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RESEARCH CITATIONS RUTIN
Exp Biol Med (Maywood). 2013 Apr;238(4):410-7. doi: 10.1177/1535370213477975.
Rutin suppresses atopic dermatitis and allergic contact dermatitis.
Choi JK1, Kim SH.
Atopic dermatitis (AD) and allergic contact dermatitis (ACD) is a common allergic inflammatory skin disease caused by a combination of eczematous, scratching, pruritus and cutaneous sensitization with allergens. The aim of our study was to examine whether rutin, a predominant flavonoid having anti-inflammatory and antioxidative potential, modulates AD and ACD symptoms. We established an atopic dermatitis model in BALB/c mice by repeated local exposure of house dust mite (Dermatophagoides farinae) extract (DFE) and 2,4-dinitrochlorobenzene (DNCB) to the ears. In addition, 2,4-dinitroflourobenzene-sensitized a local lymph node assay was used for the ACD model. Repeated alternative treatment of DFE/DNCB caused AD symptoms. Topical application of rutin reduced AD based on ear thickness and histopathological analysis, in addition to serum IgE levels. Rutin inhibited mast cell infiltration into the ear and serum histamine level. Rutin suppressed DFE/DNCB-induced expression of interleukin (IL)-4, IL-5, IL-13, IL-31, IL-32 and interferon (INF)-γ in the tissue. In addition, rutin suppressed ACD based on ear thickness and lymphocyte proliferation, serum IgG2a levels, and expression of INF-γ, IL-4, IL-5, IL-10, IL-17 and tumour necrosis factor-α in ACD ears. This study demonstrates that rutin inhibits AD and ACD, suggesting that rutin might be a candidate for the treatment of allergic skin diseases.
J Sci Food Agric. 2015 May 9. doi: 10.1002/jsfa.7251. [Epub ahead of print]
(Anti)mutagenic and immunomodulatory properties of quercetin glycosides.
Valentová K1, Šíma P1, Rybková Z2, Křížan J1, Malachová K2, Křen V1.
Quercetin-3-O-β-d-glucopyranoside (isoquercitrin) and quercetin-3-O-rutinoside (rutin) are common components of a normal human diet and are increasingly used in food supplements. Here their effect on mutagenesis and immunity is shown.
The in vitro (anti)mutagenic potential was compared with that of quercetin using the Ames test in Salmonella typhimurium His- strains TA100, TA98 and TA102. Isoquercitrin only slightly increased the number of revertants, while rutin was totally non-mutagenic. On the other hand, all compounds displayed dose-dependent protective activity against H2 O2 - and tert-butyl hydroperoxide-induced oxidative damage to the TA102 strain and at 75 µmol L-1 inhibited H2 O2 /Fe2+ -induced formation of the open circular and linear forms of the DNA plasmid pBSIISK(-). In mice, none of the flavonols (0.86 µmol day-1 , 34 days) induced harmful effects. In immunized animals, all compounds enhanced ex vivo B cell proliferation; quercetin stimulated lymphocyte basal proliferation and increased the number of IgM-producing lymphocytes. Rutin promoted NK cytotoxic activity, supported T cells and enhanced gut epithelium renewal. No effect on IgG-forming cells was found.
Isoquercitrin displayed negligible and rutin no mutagenicity, but both showed significant antimutagenic and DNA-protective effects against oxidative damage. In vivo, they supported the readiness of the immune system for specific humoral immune response. © 2015 Society of Chemical Industry.
Exp Toxicol Pathol. 2011 Jul;63(5):459-65. doi: 10.1016/j.etp.2010.03.005. Epub 2010 Apr 17.
Investigation of cytotoxic, apoptosis-inducing, genotoxic and protective effects of the flavonoid rutin in HTC hepatic cells.
Cristina Marcarini J1, Ferreira Tsuboy MS, Cabral Luiz R, Regina Ribeiro L, Beatriz Hoffmann-Campo C, Ségio Mantovani M.
Rutin is a flavonoid with antioxidant, vasodilatory, anti-inflammatory and immune-stimulating activities. To study the toxicity of rutin and its protective effect, this work investigated the cytotoxic, apoptosis-inducing, genotoxic and protective effects of rutin in HTC cells. In the MTT assay, the highest concentration tested (810 μM) showed cytotoxicity after 72 h of treatment, where cell viability and cell proliferation was diminished. None of the concentrations of rutin tested induced apoptosis after 24h treatment. The highest concentration of rutin after 24h treatment induced DNA damage, shown in the comet assay, but did have a genotoxic effect in the micronucleus test. Rutin was tested against the pro-carcinogenic agent benzo(a)pyrene, at concentrations of 90, 270 and 810 μM, and was found to reduce induced DNA damage significantly. This protective effect of rutinagainst a pro-carcinogen, suggests an important biological activity for this compound, which can contribute to human health through the diet.
Copyright © 2010 Elsevier GmbH. All rights reserved.
Exp Ther Med. 2015 Feb;9(2):451-455. Epub 2014 Nov 26.
Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes.
Wang YB1, Ge ZM2, Kang WQ3, Lian ZX4, Yao J1, Zhou CY1.
Diabetic cardiomyopathy (DCM), an independent coronary heart disease that develops in diabetic individuals, is characterized by changes in the myocardial structure and function. The aim of the present study was to investigate the protective effect of rutin on DCM in a streptozotocin-induced diabetic rat model. Rutin was orally administrated at a dose of 8 mg/kg body weight. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. The expression levels of cellular proteins associated with apoptosis were measured by western blot analysis, while the levels of inflammatory factors were assessed by immunohistochemical analyses. Rats with DCM exhibited an abnormal metabolic profile, aberrant myocardial enzymes, elevation of oxidative stress markers, increased levels of inflammatory factors and enhanced apoptotic cell death. Notably, rutin was shown to protect and improve myocardial dysfunction, oxidative stress, apoptosis and inflammation in the hearts of the diabetic rats. In conclusion, these results indicated that rutin may have great therapeutic potential in the treatment of DCM, and possibly other cardiovascular disorders, by preventing oxidative stress, inflammation and cell death. However, further detailed studies are required to reveal the exact
RESEARCH CITATIONS QUERCETIN
PLoS One. 2012;7(3):e33805. doi: 10.1371/journal.pone.0033805. Epub 2012 Mar 28.
Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.
Weng Z1, Zhang B, Asadi S, Sismanopoulos N, Butcher A, Fu X, Katsarou-Katsari A, Antoniou C, Theoharides TC.
Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell "stabilizer", is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD(2). Que and cromolyn also inhibit histamine, leukotrienes and PGD(2) from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption.
Bratisl Lek Listy. 2011;112(1):9-12.
Acute bronchodilator effect of quercetin in experimental allergic asthma.
Joskova M1, Franova S, Sadlonova V.
The aim of our study was to investigate the acute effect of quercetin on experimental allergic asthma after single-dose oral administration.
Airway hyperresponsiveness is one of the main features of allergic asthma. None of quercetin experimental studies analysed the acute effect of this flavonol on the reactivity of airways both, in vivo and in vitro conditions.
Our experiment was realized 21 days after the sensitization of guinea pigs with ovalbumin suspension. Changes in the reactivity of airways were studied using the whole body plethysmography in order to compare changes of the specific airway conductance between groups with and without quercetin treatment. Also changes in the reactivity of the tracheal smooth muscle dipped into the organ bath with Krebs-Henseleit solution were measured as the reaction on cumulative doses of the bronchoconstrictor mediators histamine and acetylcholine. Quercetin was added into the solution 30 minutes before the chemical mediators. The amplitude of tracheal smooth muscle precontracted with histamine or acetylcholine was used as a tracheal smooth muscle reactivity parameter in vitro.
Our results showed that quercetin (20 mg/kg) caused significant bronchodilation, both in vivo and in vitro.
Quercetin proved in laboratory conditions its ability to reduce hyperreactivity of airways as one of the main attribute of allergic asthma (Fig. 2, Ref. 23).
Oncotarget. 2015 May 20;6(14):12603-24.
Quercetin-induced apoptosis prevents EBV infection.
Lee M1, Son M1, Ryu E1, Shin YS2, Kim JG3, Kang BW3, Cho H4, Kang H1.
Epstein-Barr virus (EBV) is a human gamma-1 herpesvirus that establishes a lifelong latency in over 90% of the world's population. During latency, virus exists predominantly as a chromatin-associated, multicopy episome in the nuclei of a variety of tumor cells derived from B cells, T cells, natural killer (NK) cells, and epithelial cells. Licorice is the root of Glycyrrhiza uralensis or G. glabra that has traditionally cultivated in eastern part of Asia. Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth. Quercetin and isoliquiritigenin are produced from licorice and highly similar in molecular structure. They have diverse bioactive effects such as antiviral activity, anti-asthmatic activity, anti-cancer activity, anti-inflammation activity, monoamine-oxidase inhibitor, and etc. To determine anti-EBV and anti-EBVaGC (Epstein-Barr virus associated gastric carcinoma) effects of licorice, we investigated antitumor and antiviral effects of quercetin and isoliquiritigenin against EBVaGC. Although both quercetin and isoliquiritigenin are cytotoxic to SNU719 cells, quercetininduced more apoptosis in SNU719 cells than isoliquiritigenin, more completely eliminated DNMT1 and DNMT3A expressions than isoliquiritigenin, and more strongly affects the cell cycle progression of SNU719 than isoliquiritigenin. Both quercetin and isoliquiritigenin induce signal transductions to stimulate apoptosis, and induce EBV gene transcription. Quercetin enhances frequency of F promoter use, whereas isoliquiritigenin enhances frequency of Q promoter use. Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency. Quercetin increases more the EBV progeny production, and inhibits more EBV infection than isoliquiritigenin. These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma.
Eur J Med Chem. 2015 Jun 5;97:259-74. doi: 10.1016/j.ejmech.2015.04.056. Epub 2015 Apr 29.
Exploring quercetin and luteolin derivatives as antiangiogenic agents.
Ravishankar D1, Watson KA2, Boateng SY2, Green RJ1, Greco F3, Osborn HM4.
The formation of new blood vessels from the pre-existing vasculature (angiogenesis) is a crucial stage in cancer progression and, indeed, angiogenesis inhibitors are now used as anticancer agents, clinically. Here we have explored the potential of flavonoid derivatives as antiangiogenic agents. Specifically, we have synthesised methoxy and 4-thio derivatives of the natural flavones quercetin and luteolin, two of which (4-thio quercetinand 4-thio luteolin) had never been previously reported. Seven of these compounds showed significant (p < 0.05) antiangiogenic activity in an in vitro scratch assay. Their activity ranged from an 86% inhibition of the vascular endothelium growth factor (VEGF)-stimulated migration (observed for methoxyquercetin at 10 μM and for luteolin at 1 μM) to a 36% inhibition (for thiomethoxy quercetin at 10 μM). Western blotting studies showed that most (4 out of 7) compounds inhibited phosphorylation of the VEGF receptor-2 (VEGFR2), suggesting that the antiangiogenic activity was due to an interference with the VEGF/VEGFR2 pathway. Molecular modelling studies looking at the affinity of our compounds towards VEGFR and/or VEGF confirmed this hypothesis, and indeed the compound with the highest antiangiogenic activity (methoxyquercetin) showed the highest affinity towards VEGFR and VEGF. As reports from others have suggested that structurally similar compounds can elicit biological responses via a non-specific, promiscuous membrane perturbation, potential interactions of the active compounds with a model lipid bilayer were assessed via DSC. Luteolin and its derivatives did not perturb the model membrane even at concentrations 10 times higher than the biologically active concentration and only subtle interactions were observed for quercetin and its derivatives. Finally, cytotoxicity assessment of these flavonoid derivatives against MCF-7 breastcancer cells demonstrated also a direct anticancer activity albeit at generally higher concentrations than those required for an antiangiogenic effect (10 fold higher for the methoxy analogues). Taken together these results show promise for flavonoid derivatives as antiangiogenic agents.
Copyright © 2015 Elsevier Masson SAS. All rights reserved.
RESEARCH CITATIONS ECHINACEA (in Ester C Plus)
Auton Autacoid Pharmacol. 2015 Mar 30. doi: 10.1111/aap.12024. [Epub ahead of print]
Evaluating the effect of oral administration of Echinacea hydroethanolic extract on the immune system in dog.
Torkan S1, Khamesipour F, Katsande S.
This study was designed to evaluate the effects of oral administration of Echinacea hydroethanolic extract on the dog's immune system. The study was performed on 14 dogs that were referred to the veterinary clinic. These dogs were randomly allocated to two equal treatment groups. The first group received 1 ml of 5% Echinacea hydroethanolic extract two times a day for 2 months, and the second group received a placebo (water). To do haematology and immunology tests, the dogs were bled on days 0, 30 and 60. Blood tests, including packed cell volume (PCV), haemoglobin (Hb), red blood cell count (RBC), white blood cell count (WBC), counting neutrophils (Nut), lymphocytes (Lym), monocytes (Mon), eosinophils (Eos), basophils (Baso) and B cell, were performed. Furthermore, safety factor IgM and per cent of phagocytosis and phagocyte were measured from the blood sample. The results showed that in the group which received Echinacea PCV, Hb, RBC count, WBC count, Lym, Nut, the per cent of phagocytosis and IgM significantly increased (P < 0.05). Moreover, positive effects of Echinacea plant on the immune system were observed. There was a significant change in HTC, RBC, Hb over time in the group that received Echinacea and the per cent of phagocytosis and IgM (P < 0.05). The study establishes that these extracts might have appreciable immunostimulatory activity. However, further studies are required to confirm these findings.
© 2015 John Wiley & Sons Ltd.
Adv Ther. 2015 Mar;32(3):187-200. doi: 10.1007/s12325-015-0194-4. Epub 2015 Mar 18.
Echinacea reduces the risk of recurrent respiratory tract infections and complications: a meta-analysis of randomized controlled trials.
Schapowal A1, Klein P, Johnston SL.
Respiratory tract infections are common, and these infections occur frequently in children, susceptible adults, and older persons. The risk for recurrences and complications relates not only to the presence of viruses but also to immune function. Therefore, modulation of theimmune system and antiviral interventions such as echinacea might reduce the risk of recurrences and possibly the development of complications.
MEDLINE, EMBASE, CAplus, BIOSIS, CABA, AGRICOLA, TOXCENTER, SCISEARCH, NAHL, and NAPRALERT were searched for clinical trials that studied recurrent respiratory infections and complications on treatment with echinacea extracts in a generally healthy population. Two independent reviewers selected randomized, placebo-controlled studies of high methodological quality and a Jadad score of ≥4. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated according to a fixed effect model.
Six clinical studies with a total of 2458 participants were included in the meta-analysis. Use of echinacea extracts was associated with reduced risk of recurrent respiratory infections (RR 0.649, 95% CI 0.545-0.774; P < 0.0001). Ethanolic extracts from echinacea appeared to provide superior effects over pressed juices, and increased dosing during acute episodes further enhanced these effects. Three independent studies found that in individuals with higher susceptibility, stress or a state of immunological weakness, echinacea halved the risk of recurrent respiratory infections (RR 0.501, 95% CI 0.380-0.661; P < 0.0001). Similar preventive effects were observed with virologically confirmed recurrent infections (RR 0.420, 95% CI 0.222-0.796; P = 0.005). Complications including pneumonia, otitis media/externa, and tonsillitis/pharyngitis were also less frequent with echinacea treatment (RR 0.503, 95% CI 0.384-0.658; P < 0.0001).
Evidence indicates that echinacea potently lowers the risk of recurrent respiratory infections and complications thereof. Immunemodulatory, antiviral, and anti-inflammatory effects might contribute to the observed clinical benefits, which appear strongest in susceptible individuals.
Nat Prod Commun. 2014 Apr;9(4):511-4.
Immune enhancing effects of Echinacea purpurea root extract by reducing regulatory T cell number and function.
Kim HR, Oh SK, Lim W, Lee HK, Moon BI, Seoh JY.
Echinacea purpurea preparations (EPs) have been traditionally used for the treatment of various infections and also for wound healing. Accumulating evidence suggests their immunostimulatory effects. Regulatory T cells (Tregs) are known to play a key role in immune regulation in vivo. However, there have been no reports so far on the effects of EP on the frequency or function of Tregs in vivo. Therefore, in the present study, we investigated the quantitative and functional changes in Tregs by in vivo administration with EP. The frequencies of CD4+FoxP3+ and CD4+CD25+ Tregs in the spleens of BALB/c mice administered with EP for 3 weeks were investigated by flow cytometry. The suppressive function of CD4CD25+ Tregs in association with the proliferative activity of CD4+CD25 effector T cells (Teffs) and the feeder function of CD4 antigen-presenting cells (APCs) were analyzed by carboxyfluorescein succinimidyl ester-dilution assay. The results showed a lowered frequency of CD4+FoxP3+ and CD4+CD25+ Tregs and attenuated suppressive function of CD4+CD25+ Tregs, while the feeder function of APCs was enhanced in the EP-administered mice. On the other hand, the proliferative activity of Teffs was not significantly different in the EP-administered mice. The results suggest that decreased number and function of Tregs, in association with the enhanced feeder function of APCs, may contribute to the enhancement of immune function by EP.
RESEARCH CITATIONS BETA CAROTENE (in Ester C Plus)
J Agric Food Chem. 2010 Jun 23;58(12):7180-6. doi: 10.1021/jf100519x.
Dietary carotenoids inhibit oral sensitization and the development of food allergy.
Sato Y1, Akiyama H, Matsuoka H, Sakata K, Nakamura R, Ishikawa S, Inakuma T, Totsuka M, Sugita-Konishi Y, Ebisawa M, Teshima R.
Type-I allergic disorders and particularly food hypersensitivities are becoming increasingly common worldwide. This study investigated whether dietary enrichment with carotenoids inhibited oral sensitization to an antigen and the development of food allergies. The effects of a diet high in carotenoids were investigated in B10A mice that were orally sensitized to ovalbumin (OVA). The serum titers of OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a were inhibited in mice fed ad libitum on a diet high in alpha- or beta-carotene compared to the control mice when orally sensitized to OVA. High alpha- and beta-carotene diets inhibited the immediate reduction in body temperature and rise in serum histamine associated with active systemic anaphylaxis in OVA-sensitized B10A mice. After re-stimulation with OVA in vitro, the production of T-helper 2-type cytokines by splenocytes from mice fed a diet high in carotenoids was lower than in control mice. Furthermore, the proportion of CD4(+) CD103(+) T cells in Peyer's patches of mice fed a carotenoid-rich diet was significantly lower than in control mice. These results suggest that an increased oral intake of carotenoids inhibits OVA-specific IgE and IgG1 production and antigen-induced anaphylactic responses by inhibiting specific T-cell activation in the mucosal immune system. A diet high in carotenoids might therefore prevent the development of food allergies.
Food Funct. 2014 Jan;5(1):140-8. doi: 10.1039/c3fo60309a.
Effects of all-trans retinoic acid, retinol, and β-carotene on murine macrophage activity.
Lo HM1, Wang SW, Chen CL, Wu PH, Wu WB.
Previous studies have demonstrated that vitamin A and carotenoids regulate immune function in lymphocytes and splenocytes, and that the carotenoid lutein regulates matrix metalloproteinase-9 (MMP-9) production in macrophages. In this study, we investigated the effects of all-trans retinoic acid (atRA, a bioactive vitamin A metabolite), retinol (vitamin A), and β-carotene (vitamin A precursor) on the activity of murine RAW264.7 and peritoneal macrophages. Our results indicated that atRA and retinol could induce GM-CSF and IL-16 expression, whereas all these tested substances enhanced MMP-9 production. Interestingly, the expression of GM-CSF, IL-16, and MMP-9 was distinctly regulated by these three substances. AtRA and retinol affected GM-CSF and IL-16 expression mainly through RA receptor β (RARβ). However, atRA induced MMP-9 production was via RARα activation and retinol and β-carotene caused MMP-9 production via RARα and β activation. These were supported by the observations that the RARα and β agonists/antagonists differentially affected MMP-9 production and that atRA and β-carotene enhanced RARE-mediated and MMP-9 promoter luciferase activity. In parallel, while the MMP-9 induction by atRA was not affected by the MAPKs inhibitors, its induction by retinol and β-carotene was repressed by the inhibitor targeting ERK1/2. Finally, we show that all the tested substances could functionally enhance macrophage phagocytosis. Taken together, we provide evidence here for the first time that atRA, retinol, and β-carotenedifferentially regulate GM-CSF, IL-16, and MMP-9 production in macrophages, explaining at least in part why these vitamin A-related substances are beneficial for immunity.
Br J Nutr. 2014 Jan 28;111(2):247-53. doi: 10.1017/S0007114513002195. Epub 2013 Jul 8.
Effects of supplemental β-carotene on mucosal IgA induction in the jejunum and ileum of mice after weaning.
Nishida K1, Sugimoto M1, Ikeda S1, Kume S1.
An adequate immune system is required to prevent diarrhoea in neonates, and IgA provides protection against microbial antigens on mucosal surfaces. Although β-carotene supplementation has been expected to enhance the retinoic acid (RA)-mediated immune response in neonates, the exact mechanism of the enhancement of mucosal IgA production in the small intestine by β-carotene is still unclear. In the present study, we investigated the effect of supplemental β-carotene on the concentrations of IgA, the numbers of IgA antibody-secreting cells (ASC) and the mRNA expressions of IgA C-region, CCL25, retinoid X receptor (RXR) α, retinoic acid receptor (RAR) α and RARγ in the jejunum and ileum of weanling mice. Weanling mice were fed rodent feed or 50 mg/kg β-carotene-supplemented rodent feed for 7, 14 or 21 d. The concentrations of IgA and the numbers of IgA ASC in the jejunum and ileum of mice increased markedly with age, and supplemental β-carotene increased the concentrations of IgA, the numbers of IgA ASC and the mRNA expressions of IgA C-region, CCL25 and RARγ in the jejunum after 14 and 21 d of treatment. Supplemental β-carotene increased the numbers of IgA ASC in the ileum after 14 and 21 d of treatment, but the concentrations of IgA in the ileum were not affected by β-carotene supplementation. The mRNA expressions of RXRα and RARα in the jejunum and those of RXRα and RARγ in the ileum after 21 d of treatment were enhanced by β-carotene supplementation. These results indicate that β-carotene supplementation in weanling mice is effective to enhance mucosal IgA induction in the jejunum or ileum and that the effects are mainly due to the RA-mediated immune response.
J Nutr Sci Vitaminol (Tokyo). 2011;57(3):216-23.
β-Carotene and lutein inhibit hydrogen peroxide-induced activation of NF-κB and IL-8 expression in gastric epithelial AGS cells.
Kim Y1, Seo JH, Kim H.
Reactive oxygen species (ROS) including hydrogen peroxide (H(2)O(2)) are involved in the pathogenesis of gastric inflammation. Interleukin-8 (IL-8) is a potent mediator of the inflammatory response by activating and recruiting neutrophils to the site of infection. Oxidant-sensitive transcription factor NF-κB regulates the expression of IL-8 in the immune and inflammatory events. Carotenoids (carotenes and oxygenated carotenoids) show antioxidant and anti-inflammatory activities. Low intake of β-carotene leads to high risk of gastric cancer. Oxygenated carotenoid lutein inhibited NF-κB activation in experimental uveitis. The present study aims to investigate whether β-carotene and lutein inhibit H(2)O(2)-induced activation of NF-κB and expression of IL-8 in gastric epithelial AGS cells. The cells were treated with carotenoids 2 h prior to the treatment of H(2)O(2). mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR analyses. IL-8 level in the medium was determined by enzyme-linked immunosorbent assay. NF-κB activation was assessed by electrophoretic mobility shift assay. ROS levels of the cells were detected by confocal microscopic analysis for fluorescent dichlorofluorescein. As a result, H(2)O(2 )induced the activation of NF-κB and expression of IL-8 in AGS cells time-dependently. β-Carotene and lutein showed inhibitory effects on H(2)O(2)-induced increase in intracellular ROS levels, activation of NF-κB, and IL-8 expression in AGS cells. In conclusion, supplementation of carotenoids such as β-carotene and lutein may be beneficial for the treatment of oxidative stress-mediated gastric inflammation.
RESEARCH CITATIONS ASTAXANTHIN
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015 Apr;23(2):552-6. doi: 10.7534/j.issn.1009-2137.2015.02.050.
[Effect of astaxanthin on oxidative stress of red blood cells and peroxidation damage of membrane].
[Article in Chinese]
Wang SL1, He LJ1, He TB2, Han W1, Wang Q3.
To explore the effect of astaxanthin (ASTA) on oxidative stress of intra- and extra- red blood cells during stored period and the protective function for cell membrane.
The blood of volunteers was collected to prepare suspended red blood cells without leukocytes. Then the red blood cells were randomly divided into group A, group B, group C and group D. The ASTA was added into MAP preservation solution of group B, group C and group D, the final concentration of ASTA was 5, 10 and 20 µmol/L respectively. Group A was used as control group, in which only the dissolved liquid DMSO of ASTA was added. The red blood cells were stored in refrigerator at 2 °C-6 °C. On day 7, 14, 28 and day 42 of storage, the content of reactive oxygen species (ROS) in red blood cells was detected by fluorescence microplate reader. The content of malondialdehyde (MDA) was detected with TBA method. The content of hydrogen peroxide (H2O2) outside cell was detected with spectrophotometric method. The mean corpuscular volume(MCV) was detected with blood cell analyzer. The content of free hemoglobin(FHb) was detected with chemical colorimetry.
The ROS, MDA, FHb and H2O2 levels in B, C and D groups were lower than those in control group during the stored period. On day 7 and 14 of storage, among group B, group C, group D and group A, the MCV showed no difference in comparison with control group. On day 28 and 42 of storage, the MCV in B, C and D groups was lower than that in control group.
The ASTA can reduce the oxidative stress level of stored red blood cells inside and outside, relieve the peroxidation damage of cell membrane.
Cell Mol Neurobiol. 2015 May 14. [Epub ahead of print]
Anti-inflammatory Effect of Astaxanthin on the Sickness Behavior Induced by Diabetes Mellitus.
Ying CJ1, Zhang F, Zhou XY, Hu XT, Chen J, Wen XR, Sun Y, Zheng KY, Tang RX, Song YJ.
Chronic inflammation appears to play a critical role in sickness behavior caused by diabetes mellitus. Astaxanthin has been used in treating diabetes mellitus and diabetic complications because of its neuroprotective and anti-inflammatory actions. However, whether astaxanthin can improve sickness behavior induced by diabetes and its potential mechanisms are still unknown. The aim of this study was to investigate the effects ofastaxanthin on diabetes-elicited abnormal behavior in mice and its corresponding mechanisms. An experimental diabetic model was induced by streptozotocin (150 mg/kg) and astaxanthin (25 mg/kg/day) was provided orally for 10 weeks. Body weight and water consumption were measured, and the sickness behavior was evaluated by the open field test (OFT) and closed field test (CFT). The expression of glial fibrillary acidic protein (GFAP) was measured, and the frontal cortical cleaved caspase-3 positive cells, interleukin-6 (IL-6), and interleukin-1β (IL-1β) expression levels were also investigated. Furthermore, cystathionine β-synthase (CBS) in the frontal cortex was detected to determine whether the protective effect ofastaxanthin on sickness behavior in diabetic mice is closely related to CBS. As expected, we observed that astaxanthin improved general symptoms and significantly increase horizontal distance and the number of crossings in the OFT and CFT. Furthermore, data showed thatastaxanthin could decrease GFAP-positive cells in the brain and down-regulate the cleaved caspase-3, IL-6, and IL-1β, and up-regulate CBS in the frontal cortex. These results suggest that astaxanthin provides neuroprotection against diabetes-induced sickness behavior through inhibiting inflammation, and the protective effects may involve CBS expression in the brain.
Postepy Hig Med Dosw (Online). 2015 Apr 7;69:418-28.
[Carotenoids as natural antioxidants].
[Article in Polish]
Igielska-Kalwat J1, Gościańska J1, Nowak I1.
Human organisms have many defence mechanisms able to neutralise the harmful effects of the reactive species of oxygen. Antioxidants play an important role in reducing the oxidative damage to the human organism. Carotenoids are among the strongest antioxidants. They have 11 coupled double bonds, so they can be classified as polyisoprenoids, show low polarity and can occur in acyclic, monocyclic or bicyclic forms. The carotenoids of the strongest antioxidant properties are lycopene, lutein, astaxanthin and β-carotene. Carotenoids with strong antioxidant properties have found wide application in medical, pharmaceutical and cosmetic industries. These compounds are highly active against both reactive oxygen species and free radicals. Comparing β-carotene, astaxanthin and lycopene with other antioxidants (e.g. vitamin C and E), it can be concluded that these compounds have higher antioxidant activity, e.g. against singlet oxygen. Astaxanthin is a stronger antioxidant compared to β-carotene, vitamin E and vitamin C, respectively 54, 14 and 65 times. Carotenoids have a salutary effect on our body, making it more resistant and strong to fight chronic diseases. The purpose of this article is to review the literature concerning free radicals and their adverse effects on the human body and carotenoids, as strong, natural antioxidants.
New Study on BioCell Collagen Published in the
Journal of the International Society of Sports Nutrition (JISSN)
Supplementation with BioCell Collagen was shown to favorably impact key biochemical markers of connective tissue and enhance stress resilience following weight training exercise.
Newport Beach, CA - February, 23 2015 – BioCell Technology announced today the publication of a new clinical study on BioCell Collagen®. The study, now indexed on PubMed (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271657/ ), describes the potential of BioCell Collagen® for protecting the connective tissue of the musculoskeletal system and enhancing recovery from intense exercise. The randomized, double blind, placebo-controlled study was carried out by investigators at the Center for Applied Health Sciences (CAHS) who presented data in June at the 2014 International Society of Sports Nutrition (ISSN) Conference in Clearwater Beach, Florida, USA.
Earlier clinical studies of BioCell Collagen® have substantiated its safety and efficacy in promoting joint health and skin beauty. As these studies provide evidence that the patented healthy aging ingredient supports various connective tissues throughout the body, this proof-of-concept study was conducted to investigate whether daily intake of BioCell Collagen® for six weeks could protect skeletal muscle connective tissue following an intense exercise challenge, and also enhance recovery. Data from the study showed that BioCell Collagen® attenuated deleterious changes in muscle tissue damage and inflammatory biomarkers including creatine kinase, lactate dehydrogenase, and C-reactive protein. In addition, subjects who took BioCell Collagen® appeared to show a more robust “repeated bout effect” as compared to placebo, suggesting augmented tissue recovery and remodeling.
“Extending its market-leading position as a key joint and skin health ingredient, this new clinical study in recreationally active healthy subjects provides intriguing dataset suggesting that this patented, research-backed dietary supplement has promising new applications in sports nutrition” says Suhail Ishaq, president of BioCell Technology, “This opens up a new category in sports nutrition regarding connective tissue protection and recovery from post-workout soreness and limiting repetitive, overuse related injuries.”
Healthy joints are essential for any sports related activity, from cardio to resistance training. Equally important are the neighboring connective tissues surrounding the joints such as tendons and ligaments, which help facilitate flexibility and movement while protecting against injury. Whether you are aiming for prevention or trying to return to normal training after an injury, you need a consistent supply of connective tissue-specific nutrients that provide the biochemical precursors and building blocks needed to promote optimal joint health. BioCell Collagen has these molecular components which were found to impact key biochemical markers of connective and skeletal muscle tissue damage and enhance stress resilience following intense resistance exercise - without the potential undesirable side effects of pain medications.
The details of the abstract are published in the JISSN website:
About BioCell Collagen®:
BioCell Collagen® is a science based clinically substantiated dietary ingredient that promotes active joints, younger looking skin, and healthy connective tissues. Unlike other collagen and hyaluronic acid ingredients on the market, BioCell Collagen® contains a patented composition of naturally occurring hydrolyzed collagen type II, chondroitin sulfate, and hyaluronic acid in a highly absorbable matrix form that has been the subject of numerous human clinical trials including safety, efficacy, and bioavailability. BioCell Collagen® is a registered trademark of BioCell Technology, LLC (Protected by US and International Patents ). The BioCell Collagen® logo of authenticity is proudly displayed on the labels of finished products that contain BioCell Collagen®. For more information and a directory of where to buy products made with BioCell Collagen®, visit www.BioCellCollagen.com.
About BioCell Technology:
BioCell Technology LLC, is in the business of researching, developing, branding, and distributing innovative, science based raw material ingredients that have applications in health and beauty. The company is headquartered in Newport Beach, California USA and operates facilities in Anaheim, California, and Elmshorn, Germany. The company’s executive management team is composed of industry veterans and scientists with decades of experience. Founded in 1997, the company's goal is to provide non-invasive, economically feasible, long-term solutions that improve quality of life for people all over the globe. As a steward of quality and integrity, BioCell Technology believes that licensing is the best way to ensure the quality, safety, and efficacy of the innovative finished products that contain their branded ingredients in the market. The company’s products are rooted in quality and science and were developed with sustainability in mind. The company does not sell finished products, but rather licenses its branded ingredients to leading consumer packaged goods companies for use in their finished products. Each of the branded ingredients have a trademarked logo of authenticity that is proudly displayed on the labels of finished products licensed by BioCell Technology and marketed by leading consumer packaged goods companies under their own brand names or formulas.
Research Abstracts for DMG
J Infect Dis. 1981 Jan;143(1):101-5.
Immunomodulating Properties of Dimethylglycine in Humans.
Graber CD, Goust JM, Glassman AD, Kendall R, Loadholt CB.
Dimethylglycine (DMG), a tertiary amino acid, has had wide acceptance as a nonfuel nutrient; presumably it enhances oxygen utilization by tissue and complexes free radicals. Its potential as an immunoadjuvant has also been suggested by a study of an analog of DMG, calcium pangamate. A double-blind study in 20 human volunteers showed a fourfold increase in antibody response to pneumococcal vaccine in those receiving DMG orally as compared with controls (P less than 0.01). Production of leukocyte inhibitory factor in response to concanavalin A was similar in the two groups, but those taking DMG tablets had a significantly highr mean response of leukocyte inhibition factor to streptokinase-streptodornase (P less than 0.001). The in vitro responses of lymphocytes from patients with diabetes and those with sickle cell disease to phytohemagglutinin, convanavalin A, and pokeweed mitogen were increased almost threefold after addition of DMA. These results suggest that DMG enhances both humoral and cell-mediated immune responses in humans.
PMID: 6163829 [PubMed - indexed for MEDLINE]
J Pharm Pharmacol. 2000 Dec;52(12):1519-22.
Effect of Dimethylglycine on Gastric Ulcers in Rats.
Hariganesh K1, Prathiba J.
Dimethylglycine is an anti-stress nutrient with antioxidant properties. Recently, studies have implicated the generation of oxygen-derived free radicals and lipid peroxidation as one of the mechanisms in the pathogenesis of gastric ulcer. Hence, we evaluated the antiulcer activity of dimethylglycine in various rat models of ulcer and also investigated the probable antioxidant mechanism of the anti-ulcer effect. Dimethylglycine at a dose of 25 and 35 mg kg(-1) significantly reduced ulcer number, ulcer size and ulcer index in pyloric-ligation-, ibuprofen- and stress-induced ulcers. The 35 mg kg(-1) dose was more effective than 25 mg kg(-1) and was comparable to famotidine. Dimethylglycine did not produce any significant change in acid secretion, unlike famotidine. There was a significant increase in plasma and tissue malondialdehyde levels in pyloric-ligated rats but these levels fell following dimethylglycine treatment. Also, there was a significant reduction in glutathione levels after dimethylglycine treatment. The results suggest that the gastroprotective effect of dimethylglycine could be mediated by its free radical scavenging activity and cytoprotection of gastric mucosa.
PMID: 11197081 [PubMed - indexed for MEDLINE]
J Anim Physiol Anim Nutr (Berl). 2010 Dec;94(6):e339-47. doi: 10.1111/j.1439-0396.2010.01018.x.
Maitake PD-Fraction Research Abstracts
J Med Food. 2003 Winter;6(4):371-7.
Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients.
Kodama N1, Komuta K, Nanba H.
Maitake D-Fraction, extracted from maitake mushroom, has been reported to exert its antitumor effect in tumor-bearing mice by enhancing the immune system through activation of macrophages, T cells, and natural killer (NK) cells. In a previous study, the combination of immunotherapy with the maitake D-Fraction and chemotherapy suggested that the D-Fraction may have the potential to decrease the size of lung, liver, and breast tumors in cancer patients. In the present study, we administered maitake D-Fraction to cancer patients without anticancer drugs, and at the same time NK cell activity was monitored to investigate whether the activity is closely related with disease progression. The numbers of CD4(+) and CD8(+) cells in the peripheral blood were measured in 10 patients, and NK cell activity was assessed using K-562 cells as target cells. Serum soluble interleukin-2 receptor (sIL-2R) levels in three patients and the expression of tumor markers in four patients were determined by enzyme-linked immunosorbent assay. The slight changes observed in the CD4(+) and CD8(+) cell numbers were independent of disease severity or stage as well as serum sIL-2R levels. In contrast, maitake D-Fraction hindered metastatic progress, lessened the expression of tumor markers, and increased NK cell activity in all patients examined. Thus maitake D-Fraction appears to repress cancer progression and primarily exerts its effect through stimulation of NK activity. In addition, we conclude that measurement of NK cell activity may be a useful clinical parameter in monitoring disease progression during and following immunotherapy with maitake D-Fraction.
PMID: 14977447 [PubMed - indexed for MEDLINE]
Ann Transl Med. 2014 Feb;2(2):14. doi: 10.3978/j.issn.2305-5839.2014.01.05.
Immune-enhancing effects of Maitake (Grifola frondosa) and Shiitake (Lentinula edodes) extracts.
Vetvicka V1, Vetvickova J1.
The role of glucan in stimulation of immune reactions has been studied for several decades. In this report, we focused on the effects of orally administered glucan Maitake and Shiitake on immune reactions.
MATERIALS AND METHODS:
We measured phagocytosis, NK cell activity, and secretion of IL-6, IL-12, IFN-γ as well as C-reactive protein (CRP) after 14 days of oral application of tested glucans. For comparison, active hexose correlated compound (AHCC) was used in all reactions.
We found significant stimulation of defense reaction. In all cases, the most active was the Maitake-Shiitake combination, with Maitakealone being the second strongest, followed by Shiitake on its own and AHCC.
Short-term oral application of natural immunomodulating glucans from Maitake and Shiitake mushrooms strongly stimulated both the cellular and humoral branch of immune reactions. These activities were significantly higher than those of AHCC.
PMID: 25332990 Full text of this article found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202470/
Exp Mol Med. 2010 Feb 28;42(2):143-54. doi: 10.3858/emm.2010.42.2.016.
Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-alpha production and its signaling.
Lee JS1, Park SY, Thapa D, Choi MK, Chung IM, Park YJ, Yong CS, Choi HG, Kim JA.
TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-alpha action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 micg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha-induced reactive oxygen species production and NF-kappaB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha production, which is known to be mediated through NF-kappaB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-alpha as well as its signaling through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.
PMID: 20054232 Full text of this article found here:
Cancer Lett. 2001 Oct 30;172(2):193-8.
Effects of maitake (Grifola frondosa) D-Fraction on the carcinoma angiogenesis.
Matsui K1, Kodama N, Nanba H.
We have reported that D-Fraction extracted from maitake (Grifola frondosa), activates immune competent cells, and indicates anti-tumor activities. The D-Fraction was observed to induce angiogenesis in vivo and to enhance the proliferation capability and migration capability of human vascular endothelial cell in vitro. The D-Fraction also increased plasma vascular endothelial growth factor (VEGF) concentration significantly. Also VEGF and TNF-alpha production by the activated peritoneal macrophages were enhanced. These results suggest that the anti-tumor activity of the D-Fraction is not only associated with the activation of the immuno-competent cells but also possibly related to the carcinoma angiogenesis induction.
Cancer Immunol Immunother. 2015 Feb;64(2):237-47. doi: 10.1007/s00262-014-1628-6. Epub 2014 Oct 29.
Maitake mushroom extract in myelodysplastic syndromes (MDS): a phase II study.
Wesa KM1, Cunningham-Rundles S, Klimek VM, Vertosick E, Coleton MI, Yeung KS, Lin H, Nimer S, Cassileth BR.
Myelodysplastic syndromes (MDS) are characterized by ineffective erythropoiesis with dysplastic bone marrow leading to peripheral cytopenia, risk of infection, and progression to acute myelogenous leukemia. Maitake mushroom beta-glucan, a dietary supplement, stimulates hematopoietic progenitor cell differentiation, granulocyte colony-stimulating factor production, and recovery of peripheral blood leukocytes after bone marrow injury. This phase II trial examined the effects of Maitake on innate immune function in MDS.
Myelodysplastic syndromes patients with International Prognostic Scoring System Low- and Intermediate-1-risk disease received oralMaitake extract at 3 mg/kg twice daily for 12 weeks. Primary endpoints included neutrophil count and function tested as endogenous or stimulated neutrophil production of reactive oxygen species (ROS) by flow cytometry compared with age-matched healthy controls (HC). ROS activators were Escherichia coli, phorbol ester, and the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Complete blood counts, chemistry panels, iron studies, and monocyte function were evaluated.
Of 21 patients enrolled, 18 completed the study and were evaluable. Maitake increased endogenous (basal) neutrophil (p = 0.005) and monocyte function (p = 0.021). Pre-treatment monocyte response to E. coli was reduced in MDS patients compared with HC (p = 0.002) and increased (p = 0.0004) after treatment. fMLP-stimulated ROS production response also increased (p = 0.03). Asymptomatic eosinophilia occurred in 4 patients (p = 0.014). Other changes in albumin, hemoglobin, and total protein were not clinically relevant.
Maitake was well tolerated. Enhanced in vitro neutrophil and monocyte function following treatment demonstrate that Maitake has beneficial immunomodulatory potential in MDS. Further study is warranted.
Full text of this article found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317517/
Adv Ther. 2006 Jan-Feb;23(1):171-8.
Safety and tolerance of ester-C compared with regular ascorbic acid.
Gruenwald J, Graubaum HJ, Busch R, Bentley C.
Analyze and Realize AG, Berlin, Germany.
The goal of this randomized, double-blind crossover clinical trial in 50 healthy volunteers sensitive to acidic foods was to evaluate whether Ester-C calcium ascorbate causes fewer epigastric adverse effects than are produced by regular ascorbic acid (AA). Volunteers were randomly separated into 2 groups of 25. The study comprised an observation period of 9 days (phase 1 medication for 3 consecutive days, washout phase for 3 consecutive days, phase 2 medication for 3 consecutive days). Participants took 1000 mg vitamin C as Ester-C during phase 1 of the study followed by 1000 mg of vitamin C as AA during phase 2, or vice versa. During the course of the study, 3 examinations for the evaluation of epigastric adverse effects were performed (on days 0, 3, and 9). Participants used a diary to record epigastric adverse effects on a daily basis. In total, 28 (56%) of 50 participants reported 88 epigastric adverse effects of mild to moderate intensity. Of these 88 adverse effects, 33 (37.5%) occurred after intake of Ester-C and 55 (62.5%) were noted after intake of AA. The tolerability of Ester-C was rated "very good" by 72% of participants, whereas AA was rated "very good" by only 54%. This difference is statistically significant (P<.05). Investigators concluded that Ester-C compared with AA caused significantly fewer epigastric adverse effects in participants sensitive to acidic foods and that Ester-C is much better tolerated.
RESEARCH CITATIONS FOR ACTIVIN (GRAPE SEED EXTRACT)
Indian J Exp Biol. 2002 Jun;40(6):717-26.
Mechanistic pathways of antioxidant cytoprotection by a novel IH636 grape seed proanthocyanidin extract.
Bagchi D1, Ray SD, Bagchi M, Preuss HG, Stohs SJ.
To understand the bioavailability and mechanistic pathways of cytoprotection by IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) a series of in vitro and in vivo studies were conducted. Comparative protective abilities of GSPE, and vitamins C and E, singly and in combination, were assessed against smokeless tobacco extract (STE)-induced oxidative stress, DNA fragmentation and apoptotic cell death in a primary culture of normal human oral keratinocytes. GSPE protected against STE-induced oxidative stress, DNA damage and apoptotic cell death, and provided better protection as compared to vitamins C and E, singly and in combination. The bioavailability and protective ability of GSPE were examined against acetaminophen (AP)-induced hepato- and nephrotoxicity, amiodarone (AM)-induced lung toxicity, doxorubicin (DX)-induced cardiotoxicity and dimethylnitrosamine (DM)-induced spleenotoxicity in mice. GSPE-fed animals were compared with GSPE-untreated mice to evaluate the protective ability of GSPE against these structurally diverse drugs/chemicals. Serum chemistry changes, histopathology and DNA damage were evaluated. Results indicate that GSPE preexposure prior to the drugs/chemicals such as AP, AM, DX or DM treatment, provided near complete protection in terms of serum chemistry changes and inhibition of both forms of cell death, e.g., apoptosis and necrosis. DNA damage in various tissues triggered by these agents was significantly reduced in GSPE-fed animals. Histopathological examination of multiple target organs provided similar data. The results suggest that GSPE exposure is bioavailable and provides significant multiorgan protection against structurally diverse drug- and chemical-induced toxic assaults. Further, these studies exhibited a series of mechanistic information including free radical scavenging ability, anti-endonucleolytic activity, cytochrome P450 2E1 inhibitory activity, anti-necrotic, anti-apoptotic and anti-carcinogenic activities, modulatory effects on antioxidative and apoptotic regulatory genes such as Bcl2, c-myc and p53, which may be responsible for the novel chemoprotective properties exhibited by GSPE.
Free Radic Res. 2002 Aug;36(8):819-25.
Activin, a grape seed-derived proanthocyanidin extract, reduces plasma levels of oxidative stress and adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in systemic sclerosis.
Kalin R1, Righi A, Del Rosso A, Bagchi D, Generini S, Cerinic MM, Das DK.
This study evaluated whether a new generation antioxidant Activin derived from the grape seed proanthocyanidins, could reduce the induction of the adhesion molecules as a result of inflammatory response in the plasma of systemic sclerosis (SSc) patients. SSc patients were divided into two groups: one group was treated with Activin, a grape seed-derived proanthocyanidins, while the other group served as control. Patients were givenActivin 100 mg/day orally for one month after which the blood samples were withdrawn from both groups of the patients. Blood was also taken from normal human volunteers. Plasma was obtained in fasting state between 8 to 9 A.M. from two groups of SSc patients and controls. Soluble adhesion molecules including ICAM-1, VCAM-1, E-selectin and P-selectin as well as malonaldehyde, a marker for oxidative stress, were measured. The results of our study demonstrated up-regulation of these soluble adhesion molecules except for P-selectin, in the plasma of the SSc patients compared to those obtained from human volunteers. Activin significantly attenuated the increased expression of these adhesion molecules. In addition, there was a significant increase in the amount of malondialdehyde formation in the plasma of the SSc patients, which was also attenuated by Activin. The results of this study demonstrated that Activin could reduce the inflammatory response and the oxidative stress developed in SSc patients.
Int Immunopharmacol. 2013 Sep;17(1):79-87. doi: 10.1016/j.intimp.2013.05.026. Epub 2013 Jun 10.
Grape seed proanthocyanidin extract has potent anti-arthritic effects on collagen-induced arthritis by modifying the T cell balance.
Ahmad SF1, Zoheir KM, Abdel-Hamied HE, Ashour AE, Bakheet SA, Attia SM, Abd-Allah AR.
Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the synovial joints, joint malformations, and disability. The continuous use of conventional anti-inflammatory drugs is associated with severe adverse effects. Grape seed proanthocyanidin extract (GSPE) is considered to have protective effects against several diseases. In this study based on the mouse adjuvant-induced-arthritis (AIA) model, we examined the effects of GSPE on the key mediators of arthritic inflammation, namely T cell subsets, glucocorticoid-induced tumour necrosis factor receptor (GITR) expressing cells, CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, Th17 cells, Th1/Th2 cytokines, and inflammatory mediator gene expression. We treated BALB/c mice with 25, 50, or 100 mg/kg GSPE or saline daily (14 days) per orally (p.o.) at the onset of AIA. At the peak phase of AIA (day 14), the heparinised whole blood and ankle joints of all groups were collected and tested. GSPE-treated mice showed a substantial reduction in the levels of T cell subsets, GITR-expressing cells, and Th1 cytokines as well as the inflammatory mediators (MCP-1, MIP-2, and ICAM-1) that induce them compared with the vehicle-treated (saline) and arthritic mice. However, GSPE significantly upregulated the number of Tregs and Th2 cytokine producing cell number or it also induced Th17/Treg rebalance and orchestrated various pro-inflammatory and anti-inflammatory cytokines and the gene expression of their mediators that mediate cellular infiltration into the joints. This might, contribute to its anti-arthritic activity. Our results suggest that p.o. treatment with GSPE attenuated AIA in mice might offer a promising alternative/adjunct treatment for RA.
Copyright © 2013 Elsevier B.V. All rights reserved.
Adjuvant-induced-arthritis (AIA) model; Arthritis; Cytokines; Grape seed proanthocyanidin extract; Inflammatory mediators; T regulatory cells
PLoS One. 2012;7(12):e51377. doi: 10.1371/journal.pone.0051377. Epub 2012 Dec 10.
Grape-seed proanthocyanidin extract as suppressors of bone destruction in inflammatory autoimmune arthritis.
Park JS1, Park MK, Oh HJ, Woo YJ, Lim MA, Lee JH, Ju JH, Jung YO, Lee ZH, Park SH, Kim HY, Cho ML, Min JK.
Chronic autoimmune inflammation, which is commonly observed in rheumatoid arthritis (RA), disrupts the delicate balance between bone resorption and formation causing thedestruction of the bone and joints. We undertook this study to verify the effects of natural grape-seed proanthocyanidinextract (GSPE), an antioxidant, on chronic inflammation and bone destruction. GSPE administration ameliorated the arthritic symptoms of collagen-induced arthritis (CIA), which are representative of cartilage and bone destruction. GSPE treatment reduced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and osteoclast activity and increased differentiation of mature osteoblasts. Receptor activator of NFκB ligand expression in fibroblasts from RA patients was abrogated with GSPE treatment. GSPE blocked human peripheral blood mononuclear cell-derived osteoclastogenesis and acted as an antioxidant. GSPE improved the arthritic manifestations of CIA mice by simultaneously suppressing osteoclast differentiation and promoting osteoblast differentiation. Our results suggest that GSPE may be beneficial for the treatment of inflammation-associated bone destruction.
Beneficial effects of a novel IH636 grape seed proanthocyanidin extract in the treatment of chronic pancreatitis.
Banerjee B1, Bagchi D.
Oxygen-derived free radicals mediate tissue damage in acute and chronic pancreatitis. Low levels of natural antioxidants in pancreatitis indicate their increased utilization as scavengers of free radicals. Combination therapy with selenium, beta-carotene, methionine, and vitamins C and E are known to improve symptoms of chronic and recurrent pancreatitis. This, however, requires many tablets to be taken daily, which is impractical and may reduce compliance. Three patients with chronic pancreatitis (two with a history of alcohol excess and one idiopathic) are reported. Treatment with narcotic analgesics and pancreatic enzyme supplements had failed to control their symptoms. The addition of a commercially available IH636 grapeseed proanthocyanidin extract (commercially known as ActiVin) to their treatment regimen led to a reduction in the frequency and intensity of abdominal pain as well as resolution of vomiting in 1 patient.
Copyright 2001 S. Karger AG, Basel
RESEARCH CITATIONS VITAMIN K2 (AS MK-7)
Osteoporos Int. 2013 Sep;24(9):2499-507. doi: 10.1007/s00198-013-2325-6. Epub 2013 Mar 23.
Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women.
Knapen MH1, Drummen NE, Smit E, Vermeer C, Theuwissen E.
We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss.
Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K's role in maintenance of normal bone. In line with EFSA's opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bonehealth.
Healthy postmenopausal women (n = 244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment.
MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae.
MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation.
Thromb Haemost. 2015 Feb 19;113(5). [Epub ahead of print]
Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: double-blind randomised clinical trial.
Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C1.
Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 µg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index β significantly decreased in the total group, whereas distension, compliance, distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness.
Arterial stiffness; Stiffness Index β; carotid intima-media thickness; menaquinone-7; pulse wave velocity
Int J Mol Med. 2011 Jan;27(1):3-14. doi: 10.3892/ijmm.2010.562. Epub 2010 Nov 11.
Vitamin K2 stimulates osteoblastogenesis and suppresses osteoclastogenesis by suppressing NF-κB activation.
Yamaguchi M1, Weitzmann MN.
Several bone protective factors are reported to exhibit stimulatory activities on bone formation coupled with inhibitory effects on bone resorption; one such factor is vitamin K2. Vitamin K species [K1 (phylloquinone) and K2 (menaquinone)] have long been associated with bone protective activities and are receiving intense interest as nutritional supplements for the prevention or amelioration of bone disease in humans. However, the mechanisms of vitamin K action on the skeleton are poorly defined. Activation of the nuclear factor κB (NF-κB) signal transduction pathway is essential for osteoclast formation and resorption. By contrast, NF-κB signaling potently antagonizes osteoblast differentiation and function, prompting us to speculate that NF-κB antagonists may represent a novel class of dual anti-catabolic and pro-anabolic agents. We now show that vitamin K2 action on osteoblast and osteoclast formation and activity is accomplished by down-regulating basal and cytokine-induced NF-κB activation, by increasing IκB mRNA, in a γ-carboxylation-independent manner. Furthermore, vitamin K2 prevented repression by tumor necrosis factor α (TNFα) of SMAD signaling induced by either transforming growth factor ß (TGFß) or bone morphogenetic protein-2 (BMP-2). Vitamin K2further antagonized receptor activator of NF-κB (RANK) ligand (RANKL)-induced NF-κB activation in osteoclast precursors. Our data provide a novel mechanism to explain the dual pro-anabolic and anti-catabolic activities of vitamin K2, and may further support the concept that pharmacological modulation of NF-κB signal transduction may constitute an effective mechanism for ameliorating pathological bone loss and for promoting bone health.
Nutr J. 2012 Nov 12;11:93. doi: 10.1186/1475-2891-11-93.
Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women.
Sato T1, Schurgers LJ, Uenishi K.
Vitamin K₂ contributes to bone and cardiovascular health. Therefore, two vitamin K₂ homologues, menaquinone-4 (MK-4) andmenaquinone-7 (MK-7), have been used as nutrients by the food industry and as nutritional supplements to support bone and cardiovascular health. However, little is known about the bioavailability of nutritional MK-4. To investigate MK-4 and MK-7 bioavailability, nutritional doses were administered to healthy Japanese women.
Single dose administration of MK-4 (420 μg; 945 nmol) or MK-7 (420 μg; 647 nmol) was given in the morning together with standardized breakfast. MK-7 was well absorbed and reached maximal serum level at 6 h after intake and was detected up to 48 h after intake. MK-4 was not detectable in the serum of all subjects at any time point. Consecutive administration of MK-4 (60 μg; 135 nmol) or MK-7 (60 μg; 92 nmol) for 7 days demonstrated that MK-4 supplementation did not increase serum MK-4 levels. However, consecutive administration of MK-7 increased serum MK-7 levels significantly in all subjects.
We conclude that MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues.
PMID: 23140417 Free full text article found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502319/
Transplantation. 2010 Feb 27;89(4):458-64. doi: 10.1097/TP.0b013e3181c46b69.
Dietary vitamin K2 supplement improves bone status after lung and heart transplantation.
Forli L1, Bollerslev J, Simonsen S, Isaksen GA, Kvamsdal KE, Godang K, Gadeholt G, Pripp AH, Bjortuft O.
Osteoporosis is a problem after transplantation. Studies since the last year indicate that vitamin K plays a role in optimal bone health. The aim of this randomized, double blind, prospective longitudinal study was to investigate the effect of a dietary supplement with vitamin K2(180 microg menakinon-7) on bone mass, the first year after lung and heart transplantation.
After preoperative baseline investigation of bone mass and bone-related biochemistry, 35 lung and 59 heart recipients were postoperatively randomized to vitamin K2 or placebo and reinvestigated the following year.
In all recipients, 1 year after solid organ transplantation, the difference between vitamin K2 and placebo for the lumbar spine (L2-L4) bone mineral density (BMD) was 0.028 (SE 0.014) g/cm(2), P=0.055 and for L2 to L4 bone mineral content was 1.33 (SE 1.91) g/cm(2) (P=0.5). In lung recipients separately, the difference for bone mineral content was 3.39 g (SE 1.65), P=0.048 and in heart recipients 0.45 (SE 0.02) g, P=0.9 after controlling for baseline measures. In a forward stepwise linear regression analysis fitted to model differences in the L2 to L4 BMD, controlled for possible confounding variables (including use of bisphosphonate), and the only significant predictors were organ (B=-0.065 g/cm(2), P<0.001) and vitamin K2 (B=0.034 g/cm(2), P=0.019). Insufficient vitamin D status was common, and the parathyroid hormone was highest in the K2 group indicating a higher need for vitamin D.
One year of vitamin K2 supplement suggest a favorable effect on lumbar spine BMD with different response in lung and heart recipients. Vitamin D status should receive more attention.
RESEARCH CITATIONS NEPTUNE KRILL OIL
J Am Coll Nutr. 2007 Feb;26(1):39-48.
Evaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptoms.
a) To evaluate the effect of Neptune Krill Oil (NKO) on C-reactive protein (CRP) on patients with chronic inflammation and b) to evaluate the effectiveness of NKO on arthritic symptoms.
Randomized, double blind, placebo controlled study. Ninety patients were recruited with confirmed diagnosis of cardiovascular disease and/or rheumatoid arthritis and/or osteoarthritis and with increased levels of CRP (>1.0 mg/dl) upon three consecutive weekly blood analysis. Group A received NKO (300 mg daily) and Group B received a placebo. CRP and Western Ontario and McMaster Universities (WOMAC) osteoarthritis score were measured at baseline and days 7, 14 and 30.
After 7 days of treatment NKO reduced CRP by 19.3% compared to an increase by 15.7% observed in the placebo group (p = 0.049). After 14 and 30 days of treatment NKO further decreased CRP by 29.7% and 30.9% respectively (p < 0.001). The CRP levels of the placebo group increased to 32.1% after 14 days and then decreased to 25.1% at day 30. The between group difference was statistically significant; p = 0.004 at day 14 and p = 0.008 at day 30. NKO showed a significant reduction in all three WOMAC scores. After 7 days of treatment, NKO reduced pain scores by 28.9% (p = 0.050), reduced stiffness by 20.3% (p = 0.001) and reduced functional impairment by 22.8% (p = 0.008).
The results of the present study clearly indicate that NKO at a daily dose of 300 mg significantly inhibits inflammation and reduces arthritic symptoms within a short treatment period of 7 and 14 days.
Altern Med Rev. 2004 Dec;9(4):420-8.
Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia.
Bunea R1, El Farrah K, Deutsch L.
To assess the effects of krill oil on blood lipids, specifically total cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
A multi-center, three-month, prospective, randomized study followed by a three-month, controlled follow-up of patients treated with 1 g and 1.5 g krill oil daily. Patients with hyperlipidemia able to maintain a healthy diet and with blood cholesterol levels between 194 and 348 mg per dL were eligible for enrollment in the trial. A sample size of 120 patients (30 patients per group) was randomly assigned to one of four groups. Group A received krill oil at a body mass index (BMI)-dependent daily dosage of 2-3 g daily. Patients in Group B were given 1-1.5 g krill oil daily, and Group C was given fish oil containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA) per gram of oil at a dose of 3 g daily. Group D was given a placebo containing microcrystalline cellulose. The krill oil used in this study was Neptune Krill Oil, provided by NeptuneTechnologies and Bioresources, Laval, Quebec, Canada.
Primary parameters tested (baseline and 90-day visit) were total blood cholesterol, triglycerides, LDL, HDL, and glucose.
Krill oil 1-3 g per day (BMI-dependent) was found to be effective for the reduction of glucose, total cholesterol, triglycerides, LDL, and HDL, compared to both fish oil and placebo.
The results of the present study demonstrate within high levels of confidence that krill oil is effective for the management of hyperlipidemia by significantly reducing total cholesterol, LDL, and triglycerides, and increasing HDL levels. At lower and equal doses, krill oil was significantly more effective than fish oil for the reduction of glucose, triglycerides, and LDL levels.
Free full text article found here: http://www.altmedrev.com/publications/15/1/84.pdf
Altern Med Rev. 2003 May;8(2):171-9.
Evaluation of the effects of Neptune Krill Oil on the management of premenstrual syndrome and dysmenorrhea.
Sampalis F1, Bunea R, Pelland MF, Kowalski O, Duguet N, Dupuis S.
To evaluate the effectiveness of Neptune Krill Oil (NKO) for the management of premenstrual syndrome and dysmenorrhea.
To compare the effectiveness of NKO for the management of premenstrual syndrome and dysmenorrhea with that of omega-3 fish oil.
Double-blind, randomized clinical trial.
Seventy patients of reproductive age diagnosed with premenstrual syndrome according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R).
Treatment period of three months with either NKO or omega-3 fish oil.
Self-Assessment Questionnaire based on the American College of Obstetricians and Gynecologists (ACOG) diagnostic criteria for premenstrual syndrome and dysmenorrhea and number of analgesics used for dysmenorrhea.
In 70 patients with complete data, a statistically significant improvement was demonstrated among baseline, interim, and final evaluations in the self assessment questionnaire (P < 0.001) within the NKO group as well as between-group comparison to fish oil, after three cycles or 45 and 90 days of treatment. Data analysis showed a significant reduction of the number of analgesics used for dysmenorrhea within the NKO group (comparing baseline vs. 45- vs. 90-day visit). The between-groups analysis illustrated that women taking NKO consumed significantly fewer analgesics during the 10-day treatment period than women receiving omega-3 fish oil (P < 0.03).
Neptune Krill Oil can significantly reduce dysmenorrhea and the emotional symptoms of premenstrual syndrome and is shown to be significantly more effective for the complete management of premenstrual symptoms compared to omega-3 fish oil.
Free full text article found here: http://www.altmedrev.com/publications/8/2/171.pdf
Altern Med Rev. 2007 Sep;12(3):207-27.
Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.
The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.
Free full text article found here: http://www.seekinghealth.com/media/research/krill%20oil%20vs%20fish%20oil%20in%20mood.pdf
RESEARCH CITATIONS SILIPHOS (MILK THISTLE)
Int J Pharm. 2014 Aug 25;471(1-2):173-81. doi: 10.1016/j.ijpharm.2014.05.026. Epub 2014 May 22.
Phyto-liposomes as nanoshuttles for water-insoluble silybin-phospholipid complex.
Angelico R1, Ceglie A2, Sacco P3, Colafemmina G4, Ripoli M5, Mangia A5.
Among various phospholipid-mediated drug delivery systems (DDS) suitable for topic and oral administration, phytosome technology represents an advanced innovation, widely used to incorporate standardized bioactive polyphenolic phytoconstituents into phospholipid molecular complexes. In order to extend their potential therapeutic efficiency also to other routes of administration, we proposed a novel phytosome carrier-mediated vesicular system (phyto-liposome) as DDS for the flavonolignan silybin (SIL), a natural compound with multiple biological activities related to its hepatoprotective, anticancer and antioxidant (radical scavenging) effects. We screened the optimum fraction of its phytosome, available in the market as Siliphos™, into liposomes prepared by extrusion, such that vesicle sizes and charges, monitored through dynamic light scattering and laser doppler velocimetry, satisfied several quality requirements. Special emphasis was placed on the study of host-guest interaction by performing UV-vis absorption, spectrofluorimetry and NMR experiments both in aqueous and non-polar solvents to probe the effect of the presence of phospholipids on the electronic properties of SIL and its propensity to engage H bonding with the lipid headpolar groups. Finally, fluorescence microscopy observations confirmed the ability of phyto-liposomes to be internalized in human hepatoma cells, which was promising for their potential application in the treatment of acute or chronic liver diseases.
Copyright © 2014 Elsevier B.V. All rights reserved.
Physicochemical properties; Phyto-liposome; Phytosome; Silybin; Silybin–phospholipids interactions
Surg Endosc. 2012 Jul;26(7):1856-64. doi: 10.1007/s00464-011-2114-2. Epub 2012 Jan 19.
Perioperative polyphenon E- and siliphos-inhibited colorectal tumor growth and metastases without impairment of gastric or abdominal wound healing in mouse models.
Yan X1, Gardner TR, Grieco M, Herath SA, Jang JH, Kirchoff D, Njoh L, Shantha Kumara HM, Naffouje S, Whelan RL.
Perioperative anticancer therapy that does not impair wound healing is needed to counter the persistent proangiogenic plasma compositional changes that occur after colorectal resection. Polyphenon E (PolyE), a green tea derivative (main component EGCG), and Siliphos(main component silibinin), from the milk thistle plant, both have antitumor effects. This study assessed the impact of PolyE/Siliphos (PES) on wound healing and the growth of CT-26 colon cancer in several murine models.
One wound healing and three tumor studies were performed. Tumor Study (TS)1 assessed the impact of PES on subcutaneous tumor growth, whereas TS2 assessed PES's impact on subcutaneous growth when given pre- and post-CO(2) pneumoperitoneum (pneumo), sham laparotomy, or anesthesia alone. TS3 determined the ability of PES to limit hepatic metastases (mets) after portal venous injection of tumor cells. In the final study, laparotomy and gastrotomy wound healing were assessed several ways. BALB/c mice were used for all studies. The drugs were given via drinking water (PolyE) and gavage (Siliphos), daily, for 7-9 days preprocedure and for 7-21 days postoperatively. Tumor mass, number/size of hepatic mets, and proliferation and apoptosis rates were assessed. The abdominal breaking strength and energy to failure were measured postmortem as was gastric bursting pressures.
PES significantly inhibited subcutaneous growth in the nonoperative setting. PES also significantly decreased the number/size of liver mets when given perioperatively. Abdominal wound breaking strength, energy to wound failure, and collagen content were not altered by PES; gastrotomy bursting strength also was not affected by PES. Neither drug alone had a significant impact on tumor growth.
The PES combination inhibited subcutaneous and hepatic tumor growth yet did not impair wound healing. PES holds promise as a perioperative anticancer therapy.
J Pharmacol Exp Ther. 2010 Mar;332(3):922-32. doi: 10.1124/jpet.109.161612. Epub 2009 Dec 11.
A silybin-phospholipid complex prevents mitochondrial dysfunction in a rodent model of nonalcoholic steatohepatitis.
Serviddio G1, Bellanti F, Giudetti AM, Gnoni GV, Petrella A, Tamborra R, Romano AD, Rollo T, Vendemiale G, Altomare E.
Mitochondrial dysfunction and oxidative stress are determinant events in the pathogenesis of nonalcoholic steatohepatitis. Silybin has shown antioxidant, anti-inflammatory, and antifibrotic effects in chronic liver disease. We aimed to study the effect of the silybin-phospholipid complex (SILIPHOS) on liver redox balance and mitochondrial function in a dietary model of nonalcoholic steatohepatitis. To accomplish this, glutathione oxidation, mitochondrial oxygen uptake, proton leak, ATP homeostasis, and H(2)O(2) production rate were evaluated in isolated liver mitochondria from rats fed a methionine- and choline-deficient (MCD) diet and the MCD diet plus SILIPHOS for 7 and 14 weeks. Oxidative proteins, hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and mitochondrial membrane lipid composition were also measured. Treatment with SILIPHOS limited glutathione depletion and mitochondrial H(2)O(2) production. Moreover, SILIPHOS preserved mitochondrial bioenergetics and prevented mitochondrial proton leak and ATP reduction. Finally, SILIPHOS limited the formation of HNE- and MDA-protein adducts. In conclusion,SILIPHOS is effective in preventing severe oxidative stress and preserving hepatic mitochondrial bioenergetics in nonalcoholic steatohepatitis induced by the MCD diet. The modifications of mitochondrial membrane fatty acid composition induced by the MCD diet are partially prevented bySILIPHOS, conferring anti-inflammatory and antifibrotic effects. The increased vulnerability of lipid membranes to oxidative damage is limited bySILIPHOS through preserved mitochondrial function.
PMID: 20008062 Free full text article found here:
RESEARCH CITATIONS FOR C3 COMPLEX (CURCUMIN)
Cancer Prev Res (Phila). 2013 Feb;6(2):119-28. doi: 10.1158/1940-6207.CAPR-12-0281. Epub 2012 Dec 11.
Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration--a clinical pilot study including assessment of patient acceptability.
Irving GR1, Howells LM, Sale S, Kralj-Hans I, Atkin WS, Clark SK, Britton RG, Jones DJ, Scott EN, Berry DP, Hemingway D, Miller AS, Brown K, Gescher AJ,Steward WP.
Curcumin, the main constituent of turmeric, is suspected to possess cancer chemopreventive properties. Pharmacokinetic and pharmacodynamic parameters have been reported, but few data exist describing whether methodologies are suitably robust for curcuminoid detection in colonic biopsy specimens. Information on the acceptability of prolonged administration of daily curcumin is not available. This is of vital importance to implement chemoprevention strategies. This study aimed to quantify levels of curcuminoids in colorectal mucosa of patients undergoing colorectal endoscopy or surgical resection and to obtain information on the acceptability and compliance with daily curcumin. Curcumin C3 complex (2.35 g) was administered to patients once daily for 14 days before endoscopic biopsy or colonic resection. Safety and tolerance were monitored. Analysis of curcuminoids in plasma, urine, and colonic mucosa was conducted by ultraperformance liquid chromatography (UPLC)-UV with characterization by liquid chromatography/tandem mass spectrometry (LC/MS-MS). Twenty-four of 26 patients commencing curcumin completed the course. Six patients reported mild gastrointestinal adverse events. Curcuminoids were detectable in nine of 24 plasma samples, 24 of 24 urine samples, and in the colonic mucosa of all 23 biopsied participants. Mean tissue levels were 48.4 μg/g (127.8 nmol/g) of parent curcuminoids. The major conjugate,curcumin glucuronide, was detectable in 29 of 35 biopsies. High levels of topical curcumin persisted in the mucosa for up to 40 hours postadministration. Sixteen participants (67%) stated that they would take curcumin long-term should it be of proven benefit. In summary, pharmacologically active levels of curcumin were recovered from colonic mucosa. The regimen used here seems safe, and patients support its use in long-term trials.
Chem Biol Interact. 2015 Apr 11. pii: S0009-2797(15)00150-7. doi: 10.1016/j.cbi.2015.04.006. [Epub ahead of print]
Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative damage, dyslipidemia and hepatic mitochondrial toxicity in rats.
Muthumani M1, Miltonprabu S2.
Arsenic (As) is a well-known human carcinogen and a potent hepatotoxin. Environmental exposure to arsenic imposes a serious health hazard to humans and other animals worldwide. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, exhibits many of the same physiological and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than the curcumin. It has been reported that THC has antioxidant efficacy attributable to the presence of identical β-diketone of 3rd and 5th substitution in heptane moiety. In the present study, rats were orally treated with arsenic alone (5mgkg-1bw/day) with THC (80mgkg-1bw/day) for 28days. Hepatotoxicity was measured by the increased activities of serum hepatospecific enzymes, namely aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin along with increased elevation of lipid peroxidative markers, thiobarbituric acid reactive substances. And also elevated levels of serum cholesterol, triglycerides, free fatty acids and phospholipids were observed in arsenic intoxicated rats. These effects of arsenic were coupled with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase, Ca2+ATPase and a decrease in mitochondrial calcium content. The toxic effect of arsenic was also indicated by significantly decreased activities of enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase along with non-enzymatic antioxidant such as reduced glutathione. Administration of THC exhibited significant reversal of arsenic induced toxicity in hepatic tissue. All these changes were supported by the reduction of arsenic concentration and histopathological observations of the liver. These results suggest that THC has a protective effect over arsenic induced toxicity in rat.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Arsenic; Liver; Mitochondria; Rat; Tetrahydrocurcumin
Yao Xue Xue Bao. 2014 Nov;49(11):1483-90.
[Recent advances in curcumin and its derivatives for treatment of liver diseases].
[Article in Chinese]
Sun Y, Peng ML.
Curcumin is a principal polyphenolic curcuminoid extracted from turmeric rhizome, which has been used for treating inflammation of joints, ulcers, jaundice and other disorders in Asian traditional medicine. In recent years, many studies have indicated that curcumin plays important roles in treatment of liver diseases. Curcumin attenuates liver injury and non-alcoholic fatty liver disease by lowering the release of inflammation cytokines, minimizing oxidative stress, enhancing the sensitivity of insulin and altering lipid metabolism. Curcumin shows potent anti-fibrosis activity, contributing to inhibit the activation of hepatic stellate cells and reduce the deposition of extracellular matrix by its regulation of PPAR-γ, NF-ΚB and TGF-β signaling pathways. Moreover, curcumin exhibits anti-cancer effect by inducing G2/M phase cell cycle arrest and apoptosis in several hepatoma cell lines. However, poor water solubility and low bioavailability of curcumin limit its clinical applications. To overcome its limited systemic bioavailability, many new approaches have been explored to deliver curcumin effectively. This article focuses on advances in the effects of curcuminand its derivatives for treatment of liver injury, non-alcoholic fatty liver disease, liver fibrosis and hepatocarcinoma.
Asian Pac J Cancer Prev. 2015;16(1):103-8.
Hepatoprotective effects of curcumin against diethyl nitrosamine induced hepatotoxicity in albino rats.
Kadasa NM1, Abdallah H, Afifi M, Gowayed S.
Curcumin is widely used as a traditional medicine. This work was aimed to investigate its possible protective effect against chemically induced hepatocellular carcinoma (HCC) in rats. Fifty male albino rats were divided into five groups (n=10, each). The control group received a single dose of normal saline, the diethylnitrosamine (DENA) group received a single intra-peritoneal dose at 200mg/kg body weight, and the 3rd, 4th and 5th groups were given DENA and daily administrated curcunine (CUR) via intra-gastric intubation in doses of 300,200 and 100 mg/kg b.wt. respectively for 20 weeks. Serum, and liver samples were used for determination of alpha feto-protein (AFP), interleukin-2 (IL-2), interleukine-6 (IL-6), serum liverenzymes (AST, ALT, ALP and GGT) levels as well the activities and gene expression of glutathione peroxidise (GPx), glutathione reductase (GR), catalase (CAT) and super oxide dismutase (SOD). Curcumin significantly lowered the serum levels of AFP, IL-2 and IL-6, ALT, ALT, and malondialdehyde (MDA) as well gene expression of IL-2 and IL-6. In contrast it increased the gene expression and activities of Gpx, GRD, CAT and SOD. The protective effect of CUR against DEN-induced hepatocarcinogenesis in albino rats was proven.
RESEARCH CITATIONS BACILLUS COAGULANS
World J Microbiol Biotechnol. 2015 Mar 10. [Epub ahead of print]
Potential probiotic attributes of a new strain of Bacillus coagulans CGMCC 9951 isolated from healthy piglet feces.
Gu SB1, Zhao LN, Wu Y, Li SC, Sun JR, Huang JF, Li DD.
A new strain of Bacillus coagulans CGMCC 9551, which has a broad range of antibacterial activities against six main pathogenic bacteria including Escherichia coli O8, Staphylococcus aureus, Salmonella enterica subsp. enterica serovar enteritidis, Streptococcus suis, Listeria monocytogenes and Pasteurella multocida, was isolated from healthy piglet feces. In adhesion assay, the isolate exhibited a stronger adhesion to pig intestinal mucus than that of B. subtilis JT143 and L. acidophilus LY24 respectively isolated from BioPlus®2B and FloraFIT® Probiotics (P < 0.05). The adhesion activity reached 44.5 ± 3.2, 48.9 ± 2.6, 42.6 ± 3.3 and 37.6 ± 2.4 % to jejunum, ileum, transverse colon and sigmoid colon, separately. The survival rate of B. coagulans CGMCC 9551 was reduced by only 20 % at 4 h exposure under 0.9 % w/v bile salt. The strain was fully resistant to pH 2 for 2 h with 90.1 ± 3.5 % survival and susceptible to 15 antibiotics commonly used in veterinary medicine. Additionally, the bacteria showed amylase, protease and cellulase activities. The safety assessment demonstrated the lack of toxicity potential in B. coagulans CGMCC 9551 by ligated rabbit ileal loop assay, acute and subchronic toxicity test. These results implied that that the new strain of B. coagulans CGMCC 9951 isolated from healthy piglet feces has promising probiotic characteristics and offers desirable opportunities for its successful commercialization as one excellent candidate probiotic.
Anaerobe. 2014 Dec;30:75-81. doi: 10.1016/j.anaerobe.2014.09.002. Epub 2014 Sep 16.
Effect of prebiotics on the fecal microbiota of elderly volunteers after dietary supplementation of Bacilluscoagulans GBI-30, 6086.
Nyangale EP1, Farmer S2, Keller D2, Chernoff D3, Gibson GR4.
In advancing age, gut populations of beneficial microbes, notably Bifidobacterium spp., show a marked decline. This contributes to an environment less capable of maintaining homoeostasis. This in vitro investigation studied the possible synergistic effects of probiotic supplementation in modulating the gut microbiota enabling prebiotic therapy to in elderly persons. Single stage batch culture anaerobic fermenters were used and inoculated with fecal microbiota obtained from volunteers after taking a 28 day treatment of Bacillus coagulans GBI-30, 6086 (GanedenBC30 (BC30)) or a placebo. The response to prebiotic supplements fructooligosaccharides (FOS) and galactooligosaccharides (GOS) in the fermenters was assessed. Bacterial enumeration was carried out using fluorescent in situ hybridisation and organic acids measured by gas chromatography. Baseline populations of Faecalibacterium prausnitzii, Clostridium lituseburense and Bacillus spp. were significantly higher in those having consumed BC30 compared to the placebo. Both prebiotics increased populations of several purportedly beneficial bacterial groups in both sets of volunteers. Samples from volunteers having ingested the BC30 also increased populations of C. lituseburense, Eubacterium rectale and F. prausnitzii more so than in persons who had consumed the placebo, this also resulted in significantly higher concentrations of butyrate, acetate and propionate. This shows that consumption of BC30 and subsequent use of prebiotics resulted in elevated populations of beneficial genres of bacteria as well as organic acid production.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Free full text article found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129566/
BMC Immunol. 2010 Mar 24;11:15. doi: 10.1186/1471-2172-11-15.
GanedenBC30 cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro.
Jensen GS1, Benson KF, Carter SG, Endres JR.
This study was performed to evaluate anti-inflammatory and immune modulating properties of the probiotic, spore-forming bacterial strain: Bacillus coagulans: GBI-30, (PTA-6086, GanedenBC30TM). In addition, cell wall and metabolite fractions were assayed separately to address whether biological effects were due to cell wall components only, or whether secreted compounds from live bacteria had additional biological properties. The spores were heat-activated, and bacterial cultures were grown. The culture supernatant was harvested as a source of metabolites (MTB), and the bacteria were used to isolate cell wall fragments (CW). Both of these fractions were compared in a series of in vitro assays.
Both MTB and CW inhibited spontaneous and oxidative stress-induced ROS formation in human PMN cells and increased the phagocytic activity of PMN cells in response to bacteria-like carboxylated fluorospheres. Both fractions supported random PMN and f-MLP-directed PMN cell migration, indicating a support of immune surveillance and antibacterial defense mechanisms. In contrast, low doses of both fractions inhibited PMN cell migration towards the inflammatory mediators IL-8 and LTB4. The anti-inflammatory activity was strongest for CW, where the PMN migration towards IL-8 was inhibited down to dilutions of 1010.Both MTB and CW induced the expression of the CD69 activation marker on human CD3- CD56+ NK cells, and enhanced the expression of CD107a when exposed to K562 tumor cells in vitro.The fractions directly modulated cytokine production, inducing production of the Th2 cytokines IL-4, IL-6, and IL-10, and inhibiting production of IL-2.Both fractions further modulated mitogen-induced cytokine production in the following manner: Both fractions enhanced the PHA-induced production of IL-6 and reduced the PHA-induced production of TNF-alpha. Both fractions enhanced the PWM-induced production of TNF-alpha and IFN-gamma. In addition, MTB also enhanced both the PHA- and the PWM-induced expression of IL-10.
The data suggest that consumption of GanedenBC30TM may introduce both cell wall components and metabolites that modulate inflammatory processes in the gut. Both the cell wall and the supernatant possess strong immune modulating properties in vitro. The anti-inflammatory effects, combined with direct induction of IL-10, are of interest with respect to possible treatment of inflammatory bowel diseases as well as in support of a healthy immune system.
BMC Complement Altern Med. 2010 Jan 12;10:1. doi: 10.1186/1472-6882-10-1.
Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial.
Mandel DR1, Eichas K, Holmes J.
Lactic acid-producing bacteria (LAB) probiotics demonstrate immunomodulating and anti-inflammatory effects and the ability to lessen the symptoms of arthritis in both animals and humans. This randomized, double-blind, placebo-controlled, parallel-design, clinical pilot trial was conducted to evaluate the effects of the LAB probiotic preparation, Bacillus coagulans GBI-30, 6086, on symptoms and measures of functional capacity in patients with rheumatoid arthritis (RA) in combination with pharmacological anti-arthritic medications.
Forty-five adult men and women with symptoms of RA were randomly assigned to receive Bacillus coagulans GBI-30, 6086 or placebo once a day in a double-blind fashion for 60 days in addition to their standard anti-arthritic medications. Arthritis activity was evaluated by clinical examination, the American College of Rheumatology (ACR) criteria, the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI), and laboratory tests for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
Subjects who received Bacillus coagulans GBI-30, 6086 experienced borderline statistically significant improvement in the Patient Pain Assessment score (P = .052) and statistically significant improvement in Pain Scale (P = .046) vs placebo. Compared with placebo, Bacilluscoagulans GBI-30, 6086 treatment resulted in greater improvement in patient global assessment and self-assessed disability; reduction in CRP; as well as the ability to walk 2 miles, reach, and participate in daily activities. There were no treatment-related adverse events reported throughout this study.
Results of this pilot study suggest that adjunctive treatment with Bacillus coagulans GBI-30, 6086 LAB probiotic appeared to be a safe and effective for patients suffering from RA. Because of the low study population size, larger trials are needed to verify these results.
PMID: 20067641 Free full text article found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826289/
RESEARCH CITATIONS CLA (in TONALEAN)
J Agric Food Chem. 2012 Nov 7;60(44):11071-9. doi: 10.1021/jf3031138. Epub 2012 Oct 26.
Caenorhabditis elegans as a model to study the effectiveness and metabolic targets of dietary supplements used for obesity treatment: the specific case of a conjugated linoleic acid mixture (Tonalin).
Martorell P1, Llopis S, González N, Montón F, Ortiz P, Genovés S, Ramón D.
The antiobesity effect of conjugated linoleic acid (CLA) has previously been described in different animal models. The aim of the present study was to investigate the effect of a commercial mixture (Tonalin) on Caenorhabditis elegans to assess their potential use for functional ingredient screenings. Body-fat reduction with Tonalin was demonstrated in wild-type strain N2. The 1 μg/mL dose was the most effective, either alone or added to a food matrix, and also significantly decreased triglyceride content in nematodes fed on the CLA mixture. Furthermore, the antiobesity effect was related to the CLA isomer trans-10, cis-12. Finally, the transcriptional study showed C. elegans fed with Tonalin (1 μg/mL) underwent an upregulation of energy metabolism, reproduction, protein metabolism and oxidative stress processes. In conclusion, the results presented here clearly correlate well with other animal studies, demonstrating the value of C. elegans as a useful model to evaluate antiobesity compounds/ingredients.
Br J Nutr. 2007 Oct;98(4):860-7. Epub 2007 Jul 11.
Effects of milk supplementation with conjugated linoleic acid (isomers cis-9, trans-11 and trans-10, cis-12) on body composition and metabolic syndrome components.
Laso N1, Brugué E, Vidal J, Ros E, Arnaiz JA, Carné X, Vidal S, Mas S, Deulofeu R, Lafuente A.
The effects of conjugated linoleic acid (CLA) on body weight and body composition in man are controversial. The aim of this study was to investigate the effects of milk supplementation with CLA on body composition and on the biochemical parameters of the metabolic syndrome. This was a randomised, double-blind, placebo-controlled trial. Subjects were randomised to a daily intake of 500 ml milk supplemented with 3 g CLA (using a mixture of the bioactive isomers cis-9, trans-11 and trans-10, cis-12, marketed as Tonalin, Naturlinea; Central Lechera Asturiana) or placebo for 12 weeks. Sixty healthy men and women (aged 35-65 years) with signs of the metabolic syndrome participated (BMI 25-35 kg/m2). Dual-energy X-ray absorptiometry was used to measure body composition (week 0 baseline and week 12). Total fat mass in the CLA-milk subgroup with a BMI < or = 30 kg/m2 decreased significantly while no changes were detected in the placebo group (approximately 2 %, P = 0.01). Trunk fat mass showed a trend towards reduction (approximately 3 %, P = 0.05). CLA supplementation had no significant effect on the parameters of the metabolic syndrome, nor was it associated with changes in haematological parameters or renal function. The supplementation of milk with 3 g CLA over 12 weeks results in a significant reduction of fat mass in overweight but not in obese subjects. CLA supplementation was not associated with any adverse effects or biological changes.
PLoS One. 2015 Apr 15;10(4):e0123854. doi: 10.1371/journal.pone.0123854. eCollection 2015.
Subcutaneous and Segmental Fat Loss with and without Supportive Supplements in Conjunction with a Low-Calorie High Protein Diet in Healthy Women.
Falcone PH1, Tai CY1, Carson LR1, Joy JM1, Mosman MM1, Vogel RM2, McCann TR3, Crona KP4, Griffin JD5, Kim MP1, Moon JR6.
Weight loss benefits of multi-ingredient supplements in conjunction with a low-calorie, high-protein diet in young women are unknown. Therefore, the purpose of this study was to investigate the effects of a three-week low-calorie diet with and without supplementation on body composition.
Thirty-seven recreationally-trained women (n = 37; age = 27.1 ± 4.2; height = 165.1 ± 6.4; weight = 68.5 ± 10.1; BMI = 25.1 ± 3.4) completed one of the following three-week interventions: no change in diet (CON); a high-protein, low-calorie diet supplemented with a thermogenic, conjugated linoleic acid (CLA), a protein gel, and a multi-vitamin (SUP); or the high-protein diet with isocaloric placebo supplements (PLA). Before and after the three-week intervention, body weight, %Fat via dual X-ray absorptiometry (DXA), segmental fat mass via DXA, %Fat via skinfolds, and skinfold thicknesses at seven sites were measured.
SUP and PLA significantly decreased body weight (SUP: PRE, 70.47 ± 8.01 kg to POST, 67.51 ± 8.10 kg; PLA: PRE, 67.88 ± 12.28 kg vs. POST, 66.38 ± 11.94 kg; p ≤ 0.05) with a greater (p ≤ 0.05) decrease in SUP than PLA or CON. SUP and PLA significantly decreased %Fat according to DXA (SUP: PRE, 34.98 ± 7.05% to POST, 32.99 ± 6.89%; PLA: PRE, 34.22 ± 6.36% vs. POST, 32.69 ± 5.84%; p ≤ 0.05), whereas only SUP significantly decreased %Fat according to skinfolds (SUP: PRE, 27.40 ± 4.09% to POST, 24.08 ± 4.31%; p ≤ 0.05). SUP significantly (p ≤ 0.05) decreased thicknesses at five skinfolds (chest, waist, hip, subscapular, and tricep) compared to PLA, but not at two skinfolds (axilla and thigh).
The addition of a thermogenic, CLA, protein, and a multi-vitamin to a three-week low-calorie diet improved weight loss, total fat lossand subcutaneous fat loss, compared to diet alone.