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The 6 Step Leptin Resistance Treatment Guide

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Are you tired of gaining weight despite eating very little and exercising?

Have you dieted off and on your entire life but just can't keep your weight off?

Do you eat like a bird compared to friends and family yet you can't lose weight like you once could?

Are you eating less than you ever have but are still gaining weight?

Do you feel like something is wrong with your metabolism yet your labs always come back "normal?"

If you answered yes to any of these questions, you are likely dealing with leptin resistance.

In this article I will discuss leptin resistance, how to diagnose it, and give you a 6 step treatment guide that you can use to help reverse leptin resistance.

Here we go...

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What is Leptin Resistance?

Leptin​


It is highly likely that you have never heard of this hormone, much less know what it does in the body.

Don't feel bad.  Most doctors have little to no knowledge of leptin either.

I myself was unaware of leptin until just a couple of years ago.

Leptin is called the "satiety hormone."  It is produced primarily by fat cells.

Its primary function is to signal the hypothalamus in the brain that we have plenty of fat stores and we don't need to store anymore.

This causes our appetite to reduce and our metabolism to increase so we can burn the stored fat.

There is another hormone called ghrelin which basically does the exact opposite of leptin.  It makes us hungry and slows our metabolism.

The 2 hormones together normally strike a healthy middle ground to keep us in energy ​balance.


Leptin Resistance

So what is leptin resistance? 

For reasons we don't completely understand, the brain begins to ignore the elevated leptin levels and continues to signal to our body that we are hungry and need to store more fat.

When you brain ignores the leptin signal, it goes into starvation mode.

Think of someone stranded on a desert island without food.  What would their body do to compensate?

Their metabolism would slow down to conserve energy, and their appetite would increase to stimulate them to find food.

The same thing happens in leptin resistance even though the patient has an excess of fat stores.

This leads to more weight gain and higher leptin levels which just worsens the cycle.

Connection with Insulin Resistance

A similar thing happens with insulin resistance.

With insulin resistance, the body ignores the elevated insulin levels and it therefore requires more and more insulin to move the sugar from the blood stream into the cells to be used for energy.

The insulin causes an increase of inflammation in the body which worsens the insulin resistance.

High levels of insulin cause you to store calories that you eat in the form of belly fat.​

At some point the blood sugar levels begin rising and type II diabetes develops.

Leptin resistance and insulin resistance typically run hand-in-hand.  It is rare to find one without the other.

Both conditions cause the metabolism of the body to slow which results in weight gain and obesity.

Read more about treating insulin resistance in my article found here.


Connection with Hypothyroidism

In leptin resistance, as your leptin level increases and your metabolism slows, your reverse T3 levels will increase.

This is a normal compensatory response by the body.

Thyroid hormone is responsible for the majority of the metabolism in the body.

As your leptin levels rise in leptin resistance, your overall basal metabolic rate slows.

This decrease in metabolic rate signals the body to convert T4 to more reverse T3 and convert less to active T3.​

Here are the results from a recent patient of mine that demonstrate this:

Reverse T3 serves as a brake for your metabolism.​  As your leptin levels rise your reverse T3 levels will also rise.

Reverse T3 actually competes on your cells for binding with the free and active T3 hormone.

This results in a further lowering of your metabolism and causing damage to it.

​A prolonged elevation of reverse T3 is called thyroid resistance.


Signs and Symptoms of Leptin Resistance

The typical patient with leptin resistance has problems losing weight unless they are on an extremely strict diet.

The damage to their metabolism means they have to eat an extremely calorie-restricted diet just to maintain their weight.

Even just occasional cheating will cause them to put on pounds.

Patients with leptin resistance tend to experience at least 2 of the following symptoms:​

    • Inability to lose weight despite eating a calorie-restricted diet and exercising regularly
    • Constant weight gain accompanied by a ravenous appetite
    • Constant food cravings, even after eating a large meal
    • Constant fatigue, low energy, or feeling "sluggish"
    • Cold body temperature (less than 98.0 degrees F)
    • Low resting heart rate (defined as 50-60 first thing in the morning assuming that the patient is overweight and not aerobically conditioned)
    • Worsening symptoms of hypothyroidism (hypothyroidism frequently accompanies leptin resistance)

​Having 2 or more of these symptoms doesn't guarantee that a person has leptin resistance, but it means there is a high chance that they do.


Diagnosing Leptin Resistance

The only way to definitely diagnose leptin resistance is by doing labwork.

You will have to ask your doctor specifically to order these tests.  Remember, there is a strong possibility that he or she will not know what leptin is or know how to interpret the results.

The gold standard for diagnosing leptin resistance is by checking the fasting serum leptin level.

Your serum leptin level should be less than 10-12.

If you are at least 20 pounds overweight and your fasting serum leptin level is > 12, the diagnosis of leptin resistance can be made.

Please note that most labs will list a reference range that is based off of your BMI.

Don't let this fool you into thinking your leptin level is normal just because it falls within the reference range.

Of course leptin levels will go up as your BMI increases.  That is the point of this article!

That just confirms that the majority of obese people have leptin resistance.

I would also recommend ordering the following tests in addition to the serum leptin level:

    • Uric Acid
    • Complete Thyroid Panel (specifically a reverse T3)
    • Fasting Total Insulin Level
    • Hemoglobin A1c

Uric acid is an indicator of how well your body is metabolizing fructose.  This is important because fructose combined with a high fat diet can worsen leptin resistance.

If you uric acid level is > 5, that indicates that you are consuming too much fructose or your liver is having a hard time metabolizing it.

​A reverse T3 level > 15 indicates thyroid resistance that also needs to be addressed.

A fasting total insulin level and hemoglobin A1c will indicate the presence of insulin resistance.

A fasting total insulin level > 5 is indicative of a problem.  So is a hemoglobin A1c level > 5.3.​

Like I said earlier, it is very rare to find leptin resistance without insulin resistance.


Leptin Resistance Treatment Guide

So, now you have the lab tests you need.  Based on those results and the symptoms you are having, the diagnosis of leptin resistance can be made.

So what can you do about it?

This is a difficult condition to reverse, but it can be done if you are fully dedicated.

The vast majority of treatments will be up to you.  How committed you are to reversing this will determine your level of success.​

Trying just one or two steps in this guide will only give you limited success.

To ensure the best chance at success, you will need to incorporate as many steps as possible.​

Finding a​ doctor that understands leptin resistance and how to manage it will also be important if the first few steps are not enough to reverse the condition.

1.  Improve Your Diet​

Changing your diet is critical to reversing leptin resistance.​

- Get rid of all processed foods and eat only whole, natural foods.

The Standard American Diet is full of processed foods that increase inflammation in the body.

Inflammation causes the leptin levels to increase and only worsens the condition.​

Dietary changes alone will probably not drop your leptin levels to normal, but you will never be successful with reversing leptin resistance if you don't change your diet.​

By the way, there is something very important that you need to keep in mind.  Too much protein can actually increase your leptin.​

Protein increases leptin by interacting with mTOR.​

Many of the currently popular low carb diets are also high protein, which can actually increase leptin levels!​

Carbohydrates cause an increase in insulin levels which signals the body to store fat and gain weight.

Eating protein increases mTOR levels which can also signal the body to store fat and slow metabolism.

Fat does not send such a signal to the body.​

It is therefore important to get 60% of your total calorie intake from good, healthy fats.

20% of your calories should come from high quality complex carb sources.

The remaining 20% of your calories should come from high quality, organic proteins.

Eating this way will allow all 3 levels to decrease - your leptin, insulin, and mTOR.

- No more calorie restricted diets!​

​It has erroneously been pounded into our brains that in order to lose weight, we need to reduce our calories.

Yes, we need to stop over-eating, but many times people take it too far.

​If you don't eat enough calories, you body will go into starvation mode and lower your metabolism to conserve energy.

​If you do this long enough, you metabolism can get damaged permanently.

The best thing to do is listen to your body - if you're hungry, eat.  When you're full, stop eating.  However, be careful with this rule if your leptin level is high.

Quit paying attention to calories except to make sure you percentages of macros - carbs, proteins, and fats - are in the recommended levels.

- Try Intermittent Fasting

Another popular but wrong concept is eating several small meals throughout the day to keep your metabolism burning.  I have been guilty in the past of telling my patients this very thing.

In effect, eating multiple small meals increases the time our body spends processing calories.  This causes the insulin levels to surge which can ultimately lead to insulin resistance.

If you eat larger but less frequent meals, your body will spend more time without insulin which will sensitize it to the insulin and allow it to work more efficiently.​

This is called intermittent fasting - you eat the same amount of calories per day, but you eat it in fewer meals.

An example would be skipping breakfast 2 or 3 days per week. 

Remember, it's important to still get your total calories in for that day.  That means lunch and dinner need to be larger than they would be if you ate breakfast.​

There are other types of intermittent fasting that are more effective, but I would recommend starting with this first.


2.  Start HIIT Exercise Training

Exercise is important to reduce leptin resistance, but doing the right type and amount of exercise is critical.

Going for a casual walk or bike ride are great for family time, but not so much for weight loss or leptin resistance.

Conversely, over-exercising can be just as harmful.  This is because if causes cortisol levels to rise, which affect insulin levels, which will make losing weight and lowering leptin difficult.

The best exercise for leptin resistance is High Intensity Interval Training (HIIT).

HIIT training has been shown to lower leptin levels - but it could take months.

HIIT training is simple to do and doesn't require extra equipment.

Instead of just walking, try walking as fast as you can for about 30 seconds then drop back to a slow pace to allow your heart rate to come back down.  Once it does (usually about a minute later) repeat the process.​  Do this at least 5 times.

The same thing can be done on a bicycle, rowing machine, treadmill, elliptical, etc.​

The heart rate variability is what increases metabolism and helps lower the leptin level.​

If you are not currently exercising, make sure you take it slow so as not to cause a cortisol increase.

Start with 1 session per week for 10-30 minutes then increase your frequency and intensity as tolerated.  Let your level of fatigue be your guide to show you when it is time to increase.


3.  Improve Your Sleep

If you aren't sleeping well, it will be much harder to lose weight.

Lack of sleep has been found to increase leptin levels and leptin resistance.

Getting good sleep will help to accelerate weight loss, while poor sleep will slow it down.

Sometime just breaking bad habits can make a huge difference.

For example, avoid caffeine or other stimulants in the evenings.

Set a consistent sleep schedule - go to bed at the same time every night and get up at the same time every morning.

Cut off all electronic stimulation (TV, phone, computer) at least 2 hours before bedtime.

Make sure you have a comfortable, supportive bed and a good, supportive pillow.

If that still isn't enough, there are some great supplements that ​can help.

How to Supplement to Improve Your Sleep


Why I Like It

May help improve energy levels

May help to decrease levels of inflammation


May help reduce brain fog and mental slowness

Requires lifestyle change for best results

How to Tell if You Need It

    • You should be getting 8 hours of quality sleep every night.
    • If you find yourself waking up exhausted then you should consider checking for sleep apnea or a trial of the following supplements to improve sleep

How to Use

    • Take each supplement as indicated on the bottle or as recommended below
    • In addition to these supplements make sure you practice adequate sleep hygiene, that means: black out curtains for your bedroom, noise cancelling ear plugs, having a consistent sleep schedule, and avoiding all electronics 3 hours prior to your scheduled bed time

My Recommended Brand and Product

For minor sleep issues start with supplements containing 5-HTP which may promote proper melatonin production and induce sleep naturally (take 100mg 30 minutes before your scheduled bed time):

For more difficult cases consider the addition of melatonin + 5-HTP, start with 1-3mg of melatonin and don't be afraid to use melatonin if you need it.

For more the most difficult cases consider using serotonin and GABA potentiators. These supplements help enhance GABA and serotonin neurotransmitters in the brain and help induce deep sleep.


4.  Treat Insulin Resistance

As I discussed earlier, insulin resistance and leptin resistance are usually both present at the same time.

If you follow all of the steps in these leptin resistant treatment guidelines​, your insulin level will drop as your leptin level drops.

Several hormonal abnormalities have already hit by the time leptin resistance develops.

Since insulin resistance is present in about 50% of the population, chances are you may have it whether you know it or not.​

If your fasting insulin level is >5 and your hemoglobin A1c is > 5.3, you are already showing evidence of insulin resistance and are on the road to developing Type II diabetes if you don't make the changes we have discussed.

You may want to consider using these supplements to help lower your blood sugar and insulin levels.

5.  Treat Thyroid Issues

- Is Your Thyroid Medication Correct?

As discussed earlier, elevated leptin causes an increase in conversion of T4 to reverse T3, which means less is converted to active T3.

Giving T4 thyroid medication to a patient with elevated reverse T3 only adds fuel to that fire.​

​That's why the addition of T3 medication such as Cytomel or sustained release T3 can be very beneficial.  It allows you to completely bypass the whole conversion process.

This forces the active T3 levels higher and lowers the reverse T3 levels.

Reducing your T4 dose can also help by removing the substrate that is converted to reverse T3.  This includes T4 only medication like Synthroid but also NDT medication such as Armour Thyroid or Nature-throid.

- Improve your T4 to T3 Conversion

Many hypothyroid patients are deficient in nutrients that are essential for normal thyroid function.

By boosting these nutrient levels in the body, it can help with the conversion of T4 to active T3.

Supplementing for the 2 most common nutrients needed for T4 to T3 conversion can often be very helpful.​  Click on each to see my preferred brands.

    • Zinc - Zinc is a powerful anti-inflammatory and helps with the conversion of T4 to T3.  Use in doses of 30-60mg daily (60mg is best in leptin resistance).
    • Selenium - Selenium helps reduce inflammation, balance the immune system, and helps with T4 to T3 conversion.  Doses range from 200-400 mcg daily.

6.  Consider a GLP-1 Agonist

​Steps 1 through 5 of this Leptin Resistance Treatment Guide are critical to reduce leptin resistance.

However, they may not be enough to completely reduce the leptin levels back into the normal range.

It may require a certain medication for a short time.

GLP-1 agonists have been shown to dramatically reduce leptin levels and lead to significant weight loss.​

This class of medications includes Victoza, Byetta, Bydureon, Adlyxin, Tanzeum, and Trulicity.

These meds treat many of the issues that occur with leptin resistance:​

  1. They reduce leptin levels.
  2. They cause significant weight loss even in the absence of diabetes.
  3. They reduce the rise in leptin levels that often occurs after rapid weight loss which can help patients keep off the weight long term.​
  4. They reduce insulin resistance and blood sugar.

The medication may only be needed for a few months but will need to be monitored closely.

The trick will be finding a doctor that understands leptin resistance and how it relates to insulin and thyroid resistance and who is willing to prescribe it in this scenario.


Summary

Leptin is a largely unknown, but an extremely important hormone.

Leptin resistance is a common cause of obesity and a big reason why many people can't lose weight and keep it off.

In order to improve leptin resistance, it typically takes a multi-faceted approach which includes diet, exercise, improving sleep, reducing insulin resistance, optimizing thyroid function, and even medication.

Only doing 1 or 2 of the steps in the Leptin Resistance Treatment Guide will most likely not be enough.

It is critical for you to find a doctor that is knowledgeable about leptin resistance who can walk through the treatment with you.

Now it's your turn...

Do you think you may have leptin resistance?

Have you been diagnosed with leptin resistance?

What has helped you in your treatment?

Leave your comments below.

About the Author Dr. Jeff Whelchel

Dr. Whelchel is a family physician who specializes in functional medicine, especially hormone optimization. He has over 20 years experience in private practice managing patients with various medical issues. His passion is helping patients reach their full potential of wellness and quality of life. He grew up in the Texas Panhandle where he currently lives. He is married and has 3 awesome children.

Leave a Comment:

6 comments
Liz Pepper says August 5, 2017

Jeff, so much of this sounds like me. Would you consider seeing me?

Reply
    Dr. Jeff Whelchel says August 9, 2017

    Hi Liz. My medical practice is way too full currently. However, I will be launching an online hormone practice soon. I will notify you when that occurs. I hope you are doing well.

    Reply
Tracy Taylor says February 27, 2018

Great article! Im 42, eat a GF, DF diet and no alcohol or even caffeine. I do HIIT 2 times a week and brisk power walking with light jogging the other days. I eat a whole foods diet and take a ton of supplements like omega 3s, curcumin, adrenal support as well as metformin. Have been on too high a dose of NDT for some time now and RT3 is 17, T3 is pooling high and leptin is 35. Full battery of fasting labs show inflammation is normal, iron is normal, saliva cortisol shows slight day increase but still dropping for sleep at night ( I sleep 8 hours faithfully) Had MD stop NDT and give me 45 mgs of cytomel daily to get the RT3 down. Sex hormones are all within range. Glycemic panel on labs looked great, just a slight bit of IR. I wonder how long before the hypo symptoms let up and I drop the 15 lbs I gained with this leptin + high T4+ high RT3+ pooling T3 issue. Any advice? I need to check out your hormone practice!

Reply
    Dr. Jeff Whelchel says February 27, 2018

    Hi Tracy. I would suggest adding some intermittent fasting (read my article). If your leptin doesn’t drop much over the next 2-3 months, you may want to talk to your doctor about trying a GLP-1 agonist such as Bydureon or Victoza.

    Reply
Sherri Chambliss says August 9, 2018

Hi Dr Welchle I’m one of your patiences. I. Reading your blog and I was wondering about getting on ALA,or any of the meds that help reduce the leptin resistance like Victoza, Byetta, Bydureon, Adlyxin, Trulicity, or Tanzeum. I just received my LDN first dose was yesterday.

Reply
    Dr. Jeff Whelchel says August 16, 2018

    Hi Sherri. Come see me at your next scheduled appointment and we can discuss.

    Reply
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