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Lactoferrin, Green tea, Milk thistle, Omega-7, and Testosterone

May 2016

By Life Extension

Green tea

Effects of single dose and regular intake of green tea (Camellia sinensis) on DNA damage, DNA repair, and heme oxygenase-1 expression in a randomized controlled human supplementation study.

Regular intake of green tea (Camellia sinensis) lowers DNA damage in humans, but molecular mechanisms of genoprotection are not clear. Protection could be via direct antioxidant effects of tea catechins, but, paradoxically, catechins have pro-oxidant activity in vitro, and it is hypothesized that mechanisms relate to redox-sensitive cytoprotective adaptations. We investigated this hypothesis, focusing particularly on effects on the DNA repair enzyme human oxoguanine glycosylase 1 (hOGG1), and heme oxygenase-1, a protein that has antioxidant and anti-inflammatory effects. A randomized, placebo-controlled, human supplementation study of crossover design was performed. Subjects (n = 16) took a single dose (200 mL of 1.5%, w/v) and 7-days of (2 × 200 mL 1%, w/v per day) green tea (with water as control treatment). Lymphocytic DNA damage was ∼30% (p < 0.001) lower at 60 and 120 min after the single dose and in fasting samples collected after 7-day tea supplementation. Lymphocytic hOGG1 activity was higher (p < 0.0001) at 60 and 120 min after tea ingestion. Significant increases (p < 0.0005) were seen in hOGG1 activity and heme oxygenase-1 after 7 days. Results indicate that molecular triggering of redox-sensitive cytoprotective adaptations and posttranslational changes affecting hOGG1 occur in vivo in response to both a single dose and regular intake of green tea, and contribute to the observed genoprotective effects of green tea.

Mol Nutr Food Res. 2014 Jun;58(6):1379-83

Redox-linked effects of green tea on DNA damage and repair, and influence of microsatellite polymorphism in HMOX-1: results of a human intervention trial.

Green tea has many reported health benefits, including genoprotective and antioxidant effects, but green tea has pro-oxidant activity in vitro. A tea-induced pro-oxidant shift that triggers cytoprotective adaptations has been postulated, but human data are lacking. We investigated effects on oxidation-induced DNA damage and redox-linked cytoprotective factors, including 8-oxoguanine glycosylase (hOGG1) and heme oxygenase 1 (HMOX-1) in lymphocytes in a randomised, placebo-controlled, cross-over supplementation trial. hOGG1 catalyses the first step in base excision repair; increased HMOX-1 is a sign of cytoprotective response to pro-oxidant change. The influence of microsatellite polymorphisms in the HMOX-1 promoter region was also explored. Higher numbers of GT repeats [GT(n)] in this region reportedly diminish response to pro-oxidant change. Green tea [2 × 150 ml of 1% w/v tea/day (or water as control)] was taken for 12 weeks by 43 Type 2 diabetes subjects {20 with short [S/S; GT(n) < 25] and 23 with long [L/L; GT(n) ≥ 25]}. Fasting venous blood was collected before and after each treatment. The formamidopyrimidine DNA glycosylase-assisted comet assay was used to measure DNA damage in lymphocytes. For measuring hOGG1 activity, we used photo-damaged HeLa cells incubated with lymphocyte extracts from test subjects, in combination with the comet assay. Lymphocyte HMOX-1 and hOGG1 protein concentrations and expression (mRNA) of redox-sensitive genes, including HMOX-1 and hOGG1, were also investigated. Results showed significantly (P < 0.01) lower (~15%) DNA damage, higher (~50%) hOGG1 activity and higher (~40%) HMOX-1 protein concentration after tea. No changes in mRNA expression were seen. Baseline HMOX-1 protein and hOGG1 activity were higher (P < 0.05) in the S/S group, but tea-associated responses were similar in both GT(n) groups. Green tea is clearly associated with lowered DNA damage, increased hOGG1 activity and higher HMOX-1 protein levels. Further study is needed to confirm a cause and effect relationship and to establish if these effects are mediated by post-translational changes in proteins or by increased gene expression.

Mutagenesis. 2015 Jan;30(1):129-37

Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases.

Oxidative stress and low-grade inflammation are the hallmarks of the aging process and are even more enhanced in many age-related degenerative diseases. Mitochondrial dysfunction and oxidative stress can provoke and potentiate inflammatory responses, but the mechanism has remained elusive. Recent studies indicate that oxidative stress can induce the assembly of multiprotein inflammatory complexes called the inflammasomes. Nod-like receptor protein 3 (NLRP3) is the major immune sensor for cellular stress signals, e.g., reactive oxygen species, ceramides, and cathepsin B. NLRP3 activation triggers the caspase-1-mediated maturation of the precursors of IL-1b and IL-18 cytokines. During aging, the autophagic clearance of mitochondria declines and dysfunctional mitochondria provoke chronic oxidative stress, which disturbs the cellular redox balance. Moreover, increased NF-κB signaling observed during aging could potentiate the expression of NLRP3 and cytokine proforms enhancing the priming of NLRP3 inflammasomes. Recent studies have demonstrated that NLRP3 activation is associated with several age-related diseases, e.g., the metabolic syndrome. We will review here the emerging field of inflammasomes in the appearance of the proinflammatory phenotype during the aging process and in age-related diseases.

Cell Mol Life Sci. 2012 Sep;69(18):2999-3013

Chronic kidney disease: a clinical model of premature aging.

Premature aging is a process associated with a progressive accumulation of deleterious changes over time, an impairment of physiologic functions, and an increase in the risk of disease and death. Regardless of genetic background, aging can be accelerated by the lifestyle choices and environmental conditions to which our genes are exposed. Chronic kidney disease is a common condition that promotes cellular senescence and premature aging through toxic alterations in the internal milieu. This occurs through several mechanisms, including DNA and mitochondria damage, increased reactive oxygen species generation, persistent inflammation, stem cell exhaustion, phosphate toxicity, decreased klotho expression, and telomere attrition. Because recent evidence suggests that both increased local signaling of growth factors (through the nutrient-sensing mammalian target of rapamycin) and decreased klotho expression are important modulators of aging, interventions that target these should be tested in this prematurely aged population.

Am J Kidney Dis. 2013 Aug;62(2):339-51

Systematic Analysis of the Multiple Bioactivities of Green Tea through a Network Pharmacology Approach.

During the past decades, a number of studies have demonstrated multiple beneficial health effects of green tea. Polyphenolics are the most biologically active components of green tea. Many targets can be targeted or affected by polyphenolics. In this study, we excavated all of the targets of green tea polyphenolics (GTPs) though literature mining and target calculation and analyzed the multiple pharmacology actions of green tea comprehensively through a network pharmacology approach. In the end, a total of 200 Homo sapiens targets were identified for fifteen GTPs. These targets were classified into six groups according to their related disease, which included cancer, diabetes, neurodegenerative disease, cardiovascular disease, muscular disease, and inflammation. Moreover, these targets mapped into 143 KEGG pathways, 26 of which were more enriched, as determined though pathway enrichment analysis and target-pathway network analysis. Among the identified pathways, 20 pathways were selected for analyzing the mechanisms of green tea in these diseases. Overall, this study systematically illustrated the mechanisms of the pleiotropic activity of green tea by analyzing the corresponding "drug-target-pathway-disease" interaction network.

Evid Based Complement Alternat Med. 2014;2014:512081

Coffee and tea: perks for health and longevity?

PURPOSE OF REVIEW: Tea and coffee, after water, are the most commonly consumed beverages in the world and are the top sources of caffeine and antioxidant polyphenols in the American diet. The purpose of this review is to assess the health effects of chronic tea and/or coffee consumption. RECENT FINDINGS: Tea consumption, especially green tea, is associated with significantly reduced risks for stroke, diabetes and depression, and improved levels of glucose, cholesterol, abdominal obesity and blood pressure. Habitual coffee consumption in large epidemiological studies is associated with reduced mortality, both for all-cause and cardiovascular deaths. In addition, coffee intake is associated with risks of heart failure, stroke, diabetes mellitus and some cancers in an inverse dose-dependent fashion. Surprisingly, coffee is associated with neutral to reduced risks for both atrial and ventricular arrhythmias. However, caffeine at high doses can increase anxiety, insomnia, calcium loss and possibly the risk of fractures. SUMMARY: Coffee and tea can generally be recommended as health-promoting additions to an adult diet. Adequate dietary calcium intake may be particularly important for tea and coffee drinkers.

Curr Opin Clin Nutr Metab Care. 2013 Nov;16(6):688-97

Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats.

OBJECTIVES: One cause of cigarette smoking is oxidative stress that may alter the cellular antioxidant defense system, induce apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. It has been shown that Chinese green tea (CGT) (Lung Chen Tea) has higher antioxidant property than black tea. In this paper, we will explore the preventive effect of CGT on cigarette smoke-induced oxidative damage, apoptosis and tissues inflammation in albino rat model. MATERIALS AND METHODS: Albino rats were randomly divided into four groups, i.e. sham air (SA), cigarette smoke (CS), CGT 2% plus SA or plus CS. The exposure to smoking was carried out as a single daily dose (1 cigarette/rat) for a period of 90 days using an electronically controlled smoking machine. Sham control albino rats were exposed to air instead of cigarette smoke. Tissues were collected 24 hr after last CS exposure for histology and all enzyme assays. Apoptosis was evidenced by the fragmentation of DNA using TUNEL assay. RESULTS: Long-term administration of cigarette smoke altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. All these pathophysiological and biochemical events were significantly improved when the cigarette smoke-exposed albino rats were given CGT infusion as a drink instead of water. CONCLUSION: Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT.

Iran J Basic Med Sci . 2014 Oct;17(10):740-6

Green tea extract supplementation does not hamper endurance-training adaptation but improves antioxidant capacity in sedentary men.

The purpose of this study was to investigate the effect of green tea extract (GTE) supplementation combined with endurance training on endurance capacity and performance in sedentary men. Forty untrained men (age: 20 ± 1 years) participated in this study. Subjects were assigned to 1 of 4 treatments: (i) placebo-control (CTRL), (ii) GTE, (iii) endurance training (Ex), and (iv) endurance training with GTE (ExGTE). During the 4-week intervention, exercise training was prescribed as 75% oxygen uptake reserve for three 20-min sessions per week, and either GTE (250 mg/day) or placebo was provided. Endurance capacity, malondialdehyde (MDA), total antioxidant status (TAS), and creatine kinase (CK) were examined. Ex and ExGTE but not GTE improved exhaustive-run time (Ex: +8.2%, p = 0.031; ExGTE: +14.3%, p < 0.001); in addition, Ex and ExGTE significantly increased maximal oxygen uptake by ∼14% (p = 0.041) and ∼17% (p = 0.017) above the values of the CTRL group, respectively. Both Ex and ExGTE significantly decreased the increase of CK by ∼11%-32% below that of CTRL following an exhaustive run (Ex: p = 0.007; ExGTE: p = 0.001). Moreover, TAS levels increased by ∼11% in ExGTE after training (p = 0.040), and GTE, Ex, and ExGTE markedly attenuated exercise-induced MDA production (p = 0.01, p = 0.005, p = 0.011, respectively). In conclusion, this investigation demonstrated that daily ingestion of GTE during endurance training does not impair improvements in endurance capacity. Moreover, endurance training combined with GTE not only increases antioxidant capacity without attenuating endurance training adaptations, but also further attenuates acute exercise-induced CK release.

Appl Physiol Nutr Metab. 2015 Oct;40(10):990-6

Dietary supplementation with green tea extract promotes enhanced human leukocyte activity.

BACKGROUND: Leukocytes play a vital role in the host defence and inflammatory systems, the latter being responsible for the pathogenesis of a wide spectrum of acute and chronic diseases. Green tea is a popular beverage, which is consumed worldwide and its active ingredients are epicatechin derivatives, which possess distinct anti-inflammatory properties. The purpose of this study was to investigate if a green tea extract could enhance leukocyte function in humans. METHODS: Volunteers were asked to take 300 mg of the green tea extract daily for 14 days and the capacity of circulating leukocytes to release both myeloperoxidase and lactoferrin was assessed. Whole blood from volunteers was stimulated with the bacterial peptide Formyl-Methionine-Leucine-Phenylalanine (fMet-Leu-Phe). Myeloperoxidase an enzyme that converts hydrogen peroxide to hypochlorous acid and is stored and secreted from the granules of neutrophils and monocytes and was measured as well as lactoferrin which is an iron-binding protein stored and secreted from the neutrophils. In conjunction the antioxidant capacity of the blood of the volunteers was also determined using a chemiluminescence method that measures the capacity of plasma to scavenge superoxide. RESULTS: After 14 days of treatment there was a significant increase in the release of myeloperoxidase and lactoferrin when whole blood was stimulated with fMet-Leu-Phe (p<0.05), which activates a number of leukocytes including mature neutrophils and monocytes. This was mirrored by a significant increase in the total antioxidant status after 14 days of green tea ingestion (p0.05). After the "wash-out" period of 4 weeks, all parameters were consistent with those observed at the start of the trial (day 0). Treatment with the green tea extract also caused a slight but non-significant decrease in the number of circulating leukocytes, but the counts remained within published "normal" ranges for healthy human adults. CONCLUSIONS: This study indicates that a green tea extract when taken as a dietary supplement for 14 days can increase the leukocyte activity and the total plasma antioxidant status and may have role to play in the prevention of inflammatory disease.

J Complement Integr Med. 2015 Dec;12(4): 277-82

Associations of green tea and rock tea consumption with risk of impaired fasting glucose and impaired glucose tolerance in Chinese men and women.

OBJECTIVE: To explore the associations of green tea and rock tea consumption with risk of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). METHODS: A multistage, stratified, cluster, random-sampling method was used to select a representative sample from Fujian Province in China. In total, 4808 subjects without cardiovascular disease, hypertension, cancer, or pancreatic, liver, kidney, or gastrointestinal diseases were enrolled in the study. A standard questionnaire was used to gather data on tea (green, rock, and black) consumption and other relevant factors. The assessment of impaired glucose regulation (IGR) was using 75-g oral glucose tolerance test (OGTT), the diagnostic criteria of normal glucose tolerance was according to American Diabetes Association. RESULTS: Green tea consumption was associated with a lower risk of IFG, while rock tea consumption was associated with a lower risk of IGT. The adjusted odds ratios for IFG for green tea consumption of <1, 1-15, 16-30, and >30 cups per week were 1.0 (reference), 0.42 (95% confidence intervals (CI) 0.27-0.65), 0.23 (95% CI, 0.12-0.46), and 0.41 (95% CI, 0.17-0.93), respectively. The adjusted odds ratios for IGT for rock tea consumption of <1, 1-15, 16-30, and >30 cups per week were 1.0 (reference), 0.69 (95% CI, 0.48-0.98), 0.59 (95% CI, 0.39-0.90), and 0.64 (95% CI, 0.43-0.97), respectively. A U-shaped association was observed, subjects who consumed 16-30 cups of green or rock tea per week having the lowest odds ratios for IFG or IGT. CONCLUSIONS: Consumption of green or rock tea may protect against the development of type 2 diabetes mellitus in Chinese men and women, particularly in those who drink 16-30 cups per week.

PLoS One. 2013 Nov 18;8(11):e79214