#62

The major issue with diabetes is micro vascular end organ damage to vessels, kidneys, retina, and neurons. But even in diabetics, the incidence of retinopathy and nephropathy is virtually nil under an A1C of 7. There would appear to be no risk of microvascular complications at A1C of 5.6 to 6.
Two thirds of prediabetics don’t develop diabetes.
As regards to metformin, there’s always some risk with any drug. I find a significant decrease in my stamina with it. You had hypoglycemia. Is there a proven longevity benefit?
In my 20’s I’d play tennis in the day and martial arts at night. My A1C was 5.9. I didn’t develop diabetes or any end organ damage whatsoever.

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#63

I personnaly order directly on Alibaba (not to confuse with Aliexpress). The downside is that you need to commit to a relatively big quantity. A least 0,5 kg.

#64

I try to avoid calories that where not produced in North America for environmental reasons. Also avoir dairy (butter) for the same reason. That’s why I choose peanut oil over olive oil even if olive oil has a better fatty acid profile.

#65

Alexchamp,

Just curious, why do you feel the need to take Rapamycin at such a young age? Again, just curious.

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#66

Same reason I invest money every month instead of switching car every year :wink:

Trying to build my future in the best way I can. 200 CAD a year for Rapa seems like a good return on investment.

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#67

Terri, see here: The Case for Starting Rapamycin Earlier in Life (e.g. late 20s) vs middle age (e.g. 50s)

#68

I agree with this. I wish I had started all my interventions decades ago.

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#69

Interesting! What about pre-diabetic associated issues - Metabolic Syndrome and PCOS?

#70

As I have posted before, metformin has other uses other than its antihyperglycemic effects,

Metformin Beyond Diabetes: Pleiotropic Benefits of Metformin in Attenuation of Atherosclerosis

Figure 8. Schematic proposed model for the mechanisms underlying vasculoprotective roles of metformin. By disrupting AT1R, metformin can attenuate many of the pathways that can lead to atherosclerosis, including the ones that can be triggered by HFD, and result in worsening vascular senescence. Moreover, perhaps through its effect on activation of AMPK, metformin can lead to weight loss by switching cells from an anabolic state to a catabolic energy consuming state. Also, some of the vasculoprotective effects of metformin can be through its effect on upregulation of SOD1, an antioxidant enzyme. (Dotted lines indicate the possibility of mediators for the presented effects of metformin.) AMPK indicates AMP kinase; AT1R, angiotensin II type 1 receptor; HFD, high‐fat diet; SOD1, superoxide dismutase‐1.

Benefits of Metformin in Attenuating the Hallmarks of Aging

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"Recently, metformin’s extraordinary ability as a gerotherapeutic is estab-

lished through several experimental, clinical, and observational

evidence (Novelle et al. 2016; Piskovatska et al., 2019; Gloss-

mann and Lutz, 2019; Soukas et al., 2019). Moreover, in older

human adults, we recently demonstrated metformin’s efficacy

in targeting multiple age-associated metabolic and non-meta-

bolic pathways and reverting derangements, using cardiometa-

bolic and transcriptomic outcomes (Kulkarni et al., 2018).

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#71

Yeah, it seems to help in mice and diabetic humans. No evidence of life extension. Some definite evidence of deleterious effects on mitochondria. Can reduce exercise tolerance.

When they say that it’s an extraordinary geroprotector, that seems a bit exaggerated.

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#72

Certainly diabetes itself is a part of metabolic syndrome. Obesity and genetics are more causal than pre diabetes.

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#73

As I also said before, I am not recommending it to anyone else.

I will continue to take it. At 81yo, I can tell you there aren’t any 81-year-olds at the gym or among my acquaintances that look younger than I do. Also, I have no current health issues, nada. (except for the effects of occasional overdosing with rapamycin: grin:)
My blood pressure and glucose levels are below normal for my age. Yes, I know, n=1, subjects. Since I have been taking metformin for decades now, I cannot discount it as a significant contributing factor.

It seems odd to me that you aren’t criticizing, mouse, rat, or cellular studies when it comes to rapamycin, but are quick to discount these types of studies when it comes to metformin.

This is fact, not supposition:
“Metformin also inhibits vascular inflammation that can lead to plaque formation by blockading the phosphatidylinositol 3′-kinase (PI3K)-protein kinase B (Akt) pathway and its downstream NF-κB pathway.2”

“Metformin’s protective effects have been confirmed in both animal and human studies.”

“The risk of fatal cancer development increases exponentially with age, and around 60% of cancers are diagnosed in people aged 65 or older. Activation of oncogenes and shutdowns of tumor suppressor genes result in reprogrammed energy metabolism and uncontrolled cell proliferation.37 Multiple studies have shown metformin to be effective against various cancers, including lung, breast, and colorectal cancer.38 Metformin delayed the first tumor onset by 22% and 25% respectively in female mice at the age of 3 and 9 months”

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https://onlinelibrary.wiley.com/doi/full/10.1002/agm2.12135

IMO, many more reasons to take metformin than not.

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#74

I’m not really critical of the drug itself and I’m glad that it helps you. It also may have benefits outside of its blood glucose lowering effects. It does seem to reduce cancer incidence especially in diabetics, though that might be secondary in part to its mTOR inhibition.

My biggest complaint is that I’m positive through multiple attempts at using it that it impairs my exercise tolerance, and the mechanism may be through some degree of mitochondrial dysfunction.

If it helps you then absolutely continue it. I am , however, very skeptical that it has life extending abilities anywhere near rapamycin.

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#75

“I am, however, very skeptical that it has life-extending abilities anywhere near rapamycin.”

I agree, melatonin and metformin were my life-extending supplements before I ever heard of rapamycin.
I have been going to the gym for the last 15+ years and have read that it might inhibit muscle growth or make some people tire more quickly at the gym. So, I tried cycling metformin to avoid taking it on days when I was going to the gym, and didn’t feel any different. You are most probably a hard exerciser compared to me.

#76

I’ll be honest, I really wanted to take metformin. I tried it on 3 separate occasions. I swim in the summer and hike in the winter and I’d really feel the negative effects in the winter when I’d hike uphill at a fast clip. Just couldn’t do it. Like someone pulled the plug.
The odd thing is, it took about 2-4 weeks for the effect to set in, but it resolved in just days after stopping it. It happened every time.

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#77

I’ll tell you something else desertshores , I’d be very happy to be anywhere near your overall health and condition when, and if, I hit 81.

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#78

For me to gain muscle back then - was slightly >4,000/day for calorie surplus. Really depends on tested RMR * activity factor, then a separate calibration factor. Never went past 14% body fat and one can do a mild calorie deficit at ~3,000/day at those stats down

#79

You are certainly on the right track at an earlier age than I was.

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#80

I am 79 and just started rapa 3 months ago. Not sure I feel any difference so far. I have been taking 500 mg of Metformin for 20
years just to keep my high glucose around 90 to 100 range. Previous
blood tests were always around 123. I spoke to my POP about my high glucose and said “it is not that bad yet, let’s keep a eye on it”. I had a coworker that was diabetic that had to have his lower leg removed. I was not going to “keep a eye on it”. Started low carb diet, will admit my diet at the time was not the best.
I searched and found I could get Metformin from New Zealand.
An after thought, my A1c was always just in range but to high side,
and taking 5mg rapa with GFJ and EVOO.

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#81

Not early enough. I’m not sure what the ideal age is to start rapamycin but I would think around 50, but it might be sooner.