Are there any?
Edited by EmbraceUnity, 29 June 2010 - 01:36 PM.
Posted 29 June 2010 - 01:30 PM
Edited by EmbraceUnity, 29 June 2010 - 01:36 PM.
Posted 29 June 2010 - 01:38 PM
Posted 29 June 2010 - 01:58 PM
Posted 29 June 2010 - 02:03 PM
The only one I'm aware of... it lowers testosterone levels.
Posted 29 June 2010 - 02:33 PM
The only one I'm aware of... it lowers testosterone levels.
And how exactly is this a health risk?
Posted 29 June 2010 - 02:40 PM
The only one I'm aware of... it lowers testosterone levels.
And how exactly is this a health risk?
Low Serum Testosterone and Mortality in Older Men
Results: During an average 11.8-yr follow-up, 538 deaths occurred. Men whose total testosterone levels were in the lowest quartile (<241 ng/dl) were 40% [hazards ratio (HR) 1.40; 95% confidence interval (CI) 1.14–1.71] more likely to die than those with higher levels, independent of age, adiposity, and lifestyle.
Posted 29 June 2010 - 02:53 PM
It could go either way, but without knowing which, it is definitely a health risk to take a drug known to lower testosterone levels.But is the higher mortality due to low testosterone levels or do low testosterone levels indicate bad overall health?Low Serum Testosterone and Mortality in Older Men
Results: During an average 11.8-yr follow-up, 538 deaths occurred. Men whose total testosterone levels were in the lowest quartile (<241 ng/dl) were 40% [hazards ratio (HR) 1.40; 95% confidence interval (CI) 1.14–1.71] more likely to die than those with higher levels, independent of age, adiposity, and lifestyle.
Edited by Michael, 18 June 2011 - 05:21 PM.
trim quotes
Posted 29 June 2010 - 04:22 PM
Posted 29 June 2010 - 05:25 PM
Yes, search the forums. Metformin without insulin potentially creates beta amyloid plaque! Be careful!
Posted 29 June 2010 - 05:29 PM
Yes, search the forums. Metformin without insulin potentially creates beta amyloid plaque! Be careful!
300 mg/kg/day was used in that study I believe.
A 76kg male would have to take 22.8 grams of Metformin to meet dosage in the study. That is a far cry above the 1.5g or so that seems to be the normal clinical dose.
Posted 29 June 2010 - 05:31 PM
Posted 29 June 2010 - 05:33 PM
This threw the whole study off for me. They are comparing brain levels of metformin in the mice to serum levels in humans. To me this is a rather large flaw in logic.
Posted 29 June 2010 - 05:35 PM
Edited by mikeinnaples, 29 June 2010 - 05:39 PM.
Posted 29 June 2010 - 05:37 PM
Posted 29 June 2010 - 06:32 PM
Yes, search the forums. Metformin without insulin potentially creates beta amyloid plaque! Be careful!
Posted 29 June 2010 - 07:04 PM
Actually, with metabolic scaling, the dose they used could potentially mimic a ~2g human dose.
Notice I did use the word potentially. But I really don't think that kind of evidence should be discarded.
Posted 29 June 2010 - 07:06 PM
Insulin and IGF-1 speed up aging and thus I would completely advise against the idea of increasing insulin or IGF-1 to protect against the increase in Abeta by metformin.
Posted 01 July 2010 - 05:48 AM
Do we have any positive life extension studies on normal rodents by people who are good at animal husbandry? Michael's recent article doesn't list any.Thus 15mg/kg should be safe, this would mean 1050mg for a person of 70kg, which is much higher than what I would advise for life extension purposes.
I mentioned this to my fiancee, who worked as a vet tech in a university mouse facility, and she mentioned that ad libitum feeding is simply cheap and easy. It takes an animal tech a lot less time to just top off the food on a semi-regular basis. Measuring out food every day for every cage takes a lot more time and manual labor, and would thus cost a lot more. Plus that introduces the risk that someone will forget to feed the mice one day; my fiancee mentioned that this happened once every few weeks for the calorie restricted mice.
Posted 13 August 2010 - 04:28 PM
Presuming that you mean, " positive life extension studies of metformin in normal rodents by people who are good at animal husbandry", then AFAIK there are none. That was rather the point of that post .Do we have any positive life extension studies on normal rodents by people who are good at animal husbandry? Michael's recent article doesn't list any.Thus 15mg/kg should be safe, this would mean 1050mg for a person of 70kg, which is much higher than what I would advise for life extension purposes.
http://www.sens.org/...science-caf/738
That's a hell of a lot of it; even some otherwise very respectable researchers, like Christian Leeuwenburgh, generally fail on this front. The animals (especially CR animals (2)!) are also often malnourished, or they don't keep a good lid on pathogens (as in the aspartame cancer scare study, and the SkQ1 bunk (maximum LS 800 d, almost all the "life extension" from preventing death from prevalent infectious disease -- and the TREATED animals got a HIGHER incidence of mammary gland adenocarcinoma!).A common rejoinder to the good husbandry stipulation is that we might not know how to do proper human husbandry. Could it be that the secret sauce is as simple as not letting the animals eat themselves into obesity? [1]
Posted 11 December 2010 - 05:27 PM
Posted 12 December 2010 - 11:53 AM
Posted 13 December 2010 - 04:07 AM
Posted 13 December 2010 - 12:29 PM
The less man-made chems in your body the better IMO.
Posted 30 June 2017 - 03:11 PM
This is an old thread, but I was looking at the Chen paper again and some papers on metformin.
I think one of the problems with this Chen paper is the method of administration. The fact that metformin was administered on a near continuous basis through drinking water, rather than on a pulsatile manner is part of the problem with this study. I don't doubt that continuous metformin elicits beta-amyloid, but I think a pulsatile administration concurrent with a meal (and insulin release) probably wouldn't see the same effects. Any thoughts?
Also, if anyone knows how Chen gets the math from 2 mg/mL in mouse drinking water to 300 mg/kg per day (in C57/BL6 mice?), I'd love some help with the math there. I guess that translates to a HED of ~1,700 mg per day in a 70 kg adult. Seems like s123's prior comments in the thread make sense. A lower ~500 mg per day dose of metformin is probably fine.
EDIT:
This Senesi paper suggests that C57/BL6 drink 7 mL per day. Therefore, the Chen mice probably got about 14 mg of metformin throughout the day, meaning the mice must weigh about 21.4 g. That is relatively in-line with this data.
That still suggests ~1,700 per day for a 70 kg is the level on a continuous dose basis is what produced amyloid beta.
Chen, Y., Zhou, K., Wang, R., Liu, Y., Kwak, Y., & Ma, T. et al. (2009). Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proceedings Of The National Academy Of Sciences, 106(10), 3907-3912. doi:10.1073/pnas.0807991106
Senesi, P., Montesano, A., Luzi, L., Codella, R., Benedini, S., & Terruzzi, I. (2016). Metformin Treatment Prevents Sedentariness Related Damages in Mice. Journal Of Diabetes Research, 2016, 1-11. doi:10.1155/2016/8274689
Edited by prophets, 30 June 2017 - 05:37 PM.
Posted 30 June 2017 - 05:38 PM
I think one of the problems with this Chen paper is the method of administration. The fact that metformin was administered on a near continuous basis through drinking water, rather than on a pulsatile manner is part of the problem with this study. I don't doubt that continuous metformin elicits beta-amyloid, but I think a pulsatile administration concurrent with a meal (and insulin release) probably wouldn't see the same effects. Any thoughts?
Metformin is normally dosed several times a day and/or in extended-release forms, so this seems reasonable. One might expect the drug to work better the more evenly it were spread out.
Also, if anyone knows how Chen gets the math from 2 mg/mL in mouse drinking water to 300 mg/kg per day (in C57/BL6 mice?), I'd love some help with the math there. I guess that translates to a HED of ~1,700 mg per day in a 70 kg adult. Seems like s123's prior comments in the thread make sense. A lower ~500 mg per day dose of metformin is probably fine.
Ideally, they would have weighed their mice and measured their water consumption, but if that's what they did they don't seem to have documented it. However, a young C57Bl/6J mouse is typically 25 g, and per several websites mice can be expected to consume 4-5 mL water/day, so that's 320-400 mg/kg/d. The supplemental info on this study indicates that 2 mg/mL fluoxetine in the drinking water yielded ~300 mg/kg/day. This PowerPoint of studies on antibiotics gives doses like Enrofloxacin or Amoxicillin 50 mg/kg/day = 0.25 mg/mL and Doxycycline 10 mg/kg/day = 0.05 mg/mL, any of which would mean 2 mg/mL = 400 mg/kg/day.This study of relatively small numbers of mice aged 65-74 days reports 25 g mice consumed 6.2 mL/d.
Posted 30 June 2017 - 05:48 PM
Metformin is normally dosed several times a day and/or in extended-release forms, so this seems reasonable. One might expect the drug to work better the more evenly it were spread out.
Also, if anyone knows how Chen gets the math from 2 mg/mL in mouse drinking water to 300 mg/kg per day (in C57/BL6 mice?), I'd love some help with the math there. I guess that translates to a HED of ~1,700 mg per day in a 70 kg adult. Seems like s123's prior comments in the thread make sense. A lower ~500 mg per day dose of metformin is probably fine.
Ideally, they would have weighed their mice and measured their water consumption, but if that's what they did they don't seem to have documented it. However, a young C57Bl/6J mouse is typically 25 g, and per several websites mice can be expected to consume 4-5 mL water/day, so that's 320-400 mg/kg/d. The supplemental info on this study indicates that 2 mg/mL fluoxetine in the drinking water yielded ~300 mg/kg/day. This PowerPoint of studies on antibiotics gives doses like Enrofloxacin or Amoxicillin 50 mg/kg/day = 0.25 mg/mL and Doxycycline 10 mg/kg/day = 0.05 mg/mL, any of which would mean 2 mg/mL = 400 mg/kg/day.This study of relatively small numbers of mice aged 65-74 days reports 25 g mice consumed 6.2 mL/d.
Thx Michael. Insightful, as always.
It just seems to me like the issue with AMPK activators is the dose/duration makes the poison. A pulsatile release or very low dose, extended/continuous dose seems to be the only plausible route with Metformin. In agreement with others in the thread, the ~1700 mg dose seems high to me, compared to what a preventive, life extension dose might be.
Thx again.
Posted 30 June 2017 - 07:09 PM
In agreement with others in the thread, the ~1700 mg dose seems high to me, compared to what a preventive, life extension dose might be.
Thx again.
Metformin does not extend lifespan in normal, otherwise-healthy (but aging) mammals.
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