How to Diagnose Leptin Resistance Using Lab Tests & Symptoms

Question: what do you think all of these symptoms have in common?

The inability to lose weight even with calorie restriction.
The presence of food cravings even immediately after eating a large meal.
Hair loss
Cold body temperature
And the presence of other hormone problems

Answer: they are all caused by a condition known as leptin resistance.

And in this article, I’m going to walk you through how to diagnose this condition using a combination of a simple blood test and your symptoms.

Let’s jump in:

How do You Diagnose Leptin Resistance?

This is both easy and somewhat complicated.

Difficult in the sense that there really isn’t an agreed-upon way to diagnose leptin resistance (1), but easy in the sense that most people agree if you have an elevated leptin level and you are unable to lose weight, you have the problem.

The most agreed-upon way to assess for the presence of this condition is by ordering a simple serum leptin level.

All this test evaluates is how much leptin there is in your bloodstream at any given time.

From this data, you can extrapolate a fair amount of information about the function of this important hormone.

For instance:

If your fasted serum leptin is greater than 10 ng/ml and you have the symptoms of leptin resistance (which we will soon discuss) then you can say with a high degree of certainty that you have the condition of leptin resistance.

To put this into perspective, here’s a real-world example:

In addition to her leptin level of 52.1 ng/ml, this particular patient was also experiencing weight loss resistance, a cold body temperature, hair loss, disordered appetite signals, and other symptoms of hypothyroidism.

This would be a very classic example of someone with leptin resistance which is quite obvious with some simple lab testing.

What some patients get confused about is the scaling of leptin with BMI.

They will see that their leptin is “normal” for their set BMI and think everything is okay.

Don’t fall for this.

All this scaling value suggests is that as BMI increases, their leptin level increases as well.

While this is true, it’s fairly meaningless as far as a “normal” value is concerned.

You absolutely don’t want to compare your own leptin level to someone with the same BMI as you because that just indicates that you both have the same problem: obesity.

Instead of looking at the scaling value of leptin, look to see if your leptin level is elevated.

If it is, and you have any of the symptoms we are about to discuss, you have enough information to say that you are leptin-resistant.

Why Diagnosing Leptin Resistance Matters

Leptin’s primary job is to regulate your body weight (2) and metabolism (3).

And it does this job by interacting directly with thyroid hormone, another major player in metabolism regulation (4).

These two systems play together to help your brain set your appetite, help your brain regulate and set your metabolism, and help your brain communicate with your fat cells.

When done correctly, these two systems help you maintain a normal and healthy body weight.

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When either becomes dysregulated (either your thyroid or leptin levels), it becomes very difficult to manage your weight.

And this is precisely why the presence of leptin resistance matters.

It provides you with an explanation for why you may (or may not) be able to lose weight.

And understanding its presence can change things because it means you can more specifically target therapies to treat it.

Signs and Symptoms You Are Resistant To The Hormone Leptin

One of the best ways to evaluate for the presence of leptin resistance is by taking a look at how you are feeling.

You might be tempted to think that it’s easier to just get a lab test to confirm the presence of leptin resistance but here’s where you’d be wrong.

While the test is relatively easy to obtain once you know what to test for, getting your doctor to order it may be difficult.

But evaluating your leptin level may not even be necessary because you can glean a lot from your symptoms.

Symptoms that may indicate you have leptin resistance include:

The inability to lose weight even with calorie restriction and extreme exercise (if you are eating fewer than 1,000 calories per day and NOT losing weight then that is an indicator you may have leptin resistance)
Extreme cravings for food even if you’ve recently eaten (6)
A slower than normal or damaged metabolism (7) (you are burning fewer calories than normal)
Persistent weight gain despite attempts at weight loss
Lower than normal body temperature
Lower than normal resting heart rate
Presence of other hormone imbalances (including hypothyroidism, estrogen dominance, low progesterone, low testosterone, or high cortisol)

Is a High Leptin Good?

You may hear in various places on the internet that having a high leptin is actually good, not bad.

But how can this be if I just told you that a high leptin is the standard with which we use to diagnose leptin resistance?

This very topic is the source of a lot of confusion among people who are trying to evaluate their leptin status.

While it is somewhat nuanced, it’s not very complicated:

As it stands, leptin is not a bad hormone, as long as it remains functional.

What trips people up is the difference between an elevated leptin and the state of leptin resistance.

In the healthy state, once you start to gain weight, your body will increase leptin production which acts to help you get back to your old weight.

This is good and what is supposed to happen.

But if your leptin stays elevated for long enough, eventually you will become resistant to the hormone.

This is bad and not what is supposed to happen.

But, initially, you do want to see that rise in leptin and this is why some people will talk about increasing leptin for fat loss.

Assuming you are sensitive to it, increasing your leptin will be helpful.

But if you are resistant to it, increasing your leptin will only make your resistance worse.

Both statements are true, it just depends on where you are at in your disease progression as to whether or not increasing leptin will be helpful or harmful.

Severity and Treatment of Leptin Resistance

Testing your leptin level is very important because the absolute level of leptin in your body in the fasted state can help you determine just how resistant you are.

Imagine leptin resistance on a spectrum or a continuum.

On one side you have a very minor, relatively easy-to-treat leptin resistance which only causes a minor difficulty in weight loss, and one which responds to simple lifestyle changes such as diet, supplements, and exercise (8).

People who have minor leptin resistance may only have a fasted serum leptin level in the 14-20 ng/ml range.

On the other side, you have a very difficult-to-treat version of leptin resistance which only responds to therapies that include medications, hormones, supplements, and dietary changes.

People with moderate to high leptin resistance often have a fasted leptin level greater than 40 ng/ml (sometimes even much higher than this).

Generally, the higher your leptin level is the more difficult it will be for you to both treat the condition and for you to lose weight.

It also helps give you information about what kind of therapies you are likely to need to treat your condition.

One of the biggest problems with leptin resistance is that it is not always appreciated in the conventional medical community.

Doctors such as your endocrinologist or primary care physician are probably not aware of leptin resistance or how to treat it.

As you become more leptin-resistant, the therapies that you need start to require medications (9) and hormones which can be difficult to get unless you have a doctor working with you.

Treatments that fit into this category include GLP-1 agonists, T3 thyroid hormone, dietary changes, and supplements.

If you have severe leptin resistance you will most likely also have to look at other hormone imbalances such as low T3 syndrome and hypothyroidism.