Does Piperine Have Health Benefits? The Current Research Examined

It seems that everyone is blogging about piperine these days. There is lots of excitement on the blogosphere about the seemingly endless health benefits of this everyday kitchen spice.

Beyond health benefits, piperine is the secret ingredient in the some of the more expensive gins on the market and can even be mixed with cheaper gin to get some extra pzazz.

If you don’t want to eat or drink piperine, then you can wear it as the ‘middle-note’ in expensive perfumes.

Piperine features in Salman Rushdie’s book ‘The Moor’s Last Sigh’ where it is described as the ‘Black Gold of Calabar’.

If all the claims about piperine are true, then it is no wonder that it has been called the ‘King Of Spices’. But is any of the hype actually true?

For starters, it has been said that piperine was discovered by Hans Christian Oersted in 1819. The truth is that piperine was ‘discovered’ long before Mr Oersted was born. (Sorry Mr Oersted). The real truth is that piperine has been a cornerstone of Ayurvedic medicine for centuries where it is commonly co-prescribed with ginger and known as Trikatu (8).

It is time to tidy up the blogosphere with some actual scientific facts on piperine.

What is Piperine?

Piperine is an alkaloid found in black pepper (Piper nigrum), long pepper (Piper longum), and other Piper species fruits belonging to the family of Piperaceae.  To be geeky, it has the chemical formula C17H19N03.

Black pepper comes from unripe fruit while white pepper comes from ripe fruit.

Piperine is one of the most widely used spices worldwide. It grows particularly well in Asia. Vietnam is currently the lead supplier and exporter of pipeline worldwide.

Almost every kitchen worldwide has either ground black pepper, black peppercorns or a pepper mill. Cooking channels show master chefs and wannabe chefs grinding peppercorns and sprinkling the ground pepper with great aplomb on the ‘dish du jour’.

Nowadays, piperine is used primarily as a food flavoring.  In the past it was used to prevent bio-deterioration and contamination of food.

Black pepper is an aromatic compound which means that it can easily be lost in the heating and cooking process. For the same reason, it needs to be stored in an airtight container.

How Much Research Is There?

Despite the popularity of piperine among health bloggers, there are only 21 clinical trials on piperine. Yes, all that excitement comes from 21 human studies. To put this in perspective, there are over almost 200 clinical trials on curcumin and 6,500 clinical trials on the antibiotic penicillin.

Most of the research on piperine relates to its role as a bioenhancer. This means that it can increase the absorption of some pharmaceutical drugs and/or nutrients.

Studies have shown that piperine can increase the absorption of anti epileptic medications  (phenytoin), blood pressure medications (propanolol), treatments for tuberculosis (rifampicin), painkillers (diclofenac) and some anticancer drugs (7).

Piperine does this in two main ways. It boosts important drug transporters which increases the absorption of some drugs. It also slows down the activity of key enzymes which break down drugs. For some drugs, this means that more of the drug enters the body and less of the drug is broken down which means an overall double-hit increase on the circulating drug levels.

At least part of the e-popularity of piperine relates to its alleged role as a bioenhancer of micronutrients. However this is not as simple as many bloggers have described.

Does Piperine Help The Absorption Of Other Nutrients?

The key study on the effect of piperine on nutrients was done by Shoba and colleagues who demonstrated that piperine increases the absorption of curcumin/turmeric by 2000% (17). This is the rationale for the recommendation to take turmeric with black pepper (3). It is no wonder that many Ayurvedic formulations involve a blend of spices an herbs.

However more does not always mean better.  A study in diabetic rats showed that piperine counteracted the beneficial antioxidant effects of curcumin (1).

Another key human clinical study showed that piperine supplementation at a low dose resulted in a significant increase in betacarotene levels (2).  The same study showed no effect of piperine on the absorption of vitamins A, E or C. So far so good.

However, in the discussion section of the Badmaev paper, the authors of the study casually mention that they have previously conducted studies looking at the effect of piperine on vitamin B6, vitamin C, selenium, and coenzyme Q. They say that they found that piperine increased the levels of all of these micronutrients.

A number of bloggers take this as fact and categorically state that ‘piperine increases levels of vitamins B6, C, selenium and coenzyme Q’.  The problem is that it is not safe to just assume that this is true for the following reasons.

Firstly, the authors of the study do not provide any information or figures to back up this claim or to help us asses the magnitude of the effect. Was it a little? Was it a lot? Did it actually happen?

Additionally this information is not published anywhere else and so cannot be cross-checked or verified.

Finally, the authors do not comment on the fact that there is a discrepancy between their unpublished data on vitamin C and the results of their own published study. Curiouser and curiouser.

The authors of the study (and sole keepers of the source information) believe that there is a significant difference in the way piperine affects nutrients versus pharmaceutical drugs. They believe that nutrients are essential building blocks of the body and are processed by the body differently to drugs.

They also suggest that the specific mechanism by which piperine affects drug levels is entirely different to a non-specific mechanism by which piperine effects nutrients.

In this paper, they propose a ‘thermogenic theory’ suggesting that locally ingested piperine causes a local thermogenic reaction, which increases the absorption of micronutrients.

Lack of data plus unproven theories are not a good basis for making e-recommendations.

Summary: Available data on piperine-nutrient interactions only supports the fact that piperine increases the beta-carotene.

Does Piperine Help Immune Function?

There are no human clinical studies looking at the effect of piperine on human immunity. There are a number of laboratory studies but it is impossible to draw any over arching conclusions. This is partly because the ‘immune system’ is not a single entity. It is a complex collaboration between cells, antibodies, proteins and messengers. It is way too simplistic to say that anything ‘increases/decreases the immune system’.  Things may affect part of the immune system but not the ‘immune system’ in its entirety

Here are some examples of the published literature on immunity and piperine. One study found that piperine had a significant immunosuppressive effect in laboratory mice (18).  Another study found that piperine improved the ability of a subset of white cells (macrophages) in the abdominal cavity of mice to fight bacteria (12). A third study showed that piperine had a significant beneficial effect on tuberculosis which appeared to be a combination of improving the immune response to tuberculosis plus improving the drug levels of a key component of antitubercular therapy known as rifampicin (9). A fourth paper  summarised the antimicrobial properties of piperine (5). All very interesting but utterly confusing and totally inconclusive.

Summary: There are no human clinical trials looking at the effect of piperine on ‘the immune system’.

Does Piperine Treat Depression?

There is only one clinical study evaluating the effect of piperine in depression. In this study, 111 patients on standard antidepressant therapy were randomized to either receive a curcumin-piperine combination (1,000/10 mg daily) for six weeks or nothing extra. The study showed a statistically significant improvement in depression score in patients who received the curcumin-piperine combination.

The challenge with the study lies in the study design. Patients in the intervention arm received both curcumin and piperine. This makes it impossible to disentangle the effect of curcumin versus piperine.

The other key issue is that it is unclear whether piperine was acting as a antidepressant  itself or whether its role was as a bioenhancer to improve the bioavailability and the drug absorption of the curcuminoids?

Summary: The only clinical trial involving piperine in depression was limited by the fact that the piperine was co-administered with curcumin.

Does Piperine Have Anti Cancer Properties?

There are no quality human clinical trials looking at piperine for cancer. A comprehensive review of the role of piperine in cancer was published in May of this year. The study authors parse the data by saying that piperine is a promising candidate for further development (10). That is the verdict of the most recent paper written by experts on the subject.

Pre-clinical studies suggest that piperine may exert anti-cancer properties by directly killing tumor cells, affecting hormone expression and/or increasing the levels of chemotherapy drugs. Pre-clinical studies suggest that piperine may be show some promise for the care of patients with cancer of the breast, prostate, colon, melanoma and osteosarcoma.

Summary: There is no hard clinical information on the anticancer properties of piperine.

Does Piperine Assist Weight Loss?

There are three clinical studies looking at the affect of piperine on obesity. All studies used piperine in combination with other agents which again limits the usefulness of the data.

The first study looked at decaffeinated green tea plus piperine versus placebo (6). The green tea was specially formulated with phospholipids to increase the absorption of the green tea. The study participants also undertook significant lifestyle interventions. The study found that study participants who received the combination of green tea plus  piperine were more likely to maintain any weight lost. Of note, the study was sponsored by a company producing a branded version of green tea plus piperine

The second study involved a combination of bioactive food ingredients (including piperine) over a period of eight weeks in 37 study participants (14). The study found an increase sensation of fullness at the end of the study but did not comment on weight loss.

The third study looked at the effect of bioactive foods (including piperine) as part of a lifestyle intervention in 86 subjects. The results of the study showed that participants who had bioactive foods had a significant reduction in their body mass index (15).

Animal studies suggest that increased resting activity of skeletal muscle may contribute to weight loss and explain the mechanism behind any anti-obesity effects of piperine (11).

Summary: Three small clinical studies suggest that piperine may help with weight reduction. However these studies looked at piperine in combination with other agents.

Is Piperine Safe?

There is too little clinical information on piperine to make any decision about its safety. Piperine is usually well-tolerated when used for culinary purposes. Doses of piperine used for cooking would be significantly lower than doses used for medicinal purposes.

A key consideration when considering taking piperine is the potential for piperine-drug and piperine-herb/nutrient interactions. The ability of piperine to increase levels of drugs or nutrients could lead to side effects from the increased levels. Doses of drugs or herbs/nutrients which are usually well tolerated may be toxic when they are co-administered with piperine.

Summary

In summary, I would recommend moving ‘Black Gold’ from the medicine cabinet back into the kitchen and enjoying it in food (and drinks) while waiting for the evidence base for piperine to hit a more respectable triple digits.

References

  1. Arcaro CA, Gutierres VO, Assis RP, Moreira TF, Costa PI, Baviera AM, Brunetti IL. Piperine, a natural bioenhancer, nullifies the antidiabetic and antioxidant activities of curcumin in streptozotocin-diabetic rats. PLoS One. 2014 Dec 3;9(12):e113993. doi: 10.1371/journal.pone.0113993. eCollection 2014.
  2. Badmaev V, Majeed M, Prakash L. Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation. J Nutr Biochem. 2000 Feb;11(2):109-13.
  3. Bisht S, Maitra A. Systemic delivery of curcumin: 21st century solutions for an ancient conundrum. Curr Drug Discov Technol. 2009 Sep;6(3):192-9. Epub 2009 Sep 1. Review.
  4. Derosa G, Maffioli P, Sahebkar A. Piperine and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;928:173-184. Review.
  5. Bisht S, Chavannavar SV, Kanchanashri B, Niveditha SB. Pharmaceutical Perspectives of Spices and Condiments as Alternative Antimicrobial Remedy. J Evid Based Complementary Altern Med. 2017 Jan 1:2156587217703214. doi: 10.1177/2156587217703214. [Epub ahead of print]
  6. Gilardini L, Pasqualinotto L, Di Pierro F, Risso P, Invitti C. Effects of Greenselect Phytosome® on weight maintenance after weight loss in obese women: a randomized placebo-controlled study. BMC Complement Altern Med. 2016 Jul 22;16:233. doi: 10.1186/s12906-016-1214-x.
  7. Hu Z, Yang X, Ho PC, Chan SY, Heng PW, Chan E, Duan W, Koh HL, Zhou S. Herb-drug interactions: a literature review. Drugs. 2005;65(9):1239-82. Review.
  8. Johri RK, Zutshi U. An Ayurvedic formulation ‘Trikatu’ and its constituents. J Ethnopharmacol. 1992 Sep;37(2):85-91. Review.
  9. Kumar S, Kamboj J, Suman, Sharma S. Overview for various aspects of the health benefits of Piper longum linn. fruit. J Acupunct Meridian Stud. 2011 Jun;4(2):134-40. doi: 10.1016/S2005-2901(11)60020-4. Review
  10. Manayi A, Nabavi SM, Setzer WN, Jafari S. Piperine as a potential anti-cancer agent: a Review on Preclinical studies. Curr Med Chem. 2017 May 23. doi: 10.2174/0929867324666170523120656. [Epub ahead of print]
  11. Nogara L, Naber N, Pate E, Canton M, Reggiani C, Cooke R. Piperine’s mitigation of obesity and diabetes can be explained by its up-regulation of the metabolic rate of resting muscle. Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13009-13014. Epub 2016 Oct 31.
  12. Pan H, Xu LH, Huang MY, Zha QB, Zhao GX, Hou XF, Shi ZJ, Lin QR, Ouyang DY, He XH. Piperine metabolically regulates peritoneal resident macrophages to potentiate their functions against bacterial infection. Oncotarget. 2015 Oct 20;6(32):32468-83. doi: 10.18632/oncotarget.5957.
  13. Panahi Y, Badeli R, Karami GR, Sahebkar A. Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder. Phytother Res. 2015 Jan;29(1):17-21. doi: 10.1002/ptr.5211. Epub 2014 Aug 4.
  14. Rondanelli M, Opizzi A, Perna S, Faliva M, Solerte SB, Fioravanti M, Klersy C, Edda C, Maddalena P, Luciano S, Paola C, Emanuela C, Claudia S, Donini LM. Acute effect on satiety, resting energy expenditure, respiratory quotient, glucagon-like peptide-1, free fatty acids, and glycerol following consumption of a combination of bioactive food ingredients in overweight subjects. J Am Coll Nutr. 2013;32(1):41-9. doi: 10.1080/07315724.2013.767667.
  15. Rondanelli M, Opizzi A, Perna S, Faliva M, Solerte SB, Fioravanti M, Klersy C, Cava E, Paolini M, Scavone L, Ceccarelli P, Castellaneta E, Savina C, Donini LM. Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months’ consumption of a combination of bioactive food ingredients in overweight subjects. Endocrine. 2013 Oct;44(2):391-401. doi: 10.1007/s12020-012-9863-0. Epub 2012 Dec 28. Erratum in: Endocrine. 2013 Oct;44(2):402.
  16. Sharma S, Kalia NP, Suden P, Chauhan PS, Kumar M, Ram AB, Khajuria A, Bani S, Khan IA. Protective efficacy of piperine against Mycobacterium tuberculosis. Tuberculosis (Edinb). 2014 Jul;94(4):389-96. doi: 10.1016/j.tube.2014.04.007. Epub 2014 May 9.
  17. 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 May;64(4):353-6.
  18. Soutar DA, Doucette CD, Liwski RS, Hoskin DW. Piperine, a Pungent Alkaloid from Black Pepper, Inhibits B Lymphocyte Activation and Effector Functions. Phytother Res. 2017 Mar;31(3):466-474. doi: 10.1002/ptr.5772. Epub 2017 Jan 19.
  19. Zheng J, Zhou Y, Li Y, Xu DP, Li S, Li HB. Spices for Prevention and Treatment of Cancers. Nutrients. 2016 Aug 12;8(8). pii: E495. doi: 10.3390/nu8080495. Review.
  20. Zhou S, Lim LY, Chowbay B. Herbal modulation of P-glycoprotein. Drug Metab Rev. 2004 Feb;36(1):57-104. Review.
Summary
Does Piperine Have Health Benefits? The Current Research Examined
Article Name
Does Piperine Have Health Benefits? The Current Research Examined
Author
Healthy But Smart

1 Comment Does Piperine Have Health Benefits? The Current Research Examined

  1. Ken

    “It seems that everyone is blogging about piperine these days. There is lots of excitement on the blogosphere about the seemingly endless health benefits of this everyday kitchen spice.”

    In that and other sentences, you confuse black pepper with piperine, which is a constituent of black pepper (Piper nigrum).

    Reply

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