#22

I think the issue about glucose is that at higher glucose levels the mitochondria produce more ROS. It appears the first threshold is 8mmol/144mg as this is the polyol pathway threshold. That may exist in an attempt to protect the mitochondria from even higher glucose concentrations.

With more ROS you get more mtDNA damage and less efficient mitochondria.

I am not taking either metformin or acarbose although I do take berberine, but mainly because it is an HDAC inhibitor. Over the past two years it appears I have improved my glucose handling so it normally stays below 8mmol/l apart from when I eat a packet of crisps. Hence I don’t think I will look at this as an option today.

I will, however, continue intermittently using a CGM to see where I am at. If I found I was as I was about 2 years ago then this is an option to consider. However, I think fixing the glucose handling is better than just trying to suppress it.

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#23

Where I subtly disagree with this is that I think the issue with high concentrations of glucose is that the proportion of metabolism that goes wrong is higher. If mitochondria are rapidly producing ATP, but efficiently such as in bats wing muscles then little harm is done as the proportion of ROS is handled by endogenous anti-oxidants (mainly melatonin).

#24

Thank you for that. I understand those points. My diet is whole-food, plant-based, which theoretically provides me with a good amount of SCFAs. My blood markers are very good, so would it be beneficial for me to aim for an HbA1c close to 4%? We don’t have data to support that. Maybe it would be, but what are the trade-offs? Similarly, my insulin is low (a “Longevity” doctor once prescribed insulin because it was considered too low, but I never took it). Do you have any suggestions for proven biomarkers that would be useful to track?

Thank you!

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#25

Agreed. If you are metabolic heathland a physically active person, you should be able to handle this.
Exercises also produce a lot of ROS, but we know that it has a net positive effect on the total.

#26

We are all different, especially our gut.
I was referring to rice milk, since I have a whole food plant-based diet.
You can retest also at different times of the day to see the effects. Do you feel anything more?

#27

pmol/L NOT μU/mL. So it’s about 2.3 μU/mL

#28

its 16 pmol/L, the reference here is 18,0 to 173,0
my Homa IR is 0.5

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#29

How did you accomplish this? Was it more than your citrate protocol? Melatonin? HDAC inhibitors? Losing weight? Better sleep?

Losing weight had to help clear the ectopic fat from your muscles and pancreas and liver.

#30

I had lost most of my weight before the first glucose measurement. I cannot guarantee what aspect of my broader protocol caused this improvement as it is a mixture of things, but I think it started with the citrate.

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#31

Cow’s milk has a significant amount of sugar (lactose). Like human breastmilk.

#32

DrFraser, what dose of Acarbose do you take?

#33

I take 50 mg with my 2 daily meals on the acarbose, and have had HbA1C’s 4.6-5.2% and have good insulin sensitivity.

@Thiago Great on the values, and yes, HOMA-IR of 0.5 is perfect.

I cannot make an argument for you to take Acarbose. I think it is synergistic with rapamycin, and on a risk/benefit as long as no major GI side effects, I’d still favor taking it, but not as a high priority. But if trying to push the envelope to every advantage …

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#34

Though, perhaps oddly and confined to me, drinking a glass of whole milk has very little effect on my blood glucose level.

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#35

Do you have the genes to digest lactose? If not, like me, the lactose goes to the intestine where it’s digested by the bacteria instead of being split by lactase and going into the blood so not much of a spike if any for me with milk.

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#36

This indicates you are lactose intolerant - like ~65% of adults, though it varies significantly by ethnicity

#37

Thank you DrF for the dosage info. Do you think one can have too low a fasting insulin and thus should avoid adding Acarbose to the longevity mix? I ask given my two recent fasting insulin numbers were 1.8 (3 months ago) and 1.9 (6 months ago) range: 2.6-24.9)? I do take 1500 mg of Metformin daily (split up twice into 2 daily doses) and my A1c is normally 5.0-5.1.

#38

There might be evidence that you’d want lower than your ~5% though and to consider avoiding your spikes above 140.

Here is one place to look a bit about the rationale for that:

And here he gives his view on that lower average glucose is better* and puts that in context of success with a patient who came down to 84 mg/dL and hence at or below a predicted 4.6% HbA1c:

To recap my position and interpretation of the data available (more of which you can find in the AMA 24 show notes), lower is better than higher when it comes to average glucose, glucose variability, and glucose peaks, even in nondiabetics. In other words, there’s a lot of evidence suggesting that people with glucose in the normal range can benefit from lowering their numbers.

Let me give you an anecdote, among several I could share, to demonstrate why I find CGM useful in nondiabetics. I have a patient who came to me with normal glucose tolerance by standard metrics. He began CGM and after about two weeks it revealed an average glucose of 104 mg/dL over that time. The standard deviation in his glucose readings, which is a metric of glucose variability, was 17 mg/dL. He averaged more than five events per week in which his glucose levels exceeded 140 mg/dL. All three of these metrics are considered normal by conventional standards, but does that mean there’s no room for improvement? I like to see my patients with a mean glucose below 100 mg/dL, a glucose variability below 15 mg/dL, and, as noted above, no excursions of glucose above 140 mg/dL. After about a four-week intervention that included exercise changes and nutritional modifications his average glucose fell to 84 mg/dL [~at or below 4.6 HbA1c] , his glucose variability to 13 mg/dL, and he had zero events exceeding 140 mg/dL. If he can maintain this way of living in the long-run, it’s likely to translate into an improvement in healthspan and reduce his risk of glucose impairment.

See here: Cardiovascular Health - #184 by Neo

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#39

In general, I don’t think metformin is a great longevity medication in non-diabetics, and promotes sarcopenia. I don’t think I have any non-diabetic or non-PCOS patients on this, but have a lot of patients who are non-diabetic on acarbose.

As much as agents like metformin, acarbose, GLP-1’s, and SGLT2-i individually don’t cause hypoglycemia, which is a bad thing, I think most people tolerate the last 3 in combination, even with no T2DM and without having hypoglycemia.

I’m more excited about the last 3 than metformin.

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#40

There is potentially an issue of frailty with the drugs which reduce appetite or glucose.

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#41

I don’t think we see the sarcopenia issue with acarbose, SGLT2i’s, or GLPs all of which I advocate taking if tolerated and seem safe for the individual (talk with your physician).

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