DefinitiveGuideToMetformin
DefinitiveGuideToMetformin
net/publication/338844052
The Definitive Guide To Metformin: How to Use The World's Most Studied
Drug For Living A Long And Healthy Life
CITATIONS READS
0 6,095
2 authors, including:
Khaled Hamlaoui
Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences
48 PUBLICATIONS 3 CITATIONS
SEE PROFILE
All content following this page was uploaded by Khaled Hamlaoui on 27 January 2020.
Metformin is one of the very few drugs on the planet I will happily bet my life
on.
Out of all the supplements and medications I have EVER used, it remains one
of my top 3 of all time.
I’m confident the now-funded TAME study (Targeting Aging with Metformin)
will prove my unyielding and unwavering love for it's ability to enhance and
optimize human health:
"Targeting Aging with Metformin (TAME) is a novel clinical trial, that will test
whether the drug metformin, a widely-used treatment for type 2 diabetes,
can delay the onset of age-related diseases and conditions including
cancer, cardiovascular disease and Alzheimer’s disease."
A quick Google search of “Metformin + {any age-related disease you can think
of}” will pull up an abundance of positive results.
What is Metformin?
Metformin is derived from natural compounds in the French Liliac plant
(Galega officinalis), which has been used to treat diabetes since the Middle
Ages.
It was first discovered in 1922 but was not used as a medicine until 1957,
where it was first used in France for treating type 2 diabetes (i.e. adult onset
diabetes).
So while it’s technically a “drug” in the most literal sense, Metformin can be
considered as a plant that grows in the ground.
Since its inception, Metformin has been proven time and time again to be a
powerful “therapeutic wonder drug” for optimizing human life.
"It has been used for over 100 years in diabetics and is extremely safe.
It is my opinion that every living person can benefit from using it."
Now that you know Metformin is the holy grail of life extension medications,
let's examine how it works in the human body.
Metformin’s Mechanism of Action
If we’re looking at Metformin’s mechanism of action in the context of treating
diabetes, it is quite straightforward as it behaves the same way other
biguanides do:
Increasing the effect of insulin on your body [your body’s tissues become
more sensitive to insulin]"
As for type 1 diabetes, a very recent study found that metformin was able to
lower blood sugar concentrations AND lower the required dose for insulin in
patients taking insulin therapy.
The graphic below shows everything in spectacularly fine detail (if you
understand medical terminology at the cellular level).
(Source)
Here’s what the study Metformin As a Tool to Targeting Aging has to say:
(1) Metformin affects the receptors in pathways that are activated with aging
and longevity (when modulated)
(2) Within the cell, Metformin inhibits the inflammatory pathway and
activates AMPK (thereby increasing mTOR inhibition), while also
modulating oxidative stress
The most probable explanation for why Metformin provides these profound
benefits is due to it lowering systemic inflammation which often leads to insulin
resistance (IR).
And as I’ve said before, inflammation is the ROOT of all aging diseases -
cancer, dementia, heart disease, and much more.
FYI: Insulin resistance takes place when the beta cells in your pancreas can’t
produce enough insulin to keep sugar out of your bloodstream.
This leads to a rapid and dangerous rise in blood sugar, which then results in a
wide variety of undesired health problems ie the diseases of aging.
Although it’s been safely used in diabetics for decades, it is also one of the
most studied substances in all of medical history.
It is extremely safe and it is very well tolerated — both for normal people and
for patient population groups who are severely compromised.
There are hundreds of thousands of patient years invested into studying this
drug (and counting!), all of which have revealed the following positive benefits
of using Metformin…
Metformin Extends Lifespan
If you take nothing else away from this article, just remember that Metformin is
the closest thing in existence to “life extension in a pill”.
And guess what? The diabetics on metformin lived longer than even their
non-diabetic patient-matched counterparts.
And the study was massive, following 78,241 subjects over a five and a half
year period.
This is nothing to scoff at - the study quoted above also examined +90,000
people without diabetes, and more than 12,000 people who were on
sulphonylurea monotherapy.
This is only the tip of the iceberg when it comes to the full extent of
understanding Metformin’s anti-aging and life-extending properties.
(Don't forget to also google 'Jay Campbell + Metformin' to see how far back
I've been writing on its potential to transform human health)
Nearly 42,000 elderly adult US veterans with type 2 diabetes were recruited in
this study.
“At the cellular level, metformin suppresses the inflammation in many cases
and reduces or eliminates inflammatory factors mainly through dependent
mechanisms and sometimes independent of AMPK at the cellular level and
through other ways at the systematic levels.
And just like its anti-cancer effects, the anti-inflammatory effects are also direct
and indirect:
“Recent preclinical and clinical studies have suggested that metformin not
only improves chronic inflammation through the improvement of metabolic
parameters such as hyperglycemia, insulin resistance and atherogenic
dyslipidemia, but also has a direct anti-inflammatory action.
Using metformin would be a smart idea for anyone looking to optimize their
inflammatory biomarkers.
More specifically, your gut microbiome (the bacteria cultures in your gut) plays
a large role in your digestive health and immune function.
When the mucin layer lining the gut is maintained, the translocation of pro-
inflammatory lipopolysaccharides is reduced, thus controlling fat storage,
adipose tissue metabolism, and glucose homeostasis, according to the
experts."
In short, Metformin promotes the growth of “good” bacteria” and inhibits the
production of “bad” bacteria.
When women and men ask me, "What is the best fat burning supplement you
know of", I instantly have always retorted, 'Metformin'.
Let me explain why I provide that answer as I wrote about it extensively in The
TOT Bible:
Glucose uptake and fat oxidation are up-regulated, while fat synthesis is
inhibited.
Exercise works in the same fashion, and supplemental curcumin also helps
you lose fat through the same AMPK pathway.
If you understand any of this, you know why I'm such a big proponent of
fasting and using Metformin in combination with dessicated thyroid (porcine)
as all of them act synergistically as a metabolic accelerant to torch body fat
levels.
Metformin Is Cardioprotective
Metformin has become of great interest to heart health experts as diabetics
are far more likely to suffer serious cardiovascular problems.
And based on the emerging research, scientists are encouraging the FDA to
remove congestive heart failure as a contra-indication from its packaging.
Why?
So not only does it significantly lower your risk of heart disease, but it also
improves blood flow through elevated nitric oxide (NO) production!
One of the main ways in which Metformin improves heart health is by reducing
the formation of AGEs (advanced glycation end-products).
AGEs are nasty little compounds responsible for plaque build-up in your
arteries, leading to atherosclerosis.
As you can see, Metformin’s potential for inverting the entire “sick care”
medical system is limitless.
But if you really want to take a deeper dive into Metformin’s MANY other
benefits, Dr. Jeffrey Dach compiled all the information you need in 2014 and it
still stands the test of time.
While Metformin has gained notable popularity for its positive health benefits, it
has received an equal amount of backlash.
Why?
Put simply, it is NOT in the best interest of pharmaceutical companies to
have this drug easily available to normal and healthy people.
Metformin has the ability to collapse Big Pharma's 'sick care medicine model' if
its use was to become widespread.
For the past 60 years Big Pharma aka Sick Care Medicine has prevented
doctors from prescribing Metformin in any other context outside of type 2
diabetes.
"If Metformin was placed into the global water supply, hospitals
worldwide would shut down. "
If I haven't made myself clear enough yet, let me put it in bolder terms.
Metformin is the most effective and efficient drug known to man for the
following mechanisms of action:
Like the old saying goes: “If you want to own a person, take control of their
mind”.
As I've already indicated and by now you know, we are at a point in society
where “sickness is the business”.
I'm in the process of manifesting a golden age and the abolition of the sick
care system is directly in my cross hairs.
People with lactic acidosis have problems with their liver(and sometimes
their kidneys) being able to remove excess acid from their body.
If lactic acid builds up in the body more quickly than it can be removed,
acidity levels in bodily fluids — such as blood — spike.
Common symptoms include extreme fatigue, abdominal pain, shallow & rapid
breathing, muscle cramps, and body weakness.
That metformin can itself cause lactic acidosis is supported by the finding of
lactic acidosis in people who took overdoses.”
And if you really want to do the math, the chances of FATAL lactic acidosis are
so insignificant they aren’t even worth a concerned thought.
3 cases for every 100,000 patient years involve fatal lactic acidosis in
association with Metformin use, and this is all occurring in patients with renal
failure.
I’m talking about obese Type 2 diabetics who suffer from metabolic disorder
and have high levels of insulin resistance.
What?
That’s also not including the obscenely high dosages of Metformin being
consumed…the studies would use dosages between 6-9 grams PER DAY!!!
Myself, I’ve never gone above 1 gram of Metformin taken twice a day(2gms)
and I am in supremely high levels of health.
As anyone who is familiar with using medications knows, the correct dosage
determines whether it delivers a miracle cure or cellularly toxic poison.
In short, these studies are not using Metformin in the way I recommend, nor in
the way anyone would use Metformin for all the various reasons previously
listed.
You cannot take the results from these studies and apply them towards
healthy, normal adults (or even fully optimized people for that matter).
The only time Metformin was proven to have an adverse reaction in patients
who had BOTH type 2 diabetes and moderate chronic kidney disease.
“The revised guidelines stated that the use of metformin is only absolutely
contraindicated in patients with severe chronic kidney disease (CKD)
(eGFR < 30 ml/min/1.73 m2 ).
In plain English, even patients with compromised renal function can benefit
from using Metformin.
“A person taking a drug that contains NDMA at or below the ADI every day
for 70 years is not expected to have an increased risk of cancer.”
However, NDMA being “over the limit” largely has no meaning from a risk
perspective unless you show HOW HIGH over the limit it is.
And although the results are not in just yet, there is ZERO reason to panic:
The additional risk posed by NDMA from metformin, at the levels detected,
is considered very low.”
The only way this would have ANY significant impact on your health is if you
over-dosed Metformin at 6 grams a day for 70 years straight.
NDMA has also been found in many other drugs (see the table for yourself),
and even the FDA themselves say the risk of any negative effect is extremely
low:
“NDMA ESTIMATED RISK: FDA estimated that if 8,000 people took the
highest valsartan dose (320 mg) containing NDMA from the recalled
batches daily for four years, there may be one additional case of cancer
over the lifetimes of the 8,000 people.”
MYTH #5: Metformin Inhibits Mitochondrial
Adaptions To Exercise
Recently, the New York Times released an article titled “An Anti-Aging Pill?
Think Twice” had this to say about Metformin:
"A popular diabetes drug sometimes taken to slow aging may diminish
some of the expected health benefits of aerobic exercise in healthy older
adults, according to a new report.
The drug, metformin, can blunt certain physical changes from exercise that
normally help people to age well."
Here’s an excerpt from the study they used to make this claim:
“The purpose of this study was to test the hypothesis that metformin
diminishes the improvement in insulin sensitivity and cardiorespiratory
fitness after aerobic exercise training (AET) by inhibiting skeletal muscle
mitochondrial respiration and protein synthesis in older adults (62 ± 1
years).
They’re not looking at resistance training (i.e weight training) - the exercise
modality for the study was nothing more than 45 minutes of cardio.
In this 63 patient cohort(a very small sample of patients I might add especially
knowing that every patient is N-of-1), they did not look at critically important
factors such as diet and body fat levels.
It’s rather unfortunate so many studies typically forget to account for such
factors, and conduct them in compromised patients while refusing to control
they things they SHOULD be controlling for.
Notable health experts (Dave Asprey and Dr. Chandler Marrs) have often
quoted this exercise study, in addition to a singular study done in lean and
diabetic rats to make their case:
To put this dosage in a human context, a 170 pound man (77 kg) is taking 2.31
g of Metformin per day at 30mg/kg/day.
That also means 100 mg/kg/day translates to 7.7 g of Metformin daily, and
21.3 GRAMS PER DAY for 300 mg/kg/day.
These rats are heavily overdosed while being placed in an isolated and well-
controlled environment.
It is also important to mention that few if any studies ever done are able to be
replicated.
Not only that, but why would anyone educated to the modern art of peer
review science take any study seriously?
You’ve been fooled into thinking studies are foolproof, credible and valid
when they are NOTHING OF THE SORT.
Studies today are almost worthless and certainly cannot be taken at face
value from anyone.
Their designs have been manipulated to achieve a specific result, and a large
As a result, you have to learn how to “study the study” and “follow the
money.”
There are many who live and die by the ‘infallible’ scientific method, and yet
they fail to see its inherent flaws and biases.
The Wired article covers social sciences specifically, but the issue is
present across all fields.
A brief Google search will even show you the dirty underbelly of modern
research.
But one population group that often expresses skepticism over using
Metformin are athletes.
Why?
Many researchers will use this fact to promote the idea that Metformin will
inhibit both strength gains and muscle gains.
Following their train of logic, Metformin should be avoided by people who are
frequently exercising.
For the above reasons, Peter stopped taking metformin and has instead
decided to focus more on exercise
The more you exercise, and the healthier you are, the less benefit, and
potentially more detriment, you could experience from metformin”
And furthermore, due to the slight reduction in glucose uptake, elite athletes
may find their maximum power output is decreased.
They will often quote studies like the Metformin to Augment Strength Training
Effective Response in Seniors (MASTERS) to back their case up:
“Although responses to PRT varied, placebo gained more lean body mass
(p = .003) and thigh muscle mass (p < .001) than metformin. CT scan
showed that increases in thigh muscle area (p = .005) and density (p =
.020) were greater in placebo versus metformin. There was a trend for
blunted strength gains in metformin that did not reach statistical
significance.
These results underscore the benefits of PRT in older adults, but metformin
negatively impacts the hypertrophic response to resistance training in
healthy older individuals”
(While this study was designed well, strength was measured using a one rep
max on a knee extension exercise…hardly an effective way to measure
strength)
These are super-lean (sub 10% body fat), 250 lb+ dudes who are also using
supra-physiologic dosages of other drugs.
As pro bodybuilder Stan Efferding told me in a podcast I did with him, the
mTOR-limiting factor is irrelevant because many competitors(BB, strong men,
other performance athletes) who use Metformin are often “enhanced”.
But I would go as far as to argue that Metformin is STILL a very necessary
drug, especially considering that it will dramatically lower insulin resistance.
And granting the idea maximum power output is reduced slightly, Metformin is
still worth it in the big picture for its overall ability to extend life through its
suppression of insulin & systemic inflammation.
The slight reduction in glucose uptake MAY lower your power output, but don’t
get me wrong.
Many strongmen have giant barrel chests, high visceral and abdominal
adiposity, and are systemically inflamed.
Do you want to be the person who lifts 600+ on each of the Big 3 lifts yet dies
at 50 years of age from a myocardial infarction?
Or do you want to be the guy on Metformin who doesn’t have these problems
and lives a lot longer?
Truth be told, the odds are you will die earlier if you don’t use Metformin.
This very minor issue is not going to magically over-ride all of the advantages
and benefits of Metformin, and even then it’s arguable whether a competitive
athlete’s performance is going to be noticeably hindered.
Metformin is research and empirically proven to do so many amazing things
for biological systems, IMO, it’s not even WORTH thinking whether Metformin
should be used or not.
Get lean and muscular, lower your inflammation and virtually 10 times out of
10 you’ll find that these “problems” are just made-up stories in your head.
And like I said on Twitter, what kind of imbecile would use Metformin and NOT
exercise (via weight training and regular cardio) at the same time?
Use therapeutic testosterone, train to positive muscular failure, and all of the
hype regarding very minimal losses in strength and muscle (assuming there’s
any) is BS.
In every single one of these cases, the issue can be traced to a damaged and
infected gut microbiome.
Eating a shitty diet high in sugar, processed carbs and drinking too much
alcohol.
It’s the food you put in your mouth that’s cause the issue, not Metformin itself.
This “adaptation phase” normally lasts between 7-14 days in people who
typically have a really bad diet and are new to taking Metformin.
But be warned.
While it does blunt the insulin response to crappy foods (hence why it’s given
to diabetics who won’t change their lifestyle), you can’t keep eating like crap
and expect to gain any noticeable benefit.
Metformin will not give you all the positive health benefits it has to offer if you
do not change your lifestyle from the ground up.
You need to live an insulin-controlled lifestyle for it to work fully and properly.
That means lowering your body fat, optimizing your hormones, eating a
clean diet, engaging in regular strength and cardiovascular training, and
anything else that will massively improve your overall health.
Metformin is indeed a very powerful medication when used consciously and
sensibly by people who want to extend their life, improve their aging process,
while reducing their body fat, and risk of disease.
But like everything else when living in the Matrix aka earth realm, if you want
the best results out of Metformin, you have to 'tend the garden' aka PUT IN
THE WORK.
I know multiple people who are “top of the chain” in the supplement industry,
and they told me the results were “not good” after testing many Berberine
products available.
And since you can get Metformin at a much lower cost (and legally), why
bother?
“We highly recommend a dosage of 500-1000 mg twice per day for men
and 250-500 mg twice per day for women (once in the morning and once at
night).
The morning dose should be taken on an empty stomach for best results
(i.e. reducing insulin levels), while the second dose can be taken right
before your evening meal.”
Personally, I take 1 gram twice a day and this has proven to be highly effective
in reducing my insulin levels and improving my inflammatory biomarkers.
Don’t wait until you are older - you can be as young as 25 and still benefit
greatly from Metformin.
I can personally attest to this, having been a long-time user of Metformin for
the past 19 years.
I am 49 years old and I look better than 99.99% of the human population with
my shirt off.
More importantly, I have the lab work and pristine biomarkers proving,
exceptional metabolic health, as I’ve been meticulously tracking them for more
than 2 decades.
I don’t say this to brag — I say this to show you what Metformin can do for
people who are fully dialed in from a full spectrum optimization standpoint, ie
lifestyle, nutrition, training, hormones and mindfulness/inner work.
And remember…
All of your lifestyle habits (exercise, diet, sleep, supplementation, stress, inner
work etc.) are worth considering.