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  • Nathan Waters

Metformin

Metformin is a drug prescribed for the management of diabetes. It is normally used before the disease has progressed enough to need insulin. Metformin helps to utilize glucose more efficiently, but not in the same way that insulin does. It reduces the output of glucose by the liver, decreases intestinal absorption of glucose, and increases insulin sensitivity in certain organs and peripheral tissues.


Metformin lowers blood sugar but it is less likely to cause hypoglycemia, than insulin if the dose is accidentally misjudged. This is one of the reasons why it is used before insulin. It is also why bodybuilders tend to start with metformin before progressing on to insulin use, they see it as being less risky.


Metformin also has many other benefits besides lowering blood glucose levels which is why it is often used in the anti-aging / longevity crowds. Some of the benefits to using metformin are:

  • Lowers glucose levels

  • Increases insulin sensitivity

  • Increases fatty acid oxidation

  • Lowers inflammation and oxidative stress

  • Is neuro protective

  • Has anti-cancer effects

  • Can improve gut health

  • It is cardio-protective

There are many benefits from a longevity standpoint. Dr. David Sinclair talks about many of these potential benefits in is book Lifespan. He says that metformin inhibits cancer cell metabolism, increases mitochondrial activity, and removes misfolded proteins. Metformin impacts many diseases, through AMPK activation, making more NAD, and turning on sirtuins and other defences against aging as a whole – engaging the survival circuit upstream of these conditions, slowing the loss of epigenetic information and keeping metabolism in check, so all organs stay younger and healthier.


He goes on to explain that metformin can increase lifespan. In mice, a very low dose of metformin increased lifespan by nearly 6%. This was the equivalent of five extra healthy years for humans. The mice showed reduced LDL and cholesterol levels and improved physical performance.


In a human study, metformin even helped diabetic patients live longer than non-diabetics placed on a placebo.


Metformin mimics calorie restriction. It increases AMPK, an enzyme known for its ability to respond to low energy levels and restore the function of the mitochondria. It also activates SIRT-1. These sirtuins have been shown to increase lifespan.


Dr. Sinclair also mentions a study where more than 41,000 metformin users between the ages of 68 and 81 concluded that metformin reduced the likelihood of dementia, cardiovascular disease, cancer, frailty, and depression. In one group of already frail subjects, metformin used over a 9-year period reduced dementia by 4%, depression by 16%, cardiovascular disease by 19%, frailty by 24%, and cancer by 4%.


In some studies, cancer was decreased by 40%, mostly for lung, colorectal, pancreatic, and breast cancer.


In 26 studies of rodents treated with metformin, 25 showed protection from cancer.

When it comes to fatty acid oxidation Dr. Sandra Kaufmann explains that lowered glucose levels allow lipids (fats) to become the primary energy source. The body utilizes stored fat preferentially over glucose and metformin also prevents lipogenesis, the formation of new fat.


Metformin is even used to improve ovulation in women with infrequent or prolonged menstrual periods as a result of polycystic ovary syndrome (PCOS).


As you can see there are many benefits to taking metformin. The good news is that side effects are minimal as well. Some potential side effects are diarrhea, nausea / vomiting, flatulence, weakness, indigestion, abdominal discomfort, and headache. These side effects typically go away after the first few days of use and are seen more often when the dose is high. This is why it is recommended to titrate the dosage up as needed.


Another thing to consider is supplementing with vitamin B12 when taking metformin as it has been shown to impair the absorption of B12.


A very rare side effect you will often see written about is lactic acidosis which is a very serious and often fatal metabolic disorder where there is an increase in lactate levels and a decrease in blood pH. This is definitely something to be careful of but as Jay Campbell said, this was seen in just one study and they were a heavily compromised patient population. They had end stage renal failure, were diabetic, and obese. The dosage used was also very high.


Metformin is very cheap. It costs about $7.50 for 100 x 500 mg tablets in Australia. It can also come under the trade name Glucophage, which translates to “glucose eater”, so you may see it under this name as well.


Metformin is commonly prescribed in tablets of 500, 850, and 1,000 mg tablets. There is also an extended-release formula.


Peak plasma concentrations tend to be about 1-3 hours and for the extended-release formula, 4-8 hours.


When using metformin for blood glucose control, it is recommended to start with a low dose and titrate up as needed for adequate glycemic control. The goal is normally to decrease fasting glucose and HBA1C levels, using the lowest effective dose. This dose could be anywhere between 500 – 2,000 mg per day.


For general health and longevity, the common dose is about 500 – 1,000 mg per day. Men typically have 500 mg in the morning and again in the evening, and women 250 mg at these same times. Same people take more than this but these are pretty general and safe guidelines.


William Lewellyn says that bodybuilders typically take 850 mg once or twice per day. If taken once, they tend to take it 1-2 hours before training, so that the drug can have its peak effect during the early stages of recovery.


Metformin has been used for a long time, it has been researched a lot, it is cheap, and side effects seem to be minimal, so it may be something you want to consider. Like all things though, it is not a magic pill, you still have to ensure you aren’t eating crappy food, you are exercising, you have your sleep in order, and you have all the other general health practices in place.


References:

Lifespan – David Sinclair

The Kaufmann Protocol – Sandra Kaufmann

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