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Leptin

Leptin is a well-known 'adipokine' (signalling molecule made in body fat) that acts as a nutrient sensor, and increases metabolic rate during periods of overfeeding; its secretion is sensitive to carbohydrate ingestion, and its elevation during dieting desired.

Our evidence-based analysis on leptin features 5 unique references to scientific papers.

Research analysis led by Kamal Patel.
All content reviewed by the Examine.com Team. Published: Jul 16, 2013
Last Updated:

Frequently Asked Questions about Leptin

Is sugar more filling than HFCS?

Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what supplements affect leptin
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b Minor High See all 3 studies
Mixed influences on leptin, but melatonin may be able to increase leptin levels following acute administration
grade-c Notable - See study
An increase in circulating leptin has been noted with supplementation of pharmacological doses of niacin in subjects with metabolic syndrome.
grade-c Minor - See study
May decrease leptin, but is confounded with weight loss
grade-c Minor - See study
An increase in leptin has once been noted with usage of marijuana.
grade-c
Minor
- See 2 studies
Normalizing a zinc deficiency increases leptin (which is suppressed during deficiency), but elsewhere the abnormal elevation of zinc seen in morbid obesity has been reduced alongside weight loss and insulin sensitization from zinc.
grade-c - - See study
No significant influence on circulating leptin concentrations when compared to control.
grade-c - Very High See 2 studies
Not enough evidence to support alterations in circulating leptin due to CLA ingestion.
grade-c - - See study
No significant influences detected on circulating leptin levels with fenugreek
grade-c - Very High See 2 studies
No significant influence on Leptin in serum
grade-c - - See study
In a study that noted an increase in adiponectin in persons with metabolic syndrome, there was no influence on circulating leptin concentrations.
grade-c - - See study
No significant influence on leptin in otherwise healthy and lean individuals
grade-d Minor High See all 3 studies
Mixed evidence suggesting a possible small reduction in people with non-alcohol fatty liver disease.

Scientific Research on Leptin

  • Leptin equates to a level of "available energy" for your body

    • Secreted by your fat cells (specifically white fat cells)

    • In rats, obese mice had no leptin. Following injection with leptin rapid fat loss occurred.

    • Rage over leptin as the miracle weight-loss hormone

    • Contrary to rats, overweight human beings had high leptin levels

      • Overweight people had developed resistance to leptin (similar to insulin resistance)

      • Essentially the signal from leptin to brain was broken somewhere

    • Injecting overweight humans with leptin provided no real weight loss

    • Leptin scales with subcutaneous fat (higher in woman) (Inversely, insulin scales with visceral fat, higher in men)

      • Estrogen seems to increase response of leptin

    • Leptin levels do not change quickly (can take hours)

    • Males below 10% bodyfat have almost no leptin in their bloodstream

      • Women have 2-3x leptin compared to men with equal BF%

    • Leptin seems to respond directly with carbohydrate metabolism in fat cells

      • Responds to both over and under-feeding

    • After a week of dieting, leptin drops 30-50%

    • Short-term carb overfeeding can bring leptin levels up (faster than fat is gained)

      • Only responds to carb-intake. Overfeeding on fat does not produce a similar response

      • Refeeds are used for both leptin and insulin

    • Leptin basically tells your body:

      1. How much fat you are carrying
      2. How much you are eating
    • Leptin is involved in a lot of stuff, including:

      • Fat oxidation

      • Liver metabolism

      • Immune system

      • Hunger regulation

      • Libido

        • Too much body fat also impacts libido negatively due to insulin resistance

      • Possibly more

    • Levels are critical for puberty and fertility

      • Need a minimum level of fat for puberty. Childhood obesity -> higher leptin levels -> earlier puberty

      • Without enough leptin ("energy"), body decides reproduction not as important, shuts down reproductive system

        • Raising leptin brings back reproductive function without weight gain

    • Leptin is basically a safeguard from starving. With not enough "energy" body slows itself down

    • Lower levels of leptin could also impact dopamine signalling (aka increased resistance)

    • Existing fat levels matter. Losing 5% of BF at 30% BF does not trigger the same response as losing 5% of BF at 10% BF

    • Low leptin levels also make it hard to feel satiated

      • Conversely, in the short term, leptin tells your body it is full

    • As a supplement, leptin has to be injected. Pretty much impossible to get and very expensive

    • Best way to raise leptin is a high carb/high calorie refeed of at least two meals (eg lunch + snack).

      • Need multiple meals as leptin does not change quickly like insulin

      • The leaner you are, the more refeeds are important in restoring leptin levels Zinc and Vitamin E may have an impact on leptin production Exercise and fish oil also may improve leptin transport (aka sensitivity)

    • Blood triglycerides seem to be cause of resistance (lower in high fat diets)

    • Insulin (not excessive amounts) and epinephrine increase leptin transport

    • Inflammation (omega 6/3 ratio) also increases leptin resistance

    • Refeeds should be high carb, moderate protein, low fat

      • Post workout is optimal time

      • Eg, Mark Sisson recommends 250-300g. Martin Berkhan targets 100-150g.

    • Short term cortisol increase can help leptin levels

    • Intermittant fasting (IF) is possibly positive - during fasting it falls, but breaking fast/refeed elevates it

      • In one study, mean leptin levels are increased. In a Ramadan study, the mean was the same

    • High amounts of fructose increases leptin resistance

References

  1. Melanson KJ, et al. Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. Nutrition. (2007)
  2. Monsivais P, Perrigue MM, Drewnowski A. Sugars and satiety: does the type of sweetener make a difference. Am J Clin Nutr. (2007)
  3. Soenen S, Westerterp-Plantenga MS. No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads. Am J Clin Nutr. (2007)
  4. Melanson KJ, et al. High-fructose corn syrup, energy intake, and appetite regulation. Am J Clin Nutr. (2008)
  5. Stanhope KL, et al. Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. Am J Clin Nutr. (2008)