Will a Leptin Supplement Help Weight Loss?

Leptin is a hormone that is derived from fat cells. It is involved in regulating appetite, maintaining energy balance,  body mass, and reproductive function.

When the number of fat cells in a body increases, leptin levels also increase, sending signals to the brain to block food intake and increase energy expenditure.

On the other hand, leptin levels decrease during fasting or energy restriction.

The following article covers leptin supplements, potential benefits, and safety concerns.

Will a Leptin Supplement Help With Weight Loss?

Several health claims have been proposed for leptin supplements.

Some of the common claims made by manufacturers and promoters of leptin supplements include the following:

• Appetite suppression and reduced food cravings
• Enhanced metabolism and fat-burning
• Potential support for leptin sensitivity

However, the benefits of leptin supplements are unclear due to limited studies and conflicting results.

It is important to support a healthy body weight through lifestyle modifications and not solely rely on supplements.

What Is Leptin?

Given that leptin reduces appetite, interest in using leptin supplements as a weight loss strategy has grown.

While people with obesity have higher concentrations of leptin due to their greater body fat amount compared to lean people, obesity is associated with genetic mutations (changes in DNA sequencing) that affect leptin signaling. These genetic mutations lead to leptin deficiency, or high but ineffective leptin, and leptin resistance.

Leptin resistance occurs when leptin cannot reach the target cells to produce an appetite-suppressing effect.

Although both leptin and adiponectin are hormones derived from fat cells, adiponectin has the opposite effect of leptin by working to stimulate food intake instead.

Ghrelin, also known as the “hunger hormone,” is produced and released in the stomach. Unlike leptin, it is an appetite-stimulating hormone.

Resistance to leptin causes reduced satiety (a satisfied feeling of fullness), which in turn causes overconsumption of food and weight gain.

Because leptin supplementation alone is insufficient to overcome leptin resistance associated with obesity, some studies have looked further at leptin sensitizers.

Leptin sensitizers are compounds that boost the effect of leptin. For example, one study done in mice found that the natural compound celastrol promoted leptin sensitivity and produced anti-obesity effects.

As the study was conducted in mice, it is unclear if celastrol would also promote leptin sensitivity in humans.

What Is a Leptin Supplement?

Leptin supplements do not contain the leptin hormone. Instead, leptin supplements consist of a combination of herbs that help suppress appetite.

Some of the supplements that purportedly impact leptin levels include the following:

• Irvingia gabonensis (I. gabonensis): Known as African mango, I. gabonensis has maintained leptin concentrations in people with obesity. The results indicate the beneficial effect of I. gabonensis in preventing a decrease in leptin levels.
• Conjugated linoleic acid (CLA): Although CLA has reduced leptin levels, one study showed that CLA supplementation did not affect them.
• Glycosaminoglycans (GAGs): Glycosaminoglycans are long-chain carbohydrate molecules that play a role in cell adhesion, growth, and signaling. A test-tube study done in a bovine (cow) model showed that as leptin levels increased, the rates of GAG production decreased.
• Green coffee bean extract: Combining green coffee bean extract and an energy-restricted diet significantly decreased leptin levels. Because energy restriction alone reduces leptin levels, it is unclear if green coffee bean extract alone would exert a similar effect.
• Raspberry ketone: In a rat study, raspberry ketone decreased leptin and improved leptin resistance.
• Garcinia cambogia (GC): Hydroxycitric acid is one of the main compounds found in GC and is responsible for its beneficial effects on obesity and inflammation. Based on an analysis of a collection of studies, supplementing with GC decreased leptin levels in the blood. However, further research is needed as other studies yielded conflicting results.
• Caffeine: In one study, the consumption of coffee was associated with reduced leptin concentration. Further clinical studies are needed since other studies showed contradictory results.
• Green tea: An analysis of a group of studies found that drinking green tea for more than 12 weeks increased leptin concentration. However, more long-term studies are needed to confirm the results.

The above supplements are typically marketed to support weight loss by affecting leptin levels. 

Although it is counterintuitive to think that lowering leptin levels improves weight loss because leptin is considered a satiety hormone, reducing leptin levels appears to improve leptin sensitivity in people with obesity.

Even though leptin reduces appetite, elevated levels of leptin in people with obesity may promote inflammation, thereby increasing the risk of heart disease and type 2 diabetes and leading to leptin resistance.

Conversely, reduced levels of leptin found in people who are malnourished have been linked to decreased immunity.

High leptin levels do not necessarily mean less hunger since people with obesity can have increased leptin levels and leptin resistance. Thus, some studies have focused on analyzing the effects of using both leptin and leptin sensitizers. 

While leptin supplements do not actually contain the hormone leptin, prescription leptin replacement therapies do. For instance, Myalept (metreleptin) is a leptin replacement therapy used to treat leptin deficiency in people with generalized lipodystrophy (loss of fat tissues).

Alternatives to Improve Weight Management

Besides supplements, there are other ways to improve weight management. 

Some weight-management strategies include the following:

• Eating a balanced diet consisting of high-fiber foods, lean protein, healthy fats, anti-inflammatory food, lower starch vegetables, fruits, etc.
• Avoiding diets high in fat, carbohydrates, fructose, and sucrose (also known as table sugar) and low in protein
• Reducing stress through relaxation techniques, such as yoga, acupuncture, meditation, etc.
• Obtaining adequate, good-quality sleep
• Engaging in physical activity
• Fasting (which has been suggested to improve leptin sensitivity)

While intermittent fasting (IF) has helped support weight loss, the use of IF in people with diabetes poses a risk of low blood sugar levels in the blood. It may also not be an optimal approach for individuals with disordered eating or eating disorders.

Speak with your healthcare provider before making any dietary changes, especially if you have diabetes.

Safety and Potential Risks

While leptin supplements are generally well-tolerated, some common side effects have been reported in some leptin supplements.

Possible Side Effects

Side effects are possible with leptin supplements, including the following:

• Irvingia gabonensis: Headaches, difficulty sleeping, and intestinal flatulence
• Conjugated linoleic acid: Stomach discomfort, diarrhea, fatigue, and nausea
• Green coffee bean extract: stomach irritation, dizziness, nausea, headache
• Raspberry ketone (RK): Side effects on reproduction and heart functions in animal models, making human clinical studies necessary to investigate such side effects
• Garcinia cambogia (GC): Stomach discomfort, dizziness, and increased urination
• Caffeine: Shakiness, difficulty sleeping, headaches, dizziness, fast heart rate, dehydration, and anxiety

Most leptin supplements appear to decrease leptin levels, which would likely improve leptin sensitivity in people with obesity.

Interactions

Several interactions are possible with supplements that may be used to impact leptin, and other supplements or medications.

Irvingia gabonensis

Interactions with blood-sugar-lowering drugs may occur. I. gabonensis has been shown to decrease blood sugar levels.

Therefore, caution should be taken if you take blood-sugar-lowering drugs or supplements.

Conjucated Linoleic Acid

The following interactions may occur:

• Blood-sugar-lowering drugs: Studies on the anti-diabetic effects of CLA are unclear. However, it has been suggested that CLA reduces insulin sensitivity, contrary to the action of some anti-diabetes medications.
• Retinol (vitamin A): CLA has been shown to increase retinol levels in the tissues.
• Cholesterol-lowering drugs: CLA has been shown to decrease levels of low-density lipoprotein (LDL) cholesterol (“bad” cholesterol). Therefore, taking cholesterol-lowering medications, such as statins, may have an additive effect.

Green Coffee Bean Extract

Interactions may occur with stimulant drugs. A high intake of chlorogenic acid, the main antioxidant in green coffee bean extract, may cause increased blood pressure.

Since stimulant drugs increase blood pressure, the combination of such drugs with green coffee bean extract may further increase blood pressure.

Raspberry Ketone

The following interactions may occur:

• Stimulants: Taking raspberry ketone with stimulants might increase the heart rate and blood pressure.
• Jantoven (warfarin): Raspberry ketone might decrease the effects of the blood thinner warfarin, which, in turn, increases the risk of blood clots. It is important to talk with your healthcare provider before starting any supplements if you take warfarin.

Garcinia Cambogia

The following interactions may occur:

• Liver-toxic drugs: Liver toxicity has been reported with the use of Garcinia-containing products. As a result, the use of drugs that increase the risk of liver damage along with G. cambogia should be avoided.
• Serotonergic drugs: Cases of serotonin toxicity have been reported. Therefore, the combination of G.cambogia and other serotonergic drugs (e.g., certain antidepressants) should be avoided due to the risk of serotonin syndrome. 

Caffeine

Caffeine impacts the absorption of many medications and supplements. When a medication’s absorption changes, this may impact how well your body can use it.

Caffeine decreases the absorption of the following medications:

This means that the effects of these medications may be reduced by green tea.

Caffeine increases the absorption of the following medications:

This means that green tea may amplify these medications’ effects.

Caffeine blocks the breakdown of the following medications:

• Melatonin, widely used for sleep support
• Dextromethorphan, an over-the-counter cough suppressant
• Jantoven (warfarin), used to prevent blood clots
• Inderal (propranolol), for anxiety, high blood pressure, and other heart conditions
• Elavil (amitriptyline), used for depression, chronic pain, and migraines (off-label use).
• Luvox (fluvoxamine), a selective serotonin reuptake inhibitor (SSRI) for depression, obsessive-compulsive disorder, and social anxiety

Caffeine increases the elimination of the following minerals and vitamins:

This is not a comprehensive list of medications that caffeine may impact. Check with your pharmacist or healthcare provider for more information.

Green Tea

Green tea reduces the rate of absorption of the following prescription medications:

This can impact how well your body uses these medications.

Precautions

Specific groups of people may need to exercise additional caution when taking supplements that may impact leptin.

In general, please consult with your healthcare provider if you are pregnant or breastfeeding before starting any of the above supplements. 

Irvingia Gabonensis

Since I. gabonensis decreases blood sugar levels, precaution should be taken if you have diabetes.

Conjugated Linoleic Acid

Precautions should be taken with the following conditions:

• Insulin resistance: Lab and mouse studies suggested CLA may contribute to insulin resistance. Therefore, caution should be taken with CLA supplements, especially if you have diabetes.
• Liver toxicity: In a mouse study, CLA caused liver enlargement and fatty liver disease due to elevated triglyceride levels. While it is unclear if such findings apply to humans, caution should be exercised in using CLA supplements long-term.
• Heart conditions: CLA has been associated with higher levels of inflammatory markers in the urine of healthy females who are postmenopausal. In addition, CLA has been shown to increase triglycerides and LDL levels. Please consult with your healthcare provider before starting CLA supplements if you have heart conditions.

Green Coffee Bean Extract

Precautions should be taken when pregnant or breastfeeding. Avoid use at these times due to insufficient safety data. 

Green coffee bean extract may contain caffeine.

Caffeine may worsen the following medical conditions:

Raspberry Ketone

Animal studies showed that raspberry ketone supplementation decreases fasting blood sugar and insulin levels. It is unclear whether this finding may apply to humans.

However, caution should be taken if you have diabetes.

Garcinia Cambogia

Severe side effects have been reported with the use of dietary supplements containing G. cambogia, including the following:

Garcinia cambogia should be avoided if you have the above medical conditions or take certain antidepressant medications.

Green Tea

Green tea extract has been shown to increase the level of liver enzymes. Therefore, caution should be taken if you have liver problems. 

Since green tea contains caffeine, caution should be taken if you have anxiety disorders, difficulty sleeping, or high blood pressure.

Summary

Leptin supplements contain a combination of herbs that affect leptin levels, with a reduction in leptin levels being associated with improved leptin sensitivity. 

However, if you take certain prescription medications or have certain medical conditions, it is important to consult your healthcare provider before taking leptin supplements.

Alternative ways to improve weight management include dietary and lifestyle changes. Consider working with your healthcare provider or a registered dietitian nutritionist to meet your health goals.