As a pharmacist I get asked questions about supplements all the time. One in particular keeps coming up and it’s about leptin supplements.
Patients tell me they are hungry all the time and wonder if leptin supplements will curb their appetite. They have heard that leptin is a hormone, made by fat cells in the body, which decreases your appetite.
So naturally, one would think that having more leptin would decrease appetite.
I can see why patients believe this to be true of leptin. Even scientists, upon first discovering leptin in 1994, thought that leptin would be the wave of the future as a weight loss treatment.
Unfortunately, leptin did not turn out to be the magic bullet people hoped for, and here’s why…
What Is Leptin?
Leptin is a protein made in our bodies’ fat cells. The protein is released into the bloodstream when we have enough energy stored in our fat cells to perform our bodily functions. Once in the bloodstream, leptin travels to the brain and tells it that you have enough energy for now. In other words, you can stop taking in calories. You can think of leptin as a mechanism similar to how you charge your cell phone. When the battery is full and green, your brain tells you it’s okay to unplug it from the charger.
Now let’s say you use the phone for several hours (i.e. burn calories) and the battery is no longer fully charged. Some people like to charge their batteries when they see the battery turn red; others like to charge before that. Still others let it completely die. Everyone is different.
This is similar to how leptin works. When you use up your stored energy, your body has a certain leptin level it likes to keep, and when it falls below that level, your brain thinks that you are starving and need to consume more energy.
That is why leptin is also known as the “starvation hormone,” even though it’s more commonly called the “satiety hormone.”
Once your brain thinks you are starving, several processes begin within the body to raise leptin levels back up.
One process includes stimulation of the vagus nerve. The vagus nerve is the super highway that runs between the brain and the abdomen.
It’s also been dubbed the “hunger nerve” because when activated, you get hungry, and your body attempts to store more energy in your fat cells.
This is all done to get leptin levels back to where your body likes it.
So How Does Leptin Influence Overall Weight?
Good question. If your body knows where it likes leptin levels to be, then why do you keep eating after that level is reached? Shouldn’t everything stay in balance?
Unfortunately, even when the leptin mechanism is doing its job, there are other factors in play. This became readily apparent when researchers found that overweight people actually have large amounts of leptin circulating in their blood.
The leptin signal to stop eating was there, but the brain wasn’t listening.
This phenomenon is called “leptin resistance.”
You may have heard of “insulin resistance” associated with type 2 diabetes. This is where the pancreas produces large amounts of insulin, but the body doesn’t respond to it correctly. Leptin resistance works in a similar fashion.
In leptin resistance, leptin levels are high and a signal is being sent, but due to other conditions in the body, the brain can’t respond to the signal. When this happens your brain acts as if there isn’t enough leptin, and the result is that you overeat.
What makes this worse is that food, especially sugary, salty, and fattening foods, are addicting and play into a reward system in our brains. We crave these foods because they bring us a sense of satisfaction, like a reward, and leptin plays a role in the intensity of that reward.
When we are starving and leptin levels are low, the more rewarding and satisfying food becomes. Then when leptin levels are high the less tempted we are by food.
However, with leptin resistance, food remains tempting because your brain isn’t responding properly even after you’ve eaten your favorite candy bar.
The end result is that you crave more rewarding food but are never fully satisfied. Sounds like a drug addiction right? Well it can be, and this is the vicious cycle that leads to obesity.
Can Leptin Treat Obesity?
Leptin was definitely an attractive candidate for treating obesity when it was first discovered in 1994.
Previous to leptin’s discovery, obesity was thought to be the outcome of a person’s choice to overeat or a lack of willpower towards food.
Knowing that there was a hormone that controlled hunger made scientist and overweight people excited because now there was a physiological explanation for obesity. This meant that manipulating this hormone could lead to weight loss.
The rationale seemed clear enough to scientists … overweight people must be leptin-deficient, so giving them leptin would raise their leptin levels and signal them to stop overeating. Based on this theory, clinical trials began using exogenous leptin, but the outcome was not what scientist expected.
As it turned out most obese people already had high levels of leptin, not low levels. After many more trials, scientist finally concluded that “leptin resistance” was more to blame for obesity than leptin-deficiency.
This meant that only people who had a true congenital leptin-deficiency would benefit from leptin injections, and that is only a tiny segment of the obese population.
As of 2015 studies have not concluded otherwise, except to say that leptin may play a role in weight loss maintenance.
The rationale is that leptin levels drop when a person loses weight. This signals the brain to eat in order to bring leptin levels back up. This increase in appetite could cause a person to regain the weight they lost and return to their “set weight”.
Do Leptin Supplements Work?
Leptin is given as a subcutaneous injection, and can’t be given in pill form. This is because leptin is a digestible protein that is broken down in the stomach before it ever reaches the blood stream.
This means that leptin supplements don’t contain any leptin. If you read closely, most of the supplements that contain the word leptin also have words like enhancer, control, or support.
These supplements attempt to control factors that would decrease leptin or increase the body’s response to leptin.
For example, a supplement may include melatonin to promote better sleep, because sleep deprivation is thought to lower leptin levels.
You may also see appetite suppressants or soluble fibers that help you feel full. Or you might see L-carnitine which is thought to balance leptin, conjugated linoleic acids (cla) to lower leptin levels and blood sugar in people whose leptin is too high, and many other ingredients that promote overall health.
Aiding in leptin functioning in this indirect manner, via the use of supplements, hasn’t been fully proven to balance leptin or improve resistance. Researchers are still trying to elucidate exactly what causes leptin resistance in the first place.
Leptin resistance may to be tied to the same health factors that cause insulin resistance. This includes excess weight and physical inactivity.
Excess weight, especially visceral fat in the belly area, is thought to cause low-level chronic inflammation that contributes to the development of insulin resistance and concomitantly leptin resistance.
That being the case,supplements that contain antioxidants to fight this inflammation may be of some use, but what seems more useful is managing food intake.
Diets high in processed sugar and fat lead to increased levels of insulin, triglycerides, and free fatty acids which all appear suspect in the development of both insulin and leptin resistance.
The underlying message here is that leptin resistance is more to blame for obesity than low levels of leptin, and practical measures like improved diet and exercise are still the best options to solve the root of the problem.
What Other Roles Does The Leptin Hormone Play?
Taking leptin exogenously for weight loss didn’t end up being the revolutionary treatment everyone hoped for, but that doesn’t mean the hormone didn’t tell us anything useful. If the hormone was never discovered, we wouldn’t know about leptin resistance, and that it needs to be managed.
Plus it turns out leptin plays other roles in the body. Like most hormones, leptin doesn’t just affect one system, and it isn’t only found in the adipocytes and blood stream.
Leptin has been detected to a lesser extent in the hypothalamus, pituitary, stomach, skeletal muscle, mammary epithelia, chondrocytes, and a variety of other tissues. This means irregularities in the leptin feedback loop, such as inadequate signaling, high leptin, leptin deficiency, and leptin resistance can negatively affect other systems.
High leptin in combination with leptin resistance may cause hormonal imbalances, abnormalities in thermoregulation, increased bone mass, infertility, and immune and hematopoietic defects. Congenital leptin deficiency is associated with hypgondotropichypogonadism, morbid obesity and frequent infections. (3)
Complications from all these imbalances may lead to bigger problems, such as cancer and cardiovascular disease.
So as you see, leptin is fully integrated and complex, so there’s much more to learn and discover from this hormone.
There may yet be a solid treatment method that springs from what we learn. Until then, the best way to help yourself is to reduce your body fat percentage through proper nutrition and exercise.