Leptin is a hormone that plays a key role in regulating energy balance and weight. It is produced primarily by fat cells and works to signal the brain when enough energy (fat) is stored, suppressing appetite and increasing energy expenditure (1).
Some proponents of intermittent fasting claim that it can help reset leptin levels and reverse leptin resistance, improving weight loss. But does the research support these claims? Let’s take a detailed look at the science behind leptin and whether fasting can really reset it.
What is Leptin and How Does it Work?
Leptin is a hormone secreted by adipose (fat) tissue that helps regulate body weight by inhibiting hunger. Leptin binds to receptors in areas of the brain that control appetite and energy expenditure, signaling that enough energy is stored as fat (2).
Specifically, leptin works to:
- Suppress appetite – High leptin levels decrease appetite and food intake.
- Increase energy expenditure – Leptin increases metabolism to burn more calories.
- Regulate glucose levels – Leptin modulates glucose metabolism.
- Manage fat storage – Leptin inhibits the formation of new fat cells and promotes lipolysis (fat breakdown).
When working properly, leptin keeps weight stable by creating an energy balance between calorie intake and expenditure. As fat mass increases, leptin levels rise, signaling to the brain to reduce appetite until weight is lost.
This system can become dysregulated, however, leading to leptin resistance.
Leptin Resistance
Leptin resistance occurs when the brain no longer responds appropriately to leptin’s signals (3). The body produces more and more leptin, but appetite and fat storage aren’t properly regulated.
Leptin resistance promotes weight gain and is associated with obesity. Obese individuals generally produce high levels of leptin but the brain cannot detect these signals.
Potential causes of leptin resistance include (4):
- Inflammation
- Stress
- High blood triglycerides
- Consumption of inflammatory foods
- Poor sleep
- Insulin resistance
Resetting leptin sensitivity is one proposed way to improve weight loss in overweight and obese individuals with leptin resistance. This is where fasting comes in.
Does Fasting Reset Leptin Levels?
Proponents of intermittent fasting claim that it can help reverse leptin resistance by lowering leptin levels. By abstaining from food for set periods of time, intermittent fasting may:
- Lower leptin levels – Fasting for more than 24 hours has been shown to significantly decrease leptin (5).
- Increase leptin sensitivity – Animal studies indicate intermittent fasting may improve leptin signaling in the brain (6).
- Reduce inflammation – Fasting may help decrease inflammatory markers like IL-6 and CRP, which are linked to leptin resistance (7).
- Improve insulin sensitivity – Intermittent fasting can improve sensitivity to insulin, another hormone linked to leptin (8).
Based on this, proponents claim that lowering leptin levels through fasting can reverse leptin resistance. As levels drop, sensitivity increases, allowing leptin to work properly again.
But does the research actually support these hypothesized benefits of fasting for leptin?
Evidence on Fasting and Leptin
Some research has found links between fasting and leptin, including:
- One study in mice found intermittent fasting reversed leptin resistance and normalized body weight (6).
- Studies show fasting for over 24 hours decreases leptin levels by 50% or more (5, 9).
- Three days of alternate day fasting reduced leptin levels and body weight in obese adults (10).
- Ramadan fasting in humans lowered 24-hour leptin levels (11).
However, other studies show mixed results:
- Short fasts of less than 24 hours may not affect leptin levels (12).
- Weight loss from calorie restriction does more to reduce leptin than intermittent fasting (13).
- Although fasting lowers leptin acutely, levels increase during refeeding (14).
- Some research found no benefits of fasting for leptin compared to continuous calorie restriction (15).
Overall, the research suggests intermittent fasting can help decrease short-term leptin levels. But it’s not clear if this directly translates to reversing leptin resistance or sustained weight loss.
More long-term human research is needed on how various fasting protocols impact leptin sensitivity over time.
Other Potential Effects of Fasting on Weight
Although more research is needed, intermittent fasting may aid weight loss and metabolic health via other mechanisms besides lowering leptin levels, including:
Decreasing Insulin Levels
Like leptin, the hormone insulin can become dysregulated in obesity, contributing to weight gain. Fasting decreases insulin levels, which may improve insulin sensitivity (16).
Increasing Adrenaline
Fasting for as little as 48 hours can increase levels of the hormone adrenaline, which signals the body to start burning fat stores for fuel (17).
Reducing Inflammation
Some studies indicate intermittent fasting can reduce systemic inflammation, which is linked to leptin resistance and obesity (18).
Changing Gut Bacteria
Animal research suggests intermittent fasting may support weight loss by changing the composition of intestinal bacteria (19).
So while fasting may help restore leptin sensitivity, other factors like lowered insulin, adrenaline, inflammation, and gut microbiome changes may also contribute to weight loss during intermittent fasting.
Types of Intermittent Fasting
There are several popular types of intermittent fasting, including:
16/8 Method
This involves fasting for 16 hours per day (such as overnight) and restricting food intake to an 8-hour window, like 11am to 7pm. It’s one of the most popular IF methods.
5:2 Diet
This type of intermittent fasting involves eating normally 5 days per week while restricting calories to ~500-600 calories on two fasting days per week.
Alternate Day Fasting
As the name implies, this method involves alternating fasting and non-fasting days. For example, no food or a single small meal one day, followed by normal eating the next.
Periodic Fasts
Some intermittent fasters will do periodic extended fasts such as 24-48 hours every so often, such as once per week or month.
The various intermittent fasting approaches share effects on leptin levels, insulin, inflammation, and gut health. But longer fasts beyond 24 hours may have more dramatic effects.
Tips for Intermittent Fasting
If you want to try intermittent fasting, here are some tips to make it safer and easier:
- Stay hydrated – Drink water, herbal tea, broth, coffee and other non-caloric beverages while fasting.
- Get enough sleep – Poor sleep is linked to leptin resistance. Aim for 7-9 hours per night.
- Exercise during fasting periods – Exercising while fasted can further boost catecholamines for fat burning.
- Include protein during eating periods – Eating protein helps retain muscle mass when calorie restricting.
- Supplement if needed – Electrolytes, B vitamins and magnesium can help side effects.
- Start slowly – Begin with shorter fasts like 12-14 hours and work your way up.
Pay attention to how you feel. If any concerning symptoms arise, stop fasting and see a doctor. Those with medical conditions or on medication should consult their physician first.
Should You Try Intermittent Fasting?
Research shows intermittent fasting can aid short-term weight loss and improve health markers like blood sugar in overweight individuals (20). Findings related to leptin are promising but limited.
Here are some key points on whether intermittent fasting is right for you:
- Benefits still being researched – More human data is needed to confirm effects on hormones like leptin.
- May aid weight loss via multiple mechanisms – Beyond leptin, fasting offers unique benefits for overweight individuals.
- Individual response varies – Fasting is not right for everyone; listen to your body.
- Safety first – Those with medical conditions or on medication should be cautious.
- Consult a professional – Discuss fasting with your doctor, especially if you have diabetes or take blood sugar medications.
If you have trouble controlling appetite and food intake, intermittent fasting under medical guidance may help. But more research is still needed on how fasting protocols truly impact weight regulation and metabolic health over the long-term.
The Bottom Line
Some evidence indicates intermittent fasting may help reset leptin levels and improve leptin resistance, a key driver of weight gain.
However, human data is limited and mixed. More research is needed to clarify fasting’s effects on hormones long-term.
Regardless, fasting offers unique metabolic benefits for health beyond lowering leptin. While no single diet is right for everyone, intermittent fasting is one approach that can help regulate appetite and aid weight loss when done safely and under medical supervision.