an increased risk of vitamin B12 deficiency,” according to an “analysis of data from more than 30,000 people with type 2 diabetes.” The study revealed that “using metformin for four or more years increased the risk of vitamin B12 deficiency by 41%, with each additional year of use increasing the risk of deficiency by 5%.” The findings were published online ahead of print in the journal Endocrine Practice.

1 Like
#118

You take Rapamycin. Then you need Metformin to deal with high blood sugar. Then you need to take B-12 to deal with depletion from Metformin.

Seems like an old nursery rhyme.

There was an old woman who swallowed a fly…

But with Rapamycin, perhaps she won’t die? :wink:

9 Likes
#119

Another Metformin benefit?

Metformin, the muscle protector?

4 Likes
#120

It’s well known it depletes VitB12 and I think some of the reported negative noise in the data when it comes to its effects might be attributable to unaddressed vit B12 depletion. Needs to be taken with a mega dose of bit B12 to not do harm.

2 Likes
#121

Good find. The open access paper is available here: https://doi.org/10.1111/acel.13936.

This study dosed metformin for two weeks. The papers that investigate metformin’s exercise-blunting effects generally dose metformin for longer (from 12 weeks to 6 months). I’m gradually gathering evidence about the effects of shorter dosing durations and hadn’t spotted this paper. Thanks!

6 Likes
#122

Maybe senescence (that metformin inhibits) is needed for adaptation to exercise? We used to take ibuprofen to reduce post exercise inflammation but later found it delayed healing. I wonder if a similar mechanism is in play here. Pattern recognition only; it’s a wild guess.