Bioperine
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Bioperine
Bioperine® - The most studies of the natural nutrients enhancer from Piperine
Piperine is an alkaloid from black pepper (Piper nigrum) giving it that pungent taste. It is produced using exclusively ethanol, including the oleoresinic part (undoubtedly the only currently rich in piperine extract).
Used before 1997, Bioperine (95-98% piperine) is black pepper (Piper nigrum) extract, well-documented and patented for its action to boost absorption of nutrients (different tests and studies have been conducted many times, including beta carotene and so other carotenoids, CoQ10, Resveratrol, Minerals such as Iron, Selenium, .... liposoluble vitamins, curcuminoids, etc ...).
Bioperine was declared not novel foods in March 2011 by the Belgium authorities. As an activity of "nutrient enhancer," it is not subject to the EFSA authorizations since improving bioavailability may not be a claim (the claims are linked to the nutrient itself). It is produced using only ethanol, including the oleoresinic part (undoubtedly the only currently-rich extract piperine). Its use is oral, 5mg per dose, and patented - including Europe (use of piperine as a gastrointestinal absorbation enhancer).
Its counterpart for topical use is Cosmoperine (tetra hydropiperin, so hydrogenation) extract from piper nigrum as well.
Number of internal - by Sabinsa - and external studies have shown that the safety of Bioperine - and the history of its use (millions of doses already consumed) - is one of the best evidence. The controversial studies sometimes highlighted were carried out at doses up to 1000 times higher than those recommended.
Many in-vivo studies are available, last one on the bioavailability of Iron, especially in sport nutrition.
5 mg per dose 3 times a day. It can be used for feed as well.
Using Bioperine, you use the reference, and get the studies, name and history of uses.
Sabinsa Corporation specifically discovered that this 95% purified extract of an important alkaloid from black pepper can enhance the bioavailability of many nutrients with virtually no loss to them in the body.
Black pepper - Historical spice and medicine
Black pepper (Piper nigrum, Piperaceae) has been used in human diet from ancient times and is one of the most widely used spices throughout the world. It has also been used in various traditional medicines, preservatives and health supplements.
The Materia Medica of Ayurveda, documents black pepper as one of the three herbs essential for several prescriptions and formulations.
Piperine, one of our principal black pepper extracts, corresponds to the alkaloid responsible for the pungency of black pepper and long pepper. It has been used in some forms of traditional medicine. The usual dose of 5mg correspond to ... a well peppered foodstuff.
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Studies & Documents(17)
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News(4)
Enhancing bioavailability of resveratrol with Bioperine
Trans-Resveratrol (purity >95%) and piperine (purity >96.6%) were provided by Sabinsa
Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed to study the mechanism of improved bioavailability of resveratrol via its combination with piperine as well as its effect on resveratrol metabolism.
Scope : Resveratrol (3,5,4′-trihydroxystilbene) is a phytoalexin shown to possess a multitude of health-promoting properties in pre-clinical studies. However, the poor in vivo bioavailability of resveratrol due to its rapid metabolism is being considered as a major obstacle in translating its effects in humans. In this study, we examined the hypothesis that piperine will enhance the pharmacokinetic parameters of resveratrol via inhibiting its glucuronidation, thereby slowing its elimination.
Methods and results : Employing a standardized LC/MS assay, we determined the effect of piperine co-administration with resveratrol on serum levels resveratrol and resveratrol-3-O-β-Dglucuronide in C57BL mice. Mice were administered resveratrol (100 mg/kg; oral gavage) or resveratrol (100 mg/kg; oral gavage) + piperine (10 mg/kg; oral gavage), and the serum levels of resveratrol and resveratrol-3-O-β-D-glucuronide were analyzed at different times. We found that the degree of exposure (i.e. AUC) to resveratrol was enhanced to 229% and the maximum serum concentration (Cmax) was increased to 1544% with the addition of piperine.
Conclusion : Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed to study the mechanism of improved bioavailability of resveratrol via its combination with piperine as well as its effect on resveratrol metabolism.
Keywords Absorption; Bioavailability; Pharmacokinetics; Piperine; Resveratrol
Conclusion (partial) : In conclusion, our study represents the first evaluation of piperine modulating the pharmacokinetic parameters of resveratrol. Our data indicate that piperine increases the Cmax and degree of exposure (i.e. AUC) to resveratrol, which appears to be through the inhibition of glucuronidation of resveratrol by piperine. While mechanistic details of this effect remain to be elucidated, our study could have direct application to human studies evaluating the pharmacokinetic profile of resveratrol. For instance, clinical studies have used doses as high as 5 g daily, which is the equivalent of ten capsules (500 mg each). This represents a significant shortcoming in the long-term translational development of resveratrol as described above. One study in particular has shown that 1 g of resveratrol, which is the equivalent of two capsules, was administered daily for 28 days and was well tolerated [29]. All documented adverse events were grade 1 or 2 Common Toxicity Criteria, with many being very mild and transient. Given our results, the strategy of piperine coadministration may allow for a significant decrease in the dose of resveratrol (and capsules) in clinical settings. As a result, we are currently in the process of enrolling subjects into a phase I clinical trial in healthy volunteers to study the effect of piperine on the bioavailability of resveratrol in a clinical setting. Finally, piperine has been shown to be well tolerated in animals and humans; however, it is possible that through the inhibition of glucuronidation, there could the potential to increase the degree of exposure (i.e. AUC) to pharmaceuticals metabolized by glucuronidation. To minimize the systemic effects of piperine, our future work is focused on optimizing the dose of piperine to ensure local gastrointestinal effects as a strategy to prevent adverse drug interactions.
Enhancing the bioavailability of resveratrol by combining it with piperine - Jeremy J. Johnson, Minakshi Nihal, Imtiaz A. Siddiqui, Cameron O. Scarlett, Howard H. Bailey, Hasan Mukhtar and Nihal Ahmad, Mol Nutr Food Res. 2011 August ; 55(8)
Bioperine enhancing the bioavailability of resveratrol
A study published in the August Volume of Molecular Nutrition / Food Research found that the absorption of resveratrol was significantly increased when combined with piperine (black pepper extract). The resveratrol used in the study was Sabinsa’s Resvenox® and the piperine used was Sabinsa’s patented ingredient BioPerine®.
A study published in the August Volume of Molecular Nutrition / Food Research (Special Issue: Resveratrol – Current Status and Outlook) entitled Enhancing the bioavailability of resveratrol by combining it with piperine, found that the absorption of resveratrol was significantly increased when combined with piperine (black pepper extract). The resveratrol used in the study was Sabinsa’s Resvenox® and the piperine used was Sabinsa’s patented ingredient BioPerine®.
Poor bioavailability and rapid metabolism of resveratrol, one of the most touted natural compounds for human health and nutrition in recent times, is considered a major barrier in humans receiving the significant health benefits of resveratrol that have been found in mouse studies, with prohibitively large amounts needed for humans to realize the health promoting effects.
The study, conducted by Jeremy J. Johnson, Minakshi Nihal, Imtiaz A. Siddiqui, Cameron O. Scarlett, Howard H. Bailey, Hasan Mukhtar and Nihal Ahmad found that piperine significantly increases the bioavailability of Resveratrol by 229%. The Cmax for Resveratrol occurs at 0.25h with piperine and it is enhanced by 1544%. These results have led the researchers to speculate that this bioavailability enhancing effect of piperine will translate into lower amounts of Resveratrol being needed. These results have encouraged the researchers to plan a Phase I study using Resveratrol-‐Piperine combination. While piperine enhances the bioavailability of resveratrol, it decreases slightly the bioavailability of its major metabolite.
The Conclusion of the study read, “Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol.” The authors are planning to conduct a similar clinical study in humans.
Scope: Resveratrol (3,5,4′‐trihydroxystilbene) is a phytoalexin shown to possess a multitude of health‐promoting properties in pre‐clinical studies. However, the poor in vivo bioavailability of resveratrol due to its rapid metabolism is being considered as a major obstacle in translating its effects in humans. In this study, we examined the hypothesis that piperine will enhance the pharmacokinetic parameters of resveratrol via inhibiting its glucuronidation, thereby slowing its elimination.
Methods and results: Employing a standardized LC/MS assay, we determined the effect of piperine co‐administration with resveratrol on serum levels resveratrol and resveratrol‐3‐O‐β‐D‐glucuronide in C57BL mice. Mice were administered resveratrol (100 mg/kg; oral gavage) or resveratrol (100 mg/kg; oral gavage)+piperine (10 mg/kg; oral gavage), and the serum levels of resveratrol and resveratrol‐3‐O‐β‐D‐glucuronide were analyzed at different times. We found that the degree of exposure (i.e. AUC) to resveratrol was enhanced to 229% and the maximum serum concentration (Cmax) was increased to 1544% with the addition of piperine.
Conclusion: Our study demonstrated that piperine significantly improves the in vivo bioavailability of resveratrol. However, further detailed research is needed to study the mechanism of improved bioavailability of resveratrol via its combination with piperine as well as its effect on resveratrol metabolism.
Enhancing the bioavailability of resveratrol by combining it with piperine Jeremy J. Johnson Minakshi Nihal Imtiaz A. Siddiqui Cameron O. Scarlett Howard H. Bailey Hasan Mukhtar Nihal Ahmad
Piperine increases the plasma levels of Coenzyme Q10 (CoQ10)
Supplementation of 120 mg coenzyme Q10 with piperine for 21 days produced a statistically significant (p below 0.0348), approximately 30% greater, area under the plasma curve than was observed during supplementation with coenzyme Q10 plus placebo. It is postulated that the bioenhancing mechanism of piperine to increase plasma levels of supplemental coenzyme Q10 is nonspecific and possibly based on its description in the literature as a thermonutrient
An extract from the fruits of black pepper consisting of a minimum of 98% pure piperine was evaluated in a clinical study using a double-blind design. The relative bioavailability of 90 mg and 120 mg of coenzyme Q10 administered in a single-dose experiment or in separate experiments for 14 and 21 days with placebo or with 5 mg of piperine was determined by comparing measured changes in plasma concentration. The inter-subject variability was minimized by limiting the selection of individuals to healthy adult male volunteers with (presupplementation) fasting coenzyme Q10 values between 0.30 and 0.60 mg/L. The results of the ingle-dose study and the 14-day study indicate smaller, but not significant, increases in plasma concentrations of coenzyme Q10 in the control group compared with the group receiving coenzyme Q10 with a supplement of piperine. Supplementation of 120 mg coenzyme Q10 with piperine for 21 days produced a statistically significant (p below 0.0348), approximately 30% greater, area under the plasma curve than was observed during supplementation with coenzyme Q10 plus placebo. It is postulated that the bioenhancing mechanism of piperine to increase plasma levels of supplemental coenzyme Q10 is nonspecific and possibly based on its description in the literature as a thermonutrient
Conclusion : Our results suggest that piperine supplementation may result in improved absorption of coenzyme Q10 in healthy subjects. It also appears that a longer period of coadministration of piperine with 120 mg rather than 90 mg of coenzyme Q10 per day may result in significantly better absorption of coenzyme Q10 as measured by its plasma levels. The mechanism(s) by which piperine increases the absorption of coenzyme Q10 is likely nonspecific and operates directly in the gastrointestinal tract. These mechanisms, based on literature data, may involve increased gastrointestinal blood supply, increased micelle formation, and epithelial cell wall modification due to the lipophilic nature of the compound. The most interesting mode of action of piperine may be due to its postulated thermogenic properties and the increase in bioenergetic processes in the gastrointestinal epithelium described in our previously published study on its thermonutrient activity. This preliminary report on increased gastrointestinal absorption of the coenzyme Q10 with piperine presents an interesting concept to be further evaluated. The combined supplementation of coenzyme Q10 with piperine may be a practical approach to enhance this nutrient bioavailability, especially in patients diagnosed with low plasma levels of coenzyme Q10 and in elderly individuals with poor gastrointestinal absorption.
Piperine derived from black pepper increases the plasma levels of following oral supplementation , J. Nutr. Biochem. 11: 109 – 113, 2000
Piperine increases bioavailabiity of beta-carotene
Piperine, an alkaloid derived from black pepper increases serum response of beta-carotene during 14-days of oral beta-carotene supplementation
The effectiveness of an extract from the fruit of black pepper, consisting of a minimum of 98.0% pure alkaloid piperine, was evaluated for its ability to improve serum response of beta-carotene during oral supplementation using a double-blind, crossover study design. Subjects were randomly selected to ingest a daily beta-carotene dose (15 mg) either with 5 mg of piperine or placebo during each of two 14-day supplementation periods. Inter-subject variability in pre-supplementation serum beta-carotene levels was minimized by limiting the selection of volunteers to healthy, adult males with fasting serum beta-carotene values below 20 μg/dL. The results indicate that significantly greater increases (P below 0.0001) in serum beta-carotene occurred during supplementation with beta-carotene plus piperine (49.8±9.6μg/dL vs. 30.9±5.4μg/dL) compared to beta-carotene plus placebo. Supplementation with beta-carotene plus piperine for 14-days produced a 60% greater increase in area under the serum beta-carotene curve (AUC) than was observed during supplementation with beta-carotene plus placebo. We suggest that the serum response during oral beta-carotene supplementation is improved through the non-specific, thermogenic property(s) of piperine, described in this paper as thermonutrient in action.
Published 1999 Biology Nutrition Research. V. Badmaev, M. Majeed, E. Norkus
Bioavailability of Selenium and B6 with and without Bioperine supplementation
The serum selenium levels were approximately 30% higher in the group receiving selenium with BioPerine.
The maximum serum levels of vitamin B6 were attained after two hours and they were 2.5 times higher in the group receiving vitamin B6 with BioPerine.
Bioavailability of Selenium
The bioavailability of selenium was evaluated in a double blind study with ten volunteers, five receiving 50 μg L(+)selenomethionine alone and five receiving 50 μg L(+)selenomethionine supplemented with a small amount of naturally derived pure alkaloid piperine in the form of a preparation known as BioPerine®. Over the course of a six week supplementation regimen, serum selenium levels were evaluated before, after two, after three and after six weeks. The serum selenium levels were approximately 30% higher in the group receiving selenium with BioPerine. This increase was detected after two weeks of supplementation, with a plateau in the subsequent time-points tested. None of the volunteers in both experimental groups reported any untoward effects from the supplementation. The serum selenium levels were within normal limits in both groups at all time-points tested. These preliminary results indicate that the bioavailability of selenium can be safely increased
Bioavailability of B6
This study compared the bioavailability of a single dose of 100 mg of vitamin B6 ingested by six healthy volunteers: three participants received the vitamin with BioPerine and three received the vitamin alone. The bioavailability of vitamin B6 was determined by comparing changes in serum concentrations at time zero (before supplement ingestion), and at two and four hours after the supplement ingestion. The maximum serum levels of vitamin B6 were attained after two hours and they were 2.5 times higher in the group receiving vitamin B6 with BioPerine as compared to the control group receiving the vitamin supplementation alone. At four hours testing, the concentrations of vitamin B6 leveled off in both groups, with the vitamin B6 levels in the group who received BioPerine 1.4 times higher as compared to the time-matched control group. None of the volunteers complained of any side effects during the course of the trial, as well in the seven days follow-up period.
Comparison of nutrient bioavailability when ingested alone and in combination with Bioperine Selenium B6 - Vladimir Badmaev, M.D. Ph.D. and Muhammed Majeed, Ph.D.
Bioavailability Enhancement of Iron with Bioperine
Supplementation with a natural product, Bioperine®, in the form of black pepper, as a bioavailability enhancer, could have a potential application as an athlete Fe supplement for improving hematological parameters. Therefore, it is proposed as an innovative food therapy without side effects in ID patients supplemented with Fe for the control of Fe status with or without anemia.
BioPerine has the potential to be applied in the formulation of supplements to improve sustained and controlled release bioavailability, to allow a decrease in dosage and dosing frequency, which would increase patient compliance and tolerance
Abstract: Black pepper (Piper nigrum L.) has been employed in medicine (epilepsy, headaches, and diabetes), where its effects are mainly attributed to a nitrogen alkaloid called piperidine (1-(1-[1,3-benzodioxol-5-yl]-1-oxo-2,4 pentenyl) piperidine). Piperine co-administered with vitamins and minerals has improved its absorption. Therefore, this study aimed to describe the impact of the joint administration of iron (Fe) plus black pepper in physically active healthy individuals. Fe is a micronutrient that aids athletic performance by influencing the physiological functions involved in endurance sports by improving the transport, storage, and utilization of oxygen. Consequently, athletes have risk factors for Fe depletion, Fe deficiency, and eventually, anemia, mainly from mechanical hemolysis, gastrointestinal disturbances, and loss of Fe through excessive sweating. Declines in Fe stores have been reported to negatively alter physical capacities such as aerobic capacity, strength, and skeletal muscle recovery in elite athletes. Thus, there is a need to maintain Fe storage, even if Fe intake meets the recommended daily allowance (RDA), and Fe supplementation may be justified in physically active individuals, in states of Fe deficiency, with or without anemia.
Females, in particular, should monitor their Fe hematological profile. The recommended oral Fe supplements are ferrous or ferric salts, sulfate, fumarate, and gluconate. These preparations constitute the first line of treatment; however, the high doses administered have gastrointestinal side effects that reduce tolerance and adherence to treatment. Thus, a strategy to counteract these adverse effects is to improve the bioavailability of Fe. Therefore, piperine may benefit the absorption of Fe through its bioavailability enhancement properties. Three research studies of Fe associated with black pepper have reported improvements in parameters related to the metabolism of Fe, without adverse effects. Although more research is needed, this could represent an advance in oral Fe supplementation for physically active individuals.
Standard daily intake levels, and even 250-times higher levels, of either black pepper or its active ingredient piperine showed no adverse effects on the parameters evaluated, such as growth, organ weight, and blood components
Keywords: iron; bioavailability; black pepper; piperine; supplementation; physical activity
Iron and Physical Activity: Bioavailability Enhancers, Properties of Black Pepper (Bioperine®) and Potential Applications - Diego Fernández-Lázaro, Juan Mielgo-Ayuso, Alfredo Córdova Martínez and Jesus Seco-Calvo - Nutrients 2020
Influence of Piperine on pharmacokinetics of Curcumin
In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal flucoronidation was evaluated (...) the bioavailability was significantly increase by 154% to 2000%.
The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.
Abstract : The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.
Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers, Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers; G Shoba, D Joy, T Joseph, M Majeed, R Rajendran, P S Srinivas.
BioPerine improves Iron supplementation in case of iron deficiency anaemia
BioIron tablet contains organically bound iron from green gram and BioPerine®
Without any adverse events or serious adverse events, an appreciable statistical significance has been observed with respect to Hb level, total iron binding capacity and other laboratory parameters. Hence it can be reckoned that BioIron is safe and effective for the management of IDA.
AIM: To assess the efficacy and safety of BioIron tablet as a herbal iron supplement for repletion in iron deficiency anaemic patients.
METHODS: Thirty subjects were evaluated in 5 sessions: screening, baseline, 14th, 28th and 56th day accompanied with a follow up assessment at least 7 days from the last visit (day 63). The efficacy parameters, such as complete blood count (CBC), red blood cell indices, erythrocyte sedimentation rate (ESR), serum iron, total iron binding capacity and serum ferritin were evaluated. Subjects were assessed using SF-36 Health Questionnaire and Fatigue Severity Scale. Safety of the investigational product was assessed by physical examination, vital signs and adverse events.
RESULTS: BioIron showed a significant efficacy in 56 days as evaluated by an increase in Haemoglobin (Hb) levels (p max 0.0001) and decrease erythrocyte sedimentation rate (p max 0.001). An increase in serum iron could be correlated to the immediate release of iron from BioIron in systemic circulation. This depicts the increased health status of subjects response to SF-36 Health Questionnaire (p max 0.0001) and decreased fatigability (p max 0.0001) assessed by Fatigue Severity Scale during the study course.
CONCLUSIONS: Without any adverse events or serious adverse events, an appreciable statistical significance has been observed with respect to Hb level, total iron binding capacity and other laboratory parameters. Hence it can be reckoned that BioIron is safe and effective for the management of IDA.
Current clinical study shows haematinic potential of BioIron with significant results for the management of IDA. Further, subjects enrolled in this study with IDA showed an exponential increase in Hb level when compared from screening to day 56 in correction of haematological parameters. BioIron was observed to directly affect the body stores of iron. Thus, for an iron deficient individual, this preparation is beneficial in replenishing iron stores of the body. Unlike the conventional therapy, BioIron did not impart any side effects thus, claiming BioIron to be safe for internal administration. With no abnormal laboratory values, clinical findings or changes in vital signs and with statistical significance with respect to Hb and total iron binding capacity and other laboratory parameters, it can be proposed that BioIron is effective and safe for oral consumption in the management of IDA.
KEYWORDS: BioIron, Haemoglobin, Erythrocyte Sedimentation Rate, Ferritin, SF-36 Health Questionnaire, Fatigue Severity Scale.
A Clinical study on iron deficiency anaemia with BioIron - Muhammed Majeed, Priti Vaidyanathan, Pallavi Kiradi, Prachi Subhash Lad, Kiran Kumar Vuppala - International Journal of Ayurveda and Pharma Research
Resveratrol and Sabinsa’s Bioperine® increase mitochondrial capacity with exercise
A recent human clinical study by the University of Georgia Department of Kinesiology in Athens, Georgia found that Resveratrol fortified with Sabinsa’s BioPerine® increases mitochondrial function. The study, Influence of exercise training with resveratrol supplementation on skeletal muscle mitochondrial capacity by Kristine R. Polley, Nathan Jenkins, Patrick O’Connor, and Kevin McCully, was published. Skeletal muscle mitochondrial performance was shown to increase with consumption of Resveratrol (500mg) and BioPerine (10mg) in this double blind study.
A recent human clinical study by the University of Georgia Department of Kinesiology in Athens, Georgia found that Resveratrol fortified with Sabinsa’s BioPerine® increases mitochondrial function. The study, Influence of exercise training with resveratrol supplementation on skeletal muscle mitochondrial capacity by Kristine R. Polley, Nathan Jenkins, Patrick O’Connor, and Kevin McCully, was published in Applied Physiology, Nutrition and Metabolism (41: 26–32 (2016) dx.doi.org/10.1139/apnm - 2015 -0370). Skeletal muscle mitochondrial performance was shown to increase with consumption of Resveratrol (500mg) and BioPerine (10mg) in this double blind study.
Mitochondria act as the power producers of cells in the body, and are also involved in other cell processes such as cell division and growth. The enzyme triumvirate, PGC1α-‐SIRT1-‐AMPK plays a crucial role in mitochondrial biogenesis and Resveratrol aids greatly in the process by enhancing the expression of these three enzymes. BioPerine, by enhancing the bioavailability of Resveratrol, plays an amplifying role.
The study was conducted on participants who ingested the combo Resveratrol + BioPerine for four weeks with moderate exercise. Near infrared spectroscopy was used to study the mitochondrial capacity of wrist flexor muscle of one arm while the other arm served as the control.
“The study is especially significant for the general population who may be unable to perform high intensity exercise,” said Nagabhushanam Kalyanam, PhD, President of R / D, Sabinsa. “Functionally beneficial mitochondrial-‐performance is realized even with low intensity exercise with Resveratrol plus BioPerine supplementation.”
This is not the first study to show such activity. Earlier cellular and animal studies published about four years ago by University of Wisconsin demonstrated higher bioavailability of Resveratrol with concomitant administration of BioPerine. The University of Georgia human study further adds credence to the significant role played by BioPerine in augmenting the role of Resveratrol.
Applied Physiology, Nutrition and Metabolism (41: 26–32 (2016) dx.doi.org/10.1139/apnm - 2015 -0370).
Toxicology of piperine
The doses of Bioperine recommended for bioavailability enhancement are relatively low when compared to the toxic doses, and translate to a dose of pure piperine in a range of 2.5-15 mg per dose. That dose equates to an average daily dose of 0.04-0.25* mg of piperine/kg body weight
Black pepper, which contains approximately 5-9% piperine, is listed by the US Food and Drug Administration (FDA) as a herb generally recognized as safe (GRAS) for its intended use as a spice, seasoning and flavoring (21 CFR 100,01 182,10, 1 82-20). Based on black pepper imports, it is estimated that the average consumption of black pepper in the US is about 359 mg per person per day. From this statistical data the average consumption of piperine per person per day is calculated as 17.95 - 32.3
Getting the Most Out of Your Health Food Supplements with Black Pepper Extract
WriteUp Bioperine "Getting the Most Out of Your Health Food Supplements with Black Pepper Extract"
When Bioperine® was administered orally to healthy humans in a dose of five milligrams per person per day, the serum levels of different tested nutrients significantly increased.
Sabinsa Corporation discovered that a 95% purified extract of an important alkaloid from black pepper can enhance the bioavailability of many nutrients with virtually no loss to them in the body. It is known as Bioperine and has been awarded two US Patents. Its active constituent, Piperine, is what gives pepper its unique pungency. This remarkable warming sensation in the gut, enables not only food, but also nutrients in supplemental form to be more readily absorbed and put to use.
A number of scientific experiments have proven this to be so time and again. When Bioperine® was administered orally to healthy humans in a dose of five milligrams per person per day, the serum levels of different tested nutrients significantly increased. Blood levels of fat-soluble beta carotene, for instance, when taken with Bioperine® for two weeks, increased by 60% over the control values, receiving the vitamin alone. When one of the B-Complex groups, Vitamin B-6 was ingested with Bioperine® it resulted in 2.5 times higher blood levels in only two hours.
Furthermore, a six week supplementation program of selenium (in the form of selenomethionine) with and without this incredible ingredient, resulted in a 30% increase in serum levels of selenium in the Bioperine® group as compared to the control group. A recently completed human study involving the simultaneous administration of Bioperine® with CoQ10 yielded an absolute increase in blood serum levels of 30% as well.
When Bioperine® was administered orally to healthy humans in a dose of five milligrams per person per day, the serum levels of different tested nutrients significantly increased. Blood levels of fat-soluble beta carotene, for instance, when taken with Bioperine® for two weeks, increased by 60% over the control values, receiving the vitamin alone. When one of the B-Complex groups, Vitamin B-6 was ingested with Bioperine® it resulted in 2.5 times higher blood levels in only two hours. Furthermore, a six week supplementation program of selenium (in the form of selenomethionine) with and without this incredible ingredient, resulted in a 30% increase in serum levels of selenium in the Bioperine® group as compared to the control group. A recently completed human study involving the simultaneous administration of Bioperine® with CoQ10 yielded an absolute increase in blood serum levels of 30% as well.
Genotoxicity of piperine using Salmonella typhimurium and somatic germ cells
Piperine thus appears to be a non-genotoxic chemical
Piperine (CAS 94-62-2) is a constituent of various spices and is used as a common food additive all over the world. The genotoxic potential of piperine was assessed using four different test systems, namely, Ames test using Salmonella typhimurium, micronucleus test, sperm shape abnormality test and dominant lethal test using Swiss albino mice. In the Ames test, six different doses of piperine, in the range of 0.005-10 mumol/plate, did not induce his+ revertants, with or without metabolic activation, indicating its nonmutagenic nature. In the bone narrow micronucleus test using two doses in the range of therapeutic usage (10 and 20 mg/kg body weight), piperine itself was non-mutagenic. Like in somatic cells, piperine (10 and 50 mg/kg body weight) failed to induce mutations in male germ cells of mouse as assessed by using the sperm shape abnormality and dominant lethal tests. Piperine thus appears to be a non-genotoxic chemical
Assessment of genotoxic effect of piperine using Salmonella typhimurium and somatic and germ cells of Swiss albino mice Bioperine - Karekar VR, Mujumdar AM, Joshi SS, Dhuley J, Shinde SL, Ghaskadbi S. - Arzneimittel forschung. 1996 Oct; 46 (10):972- 5
Role of Piperine As A Bioavailability Enhancer
It is speculated that piperine may act as a so-called thermonutrient and increase the absorption of certain nutritional substances from the gastrointestinal tract by producing a local thermogenic action. The present review is an attempt to highlight the bioenhancing ability of piperine when it is given along with various drugs and nutrients.
Abstract : Piperine is an alkaloid responsible for the pungency of black pepper and long pepper, along with chavicine (an isomer of piperine). It has also been used in some forms of traditional medicine and as an insecticide. Long pepper (Piper longum) and Black pepper (Piper nigrum), the active compound in both Piper longum and Piper nigrum is piperine (1-piperoyl piperidine) which is responsible for bioenhancing effect. It is shown to possess bioavailability enhancing activity with various structurally and therapeutically diverse drugs. It has been found that piperine's bioavailability enhancing property may be attributed to increased absorption, which may be due to alteration in membrane lipid dynamics and change in the conformation of enzymes in the intestine. Piperine has been demonstrated to increase the serum levels and lengthen the serum half lives of some nutritional substances, such as coenzyme Q10 and beta-carotene. The mechanism of this action is unknown. It is speculated that piperine may act as a so-called thermonutrient and increase the absorption of certain nutritional substances from the gastrointestinal tract by producing a local thermogenic action. The present review is an attempt to highlight the bioenhancing ability of piperine when it is given along with various drugs and nutrients.
Conclusion : Piperine (1-piperoyl piperidine) which is the active compound in both Piper longum and Piper nigrum is mainly responsible for the bioenhancing activity. The mechanisms for the bioenhancer activity of piperine have been proposed including DNA receptor binding, modulation of cell signal transduction and inhibition of drug efflux pump. Piperine has been demonstrated to increase the serum levels and lengthen the serum half lives of some nutritional substances, such as coenzyme Q10 and beta-carotene. Major categories of drugs that have shown increased bioenhancement include cardiovascular, respiratory, CNS, GIT antibiotics and anticancers. Some examples include tetracyclines, sulfadiazine, vasicine rifampicin, INH, pyrazinamide, ethambutol phenytoin, phenobarbitone, carbamazepine nimesulide, indomethacin beta-carotene coenzyme Q10 (CoQ10), ciprofloxacin curcumin, dapsone, amino acids, glucose and several other classes of drugs. In this systematic review, an attempt is made to highlight the bioenhancing ability of piperine when it is given along with various drugs and nutrients.
Role of Piperine As A Bioavailability Enhancer, People’s Institute of Pharmacy & Research Centre, People’s University, Bhanpur, Bhopal-462037 (M.P.), India - International Journal of Recent Advances in Pharmaceutical Research, October 2011; 4: 16 - 23
The world’s safest and most clinically studied black pepper extract
Sabinsa has published the list of available studies on the most clinically studied black pepper extract, BioPerine®, with 63 Clinical studies, 87 publications (as per 2022).
Sabinsa’s BioPerine®, a standardized extract prepared from dried fruits of Piper nigrum, contains a minimum of 95% piperine. It has been shown to significantly enhance the bioavailability of several supplement nutrients, such as β-carotene, L(+)-Selenomethionine, Se-methyl-L-selenocysteine, vitamin B6, vitamin C, coenzyme Q10 (CoQ10), curcumin, resveratrol, ginseng and elemental iron through their increased absorption.
As of now, there are 8 clinical studies to support BioPerine®’s bioavailability enhancing property and more than 63 clinical studies published on other health benefits. With all of the clinical data available, BioPerine® becomes the most clinically studied black pepper extract brand in the world.
The most safety Data : Sabinsa’s BioPerine® is one such product standardized to 95% piperine and is the only product sourced out of black pepper to obtain an original patented status for its bio-enhancing property of nutrients, and is the only source from black pepper to get validated for its safety and efficacy for nutritional use. The dose of BioPerine® (2.5-15 mg per dose) recommended for bioavailability enhancement is relatively low when compared to the toxic doses. It has received GRAS status in April 2010, after a comprehensive review of safety and toxicology data by an independent panel of scientists with international repute.
Piperine multiplies the strength of many supplements and drugs
Piperine is one of those delightful surprises that occasionally come to light in spite of there being no reason to expect them to exist at all. How remarkable that pepper plants should produce a substance that turns out to be so useful and versatile! Certainly the pepper plants didn’t invent piperine in order to please human beings — they have undoubtedly been producing this substance since long before human beings existed, and for reasons that we can only guess at. The fact that it is a bioavailability enhancer for our drugs and supplements seems to be a lucky coincidence.
Piperine is one of those delightful surprises that occasionally come to light in spite of there being no reason to expect them to exist at all. How remarkable that pepper plants should produce a substance that turns out to be so useful and versatile! Certainly the pepper plants didn’t invent piperine in order to please human beings — they have undoubtedly been producing this substance since long before human beings existed, and for reasons that we can only guess at. The fact that it is a bioavailability enhancer for our drugs and supplements seems to be a lucky coincidence.
We are also lucky that piperine is made by plants. If it were a purely man-made chemical our access to it would have been blocked by government bureaucrats, who would have run the development costs up so high that no company would have found it worthwhile to develop it as a product. We can only hope that there are lots more such substances waiting to be discovered in the biological world, and that we can continue to foil attempts by government agencies to strip away our rights to use them.
Aside from its effects on bioavailability, piperine has a number of other actions in the body. (It is suspected, but not proven, that some of these actions result from piperine’s effects on the bioavailability of other substances.) These actions include:
Increasing the brain’s production of beta-endorphins
Pain relief
Increasing the brain’s production of serotonin
Anticonvulsant, anti-epileptic action
Increasing the adrenal glands’ production of epinephrine (adrenaline)
Altering contractions in the upper and lower digestive tract
Reducing the stomach’s production of acid (for about 1 hour)
Decreasing ulceration of the stomach
Increasing the pancreas’s production of digestive enzymes (amylase, lipase, trypsin and chymotrypsin)
Stimulating production of melanin
Reducing inflammation due to irritation or allergy
Relieving asthma symptoms
Piperine multiplies the strength of many supplements and drugs, by Russell Mills / Delano Report
Analgesic Activity of Piper Nigrum Extract
The findings suggest that the Piper nigrum extract significantly increased the analgesic activity of diclofenac sodium and pentazocine.
Objective: To evaluate the analgesic activity of Piper nigrum extract per se and its interaction with diclofenac sodium and pentazocine in albino mice.
Materials and Method: Healthy albino mice of either sex weighing 25-30 grams were taken and divided into 4 groups of 8 animals each. Peripheral analgesic activity was evaluated by acetic acid induced writhing test, using diclofenac sodium (5 mg/kg), Piper nigrum extract (10 mg/kg) and their combination (5+10 mg/kg) orally. Similarly central analgesic activity was studied using tail flick method and pentazocine (5 mg/kg) orally was used instead of diclofenac sodium.
Results: Piper nigrum extract alone did not show any significant analgesic activity in tail flick and writhing methods. However results of acetic acid induced writhing model showed that diclofenac sodium reduces writhing 54.90% with respect to control when administered alone, but showed significant decrease in writhes 78.43% with respect to control when Piper nigrum extract was co administered with diclofenac sodium. When Piper nigrum extract combined with pentazocine showed significant increase in tail flick latency in comparison with pentazocine alone and control group (P<0.05).
Conclusion: The findings suggest that the Piper nigrum extract significantly increased the analgesic activity of diclofenac sodium and pentazocine.
Keywords: Piper nigrum extract, tail flick latency, writhing
Analgesic Activity Of Piper Nigrum Extract Per Se And Its Interaction With Diclofenac Sodium And Pentazocine In Albino Mice, The Internet Journal of Pharmacology 2007 : Volume 5 Number 1 - S. Pooja, R. P. Agrawal, P. Nyati, V. Savita and P. Phadnis
Biological role of Black pepper
This review based on the biological role of Piper nigrum can provide that the peppercorn or other parts can be used as crude drug for various diseases while the secondary metabolites such as piperine can be used for specific diseases.
Piper nigrum L. is considered the king of spices throughout the world due to its pungent principle piperine. Peppercorn of Piper nigrum as a whole or its active components are used in most of the food items. Different parts of Piper nigrum including secondary metabolites are also used as drug, preservative, insecticidal and larvicidal control agents. Biologically Piper nigrum is very important specie. The biological role of this specie is explained in different experiments that peppercorn and secondary metabolites of Piper nigrum can be used as Antiapoptotic, Antibacterial, Anti-Colon toxin, Antidepressant, Antifungal, Antidiarrhoeal, Anti-inflammatory, Antimutagenic, Anti-metastatic activity, Anti oxidative, Antiriyretic, Antispasmodic, Antispermatogenic, Antitumor, Antithyroid, Ciprofloxacin potentiator, Cold extremities, Gastric ailments, Hepatoprotective, Insecticidal activity, Intermittent fever and Larvisidal activity. Other roles of this specie includes protection against diabetes induced oxidative stress; Piperine protect oxidation of various chemicals, decreased mitochondrial lipid peroxidation, inhibition of aryl hydroxylation, increased bioavailability of vaccine and sparteine, increase the bioavailability of active compounds, delayed elimination of antiepileptic drug, increased orocecal transit time, piperine influenced and activate the biomembrane to absorb variety of active agents, increased serum concentration, reducing mutational events, tumour inhibitory activity, Piperine inhibite mitochondrial oxidative phosphorylation, growth stimulatory activity and chemopreventive effect. This review based on the biological role of Piper nigrum can provide that the peppercorn or other parts can be used as crude drug for various diseases while the secondary metabolites such as piperine can be used for specific diseases.
Biological role of Piper nigrum L. (Black pepper): A review - Asian Pacific Journal of Tropical Biomedicine, (2012) S1945 - S1953 - Nisar Ahmad, Hina Fazaf, Bilal Haider Abbasi, Shahid Farooq, Mohammad Ali and Mubarak Ali Khan
Research published on Curcumin C3 complex® / Bioperine® combination as adjuvant therapy in covid-19 patients
June 24, 2021 : C3 Complex® with BioPerine® was used as adjuvant therapy for COVID-19 in a double-blind, randomized controlled clinical trial conducted on 140 COVID-19 patients with mild, moderate, and severe symptoms.
Iron Deficiency and Physical Activity
Iron deficiency anaemia (IDA) is the most ubiquitous nutritional deficiency worldwide, and is particularly prevalent in women and infants. A new study explain the mechanism of action, and the Supplementation with a natural product, Bioperine.
Malignant Mesothelioma Cells
Study Shows Inhibitory Effect of Curcumin C3 Complex® and BioPerine® Combination on Malignant Mesothelioma Cells
Curcumin and Taurine - Hepatocellular
Pilot Study Published Examining Curcumin C3 Complex® and BioPerine® With Taurine as Treatment for Hepatocellular Carcinoma
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