What is Leptin?
To learn more about normal leptin levels and what this hormone does in the body, read the first part of this series.
This post will focus on the dangers of high leptin. Elevated leptin levels are associated with obesity, overeating, and inflammation-related diseases – including high blood pressure, metabolic syndrome, and heart disease .
Leptin’s Role in Weight
To recap, leptin is one of the big 4 hormones that determine your weight. It is made in fat tissue, while receptors for it are dense in two important brain regions (the hypothalamus and hippocampus) .
Leptin acts as a signal to the brain to inhibit food intake and enable the storage of surplus calories (in fat cells).
At the same time, it protects non-fat tissue from fat overload. Increased leptin is associated with higher body fat mass, a larger size of individual fat cells, and the act of overeating/hunger. In rodents, it increases energy expenditure by using brown fat for energy .
The more fat you have, the more leptin you produce, which is supposed to make you thinner, keeping your weight in homeostasis .
This is what’s supposed to happen in healthy people:
Eating->Increased body fat->Increased leptin->Decreased appetite, increased energy expenditure.
High leptin levels can be caused by:
- Overeating [9, 10]
- Emotional stress 
- Inflammation [9, 12]
- Obesity 
- Pregnancy 
- Pre-eclampsia 
- Gestational diabetes 
- Sleep apnea 
Negative Health Effects
1) Increases Inflammation
Leptin is an inflammatory marker, as it responds to inflammatory cytokines from fat tissues.
Multiple studies have demonstrated elevated levels of leptin in chronic inflammatory conditions .
Elevated leptin is associated with higher white blood cell (WBC) counts in both men and women . WBC‘s increase inflammation in the body.
This may be one reason why the thin people that I deal with seem to have lower WBC counts (lower leptin, lower WBCs).
2) Causes Fatigue and CFS
Leptin increases were associated with greater fatigue scores in people with CFS, and it’s assumed that it plays a causal role in CFS .
In people with CFS, leptin increases more in response to cortisol .
Why Are People With CFS More Susceptible to Leptin?
Note that leptin isn’t necessarily higher in people with CFS. Some studies show it is and some studies show it isn’t.
Rather, it triggers inflammation in people with CFS more so than it does in healthy people.
According to Dr. Younger, people with CFS have microglia that is more primed to activate, and leptin is the trigger, which causes a spike in fatigue.
Interestingly, leptin receptors are increased by pro-inflammatory signals . This means that if you have inflammation, you will get an increased response from leptin – at least in some ways.
3) Causes Th1 Dominance
It was also found to be necessary for Th1 dependent inflammatory processes, acting as a critical regulator of CD4 T cells .
The effect of leptin polarizing T cells towards a Th1 response seems to be mediated by stimulating the synthesis of IL-2, IL-12, and IFN-gamma (all Th1 cytokines) and inhibiting the production of IL-10 and IL-4 [33, 34].
Th1 dominance correlates with excess leptin in this study of dialysis patients . If you’re Th2 dominant, it doesn’t mean leptin isn’t causing you problems. It simply means that it’s causing you different problems.
Real world example:
People often have more inflammation upon awakening. It’s known that people with arthritis have worse joint pain in the morning .
Well, leptin rises as the day goes on and peaks at midnight and continues to be elevated while you’re sleeping (to prevent you from getting hungry in the middle of the night)  – and that may spike inflammation, which you will feel the next morning.
4) Mast Cells and Histamine Intolerance
Leptin may have to do with histamine intolerance. Mast cells in human skin, lungs, gut, and the urogenital tract contains leptin and leptin receptors , suggesting that it has some effect on mast cells.
It seems like leptin causes mast cells to be more inflammatory .
In metabolic syndrome patients, there was a positive correlation between leptin levels and the number of fat tissue mast cells, suggesting that leptin may stimulate mast cells .
Leptin correlates with (probably increases) mast cell activation in children with asthma who exercised .
5) Chronic Inflammatory Response Syndrome (CIRS)
Many people with CIRS gain weight, and it’s thought that this is from leptin resistance.
My theory is that people get inflammation and mount an anti-inflammatory SOCS3 response, which causes leptin resistance. I believe this is somewhat unique in CIRS patients, who are mainly Th2 dominant, compared to other people with CFS.
SOCS3 is increased by a variety of cytokines. It blocks leptin function .
Therefore, leptin probably contributes to the inflammatory state of CIRS. With that said, leptin is not all that bad for CIRS.
Real world scenario:
I have a client with CIRS who tells me that they feel better when they fast and, oddly, when they sleep less. In both cases, leptin declines, which would cause less inflammation in some ways. This might explain why they feel better when they sleep less (not recommended, because in the long term it’s bad for you).
6) Lowers T Regulatory (TREG) Cells
So when you ingest or breathe something and it causes you an inflammatory reaction, it’s in part because of lower Tregs.
7) Activates the HPA Axis
Leptin increases the stress response and the activity of the sympathetic nervous system (fight or flight) .
8) Promotes the Growth of Cancer
Leptin promotes the growth and spread of cancer. This is one reason why obesity is a risk factor for cancer .
It increases angiogenesis by increasing vascular endothelial growth factor (VEGF) levels.
9) May Cause Heart Disease
In obese subjects, leptin levels are the most significant predictor of higher levels of fibrinogen, a clotting factor considered to be one of the most important risk factors for heart disease .
10) Increases Pain Sensitivity
In a study of 3 fibromyalgia patients, they reported higher pain levels on days when they had increased leptin in their blood. A cohort study of 5,600 postmenopausal women showed similar results .
Leptin may increase pain by activating inflammatory markers (IL-1B, IL-6, IL-18) or preventing pain modulating signaling .
11) Reduces the Absorption of Amino Acids and Sugar
It is secreted by the stomach and enters the small intestine. Several studies have shown that leptin interferes with the absorption of some nutrients.
On the one hand, I could see this being both bad and good. If it blocks absorption of glucose and amino acids, it can help weight loss.
However, blocking glucose uptake gives a better chance for SIBO to arise or for malnutrition from not absorbing amino acids.
10) Increases the Risk of Leptin Resistance
Chronically high leptin levels can lead to leptin resistance. Symptoms of leptin resistance include :
- Weight gain and difficulty losing weight
- Urge to snack soon after meals
How to Lower Leptin
When stressed, you release leptin and the more you release, the more you eat comfort foods after .
Since I’m Th1 dominant, decreasing leptin would be beneficial for me, with regards to inflammation.
1) Refrain from Over Eating & Change Your Diet
Consume a diet low in carbohydrates and fat .
Incorporate more anti-inflammatory foods in your diet, such as fatty fish, olive oil, nuts, fruits, and vegetables .
2) Reduce Stress
De-stress on a regular basis to lower your leptin levels.
3) Reduce Toxin Exposure & Inflammation
- Endotoxin in both rodents and humans leads to increased leptin levels [69, 70].
- Inflammatory cytokines such as TNF/IL-1 increase leptin [71, 72]
- Interferon-gamma and LPS mixture in fat cell cultures raises leptin 
Try to uncover the underlying cause of your inflammation.
4) Check Your Estrogen Levels
5) Rule Out Sleep Apnea
Sleep apnea increases leptin in obese people. Their levels go back to normal after CPAP treatment .
6) Try Fasting
Short-term fasting decreases leptin (24-72 hours) .
You can start with intermittent fasting, unless you have a medical condition or are on any medications (in those cases consult with your doctor first) .
6) Get More Exercise
7) Take Cold Showers
8) Other Strategies to Look Into
All the following lower leptin:
- Adrenaline, Norepinephrine, and Dopamine (catecholamines) 
- Thyroid hormones (T3/T4) 
- Testosterone  and androgens 
- cyclic AMP  – you can increase cAMP by taking forskolin.
- Nitric Oxide in fat cell cultures. This would translate to making sure you have good circulation 
- PPAR alpha and PPARgamma 
For example, your leptin might be high because your thyroid hormones or testosterone are low. Check your levels to see if they are in the normal range.
Supplements that can help include:
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