Best Supplements for Leptin Resistance Explained

Weight-loss supplements are nothing new. They’ve been around since the late 1800s when attitudes began to change about the female form. At that time, a slimmer silhouette became the popular look. Of course, supplements have evolved over the years. A relatively new category that’s emerging revolves around the hormone leptin. What is leptin, how is it involved in weight loss, and what are the best supplements for leptin resistance?

What Is Leptin?

Metabolism cycle for maintaining your body mass
Leptin is a metabolic hormone that essentially controls how much food the body intakes.

Many hormones within the body affect appetite and hunger. 1 These include insulin, ghrelin, cortisol, estrogen, neuropeptide Y, and you guessed it, leptin. And, leptin may be one of the most important metabolic hormones.

Researchers discovered leptin rather recently, in 1994. Subsequently, they’ve studied its role in weight loss ever since. 2 It’s produced by fat cells, and if the body is starving or experiencing a shortage of food, levels decrease. In response, hunger levels increase to encourage the body to eat more.

Leptin also plays important roles in heart and bone health. It’s vital for immune system functioning, a healthy response to inflammation, and fertility. And it’s needed for the regulation of the thyroid and adrenal glands. Finally, it plays a role in growth hormone production. 3

Additional Facts on Leptin

Made within fat cells, leptin then travels through the blood and sends signals to the brain. It’s known as the “obesity hormone” or “fat hormone.” Perhaps most accurately, it’s known as our “starvation hormone” or “satiety hormone.” And, when everything is working correctly, leptin sends messages to the brain when the body’s got plenty of food as well as fat stored. In other words, it tells the brain there’s no need to keep eating.

If levels of fat are low, then levels of leptin are also low. Thus, the messages change, and brain receives the signal to send more food please. Thus, appetite increases and fat burning slows.

Therefore, leptin’s key role is to prevent starvation and overeating, so the body is able to balance its energy and thermostat. It’s a beautiful system—as long as it’s working well.

If you’re overweight, you might think this means the body needs more leptin, so it turns off hunger, and you can lose weight. If only it were so easy.

Leptin Resistance and Obesity

Having unhealthy food that may develop more issues in your body
If the brain cannot detect leptin, it thinks you are starving. In turn, the brain then triggers cravings and you need to eat more to feel satiated. In addition and to conserve calories, your metabolism rate slows down so you burn fewer calories at rest.

When leptin was first discovered, researchers immediately started giving overweight folks more leptin to see if it could help fight obesity.

Unfortunately, the problem isn’t that there is not enough leptin circulating in the body. Rather, it’s that the body is insensitive to the leptin that’s already circulating. In fact, research has found that obese individuals actually have higher leptin levels than average-sized people. 4

In other words, even if there’s plenty of leptin circulating to let the brain know it’s time to reduce appetite and burn more calories, the brain either doesn’t get the message or ignores the signal. That can lead you to continue overeating. 5 Increasing leptin levels, therefore, isn’t the answer.

In addition to getting the message to overeat, it appears the brain also believes it needs to save energy, so it lowers metabolic rate to burn calories more slowly. 6

Final Thoughts on Reversing Leptin Resistance


Finally, when you decrease energy (i.e., calorie) intake, say on a diet to lose weight, the cells produce less leptin. Again, when leptin levels drop, the brain may think the body is starving. Therefore, it sends out messages to increase leptin levels, which can then turn on hunger. It also makes food more rewarding and more enticing. This can become a vicious cycle of dieting, intense hunger, followed by weight gain.

While leptin resistance may not be the initial cause of weight gain, it can may make weight gain that much more likely in the “right” circumstances, including insulin resistance.

Another way to describe leptin resistance is when the “brain is starving but the body is obese.” Individuals with the condition often find that they need even more food to feel full or satiated even when they’ve eaten enough and have an abundance of fat stored.

Leptin versus Ghrelin

How leptin and ghrelin impacts to your body
Leptin and ghrelin are both hormones that help manage weight naturally.

Two of the most important hormones that regulate appetite, metabolism, and weight are leptin and ghrelin. Leptin, again, is considered the “satiety hormone,” as it helps with appetite control (when working correctly). Ghrelin, on the other hand, increases the need to eat and thus is considered the “hunger hormone.”

If the balance is disrupted on either side, then you can lose the ability to eat when hungry and stop once you’re full. Consequently, this can lead to drastic changes in weight. Thus, these two hormones need to work together as a check and balance.

Supplements to Help Leptin Resistance

Yellow pills supplement for leptin harmone issue
The best supplements for leptin resistance have ingredients that naturally reduce inflammation which is the cause of leptin resistance.

Now we know how important leptin balance and leptin sensitivity is to weight loss. The goal isn’t actually to increase levels of the leptin hormone but rather to decrease leptin resistance. Several supplements to help leptin resistance have hit the market.

Some manufacturers, for instance, design supplements to address the inflammation associated with obesity. Others may seek to reverse the decrease in leptin that occurs due to dieting. 7

In one study, researchers found, for example, conjugated linoleic acid (CLA) decreased leptin levels. Unfortunately, however, it did not alter appetite. 8 Researchers have also studied alpha-lipoic acid (ALA) and it may mildly induce weight loss. 9 Other supplements to help leptin resistance include omega-3 fatty acids. 10

Best Supplements for Leptin Resistance

African mango extract naturally helps in weight loss
Irvinginia gabonesis, also known as African mango, is a great ingredient for weight loss supplements because it naturally reduces inflammation and helps reverse leptin resistance.

One of the best supplements for leptin resistance is Irvingia gabonensis (also known as African mango and the patented IGOB131). According to research, it may help reduce body weight and improve metabolic parameters in overweight individuals. 11

In addition to decreasing body weight, African mango may help decrease glucose, cholesterol, and triglyceride concentrations. 12 In a double-blind, randomized, placebo-controlled clinical trial, researchers report it may significantly decrease body weight, fat mass, and waist circumference in overweight and obese volunteers. 13 In this 10-week study, in fact, researchers found overweight subjects lost an average of 28 pounds. They also lost 6.7 inches from their waists and decreased body fat by 18.4%.


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Additional Suggestions for Reversing Leptin Resistance

Another best supplement for leptin resistance to consider is Dichrostachys glomerata (aka Dyglomera®). This fruit has a long history as a culinary spice. In a randomized, double-blind, placebo-controlled trial, subjects lost up to 24.5 pounds. In addition, they lost up to 4.2 inches off their waists, up to 3.5 inches off their hips, and up to 11.3% body fat. They also experienced improvements associated with their metabolic function, blood fats, and blood sugar. 14

In another eight-week study, when Irvingia gabonensis was combined with Dichrostachys glomerate (aka Dyglmera™), the researchers found significant weight reductions. 15 It was, however, noted that the changes were much more noticeable after eight weeks than after four, so individuals should not expect immediate results. Rather, if you are considering the best supplements for leptin resistance, have patience. It may take some time before you enjoy the full effects on your metabolism.

Other Ingredients to Help Reverse Leptin Resistance

Light walk at night is very good for your physical and mental health
Getting a good night’s sleep is important for anyone looking to lose weight. Getting enough sleep helps reduce inflammation and keeps your metabolic hormones balanced which helps aid in long term weight loss.

Another perhaps surprising supplement to help leptin resistance is melatonin. Best known for helping support a good night’s sleep, melatonin may also support weight-loss success. To begin with, sleep deprivation and decreased melatonin levels have been shown to throw leptin levels out of balanced. 16 And a good night’s sleep is key to keeping cravings under control and ensuring weight loss.

By affecting leptin levels, melatonin has been shown to play a critical role in the regulation of body mass and energy balance. 17, 18 And the absence of melatonin has been shown to lead to long-term leptin resistance as well as increased weight in animal studies. 19

Improving Leptin Resistance

Dealing with leptin resistance can be a challenge. While we typically want to lose excess body fat, the body naturally wants to hold onto fat stores. Levels of leptin are intended to prevent the body from losing body weight as that can be a survival threat. So, helping balance the system takes more than just supplements to help leptin resistance.

Fortunately, in addition to trying the best supplements for leptin resistance, there are lifestyle factors that have been shown to help. These include:

Light Weight exercise that is best to build  resistance
Anaerobic exercise helps reverse leptin resistance quicker than any other option because it helps boost metabolism while also burning calories.

Increasing exercise and physical activity to at least 30 minutes daily. Include both cardio and strength training in your routine.
Adding high-intensity interval training (HIIT) to your regular exercise program.
Decreasing the consumption of high-sugar beverages and foods.
Avoiding highly processed foods, especially those high in refined carbohydrates and fats like cakes, cookies, donuts, candies, ice cream, etc.
Eating more fish, especially fatty fish like salmon and sardines, or using an omega-3 fatty acid supplement if fish isn’t your favorite.
Eating more fiber while reducing simple, refined carbs like white bread and pasta.

Additional Suggestions

 High protein food roasted lamb
Eating foods like roasted lamb that are high in protein helps increase metabolism rate while naturally lowering caloric intake.

Consuming a nutrient-dense diet that makes you feel full, satisfied, and happy. In other words, eat foods that are both healthy and that you enjoy.
Ensuring you’re getting enough protein, especially with breakfast.
Eating mindfully. That is, don’t eat while distracted or multi-tasking.
Occasionally (no more than once a week) consider consuming higher calories than usual to help “trick” your brain into thinking you’re overeating. 20
Avoiding severe calorie restriction.


Practicing intermittent fasting. 21
Making sure you’re getting good sleep—7 to 9 hours every night.
Supporting your circadian rhythm with a healthy sleep/wake schedule and enjoying sunlight first thing in the morning.
Reducing stress throughout the day to help prevent emotional eating.
Decreasing triglyceride levels.

Researchers are still discovering the importance of leptin in the body. But remember, it’s not about increasing the amount of leptin that circulates in the body. Rather, it’s about helping your body become more sensitive to the leptin it already has.

Fortunately, lifestyle changes along with considering the best supplements for leptin resistance may help in the effort to lose weight and maintain a healthy body weight.

Concluding Thoughts on the Best Supplements for Leptin Resistance

Leptin is an important hormone that’s produced in fat cells. Along with ghrelin, one of its main roles is in the regulation of appetite and weight. When there’s an imbalance between these two hormones, and especially when the brain is no longer receiving the signals from leptin, it’s difficult to eat only when hungry and stop when full. Thus, it’s easy to put weight on and harder to take it off.

While researchers are still learning more about leptin and how it works within the body, discoveries have been made on supplements to help leptin resistance. In addition, there are simple lifestyle changes you can also make to support leptin sensitivity and make it easier to lose weight and keep it off.


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4 Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF. Serum immunoreactive-leptin concentrations in normal-weight and obese humans – PubMed. New England Journal of Medicine. 1996 Feb 1;334(5):292-5.

Additional References

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7 Sáinz N, González-Navarro CJ, Martínez JA, Moreno-Aliaga MJ. Leptin signaling as a therapeutic target of obesity – PubMed. Expert Opinion on Therapeutic Targets. 2015 Jul 3;19(7):893-909.

Additional References

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9 Li N, Yan W, Hu X, Huang Y, Wang F, Zhang W, Wang Q, Wang X, Sun K. Effects of oral α‐lipoic acid administration on body weight in overweight or obese subjects: A crossover randomized, double‐blind, placebo‐controlled trial – PubMed. Clinical Endocrinology. 2017 May;86(5):680-7.

10 Sabour H, Norouzi Javidan A, Latifi S, Shidfar F, Heshmat R, Emami Razavi SH, Vafa MR, Larijani B. Omega-3 fatty acids’ effect on leptin and adiponectin concentrations in patients with spinal cord injury: A double-blinded randomized clinical trial. The Journal of Spinal Cord Medicine. 2015 Sep 1;38(5):599-606.

11 Ross SM. African mango (IGOB131): A proprietary seed extract of Irvingia gabonensis is found to be effective in reducing body weight and improving metabolic parameters in overweight humans – PubMed. Holistic Nursing Practice. 2011 Jul 1;25(4):215-7.

Additional References

12 Martínez-Abundis E, Mendez-del Villar M, Pérez-Rubio KG, Zuñiga LY, Cortez-Navarrete M, Ramírez-Rodriguez A, González-Ortiz M. Novel nutraceutic therapies for the treatment of metabolic syndrome. World Journal of Diabetes. 2016 Apr 10;7(7):142.

13 Ngondi JL, Etoundi BC, Nyangono CB, Mbofung CM, Oben JE. IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation – PubMed. Lipids in Health and Disease. 2009 Dec 1;8(1):7.

Additional References

14 Kuate D, Etoundi BC, Ngondi JL, Muda W, Oben JE. Anti-inflammatory, anthropometric and lipomodulatory effects Dyglomera® (aqueous extract of Dichrostachys glomerata) in obese patients with metabolic syndrome – Functional Foods in Health and Disease. Functional Foods in Health and Disease. 2013 Nov 18;3(11):416-27.

15 Azantsa B, Kuate D, Chakokam R, Paka G, Bartholomew B, Nash R. The effect of extracts of Irvingia gabonensis (IGOB131) and Dichrostachys glomerata (Dyglomera™) on body weight and lipid parameters of healthy overweight participants – Functional Foods in Health and Disease. Functional Foods in Health and Disease. 2015 Jun 9;5(6):200-8.


16 Dzherieva IS, Rapoport SI, Volkova NI. Relationship between insulin, leptin, and melatonin contents in patients with metabolic syndrome. Clinical Medicine. 2011(6):46.

17 Alonso-Vale MI, Andreotti S, Peres SB, Anhê GF, das Neves Borges-Silva C, Neto JC, Lima FB. Melatonin enhances leptin expression by rat adipocytes in the presence of insulin – American Journal of Physiology. American Journal of Physiology-Endocrinology and Metabolism. 2005 Apr;288(4):E805-12.

Additional References

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21 Longo VD, Mattson MP. Fasting: Molecular mechanisms and clinical applications. Cell Metabolism. 2014 Feb 4;19(2):181-92.



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