How To Reset Your Leptin Sensitivity And Master Your Metabolism

Leptin Sensitivity

You have a “stop eating!” hormone that plays an instrumental role in your hunger and weight management, and it’s called leptin.  The word leptin comes from the Greek word leptos – it means thin.

It puts the brakes on hunger by sending a signal to the brain when your body’s energy needs have been met, and it controls energy expenditure over the long term.  It’s that overwhelming full feeling that happens before you want to eat that second serving of sweet potatoes.

A properly working leptin system leads to better metabolic performance, brain function, mental sharpness, memory, coordination and it can even affect the regulation of mood and emotion. (1) (2)  But when it’s been hijacked, it can lead to obesity.

The Bulletproof Diet book has a lot of info about how to control your leptin levels – the rest of this post is about how to reset your leptin sensitivity if you think it’s gone awry.  The book also talks about ghrelin, which gets broken before leptin fails. (BTW, this is one of the several reasons Bulletproof Coffee profoundly turns off hunger…it’s easier to hack ghrelin than leptin.)


What is leptin and how does it work?

Fat cells produce leptin in proportion to body-fat levels: the more fat you have, the more it makes leptin.

It enters the bloodstream via your circulatory system. Leptin binds to protein in the blood, and when leptin reaches capillaries in the brain, it travels across the blood-brain barrier, binding to leptin receptors on the arcuate nucleus of the hypothalamus.  Leptin lets your hypothalamus know when it’s time for you to stop eating, then it increases your metabolic rate in order to achieve energy balance (known as homeostasis). (3) (4) (5)

Conversely, leptin also tells us when to eat – when you have less body fat, less leptin signals the brain, and you get the message  “I’m hungry!”


Treat a hormone badly, there are consequences

Many diets boast that less fat or less calories as the gateway for weight loss, but that strategy only goes so far. Over time, caloric deprivation contributes to lower leptin levels and slows down your metabolism, making it virtually impossible to lose all the weight you want. Hello brick wall “or plateau” as hopeful low-fat dieters like to think!

Leptin can also bite back if you ignore its “stop eating” warning signals in the form of (cue the doom music)…leptin resistance.  Overeating beyond normal energy maintenance levels harms your body’s ability to distinguish whether your fat levels are too high or not, and the worst part – your leptin receptors in the brain become numb to the “stop eating” warning.  As excessive eating continues, the more the leptin resistant the whole system becomes and weight becomes a dangerous issue. (6)

Leptin Resistance is also a predictive of insulin resistance, which may mean that leptin plays a role in controlling insulin sensitivity. Insulin sensitivity itself can lead to Type 2 Diabetes and obesity. (7)

More studies show that eating high amounts of fructose, exposure to toxins or stressors can lead to Leptin Resistance and exacerbate weight gain. (8) (9) (10) Now you know one of the reasons The Bulletproof Diet infographic is so specific…


Leptin and thyroid are frenemies

The thyroid and leptin have a precarious but meaningful relationship. Your thyroid secretes hormones that act throughout the body, influencing metabolism, growth and development. The amount of leptin available to your brain has a major influence on how many thyroid hormones are released into the body.

Leptin holds the purse strings on your energy spend, based on our available food supply.  When your body can’t use leptin efficiently, it goes into a fake starvation mode known as leptin resistance. Leptin Resistance throws a monkey wrench into your thyroid function.  Leptin tells the TRH (thyroid releasing hormone) in your hypothalamus to set the thyroid hormones on low energy, otherwise the body may perish from starvation. (11)

In turn, the hypothalamus impacts how much TSH (thyroid stimulating hormone) your pituitary gland will produce. Subsequently, your brain unwittingly depresses your metabolism so that you can survive a faulty famine, making weight loss nearly impossible and even promoting weight gain.

Plus, you’ll be tired all the time because when your thyroid is low, you make less energy in your cells. You feel like a flashlight with only half a battery left.

Researchers also believe that small elevations in TSH may indicate a leptin and insulin problem connected to weight gain, rather than a thyroid problem. Another study shows that leptin-influenced weight gain can inflame the thyroid and invite the production of thyroid antibodies, which aggravate the gland. (12) (13) It’s possible that leptin resistance leads to Hashimoto’s! See Bulletproof Radio #137 for more on this thyroid condition.


Now, the GOOD NEWS: you can reset your leptin sensitivity!

(Cue Superman theme song)

Armed with this knowledge, sensitizing your body to leptin once again is within your power!

The Bulletproof Diet is designed to keep inflammation and triglycerides low by limiting fructose, eliminating toxins, and reducing food rewards and cravings, all of which reset leptin levels and allow for effortless weight loss. Leptin levels also drop during short term fasting and return to normal after eating, making it one reason that Bulletproof Intermittent Fasting is a painless but powerful way to retain leptin sensitivity. (14)

Here are some more key hacks:

If you are leptin resistant, add 28-50 grams (4-7 Tbs)  of Upgraded Collagen to your Bulletproof Coffee in the morning for 30-60 days.

  •    Consume healthy fats and protein in the morning to create building blocks for your hormones.

Use Bulletproof Intermittent Fasting sparingly until your leptin sensitivity has returned

  •    Eliminate fructose and sugar of any kind from your diet
  •    Eliminate refined or processed foods

Avoid high lectin foods – in the Bulletproof Diet I presented evidence that lectins from food can cause leptin resistance! (buy it here!)

  •    Limit your carb intake during the day, and time it as recommended in the Bulletproof Diet.
  •    Eat to eliminate food cravings and give your liver and hormones a rest.  Your liver needs to use gluconeogenesis again when you are awake and asleep. Snacking destroys the timing and circadian clocks that work in unison with leptin (14)
  •    Allow 4-5 hours between food and sleep (not counting the sleep hacking recommendations for energy maintenance during sleep)
  •    Make sure you’re getting enough Omega 3 in your diet from grass-fed meat, fish or high quality oils such as Krill
  •    Use Brain Octane oil to reduce cravings, and be liberal with quality coconut oil
  •    Lower Omega 6 consumption from grains, conventional meats, processed and vegetable oils
  •    Don’t workout an hour before or after breakfast
  •    For severe cases, get to bed by 10pm each night and optimize your sleep
  •    Don’t count calories, let the food do the healing


How will I know it’s working?

Now that the formula is laid out, here’s what to expect.

Most people experience weight loss quickly, but some people take a few weeks to get it going. Your mood should improve and your sleep quality will increase, especially if you monitor it. Next, look for a lot more energy – enough that you want to work out, and you still feel good when you’re done.

Taking control of your leptin is a useful approach to owning your metabolic system, obesity and to overall becoming Bulletproof. It’s even currently being used successfully in studies the reverse Diabetes.(15) However, if you saw my talks at PaleoFX and Longevity Now, you know that ghrelin changes before leptin, and by hacking that, you can get even more control!

Let’s hear your results from resetting your leptin levels or any other hacks you’ve used.



[expand title=”Click to read the complete list of references.” swaptitle=”Click to hide references.”]

1- The leptin hypothesis of depression: a potential link between mood disorders and obesity?

2- TRH, Leptin, and CoordinationLeptin: a pivotal regulator of human energy homeostasis.

3- Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting.

4- Leptin Signaling Pathways (Homo sapiens)

5- Leptin resistance in obesity: An epigenetic landscape

6- The Bulletproof Diet, Chapter 1, page 14

7- Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity.

8- Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding

9- Toxic Effects of Phthalates and Parabens

10-  Bisphenol A: Perinatal exposure and body weight

11-  Leptin, Thyroid, and Weight Loss

12-  Obesity, energy regulation and thyroid function: is borderline elevated TSH-level the cause or secondary phenomenon of obesity

13-  Thyroid Function and Structure Are Affected in Childhood Obesity

14-  Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1.

15-  Leptin-controlled gene can reverse diabetes





Not Harder

Smarter Not Harder: The Biohacker’s Guide to Getting the Body and Mind You Want is about helping you to become the best version of yourself by embracing laziness while increasing your energy and optimizing your biology.

If you want to lose weight, increase your energy, or sharpen your mind, there are shelves of books offering myriad styles of advice. If you want to build up your strength and cardio fitness, there are plenty of gyms and trainers ready to offer you their guidance. What all of these resources have in common is they offer you a bad deal: a lot of effort for a little payoff. Dave Asprey has found a better way.

Also Available


Start hacking your way to better than standard performance and results.

Receive weekly biohacking tips and tech by becoming a Dave Asprey insider.

By sharing your email, you agree to our Terms of Service and Privacy Policy