All About Black Pepper

Originally published in All About Spices, reprinted by permission

Sections:

    1. Basic information
    2. Pepper and metabolism
    3. Pepper as an anti-inflammatory
    4. Cannabinoids in pepper
    5. Pepper in wine
    6. Pepper and Vitiligo
    7. Black pepper and the pancreas
    8. Black pepper and Epilepsy
    9. Non-dietary uses for black pepper (including its essential oil)
  10. Glossary
  11. References

A glossary is provided at the end, rather than trying to explain all the scientific and medical terms within the text itself.

Basic information

Black pepper, from either piper nigrum or piper longa, is a small fruit with a single hollow seed. It grows on a long woody vine that climbs up whatever support it can find, and eventually trails over the top and grows back down. Pepper is a tropical plant, available to plant outdoors in tropical areas of the US, and as a house plant in temperature climates. Logee's, a tropical plant supplier in the US, sells pepper seedlings, as do several other companies.[1].

The fruit itself is in several very thin layers (called the exocarp, the mesocarp and the endocarp) over the seed. The entire fruit and seed contain piperine, the active ingredient most often discussed.

Black pepper is made by picking the fruit when it's nearly ripe, and then allowing it to dry in the sun. The outer layers of the fruit ferment, oxidize and turn black as they dry up. White pepper starts out as unripe green peppercorns. They are soaked in water until the outer layers of the fruit begin to slough off (a process called retting). Then the seeds are polished to remove any remaining bits of the fruit. Thus white pepper consists only of the seed portion of the original fruit. For that reason, it also has more piperine per volume than either black or green peppercorns. Green peppercorns are picked and sold unripe with little additional processing. They are subject to mold and other contamination because of the moisture content. So they are often sold pickled or freeze-dried. Mature red peppercorns are also sometimes sold in pepper mixtures. However, the pink ‘peppercorns’ in many mixtures are not pepper, but the fruit of another plant and do not contain piperine.

Black pepper is one of the oldest of the commercially traded spices, with a documented history going back thousands of years. It originated in India, and is still widely grown there. But other countries, primarily Vietnam, have entered the world market and now dominate it. Our organic pepper comes from India. Malabar is the most widely sold variety of piper nigrum. A distinction is made by some writers between Malabar and Tellicherry pepper. Tellicherry is not a separate variety, nor is it Malabar pepper grown on the slopes of Mt. Tellicherry, or any of the other fanciful claims made across the internet. Tellicherry is pepper that has been selected out of a harvest for the largest fruits. There are fewer of these large fruits in any given lot of harvested pepper, and Tellicherry pepper therefore costs more. That is the only difference. The variety is still Malabar.

Black pepper has as long a medical history as a culinary one. Early medical practitioners valued it to treat indigestion, constipation, joint pain, liver problems, and even sexual dysfunction-it was thought to be an aphrodaisiac. Now we know that many of those beliefs were valid (well, maybe not the aphrodaisiac!).

Pepper's effects on enzymatic substrates

One of pepper's properties is its ability to affect the metabolism of other substances, both foods and drugs. This can have both good and bad consequences. Piperine, the primary active part of black pepper, slows down the metabolism of curcumin, one of the active constituents of turmeric, and allows it to remain effective in the body for much longer than it would without the pepper. On the other hand, piperine also slows down the metabolism of opioids, most antidepressants and antipsychotics, and many other drugs whose dosage depends on the rate of clearance. Having pepper along with those drugs can result in too high a level in the bloodstream

Before you panic and throw away the pepper on your dinner table, the use of pepper to flavor foods at the table is usually not a problem. The pepper sold pre-ground for use in pepper shakers will have lost most of its piperine before it's consumed. But if you're in the habit of grinding fresh pepper all over your plate at every meal, even as much as 1 gram (approximately 1/2 tsp) has been found to inhibit metabolism of some classes of drugs. [2]

How does black pepper accomplish this feat? By way of two mechanisms. Black pepper inhibits a family of enzymes known as cytochrome P450 3A, usually abbreviated "CYP3A." There are multiple variants in this family, and pepper inhibits two of them (CYP3A4 and CYP3A5). These enzymes are expressed both in the liver and the small intestine (though the amount of CYP3A5 is very small). They participate in the metabolism of a very wide range of commonly prescribed medications, and many foods as well. Some of these are listed in this Wikipedia article. Other inhibitors and inducers of CYP3A4 are listed in the second and third columns of the table. Piperine is noted under the 'Unspecified Potency' section of the inhibitors. Other sources and research have reported it to be a moderate inhibitor.

Piperine also inhibits the drug transporter P-glycoprotein. P-gp is a protein that resides in cell membranes, and moves toxins or unwanted metabolites out of cells. In the liver, P-glycoprotein pumps them into the bile ducts. In the blood-brain barrier, it pumps them back into the capillaries. Inhibiting this function might sound like a bad thing to do, and in some cases, it is. Keeping P-gp from doing its job can result in undesirable levels of drugs or toxins in the body. On the other hand, some tumors produce large amounts of P-gp, which allows them to expel the cancer drugs used to kill them. In that case, inhibiting its mechanism is good, and pepper is being investigated for its possible role in combating cancer. It's known that pepper can enhance the mechanisms of some anti-cancer drugs, because it prevents the tumor cells from getting rid of the drugs.

Doctors have known for years that some groups of people seem to metabolize drugs differently than others, and it appears now that dietary pepper may play a part in that difference. "First-pass" metabolism (the ability to metabolize a food or drug in the liver and small intestine, before it ever reaches the bloodstream), is a problem for many drugs. Pepper's ability to inhibit this intestinal metabolism may allow drug combinations that avoid being prematurely metabolized. It may also allow doctors to prescribe smaller amounts of some drugs, if they can be combined with the piperine from pepper [3].

What should you be aware of if you're on prescription medications and you also like to have a lot of pepper? The first thing, as mentioned above, is that if you're using pre-ground pepper in a pepper shaker, you're unlikely to have any problems. If you're adding substantial amounts of freshly ground pepper to your food, keep it under one gram (approximately 1/2 teaspoonful total) a day). That's still quite a lot of pepper. And of course, talk to your doctor if you have any concern about your medication interacting with pepper.

Please note that you do not need to worry about bell peppers. They're in the capsicum family and do not contain piperine. However, hot peppers (chili peppers) do contain capsaicin, which has the same inhibitory effect on the CYP3A family as piperine. It is much less potent, though, and not typically a problem unless you consume large amounts.

Black pepper as an anti-inflammatory

Black pepper is anti-inflammatory, thus helping with many kinds of inflammation-related pain. One study looked at the effect of piperine on human chondrocytes. They were pre-treated with piperine at three different concentrations, and then exposed to IL-1ß, a known component of the inflammatory reponse. The treated cells showed a far lower expression of the COX-2 enzymes and other markers for inflammation [4].

Another study looked at the typical damage caused by rheumatoid arthritis. There are two types of specialized cells in the joints, one of which is called 'fibroplast-like synoviocytes.' These cells line the synovium and secrete chemicals that help to lubricate the joint. But when inflammatory processes begin, as in rheumatoid arthritis, they lose the properties that inhibit their proliferation and begin to reproduce far beyond their normal numbers. They also start to produce inflammatory chemicals such as interleukin-6, interleukin-8 and prostaglandins. In a study with artificially induced rheumatoid arthritis in rats, piperine was found to inhibit the growth of fibroplast-like synoviocytes and to reduce the expression of IL-6, IL-8 and prostaglandins. [5].




Black pepper has also been found to reduce the inflammation and damage caused by deliberately induced pancreatitis in mice.

…piperine pretreatment reduced the production of tumor necrosis factor (TNF)-a, interleukin (IL)-1ß, and IL-6 during cerulein-induced AP [Acute Pancreatitis]. In accordance with in vivo results, piperine reduced cell death, amylase and lipase activity, and cytokine production in isolated cerulein-treated pancreatic acinar cells. In addition, piperine inhibited the activation of mitogen-activated protein kinases (MAPKs). These findings suggest that the anti-inflammatory effect of piperine in cerulein-induced AP is mediated by inhibiting the activation of MAPKs. 

Thus, piperine may have a protective effect against AP [14].

Black pepper and epilepsy