For Europeans in the Middle Ages, pepper was a trendsetter—so valuable it was even used as currency in markets. The French phrase "Cher comme poivre" (literally "as expensive as pepper") describes extremely pricey items; legend has it that European countries even went to war over pepper.
Why was it so precious? First, it was rare (a "mysterious spice" from Southeast Asia); second, it added wonderful flavor to food; third, it masked strong body odors (a necessity in the unsanitary Middle Ages, as you can imagine).
Naturally, this treasure caught the attention of the Chinese. When pepper was introduced to China during the prosperous Tang Dynasty, it was equally precious. Legend has it that when the powerful official Yuan Zai fell from grace, 900 dan (a traditional Chinese unit of volume) of pepper was seized from his home. Fortunately, with the expansion of shipping, pepper gradually became a staple in ordinary households. Our ancestors’ wisdom in using ingredients never disappoints: beyond removing fishy smells, enhancing flavor, and cutting greasiness, pepper was also used to make tea, infuse wine, and even treat illnesses in traditional medicine.
Today, black pepper and white pepper are the most common types on the market:
- Black pepper: Harvested and processed when unripe, it has a strong, pungent aroma.
- White pepper: Made by removing the black outer skin of ripe pepper berries, it has higher medicinal value and a milder taste, often used in soups in Guangdong cuisine.
1. Pepper? No—Piperine!
In October last year, a team from the Chinese Academy of Tropical Agricultural Sciences, Huazhong Agricultural University, and the Academy of Sciences Malaysia published a study in Nature Communications. They mapped and analyzed the chromosome-level genome of pepper, uncovering its "spicy gene." It turns out that the piperine content in pepper determines its spiciness[1].
Figure Note: Pepper’s genome map—complex but impressive.
2. Piperine: Deserves an "Best Supporting Role" Award
As its name suggests, piperine is a plain-looking alkaloid found in pepper’s peel and seeds. It is the source of pepper’s spiciness and its most important bioactive component. Pepper’s medicinal value, mentioned earlier, is largely due to piperine, which has long been used in folk medicine as a broad-spectrum anticonvulsant.
Figure Note: This is the molecular structure of piperine.
While pepper now holds a place in cuisine, it remains just a condiment (a far cry from its once-royal status). Piperine seems to share this "supporting role" fate:
Research shows that one of piperine’s main uses is "helping others"—ironically, despite its own low bioavailability, it dramatically boosts the bioavailability of other substances.
Specifically, piperine enhances the bioavailability of various drugs and nutrients (e.g., cytisine, vasicine, quercetin, resveratrol, coenzyme Q10, vitamin B6). Its mechanism is not yet fully clear, but scholars speculate it may:
- Speed up the absorption of these substances in the gastrointestinal tract,
- Protect absorbed substances from being metabolized and broken down by the liver,
- Or both[2].
| Rank | Drug/Nutrient | Bioavailability Increase (%) | Reference |
|---|---|---|---|
| 1 | Curcumin | 2000 | Planta Med. 1998 May;64(4):353-6. |
| 2 | Luteolin-7-O-glucoside | 381 | Molecules. 2014 Apr 30;19(5):5624-33. |
| 3 | Vasicine | 233 | J Ethnopharmacol. 1981 Sep;4(2):229-32. |
| 4 | Resveratrol | 229 | Mol Nutr Food Res. 2011 Aug;55(8):1169-76. |
| 5 | Ginsenosides | 197 | Chin J Nat Med. 2018 Feb;16(2):143-149. |
| 6 | Fexofenadine (Antihistamine) | 190 | J Food Sci. 2010 Apr;75(3):H93-6. |
| 7 | Cytisine | 100 | J Ethnopharmacol. 1981 Sep;4(2):229-32. |
| 8 | Coenzyme Q10 | 40 | J Nutr Biochem. 2000 Feb;11(2):109-13. |
| 9 | Cyclosporine A (Immunosuppressant) | 33 | Methods Find Exp Clin Pharmacol. 2010 May;32(4):227-32. |
| 10 | More to be added... | - | - |
Curcumin benefits most from piperine. When a healthy adult takes 2g of curcumin alone, no curcumin is detected in their serum. But when 20mg of piperine is taken alongside it, curcumin becomes detectable—and in large amounts. Human trials show piperine boosts curcumin’s bioavailability by a staggering 2000%[3].
This "indirect approach" could be piperine’s strategy for anti-aging.
3. More Than a Supporting Role—Piperine Wants the Spotlight!
Piperine has impressive effects of its own, beyond aiding other substances:
- Antioxidant: Enhances the activity of antioxidant enzymes and inhibits the accumulation of lipid peroxides[4].
- Anti-inflammatory: Suppresses inflammatory factors, maintains immune balance, and prevents excessive T-cell differentiation[5].
- Antidepressant: Regulates neurohormone levels, enhances neuroregeneration, and protects cells[6].
- Antitumor: Regulates the cell cycle and inhibits invasion, metastasis, and angiogenesis[7].
- Improves metabolic syndrome: Prevents or alleviates hepatic steatosis and insulin resistance[8].
- Antipyretic and analgesic: As effective as indomethacin[9].
- Protects the musculoskeletal system: Promotes osteoblast differentiation and bone mineralization[10].
4. Piperine’s Anti-Aging Potential: Still in Its Early Stages
This is not to say piperine lacks anti-aging effects—its anti-inflammatory, antioxidant, and antitumor properties are genuine, and its "supporting role" in boosting other anti-aging substances is valuable. However, research on piperine’s direct anti-aging effects remains limited (a quick PubMed search yields few results).
That said, a handful of studies show piperine improves neurological function in aged mice. For example, after 4 weeks of piperine intervention, aged mice showed significant relief from cognitive decline—thanks to piperine’s protection of the cholinergic system and inhibition of neuroinflammation and oxidative damage[11].
Figure Note: Mechanism of piperine’s cognitive protection—piperine modulates the PI3K/AKT/GSK-3β pathway, reduces AChE activity (increasing ACh levels via ChAT upregulation), inhibits NF-κB (lowering IL-1β/TNF-α), and reduces phospho-tau and ROS, reversing cognitive decline.
An open question remains: How does the spicy sensation of piperine itself affect aging? Does spicy stimulation trigger inflammation, or do spicy foods promote longevity? Two conflicting findings highlight this ambiguity:
- A study on Chinese adults aged 65+: Increased spicy food intake may be associated with higher cardiovascular disease risk.
- A Harvard study (Harv Health Lett. 2015 Nov;41(1):8): Spicy food intake is linked to longer lifespan.
5. Should You Supplement Piperine?
Regardless of its anti-aging evidence, piperine’s health benefits are solid—at the very least, it enhances the effects of other supplements. Here’s what you need to know:
Daily Diet Is Insufficient
As a condiment, daily piperine intake is extremely low—most Chinese households do not use pepper in every meal. Commercial black/white pepper contains only 5%–11% piperine. Unless you are a spice lover, normal dietary intake will not reach the effective dose for health or anti-aging benefits. Extra supplementation is needed for specific needs.
High Safety Profile
Piperine is safe: High doses cause no genotoxicity, immunotoxicity, or mutagenicity—even doses 20 times the normal level show no adverse effects[2].
Animal studies show piperine’s LD50 (lethal dose for 50% of subjects) is:
- 15.1 mg/kg (intravenous injection),
- 43 mg/kg (intraperitoneal injection),
- 200 mg/kg (subcutaneous injection),
- 330 mg/kg (oral gavage),
- 400 mg/kg (intramuscular injection).
For a 60kg healthy adult, this means consuming approximately 20g of pure piperine (equivalent to 200g of pepper powder) in one go to risk life—a quantity so spicy it would be unbearable long before toxicity sets in.
In short, if you want to supplement piperine, it is safe to do so (though specific recommended doses remain unestablished).
Ultimately, being a "supporting role" is not a bad thing—piperine’s contributions to health and anti-aging are clear. Its potential deserves more research in the future.
References
[1] Hu L, Xu Z, Wang M, et al. The chromosome-scale reference genome of black pepper provides insight into piperine biosynthesis. Nat Commun. 2019;10(1):4702.[2] Srinivasan K. Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Crit Rev Food Sci Nutr. 2007;47(8):735-748.[3] Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64(4):353‐356.[4] Umar S, Golam Sarwar AH, Umar K, et al. Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis. Cell Immunol. 2013;284(1–2):51–59.[5] Doucette CD, Rodgers G, Liwski RS, Hoskin DW. Piperine from black pepper inhibits activation-induced proliferation and effector function of T lymphocytes. J Cell Biochem. 2015;116(11):2577–2588.[6] Mao QQ, Huang Z, Zhong XM, et al. Piperine reverses chronic unpredictable mild stress-induced behavioral and biochemical alterations in rats. Cell Mol Neurobiol. 2014;34(3):403–408.[7] Manayi A, Nabavi SM, Setzer WN, Jafari S. Piperine as a Potential Anti-cancer Agent: A Review on Preclinical Studies. Curr Med Chem. 2018;25(37):4918-4928.[8] Derosa G, Maffioli P, Sahebkar A. Piperine and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;928:173‐184.[9] Evan Prince S, Aayesha N, Mahima V, Mahaboobkhan R. Analgesic, antipyretic and ulcerogenic effects of piperine: an active ingredient of pepper. J Pharm Sci Res. 2013;5(10):203–206.[10] Kim DY, Kim EJ, Jang WG. Piperine induces osteoblast differentiation through AMPK-dependent Runx2 expression. Biochem Biophys Res Commun. 2018;495(1):1497-1502.[11] Wang C, Cai Z, Wang W, et al. Piperine regulates glycogen synthase kinase-3β-related signaling and attenuates cognitive decline in D-galactose-induced aging mouse model. J Nutr Biochem. 2020;75:108261.