Leptin Resistance Supplements: What’s Working for Weight Loss

Leptin Resistance Supplements: What’s Working for Weight Loss

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Evidence-Based

Treating Leptin Resistance Naturally

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. 

Leptin resistance, as you probably already know, is a state of resistance to leptin at the cellular level. 

Before you jump into the supplement section make sure you read to the end so you can better understand how these supplements fit into a larger weight loss picture because using them by themselves probably won’t provide you with the results you are looking for. 

5 Supplements that Work to *Lower Your Leptin

When we talk about leptin we need to figure out if we want to lower it, raise it, or keep it the same. 

For most people, you want to lower leptin levels if you are in a state of leptin resistance and if you are overweight. 

Others, including those who are actually just trying to lose 5-10 pounds (such as bodybuilders) may actually want to INCREASE leptin levels to help burn fat. 

But if you are someone who is 20+ pounds overweight and if you’ve been this overweight for 6+ months then you can almost guarantee that you want to LOWER your leptin level. 

By lowering your leptin level you will be SENSITIZING your cells to leptin which will actually help you burn fat. 

If this concept sounds confusing be sure to read this article which explains it in more detail

#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 Resistance 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 the first supplement on your mind. 

You’ll want to use at least 80mg daily if you have mild to moderate leptin resistance and up to 160mg per day if you have severe leptin 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 insulin levels, fat mass, and leptin levels (1). 

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 Victoza and Saxenda to help with leptin resistance and I consider L-glutamine to be a less effective (but much cheaper) alternative or addition to these therapies. 

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 underappreciated 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 reduce fat mass (2). 

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. 

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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 adiposopathy (3). 

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. You can get away with less if you combine it with curcumin. 

Those with advanced leptin resistance may need to double that dose. 

#4. Berberine

Another highly effective weight loss supplement is known as berberine. 

Berberine doesn’t get the attention it deserves in this arena even though it helps manage body weight in a number of different ways. 

It helps manage gut health, reduce insulin resistance, build muscle mass, help with food cravings, and more. 

But when it comes to leptin, berberine works in a somewhat indirect way. 

It works by targeting other hormones which are often involved in obesity, namely insulin resistance. 

Berberine is another supplement that also helps your body build muscle mass which improves metabolism and helps burn fat indirectly. 

So while it may not target your leptin levels directly, it will certainly affect them in a roundabout way through various other mechanisms. 

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. 

You will want to use about 500 to 1,000mg of Berberine each day

You can get away with less if you complex it to another ingredient such as alpha lipoic acid but if you use it by itself then you’ll want to use more.

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 medications that target leptin levels. 

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 yes, 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/

leptin resistance supplements

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About Dr. Westin Childs

Hey! I'm Westin Childs D.O. (former Osteopathic Physician). I don't practice medicine anymore and instead specialize in helping people like YOU who have thyroid problems, hormone imbalances, and weight loss resistance. I love to write and share what I've learned over the years. I also happen to formulate the best supplements on the market (well, at least in my opinion!) and I'm proud to say that over 80,000+ people have used them over the last 7 years. You can read more about my own personal health journey and why I am so passionate about what I do.

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18 thoughts on “Leptin Resistance Supplements: What’s Working for Weight Loss”

  1. Hi Dr. Childs! You mention using Victoza and Saxenda often, but do you have any information on Ozempic? My doctor prescribed this GLP-1 agonist for me. Curious if it is equivalent to the ones you talk about. Thanks so much!

    Reply
    • Hi Morgan,

      Any of the GLP-1 agonists have the ability to work well including Ozempic. I just use Victoza/Saxenda as a way to describe all of those medications.

      Reply
      • Thanks for responding! One more question…when I get off this medication in the future, will there be any change in my insulin response? For instance, will I have a difficult time stimulating insulin release from the pancreas without this medication? I have never had trouble with blood sugar regulation, but I’m worried coming off this medication that I might. I just don’t want my body to get “used to” having this medication, and not be able to respond naturally when getting off. Please let me know, thanks so much!

        Reply
  2. Hi, i happen to have a low body fat%, 13% on dexascan, buut i do indeed believe i am lepin resistant, the only reason i am at this body fat is exstrodinary wilpower where i am extremely hungry 24/7/365 and sometimes get seriously hindered sleep due to hunger. my metabolism is in a good place (3000 calorie maintaince), but it literally doesnt matter how much i eat i am still hugnry like my body is telling me to eat 4000-5000 calories per day. if i listened to my body’s hunger signals like a normal person i would likely pack on 50-100lbs of body fat. i was for many years on a drug that caused a large increase in my hunger compared to before i was on the drug, however its side effect only partly went away after dropping the drug and it feels like the side effect ended up being partially perminant. would a weight loss drug possible get the leptin resistance and starvation signals into a better place?

    Reply
  3. Hi dr child’s , I am interested in saxenda for weight loss as exercise and low calorie diet don’t work. But , I’m concerned about the black box warning with it. What have you seen as far as the risks of thyroid and pancreatic cancers go ?

    Reply
    • Hi Megan,

      I’ve never seen anyone have any severe or extreme reactions to saxenda/Victoza and the newer studies I’ve seen suggest that the original claim of pancreatic cancer was overblown/overestimated. My current recommendation is to always assess whether the real risks, as well as potential risks, of any medication that you use outweigh the benefits you may see from it. I believe that the pros outweigh the cons for most people when it comes to GLP-1 agonists.

      Reply
  4. Dr Childs,

    You’ve indicated that gLP-1 treatment for people with leptin resistance doesn’t have to be lifelong. How do you assess length of treatment and how to suggest weaning off to avoid weight gain?

    Reply
  5. how does one get the leptin levels checked? I have regular bloodwork done each year but looking at my chart it has never been done. I am overweight, have hardcore sugar and salt cravings and need help have tried every diet out there including going back to basics of weightloss surgery.

    Reply
  6. Will your leptin RX supplement help if my leptin is low? I am always hungry. I recently tested labs and I’m insulin resistant (A1C 5.1, fasting glucose 90, insulin 14) since reading your posts I also checked my leptin which came back at 10. (Is that low for me?) I’m 5’5 at 190lb BMI 31.

    Reply
    • Hi Jaime,

      It may help. There’s not really a good set of treatments for low leptin levels but many of the high leptin levels do seem to have at least some effect on those with low leptin.

      Reply
  7. I’m so frustrated with my weight loss. Started at 456 last January and got down to 430 by July but went all in at the end of July and now down to the 340’s. I’ve been doing Atkins and 12-16hour daily fasting with a caloric intake of 1500-1800 (2200 once a week). I’ve been exercising sometimes burning 1000-2000 in a session of climbing/hiking and started gaining the weight back. Insulin level is 16 fasting and fasting leptin was only 3. Think the 6 months of Atkins broke any resistance patterns. Last check thyroid was normal. I’ve done a 5 day fast to break the bottle and that seems to have kicked off something. Intake of micronutrients and vitamins are above daily recommended. Not sure what else to try.

    Reply

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