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Metformin vs. Acarbose for weight loss and/or life/healthspan in non diabetics.

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#1 YOLF

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Posted 29 November 2017 - 04:44 AM


Both Acarbose and Metformin are pretty impressive for their systemic effects. Here's a rundown of what caught my eye:

 

Metformin

  1. Systemically decreases insulin resistance leading to faster metabolism.
  2. Decreases glucose output from the liver
  3. Various health and lifespan trials indicate that it has health/lifespan benefits related to calorie restriction mimetics.
  4. Can be used as a weight loss drug (though it is gained back after stopping), it does this presumably by 1 and 2.
  5. Decreases hunger

 

Acarbose

  1. Increase in FGF23 levels (increases life/healthspan and turns over the ECM), very impressive as klotho is the receptor for FGFs.
  2. Increases klotho levels (increases life/healthspan)
  3. Acts in the GI tract to delay carb digestion

 

So both of these are metabolized differently, but can I take them both? How much metformin do I need to get the metabolic benefits of 1, and the hunger benefits of 5 on the metformin list? Are 1 and 2 in the Acarbose list secondary to the effect on carbohydrate digestion in the gut? How far can I lower my blood glucose for weight loss before it causes a problem?



#2 Pizzarulzz

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Posted 29 November 2017 - 12:46 PM

I have been looking for this thread, glad you asked this question also you need dosasge too, metformin killed my libido btw :(

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#3 YOLF

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Posted 30 November 2017 - 03:46 AM

Metformin raises estrogen apparently. If you're fat, you could take it with a mild aromatase inhibitor such as resveratrol and that should counterbalance the effects and leave you with only slightly higher estrogen thsn you should have, which would be slightly good for most men who don't have chronic low T. IIRC, the increase of E is about 200 points on the scale that goes up to 1150 for 20-40 year olds oslt. 

 

I've seen people talk about using metformin to get pregnant too, but I'm not sure if the effects are from raising GnRH or converting T precursors to E. If it raises GnRH, it could potentially be elevating your T to a point where your libido declines from T that is too high. I imagine there is a limit to how much GnRH and it's constituents, FSH and LSH can make T, in which case you could have other androgens or estrogens  outcompeting your T. 

 

In any case, at least one signalling hormone for GnRH is estradiol iirc which would be raised in the event of higher estrogen. So metformin will actually upregulate your T when you come off it or if you take it on and off if it doesn't get so high as to castrate you which appears not to be the case.

 

Did your libido self correct when you went off of it?



#4 YOLF

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Posted 30 November 2017 - 03:51 AM

Also, are there colors in your metformin or is it a white tablet? Some yellows and reds (they have different names in the US and India for the same thing, so I won't say which ones as I don't know all of the things all of these foreign countries call these colors) can lead to liver dysfunction that devastate your sex hormones and neurosteroids depending on what your genetics are.  They used to be a tiny minority in the US, but it's a very fast growing demographic here and our FDA GRAS colors are becoming a much bigger problem as of late. As it relates to intelligence, I imagine it's a growing minority in any developing or developed country.


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#5 Pizzarulzz

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Posted 30 November 2017 - 07:05 AM

It is complete white metformin which is simple 500 MG METFORMIN in past time i had also chronic porn thing it is also might be cause. I did then started a healthy diet full of zinc and green veggies and it took two month to get morning wood, i rarely take metformim from that time

#6 recon

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Posted 05 December 2017 - 05:50 PM

I plan to add acarbose due to the klotho effects. Anyone healthy added it to their stacks yet?

#7 Michael

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Posted 11 December 2017 - 04:16 AM

Acarbose has been shown several times to extend maximum lifespan in normal, otherwise-healthy, nonobese aging male (but not female) mice; metformin has repeatedly failed to do so.



#8 YOLF

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Posted 12 December 2017 - 06:05 PM

Does klotho make it harder to lose or maintain lower weight? It does make cells more resilient, but I don't think turnover would lead to higher obesity, if anything, in normal cells it would improve metabolism and raise calorie burning. I guess it's a none issue as it should lead to being able to lose weight easier. 

 

Hasn't metformin increased lifespan in humans though? Or just average lifespan in diabetic humans? Slightly low blood glucose does improve the appearance of skin and slow the accumulation of visible aging, in synergy with other vectors it can make the benefits permanent. Diabetics still die in their 60s, even taking metformin in my personal observation... still as a CR mimetic, it's going to be better for health and youthspan in non diabetics and improve the efficacy of other interventions.



#9 Pizzarulzz

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Posted 17 December 2017 - 01:59 AM

Diabetics are dying in their 60s because even after taking metformin their diets are still the same, no fasting, no excercise no low inflammation, I mean how can a drug which is just CR mimitic can ressolve the issues which accumulated in last 50 years

#10 YOLF

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Posted 18 December 2017 - 12:30 AM

Diabetics are dying in their 60s because even after taking metformin their diets are still the same, no fasting, no excercise no low inflammation, I mean how can a drug which is just CR mimitic can ressolve the issues which accumulated in last 50 years

 

There is plenty of proof in the FTO disorder genes that only 12% (Yes 84-88% of those tested from general populations suffer from a genetic FTO disorder) can be expected to lose weight no matter what they do. Everyone else is too good at storing and making fat for hard times. Gene therapy is the only way forward... these people aren't going to get more free time for doing loads of high intensity cardio... They just exchange their youth for being old.



#11 Michael

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Posted 27 December 2017 - 11:46 PM

Hasn't metformin increased lifespan in humans though? Or just average lifespan in diabetic humans?


DING-DING-DING-DING-DING!
 

Slightly low blood glucose does improve the appearance of skin and slow the accumulation of visible aging, in synergy with other vectors it can make the benefits permanent. Diabetics still die in their 60s, even taking metformin in my personal observation... still as a CR mimetic, it's going to be better for health and youthspan in non diabetics and improve the efficacy of other interventions.


It's not a CR-mimetic: that's a mechanistic hypothesis refuted by the lifespan studies and human data — see studies cited in the post I linked. It's also not known that metformin will give low-normal glucose levels to a normoglycemic person (as opposed to give (more) normal levels in an hyperglycemic person) — and even if it did, it's also not clear that low-normal (as opposed to normal) blood glucose is even good for you: see here, and also look through (1-9), which shows you that 
the HbA1C-mortality association data are really all over the map: everything from J-shaped curves with a mortality "sweet spot" around HbA1c 5.3 (like (1,8,9)), to mortality curves that are flat up to and including 5.0 and then rise steadily above that point, to classic, continuous relationships across the board. I haven't yet seen any serious effort to reconcile these disparate findings, but we certainly can't say at this point that truly low glucose levels are good for one.
 
References
1: Aggarwal V, Schneider AL, Selvin E. Low hemoglobin A(1c) in nondiabetic adults: an elevated risk state? Diabetes Care. 2012 Oct;35(10):2055-60. Epub 2012 Aug 1. PMID: 22855733

2: Eskesen K, Jensen MT, Galatius S, Vestergaard H, Hildebrandt P, Marott JL, Jensen JS. Glycated haemoglobin and the risk of cardiovascular disease, diabetes and all-cause mortality in the Copenhagen City Heart Study. J Intern Med. 2013 Jan;273(1):94-101. doi: 10.1111/j.1365-2796.2012.02594.x. Epub 2012 Nov 1. PubMed PMID: 23009556.

3. Barr EL, Boyko EJ, Zimmet PZ, Wolfe R, Tonkin AM, Shaw JE. Continuous relationships between non-diabetic hyperglycaemia and both cardiovascular disease and all-cause mortality: the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study. Diabetologia. 2009 Mar;52(3):415-24. doi: 10.1007/s00125-008-1246-y. Epub 2009 Jan 8. PubMed PMID: 19130039.

4: Brewer N, Wright CS, Travier N, Cunningham CW, Hornell J, Pearce N, Jeffreys M. A New Zealand linkage study examining the associations between A1C concentration and mortality. Diabetes Care. 2008 Jun;31(6):1144-9. doi: 10.2337/dc07-2374. Epub 2008 Feb 25. PubMed PMID: 18299440.

5: Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N. Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med. 2004 Sep 21;141(6):413-20. PubMed PMID: 15381514.

6: Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, Coresh J, Brancati FL. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010 Mar 4;362(9):800-11. doi: 10.1056/NEJMoa0908359. PubMed PMID: 20200384; PubMed Central PMCID: PMC2872990.

7. Chonchol M, Katz R, Fried LF, Sarnak MJ, Siscovick DS, Newman AB, Strotmeyer ES, Bertoni A, Shlipak MG. Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly. Nutr Metab Cardiovasc Dis. 2010 Jan;20(1):15-21. doi: 10.1016/j.numecd.2009.02.007. Epub 2009 Apr 11. PubMed PMID: 19364638; PubMed Central PMCID: PMC2888268.

8: Paprott R, Schaffrath Rosario A, Busch MA, Du Y, Thiele S, Scheidt-Nave C, Heidemann C. Association between hemoglobin A1c and all-cause mortality: results of the mortality follow-up of the German National Health Interview and Examination Survey 1998. Diabetes Care. 2015 Feb;38(2):249-56. doi: 10.2337/dc14-1787. Epub 2014 Nov 20. PubMed PMID: 25414153.

9: Carson AP, Fox CS, McGuire DK, Levitan EB, Laclaustra M, Mann DM, Muntner P. Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes. Circ Cardiovasc Qual Outcomes. 2010 Nov;3(6):661-7. doi: 10.1161/CIRCOUTCOMES.110.957936. Epub 2010 Oct 5. PubMed PMID: 20923991; PubMed Central PMCID: PMC4734630.


Edited by Michael, 27 December 2017 - 11:48 PM.

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#12 YOLF

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Posted 28 December 2017 - 12:47 AM

Well, hypoglycemics always look young to me. Calorie restriction also apparently looks to keep one younger or healthier looking. Ideally I suppose that one's affinity for weight loss according to FTO gene status be used to decide whether lowering blood glucose and carbs or fats is best. I'll hypothesize that the variance in FTO genes for better weight loss with low carbs vs. low lipids could yield the answer you're looking for. A good FTO stack is also lifespan extending. If someone who loses more weight on a low carb diet takes metformin they will likely loose weight, look better and live longer, if you lose more weight on a low fat diet, you wouldn't see the benefits of metformin as readily or might have to adjust your regimen appropriately. I suppose lipid lowering drugs might also be found to increase lifespan in some populations. The only ones I'm aware of however are statins... I've heard bad things, but maybe it wouldn't be so bad...



#13 StanG

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Posted 08 January 2018 - 08:50 PM

I just learned about this from a mention in the current "Fight Aging" newsletter. I'm surprised more people haven't contributed here. I know that Met hasn't lowered my desire or ability when it comes to sex and I'm 74 (just a fact - not a brag) but individual variability is such that I guess anything is possible. I'd love to have a reason to take it but i will wait for others to contribute first.



#14 Heisok

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Posted 08 January 2018 - 10:17 PM

I read at least 1 post recently where a member commented about Magnesium deficiency related to taking Metformin. I set the idea aside to research more. I can not comment whether this is significant. Yolf, I wonder if the fertility which you mention is related to PCOS patients receiving Metformin. I will say that it is best to test B12 at some point. I know of one person who was on Metformin, and ended up deficient in B12. I have taken around 300-600 mcg of B12 for many years. Both times I had mine tested I was around 1,000 pg/mL which is well above the minimum set by the labs "standard" range.

 

 

Here is a study which I noticed about Magnesium:

 

"We studied 940 non-insulin-treated patients (mean±SD age 63.4±11.6 years, 49.0% males) from the longitudinal observational Fremantle Diabetes Study Phase I (FDS1) who were followed for 12.3±5.3 years. Baseline serum magnesium was measured using stored sera. Multivariate methods were used to determine associates of prevalent and incident coronary heart disease (CHD) and cerebrovascular disease (CVD) as ascertained from self-report and linked morbidity/mortality databases. 19% of patients were hypomagnesemic (serum magnesium <0.70 mmol/L). Patients on metformin, alone or combined with a sulfonylurea, had lower serum magnesium concentrations than those on diet alone (P<0.05). There were no independent associations between serum magnesium or metformin therapy and either CHD or CVD at baseline. Incident CVD, but not CHD, was independently and inversely associated with serum magnesium (hazard ratio (95% CI) 0.28 (0.11–0.74); P = 0.010), but metformin therapy was not a significant variable in these models."

 

"The Relationship between Hypomagnesemia, Metformin Therapy and Cardiovascular Disease Complicating Type 2 Diabetes: The Fremantle Diabetes Study"

Peters, Davis et al.

https://www.ncbi.nlm...les/PMC3760872/

 

 

"The most common medication used in women with PCOS is the insulin-sensitizer metformin. Research is strongly showing that long-term use of metformin and at high doses (1.5mg or higher daily) can deplete levels of vitamin B12. A deficiency of vitamin B12 can cause permanent neurological and nerve damage as well as mood changes and decreased energy. Here’s what you need to know to avoid a vitamin B12 deficiency if you take metformin."

 

B12:

http://www.pcosnutri...com/vitaminb12/

 

 


Edited by Heisok, 08 January 2018 - 10:19 PM.


#15 recon

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Posted 09 January 2018 - 06:15 AM

Isn’t acarbose meant to stop starch digestion? I was told that it was to be taken alongside carb meals to do just that.

I wonder does the aforementioned benefits of acarbose still occur with an already low carb meal.

#16 YOLF

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Posted 11 January 2018 - 07:19 PM

Isn’t acarbose meant to stop starch digestion? I was told that it was to be taken alongside carb meals to do just that.

I wonder does the aforementioned benefits of acarbose still occur with an already low carb meal.

The MoA is to delay starch digestion until the late GI tract and only 2% is recovered from urine. That doesn't mean it has zero internal effects, it could have synergies or be very volatile internally. Has acarbose been complexed as something more bioavailable? Otherwise, the only way to find out is conjugate it to something like acetic acid or some other readily bioavailable thing and see what happens in rodents.



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#17 YOLF

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Posted 18 April 2018 - 03:05 AM

Well, mild hypoglycemia induced by metformin seems to be great for complexion in my experience. I suppose all of us have cells that don't handle glucose metabolism well and can be improved. It works especially well for maintaining youthful complexion with calorie restriction and without, though less so without and better than CR alone. CR and metformin it's very difficult to maintain, you will get hungrier than with CR alone, I found myself having binge rebounds. I can't say that the decreased appetite lasts very long, and so it may not be the best solution for weight loss, though nothing seems to do that trick consistently other than amphetamine based weight loss drugs such as phentermine which may have some safety concerns. Adderall, Dexedrine, and Vyvanse sound like much safer options if they achieve the same results. Haven't tried.

 

Acarbose... Tried it for a while also... if you're not going to eliminate carbs, I don't think it's worth it, the changes to the microbiome are less than favorable and may have even raised inflammation. I was in pretty good shape prior to taking it, but pain and inflammation symptoms have accompanied intestinal changes. I wouldn't recommend it for weight loss and overall appearance declined or got tougher to maintain. I should be able to restore my microbiome on my own, I've done it several times already.

 

Deprenyl on the other hand could be very good. I've tried it for a few days at a time so far and it certainly gives me much more youthful physical and cognitive performance. It will very likely become a staple in my regimen.

 

All in all, I'm ready to be a guinea pig for weight loss/skinny gene, gene therapy, the rest of this is complicated and gene limited to begin with... though I do have hopes for deprenyl and menatetrenone is looking like a non-serotonergic appetite suppressant. Might give statins with tons of CoQ10 a try next.


Edited by YOLF, 18 April 2018 - 03:28 AM.

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