Why Can’t You Lose the Weight? Because Your Brain May Think You’re Starving!

The Missing Hormone Problem Called Leptin Resistance

By Dr. Greg Fors, Board-certified Chiropractic Neurologist
Clinic Director, Pain and Brain Healing Center
Chief Science Officer, Biospec Nutritionals

Dr. Greg Fors is Clinic Director of Pain and Brain Healing Center and Chief Science Officer of Biospec Nutritionals.

Key Takeaways

• Leptin is your brain's fuel gauge.
• Obesity is usually associated with too much leptin, not too little.
• The brain may stop listening to leptin, so hunger stays high and weight loss becomes a biological fight.
• High leptin talks to the immune system and may drive inflammation.
• Insulin resistance and leptin resistance can reinforce each other.
• Diet comes first, and these metabolic signals can change.

You have probably heard about insulin resistance. But there is another type of resistance that you may not have heard of. It is making millions of people hungry, overweight, inflamed, and frustrated.

It is called leptin resistance.

Here is the crazy part: you can have thousands and thousands of calories stored around your belly while your brain acts as though you are running out of food. If you are constantly hungry, crave food shortly after eating, or can't understand why losing weight feels like a daily battle, leptin may be part of the problem.

Leptin Is Your Brain's Fuel Gauge

Leptin is a hormone made primarily by your fat cells. Think of leptin as your body's fuel gauge. As your fat stores increase, your fat cells normally produce more leptin. Leptin travels through your bloodstream to an area of your brain called the hypothalamus and delivers a simple message:

"We have plenty of stored energy. You don't need to keep eating. Actually, you can start burning calories."

When this system works properly, leptin helps control hunger and regulates how much energy your body uses.[1,2] But something strange happens in many people who become overweight. Their leptin doesn't become too low. It becomes very high! Yet their brain stops responding normally to the message.[2,3]

That is leptin resistance.

Your Gas Tank Is Full—But Your Brain Thinks It's Empty

Imagine filling your car's gas tank and then looking at the dashboard 10 minutes later and seeing EMPTY. You would immediately start looking for more fuel.

Something similar can happen with leptin resistance. A person can have tens of thousands of calories stored as body fat. Their fat cells may be pumping out enormous amounts of leptin, trying to communicate that fact. But the brain isn't properly receiving the message.

Instead of hearing "We have plenty of energy," the brain behaves more like it is hearing "Energy may be running low. Find food."

That can increase the biological drive to eat and make maintaining a lower body weight much harder.[1-3] This is why I don't like reducing obesity to "Just eat less and exercise more."

Calories matter. But so does the biology controlling how hungry you are, how full you feel, and how strongly your brain fights to protect its energy stores.

This Isn't Just About Willpower

When someone tells me, "Dr. Fors, I eat a meal and two hours later I'm looking for something else to eat," I listen. When someone says, "I know I shouldn't be hungry, but I can't stop thinking about food," I listen.

These people don't necessarily have a character problem. They may have a signaling problem.

The brain controls hunger through an incredibly complex network of hormones, nerves, nutrients, and brain chemicals. Leptin is one of its major signals.[1] If that signal isn't getting through properly, telling someone to simply "have more willpower" misses an enormous part of the physiology.

Insulin Resistance + Leptin Resistance: A Metabolic Double Hit

I routinely test my patients for insulin resistance because fasting glucose alone can miss years of excessive insulin production as the body desperately tries to keep glucose within the normal range. That elevated insulin can contribute to tremendous damage to tissues throughout the body over the years. I am now increasingly interested in leptin as another piece of this metabolic puzzle.

Insulin and leptin are different hormones, but their metabolic worlds overlap. High insulin, excess body fat, inflammation, abnormal brain signaling, and leptin resistance can become part of the same metabolic "soup."[3-5]

High insulin → more fat storage → more leptin → poorer leptin signaling → greater hunger → more eating → more insulin → more fat storage.

Now add chronic inflammation, and the signaling can become even more disturbed.[3-5] Each factor adds another log to the metabolic fire.

Leptin Doesn't Just Affect Your Weight—It Talks to Your Immune System

This may be the most overlooked part of the leptin story. Leptin isn't only a hunger hormone.

Leptin is an adipokine—a signaling molecule released by fat tissue—and it communicates directly with the immune system. Immune cells actually have leptin receptors. Leptin influences macrophages, T cells, and other immune cells and can promote inflammatory and abnormal immune signaling.[4-6]

That creates another vicious cycle. Inflammation can interfere with leptin signaling. Poor leptin signaling can promote additional weight gain. More body fat produces more leptin and inflammatory signals.

Research has connected this elevated leptin-inflammatory network with increased metabolic dysfunction, type 2 diabetes, cardiovascular disease, and inflammatory and autoimmune conditions.[4-7] Leptin isn't the single cause of these diseases. It is another important part of the total biological burden—the metabolic soup—that can push the body toward chronic inflammation and chronic disease.

Your Lab Says Your Leptin Is "Normal." Is It?

This is where I think conventional laboratory thinking can miss the point.

We routinely measure glucose. We measure cholesterol. Sometimes somebody even thinks to measure insulin.

But almost nobody measures leptin.

And when leptin is measured, some laboratory "normal" ranges are enormous. Remember: a laboratory reference range generally describes what is statistically common in the population being tested.

Common or average does not necessarily mean healthy.

Women naturally have higher leptin than men, partly because of differences in body-fat distribution and sex hormones.[8] But I don't want to know only whether someone's leptin fits inside a giant laboratory reference range. I want to know what the number means in the context of their metabolism.

In my functional-medicine practice, particularly in women struggling with weight and metabolic dysfunction, I generally want to see fasting leptin around 5–12 ng/mL. I don't diagnose leptin resistance from that number alone. I interpret it alongside fasting insulin, glucose, HOMA-IR, A1c, triglycerides/HDL ratio, waist circumference, body composition, inflammatory markers, hunger, food cravings, and difficulty losing or maintaining weight.

The number is a clue. The patient is the diagnosis.

What Happens When We Change the Metabolic Environment?

I have repeatedly seen something fascinating in my patients.

We remove ultra-processed foods. We remove added sugars. We remove bread, pasta, crackers, cookies, pastries, breakfast cereals, and other refined or ground carbohydrate products. We build meals around adequate protein, healthy fats, non-starchy vegetables, nuts, and seeds.

Then we watch what happens.

Glucose improves. Insulin comes down. Triglycerides improve. Body fat begins to fall. And leptin falls too.

This isn't just something I see clinically. Randomized human trials have found greater reductions in leptin with carbohydrate-restricted diets in certain populations, including a six-month trial in severe obesity and a controlled weight-maintenance trial.[9-11]

Then some patients tell me something even more important than the laboratory numbers:

"I'm just not as hungry anymore."

That changes everything. Instead of fighting their body every waking hour, their biology may finally be moving in the same direction they are.

Can Nutritional Supplements Help?

A healthy diet comes first; there is no magic "leptin resistance pill." In 40 years of practice, I have found that you can never supplement or exercise your way out of a terrible, unhealthy diet!

First, change the biological environment. Then use targeted nutrition to support it.

Some of the research is encouraging. Curcumin is particularly interesting. Multiple randomized human trials and meta-analyses have found reductions in leptin with curcumin supplementation. One large analysis of randomized trials reported an average reduction of approximately 4.5 ng/mL, along with improvements in several measures of obesity.[12]

Cinnamon also has human clinical evidence suggesting it may lower leptin, although the evidence isn't as strong.[13]

Berberine has substantial human evidence supporting glucose metabolism, insulin sensitivity, waist circumference, and other features of metabolic dysfunction.[14] Mulberry leaf also has interesting metabolic and experimental research involving glucose regulation and leptin signaling. I use botanicals such as these as part of a much larger strategy—not as replacements for diet.

Inflammation matters too. Curcumin and Boswellia can help modulate inflammatory pathways, and experimental research with Boswellia has even shown effects on insulin, inflammatory cytokines, adiponectin, and leptin.[15]

Omega-3 fatty acids—EPA and DHA—are also interesting. Human trials are mixed regarding direct leptin lowering, but omega-3s can favorably influence the inflammatory environment and adipokine biology. Some clinical trials have reported lower leptin and/or higher adiponectin, while larger analyses have produced mixed results.[16,17]

This is why I've created products for Biospec Nutritionals, such as Inflam-95 and Glucose-IR. The important point isn't that one botanical or fatty acid "fixes" leptin resistance.

We attack the problem from multiple directions.

How Do We Change the Leptin Environment?

We don't treat one hormone. We change the biological environment that created the problem.

• Remove ultra-processed foods and added sugars.
• Remove refined and ground carbohydrates.
• Control glucose and insulin spikes.
• Eat adequate protein.
• Get carbohydrates primarily from non-starchy vegetables, nuts, and seeds.
• Reduce excess visceral body fat.
• Exercise and maintain muscle.
• Sleep seven to eight hours whenever possible.
• Address sleep apnea when present.
• Reduce chronic inflammation.
• Improve gut health when dysbiosis or intestinal problems are present.
• Manage chronic stress.
• Consider targeted nutritional and botanical support when appropriate.

The goal isn't simply to force leptin lower.

The goal is to get the brain listening again.

Stop Fighting Your Body. Find Out WHY You're Hungry.

If you have struggled with your weight for years, constantly think about food, become hungry shortly after eating, or regain weight every time you lose it, there may be much more happening than calories and willpower.

Your glucose may be talking to you. Your insulin may be talking to you.

And your leptin may be screaming at your brain—but your brain may no longer be listening.

That is why I believe insulin resistance and leptin resistance need to be looked at together in many people struggling with obesity and metabolic disease.

You cannot fix what you never measure.

Blood sugar is the smoke. Insulin is the fire. And leptin may help explain why your brain keeps asking for food when your body already has plenty of fuel.

Things to Remember

• Leptin tells your brain how much stored energy you have.
• Obesity is usually associated with too much leptin—not too little—and reduced responsiveness to its signal.
• Leptin resistance can make hunger and long-term weight control biologically much harder.
• High leptin interacts with inflammation and the immune system.
• Insulin resistance, leptin resistance, excess body fat, and inflammation can reinforce one another and contribute to debilitating chronic disease.
• Diet comes first, but targeted nutritional and botanical support may help improve the metabolic environment.
• These metabolic signals can change.

Are You Fighting Your Biology?

If you have been told to simply "eat less and exercise more" but you're still hungry, gaining weight, or unable to keep the weight off, it may be time to look deeper.

At the Pain and Brain Healing Center, I evaluate the metabolic environment—not just your glucose or your weight. That can include fasting insulin, glucose, HOMA-IR, leptin, advanced lipid testing, inflammatory markers, body composition, and other factors that help us understand why your metabolism isn't working the way it should.

My goal isn't another temporary diet.

My goal is to find the metabolic problems, change the biological environment that created them, and help you take control of your health again.

References

1. Friedman JM. Leptin and the endocrine control of energy balance. Nature Metabolism. 2019;1:754-764.
2. Münzberg H, Myers MG Jr. Molecular and anatomical determinants of central leptin resistance. Nature Neuroscience. 2005;8:566-570.
3. Hu W, Zhu H, Gong F. Leptin and leptin resistance in obesity: current evidence, mechanisms and future directions. Endocrine Connections. 2025;14(9):e250521. doi:10.1530/EC-25-0521.
4. Abella V, Scotece M, Conde J, et al. Leptin in the interplay of inflammation, metabolism and immune system disorders. Nature Reviews Rheumatology. 2017;13(2):100-109. doi:10.1038/nrrheum.2016.209.
5. Pérez-Pérez A, et al. Role of leptin in inflammation and vice versa. International Journal of Molecular Sciences. 2020.
6. Kiernan K, MacIver NJ. The role of the adipokine leptin in immune cell function in health and disease. Frontiers in Immunology. 2021;11:622468.
7. Poetsch MS, Strano A, Guan K. Role of leptin in cardiovascular diseases. Frontiers in Endocrinology. 2020;11:354. doi:10.3389/fendo.2020.00354.
8. Maffei M, et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nature Medicine. 1995;1:1155-1161.
9. Ebbeling CB, et al. Effects of a low-carbohydrate diet on energy expenditure during weight-loss maintenance: randomized trial. BMJ. 2018;363:k4583.
10. Samaha FF, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. New England Journal of Medicine. 2003;348:2074-2081.
11. de Luis DA, et al. Effects of a high-protein/low-carbohydrate versus standard hypocaloric diet on adipocytokine levels and insulin resistance in obese patients. 2015.
12. Mousavi SM, et al. Effects of curcumin/turmeric supplementation on obesity indices and adipokines in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. 2023.
13. Effects of cinnamon supplementation on adipokines and appetite-regulating hormones: a systematic review of randomized clinical trials. 2023.
14. Vahed IE, et al. The effect of berberine on obesity indices: a systematic review and meta-analysis. International Journal of Obesity. 2026;50:53-73.
15. Inhibition of adiposity and related metabolic disturbances by polyphenol-rich extract of Boswellia serrata through alteration of adipo/cytokine profiles. 2018.
16. Hariri M, et al. Does omega-3 fatty acid supplementation affect circulating leptin levels? A systematic review and meta-analysis of randomized controlled clinical trials. Clinical Endocrinology. 2015;82:221-228.
17. Rausch J, Gillespie S, Orchard T, Tan A, McDaniel JC. Systematic review of marine-derived omega-3 fatty acid supplementation effects on leptin, adiponectin, and the leptin-to-adiponectin ratio. Nutrition Research. 2021;85:135-152. doi:10.1016/j.nutres.2020.11.002.

Related Reading

• America's Metabolic Epidemic: Insulin Resistance Is Destroying Our Health One Meal at a Time
• The Belly That Steals Your Brain: Why Abdominal Fat May Be Putting Your Memory at Risk
• Subclinical Insulin Resistance: The Hidden “Metabolic Drain” Destroying Human Health and Driving Chronic Pain
• Treating Brain Fog, Anxiety & Insomnia Naturally
• Is Your Brain Wired and Tired? Magnesium May Be the Missing Link

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Educational only. This is not personal medical advice.

This article is for educational purposes only and is not a substitute for individualized medical advice, diagnosis, or treatment. Do not change medications or begin a new treatment program without speaking with a qualified healthcare professional.