Piperine is the chemical that makes black pepper spicy. It may prevent inflammation and oxidative stress and holds promise in the treatment of diseases as diverse as diabetes, epilepsy, vitiligo, 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 [1].
Piperine is the active ingredient in black pepper and is responsible for a lot of its effects. It is what gives pepper its spicy, pungent taste [2, 3].
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 [4, 3].
It is also classified as a cinnamamide. These are chemicals that have sedative, anticonvulsant, and antidepressant properties [5].
Piperine has numerous potential health benefits. It may protect against inflammation, improve cognitive function, mood, allergies, cholesterol levels, and blood pressure.
It is also an antioxidant and may improve 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 potential effects on the body. These include:
- Decreasing inflammation. It may reduce the levels of cytokines that promote inflammation (IL-1b, TNF-α, and PGE2) and increase the levels of cytokines that reduce inflammation (IL-10) [6].
- 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 may increase the body’s ability to make effective use of many other compounds [7].
- Acting as an antioxidant. It acts directly as a hydroxyl and superoxide radical scavenger [8].
- Inhibiting prostaglandins (hormone-like fats). This may help with diarrhea [9].
- Increasing dopamine and serotonin in the brain – this may help improve mood, cognitive function, and fight off neurodegenerative diseases [10, 11].
- Increasing muscle metabolism by increasing ATPase activity. This may increase the use of energy by the muscles and help in weight loss [12].
Snapshot
Proponents
- May increase the availability of several drugs and supplements
- Potential antioxidant, anti-inflammatory, and sugar- and fat-lowering effects, especially in combination with curcumin
- Few mild adverse effects reported
Skeptics
- Most clinical trials combined it with 100x higher amounts of curcumin
- Most effects have only been tested in animals and cells
- High risk of interaction with drugs
Health Benefits
Likely Effective for:
Increasing Supplement/Drug Bioavailability
Piperine was identified in 1979 as the first-ever compound ever that enhances the “bioavailability” of other substances [13, 7].
In other words, piperine increases the ability of the body to use nutrients and drugs [14].
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 [7]:
- 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 increased the bioavailability of curcumin, a compound found in turmeric, in rats by 154%, and in humans by 2,000% [15].
Piperine also increased the blood concentration and persistence of the anti-seizure drug carbamazepine in 2 trials on 32 people, possibly by blocking the enzyme that breaks this drug down (CYP3A4). Similarly, it increased the bioavailability of the muscle relaxant chlorzoxazone in another trial by blocking the enzyme CYP2E1 [16, 17, 18].
An herbal extract combining piperine and curcumin increased the bioavailability of the sedative midazolam, the anti-inflammatory flurbiprofen, and the painkiller Tylenol in 8 healthy volunteers [19].
A drug delivery system composed of piperine lipospheres increased the bioavailability of both THC and CBD when compared to the FDA-approved spray Sativex in a small trial on 9 healthy volunteers [20].
All in all, the evidence suggests that piperine increases the bioavailability of many substances. Remember to consult with your doctor if it may be helpful in your case and if you should readjust the dose of any drugs or supplements after starting to take piperine.
Insufficient Evidence for:
The following purported benefits are only supported by limited, low-quality clinical studies and animal or cell-based research. There is insufficient evidence to support the use of piperine for any of the below-listed uses. Remember to speak with a doctor before taking piperine supplements. Piperine should never be used as a replacement for approved medical therapies.
Importantly, all the studies testing piperine alone were done in animals or cells, while those in humans generally used a mix with 100x more curcumin than piperine. More clinical trials testing piperine alone are needed to confirm these preliminary findings.
1) Antioxidant
Piperine may protect against oxidative stress by removing free radicals (such as hydroxyl and superoxide) from the body [8].
In a small trial on 20 people with pancreatitis, a combination of curcumin (500 mg) and piperine (5 mg) improved their antioxidant status (lower fat peroxidation and MDA and higher glutathione levels). Combinations with the same proportion of curcumin and piperine also improved antioxidant status in 3 trials on over 100 people with metabolic syndrome, almost 100 people with chronic lung disease, and 40 people with osteoarthritis [21, 22, 23, 24].
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) [25, 26].
In cell studies, low doses of piperine reduced the levels of free radicals. However, very high doses may cause free radical production [8].
2) Inflammation
In a clinical trial on over 100 people with type 2 diabetes or metabolic syndrome, a combination of curcumin and piperine had anti-inflammatory effects (measured as lower CRP levels). However, the mix contained 100x more curcumin than piperine [22].
A similar mix also reduced inflammation (reduced levels of IL4, IL-6, and CRP) in a clinical trial on 40 people with knee osteoarthritis [27].
Piperine reduced both short- and long-term symptoms of inflammation in rats [28].
In rats with arthritis, piperine reduced pain and the size of the swollen joint areas (and decreased inflammatory molecules such as IL-6, MMP13, PGE2) [29].
In rats with gum disease (periodontitis), piperine reduced gum inflammation and bone loss. It also reduced the production of the inflammatory molecules IL-1β, MMP-8 and MMP-13 [30].
It also reduced inflammation in mice with inflammation of the uterus (endometritis) [31].
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 [32].
3) Improving Blood Cholesterol
In 2 clinical trials on over 200 people with type 2 diabetes or metabolic syndrome, a combination of 1,000 mg/day curcumin and 10 mg/day piperine lowered total cholesterol and LDL- and VLDL cholesterol (the “bad”type) while increasing HDL-cholesterol (the “good” type) [33, 34].
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 decreased while HDL–cholesterol increased [35].
4) Metabolic Syndrome
As previously mentioned, the combination of curcumin (1,000 mg/day) and piperine (10 mg/day) improved oxidative, inflammatory, and blood fat status in 2 clinical trials on over 200 people [22, 34].
Supplementation with piperine in rats with 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 [36].
5) Lowering Blood Sugar
In a clinical trial on 100 people with type 2 diabetes, a combination of 500 mg/day curcumin and 5 mg/day piperine lowered blood sugar and reduced liver damage [37]
In diabetic mice, a low dose of piperine (20 mg/kg body weight) reduced blood sugar. However, higher doses increased blood sugar levels [38].
6) Vitiligo
Vitiligo is a long-term condition in which skin patches lose pigmentation. In a clinical trial on 63 people with vitiligo on the face, a combined therapy of piperine and narrowband UV-B radiation enhanced skin repigmentation [39].
Animal and Cell Research (Lack of Evidence)
No clinical evidence supports the use of piperine for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies should not be interpreted as supportive of any health benefit.
Cognitive Function
Multiple animal studies suggest that piperine can boost brain function [40, 41].
For example, rats fed piperine learned faster and retained memories longer [42].
It also enhanced brain function in rats with Alzheimer’s disease. Rats fed piperine had improved memory compared to control rats [41, 40].
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 [41, 40].
Depression
Piperine had antidepressant effects in mice subjected to chronic stress. This effect was linked to the increased production of new brain cells and increased BDNF levels in the hippocampus [43].
Similarly, another study showed that a 2-week administration of piperine reduced depression in mice. It also raised levels of serotonin in the hippocampus and the hypothalamus [44].
Depression is common in epilepsy. In rats with epilepsy, dietary piperine reduced symptoms of depression by increasing serotonin levels [11].
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 [45].
Parkinson’s Disease
In mice with Parkinson’s disease, piperine improved motor coordination. It also improved brain function and learning [46].
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, possibly increasing overall dopamine levels in the brain [10].
Piperine also prevented the death of dopamine neurons in mice. It protected neurons because it is an antioxidant, is anti-inflammatory, and prevents programmed cell death [46].
Allergies
Piperine reduces inflammation and suppresses the immune system, making it a good candidate for treating and preventing allergies [47, 48].
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 [47].
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 [49].
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 [50].
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 [51].
Weight Loss
Rats with high levels of fats and cholesterol in the blood lost weight and fat mass when piperine was added to their diet [35].
In addition, piperine increased the number of calories burned by muscle isolated from rabbits. This increase in metabolism might offer another explanation of why this compound helps with weight loss in animals [12].
Piperine prevented and slowed the production of fat cells [52].
Lowering Blood Pressure
Piperine caused a significant drop in average blood pressure when fed to rats [53].
In another study in rats, it was able to partially prevent the increase in blood pressure caused by a drug (NOS inhibitor) [54].
High blood pressure causes artery walls to be more rigid, which is a predictor of heart disease and stroke. In rats, piperine prevented artery walls from hardening, keeping arteries youthful, healthy, and flexible [54].
Preventing 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 [55].
Increasing Nutrient Uptake in the Gut
Preliminary research suggests that piperine allows the body to absorb more nutrients by making it easier for them to pass through the membrane (inner layer) of the gut. It may also increase the surface of the gut that can absorb nutrients from food, further boosting the gut’s efficiency [56].
Diarrhea
Piperine prevented diarrhea in mice. In rabbits and guinea pigs, it worked as well as loperamide, another drug used to treat diarrhea – but without causing any of loperamide’s usual side effects [9, 57].
It also has anti-spasmodic activity, meaning it may reduce muscle spasms in the digestive tract [58].
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 [59].
Heliobacter pylori is a bacteria that causes chronic stomach inflammation, peptic ulcers, and, in rare cases, stomach cancer. Piperine inhibited H. pylori from growing and sticking to cells, which may reduce the chances of infection [60].
Seizures
In many (but not all) rodent models of epilepsy, piperine reduced the number of seizures and deaths from seizures with doses as low as 10 mg per kg of body weight [61, 62, 63].
Cancer
Below, we will discuss some preliminary research on piperine’s potential anticancer effects. It’s still in the animal and cell stage and further clinical studies have yet to determine if its extract may be useful in cancer therapies.
Do not under any circumstances attempt to replace conventional cancer therapies with white piperine or any other supplements. If you want to use it as a supportive measure, talk to your doctor to avoid any unexpected interactions.
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 [64].
It also decreased tumor growth and metastasis in mice with breast cancer [65].
Piperine prevented breast cancer (with 80-90% efficacy) and decreased breast cancer growth in rats [66].
It slowed the growth of colon, prostate, and breast cancer cells [67, 68, 65].
Piperine may fight cancer in several ways. It may:
- Create free radicals in cancer cells – the same things that it protects the body against through its role as an antioxidant in normal cells [67, 69].
- Reduce the levels of cyclin B1, a protein that lets cells divide [70].
- Cause programmed cell death (apoptosis) of cancer cells by increasing p21 and activating caspase 3 [70, 69].
In addition, piperine increased the bioavailability of other tumor-fighting drugs, increasing their effectiveness, in animal models of cancer [71, 72].
Health Effects That Can Be Positive Or Negative
Animal and Cell Research (Lack of Evidence)
Lowering 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 [73].
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 [74].
Suppressing or Boosting the Immune System
T-cells and B-cells are immune system cells that fight bacteria and other invaders. In mice, piperine reduced the number of T-cells and B-cells and kept T-cells from being activated [75, 76, 77].
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 kept dendritic cells from maturing and made them less able to travel to the lymph nodes [75].
Finally, it reduced 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) [77, 76, 75].
Immune system suppression could be harmful to healthy people, but with further research, it could help in the treatment of autoimmune diseases [77].
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 [78].
Mice fed piperine were less likely to develop a bacterial infection or sepsis [78].
Slowing 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 [79].
Another mouse study showed that doses as low as 0.5 mg/kg slowed the time for food to move through the digestive system [80].
Slowing the passage of food reduces hunger, so piperine could potentially help control hunger and weight [81].
Negative Health Effects
Animal and Cell Research (Lack of Evidence)
Decreasing Fertility
One study in male mice showed that piperine damaged sperm. Piperine increased the number of harmful radicals in the epididymis, the tube where sperm is stored [82].
It also reduced the number of sperm and their ability to move in rats [82].
These fertility effects occurred with doses as low as 10 mg/kg body weight in rats [82].
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 [83].
Increasing 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 [84].
Limitations and Caveats
While piperine shows a lot of potential for treating many disorders and diseases, many of the studies were done in animals only. Human trials are therefore needed to confirm these health benefits in humans.
Side Effects & Precautions
Keep in mind that the safety profile of piperine is relatively unknown, given the lack of well-designed clinical studies. The list of side effects below is not a definite one and you should consult your doctor about other potential side effects based on your health condition and possible drug or supplement interactions.
Piperine is a generally non-toxic compound with few side effects.
One study with human volunteers reported that piperine caused no adverse effects [15].
Some people reported nausea and gut discomfort when using the supplement.
As much as 250 times the average human consumption caused no toxicity in rats [2].
Piperine was once thought to be cancer-causing because it has a similar structure to some cancer-causing chemicals. However, preliminary studies suggest that it may actually protect against cancer [85, 86].
Drug Interactions
Supplement/Herb/Nutrient-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.
Piperine is a bioavailability enhancer, meaning that it helps the body make use of other substances. As such, it may cause many drugs and supplements to have greater effects at even lower dosages [87].
It may enhance the effect of many drugs (including those metabolized by CYP3A4 and CYP2E1 enzymes):
- Diclofenac (a nonsteroidal anti-inflammatory drug) [88]
- Ibuprofen (a nonsteroidal anti-inflammatory drug) [89]
- Fexofenadine (an allergy drug) [90, 91]
- Carbamazepine (anti-epileptic) [16]
- Chlorzoxazone (muscle relaxant) [18]
- Ampicillin trihydrate (a type of penicillin, which is an antibiotic) [92]
- Norfloxacin (antibiotic) [92]
- Nevirapine (a drug used to treat HIV) [93]
- Domperidone (anti-emetic drug) [94]
- Docetaxel (anti-cancer drug) [95]
- Glimepiride (anti-diabetic) [96]
- Nateglinide (anti-diabetic) [97]
- Metformin (anti-diabetic) [98]
Piperine also enhanced the effect of supplements such as beta-carotene, curcumin, and resveratrol [99, 15, 100].
However, it prevented the antidiabetic effects of curcumin in rats [101].
Supplementation
Sources
The regular kind of black pepper that you probably have in your kitchen at home is 0.4-7.0% piperine [3].
Slightly lower amounts are found in white pepper, long pepper, and Balinese long pepper [3].
Piperine supplements are sold both as a powder and as pills.
Dosage
Because piperine is not approved by the FDA for any conditions, there is no official dose. Users and supplement manufacturers have established unofficial doses based on trial and error. Discuss with your doctor if piperine may be useful as a complementary approach in your case and which dose you should take.
In humans, a dose of 20 mg per day can increase the bioavailability of curcumin [15].
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 [51].
- To improve brain function: 5 – 50 mg/kg body weight [102].
- To lower blood pressure: 10 mg/kg body weight [53].
- For antioxidant effects: 20 mg/kg body weight [103].
Ordinary black pepper is around 0.4 – 7.0% piperine. 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 [3].
User Experiences
The opinions expressed in this section are solely those of piperine users, who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.
Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or other qualified healthcare providers because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
Most users took in piperine to enhance the absorption of other supplements or medication. They were generally satisfied with the results and reported noticing the effects of these substances at lower doses. An additional advantage of the supplement according to some users was its low price. Other users reporting good results took it as a pain reliever.
Most dissatisfied users reported not noticing any effects when combining piperine with other supplements for enhanced absorption.
However, some users complained that piperine was too effective at increasing the absorption of other substances. For instance, one complained about enhanced caffeine absorption, which resulted in nausea and an overall feeling of discomfort lasting for several hours.
