The medical field is all abuzz with so-called GLP1 agonists for obesity these days.
Don't worry..we'll explain what they are below but the more fascinating piece surrounds upstream mechanisms around craving, addiction, and…dopamine!
Semaglutide (Ozempic) is the possible blockbuster drug at around $30K annually that's driving this attention.
There is a different way to boost this same pathway with supplements such as myricetin, a common phytochemical found in red wine and other fruits or vegetables.
In fact, you can supplement myricetin directly.
My personal story with myricetin?
I'm seeing habits that have been thoroughly entrenched for decades just melt away.
For example, I've always stayed up later than I should… 12 am to 12:30 even though I know the scientific research shows a clear benefit to 11-7 circadian rhythm adherence.
I just felt like I was losing "my time" even though it was the same old scrolling, video games, etc.
Again…30 years of this pattern. Felt like it was "part of me".
2 weeks into myricetin, I'm in bed at 11 pm. That's just one example…of many.
Food choices. Appetites (plural) for all sorts of things that are not good for my health.
Yes, this is anecdotal but it's also unprecedented…in my life anyway!
What's going on here? Is it just me?
Turns out…No. There's actually literature on GLP1 agonists and this effect. So weight loss and appetite changes may just be a result of a powerful regulation of the reward system where dopamine is king and queen!
Let's take a look at this with these topics:
- A quick intro to GLP1
- GLP1 and various addictions
- GLP1 and dopamine
- How to supplement naturally for GLP1 activity
Let's get started!
A quick intro to GLP1
GLP1 is one of the many new novel pathways that we're finally starting to understand.
It's a big gut player…a signaling agent to the brain of the presence of sugar essentially.
It triggers insulin release and slows the production of glucose (via glycolysis) in the liver.
Essentially…it's a gut-based (front lines) signal that food supplies are adequate!
Gut-derived hormones, such as GLP-1, have been proposed to relay information to the brain to regulate appetite.
The net result that everyone's so excited about when boosted:
Additionally, the agonists slow gastric emptying, increase satiety, and reduce the appetite, resulting in weight reduction
Satiety. Feeling full.
The research numbers on weight loss are pretty ridiculous for such an intractable problem as obesity.
Studies have found that all GLP-1 drugs can lead to weight loss of about 10.5 to 15.8 pounds (4.8 to 7.2 kilograms, or kg) when using liraglutide.
Okay…you have our attention.
So…this class of drugs boosts (agonist) GLP1 activity in the body.
Here's where things get interesting.
GLP1 and various addictions
A "side effect" of GLP1 medications for diabetes and/or obesity was…a significant reduction in alcohol use among people that are abusing the drug.
When you block GLP1 activity, you see the opposite effect:
In further support for the endogenous GLP-1 system in addiction processes are the experimental data showing that a GLP-1 receptor antagonist increases alcohol intake.
That was just the first inkling (easy to spot since alcohol use is so common).
Then came nicotine, amphetamines, and more:
Our current review demonstrates that GLP-1 not only decreases palatable food intake, but it can also decrease cocaine, amphetamine, alcohol, and nicotine use in animal models (Supplementary Tables 1, 2).
We just listed some of the most problematic drugs in terms of craving and addiction.
Amphetamine is probably front and center!
This speaks to obesity almost being a form of food addiction. Okay…so let's go there now. Read our fats review...you'll see why that might be true.
If it's addiction…dopamine's in play.
GLP1 and dopamine
We have a massive review on rescuing dopamine since it's so key to passion, motivation, and…addiction!
We have a review of dopamine but let's cover the broad strokes as it pertains to addiction and habits.
Part of our reward system, dopamine has multiple powerful facets:
- Drives action towards rewards around survival (food, water, sex, promotion, etc.)
- It's the "do that again" player but
- It also drives novelty…loses effect with repeated source or behavior
- It's spiked by drugs of addiction creating a narrowing of focus and pleasure
All habitual and addictive behavior requires dopamine to spike in a particular area of the brain called the nucleus accumbens.
So…what on earth is a nutrient sensor in the gut doing meddling in this area?
Central GLP-1 receptor activation modulates cocaine-evoked phasic dopamine signaling in the nucleus accumbens core
So essentially, GLP1 activity prevents cocaine from adjusting our baseline dopamine levels in these very important "habit reinforcing" areas of the brain.
Moreover, GLP-1 receptor agonists prevent the ability of other addictive drugs to activate the mesolimbic dopamine system.
Mesolimbic = nucleus accumbens. Our ancient brain that is not directly under our control (sounds like cravings???).
And of course….food.
GLP-1 modulates dopamine levels and glutamatergic neurotransmission, which results in observed behavioral changes. In humans, GLP-1 alters palatable food intake and improves activity deficits in the insula, hypothalamus, and orbitofrontal cortex (OFC).
So…GLP1 is a signal from the gut to the brain to say… "we're all set down here…rachet down the 'seeking', Thank you".
Mother nature likes to multi-task and GLP1 activity appears to bleed into the full spectrum of "cravings". Not just food.
So, how can we naturally boost this activity?
How to supplement naturally for GLP1 activity
Ozempic is being rolled out en-mass to people just overweight (not with diabetes) now.
The downside (besides the $30K price tag) like with many medications is that the side effect profile is pretty extensive.
Some of this is gut related (expected) but a lot isn't. Very typical with synthetics that mirror natural players.
For example, the side effect profile for synthetic CBD called Epidiodex for seizures is completely different (much worse) than with CBD isolate.
Even synthetic progesterone is very different from bioidentical:
Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55–0.81.
Okay…33% difference in a cancer risk. Goodness..half of women are on progestins for birth control. We digress.
The point is…can we get GLP1 activity naturally?
Myricetin is a flavanoid…a class of chemicals that give fruits and vegetables their flavor and/or color.
Quercetin is a common example. In fact, myricetin chemically is like a jacked-up version of quercetin (very similar in structure).
The key point for our discussion:
The data in this study suggest that myricetin might be a potential drug candidate for the treatment of T2DM as a GLP-1R agonist.
Ding ding ding!
Look at the effects on glucose as a result of GLP1 activity following use compared to liraglutide (Victoza):
Remember...glucose is the primary signal to GLP1 pathway so it's a good indication of downstream effects.
Interestingly, there's a wide range of effects from myricetin:
In fact…myricetin appears to protect neurons surrounding…dopamine function!
Based on these results, myricetin prevents dopaminergic neuron degeneration by inhibiting microglial neuroinflammation.
Very important for Parkinson's (a loss of dopamine neurons and function).
The most important piece…safety.
It is affirmed as generally recognised as safe (GRAS) by the US Flavour and Extract Manufacturer Association (FEMA) and is considered safe by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at current estimated dietary exposures.
They were looking at massive doses:
Based on the 90-day rat toxicity study, the no observed adverse effect level (NOAEL) is 2926 mg kg(-1) day(-1) in males and 3197 mg kg(-1) day(-1) in females.
Standard supplements are around 100mg daily. For a 70kg human.
There may be some interplay with estrogen so test how you feel. Report your results since the effects can be fascinating!
This has been one of the most powerful effects I've personally seen across dozens of different supplements.
Other less potent drivers of GLP1:
In the current study, we conclude that certain herbal-based constituents, such as berberine, tea, curcumin, cinnamon, wheat, soybean, resveratrol, and gardenia, can exert an influence on GLP-1 release.
Yerba Mate is also a powerful driver of GLP1 and dopamine protection.
Administration of yerba maté induced significant increases in GLP-1 levels and leptin levels, generating anorexic effects by direct induction of satiety.
Just maybe skip the sugar addition!
This makes myrcitin a key tool in our dopamine rescue toolkit:
Be well. Take care of each other. Take care of yourself.
Top 10 Tips for Dopamine Rescue
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.