PhytoZon is revolutionary product that comes to us from a team of 15 Doctors and research Scientists
who travel the world in search of Phytonutrients that can have a positive impact on our health and wellness.

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Powerful Ingredients and Science:

The ingredients in PhytoZon, many with antioxidant activity, have been individually shown in multiple peer-reviewed and published research and clinical studies to support the following:

INGREDIENT - RNI 249

RNI249 - Is a Patented, Highly Concentrated Substance:

​RNI249 Is the only known natural substance or pharmaceutical shown to increase endogenous IGF-1 in human cells

Research supported by two National Institutes of Health: National Institute of Aging and the National Institute of Arthritis and Musculoskeletal Disease

Helps Support:

1. Endogenous IGF-1 Secretion
2. Healthy Aging

RNI 249 is a patented extract from the hypocotyls of the crucifer Lepidium meyenii (aka "Maca"), a radish-like tuber cultivated only on the inner slopes of the Andean Mountains. In a study with Case Western Reserve University, it has been shown to increase human cellular production of IGF-1 and in a clinical trial, together with Vincaria, was an effective treatment for osteoporosis.

The pituitary gland in the brain secretes human growth hormone (HGH) which in turn signals (primarily) the liver to produce and secrete insulin like growth factor 1 (IGF-1). Both HGH and IGF-1 promote whole body growth and their levels peak during puberty. IGF-1 increases protein synthesis (muscle growth), bone mineralization, low blood sugar, kidney function and insulin sensitivity. It promotes healing and repair of bone, muscle, nervous system and immune system cells.

Following puberty when its levels are at their peak, as we age, IGF-1 levels precipitously decline such that by the time we are 60 years old, the levels have decreased by approximately eighty percent (80%).

This natural decline in IGF-1 levels in adulthood, known as somatopause, is responsible for most of the signs we associate with aging. These include but are not limited to altered musculoskeletal function (e.g. muscle atrophy; associated decrease in strength; bone calcium loss/osteoporosis); altered endocrine function (i.e. a higher incidence of diabetes); altered carbohydrate and lipid metabolism; altered Integumentary function (e.g. skin thinning, wrinkles); and, altered neurological function (e.g. dementia, Alzheimer disease).

To date, RNI 249 is the only substance, natural or pharmaceutical, which has been shown to increase the body's natural production of IGF.

As proof of principle, researchers subsequently conducted a human clinical trial, sponsored in part by the NIH/NIA, in subjects with confirmed osteoarthritis. Within the 30-day period of the trial and then for most within seven days, 94% of the participants had a statistically significant improvement in mobility and flexibility and in comparison to the positive control glucosamine, a marked reduction in pain.

Scientific Studies

1. Barzilai N, Huffman D, Muzumdar R et al: The Critical Role of Metabolic Pathways in Aging. Diabetes. 2012. 61(6):1315-1322

2. Bobrowski P (PI): Enhanced IGF-1 Production in Human Cartilage. Grant No. 1R43AG024733-01, US National Institutes of Health (NIH): National Institute on Aging & National Institute of Arthritis and Musculoskeletal Disease. 2004-2005.

3. Bobrowski, PJ: Methods and compositions to enhance endogenous IGF production and their use. USPTO No. 8182847: 2012 May 22.

4. Brugts M, Ranke M, Hofland L et al: Normal Values of Circulating Insulin-Like Growth Factor-I Bioactivity in the Healthy Population: Comparison with Five Widely Used IGF-I Immunoassays. J Clin Endocrinol Metab. 2008. 93(7):2539–2545.

5. Gong Z, Kennedy O, Sun H et al: Reductions in serum IGF-1 during aging impair health span. Aging Cell. 2014. 13(3):408-18.

6. Juul A, Bang P, Hertel N at al: Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab. 1994. 78(3):744-52.

7. Mehta K, Gala J, Bhasale S et al: Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]. BMC Comp Alt Med. 2007. 7:34.

8. Miller M, Ahmed S, Bobrowski P et al: The chondroprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta. BMC Complement Altern Med. 2006. 6:13.

9. Noordam R, Gunn D, Tomlin C et al: Serum insulin-like growth factor 1 and facial ageing: high levels associate with reduced skin wrinkling in a cross-sectional study. Br J Dermatol. 2013. 168(3):533-8.

10. O’Neill C, Kiely A, Coakley M et al: Insulin and IGF-1 signaling: longevity, protein homoeostasis and Alzheimer’s disease. Biochem Soc Trans. 2012. 40(4):721-7.

11. Sandovala M, Okuhama N, Angeles F et al: Antioxidant activity of the cruciferous vegetable Maca (Lepidium meyenii). Food Chemistry, 2002, 79: 207-213. (Download PDF #10)

12. Sjögren K, Jansson J, Isaksson O et al: A model for tissue-specific inducible insulin-like growth factor-I (IGF-I) inactivation to determine the physiological role of liver-derived IGF-I. Endocrine. 2002. 19(3):249-56.

13. Xu S, Gu X, Pan H et al: Reference ranges for serum IGF-1 and IGFBP-3 levels in Chinese children during childhood and adolescence. Endocr J. 2010. 57(3):221-8.

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INGREDIENT - Vincaria

Vincaria - Is a Patented, Highly Concentrated Substance:

Clinically effective: Has been found in a preliminary study to reduce pain associated with activity in individuals with osteoarthritis of the knee.

Vincaria is a patented alkaloid-deplete extract from the Uncaria species vine shown in human clinical studies to reduce inflammation and pain associated with osteoarthritis. It’s mechanism of action is regulation of the TNF-alpha, a cytokine responsible in over 35 inflammatory pathways, via the NFkB. It also protects the gastrointestinal tract from NSAID (e.g. aspirin) induced injury, such as ulcers.

Inflammation is a key element and chronically active in many diseased states, including inflammatory bowel disease, arthritis, sepsis, gastritis, asthma, and atherosclerosis. Nuclear Factor Kappa B (NFkB) is a protein complex found in most cells that acts as the "on-off" switch for many genes involved in various types of inflammation.

Beginning in 1998, scientists at LSU Medical School and later Albany Medical College began studying the two cat’s claw species. It was discovered that UG acts as a powerful anti-inflammatory agent by regulating TNF alpha, the master "On-Off" switch in our bodies responsible for over thirty-five different types of inflammation – from arthritis to asthma. When alkaloid traces were extracted and removed from UG, a patented process which created Vincaria, it was even more therapeutic.

Subsequently, a clinical trial was conducted in which a single once-a-day 100 milligram dose of Vincaria was effective in ninety percent of patients, the majority in less than five days. It was then used as an anti-inflammatory component, both to promote healthy skeletal, muscular and gastric health in obesity.
In a separate trial, it was combined with a natural mineral supplement again successful for arthritis and later, with RNI 249, a maca extract, for osteoarthritis of the knee.

Scientific Studies

1. Bobrowski PJ: Methods and preparations of extracts of Uncaria species with reduced alkaloid content. USPTO 6,797,286: Sep 28, 2004.

2. Carvalho M, Penido C, Siani A et al: Investigations on the anti-inflammatory and anti-allergic activities of the leaves of Uncaria guianensis (Aublet) J. F. Gmelin. Inflammopharmacology. 2006.14(1-2):48-56.

3. Hunter P. The inflammation theory of disease: The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment. EMBO Reports. 2012. 13(11):968-970.

4. Hardin SR: Cat’s claw: an Amazonian vine decreases inflammation in osteoarthritis. Complement Ther Clin Pract. 2007. 13(1):25-28.

5. Mehta K, Gala J, Bhasale S et al: Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]. BMC Complement Altern Med. 2007. 7:34.

6. Miller M, Ahmed S, Bobrowski P et al: Suppression of Human Cartilage Degradation and Chondrocyte Activation by a Unique Mineral Supplement (SierraSil™) and a Cat’s Claw Extract, Vincaria®. JANA, 2004, 7(2): 32-39.

7. Miller M, Angeles F, Reuter B et al: Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis. BMC Complement Altern Med. 2001. 1:11.

8. Miller M, Mehta K, Kunte S et al: Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: a randomized controlled trial [ISRCTN38432711]. J Inflamm (Lond). 2005. 2:11.

9. Miller M, Ahmed S, Bobrowski P et al: The chondroprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta. BMC Complement Altern Med. 2006. 6:13.

10. Monaco C, Andreakos E, Kiriakidis S et al: Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis. Proc Natl Acad Sci U S A. 2004. 13;101(15):5634-9.

11. Piscoya J, Rodriguez Z, Bustamante S et al: Efficacy and safety of freeze-dried cat’s claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001.50(9):442-8.

12. Sandoval M, Okuhama NN, Zhang XJ et al: Anti-inflammatory and antioxidant activities of cat’s claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002. 9(4):325-37.

13. Urdanibia I, Michelangeli F, Ruiz MC et al: Anti-inflammatory and antitumoural effects of Uncaria guianensis bark. J Ethnopharmacol. 2013. 150(3):1154-62.

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INGREDIENTS - Zangrado and Progrado

Zangrado & Progrado - Patented, Highly Concentrated Substances:

Progrado and Zangrado are patented extracts derived from the viscous red latex of the Croton species tree found primarily in the South American rainforests and is sustainably wild-crafted. RNI original research demonstrated their mechanism of action as regulating the sensory afferent neurons that line the internal organs as well as the skin

Both extracts affect over-stimulated sensory neurons and signal the central nervous system to respond. Orally, both Progrado and Zangrado have been effective in the treatment of nausea and ulcers with implications for irritable bowel syndrome and gastroesophageal reflux disease as well as other gastrointestinal complaints. Topically, Zangrado has been shown clinically effective in reducing pain and itching associated with insect bites and stings, contact dermatitis, and plays a cicatrizing role in the healing process.

Sensory (afferent) neurons are nerves that respond to sensation - such as pain and itch - and are located throughout the body - lining the skin, organs and lungs. In a sense, coughing is your body's way of "itching" its lungs.

Additionally, in human cells, Progrado has been shown to regulate overactive matrix metalloproteinases, molecular "scissors" from breaking down cartilage while increasing cellular IGF-1 levels.

Zangrado has been used in clinical trials topically to treat the pain and itch associated with bug bites and bee stings. It has been used internally to reduce nausea (emesis), diarrhea and also itch. Coughing is a method the lungs use to "itch" themselves so intuitively, Zangrado would be effective internally for certain respiratory conditions. Progrado® has been shown to affect matrix metalloproteinase (MMPs). These are the molecular "scissors" that breakdown cartilage which is normally replaced by new cell Progrado thus allows the body to repair itself.

Importantly, as with red wine, the proanthocyanidins found in Progrado may offer benefits to the cardiovascular system.

Scientific Studies

1. Bobrowski PJ: Methods and preparations of extracts of Uncaria species with reduced alkaloid content. USPTO 6,797,286: Sep 28, 2004.

2. Carvalho M, Penido C, Siani A et al: Investigations on the anti-inflammatory and anti-allergic activities of the leaves of Uncaria guianensis (Aublet) J. F. Gmelin. Inflammopharmacology. 2006.14(1-2):48-56.

3. Hunter P. The inflammation theory of disease: The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment. EMBO Reports. 2012. 13(11):968-970.

4. Hardin SR: Cat’s claw: an Amazonian vine decreases inflammation in osteoarthritis. Complement Ther Clin Pract. 2007. 13(1):25-28.

5. Mehta K, Gala J, Bhasale S et al: Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]. BMC Complement Altern Med. 2007. 7:34.

6. Miller M, Ahmed S, Bobrowski P et al: Suppression of Human Cartilage Degradation and Chondrocyte Activation by a Unique Mineral Supplement (SierraSil™) and a Cat’s Claw Extract, Vincaria®. JANA, 2004, 7(2): 32-39.

7. Miller M, Angeles F, Reuter B et al: Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis. BMC Complement Altern Med. 2001. 1:11.

8. Miller M, Mehta K, Kunte S et al: Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: a randomized controlled trial [ISRCTN38432711]. J Inflamm (Lond). 2005. 2:11.

9. Miller M, Ahmed S, Bobrowski P et al: The chondroprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta. BMC Complement Altern Med. 2006. 6:13.

10. Monaco C, Andreakos E, Kiriakidis S et al: Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis. Proc Natl Acad Sci U S A. 2004. 13;101(15):5634-9.

11. Piscoya J, Rodriguez Z, Bustamante S et al: Efficacy and safety of freeze-dried cat’s claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001.50(9):442-8.

12. Sandoval M, Okuhama NN, Zhang XJ et al: Anti-inflammatory and antioxidant activities of cat’s claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002. 9(4):325-37.

13. Urdanibia I, Michelangeli F, Ruiz MC et al: Anti-inflammatory and antitumoural effects of Uncaria guianensis bark. J Ethnopharmacol. 2013. 150(3):1154-62.

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INGREDIENT - Lutein

LUTEIN May increase Macular Pigment Density and Vision

Lutein (Latin luteus, "yellow") is a carotenoid, a naturally occurring pigment found in the photosynthetic energy cells (chloroplasts) of plants and, in the animals that eat these plants. Its name is derived from the vegetable "carrot" to which it gives its typical orange color. Even the pink color of flamingos and salmon as well as the red in lobsters is due to carotenoids. Lutein is found dominant in some yellow flowers (i.e. dandelions) and carrots, leafy green vegetables (i.e. spinach, turnips, collard greens) and is partially responsible for the coloring seen in egg yolks. The lighter the yolk color, the less Lutein it contains. We often do not recognize Lutein because it is masked by the "green" in plants but with the changing of the seasons, the yellow that are seen in autumn leaves is in fact Lutein.

Lutein is yellow because it absorbs blue light as well as solar radiation, protecting the plant's photosensitive mechanisms. This is extremely important for humans (as well as other animals) because it is found concentrated in the macula and retina, the layer of cells that lines the inner eye. It therefore protects the eye much as it protects the plant from harmful light and radiation. It also acts as an anti-oxidant, a scavenger or "garbage man" for loose reactive oxygen molecules that act in the same manner as oxidation which causes metals to rust.

​ There has been a plethora of peer-reviewed and published human clinical studies over the past decade, and beyond, which clearly show that Lutein is of significant beneficial to the eyes. It helps prevent age-related macular degeneration (AMD) as well as increase visual acuity and function (myopia, presbyopia), contrast sensitivity and night vision. It has been associated with a reduced risk for glaucoma and cataracts and even retinopathy - retinal damage seen in premature babies.

Scientific Studies

(1) Meyers KJ, Mares JA, Igo RP Jr et al: Genetic evidence for role of carotenoids in age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Invest Ophthalmol Vis Sci. 2014 Jan 29; 55(1):587-99. http://www.ncbi.nlm.nih.gov/pubmed/24346170

(2) Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew EY, Clemons TE, Sangiovanni JP et al: Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol. 2014 Feb; 132(2):142-9.http://www.ncbi.nlm.nih.gov/pubmed/24310343

(3) Wang JJ, Buitendijk GH, Rochtchina E et al: Genetic susceptibility, dietary antioxidants, and long-term incidence of age-related macular degeneration in two populations. Ophthalmology. 2014 Mar; 121(3):667-75.http://www.ncbi.nlm.nih.gov/pubmed/24290803

(4) Kesse-Guyot E, Andreeva VA, Ducros V et al: Carotenoid-rich dietary patterns during midlife and subsequent cognitive function. Br J Nutr. 2014 Mar 14; 111(5):915-23. http://www.ncbi.nlm.nih.gov/pubmed/24073964

(5) Zou ZY, Xu XR, Lin XM et al: Effects of lutein and lycopene on carotid intima-media thickness in Chinese subjects with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 2014 Feb; 111(3):474-80. http://www.ncbi.nlm.nih.gov/pubmed/24047757

(6) Slattery ML, Lundgreen A, Wolff RK: Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer. Nutr Cancer. 2013; 65(5):729-38. http://www.ncbi.nlm.nih.gov/pubmed/23859041

(7) Lorenzoni F, Giampietri M, Ferri G: Lutein administration to pregnant women with gestational diabetes mellitus is associated to a decrease of oxidative stress in newborns. Gynecol Endocrinol. 2013 Oct; 29(10):901-3.http://www.ncbi.nlm.nih.gov/pubmed/23808391

(8) Wang MX, Jiao JH, Li ZY et al: Lutein supplementation reduces plasma lipid peroxidation and C-reactive protein in healthy nonsmokers. Atherosclerosis. 2013 Apr; 227(2):380-5.http://www.ncbi.nlm.nih.gov/pubmed/23398944

(9) Murray IJ, Makridaki M, van der Veen RL et al: Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: the CLEAR study. Invest Ophthalmol Vis Sci. 2013 Mar 11; 54(3):1781-8. http://www.ncbi.nlm.nih.gov/pubmed/23385792

(10) Yao Y, Qiu QH, Wu XW et al: Lutein supplementation improves visual performance in Chinese drivers: 1-year randomized, double-blind, placebo-controlled study. Nutrition. 2013 Jul-Aug; 29(7-8):958-64.http://www.ncbi.nlm.nih.gov/pubmed/23360692

(11) Huang YM, Yan SF, Ma L et al: Serum and macular responses to multiple xanthophyll supplements in patients with early age-related macular degeneration. Nutrition. 2013 Feb; 29(2):387-92.http://www.ncbi.nlm.nih.gov/pubmed/23312760

(12) Meinke MC, Friedrich A, Tscherch K et al: Influence of dietary carotenoids on radical scavenging capacity of the skin and skin lipids. Eur J Pharm Biopharm. 2013 Jun; 84(2):365-73.http://www.ncbi.nlm.nih.gov/pubmed/23246796

(13) Beatty S, Chakravarthy U, Nolan JM et al: Secondary outcomes in a clinical trial of carotenoids with coantioxidants versus placebo in early age-related macular degeneration. Ophthalmology. 2013 Mar; 120(3):600-6. http://www.ncbi.nlm.nih.gov/pubmed/23218821

(14) Xu XR, Zou ZY, Xiao X et al: Effects of lutein supplement on serum inflammatory cytokines, ApoE and lipid profiles in early atherosclerosis population. J Atheroscler Thromb. 2013 Feb 22; 20(2):170-7.http://www.ncbi.nlm.nih.gov/pubmed/23154578

(15) Berrow EJ, Bartlett HE, Eperjesi F et al: The effects of a lutein-based supplement on objective and subjective measures of retinal and visual function in eyes with age-related maculopathy – a randomized controlled trial. Br J Nutr. 2013 Jun; 109(11):2008-14. http://www.ncbi.nlm.nih.gov/pubmed/23084077

(16) Ros MM, Bueno-de-Mesquita HB, Kampman E et al: Plasma carotenoids and vitamin C concentrations and risk of urothelial cell carcinoma in the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2012 Oct; 96(4):902-10. http://www.ncbi.nlm.nih.gov/pubmed/22952186

(17) Ma L, Yan SF, Huang YM et al: Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration. Ophthalmology. 2012 Nov; 119(11):2290-7.http://www.ncbi.nlm.nih.gov/pubmed/22858124

(18) Ma L, Dou HL, Huang YM et al: Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial. Am J Ophthalmol. 2012 Oct; 154(4):625-634. http://www.ncbi.nlm.nih.gov/pubmed/22835510

(19) Giaconi JA, Yu F, Stone KL et al: The association of consumption of fruits/vegetables with decreased risk of glaucoma among older African-American women in the study of osteoporotic fractures. Am J Ophthalmol. 2012 Oct; 154(4):635-44. http://www.ncbi.nlm.nih.gov/pubmed/22818906

(20) Manzoni P, Guardione R, Bonetti P et al: Lutein and zeaxanthin supplementation in preterm very low-birthweight neonates in neonatal intensive care units: a multicenter randomized controlled trial. Am J Perinatol. 2013 Jan; 30(1):25-32. http://www.ncbi.nlm.nih.gov/pubmed/22773282

(21) Tanito M, Obana A, Gohto Y et al: Macular pigment density changes in Japanese individuals supplemented with lutein or zeaxanthin: quantification via resonance Raman spectrophotometry and autofluorescence imaging. Jpn J Ophthalmol. 2012 Sep; 56(5):488-96. http://www.ncbi.nlm.nih.gov/pubmed/22699751

(22) Landrum J, Bone R, Mendez V et al: Comparison of dietary supplementation with lutein diacetate and lutein: a pilot study of the effects on serum and macular pigment. Acta Biochim Pol. 2012; 59(1):167-9.http://www.ncbi.nlm.nih.gov/pubmed/22428144

(23) Graydon R, Hogg RE, Chakravarthy U et al: The effect of lutein- and zeaxanthin-rich foods v. supplements on macular pigment level and serological markers of endothelial activation, inflammation and oxidation: pilot studies in healthy volunteers. Br J Nutr. 2012 Jul; 108(2):334-42.http://www.ncbi.nlm.nih.gov/pubmed/22313522

(24) Piermarocchi S, Saviano S, Parisi V et al: Carotenoids in Age-related Maculopathy Italian Study (CARMIS): two-year results of a randomized study. Eur J Ophthalmol. 2012 Mar-Apr; 22(2):216-25.http://www.ncbi.nlm.nih.gov/pubmed/22009916

(25) Thyagarajan B, A Meyer K, Smith LJ et al: Serum carotenoid concentrations predict lung function evolution in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Am J Clin Nutr. 2011 Nov; 94(5):1211-8. http://www.ncbi.nlm.nih.gov/pubmed/21918220

(26) Shvetsov YB, Hernandez BY, Wilkens LR et al: Plasma micronutrients and the acquisition and clearance of anal human papillomavirus infection: the Hawaii HPV cohort study. Cancer Res. 2010 Dec 1; 70(23):9787-97.http://www.ncbi.nlm.nih.gov/pubmed/20935226

(27) Berson EL, Rosner B, Sandberg M et al: Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010 Apr; 128(4):403-11. http://www.ncbi.nlm.nih.gov/pubmed/20385935

(28) Perrone S, Longini M, Marzocchi B et al: Effects of lutein on oxidative stress in the term newborn: a pilot study. Neonatology. 2010; 97(1):36-40. http://www.ncbi.nlm.nih.gov/pubmed/19590244

(29) Cho H, Kim MK, Lee JK et al: Relationship of serum antioxidant micronutrients and sociodemographic factors to cervical neoplasia: a case-control study. Clin Chem Lab Med. 2009; 47(8):1005-12.http://www.ncbi.nlm.nih.gov/pubmed/19589102

(30) Ma L, Lin XM, Zou ZY et al: A 12-week lutein supplementation improves visual function in Chinese people with long- term computer display light exposure. Br J Nutr. 2009 Jul; 102(2):186-90.http://www.ncbi.nlm.nih.gov/pubmed/19586568

(31) McCall DO, McGartland CP, McKinley MC et al: Dietary intake of fruits and vegetables improves microvascular function in hypertensive subjects in a dose-dependent manner. Circulation. 2009 Apr 28; 119(16):2153-60.http://www.ncbi.nlm.nih.gov/pubmed/19364976

(32) Mignone LI, Giovannucci E, Newcomb PA et al: Dietary carotenoids and the risk of invasive breast cancer. Int J Cancer. 2009 Jun 15; 124(12):2929-37. http://www.ncbi.nlm.nih.gov/pubmed/19330841

(33) Johnson EJ, McDonald K, Caldarella SM et al: Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutr Neurosci. 2008 Apr; 11(2):75-83.http://www.ncbi.nlm.nih.gov/pubmed/18510807

(34) Johnson EJ, Chung HY, Caldarella SM et al: The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation. Am J Clin Nutr. 2008 May; 87(5):1521-9.http://www.ncbi.nlm.nih.gov/pubmed/18469279

(35) Dherani M, Murthy GV, Gupta SK et al: Blood levels of vitamin C, carotenoids and retinol are inversely associated with cataract in a North Indian population. Invest Ophthalmol Vis Sci. 2008 Aug; 49(8):3328-35.http://www.ncbi.nlm.nih.gov/pubmed/18421094

(36) Moeller SM, Voland R, Tinker L et al: Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women’s Health Initiative. Arch Ophthalmol. 2008 Mar; 126(3):354-64.http://www.ncbi.nlm.nih.gov/pubmed/18332316

(37) Palombo P, Fabrizi G, Ruocco V et al: Beneficial long-term effects of combined oral/topical antioxidant treatment with the carotenoids lutein and zeaxanthin on human skin: a double-blind, placebo-controlled study. Skin Pharmacol Physiol. 2007; 20(4):199-210. http://www.ncbi.nlm.nih.gov/pubmed/17446716

(38) Hozawa A, Jacobs DR Jr, Steffes MW et al: Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study. Clin Chem. 2007 Mar; 53(3):447-55. http://www.ncbi.nlm.nih.gov/pubmed/17234732

(39) Zhao X, Aldini G, Johnson EJ et al: Modification of lymphocyte DNA damage by carotenoid supplementation in postmenopausal women. Am J Clin Nutr. 2006 Jan; 83(1):163-9.http://www.ncbi.nlm.nih.gov/pubmed/16400064

(40) Kato I, Ren J, Visscher DW et al: Nutritional predictors for cellular nipple aspirate fluid: Nutrition and Breast Health Study. Breast Cancer Res Treat. 2006 May; 97(1):33-9. http://www.ncbi.nlm.nih.gov/pubmed/16317581

(41) Coyne T, Ibiebele TI, Baade PD et al: Diabetes mellitus and serum carotenoids: findings of a population-based study in Queensland, Australia. Am J Clin Nutr. 2005 Sep; 82(3):685-93.http://www.ncbi.nlm.nih.gov/pubmed/16155284

(42) Morganti P, Fabrizi G, Bruno C: Protective effects of oral antioxidants on skin and eye function. Skinmed. 2004 Nov-Dec; 3(6):310-6. http://www.ncbi.nlm.nih.gov/pubmed/15538079

(43) Richer S, Stiles W, Statkute L et al: Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004 Apr; 75(4):216-30.http://www.ncbi.nlm.nih.gov/pubmed/15117055

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INGREDIENT - Lycopene

Lycopene - Found in tomatoes, fruits and vegetables, such as cherries, watermelon, pink grapefruit, red bell peppers and papayas. There are many fruits and vegetables such as asparagus and parsley that also contain lycopene. (Support studies listed in the Scientific Studies)

Helps Support:

Heart Health
Prostate Health
Circulatory System Health
Enhanced Antioxidant Activity

The name "Lycopene" is derived from the Latin Solanum lycopersicum, the Linnaean name for the common Tomato. It is the bright red pigment found in tomatoes and other fruits and vegetables, such as cherries, watermelon, pink grapefruit, red bell peppers and papayas. However, there are many fruits and vegetables such as asparagus and parsley that contain lycopene yet are not red in color.

Lycopene is not water soluble so upon ingestion, it is incorporated in fat globules in the intestines and then disseminated. As it permeates the very low-density lipoproteins in the blood, those made up of triglycerides and the “bad� cholesterol, this may in some way explain its benefits in preventing/ameliorating atherosclerosis. Similarly, lycopene supplementation is associated with enhancing high density lipoprotein levels (the “good� cholesterol) and reducing blood pressure so in general, acts effectively on the cardiovascular system.

As it is hydrophobic, Lycopene primarily ends up residing in fatty tissues and organs, such as the prostate. Thus, it is logical and has been shown in studies to reduce prostate symptoms, PSA levels and perhaps, the risk of prostate cancer itself. Additionally, its concentration in the fatty tissues, such as the testes, could explain its effects on male fertility and spermatogenesis.

There are several studies that have shown it is effective in some types of inflammation; that it may reduce the risk and severity osteoporosis in postmenopausal women; and even, could play a role in reduce the risk of macular degeneration. There are some studies indicating that Lycopene can reduce the risk associated with UV damage from Sun overexposure which is consistent with the role it plays in skin pigmentation.

Lycopene is probably best known from larger studies reporting the benefits of normal tomato consumption - such as the reduction of cardiovascular incidents and increased quality and span of life as seen in the Mediterranean diet. While it is true that a higher level of serum Lycopene is associated with a healthy lifestyle, it is interesting to note that one study reported that in a subgroup with high lycopene levels, the reverse was found: poor health parameters.

Further review revealed that in this subgroup, the main source of Lycopene was in fact from ketchup. This group relied heavily on fast food restaurants for sustenance so while their levels were higher, their general lifestyle negated any perceived benefits.

Scientific Studies

1. Agarwal S, Rao A: Tomato lycopene and low density lipoprotein oxidation: a human dietary intervention study. Lipids. 1998. 33(10):981-4.

2. Burton-Freeman B, Talbot J, Park E et al: Protective activity of processed tomato products on postprandial oxidation and inflammation: a clinical trial in healthy weight men and women. Mol Nutr Food Res. 2012. 56(4):622-31.

3. Chen J, Song Y, Zhang L: Lycopene/tomato consumption and the risk of prostate cancer: a systematic review and meta-analysis of prospective studies. J Nutr Sci Vitaminol (Tokyo). 2013. 59(3):213-23.

4. Devaraj S, Mathur S, Basu A et al: A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress. J Am Coll Nutr. 2008. 27(2):267-73.

5. Di Giacomo C, Acquaviva R, Sorrenti V et al: Oxidative and antioxidant status in plasma of runners: effect of oral supplementation with natural antioxidants. J Med Food. 2009. 12(1):145-50.

6. Garrido M, González-Flores D, Marchena AM et al: A lycopene-enriched virgin olive oil enhances antioxidant status in humans. J Sci Food Agric. 2013. 93(8):1820-6.

7. Hadley C, Clinton S, Schwartz S: The consumption of processed tomato products enhances plasma lycopene concentrations in association with a reduced lipoprotein sensitivity to oxidative damage. J Nutr. 2003. 133(3):727-32.

8. Hozawa A, Jacobs D Jr, Steffes M et al: Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study. Clin Chem. 2007. 53(3):447-55.

9. Kim JY, Paik JK, Kim OY et al: Effects of lycopene supplementation on oxidative stress and markers of endothelial function in healthy men. Atherosclerosis. 2011. 215(1):189-95.

10. Maruyama C, Imamura K, Oshima S et al: Effects of tomato juice consumption on plasma and lipoprotein carotenoid concentrations and the susceptibility of low density lipoprotein to oxidative modification. J Nutr Sci Vitaminol (Tokyo). 2001. 47(3):213-21.

11. Paran E, Novack V, Engelhard YN et al: The effects of natural antioxidants from tomato extract in treated but uncontrolled hypertensive patients. Cardiovasc Drugs Ther. 2009. 23(2):145-51.

12. Riccioni G, Scotti L, Di Ilio E et al: Lycopene and preclinical carotid atherosclerosis. J Biol Regul Homeost Agents. 2011. 25(3):435-41

13. Schwarz S, Obermüller-Jevic U, Hellmis E et al: Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr. 2008. 138(1):49-53.

14. Shen YC, Chen SL, Wang CK: Contribution of tomato phenolics to antioxidation and down-regulation of blood lipids. J Agric Food Chem. 2007. 8;55(16):6475-81.

15. Silaste ML, Alfthan G, Aro A et al: Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation. Br J Nutr. 2007. 98(6):1251-8.

16. Torbergsen A, Collins A: Recovery of human lymphocytes from oxidative DNA damage; the apparent enhancement of DNA repair by carotenoids is probably simply an antioxidant effect. Eur J Nutr. 2000. 39(2):80-5.

17. Tyssandier V, Feillet-Coudray C, Caris-Veyrat C et al: Effect of tomato product consumption on the plasma status of antioxidant microconstituents and on the plasma total antioxidant capacity in healthy subjects. J Am Coll Nutr. 2004. 23(2):148-56.

18. Visioli F, Riso P, Grande S et al: Protective activity of tomato products on in vivo markers of lipid oxidation. Eur J Nutr. 2003. 42(4):201-6.

19. Xaplanteris P, Vlachopoulos C, Pietri P et al: Tomato paste supplementation improves endothelial dynamics and reduces plasma total oxidative status in healthy subjects. Nutr Res. 2012. 32(5):390-4.

20. Zhang X, Wang Q, Neil B et al: Effect of lycopene on androgen receptor and prostate-specific antigen velocity. Chin Med J (Engl). 2010. 123(16):2231-6.

21. Zou ZY, Xu XR, Lin XM et al: Effects of lutein and lycopene on carotid intima- media thickness in Chinese subjects with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 2014. 111(3):474-80.

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INGREDIENT - Astragalus

Astragalus - (Astragalus membranaceus) root, also known as Milkvetch, has been used as a traditional Chinese medicine (TCM) for over 2,000 years. While it has be traditionally used to protect the liver, for aging, stress and the heart, date reveals that it may be effective in enhancing the immune system.

Helps Support:

1. Immune System
2. Healthy Immune Cell Function
3. May help reduce seasonal allergies

Scientific Studies

1. Bao-Mei S, Xu W, Dai H et al: A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb. Biochem Biophys Res Comm. 2004. 1103–1111.

2. Block K, Mead M: Immune System Effects of Echinacea, Ginseng, and Astragalus: A Review. Int Cancer Ther. 2003. 2(3):247-267.

3. Boroujerdnia M, Azemi M, Hemmati A et al: Immunomodulatory Effects of Astragalus gypsicolus Hydroalcoholic Extract in Ovalbumin-Induced Allergic Mice Model. Iran J Allergy Asthma Immunol. 2011.  10(4):281-288.

4. Brush J, Mendenhall E, Guggenheim A et al: The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD69 expression and immune cell activation in humans. Phytother Res. 2006. 20(8):687-95.

5. Jiang D, Wang X, Su Q et al: Milkvetch root improves immune function in patients with acute exacerbation of COPD. Biomed Mater Eng. 2015. S2113-21.

6. Mao S, Cheng K, Zhou Y: [Modulatory effect of Astragalus membranaceus on Th1/Th2 cytokine in patients with herpes simplex keratitis]. [Article in Chinese] Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004. 24(2):121-3.

7. Matkovic Z, Zivkovic V, Korica M et al: Efficacy and safety of Astragalus membranaceus in the treatment of patients with seasonal allergic rhinitis. Phytother Res. 2010. 24(2):175-81.

8. Shih-Ming C, Tsai y, Lee S et al: Astragalus membranaceus modulates Th1/2 immune balance and activates PPARγ in a murine asthma model. Biochemistry and Cell Biology. 2014. 92(5):397-405.

9. Su G, Chen  X, Liu  Z et al: Oral Astragalus (Huang qi) for preventing frequent episodes of acute respiratory tract infection in children. Cochrane Database of Systematic Reviews. 2015. 11:CD011958.

10. Zwickey H, Brush J, Iacullo C et al: The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD25 expression in humans: a pilot study. Phytother Res. 2007. 21(11):1109-12.

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INGREDIENT - Vinpocetine

Coming Soon

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INGREDIENT - Piperine

Piperine - Is a purified extract from the fruit of Black and Long Peppers (Piper nigrum and Piper longum), a generally recognized as safe (GRAS) lipophilic ("fat soluble") alkaloid that is responsible for pepper's pungency ("spiciness").

Helps Support:
Increased Nutrient Absorption

It is a part of Ayurveda, the traditional medicine of India, dating back well over two thousand years ago, and one of its most widely used herbs in two-thirds of all Ayurvedic prescriptions. Together with the pungent alkaloids found in other spices like garlic, ginger, licorice and turmeric, it increases the bioavailabilty of coadministered substances such as vitamins, minerals, dietary supplements and pharmaceutics.

​Piperine acts as "bioenhancer" of various substances. Current published studies have shown that it significantly increases the absorption and bioavailabilty of vitamins (B1, B2, B3, B6, B9, B12, C), minerals (iodine, calcium, iron, zinc, copper, selenium, magnesium, potassium, manganese), amino acids (lysine, isoleucine, leucine, threonine, valine, tryptophan, phenylalanine, methionine), herbal compounds (curcumin, ginsenosides, quercetin, coenzyme Q10, resveratrol, epigallocatechin gallate from green tea, pycnogenol), and drugs (such as ibuprofen, diclofenac, rifampicin, ampicillin, tetracycline, pyrazinamide, fexofenadine). For example, it has been shown to increase curcumin levels by 2000%.

Drugs, supplements and nutrients taken by mouth (as opposed to intravenous, sublingual, intranasal, transdermal, buccal) are affected by "first pass metabolism." Essentially, they are degraded by digestion in the stomach and intestines by acids and enzymes; significantly altered in the liver; and, excreted. This affects their bioavailabilty - the amount of the substance that actually ends up in circulation - in the blood.

For example, cannabidiol (CBD) is 34-46% bioavailable intranasally; 40% when vaporized; but, approximately 6-9% when taken orally: so, for every 100mg ingested, only 9mg is available for use. Orally, aspirin is 68%, Zolpidem (i.e. Ambien) 67%, diphenhydramine (e.g. Benadryl) 40-60%, ACE inhibitors (e.g. Benazepril/Lotensin) 37% and statins (i.e. Simvastatin/Zocor) only 5% capable of being used by the body.

The bioavailabilty of a substance is based on four different processes: (1) conversion: enzymes in the gut breakdown the substance into something much less active; (2) absorption: shuttling the substance to the intestines where they can be transferred to the blood thru the intestinal lining; (3) exclusion: removing substances from the cells that cannot be used; and, (4) solubility: adding to the substance to make it unable to enter the cells. Piperine has the ability to affect all of these processes.

Piperine inhibits the enzymes in the gut and intestines that breakdown/metabolize and convert drugs and nutritive substances. It stimulates the activity of amino-acid transporters in the intestinal lining. It inhibits p-glycoprotein, the ‘pump’ protein that removes substances from cells and it decreases the intestinal production of glucuronic acid, thereby permitting more of the substances to enter the body in active form. Consequently, some of these substances are able to reach, enter, and remain within their target cells for longer periods of time than would otherwise be the case. Therefore, Piperine can sometimes turn a marginally effective therapeutic substance into a highly effective one simply by increasing its bioavailability and intracellular residency.

Scientific Studies

1. Ahmad, N, Fazal H, Abbasi B et al:  Khan, M.A. (2012) Biological Role of Piper nigrum L. (Black Pepper): A Review. Asian Pac J Trop Biomed, 2010, 5:1945-1953.

2. Ajazuddin, Alexander A, Qureshi A et al: Role of herbal bioactives as a potential bioavailability enhancer for Active Pharmaceutical Ingredients. Fitoterapia. 2014 Sep;97C:1-14.

3. Allameh A, Saxena M, Biswas G et al: Piperine, a plant alkaloid of the piper species, enhances the bioavailability of aflatoxin B1 in rat tissues. Cancer Lett. 1992 Jan 31;61(3):195-9.

4. Alodeani E, Arshad M, Izhari M: Drug likeness and physicochemical properties evaluation of the alkaloids found in black pepper: piperine, piperidine, piperettine and piperanine. Eur J Pharm Med Res, 2015, 2(6), 296-301.

5. Alvarez-Berdugo D, Jiménez M, Clavé P et al: Pharmacodynamics of TRPV1 Agonists in a Bioassay Using Human PC-3 Cells, Sci World J, 2014, ID 184526, 6 pages.

6. Atal N, Bedi K: Bioenhancers: Revolutionary concept to market. J Ayur Integ Med 2010. 1:96–9.

7. Atal C, Dubey R, Singh J: Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism.  J. Pharmacol. Exp. Ther. 1985. 232(1):258–62.

8. Atal K, Zutshi U, Rao P: Scientific evidence on the role of Ayurvedic herbals on bioavailability of drugs. J Ethnopharm 1981. 4(2): 229-32.

9. Badmaev V, Majeed M, Norkus E: Piperine, an alkaloid derived from black pepper increases serum response of beta-carotene during 14-days of oral beta-carotene supplementation. Nutri Res. 1999, 19(3): 381–388.

10. Badmaev V, Majeed M, Prakash L: Piperine derived from black pepper increases the plasma levels of coenzyme Q10 following oral supplementation. J Nutri Biochem 2000; 11(2):109–113.

11. 1.     Bajad S, Bedi K, Singla A et al: Piperine inhibits gastric emptying and gastrointestinal transit in rats and mice. Planta Medica 2001. 67: 176-179

12. 2.     Bano G, Amla V, Raina R et al: The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Medica. 1987, 53(6): 568–569.

13. 3.     Bano G, Raina R, Zutshi U et al: Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol. 1991;41(6):615-7.

14. Bedada S, Boga P, Kotakonda H: Study on influence of piperine treatment on the pharmacokinetics of diclofenac in healthy volunteers. Xenobiotica. 2017, 47(2):127-132.

15. Bhardwaj K, Glaeser H, Becquemont L et al: Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharm Exp Ther. 2002, 302(2):645-650.

16. Cai L, Liu J, Li L et al: [Effect of piperine on metabolism and distribution of nortriptyline in mice]. J Cent South Univ (Med Sci), 2014, 39(4): 349-54.

17. Chopra B, Dhingra A, Kapoor R et al: Piperine and Its Various Physicochemical and Biological Aspects: A Review. Open Chem J, 2016, 3, 75-96.

18. Dama M, Varshneya C, Dardi M et al: Effect of trikatu pretreatment on the pharmacokinetics of pefloxacin administered orally in mountain Gaddi goats. J Vet Sci. 2008 Mar;9(1):25-9.

19. Desai S, Gawali V, Naik A et al: Potentiating effect of piperine on hepatoprotective activity of Boerhaaviadiffusa to combat oxidative stress. Int J Pharmacogn, 2008, 4:393-397.

20. Di X, Wang X, Di X et al: Effect of piperine on the bioavailability and pharmacokinetics of emodin in rats. J Pharm Biomed Anal. 2015 Nov, 115:144-9.

21. Dubey R, Leeners B, Imthurn B et al: Piperine Decreases Binding of Drugs to Human Plasma and Increases Uptake by Brain Microvascular Endothelial Cells. Phytother Res. 2017, 31(12):1868-1874.

22. Dudhatra G, Mody S, Awale M et al: A Comprehensive Review on Pharmacotherapeutics of Herbal Bioenhancers. Sci World J. 2012, Sept: 637953.

23. Feng X, Liu Y, Wang X et al: Effects of piperine on the intestinal permeability and pharmacokinetics of linarin in rats. Molecules. 2014 Apr 30;19(5):5624-33.

24. Gopal V, Prakash G, Velvizhi T: Bio-Enhancer: A Pharmacognostic Perspective. Eur J Mol Biol Biochem. 2016;3(1):33-38.

25. Gorgani, L, Mohammadi M, Najafpour G et al: d, M. (2017), Piperine—The Bioactive Compound of Black Pepper: From Isolation to Medicinal Formulations. Comp Rev Food Sci Food Safe 2017. 16:124–140.

26. Gupta  P, Nagwansi D, Gupta S: Comparative standardization of a polyherbal ayurvedic formulation trikatu churna. J Chem Pharm Res, 2015. 7(12):191-196

27. Hiwale A, Dhuley J, Naik S: Effect of co-administration of piperine on pharmacokinetics of f3-lactam antibiotics in rats. Ind J Exp Bio. 2002, 40:277-281.

28. Janakiraman K, Manavalan R: Studies on Effect of Piperine on Oral Bioavailability of Ampicillin and Norfloxacin.  Afr J Trad Comp Alt Med. 2008; 5(3): 257–262.

29. Jamwal D, Singh J: Effects of piperine on enzyme activities and bioenergetic functions in isolated rat liver mitochondria and hepatocytes. J Biochem Toxicol. 1993 Dec;8(4):167-74.

30. Jhanwar J, Gupta S: Biopotentiation using Herbs: Novel Technique for Poor Bioavailable Drugs. Int J PharmT Res 2014. 6(2): 443-454.

31. Jin, M, Han, H: Effect of Piperine, a Major Component of Black Pepper, on the Intestinal Absorption of Fexofenadine and Its Implication on Food–Drug Interaction. J Food Sci., 2010. 75: H93–H96.

32. Johnson J, Nihal M, Siddiqui I et al: Enhancing the bioavailability of resveratrol by combining it with piperine. Mol Nutri Food Res. 2011, 55(8): 1169–1176.

33. Johri R, Thusu N, Khajuria A et al: Piperine mediated changes in the permeability of rat intestinal epithelial cells. The status of γ-glutamyl transpeptidase activity, uptake of amino acids and lipid peroxidation. Biochem Pharm. 1992, 43(7):1401-7.

34. Kang M, Cho J, Shim B et al: Bioavailability enhancing activities of natural compounds from medicinal plants. J Med Plant Res. 2009, 3(13): 1204–1211.

35.    Kasibhatta R, Naidu M: Influence of piperine on the pharmacokinetics of nevirapine under fasting conditions: a randomised, crossover, placebo-controlled study. Drugs R D. 2007;8(6):383-91.

36. Karan R, Bhargava V, Garg S: Effect of trikatu, an ayurvedic prescription, on the Pharmacokinetic profile of carbamazepine in rabbits. Indian J Physiol Pharmacol 1999; 43 (1): 133-136

37. Kesarwani K, Gupta R, Mukerjee A: Bioavailability enhancers of herbal origin: an overview. Asian Pac J Trop Biomed. 2013 Apr; 3(4):253-66.

38. Khajuria A, Thusu N, Zutshi U: Piperine modulates permeability characteristics of intestine by inducing alterations in membrane dynamics: influence on brush border membrane fluidity, ultrastructure and enzyme kinetics. Phytomedicine. 2002 Apr;9(3):224-31.

39. Khajuria A, Zutshi U, Bedi K: Permeability characteristics of piperine on oral absorption–an active alkaloid from peppers and a bioavailability enhancer. Indian J Exp Biol. 1998 Jan;36(1):46-50.

40. Khan I, Mirza Z, Kumar A et al: Piperine, a phytochemical potentiator of ciprofloxacin against Staphylococcus aureus. Antimicrob Agents Chemo. 2006 Feb;50(2):810-2.

41. Khan Z, Moni F, Sharmin S et al: Isolation of Bulk Amount of Piperine as Active Pharmaceutical Ingredient (API) from Black Pepper and White Pepper (Piper nigrum L.). Pharmacol Pharm, 2017, 8, 253-262.

42. Kulkarni A, Dias R: Natural products as bioavailability enhancers. Int J Inv Pharm Sci Res 2017. 5(12):24-33.

43. Kumar S, Dobos G, Rampp T: The Significance of Ayurvedic Medicinal Plants.  J Evid Base Int Med, 2017. (22)3:494-501

44. Lambert J, Hong J, Kim D et al: Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in mice.  J Nutrition. 2004. 134(8); 1948-52.

45. Lee S, Kim H, Back S et al: Piperine-mediated drug interactions and formulation strategy for piperine: recent advances and future perspectives. Expert Opin Drug Metab Toxicol. 2018 Jan;14(1):43-57.

46. Liang Y, Chen H, Su Z et al: White Pepper and Piperine Have Different Effects on Pharmacokinetics of Puerarin in Rats. Evid Based Comp Alt Med 2014.

47. Majeed M, Badmaev V, Rajendran R, Inventors; Sabinsa Corporation, assignee. Use of piperine to increase the bioavailability of nutritional compounds.  US patent 5,536,506, Jul. 16, 1996.

48. Majeed M, Badmaev V, Rajendran R, Inventors; Sabinsa Corporation, assignee. Use of piperine as a bioavailability enhancer. US patent 5,744,161. April 28, 1998.

49. Majeed M, Badmaev V, Rajendran R, Inventors; Sabinsa Corporation, assignee. Use of piperine as a bioavailability enhancer. US patent 5,972,382. October 26, 1999.

50. Makhov P, Golovine K, Canter D et al: Co-administration of piperine and docetaxel results in improved anti-tumor efficacy via inhibition of CYP3A4 activity. Prostate. 2012 May 1;72(6):661-7.

51. Mann A: Biopotency role of culinary spices and herbs and their chemical constituents in health and commonly used spices in Nigerian dishes and snacks. African J Food Sci, 2011, 5: 111-124.

52. Meghwal M, Goswami T: Piper nigrum and Piperine: An Update. Phyto Res 2013. 27(8): 1121–1130.

53. Mujumdar A, Dhuley J, Deshmukh V et al: Effect of piperine on pentobarbitore induced hypnosis in rats. Indian J Exp Biol, 1990a, 28:486-487.

54. Muneer C, Pandey V: Effect of Piperine on Oral Bioavailability of Diltiazem HCl in Rabbits. Int J Pharm App. 2012, 3(4):406-413.

55. Panahi Y, Badeli R, Karami G et al: Investigation of the Efficacy of Adjunctive Therapy with Bioavailability-Boosted Curcuminoids in Major Depressive Disorder. Phytother Res. 2015, 29(1):17-21.

56. Panahi Y, Ghanei M, Hajhashemi A et al: Effects of Curcuminoids-Piperine Combination on Systemic Oxidative Stress, Clinical Symptoms and Quality of Life in Subjects with Chronic Pulmonary Complications Due to Sulfur Mustard: A Randomized Controlled Trial. J Diet Suppl. 2016;13(1):93-105.

57. Parmar V, Jain S, Bisht K et al: Phytochemistry of genus piper. Phytochemistry 1997. 46:597-673.

58. Park T, Jeong N, Inventors; Industry-Academic Cooperation Foundation, assignee.  Piperine derivatives and uses thereof.  US patent 9,321,751. April 26, 2016.

59. Patel R, Modi I, Inventors; Cadila Laboratories Limited, assignee. Compositions containing piperine.  US patent 5,616,593. April 1, 1997.

60. Pattanaik S, Hota D, Prabhakar S et al: Pharmacokinetic interaction of single dose of piperine with steady-state carbamazepine in epilepsy patients. Phytotherapy Res. 2009, 23(9): 1281–1286.

61. Rahimnia A, Panahi Y, Alishiri G et al: Impact of Supplementation with Curcuminoids on Systemic Inflammation in Patients with Knee Osteoarthritis: Findings from a Randomized Double-Blind Placebo-Controlled Trial. Drug Res (Stuttg). 2014 Jul 22. [Epub ahead of print]

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63. Reanmongkol W, Janthasoot W, Wattanatorn W et al: Effects of piperine on bioenergetic functions of isolated rat liver mitochondria. Biochem Pharmacol. 1988 Feb 15;37(4):753-7.

64. Reen R, Jamwal S, Taneja S et al: Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine. Biochem Pharm 1993. 46(2), 229-238.

65. Reen R, Roesch S, Kiefer F et al: Piperine impairs cytochrome P4501A1 activity by direct interaction with the enzyme and not by down regulation of CYP1A1 gene expression in the rat hepatoma 5L cell line. Biochem Biophys Res Commun 1996. 218(2):562-9.

66. Samy R, Pushparaj P,  Gopalakrishnakone P: A compilation of bioactive compounds from Ayurveda. Bioinformation 2008; 3:100-110.

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68. Shanmugam S: Natural Bioenhancers: Current Outlook. Clin Pharmacol Biopharm 2015, 4:2

69. Shoba G, Joy D, Joseph T et al: Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica, 1998. 64(4): 353–356.

70. Singh A, Duggal S: Piperine- Review of Advances in Pharmacology. Int J Pharm Sci Nanotechnol. 2009. 2:615–20.

71. Singh V, Maurya J, Mishra A et al: Review article: Fast Dissolving Tablet with Piperine. Am. J. PharmTech Res. 2013; 3(6):15-37.

72. Singh V, Maurya J, Mishra A et al: Formulation and Evaluation of Mouth Dissolving Tablet of Norfloxacin with Piperine and their Antibacterial Activity. Am. J. PharmTech Res. 2013; 3(5):453-63.

73. Singh A, Pawar V, Jakhmola V et al: In vivo assessment of enhanced bioavailability of metronidazole with piperine in rabbits. Res J Pharm Bio Chem Sci. 2010, 1(4):273–278.

74. Singh V, Singh P, Mishra A et al: Piperine: delightful surprise to the biological world, made by plant “pepper� and a great bioavailability enhancer for our drugs and supplements. World J Pharm Res 2014: 3(6): 2084-2098.

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78. Tatiraju D, Bagade V, Karambelkar P et al: Natural Bioenhancers: An overview. J Pharm Phyto 2013; 2 (3): 55-60.

79. Velpandian T, Jasuja R, Bhardwaj R: Piperine in food: Interference in the pharmacokinetics of phenytoin.  Eur J Drug Met Kin, 2001, 26:241-247.

80. Venkatesh S, Durga K, Padmavathi Y et al: Influence of piperine on ibuprofen induced antinociception and its pharmacokinetics. Drug Res, 2011; 61:506–509.

81. Volak LP, Hanley MJ, Masse G et al: Effect of a herbal extract containing curcumin and Piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2013 Feb;75(2):450-62.

82. Wadhwa S, Singhal S, Rawat S: Bioavailability Enhancement by Piperine: A Review. Asian J Biomed Pharma Sci. 2014, 04(36): 1-8.

83. Wightman E, Reay J, Haskell C et al: Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation. Br J Nutr. 2014 Jul;112(2):203-13.

84. Yang J, Mao K, Huang P et al: Effect of piperine on the bioavailability and pharmacokinetics of rosmarinic acid in rat plasma using UPLC-MS/MS. Xenobiotica. 2018 Feb; 48(2):178-185

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