Metabolic syndrome in medical practice: new possibilities for correction

Metformin[edit | edit code]

Glucophage
Metformin hydrochloride

is a tablet drug for the treatment of diabetes mellitus of the biguanide class, which has the ability to reduce weight, therefore it is often used for weight loss.
Available on the market under the brand names: Metformin, Glucophage, Siofor, Bagomet, Metfogamma, Glycon, Metospanin, Gliformin, Gliminfor, Sophamet, Formetin, Langerin, Metadiene, Formin Pliva, NovoFormin, Diaformin
. Metformin has virtually no side effects when used correctly and is not hazardous to health, unlike most other fat burners. Metformin reduces levels of bad cholesterol and glucose, which are often elevated with excess weight.

A new study from Cardiff University, UK, 2014, which involved 180,000 people, showed that Metformin increases life expectancy not only in people with diabetes, but also in people without this disease.[1] Evidence has also been obtained of a slowdown in the aging process during treatment.[2]

Mechanism of action for weight loss[edit | edit code]

Mechanism of action (detailed)
Glucophage is used for weight loss due to its ability to accelerate the oxidation of fatty acids and inhibit fat synthesis [3] [4], although in various tissues it affects several points of application at once, which is expressed in diverse changes in cellular metabolism. It has also been proven that the absorption of carbohydrates from the digestive tract is reduced.

Glucophage activates AMP kinase, thereby reducing glucose levels as a result of suppressing its synthesis in the liver (suppression of gluconeogenesis). [5] Metformin also increases the sensitivity of insulin receptors to insulin, improves glucose uptake by muscles. [6] Reducing insulin when losing weight is necessary because this hormone promotes the deposition of consumed nutrients into fat, especially if the main problem area is the stomach. Immediately after eating, the level of glucose in the blood rises sharply, to which the pancreas reacts and produces insulin, which in turn forces the tissues to consume glucose, storing it in fats. That is why almost all weight loss diets recommend consuming less foods that cause a rise in blood sugar.

Finally, insulin causes hunger, so metformin helps suppress hunger when losing weight.[7]

The effectiveness of metformin decreases with increasing blood acidity, so some authors recommend eliminating exercise during the course of glucophage, since physical activity leads to the formation of lactic acid. However, recent studies have shown that exercise does not affect the overall acidity of the blood, so while taking metformin you can exercise without restrictions, thereby only increasing the effectiveness of the course.[8]

Application in bodybuilding[edit | edit code]

The mechanism of action of metformin has been established: inhibition of the mitochondrial respiratory chain, activation of AMP-dependent protein kinases, suppression of glucagon-induced cAMP formation, activation of protein kinase A, and suppression of the key anabolic mechanism mTOR through the RPS6 protein. [9][10][11]

The anabolic mechanism mTOR is very important for muscle growth, and it can be triggered by growth hormone, insulin, glucose, fatty acids, amino acids, etc. As a result, protein is synthesized in the muscles and cells begin to divide.

Thus, metformin and its analogues (glucophage) cause conditions in the body close to starvation or exhausting training, while muscle hypertrophy is almost impossible. Therefore, these drugs can only be used for weight loss, when muscle volume is of secondary importance. In addition, training is much more difficult and has little effect on the results, so these drugs are often taken without background physical activity.

How can metformin be useful in bodybuilding?

It’s no secret (and for some it’s a secret) that bodybuilders’ main weapon for fat loss is a low-carb diet. During a low-carbohydrate diet, the body receives few carbohydrates (which are the main and preferred “fuel” for the body), and therefore the body is forced to switch to fat nutrition (burns accumulated fat reserves).

Thus, we can say that a low-carbohydrate diet and taking metformin create essentially similar conditions in the body. Both lead to fat burning by limiting the amount of carbohydrates entering the body and lowering blood sugar levels.

Therefore, metformin can be used in bodybuilding in two ways: to “replace” a low-carbohydrate diet (that is, in cases where the athlete wants to burn fat without dietary restrictions, or without resorting to too strict restrictions), or to complement a low-carbohydrate diet, in order to obtain more pronounced results.

Glucophage course for weight loss[edit | edit code]

Glucophage (metformin) is a safe drug and is approved by official medicine for use by healthy people for weight loss.

• Follow a diet to lose weight
• Eliminate fast carbohydrates
• Metformin for weight loss is taken immediately before meals or during meals
  , the dose is selected individually. Most often, 500-850 mg is prescribed, 2-3 times a day (maximum dose no more than 3000 mg/day).
• If you have diarrhea, it means you are overindulging in carbohydrates.
• If you experience nausea after taking metformin, reduce your dose. Slowly increasing the dose may improve gastrointestinal tolerability.
• Perform systematic aerobic training for maximum effectiveness of the course
• If, after reducing the dosage, the symptoms of side effects do not disappear, stop taking the drug and immediately consult a doctor, as there is a possible risk of developing lactic acidosis, which can be fatal!!! If signs of lactic acidosis appear, the patient should be urgently hospitalized and, by determining the lactate concentration, confirm the diagnosis. The most effective measure for removing lactate and metformin from the body is hemodialysis. Symptomatic treatment is also carried out.

The duration of use of the drug should not exceed 18-22 days, after which a break of 1-2 months is required. A shorter break leads to adaptation of the body, and metformin is not able to fully exhibit the properties of a fat burner. The course must be agreed with a medical specialist.

Unique properties of the drug

The drug is being studied in many countries around the world. The Internet is replete with information about its unique properties. The following statements are relevant today:

• Metformin has been successfully used in the field of oncology and vascular diseases.
• A decrease in glucose occurs approximately 7-10 days after the first dose.
• The drug is combined with insulin and maninil.
• The pills promote the growth of new neurons in the brain.
• Metformin reduces the risk of death from diabetic complications by 30%.
• The medicine stabilizes weight, the excess of which is caused by antipsychotic drugs.
• Sometimes the drug is used in the absence of ovulation in the case of a diagnosis of infertility.
• Taking metformin helps create new memories. Therefore, the tablets can be taken for Alzheimer's disease.

Experts continue to debate the issue of weight loss with metformin. It cannot be perceived as an ideal anti-aging remedy. The main indication for the tablets remains type 2 diabetes.

Side effects and harm to health[edit | edit code]

Do not take Glucophage for weight loss if you have:

• Kidney diseases accompanied by insufficiency
• Heart failure
• Another disease in which the acidity of the blood is increased
• Do not take Glucophage with other glucose-lowering agents or other medications without consulting a doctor.

Possible side effects of glucophage (rare):

• Diarrhea (need to reduce carbohydrate intake)
• Headache (usually goes away quickly)
• Abdominal cramps
• Nausea (need to reduce metformin dose)
• Increased gas formation (it is necessary to reduce the amount of carbohydrates consumed)
• Lactic acidosis (in the presence of predisposing diseases), (do not combine with alcohol!!! risk of developing lactic acidosis)

As a rule, side effects of metformin occur at the beginning of the course, and then quickly pass.[12]

Metformin and inflammation

Systemic inflammation, oxidative and dicarbonyl stress play an important role in the pathogenesis of type 2 diabetes. In a study by N. MalinskaЂ et al. (2016) [14] found that metformin treatment reduced circulating levels of inflammatory response markers IL-6, TNF-α and monocyte chemotactic factor-1, while C-reactive protein (CRP) levels were not affected. Metformin significantly reduced oxidative stress (conjugated dienes and thiobarbituric acid reactive species levels) and dicarbonyl stress (methylglyoxal levels) in the left ventricle but not the kidney. In addition, metformin treatment reduces CRP-related adipose tissue lipolysis. The authors conclude that at high levels of CRP, metformin protects blood vessels from inflammation and oxidative and dicarbonyl stress in the heart, but not in the kidneys. Accordingly, these cardioprotective effects of metformin may be particularly significant in patients with type 2 diabetes and high CRP levels.

Based on current standards of care, metformin is used to treat patients with type 2 diabetes and certain other conditions such as polycystic ovary syndrome. However, it appears possible that metformin could be used as a prophylactic agent for a wider range of patients at risk of developing cardiovascular disease.

Notes[edit | edit code]

1. https://www.medicalnewstoday.com/articles/280725.php
2. https://www.medicalnewstoday.com/articles/277679.php
3. Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334(9):574–9. doi:10.1056/NEJM199602293340906.
4. Diamanti-Kandarakis E, Christakou CD, Kandaraki E, Economou FN. Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome. Eur J Endocrinol. 2010 Feb;162(2):193-212. doi: 10.1530/EJE-09-0733. Epub 2009 Oct 19.
5. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med. 2002;137(1):25–33. PMID 12093242
6. Musi N, Hirshman MF, Nygren J, et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes. 2002;51(7):2074–81. doi:10.2337/diabetes.51.7.2074
7. G Paolisso, L Amato, R Eccellente, A Gambardella, MR Tagliamonte, G Varricchio, C Carella, D Giugliano, F Donofrio. Effect of metformin on food intake in obese subjects. European Journal of Clinical Investigation 28: 6(JUN 1998):441-446
8. U Gudat, G Convent, L Heinemann. Metformin and exercise: No additive effect on blood lactate levels in healthy volunteers. Diabetic Medicine 14:2 (FEB 1997):138-142.
9. Rena G, Pearson ER, Sakamoto K (September 2013). "Molecular mechanism of action of metformin: old or new insights?". Diabetologia 56(9):1898–906.
10. Burcelin R (July 2013). "The antidiabetic gutsy role of metformin uncovered?". Gut 63(5):706–707.
11. Madiraju, Anila K.; Erion, Derek M.; Rahimi, Yasmeen; Zhang, Xian-Man; Braddock, Demetrios T.; Albright, Ronald A.; Prigaro, Brett J.; Wood, John L.; Bhanot, Sanjay; MacDonald, Michael J.; Jurczak, Michael J.; Camporez, Joao-Paulo; Lee, Hui-Young; Cline, Gary W.; Samuel, Varman T.; Kibbey, Richard G.; Shulman, Gerald I. (21 May 2014). "Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase." Nature 510(7506):542–546.
12. Drug Facts and Comparisons 2005. St. Louis, Mo: Facts and Comparisons; 2004. ISBN 1574391933