Here’s the deal:
Most people (physicians and patients alike) who know anything about losing weight and keeping it off, the right way, know about leptin.
They know that if you want to lose weight and keep it off you must target leptin levels.
But there’s one big problem:
Leptin is notoriously hard to manipulate.
And leptin resistance is not a well-known entity despite its importance in weight loss and weight loss resistance.
This has led many people to look for alternative therapies including the use of supplements to augment their existing weight loss therapies such as diet and exercise.
And that’s exactly what we are going to be talking about today.
If you are overweight, or if you are trying to lose weight, then you should understand what types of therapies work to help manage your leptin level.
Notice I said ‘manage’ your leptin level because that will come into play in just a minute.
Today we are going to discuss what I find to be the most effective supplements for managing leptin resistance.
#1. Glycosaminoglycans (GAGs)
The first, and probably most effective leptin-resistant supplement, is known as glycosaminoglycans.
GAGs, including hyaluronic acid, are so potent that I’ve included them in one of my main leptin resistance supplements Leptin Res. istance RX
What are GAGs?
Glycosaminoglycans, or GAGs for short, are proteins found within nearly every cell in your body.
They are responsible for helping your cells function and conditions such as obesity impede their ability to function properly.
We also know, from both human and animal studies, that taking GAGs in supplement form can help reduce inflammation by providing your body with these proteins.
These studies have also shown that taking GAGs can help lower leptin through this process.
This makes GAGs one of the only supplements with clinical studies showing that it is effective at lowering leptin levels.
These GAGs also help with joint pain, arthritis, and other inflammatory conditions.
If you have leptin resistance and you are looking for a supplement then this should be the first supplement on your mind.
You’ll want to use at least 80mg daily if you ha and up to 160mg per day if you have ve mild to moderate leptin resistancesevere le. ptin resistance
#2. L-Glutamine
L-glutamine is another supplement you should consider if you have leptin resistance.
L-glutamine is an amino acid that is probably most well known for its ability to help improve your gut health by improving intestinal barrier function.
It’s most often used to treat conditions like leaky gut and to help manage and curb sugar cravings.
While L-glutamine does all of these things, we are going to focus more on its ability to alter ins (1). ulin levels, fat mass, and leptin levels
We have a handful of animal and human studies that show that L-glutamine is effective at manipulating these various factors.
It’s not clear exactly how l-glutamine is doing this but it appears to be acting in a way similar to the GLP-1 agonist medications which ALSO treat leptin resistance.
I’m a big fan of using medications such as Vict and ozaSaxto help with leptin resistance and I consider L-glutamine to be a less effective (but much cheaper) alternative or addition to these therapies. enda
L-glutamine is probably helping to manage leptin by improving gut function and reducing insulin resistance.
The good news is that L-glutamine is very cheap and has an incredible safety profile.
It’s basically impossible to hurt yourself or cause any harm using it which is why I recommend it as part of a supplement regimen for leptin resistance.
To get the beneficial effects you will need to use between 5 and 10 GRAMS per. day
This is a fairly large dose compared to most supplements which is why it’s best to get it in powder form.
I recommend using it in the morning in some sort of liquid because it can also help manage sugar cravings throughout the day.
#3. Fish oil
Next on the list is fish oil.
And fish oil is probably one of the most underapprec iated weight loss supplements out there.
Most people think of fish oil as something that helps reduce inflammation, which is true, but it also has the ability to help with weight loss as well as leptin!
Fish oil helps do two very important things:
Helps build muscle mass while simultaneously helping to re (2). duce fat mass
Most therapies target just one of these things (but not both) which sets fish oil apart.
While I don’t know any studies that show that fish oil directly helps to lower leptin levels, it has been my experience that it can help.
I don’t recommend using it by itself, though.

In order to get the benefits of fish oil on leptin resistance, you will want to use it in COMBINATION with other more proven therapies such as GAGs and L-glutamine (and some of the others we will talk about below).
I’ve also found additional benefits if you combine fish oil with other anti-inflammatory ingredients.
Any therapy that reduces inflammation (which is a trend you will see in many of these supplements) tends to help with weight loss and managing leptin levels because this condition stems from (3). adiposopathy
Adiposopathy is inflammation and damage to your fat cells which prevents them from working properly.
Anti-inflammatory agents help improve fat cell signaling which helps manage your leptin.
You’ll want to use at least 500 mg per day of
fish oil.Those with advanced leptin resistance may need to double that dose.
#4. Berberine
Berberine has emerged as another great option for treating leptin resistance.
It’s been around for a while but more recently has gained attention as a “Nature’s Ozempic”.
This isn’t a great characterization, but it does drive home the point that berberine can help manage leptin.
As a botanical ingredient, it’s been shown in support gut health, lower insulin, help with building muscle mass, reduce food cravings, and more.
But when it comes to leptin, berb in a somewhat indirect way. erine works
By helping your body brown white fat and support muscle mass, it helps your body become more sensitive to leptin.
So while it may not target your leptin levels directly, it will certainly affect them in a roundabout way.
Berberine is one of my go-to supplements that I use daily (mostly to help build muscle mass), but it’s also one of my favorites for patients who are overweight and who have either leptin resistance or insulin resistance.
As far as supplements go, traditional berberine hcl dosing is around 500 to 1,000 mg per day.
But if you are using the more powerful versions that are now available (dihydroberberine) then you can get by with a much lower dose and fewer side effects.
If you are using dihydroberberine, which I would recommend, then the dosing is 200 mg twice per day which is roughly equal to 2,000 mg per day of berberine hcl.
Use Berberine in the morning because, like l-glutamine, it can help with sugar and food cravings throughout the day.
#5. Zinc
Zinc gets an honorable mention here because it’s the only nutrient with medical research studies showing that it can be effective in helping target leptin levels.
Unfortunately, this is one of those situations where the medical research doesn’t necessarily align with my real-life experience.
I’ve used zinc on a number of people for leptin resistance and weight loss resistance with minimal success.
I’m still mentioning it here, though, because there are so few supplements that can help.
I probably wouldn’t recommend jumping on zinc unless you know that your levels are deficient or if you’ve never supplemented with it before.
Also, if you plan on using zinc for your leptin levels definitely do not use it alone!
Use it as a supplemental therapy in addition to the OTHER more powerful supplements listed above.
Don’t Just Use Supplements
One of the worst things that you can do is read this article and then immediately buy 2-3 supplements and call it a day.
This simply will not work!
Leptin resistance is a notoriously difficult hormone imbalance to treat and it must be addressed through multiple avenues at once.
Over-the-counter supplements represent just one part of that regimen.
At a minimum, you will need to also adjust your diet and adjust your exercise routine in ADDITION to using these supplements.
For more advanced cases, you will probably also need to at least consider the use of prescription medic that target leptin levels. ations
I find that while supplements can be effective if combined with diet and exercise, they really shine when they are added to medications.
It’s not that they aren’t effective on their own because they can be.
It’s that using them alone with diet and exercise will just prolong your results and it will take you longer to lose the weight you are after.
If you are fine with a slow and steady approach then jump right in, but if you want to be aggressive then I would recommend going with diet, exercise, supplements, AND medications.
You should also be aware that you probably won’t see the scale move (why are you checking the scale anyway?!) for several weeks.
So don’t use your scale as a metric of success.
If you have leptin resistance you have problems with both fat mass AND muscle mass and if you start to lose weight you will start to gain muscle mass which will keep your body weight the same even though you are losing fat mass.
Final Thoughts
If you are overweight then you need to be thinking about your leptin level and thinking about whether or not leptin resistance is playing a role.
You can easily check for leptin resistance using a serum leptin test which can help guide your therapies.
You don’t HAVE to get this test done in order to use these therapies, but if you want to just have an idea of what is happening in your body then feel free to grab one.
From there, you will want to be relatively aggressive in how you manage your leptin level with the use of supplements, diet, exercise, and potentially the use of leptin resistance medications.
Now I want to hear from you:
Are you currently struggling with leptin resistance?
Have you used any of the supplements listed on this page?
If so, which ones have you used? Did they work for you?
If not, which ones are you thinking about using?
Leave your questions or comments below!
Scientific References
#1. https://www.ncbi.nlm.nih.gov/pubmed/25226827
#2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646500/
#3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658008/
