Piperine is the chemical that makes black pepper spicy. It prevents inflammation and oxidative stress and holds promise in the treatment of diseases as diverse as cancer, arthritis, epilepsy, and Parkinson’s. It may also increase metabolism and weight loss, improve cholesterol, enhance brain function, and reduce pain. Read on to learn about the many benefits of piperine.

What is Black Pepper?

Black pepper is the most widely used spice in the world.

Long before scientific research explained how it worked, black pepper was used as a folk medicine to treat a variety of conditions and diseases, including rheumatism, influenza, muscle pains, chills, fevers, migraines, and digestive problems. It was also used to enhance blood circulation and stimulate appetite [R].

Piperine is the active ingredient in black pepper and it is responsible for a lot of its effects. It is what gives pepper its spicy, pungent taste [R, R].

In pure form, it is a white or light yellow crystal powder. It tastes similar to pepper and accounts for 98% of the alkaloids found in black pepper [R, R].

It is also classified as a cinnamamide. These are chemicals that have sedative, anticonvulsant, and antidepressant properties [R].

Piperine has numerous health benefits. It protects against inflammation, may improve cognitive function, mood, allergies, cholesterol levels, and blood pressure.

It is also an antioxidant, and it improves the bioavailability of many other drugs and supplements. This means our bodies can make use of them more effectively.

Mechanism of Action

Piperine has many effects on the body. These include:

  • decreasing inflammation. It reduces the levels of cytokines that promote inflammation (IL-1b, TNF-α, and PGE2) and increases the levels of cytokines that reduce inflammation (IL-10) [R].
  • increasing bioavailability of many drugs and supplements. By inhibiting the detox enzymes that break down drugs (such as CYP3A4) and increasing drug/substance absorption in the gut, piperine increases the body’s ability to make effective use of many other compounds [R].
  • acting as an antioxidant. It acts directly as a hydroxyl and superoxide radical scavenger [R].
  • inhibiting prostaglandins (hormone-like fats). This helps with diarrhea [R].
  • increasing dopamine and serotonin in the brain – this help improves mood, cognitive function, and fight of neurodegenerative diseases [R, R].
  • Increasing muscle metabolism by increasing ATPase activity. This increases the use of energy by the muscles and helps in weight loss [R].

Health Benefits of Piperine

1) Piperine Is An Antioxidant

Piperine protects against oxidative stress by removing free radicals (such as hydroxyl and superoxide) from the body [R].

In cell studies, low doses of piperine reduced the levels of free radicals. However, very high doses may cause free radical production [R].

Along with everyday risk factors such as pollutants and radiation, a high-fat diet can cause the production of free radicals. When piperine was given to rats that had been living on a high-fat diet, the number of free radicals decreased. It also increased the levels of enzymes that neutralize free radicals (SOD, CAT, GPx, and GST) [R, R].

2) Piperine Increases Supplement/Drug Bioavailability

Piperine was identified in 1979 as the first ever compound ever that enhances the “bioavailability” of other substances [R, R].

In other words, piperine increases the ability of the body to use nutrients and drugs [R].

This means that lower or fewer doses of the drug can be used to achieve the same effect. This is very beneficial when it comes to drugs that have unpleasant side effects!

Piperine does this by [R]:

  • stopping the body from breaking down drugs by blocking drug-metabolizing enzymes in the liver (such as CYP3A4, CYP2E1, CYP1B1, and CYP1B2)
  • increasing the number of drugs and nutrients absorbed in the gut by stimulating gut transporters

For instance, piperine increases the bioavailability of curcumin, a compound found in turmeric, in rats by 154%, and in humans by 2000% [R].

3) Piperine May Combat Cancer

In skin cancer (melanoma), piperine prevented tumor cells from spreading to other parts of the body (metastasis) leading to significantly better survival rates in mice [R].

It also decreased tumor growth and metastasis in mice with breast cancer [R].

Piperine prevented breast cancer (with 80-90% efficacy) and decreased breast cancer growth in rats [R].

It slowed the growth of colon, prostate, and breast cancer cells [R, R, R].

Piperine fights against cancer in several ways. It:

  • creates free radicals in cancer cells — the same things that it protects the body against through its role as an antioxidant in normal cells [R, R].
  • reduces the levels of cyclin B1, a protein that lets cells divide [R].
  • causes programmed cell death (apoptosis) of cancer cells by increasing p21 and activating caspase 3 [R, R].

In addition, piperine increases the bioavailability of other tumor-fighting drugs, increasing their effectiveness in animal models of cancer [R, R].

4) Piperine May Improve Cognitive Function

Multiple animal studies suggest that piperine can boost brain function [R, R].

For example, rats who were fed piperine learned faster and retained memories longer [R].

It also enhanced brain function in rats with Alzheimer’s disease. Rats fed piperine had improved memory compared to control rats [R, R].

Piperine protected the hippocampus and the cerebrospinal fluid from free radicals. It also caused the growth of new brain cells in the hippocampus, a brain area heavily involved in memory [R, R].

5) Piperine May Combat Depression

Piperine had antidepressant effects in mice subjected to chronic stress. This effect was linked to the increased production of new nerve cells and increased BDNF levels in the hippocampus [R].

Similarly, another study also showed that 2-week administration of piperine reduced depression in mice. It also raised levels of serotonin in the hippocampus and the hypothalamus [R].

Depression is common in epilepsy. In a rat model of epilepsy, feeding rats piperine reduced symptoms of depression by increasing serotonin levels [R].

Piperine’s ability to enhance the effects of other drugs is also helpful when it comes to depression. Resveratrol is a compound that can reduce depression, and this antidepressant works better in mice when combined with piperine [R].

6) Piperine Could Help Treat Parkinson’s Disease

In a mouse model of Parkinson’s disease, piperine improved motor coordination. It also improved brain function and learning [R].

Increasing dopamine levels is the most common way to treat Parkinson’s disease. Piperine inhibits MAO-A and MAO-B, the enzymes that break down dopamine, thereby increasing overall dopamine levels in the brain [R].

Piperine also prevents the death of dopamine neurons in mice. It protects neurons because it is an antioxidant, is anti-inflammatory, and prevents programmed cell death [R].

7) Piperine May Decrease Inflammation

Piperine reduced both short- and long-term symptoms of inflammation in rats [R].

In the rat model of arthritis, piperine reduced pain and the size of the swollen joint areas (and decreased inflammatory molecules such as IL-6, MMP13, PGE2) [R].

In gum disease (periodontitis) in rats, piperine reduced gum inflammation and bone loss. It also reduced the production of the inflammatory molecules IL-1β, MMP-8 and MMP-13 [R].

It also reduced inflammation in a mouse model of endometritis (inflammation of the uterus) [R].

In mice with acute lung injury caused by lipopolysaccharides, piperine reduced the production of cytokines that cause inflammation. It also reduced the accumulation of white blood cells and the build-up of excess fluid in the lungs [R].

8) Piperine May Fight Allergies

Piperine reduces inflammation and suppresses the immune system [R, R]. This makes it a good candidate for treating and preventing allergic reactions.

In mice, piperine reduces sneezing, nose-rubbing, and other symptoms of allergies. It dose-dependently decreased histamine, nitric oxide, IgE, and inflammatory cytokines IL-6 and IL-1b [R].

It also prevented the release of histamine from rat mast cells (a type of white blood cells) and decreased inflammatory IL-4, IL-13, and TNF-a production [R].

9) Piperine May Relieve Pain

As little as 5 milligrams of piperine per kilogram of body weight reduced pain in mice and rats. In humans, this would be roughly equivalent to 1/6th of a teaspoon [R].

Another study in mice showed that higher doses, around 30 to 70 mg per kg body weight, had a similar effect to indomethacin, a pain-relieving drug similar to aspirin or ibuprofen [R].

10) Piperine May Improve Cholesterol

Rats with high levels of fats and cholesterol in the blood were fed piperine for three weeks. Without a change in diet, their levels of total, LDL– and VLDL-cholesterol (the bad kinds of cholesterol) decreased while HDL-cholesterol (the good kind) increased [R].

11) Piperine May Help with Weight Loss

Piperine prevents and slows the production of fat cells [R].

Rats with high levels of fats and cholesterol in the blood lost weight and fat mass when piperine was added to their diet [R].

In addition, piperine increases the number of calories burned by muscle. This increase in metabolism might offer another explanation of why this compound helps with weight loss in animals [R].

12) Piperine May Lower Blood Pressure

Piperine caused a significant drop in average blood pressure when fed to rats [R].

In another study in rats, it was able to partially prevent the increase in blood pressure caused by a drug (NOS inhibitor)[R].

High blood pressure causes artery walls to be more rigid, which is a predictor of heart disease and stroke. In rats, piperine prevents artery walls from hardening, keeping arteries youthful, healthy, and flexible [R].

13) Piperine May Combat Metabolic Syndrome

Supplementation with piperine in rat models of metabolic syndrome decreased blood pressure, improved glucose tolerance, reduced blood markers of oxidative stress and inflammation, prevented tissue damage and inflammation in the liver (fibrosis) and improved liver function [R].

14) Piperine May Prevent Gallstones

Gallstones are formed from crystallized cholesterol in the gallbladder. Piperine prevented cholesterol gallstone formation in mice by reducing the size of cholesterol crystals and decreasing the transport of cholesterol from the liver into the gallbladder [R].

15) Piperine Helps Your Gut Absorb More Nutrients

It allows the body to absorb more nutrients by making it easier for them to pass through the membrane (inner layer) of the gut [R].

It also increases the surface of the gut that can absorb nutrients from food, further boosting the gut’s efficiency [R].

16) Piperine May Help Against Diarrhea

Piperine prevents diarrhea in mice. In rabbits and guinea pigs, it works as well as loperamide, another drug used to treat diarrhea — but without causing any of loperamide’s usual side effects [R, R].

It is also anti-spasmodic, meaning that it reduces muscle spasms in the digestive tract [R].

17) Piperine (In Low Doses) May Lower Blood Sugar in Diabetes

In diabetic mice, a low dose of piperine (20 mg/kg body weight) reduced blood sugar. However, higher doses increased blood sugar levels [R].

18) Piperine May Prevent Ulcers

Piperine prevented the formation of ulcers in rats and mice. It was effective against ulcers caused by stress, hydrochloric acid, and the pain reliever indomethacin [R].

19) Piperine May Combat H. pylori

Heliobacter pylori is a bacteria that causes chronic stomach inflammation, peptic ulcers, and in rare cases of stomach cancer.

Piperine inhibits H. pylori from growing and sticking to cells, which may reduce the chances of infection [R].

20) Piperine May Protect Against Seizures

In many (but not all) rodent models of epilepsy, piperine reduced the number of seizures and reduced deaths from seizures with doses as low as 10 mg per kg of body weight [R, R, R].

Other Effects Of Piperine (Can be Positive Or Negative)

1) Piperine May Decrease Thyroid Hormones

In a study with mice, piperine (2.5 mg/kg) reduced the levels of thyroid hormones as much as standard anti-thyroid drugs did [R].

This can be good for people who have elevated thyroid hormones. However, reducing thyroid levels in healthy people could be harmful. Low levels can cause symptoms such as fatigue, joint pain, and shortness of breath [R].

2) Piperine Can Both Suppress or Boost the Immune System

T-cells and B-cells are immune system cells that fight bacteria and other invaders. In mice, piperine reduces the number of T-cells and B-cells and keeps T-cells from being activated [R, R, R].

When the body senses an invader such as bacteria, it sends dendritic cells to the lymph nodes to activate the T-cells. In mice, piperine keeps dendritic cells from maturing and makes them less able to travel to the lymph nodes [R].

Finally, it reduces the production of molecules that increase immunity (IFN-gamma, IL-2, IL-4, IgM, IgG2b, IgG3) or cause inflammation in response to invasion (IL-6, TNF-α) [R, R, R].

Immune system suppression could be harmful to healthy people, but with further research, it could help in the treatment of autoimmune diseases [R].

On the other hand, piperine can also boost the immune system. In mice, it caused an increase in the production of IL-6 and TNF-α, signal molecules that cause inflammation in response to infection [R].

Mice fed piperine were less likely to develop a bacterial infection or sepsis [R].

3) Piperine May Slow Gut Transit

One study looked at the movement of food and liquids through the digestive system in mice and rats. Low doses of piperine (1 to 1.3 mg/kg body weight) increased the time it took for solids to travel through the digestive system. There was no change for liquids [R].

Another mouse study showed that doses as low as 0.5 mg/kg slowed the time for food to move through the digestive system [R].

Slowing the passage of food reduces hunger, so piperine could potentially help control hunger and weight [R].

Piperine Negatives

1) Piperine May Decrease Fertility

One study in male mice showed that piperine damages sperm. Piperine increased the number of harmful radicals in the epididymis, the tube where sperm is stored [R].

It also reduced the number of sperm and their ability to move in rats [R].

These fertility effects can occur with doses as low as 10 mg/kg body weight in rats [R].

Finally, piperine may prevent pregnancy by stopping fertilized eggs from attaching to the uterus. In mice, piperine injections reduced the number of implanted eggs by half [R].

2) Piperine May Increase the Bioavailability of Some Toxins

This compound may increase toxin bioavailability by the same mechanisms that improve supplement and drug bioavailability.

Rats treated with piperine accumulated more aflatoxin B1 (a toxin from fungi that causes liver damage and cancer) in their tissues [R].

Limitations and Caveats

While piperine shows a lot of potential for treating many disorders and diseases, many of the studies were done in animals. Human trials are therefore needed to confirm beyond doubt these health benefits in humans.

Safety and Side Effects

Piperine is a non-toxic compound with few side effects.

One study with human volunteers reported that piperine causes no adverse effects [R].

Some people reported nausea and gut discomfort when using the supplement.

As much as 250 times the average human consumption causes no toxicity in rats [R].

Piperine was once thought to be cancer-causing because it has a similar structure to some cancer-causing chemicals. Instead, studies have shown that it actually protects against cancer [R, R].

Interactions

Piperine is a bioavailability enhancer, meaning that it helps the body make use of other substances. This means that it causes many drugs and supplements to have greater effects at even lower dosages [R].

It enhances the effect of many drugs (including those metabolized by CYP3A4 and CYP2E1 enzymes):

  • Diclofenac (nonsteroidal anti-inflammatory drug) [R]
  • Ibuprofen (nonsteroidal anti-inflammatory drug) [R]
  • Fexofenadine (an allergy drug) [R, R]
  • Carbamazepine (anti-epileptic) [R]
  • Chlorzoxazone (muscle relaxant) [R]
  • Ampicillin trihydrate (a type of penicillin, which is an antibiotic) [R]
  • Norfloxacin (antibiotic) [R]
  • Nevirapine (a drug used to treat HIV) [R]
  • Domperidone (anti-emetic drug) [R]
  • Docetaxel (anti-cancer drug) [R]
  • Glimepiride (anti-diabetic) [R]
  • Nateglinide (anti-diabetic) [R]
  • Metformin (anti-diabetic) [R]

Piperine also enhances the effect of supplements such as beta-carotene, curcumin, and resveratrol [R, R, R].

However, it prevented the antidiabetic effects of curcumin in rats [R].

Sources

The regular kind of black pepper that you probably have in your kitchen at home is 0.4-7.0% piperine [R].

Slightly lower amounts are found in white pepper, long pepper, and Balinese long pepper [R].

Piperine supplements are sold both as a powder and as pills.

Dosage

There is no official recommended dosage for piperine. In humans, a dose of 20 mg per day can increase the bioavailability of curcumin [R].

There have been few human studies for the other benefits of piperine. However, these daily doses have been effective in mice and rats:

  • For pain relief: 30-70 mg/kg body weight [R].
  • To improve brain function: 5-50 mg/kg body weight [R].
  • To lower blood pressure: 10 mg/kg body weight [R].
  • For antioxidant effects: 20 mg/kg body weight [R].

Ordinary black pepper is around 0.4-7.0% piperine [R]. Therefore, to get 1 full gram of piperine from black pepper, a person would have to eat over six teaspoons of black pepper! Unsurprisingly, it is recommended to use piperine supplements for these doses instead.

User Experiences

Positive:

“Works great with turmeric as a pain reliever.”

I love it and have been using this product for many years now without any problems. It really seems to help with the absorption of other supplements that I take, one being my thyroid medication.”

“Nice inexpensive way to increase the benefits from different food and supplements.”

Negative:

“Because of the Bioperine, my body was super effective at absorbing the caffeine which then resulted in nausea and an overall feeling of discomfort which lasted several hours.”

“I didn’t feel any extra absorption of my daily supplement when I took this product.”

“I have not experienced any noticeable effect (positive or negative) since starting this product. It’s difficult for me to determine whether the bioavailability of my vitamins or other supplements is enhanced by this product.”

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The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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