Pepper (28 page)

The healthful properties attributed to pepper some four hundred years ago—its ability to soothe the lungs, vanquish fevers, ease a variety of aches and pains, and even reduce the size of tumors—is gaining traction today. Thanks to the growing interest in natural products in the West, a small renaissance in the study of pepper as a medicine is under way. The spice and its
Piper
siblings still inspire our curiosity and enterprise, and perhaps one day a derivative of black pepper will become an important medicine for the treatment of cancer or other diseases.

Scientists in the United States, Britain, and Italy are now testing pepper's potency as an anti-inflammatory and antimicrobial agent; an anticancer therapy; a preservative; an insecticide; an antioxidant; an analgesic; and a treatment for vitiligo, a skin pigmentation disorder. A small number of studies in scientific journals even suggest that pepper could improve mood and slim the waistline. In Japan, researchers are evaluating whether inhaling the aroma of black pepper oil, which is used in the fragrance industry and is not pungent, can improve swallowing by stimulating parts of the brain in elderly people who have suffered strokes. They hope to prevent aspiration pneumonia, a common cause of death in these patients. The Japanese are also evaluating whether the smell of pepper oil can stimulate other parts of the brain to help people quit smoking.

And in China, where pepper has long been used as a folk remedy for the treatment of epilepsy, chemicals derived from the spice are now incorporated into medicines to treat epileptic seizures in children.

By far, though, the property that is drawing the most scrutiny is pepper's tendency to act as a sort of booster, or biological enabler, of medicines. In this role, the spice helps make medicines more “bioavailable” by increasing the amount of the drugs in the bloodstream and helping them to remain longer in the body. The liver and the intestine often throw up barriers that prevent medicines from doing their job. The usual culprits are metabolic enzymes that chew up medicinal compounds before they can be absorbed in the body, rendering them less useful. In the mid-1980s, a team in India discovered that piperine, a compound that is abundant in black pepper and which gives the spice its famous kick, inhibited the activity of certain enzymes in the liver and intestine. This finding sparked an interest in piperine's propensity to make medicines more effective.

Since then a number of clinical studies have shown that piperine boosts the levels of phenytoin for epilepsy, propranolol for high blood pressure, theophylline for asthma, rifampin for tuberculosis, and nevirapine for HIV infection, among other medications. The ability of black pepper to make drugs more bioavailable may be the main reason why an herbal mixture called
trikatu
is so widely prescribed along with other treatments in Ayurvedic medicine, a system that aims to prevent disease and promote well-being. By enhancing the effects of these other medicines, trikatu would serve as a sort of all-purpose medicinal amplifier.

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More than three hundred citations for scientific papers related to black pepper are in PubMed, the huge database maintained by the National Library of Medicine in the United States. The scientific work on black pepper is proving that it possesses properties that have long been exploited in Ayurvedic medicine. This system of healing has not been embraced in the West, although other alternative or complementary medicines from Asia are becoming more popular in Western countries. The British attempted to rid India of Ayurvedic medicine altogether, when, in 1835, they banned teaching the system in India. More recently, in 2000, the House of Lords issued a report saying that there wasn't evidence to support Ayurvedic's role in the diagnosis and treatment of disease. A review of studies involving some 166 plant species—from sage leaves, cinnamon, and fenugreek to nutmeg, dandelion, and white sandalwood—utilized in Ayurvedic medicine presents a different picture. The survey by Sarah Khan and Michael Balick, an ethnobotanist at the Institute of Economic Botany at the New York Botanical Garden, reveals that 43 percent of the plants had undergone testing in at least one human clinical trial and 62 percent had been evaluated in studies in animals. Although the authors acknowledge that many of the studies lack the appropriate rigor associated with the “gold-standard” of clinical testing in the West, such as adequate sample size and controls, their review suggests which plant species might be suitable for larger and better-controlled clinical trials. They conclude that the studies in the scientific and medical literature dispel “the all-too-commonly held notion that no clinical or other evidence exists to support the use of plants used in traditional medical systems.”

Spices were frequently mentioned in ancient Ayurvedic texts, and some seven hundred drugs derived from pepper, turmeric, ginger, cinnamon, and other spices were described by a physician named Sushruta the Second in about 500 B.C. It isn't surprising that people who were surrounded by spice plants found extensive uses for them. In ancient times, black pepper was a remedy for constipation, diarrhea, earache, heart disease, hernia, indigestion, liver problems, and joint pain, among other ailments. In India today, the pepper mixture trikatu is relied on to treat a wide variety of illnesses, in combination with other herbal preparations. The mixture contains black pepper, long pepper, and ginger in equal proportions, and is part of most prescriptions in traditional Ayurvedic medicine. Many are taken as pills or powders and are often consumed with honey to make them more palatable. In South Asia pepper is also widely employed in a broad array of folk remedies, especially as a treatment for diarrhea. Most medicines in the West, too, are derived from plants. Willow bark was the original source of aspirin, and the latest treatment for malaria, artemisinin, is a compound found in a shrub applied in traditional Chinese medicine.

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Among spices, turmeric, a spice in yellow mustard and Indian curry, called
haldi
in Hindi and
jiang huang
in Chinese, has been given the most attention by Western scientists because of its potential as a treatment for Alzheimer's, cancer, and other diseases. But scientists have not neglected black pepper, which shares some of turmeric's properties.

Black pepper contains many compounds, but piperine is the most abundant. First identified in 1820 by a Dutch chemist named Hans Christian Orstedt, piperine is considered an alkaloid. (Long pepper,
Piper longum,
also contains piperine.) Alkaloids are common in nature—some 10 to 20 percent of plants contain this type of chemical, according to Van Nostrand's
Scientific Encyclopedia.
Caffeine, heroin, and nicotine are also alkaloids, however there is no evidence that piperine is addictive. Most alkaloids contain the element nitrogen embedded in rings of carbons. Stronger pepper is packed with more piperine, the reason that pepper grown in Malaysia and Indonesia is more pungent than pepper grown in Brazil.

The ability of piperine to boost the effectiveness of a particular treatment for cancer is the focus of a research project underway at Fox Chase Cancer Center in Maryland led by urologic surgeon Robert Uzzo and scientist Vladimir Kolenko. They are evaluating whether the compound can make a medicine for treating advanced prostate cancer more effective and easier to tolerate. Piperine inhibits a liver enzyme that is responsible for the degradation of a drug called docetaxel, which combats various kinds of tumors. Docetaxel, itself a natural product derived from the Pacific yew tree, is a medicine approved by the U.S. Food and Drug Administration to treat men with cancers resistant to the hormones that are the usual first line of treatment. However, the drug only increases the survival of patients by two to four months and has the usual side effects associated with chemotherapy, such as vomiting, hair loss, and nausea. Docetaxel has to be administered intravenously three times a week, because the liver will destroy the drug in its pill form. Patients would be much more comfortable if the drug could be administered orally. Could the addition of piperine make this possible? If the pepper compound inhibits the liver enzyme, can it increase the amount of time the anticancer agent remains in the bloodstream? Would tumor cells be exposed to the agent for a longer period of time than is otherwise possible, enhancing the effectiveness of the chemotherapy? The physician researchers want to find the answers to these questions.

Piperine may also enhance the activity of a natural product called curcumin, the active ingredient in the spice turmeric, that is the ongoing subject of clinical studies at MD Anderson Cancer Center in Houston and elsewhere. Like pepper, turmeric is an ancient spice that is widely used in traditional medicine in India, where it is most renowned for its capacity to fight inflammation. It was this property that led Bharat B. Aggarwal, chief of the Cytokine Research Section at MD Anderson and a former scientist at the biotechnology company Genentech, to explore the feasibility of using curcumin as an anticancer agent.

Some investigators believe that piperine has the capacity to quell inflammation, which would make it an appealing compound to incorporate into treatments for a wide variety of diseases. The idea that inflammation is tied to cancer stems in part from the discovery of a substance called tumor necrosis factor, a powerful protein linked to inflammation that also appears to play an important role in driving the growth of tumors. (Aggarwal and his colleagues at Genentech purified tumor necrosis factor in the 1980s.) This protein is also produced in people with various autoimmune diseases, such as psoriatic arthritis and inflammatory bowel disease, and medicines designed to neutralize it are taken by millions of people worldwide.

The destructiveness of the protein becomes clearer through its relationship to a molecule called nuclear factor kappa beta (NF Kappa B). Tumor necrosis factor activates this molecule, which has been linked to immune and inflammatory processes, cell growth, and many other biological processes. Normal cells have lower levels of NF Kappa B than tumor cells. The interesting observation here is that curcumin and piperine have each been shown to suppress the activity of NF Kappa B. More than eight hundred compounds are also known to inhibit the molecule, though, so further research is needed to figure out if the specific activity of the spice chemicals will have any meaningful effect in the clinic.

Most intriguing are the possibilities of using piperine to improve the bioavailability of curcumin, and combining the two spice ingredients to generate a more powerful response. In a small laboratory study published in 2009 by researchers at the University of Michigan, each compound by itself and in combination inhibited the renewal, or generation, of certain stem cells in the breast that may be the source of cancer cells. Additionally, they found that the compounds did not harm normal tissue, at least in the laboratory setting. Indeed, piperine has been shown in a series of other laboratory studies to inhibit colon cancer in rats induced by a known carcinogen and to protect against DNA damage in animals with induced lung cancer.

Already the Internet is serving up a large dollop of news about pepper's anticancer properties. “Pepper's hot stuff because it contains pungent piperine, which goes into search-and-destroy mode when breast stem cells are trying to turn cancerous,” boasts a Web site bearing the headshots of “Dr. Oz” and “Dr. Mike.” “Pass the Pepper,” shouts a headline from the
National Post
in Canada, in an article that includes information about piperine's ability to increase the bioavailability of curcumin and to help with weight control, at least according to research on mice.

For anyone inspired to eat a lot of black pepper based on all of these findings and reports, there doesn't appear to be much risk. In animal studies, rats and mice fed up to one hundred times more black pepper than is normally consumed in the Indian diet did not suffer any ill consequences; their gastrointestinal tracts did just fine. Rather than cause distress, some researchers believe that piperine in very high doses may promote digestion and protect the lining of the stomach and intestine.

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While black pepper may be associated with promising areas of medical research, it isn't a panacea. Modern research is usurping the long-held notion that pepper is an excellent preservative. Krishnapura Srinivasan, who has studied the physiological effects of piperine for more than thirty years, says that pepper has “limited application” as a preservative, especially in comparison to other spices such as turmeric and garlic. Pepper also appears to fall short in another potentially exciting application, as an antioxidant that squelches rogue oxygen molecules contributing to cancer, hardening of the arteries, and other diseases. Curcumin is effective, but piperine is not.

However, black pepper may have a less exalted role in natural insect repellents. A study published in 2008 by scientists at the University of Florida and the U.S. Department of Agriculture reported that repellents containing compounds called piperidines, which are closely related to piperine, warded off mosquitoes more than three times longer than DEET, the active ingredient in most insect sprays. DEET was discovered in 1953, and scientists still do not know how it prevents insects from biting. Volunteers in the 2008 study comparing the two wore arm patches laced with the piperidine compounds and bravely held their arms in a chamber filled with about five hundred mosquitoes. The DEET kept the insects away for an average of almost eighteen days, while some of the piperidines were effective for up to seventy-three days. One of the scientists who led the research says that the new compounds have the advantage of being unsticky and unsmelly (surprising for compounds related to piperine) compared to most of today's insect repellents.

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Black pepper is not the only member of the
Piper
family of plants that is being investigated by scientists. The intriguing effects of pepper's close relative,
Piper betle,
the foundation of habit-forming betel chewing in Asia, have not gone unnoticed in the laboratory. Ever since Europeans first set foot in Asia, they have observed that betel seemed to promote good health. One of the many travelers to comment on betel's apparently life-enhancing properties was Tomé Pires, the Portuguese ambassador to China in the sixteenth century, who wrote: “It greatly helps digestion, comforts the brain, strengthens the teeth, so that men here who eat it usually have all their teeth, without any missing, even at eighty years of age. Those who eat it have good health and if they do not eat it one day their breath is unbearable.”