These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.
Please note that the physiological activity of the ingredient(s) described herein is supported by the referenced clinical trial reports. Marketers of finished products containing the ingredient(s) described herein are responsible for determining whether claims made for such products are lawful and in compliance with the laws of the country in which they will market the products.

HUMAN RESEARCH

  • Goyal R et al. Antioxidative effect of Punica granatum (pomegranate) on biochemical parameters  in patients with T2D and MI: A double blind placebo controlled trial. Int J Adv Res. 2016 May. Vol 4(Issue 5): 857-864. doi: 10.21474/IJAR01 - Patients were administered 300mg of Pomella® twice daily for 30-days as an adjunct treatment and showed significant improvements in key metabolic biomarkers. Especially significant decreases in blood glucose and HbA1c were seen compared to baseline. 

  • Goyal R et al. An antioxidative effect of Punica granatum (pomegranate) on biochemical  parameters in patients with MI: A double blind placebo controlled trial. Eur J Biomed Pharma Sci. 2016 Apr 30. Vol 3(Issue 5): 662-667. - Patients were administered 300mg of Pomella® twice daily for 30-days as an adjunct treatment and showed significant improvements in biomedical parameters such as HDL, OX-LDL, serum homocysteine, hs-CRP, and others.

  • DiSilvestro RA et al. Pomegranate extract mouth rinsing effects on saliva measures relevant to  gingivitis risk. Phytother Res. 2009. 23: 1123-1127. EPub 2009 Jan 23. doi: 10.1002/ptr.2759 - Pomella® mouthwash administered 3x daily affected saliva readings for antioxidant, anti-inflammatory, antibacterial, and bacterial enzyme inhibition compared to placebo. Further, Pomella reduced total protein count, which is associated with plaque forming bacteria.

 

PRECLINICAL RESEARCH

  • Liu C et al. Pomegranate (Punica granatum) phenolics ameliorate hydrogen peroxide-induced  oxidative stress and cytotoxicity in human keratinocytes. J Funct Foods. 2019. 54: 559-567. doi: 10.1016/j.jff.2019.02.015 - Pomella® and its phenolics (punicalagin, ellagic acid, and urolithin A) were investigated in the reduction of oxidative stress and cytotoxicity in keratinocytes, and found that the substances reduced the production of hydrogen peroxide induced ROS, increased the viability of the cells, and reduced apoptotic cell populations. This study points to Pomella having potential applications as a natural cosmeceutical for skin health.

  • Cai A et al. Pomegranate phenolics inhibit type I collagen cross-linking induced by  glycative stress.FASEB J. 2018 Apr. 32(1): 656.35. - Three of the pomegranate phenolics that Pomella® includes (punicalagin, ellagic acid, and urolithin A) were examined to determine the protective effects on collagen glycation. It was found that the phenolics inhibited fructose-induced collagen glycation by as much as 64.4%, exhibited protective effects on the secondary structure of collagen (when exposed to the denaturing effect of glycation), and inhibited the formation of Amadori products by as much as 45.7%.

  • Liu W et al. Development of a neuroprotective potential algorithm for medicinal plants. University of Rhode Island. Neurochem Int. 2016 Sep 29. 100: 164-177. - As part of a strategy to help guide the selection and evaluation of medicinal plant candidates for their neuroprotective potential, researchers at the University of Rhode Island developed a Neuroprotective Potential Algorithm (NPA) by evaluating twenty-three standardized and chemically characterized Ayurvedic medicinal plant extracts in a panel of bioassays targeting oxidative stress, carbonyl stress, protein glycation, amyloid beta (Aβ) fibrillation, acetylcholinesterase (AChE) inhibition, and neuroinflammation.

  • Yuan T et al. Pomegranate’s neuroprotective effects are mediated by urolithins, its  ellagitannin-gut microbial derived metabolites. ACS Chem Neurosci. 2015 Nov 11. doi: 10.1021/acschemneuro.5b00260 - Urolithins, gut microbial metabolites of ellagitannins, fulfilled in silico criteria required for BBB permeability, and prevented β-amyloid fibrillation in vivo. Moreover, urolithins not only prevented β-amyloid fibrillation in vitro, they also protected Caenorhabditis elegans from amyloid β1−42 induced neurotoxicity and paralysis, supporting Pomella's neuroprotective effect.

  • Ahmed AH et al. Pomegranate extract modulates processing of amyloid-β precursor protein in an  aged animal model. Current Alz Res. 2014. 11(9). - Pomella® was shown to impact cognitive function and markers of healthy brain aging in an aged transgenic AD model. Findings support a specific anti-amyloidgenic mechanism of Pomella.

  • Liu W et al. Pomegranate [Pomella] phenolics inhibit formation of advanced glycation  endproducts by scavenging reactive carbonyl species. Food Funct. 2014 Sep 11. 5: 2996-3004. doi: 10.1039/c4fo00538d - Pomella® phenolics inhibit the formation of a biologically relevant oxidative stress marker called Advanced Glycation Endproducts, or AGEs.

  • Henning SM et al. Variability in the antioxidant activity of dietary supplements from pomegranate  [Pomella], milk thistle, green tea, grape seed, goji, and acai: Effects of in  vitro digestion. J Agric Food Chem. 2014 Apr 18. 62: 4313-4321. doi: 10.1021/jf500106r - Pomella® ranked highest in antioxidant activity across a number of assays including ORAC, TEAC, FRAP, and DPPH, compared to 26 other antioxidant products.

  • Jean-Giles D et al. Inhibitory effects of polyphenol punicalagin on type-II collagen degradation in  vitro and in vivo. Chem-Bio Inter. 2013 Jun 20. 205: 90-99. EPub 2013 Jul 2. doi: 10.1016/j.cbi.2013.06.018 - Pomella’s punicalagins were shown to inhibit collagen degradation and supported anti-inflammatory effects; indicating possible joint health support opportunities.

  • Seeram NP et al. Pomegranate juice extracts provide similar levels of plasma and urinary ellagitannin metabolites in human subjects. J Med Food. 2008 Jan 23. 11(2): 390-394. doi: 10.1089/jmf.2007.650 - Pomegranate extract was found to deliver equivalent levels of ellagitannin metabolites when compared to pomegranate juice and liquid pomegranate liquid extract.

  • Seeram NP et al. Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States. J Agric Food Chem. 2008 Feb 27. 56(4): 1415-1422. EPub 2008 Jan 26. doi: 10.1021/jf073035s - Pomegranate juice was shown to have the greatest antioxidant potential of all the beverages tested in this study. Specifically, and notably, it beat out red wine, grape juice, blueberry juice, black cherry juice, açai juice, cranberry juice, and apple juice.

  • Pacheco-Palencia LA et al. Protective effects of standardized pomegranate (Punica granatum L) polyphenolic  extract in ultraviolet-irradiated human skin fibroblasts. J Agric Food Chem. 2008 Jul 18. EPub 2008 Aug 22. doi: 10.1021/jf8005307 - Pomella® was shown to be effective at protecting human skin fibroblasts from cell death following UVA and UVB exposure, while increasing the intracellular antioxidant capacity, and reducing the generation of intracellular reactive oxygen species (ROS) after UV exposure.

  • Patel C et al. Safety assessment of pomegranate fruit extract: Acute and subchronic toxicity  studies. Food Chem Toxicol. 2008 Apr 24. 46: 2728-2735. doi: 10.1016/j.fct.2008.04.035 - Results of this trial indicated that the no observed adverse effect level (NOAEL) at the highest tested level of Pomella®, was 600 mg/kg body weight/day.

  • Heber D et al. Safety and antioxidant activity of a pomeganate ellagitannin-enriched polyphenol dietary supplement in overweight individuals with increased waist size. J Agric Food Chem. 2007 Nov 28. 55(24): 10050-10054. EPub 2007 Oct 30. - A pomegranate ellagitannin-enriched polyphenol extract was prepared and administered to overweight individuals in two studies. Study 1 was designed for safety assessment, and study 2 for antioxidant assessment. It was observed  that there were no serious adverse events in any subjects in either study, and there was evidence of antioxidant activity “through a significant reduction in TBARS linked with cardiovascular disease risk.”

  • Shiner M et al. Macrophage paraoxonase 2 (PON2) expression is up-regulated by pomegranate juice phenolic antioxidants via PPAR gamma and AP-1 pathway activation. Atherosclerosis. 2007 Dec. 195(2): 313-321. EPub 2007 Feb 12. doi: 10.1016/j.atherosclerosis.2007.01.007 - Macrophages were incubated in pomegranate juice in increasing doses in an effort to determine the mechanism of action that pomegranate polyphenols have on oxidative stress. It was shown that the anti-oxidative characteristics of pomegranate polyphenol could be explained at least in part to their stimulatory effect on macrophage PON2 expression, which was shown to be associated with activation of transcription factors PPAR gamma and AP-1.

  • deNigris F et al. The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats. Nitric Oxide. 2007 Aug. 17(1): 50-54. EPub 2007 May 5. doi: 10.1016/j.niox.2007.04.005 - Pomegranate fruit extract was shown to decrease the expression of vascular inflammation markers and increase plasma nitrate and nitrite levels in effects comparable to pomegranate juice in obese Zucker rats.

  • Pomegranates for the prostate and the heart: Seeds of hope. Harv Med Health Watch. 2007 Apr. 11(9): 4-5. No Abstract Available.

  • deNigris F et al. Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis. Cardiovasc Res. 2007 Jan 15. 73(2): 414-423. EPub 2006 Sep 01. doi: 10.1016/j.cardiores.2006.08.021 - A pomegranate fruit extract rich in punicalagins was shown to reverse proatherogenic (promotion of fatty plaque build-up in the arteries) effects induced by shear stress through chronic administration.

  • Mertens-Talcott SU et al. Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum  L) polyphenols after ingestion of a standardized extract [Pomella] in healthy  human volunteers. J Agric Food Chem. 2006 Sep 6. 54(23): 8956-8961. EPub 2006 Oct 13. doi: 10.1021/jf061674h - Pomella’s patented extraction process delivers an ellagitannin rich profile standardized to punicalagin content. A single dose of Pomella led to a significant 32% increase of antioxidant activity in the blood. Bioactive punicalagin derived metabolites were detected in half an hour after dosing.

  • Seeram NP et al. Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. J Nutr. 2006 Oct. 136(10): 2481-2485. doi: 10.1093/jn/136.10.2481 - Demonstrates the length of time that polyphenols of pomegranate would persist in the human body after consumption.

  • Seeram NP et al. Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from promegranate (Punica granatum L) juice. Clinica Chimica Acta. 2004 Apr 30. 348: 63-68. doi: 10.1016/j.cccn.2004.04.029 - This study was the first to obtain direct evidence of the absorption of ellagic acids in a human from a food source. Biologically active ellagic acids and ellagitannins have important impacts on human health.

  • Cerda B et al. Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice. Eur J Nutr. 2003 Jan. 42(1): 18-28. doi: 10.1007/s/00394-003-0396-4

  • Aviram M et al. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis. 2001 Sep. 158(1): 195-198. doi: 10.1016/s0021-9150(01)00412-9 - Hypertensive pateints consumed 50 mL of pomegranate juice (1.5 mmol of total polyphenols) per day for two weeks. A 36% decrement in ACE activity and a 5% reduction in systolic blood pressure were noted; reduction in ACE activity has been shown to attenuate atherosclerosis.

 

CHEMISTRY

  • Liu Y et al. Liquid chromatography coupled with time-of-flight tandem mass spectrometry for  comprehensive phenolic characterization of pomegranate fruit and flower  extracts used as ingredients in botanical dietary supplements. J Sep Sci. 2018 May 30. Vol 41(Issue 15 - August 2018): 3022-3033. doi: 10.1002/jssc.201800480 - Pomella® phenolics are comprehensively characterized  by a validated liquid chromatography with time-of -flight tandem mass spectrometry method in the highly regarded journal, Journal of Separation Science. This study aids in quality control, authentication of study materials, and standardization of these botanical ingredients to help evaluate their potential health benefits in both completed and on-going pre-clinical and clinical studies.