Black Pepper (Piper nigrum L.): A Comprehensive Scientific Review

Description and Production

Black pepper is a woody vining plant that originates from the southwest coast of India (Malabar coast) and grows in tropical climates. The part of the plant that is usually used as a spice are the immature but fully developed fruits of the plant (black pepper grains). After harvesting, these grains are dried in the sun or processed in special drying ovens. During the drying process, the grains shrivel and take on their characteristic black color.

Apart from black pepper, white pepper (fully ripe, peeled), green pepper (unripe, undried or pickled) and red pepper (fully ripe, dried with the outer skin) can also be obtained from the same plant through different processing methods. Each of these varieties has its own unique flavor profile and chemical composition.

Biochemical Composition

The health effects of black pepper are due to its rich and diverse biochemical composition. The most important active ingredient is piperine, but it also contains other essential oils, terpenes, phenolic compounds and alkyamides:

• Piperine: It is the main active alkaloid of black pepper and gives the oil its bitter, pungent flavor. It accounts for about %5-9 of the dry weight of black pepper. Piperine is responsible for many pharmacological effects of black pepper (anti-inflammatory, antioxidant, bioavailability enhancer, etc.).
• Essential Oils It contains terpenes such as limonene, pinene, sabinene, beta-caryophyllene, myrcene and terpenoids such as terpinen-4-ol. These compounds create the characteristic aroma of black pepper and may contribute to some biological activities.
• Phenolic Compounds: It contains compounds with antioxidant properties such as flavonoids and phenolic acids.
• Alkyamides Apart from piperine, other alkamides such as piperlonguminin, piperine, chavicine are also present in trace amounts.
• Vitamins and Minerals: Contains trace amounts of vitamin K, iron, manganese and dietary fiber.

Effects on Body Functions

Black pepper and piperine have been the subject of numerous studies offering a wide range of potential effects:

1. Bioavailability Enhancement (Bioenhancer): The best known effect of piperine is that it significantly increases the absorption and bioavailability of other dietary supplements and certain medicines, notably curcumin (from turmeric), resveratrol, coenzyme Q10 and beta-carotene. This effect is mediated by piperine's inhibition of P-glycoprotein in intestinal cells and CYP450 enzymes in the liver.
   • Research Example: Shoba ve ark. (1998) tarafından yapılan klasik bir çalışmada, piperinin insanlarda kurkuminin biyoyararlanımını %2000’e kadar artırdığı gösterilmiştir. Bu, birçok modern besin takviyesinde karabiber ekstraktı (piperin) kullanılmasının temel nedenidir.
2. Antioxidant Effects: Black pepper has strong antioxidant properties thanks to its piperine and other phenolic compounds. It reduces oxidative stress by neutralizing free radicals and increasing the activity of antioxidant enzymes. Oxidative stress is one of the main factors underlying many chronic diseases (cancer, heart disease, neurodegenerative diseases).
   • Research Example: An in vitro study by Gülçin et al. (2007) showed that black pepper extract has strong antioxidant activity.
3. Anti-inflammatory Effects: Piperine exhibits potent anti-inflammatory properties by inhibiting various inflammatory pathways (e.g. NF-$\kappa$B, COX-2, iNOS). This may help in the management of joint pain, arthritis and other chronic inflammatory conditions.
   • Research Example: A review by Faizi et al. (2018) emphasized that piperine has therapeutic potential in chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis.
4. Cardiovascular Health: Black pepper and piperine show potential positive effects on cardiovascular health:
   • Cholesterol and Triglyceride Lowering: In some animal studies it has been shown to help lower cholesterol and triglyceride levels.
   • Blood Pressure Regulation: It has been found to have blood pressure lowering effects in animal models.
   • Anti-atherosclerotic: It may slow the development of atherosclerosis.
   • Research Example: An animal study by Koul and Kapil (2000) showed that piperine reduced high-fat diet-induced hyperlipidemia (high blood fats) in rats. Further clinical research in humans is needed.
5. Metabolic Health and Weight Management: Piperine may accelerate metabolism by contributing to an increase in thermogenesis (body heat production) and inhibit the differentiation of fat cells (adipogenesis). It is also thought that it may improve insulin sensitivity.
   • Research Example: A study by Kim et al. (2012) showed that piperine reduced high-fat diet-induced obesity and insulin resistance in mice.
6. Digestive Health: Black pepper has traditionally been used to stimulate digestion and relieve gas. Piperine can increase the activity of digestive enzymes and regulate intestinal motility.
   • Research Example: A review by Srinivasan (2007) stated that black pepper aids digestion by stimulating the secretion of pancreatic and intestinal enzymes.
7. Immune System: Black pepper is thought to have immunomodulatory effects. Its antioxidant and anti-inflammatory properties may optimize the function of immune cells and contribute to resistance to infections.
   • Research Example: Some in vitro studies suggest that piperine may modulate the activity of T cells and promote some immune responses (Aggarwal & Shishodia, 2006).
8. Brain Health and Neuroprotective Effects: Piperine may act as a supportive approach in the prevention of neurodegenerative diseases (Alzheimer's, Parkinson's) through its antioxidant and anti-inflammatory effects. It may also have positive effects on mood and cognitive functions by affecting neurotransmitter levels.
   • Research Example: A review by Liu et al. (2019) summarized the evidence for the neuroprotective potential of piperine in Alzheimer's and Parkinson's diseases.
9. Anticancer Potential: In laboratory and animal studies, piperine has been shown to inhibit growth in different cancer cell lines (breast, colon, prostate), promote apoptosis (programmed cell death) and may improve the efficacy of chemotherapy. However, evidence for its supportive use in human cancer patients is still limited.
   • Research Example: A comprehensive review by Prasad et al. (2020) detailed the anticancer potential and mechanisms of action of piperine in various cancer types.
10. Physical Performance: There is insufficient scientific evidence on a specific direct physical performance-enhancing effect of black pepper or piperine. However, its general effects of reducing inflammation and supporting metabolism may indirectly contribute to post-exercise recovery and overall endurance.
11. Reproductive Health: There is limited and conflicting evidence on the effects of piperine on reproductive health. Some animal studies have suggested that at high doses it may affect sperm motility or testicular function. More research is needed on its effects on human reproductive health and caution should be exercised when taking high doses as a supplement.

Areas of Use

Black pepper has a wide range of uses:

• Kitchen: As one of the world's most popular spices, it is used to add flavor and spiciness to dishes. Freshly ground black pepper has a more intense aroma and taste.
• Traditional Medicine: It has been used traditionally for various ailments such as digestive problems, colds, coughs, pain and inflammation.
• Nutritional Supplement: Piperine extract is used to increase the bioavailability of other dietary supplements, notably curcumin. It can also be found as a component of some anti-inflammatory and antioxidant supplements.
• Cosmetics: It can be used in some skin care products for its antioxidant and stimulating properties.

Side Effects and Dosage Information

Black pepper is generally considered safe when used in normal amounts in meals. However, some side effects and conditions to watch out for may occur when taking piperine in supplement form or in excessive amounts.

Side Effects:

• Gastrointestinal Irritation: High intakes of black pepper or piperine can cause digestive disorders such as heartburn, nausea, abdominal pain or diarrhea.
• Drug Interactions: Due to piperine's effect on CYP450 enzymes and P-glycoprotein, it has the potential to interact with many medicines. This may increase the blood levels of the drugs, increasing the risk of side effects or decreasing their effectiveness. In particular, those taking the following groups of medicines should be careful:
  • Blood thinners (anticoagulants): It may increase the risk of bleeding when used with medicines such as warfarin.
  • Diabetes medicines: Due to its blood sugar lowering effect, it may increase the risk of hypoglycemia when used with diabetes medications.
  • Cyclosporine It may increase the absorption of the immunosuppressant drug cyclosporine, raising its levels in the blood.
  • Some antidepressants, antiepileptics, statins and heart medicines: It can alter blood levels by affecting their metabolism.
• Allergic Reactions: Very rarely, allergic reactions to black pepper (skin rash, itching, shortness of breath) may occur.
• Pregnancy and Breastfeeding: There is insufficient data on the safety of black pepper or piperine supplement use for pregnant and breastfeeding women. It is recommended to avoid use during these periods or use with the advice of a doctor.
• Children: There is insufficient safety information on the use of high doses of piperine supplements in children.

Dosage

Because black pepper is a spice, the amounts used in the kitchen are generally safe and not set as a "dosage". The dosage of piperine supplements used for therapeutic purposes is different.

• Meals The amounts of black pepper added to normal meals are usually between a few hundred milligrams and a few grams and are safe.
• Piperine Supplement: Doses of piperine used in supplements generally range from 5 mg to 20 mg. These doses are usually determined to increase the bioavailability of other compounds (e.g. 5 mg piperine for 500 mg curcumin).

It is imperative to consult a healthcare professional (doctor, dietitian, pharmacist) before using any piperine supplements, especially if there is a chronic health condition or regular medication is being taken.

Storage Conditions

Proper storage conditions are important to preserve the quality, aroma and shelf life of black pepper grains and ground black pepper:

• Airtight Containers: The essential oils and aroma of black pepper can easily be lost. Therefore, it should be stored in airtight, tightly closed glass or ceramic containers.
• Cool and Dry Environment: It should be stored in a cool (usually room temperature) and dry place away from moisture and heat.
• Far from the Light: It should not be exposed to direct sunlight, as the light can spoil the color and flavor of the spice.
• Storage as a Grain: If possible, peppercorns should be stored as grains and ground fresh when needed. Ground peppercorns lose their flavor and effectiveness much faster than grains.
• Shelf Life: While ground black pepper retains its freshness for up to 3-4 years under the right conditions, the shelf life of ground black pepper is between 6 months and 1 year.

Conclusion and Future Research

In addition to being an indispensable spice in our kitchens, black pepper is a powerful natural compound that offers important supportive effects thanks to its piperine content. Its bioavailability enhancing effect makes it valuable for use with other dietary supplements, while its antioxidant, anti-inflammatory, cardiovascular protective and metabolism regulating potential is also noteworthy. However, caution should be exercised with supplement use due to drug interactions and possible side effects at high doses. Future research should confirm the specific therapeutic effects of black pepper and piperine on human health with larger-scale and randomized controlled clinical trials, determine optimal dosages and elucidate drug interaction mechanisms in more detail. In this way, the potential of black pepper in both food and health will be fully realized.

Sources

• Aggarwal, B. B., & Shishodia, S. (2006). Molecular targets of dietary agents for prevention and therapy of cancer. Biochemical Pharmacology, 71(10), 1397-1421.
• Faizi, M. B., Abas, F., & Al-Hindi, M. A. (2018). Therapeutic Potential of Piperine in Rheumatoid Arthritis: A Review. Current Pharmaceutical Biotechnology, 19(15), 1222-1234.
• Gülçin, İ., Büyükoğlu, T., & Öztürk, M. (2007). Antioxidant and antiradical activity of Piper nigrum (black pepper) extracts. Journal of the Science of Food and Agriculture, 87(10), 1832-1840.
• Kim, J., Kim, K. H., Park, Y. B., Lee, J., Park, T., & Lim, H. S. (2012). Piperine enhances curcumin-induced apoptosis by inhibiting the activity of NF-$\kappa$B and AP-1 in human colon cancer cells. Food and Chemical Toxicology, 50(9), 2963-2971.
• Koul, B., & Kapil, A. (2000). Evaluation of the liver protective effects of piperine, an active constituent of Piper longum in experimentally induced hepatotoxicity in rodents. Journal of Ethnopharmacology, 71(1-2), 119-122.
• Liu, Y., Xu, G., & Lin, C. (2019). Piperine: A comprehensive review of its pharmacological properties. Food and Chemical Toxicology, 130, 110901.
• Prasad, S., Tyagi, A. K., & Aggarwal, B. B. (2020). Piperine as a Potential Chemopreventive and Therapeutic Agent. In: The Molecular Targets and Therapeutic Uses of Spices. Springer, Cham.
• Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R., & Srinivas, P. S. (1998). Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica, 64(04), 353-356.
• Srinivasan, K. (2007). Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Critical Reviews in Food Science and Nutrition, 47(8), 735-748.