Metformin and Exercise; the Effects of Metformin in the

Archives of Health Science

Research Article

Archives of Health Science 1

Khaled Hamlaoui, Dario Furnari*

Department of Biomedical Sciences, Hospital, Netherland, Uk, Algeria

*Corresponding Author: Dario Furnari, Department of Biomedical Sciences, Hospital, Netherland, Uk, Algeria

Abstract:

Metformin is an oral antidiabetic used in the treatment of type 2 diabetes mellitus. More precisely, it belongs to the class of biguanides, Metformin is used in the treatment of type 2 diabetes mellitus both as monotherapy and in combination therapy with other oral antidiabetic agents or with insulin, when dietary interventions and exercise are not sufficient to control the disease.

When used in overweight diabetic patients, metformin also causes a decrease in the complications of diabetes and its use has been associated with stabilization and, albeit modest, loss of body weight.In type 2 diabetes mellitus (called also DM2 and in the past 'adult diabetes' or 'food') the insulin produced by the pancreas is unable to fully exert its action so that the body even produces it in excess, with the result on the one hand of making increasing weight and on the other hand progressively depleting the pancreas, is unable to meet the body's needs. It is as if the body were resisting the action of insulin. Metformin reduces insulin resistance. It is taken by mouth and is the only drug useful in all stages of type 2 diabetes. It also helps improve the balance of fats and, to a limited extent, blood pressure.

Metformin alone has important effects on blood sugar. Accompanied by physical exercise, weight loss and possibly other medications, it is often an effective therapy. It does not cause hypoglycemia, helps not to gain weight or even reduces it. The main feature of Metformin is to interact strongly with AMPK by regulating its expression. In fact, its down regulation leads to consuming ATP, synthesizing cholesterol and fatty acids and consuming glucose: a situation in which insulin levels are quite high (therefore energy abundance).On the contrary, its up regulation leads to the creation of ATP, consuming more fatty acids for energy purposes and it is a metabolic situation similar to caloric restriction in which insulin levels are kept low (therefore energy scarcity).

Metformin by upregulating AMPK has therefore shown to have a somewhat transversal therapeutic use in the treatment of metabolic dysfunctions.

Keywords: Exercise, Nutritional Biochemistry, Metformin, Body Building, Inflammation,

Skeletal Muscle

Introduction

The use of anabolic androgenic steroids (AAS) in bodybuilding became a

huge problem and risky factor that causes the death of many athletes, extreme ways are followed in bodybuilding especially during contest preparation and the goal is

Metformin and Exercise; the Effects of Metformin in

the Body Building to Minimize the Effects of the Use of

Anabolics: Case Report for a Randomized Controlled

Trial

Metformin and Exercise; the Effects of Metformin in the Body Building to Minimize the Effects of the Use of Anabolics: Case Report for a Randomized Controlled Trial


to get the perfect physique on stage, our goal is to help and save lives by providing scientific evidence to help the athletes and save their lives by preventing them the abuse of such drugs, in our case report series we used Metformin. Within the cell, Metformin inhibits the inflammatory pathway and activates AMPK (thereby increasing mTOR inhibition), while also modulating oxidative stress. These processes jointly affect inflammation, cellular survival, stress defense, autophagy, and protein synthesis. Metformin can increase insulin sensitivity and lower blood levels of insulin due to its ability to cleanse the microbiome, also inhibiting glucose formation in the liver, can also inhibit the release of pro-inflammatory cytokines, reduces or eliminates inflammatory factors. Metformin increases the formation of mucin-degrading Akkermansia miciniphila in the gut. Akkermansia muciniphila reduces inflammation, lowers insulin resistance so by this we can say simply that metformin boost the growth of good bacteria.

Metformin is effective and efficient drug for our case report series, because of the following mechanisms of action:

insulin & inflammation suppression

neuroprotection

anti-cancer agent

microbiome cleansing

Akkermansia producing

body fat burning

It is interesting to note that relatively recent studies suggest that Metformin can directly inhibit the action of leucine on mTOR. Not only would this be a bad sign for muscle growth, but the inhibitory effect of Metformin on mTOR should have a major effect as it correlates with the reduction in the risk of fatal cancers in diabetics. Interesting as postulated by Dr. Melnik of the University of Osnabrück in Germany: Metformin may be a direct competitor of leucine for the binding and activity of mTORC1. The doctor noted in his article that the usual daily dose in diabetics of Metformin (2 g) is in the range

of the 2 g of leucine derived from the daily consumption of 100 g of meat or cheese. Since the two substances are similar in structure and size, they can compete for the same sites in the activation of mTOR.

However, Metformin has these three

characteristics of relevant interest:

Schematic representation of Gluconeogenesis

1) Increases the number and sensitivity of

cell receptors for Insulin;

2) Decreases the amount of glucose / sugar

absorbed by the intestine;

3) It decreases the amount of glucose /

sugar produced by the liver (a primary

source for the production of hepatic glucose

are amino acids).

These three effects explain why

clinical administration of Metformin rarely

results in cases of greater hypoglycemic

effects when administering the drug alone.

However, when given in combination with

insulin and / or sulfonylureas (Glipizide)

injections there is a significant increase in

carbohydrate requirements and weight

gain.

The aforementioned characteristics

expressed by Metformin have meant that

this drug enters the arsenal of sports

pharmacological supplementation,

especially in Body Building.

Metformin and Body Builders

Generally Body Builders use the

effects of Metformin differently for different

phases:

1) During the Bulk phases, with the use of

exogenous insulin, 500-800mg of

Metformin 1-2 times a day increased the

effectiveness of the insulin. This was due to

an increase in the number and sensitivity of

the receptor sites. Metformin also decreases

the amount of insulin required for

maximum results.

2) During pancreatic regeneration or

protocols containing Glipizide, Glyburide or

other pancreatic stimulants / insulin,

Metformin increases its effectiveness and



amplifies the results. The common dose of

Metformin for this purpose is 500mg 2

times a day.

3) During the Cut phases, Body Builders use

Metformin as a means of decreasing the

production of glucose by the liver and the

absorption of glucose by the intestine. By

itself, this decreases the secretion of insulin

by the pancreas and increases the body's

dependence on fat stores for energy needs.

This is especially done while using GH and

PGF-2 and creates a synergistic effect with

AAS. As the cellular receptor sites for

insulin are more sensitive and since there is

cross stimulation between IGF-1 and insulin

(and their opposite receptor sites) the

retention of lean mass increases contained.

This effect favors the reduction of the

negative effects that a weight loss diet

exerts on the endogenous production of

IGF-1: if a co-administration of IGF-1 and

Metformin occurs, the advantage reflects on

the lower dose (of IGF-1) required and on

the better receptor efficiency.

It is known that during a calorie-

deficient diet the IGF-1 produced decreases,

and is one of the factors by which the stored

lean mass is reduced. If the cell sites are

more numerous and sensitive, stimulation

requires less IGF-1. Typically, 500mg of

Metformin per day is considered sufficient.

Metformin should be taken with

meals and never less than six hours before

going to bed. People with kidney problems

should not take Metformin and most

athletes should be aware that in some cases

the combination with 17-alpha-alkylated

drugs can induce even greater liver damage.

Experimental Procedure

Design, Setting, Partecipants

Methods

The purpose of this case report

series is to evaluate the potential

interaction between metformin and

exercise during contest prep in order to

help in different contest protocols to

minimize the use of extreme ways used

during preparations, and save the health of

bodybuilders.

The method used to measure

cortisol levels: The cobas e 411 fully

automated, system for immunoassay

analysis 6 bodybuilders with no chronic

disease and on very healthy diet.

Condition Intervention/treatment Contest prep : 5 weeks out

Participants:6 bodybuilders.

Age : 20 – 34 years

Drug: Metformin

Dosage : 1500mg/day (first 2 weeks)

2000mg/day (last 2 weeks)

0 mg (during peak week)

We increased the essential amino

acids intake and GH doses (for AAS users)

during the last two weeks, and every

bodybuilder ingested 7g of glutamine

during working out.

During contest prep the most

important thing is to get the best look lean

and dry BUT without putting the athlete’s

life on risk of any health issues.

The key thing of this experiment

was to not mess with minerals balance in

the body, we know certain anabolic steroids

cause minerals imbalance so we focused on

that and tried using metformin during the

prep and we collected blood samples from

the participants every week.

The other thing i focused on was

cortisol levels and inflammatory

biomarkers and metformin have a direct

anti-inflammatory action. Studies have

suggested that metformin suppresses

inflammatory response by inhibition of

nuclear factor κB (NFκB) via AMP-activated

protein kinase (AMPK)-dependent and

independent pathways.

We noticed an improve in gut health

and no digestion issue (no bloating) and

was just one case had diarhea.



Figure(1): Cortisol levels before the use of Metformin. The data were collected a week before the experiment daily.

Figure(2): Cortisol levels after the use of Metformin

Discussion

Therefore Metformin (by upregulating AMPK) implements:

- reduction of insulin secretion

-reduction of the synthesis of fatty acids and cholesterol from the two previous situations derives:

- increased lipolysis

- increased lipid oxidation, uptake of glucose and glycolysis in skeletal muscles

- increase in lipid oxidation and uptake of glucose by the heart

- inhibition of pro-inflammatory processes

- reduction of glucose absorption from the

gastrointestinal tract to about half

- inhibition of hepatic gluconeogenesis by

36%

- increase in the number and sensitivity of

insulin receptors,

- increasing the uptake of glucose on

peripheral structures

- increases lipid oxidation for energy

purposes



From the following meta-analysis it was found that metformin reduced by:

- 5.3% the BMI and triglycerides

- 4.5% fasting blood sugar

- 14.4% fasting insulin

- 5.6% LDL cholesterol

- 40% the onset of diabetes (in pre-diabetic subjects)

increasing HDL cholesterol by 5%. Therefore, metformin could also be used in dyslipidemic subjects with moderately altered LDL values, instead of using statins, and in association with repaglinide as it has shown on the one hand to increase insulin sensitivity and on the other to improve the lipid profile.

However, the mechanism by which it manages to activate AMPK is currently unclear, but other hypotheses on how Metformin can inhibit the hepatic production of glucose have been advanced. For example, it has been hypothesized that metformin may inhibit mitochondrial glycerol 3-phosphate dehydrogenase (mGPD) which would reduce the production of hepatic glucose from glycerol and lactate, but the shuttle system of glycerol phosphate is of little relevance.

hepatic unlike that of aspartate

malate, so much so that on an animal model

the destruction of the shuttle glycerol

phosphate did not alter glycaemia and it

could also be expected that gluconeogenesis

from lactate would not be affected since the

NADH produced by the conversion of

lactate pyruvate would have been

consumed by 3-phosphate glyceraldehydes

dehydrogenase during gluconeogenesis.

However, a link was found between

these two mechanisms, as it was found that

the upregulation of AMPK inhibited mGPD

in yeasts (very similar to that of humans),

this would explain the possible interaction

between the pathway that regulates mGPD

and the direct action that Metformin exerts

on AMPK.

Conclusion

Metformin one of the most studied

drugs, based on the collected data, we found

it’s suitable for our case report series,

because of its anti-aging and anti-

inflammatoryproperties, it helped the

athletes to benefit and minimize the risks,

and our main goal is to save many lives

possible.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405504/#!po=1.42857

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405504/#!po=1.42857



Something similar might be going on with metformin and exercise. ROS, cytokines, and myokines, for example, are involved in the adaptation process. If metformin is blunting these signals, it’s interfering with the adaptation. The perceived stress in the body may be artificially attenuated by the drug and therefore the compensatory response is, too. I will save you from all of the gory details in this email, but I may elaborate on the mechanisms and biochemistry down the road.

So, if you’re a relatively healthy person that exercises regularly and takes metformin as an anti-aging drug, should you continue taking metformin? I don’t think there’s a black and white answer at this point and it depends on how you personally respond. In the most recent study, there was a high amount of variability in the metformin group in their response to exercise-induced adaptations. For me, in response to these papers, along with my personal experience of seeing slightly higher lactate levels during zone 2 training (suggesting, perhaps, less mitochondrial efficiency), I’ve reduced my dose of metformin and only take it in the evening in an effort to reduce the amount of metformin in my system when I’m awake and exercising.

Maybe there’s an optimal dosing, timing, and scheduling of metformin, fasting, nutritional makeup, and exercise that’s superior to placebo. Maybe not. And it depends on your makeup and your individual response.

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Citation: Khaled Hamlaoui & Dario Furnari, (2020), “Metformin and Exercise; the Effects of Metformin in the Body Building to Minimize the Effects of the Use of Anabolics: Case Report for a Randomized Controlled Trial”, Arch Health Sci; 4(1): 1-9.

DOI: 10.31829/2641-7456/ahs2020-4(1)-118

Copyright: © 2020 Khaled Hamlaoui & Dario Furnari, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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