Metformin Blocks Benefits of Aerobic Exercise on Insulin Sensitivity and VO2 max

#22
I guess I just took the tone of this thread as it being a bad thing. I don’t see many downsides myself.
The tone was negative, but it's not a huge negative, limiting VO2 max, causing fatigue in some people which probably isn't noticed unless you work out with intensity.

It's really all about the anti-aging use of Metformin for people without impaired insulin control / disabilities. SHOULD healthy people take Metformin?

Clearly the benefits of Metformin for those with elevated blood glucose outweighs the problem that Metformin "inhibits mitochondrial adaptations to aerobic exercise training in older adults".

I had been taking 2x 500 ER metformin, my A1C was 5.8, in a month it went to 5.6, four days ago I measured it at 5.2. BUT I changed my diet and lost 18 lbs, so how much Met helped is debatable. It seemed to reduce my appetite for the first 20 lbs of weight loss, but now at least my appetite has returned to normal.

After the test, I quit taking Metformin, which is 4 days ago, I wanted to see how it affected my treadmill cardio and appetite control. So far my BG taken with a meter is OK, my cardio seems better. But I think the better test will be in a month to check A1C and then start Metformin again.

So I am certain with diet and exercise I can keep my A1C at 5.2, but not sure about how hard it will be to do that.

Long post, but IMO it's a little complicated.
 
#23
I’ve been on 500mg 2x day for about 3 weeks now. I’ll have to give my cardio a good test shortly here. So far I’ve not noticed a decrease but I haven’t pushed it hard either. If I sense a decrease in cardio ability I will cease use of metformin. I need my cardio at it’s absolute best for about 4 months of the year.

My a1c was 5.7 and 5.4 last 2 tests. I’ll be testing again in June. I feel leaner already but I’ve slightly cleaned up my diet. Not much though.
 
#24
1200 mg Leucine + 500 mg twice per day Metformin + probably 5 -10 mg sildenafil

I was using 500 mg twice per day of Metformin. Ordered some 25 mg viagra tablets to split them in 3. That is why I have not started. I got Leucine capsules from Amazon.
I started Met at 500mg 2x instant release about 6 weeks ago. At first it was amazing. Belly fat melted off, no bloating, I felt more relaxed and calm than normal, my flaccid hangs were bigger and relaxed, and had much improved erections (it helped more than Cialis every did and improved the effect of Cialis).

However about a week ago I started feeling super tired as well. I also got this muscle fatigue feeling, like my arms are heavy and muscles tight (maybe a little Lactic Acid?). At one point I was trying to use chopsticks and my hands were just not working well lol.

Anyways, I'm trying the EX version and just dosing 1x at night instead of the 2x per day. I'm hoping this might help as I don't want to stop. I had some fatty liver, lowish SHBG, etc., all signs of insulin resistance and metformin really helped a ton.

Anyone know if adding the leucine alleviated the fatigue? Any other things people are adding to help?
 
#26
Just an update - I lowered the dose to 500mg total per day and now have normal energy levels. I think I'm just sensitive to this drug. At 500mg a day I get the benefits but have normal levels of energy. Pretty stoked on that. I might even try taking 500mg every other day - basically taper down as much as possible while still getting the benefits.
 

dnfuss

Active Member
#28
Just an update - I lowered the dose to 500mg total per day and now have normal energy levels. I think I'm just sensitive to this drug. At 500mg a day I get the benefits but have normal levels of energy. Pretty stoked on that. I might even try taking 500mg every other day - basically taper down as much as possible while still getting the benefits.
Curious as to what are the benefits you are seeing at that dose. Is there a measurable reduction in your serum glucose levels? Most adult males see no significant reduction in blood sugar levels at metformin doses below 1,500 mg./day.
 
#30
For people who want to derive the many proven health benefits of metformin, it might be prudent to follow the dosage schedule used by Type II diabetics. According to the Physician's Desk Reference, the starting dose should be 500 mg of metformin twice a day. (An alternative option is 850 mg of metformin once a day).

After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. The maximum safe dose described in the Physician's Desk Reference is 2550 mg a day (which should be taken as 850 mg three times a day).

According to the Physician's Desk Reference, clinically significant responses in Type II diabetics are not seen at doses below 1500 mg a day of metformin. Anti-aging doctors, on the other hand, have recommended doses as low as 500 mg twice a day to healthy non-diabetics who are seeking to obtain metformin's other proven benefits such as enhancing insulin sensitivity and reducing excess levels of insulin, glucose, cholesterol and triglycerides in the blood.

It could be the dosage range is highly individualistic in healthy people, meaning some may benefit from 500 mg twice a day, while others may need 1000 mg twice a day for optimal effects. Blood tests to ascertain if the dose of metformin you are taking is improving glucose/insulin metabolism would be:

  1. Hemoglobin A1c
  2. Fasting insulin
  3. CBC/Chemistry panel that includes glucose, cholesterol
    triglycerides and indicators of liver and kidney function
A hemoglobin A1c test measures the average amount of sugar in your blood over the last 3 months. Metformin helps lower hemoglobin A1C to safe low levels (below 5-6%).

Aging and overweight people often suffer from metabolic disorders that manifest in the blood as excess serum insulin, glucose, cholesterol and triglycerides. Metformin often helps correct all of these metabolic disturbances that can lead to the development of numerous degenerative diseases. The CBC/Chemistry test provides readings on cholesterol, glucose and triglycerides and can also warn you of underlying liver-kidney impairment that would make you ineligible for metformin. The fasting insulin test indicates if metformin is adequately lowering levels of serum insulin to a safer range of below 5 (micro IU/ML).

Metformin Dosage
 
#31
I have been taking ~1000 mg of metformin ER for the last 5 months. Once in a while I take 1500 mg.
I have decided to stop taking metformin and see how it affects my cardio and blood glucose. I was able to lower my A1C from 5.8 > 5.2, but not at all sure how much the Met was responsible and how much watching diet / losing weight was responsible for better glucose control.

I would credit metformin for reducing my appetite making it easier to lose weight and it did seem to help reduce BG.

But now it seems like I can more easily control BG without metformin.

I have read lifestyle changes are even more effective than metformin for BG and anti-aging.

Partly I am just curious how not taking Metformin will work out for exercise, peak heart rate and BG. Right now it's been 13 days since I stopped metformin. BG seems OK.
 

dnfuss

Active Member
#33
I have been taking ~1000 mg of metformin ER for the last 5 months. Once in a while I take 1500 mg.
I have decided to stop taking metformin and see how it affects my cardio and blood glucose. ... Right now it's been 13 days since I stopped metformin. BG seems OK.
Have you recently measured fasting and post-prandial serum glucose levels?
 
#34
Have you recently measured fasting and post-prandial serum glucose levels?
No, I am not diabetic, but no doubt I have some sort of insulin resistance, I have never stopped testing though I think I test obsessively. I have over 700 total BG readings going back to 9/20/2018.

But you be the judge, I have copied the last the last 11 days, higher numbers are post-prandial. I made a note about the one day that I had an unusual spike to 173 and quick drop down to 78. I did a little exercise with light dumb bells to drop BG.

I usually test when I know my BG should be higher because I ate a fair number of carbs, or lower after cardio.

Though as we know, a lot of cardio on an empty stomach will cause an increase in glucose release from the liver, which I have also seen.

3/23/2019 8:52 91
3/22/2019 21:54 92
17:31 98
14:09 96
4:13 89
3/21/2019 23:15 80
23:04 80

23:03 78 Did 4 sets of dumb bell curl & press, 15 lb each)
21:44 173 (ate dinner, then ate candy after dinner so whatever for dinner + ~85 grams of carbs as hard candy)

12:28 100
7:45 96
3/20/2019 21:14 102
19:13 118
13:24 124
12:44 138
12:31 158
4:43 98
3/19/2019 20:27 90
3:35 96
19:33 116
14:12 114
3/18/2019 10:12 99
4:52 93
3/17/2019 23:23 82
17:51 88
10:47 97
7:50 115
3/16/2019 13:42 100
4:10 95
0:15 118
3/15/2019 18:36 119
17:15 88
3/14/2019 18:30 106
3/14/2019 15:05 88
8:08 95
3/13/2019 19:47 109
3/13/2019 14:56 93
11:21 102
5:08 98
2:36 99
3/12/2019 23:19 114
21:02 99
18:59 97
14:44 86
12:49 116
6:39 85
0:15 105
 

dnfuss

Active Member
#35
No, I am not diabetic, but no doubt I have some sort of insulin resistance, I have never stopped testing though I think I test obsessively. I have over 700 total BG readings going back to 9/20/2018.

But you be the judge, I have copied the last the last 11 days, higher numbers are post-prandial. I made a note about the one day that I had an unusual spike to 173 and quick drop down to 78. I did a little exercise with light dumb bells to drop BG.
I am not your doctor. Proper diagnosis would require taking a history, conducting a physical exam, and ordering and reviewing labs (including but not limited to an oral glucose tolerance test).

But since you've asked for opinions on the serum glucose levels posted, I'd say that a number of those are quite consistent with mild to moderate diabetes. The clearest example: a spike of 173 mg/dl followed by a reactive hypoglycemic rebound of 78 mg/dl. Those simply aren't normal blood sugars, nowhere near. They are demonstrative of an impaired first-phase insulin response followed by an over-compensating second phase.
 
#36
Are you diabetic? If so, are your blood sugar levels consistently within the parameters for those without diabetes?
6 years ago I was pre diabetic that was the main reason for starting with Metformin. I´am not pre diabetic anymore but keep taking them for preventive and for other health purposes
 
#37
I am not your doctor. Proper diagnosis would require taking a history, conducting a physical exam, and ordering and reviewing labs (including but not limited to an oral glucose tolerance test).

The clearest example: a spike of 173 mg/dl followed by a reactive hypoglycemic rebound of 78 mg/dl. Those simply aren't normal blood sugars, nowhere near. They are demonstrative of an impaired first-phase insulin response followed by an over-compensating second phase.
Surely you aren't saying that a blood glucose level of 78 are anywhere near hypoglycemic levels?

78 BG is a fairly common and normal reading.

I used to think I would show up as pre-diabetic on an oral glucose tolerance test, but now when I look at all the data I have on my BG, I think the OGTT would indicate no problem.

Because my BG never goes above 200 and it always falls in 2 hours below 140.

I looked at how the test is interpreted: (I do notice there are multiple different OGTT tests.)

  • Normal response: A person is said to have a normal response when the two hour glucose level is less than 140 mg/dl, and all values between 0 and 2 hours are less than 200 mg/dl.
  • Impaired glucose tolerance (IGT): A person is said to have impaired glucose tolerance when the fasting plasma glucose is less than 126 mg/dl and the two hour glucose level is between 140 and 199 mg/dl. This is sometimes referred to as "prediabetes" because people with IGT have a higher risk of developing diabetes.
Oral Glucose Tolerance Test Preparation & Results

I think I do have a problem but it isn't exactly prediabetes or diabetes. I think it could lead to becoming diabetic because I don't think I should get that high a spike up, even if it isn't high enough to be classified as Impaired glucose tolerance (IGT).

But sometime in the next 3 months I will take the Glucose Tolerance Test with Insulin (8 specimens) to see what happens.
 
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dnfuss

Active Member
#38
Surely you aren't saying that a blood glucose level of 78 are anywhere near hypoglycemic levels?
Not in and of itself, if that is close to one's average fasting level. But this is far below the other fasting levels, which are generally well into the 90s (concerning in and of itself), and only appeared after a huge upward spike. It's what is referred to as "reactive hypoglycemia" and is often seen in Type 2 diabetics who have an impaired first-phase insulin response. The underperforming pancreatic beta cells then try their best to address this with an over-compensating second-phase response.

I used to think I would show up as pre-diabetic on an oral glucose tolerance test, but now when I look at all the data I have on my BG, I think the OGTT would indicate no problem.
Post-prandial response is not the same thing as the response to OGTT. Good possibility there would be a much stronger response to an actual OGTT. And the numbers cited for OGTT are what the ADA uses as diagnostic criteria. They also say fasting glucose levels of 100-124 are not diabetic. Many knowledgeable clinicians would say those guidelines wildly underdiagnose diabetes.

Because my BG never goes above 200 and it always falls in 2 hours below 140.
In someone with truly normal blood sugars the highest reading after meals is generally not much over 100 mg/dl and almost never over 120.

But sometime in the next 3 months I will take the Glucose Tolerance Test with Insulin (8 specimens) to see what happens.
Good luck.
 
#39
I was going to try CoffeeGenic® Green Coffee Extract, 400 mg, which has chlorogenic acid 200 mg.

Chlorogenic acid inhibits the glucose-6-phosphatase enzyme that stimulates glycogenolysis and gluconeogenesis.

In people as they age, balancing mechanism of your liver's glycogenolysis and gluconeogenesis may become impaired. Normally the liver would not release glucose after a meal, but as you age sometimes your liver can dump glucose in response to a heavy meal.

At the core of pathologic glycogenolysis (release of stored blood sugar) and gluconeogenesis (synthesis of new sugar) is the enzyme glucose-6-phosphatase. Heavy meals can activate this enzyme, which in turn tells your liver to release its sugar stores and helps it to make more sugar, despite the flood of glucose from the meal you just finished.

LEF had an interesting article on this.

Suppress Blood Sugar Surges | Life Extension Magazine

Not sure this supplement (chlorogenic acid) will work, and I suspect I will resume taking metformin, but if this works it might be good to take them both.

I have felt for a long time that a heavy meal affects me more than most people.
 

dnfuss

Active Member
#40
Glycogenolysis and gluconeogenesis occur frequently in everyone in response to many common stimuli (awakening, exercise, adrenaline release, etc.). In those with truly normal blood sugars, the body's homeostasis mechanisms produce the correct release of endogenous insulin to precisely control serum glucose levels in response (and in response to ingestion of carbohydrates). That normal response is what's impaired in diabetes.

There are no magic answers. There are no OTC supplements proven effective at controlling abnormal blood sugars. Abnormally high blood sugar levels following meals are generally indicative of diabetes, at least the early stages of such, and should be treated accordingly.
 
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