Metformin

Metformin UPREGULATES the Master Switch AMP Kinase which is involved in the energy status of cells, hormone expression, and protein synthesis.

If AMP-activated protein kinase is turned ON (This is GOOD).

• ATP (Energy) is created.
• Fatty acids are predominantly consumed for energy.
• This is similar to the effects of Caloric Restriction and LOW insulin levels.

BUT

If AMP-activated protein kinase is turned OFF: (This is BAD)

• ATP is consumed.
• Glucose is burned for energy.
• Fatty acids and cholesterol are synthesized.
• This is similar to the effects of HIGH insulin levels.

• Pancreas: Decreases insulin secretion.
• Liver: Decreases fatty acid and cholesterol synthesis.
• Adipose (Storage Fat Tissue): Decreases fatty acid synthesis, increases lipolysis.
• Skeletal muscle: Increases fatty acid oxidation, glucose uptake, and glycolysis.
• Heart muscle: Increases fatty acid oxidation, and glucose uptake.

Its broad-spectrum anti-ageing properties make it a drug that most longevity enthusiasts should seriously consider asking their doctors about.

Since it long ago came off patent, metformin is a super-low cost generic that everyone can afford.

Metformin is a “Healthy Ageing” drug

• Scientific literature supports the wider use of metformin.
• Metformin could lead to improved health-span and lifespan in humans.
• Metformin-based interventions promote healthy ageing.”
• Metformin can delay ageing and the incidence of age-related diseases.

What’s more, many of these interventions are based on the study of calorie restriction mimetics, that reproduce physiological and anti-ageing effects found in CR animals.

Indeed, several studies propose that metformin’s actions resemble CR.

Microarray analyses have shown that metformin induces a gene expression profile that aligns with that of CR, although conflicting results have been shown in lifespan extension studies.

Type II diabetes is characterized by cellular insulin resistance.

The result is an excess accumulation of glucose in the bloodstream as cells become resistant to the effects of insulin.

As the type II diabetic condition progresses, many people gain weight and develop more fat cells.

Treating type II diabetes with insulin-enhancing therapy increases the risk of cardiovascular complications, induces weight gain, and fails to correct the underlying cause of the disease.

Many type II diabetics produce too much insulin in a futile attempt to drive glucose into insulin-resistant cells.

When doctors prescribe insulin-enhancing drugs to these type II diabetics, a temporary reduction of serum glucose may occur, but the long-term effects of this excess insulin can be devastating.

An ideal anti-diabetic drug would enhance cellular insulin sensitivity, inhibit excess intestinal absorption of sugar, reduce excess liver production of glucose, promote weight loss and reduce cardiovascular risk factors. 

Metformin (Glucophage) is the one drug that does all of this and more.

• Metformin works by increasing the number of muscle and adipocyte (fat cell) insulin receptors and the attraction for the receptor.
• It does not increase insulin secretion, it only increases insulin sensitivity.
• Therefore, metformin is not associated with causing hypoglycaemia.
• This activity reduces insulin levels by increasing the sensitivity of peripheral tissues to the effects of insulin by rejuvenating the response and restoring glucose and insulin to younger physiological levels that may cause weight loss and most certainly a decrease in the body's total fat content.
• In a study published by the American Diabetes Association, metformin was found to decrease the fasting plasma glucose concentration by -60 to -70mg/dl in patients with non-insulin-dependent type II diabetes.
• Metformin also reduced haemoglobin A1C levels, a blood measurement of glycosylation. One of the most devastating consequences of diabetes is protein degradation caused by the formation of advanced glycated end products.
• Reductions in serum haemoglobin A1C levels are a good indicator of consistent glucose control in the diabetic patient.

the recommended dose to take is 500 mg of metformin, two or three times per day for patients over 40 who do not have kidney or liver problems, or a history of congestive heart failure, as aging causes insulin resistance.

Metformin increases hypothalamo-pituitary sensitivity that declines with age.

As we get older, there is a loss of sensitivity of the hypothalamus and the peripheral tissues to the effects of insulin, which causes elevated blood insulin levels (hyperinsulinemia).

• Long term use of Metformin may cause malabsorption of vitamin B12.
• Long term use of Metformin may cause malabsorption of CoQ10.
• When a person begins to take Metformin, they may experience some nausea and vomiting, stomach pain, bloating, and diarrhea. The latter usually disappears once the person becomes accustomed to the drug.

In the United Kingdom Prospective Diabetes Study, the following positive benefits of Metformin included the following:

• Metformin was the only medication that reduced diabetes-related deaths, heart attacks and strokes.
• The effects of metformin were most notable on the level of endothelial (artery lining) damage that showed a decrease in artery damage.
• Decreased microvascular damage due to Metformin caused less complications and complications such diabetic retinopathy, nephropathy and neuropathy all improved due to metformin's ability to decrease damage to arterial lining.
• These small blood vessels were somewhat unblocked to provide healthier blood supply to vital tissues surrounding the eyes, kidneys and nerves.
• Metformin resulted in a decrease in total cholesterol and low density cholesterol (LDL), free fatty acids, tissue plasminogen activator antigen and insulin levels.
• individuals with visceral obesity( abdominal obesity) treated with metformin showed greater weight loss with a decrease in plasminogen activator inhibitor.
• Metformin showed a greater decrease in fasting insulin levels.
• Metformin has a significant effect on lowering blood pressure and fasting triglyceride levels
• In non-diabetic patients with hypertension, the trial showed that metformin significantly reduced fasting insulin or C-peptide levels, as well as total cholesterol, low density lipids cholesterol or apolipoprotein B levels, fasting free fatty acids and tissue plasminogen activator antigen levels. 

Polycystic ovarian syndrome is characterized by irregular or absent menstrual periods and elevated serum testosterone and androstenedione.

These patients complain of abnormal bleeding, infertility, obesity, excess hair growth, hair loss, and acne.

Polycystic ovarian syndrome seems to have a genetic component in which those who are affected often have male and female relatives with type II diabetes, obesity, elevated blood triglycerides, or high blood pressure.

They may also have female relatives with infertility, hirsutism, or menstrual problems.

For women in the reproductive age range, polycystic ovarian syndrome is a serious common cause of infertility because of the endocrine abnormalities that accompany elevated insulin levels.

As women with polycystic ovarian syndrome may be at greater risk for other medical conditions, testing is essential.

They should be tested for blood lipids, diabetes, and blood clotting factors that promote abnormal clotting.

Metformin, at doses of 500 mg to 850 mg three times per day, is shown to reverse these endocrine abnormalities.

In women with polycystic ovarian syndrome, metformin reduced systolic blood pressure, hyperinsulinemia, and insulin resistance, and facilitated menstrual regulation and pregnancy.

Metformin has been found to suppress the growth of some tumors and enhance the activity of anti-cancer drugs.

By giving the immune system a boost, metformin can improve cellular immunity.

• It has also been found to reduce the incidence of chemically induced cancer in rats.
• The way metformin improves cellular immunity is linked to its blood sugar lowering effect by improving receptor sensitivity and number.
• Bacteria, fungi, and some viruses tend to feed on sugar.
• By diminishing their fuel supply, we diminish them.
• That is why diabetics and other individuals with endocrine abnormalities tend to be more prone to infections.

Metformin is not recommended for people who have a history of kidney or liver disease, or a history of congestive heart failure.

People with a history of alcohol abuse should also avoid taking the drug, as serious lactic acidosis can develop in these individuals.

Long-term use of metformin may cause malabsorption of vitamin B12. Because of the depletion of B12, supplementation is recommended.

When a person begins to take metformin, they may experience some nausea and vomiting, stomach pain, bloating, and diarrhea.

The latter usually disappear once the person becomes accustomed to the drug.

Metformin's multiple effects benefit individuals with a propensity to develop diabetes, cardiovascular problems, endocrine problems, retinopathies, nephropathies, cancer or decreased immunity, infections, and weight gain.

As with diabetes, metformin has been shown to cause a reduction in appetite, weight, and the body's total fat content.

In associated heart disease conditions, there is plaque build-up that lines the arteries. This build-up of plaque can lead to atherosclerosis.

Metformin reduces or lowers the chances of developing atherosclerosis and reduces the rate of pro-ageing cross-linkages of collagen, which plays a role in the scar tissue build-up that occurs during wound healing.

Metformin has been shown to reduce the amount of supplemental insulin needed by type II diabetics who become insulin-dependent.

They are able to take a lower insulin dose in conjunction with metformin without the risk of becoming hypoglycaemic.

For 40 years metformin has been used to control blood glucose levels in patients with type II diabetes.

Physicians are recommending it to patients who are predisposed to diabetes for the prevention of developing the disease.

With the cluster of cardiovascular problems associated with hyperinsulinemia, metformin has proven effective in lowering total cholesterol, low-density lipids, free fatty acids, and tissue plasminogen activator antigen and insulin levels when patients present with symptoms of hypertension dyslipidemia, visceral obesity, or hyperglycemia.

Metformin prevents the acceleration of atherosclerosis and reduces the rate of pro-ageing cross-linking of collagen.

The microvascular complications of hyperinsulinemia are improved by metformin due to the arterial clearance in small blood vessels of the eyes, kidneys and nerves.

Decreased tumor growth and improved cellular immunity in individuals who are prone to chronic infections associated with high blood sugar levels.

In non-diabetics, metformin reduced low-density lipid, total cholesterol, free fatty acids, tissue plasminogen activator antigen, blood pressure, and fasting triglyceride levels.

Women suffering from polycystic ovary syndrome have been treated with metformin. 

Benefits include:

Lipid-lowering effects, reduction in systolic blood pressure, hyperinsulinemia and insulin resistance syndrome.

Metformin has also been shown to aid in normal menstrual regulation and pregnancy.