Probing the Relationship Between Declining Renal Glomerular Filtration Over the Life Span and General Biological Aging: Does the Former Provide Means to Estimate the Latter?

While a consistent, gradual decline in the renal glomerular filtration rate (GFR) is a characteristic occurrence over the human life span, the exact pathophysiology behind this event remains unresolved. Evidence to date suggests that the endogenous glucose-insulin system could be involved at some level. Diabetic-induced nephropathy, one of the most prevalent chronic renal diseases, is closely linked to a severe form of insulin resistance (IR). Nevertheless, it is less certain that the ubiquitous milder forms of IR in nondiabetics ascribed customarily to routine, poor choices in diet and exercise management can over time diminish GFR and adversely influence other renal functions to any perceptible extent.Baseline data for cross-sectional analyses were obtained from a cohort of healthy, nondiabetic volunteers (fasting blood glucose [FBG] ≤ 125 mg/dL) involved in prior clinical studies. Slope-based rather than threshold analyses were mainly employed. These measurements were applied for the most part to correlate age, FBG levels used as an estimate of IR activity, and systolic blood pressure (SBP) to a variety of metabolic parameters during aging with a primary focus on GFR.Considering cause and effect, FBG and SBP correlate positively with the diminishing GFR over a major part of the life span. The decline in GFR begins somewhere around the mid-20s and coincides with key temporal increases in FBG and SBP levels.A close time-based setting suggests that IR plays a prominent role in the declining GFR that occurs over the life span. This is perhaps due in part through deleterious effects of rising levels of insulin, glucose, and SBP individually or combined that are also popular proposed causative factors for human aging in general. On the philosophical side, the latter fact suggests that the declining GFR might provide a practical way to estimate the rate of overall human biological aging.

Interplay Between Insulin Resistance and Body Fat Mass in Evolution of Perturbations Linked to the Metabolic Syndrome in Non-Diabetics: Emphasis on Inflammatory Factors.

OBJECTIVE: Many medical disorders comprising the metabolic syndrome (MS) are becoming increasingly prominent worldwide. Accordingly, much more knowledge is necessary to design the best preventive and therapeutic regimens to combat them effectively. This investigation examines the manner and magnitude of any interplay between body fat mass (FM) and insulin resistance (IR) in the evolution of these disorders using fasting blood glucose (FBG) as the latter's surrogate. Two components of MS, IR and body FM, appear to be particularly important because they have been postulated to be primary driving forces behind the other coexisting entities. Whether and how these two components interact is uncertain to some extent. METHOD: Baseline data obtained from healthy, non-diabetic volunteers involved in a number of prior clinical studies were analyzed by examining links between FBG and FM through their individual as well as combined effects on various components of MS. RESULTS: The present study consists of three phases. Phase 1 establishes that FM, similar to FBG, acting as an independent variable correlates significantly with various components of MS. The results even imply that FM offers a better measure for estimating generalized inflammation. Further, implied from findings in phase 2 is that FM influences inflammation not only by further augmenting IR but by additional means as well. In phase 3, where quartiles were developed based upon FBG and FM levels, the combination of relatively low FM/low FBG possesses significantly less proclivity for intensifying metabolic risk factors compared to the high FM/high FBG subset. CONCLUSIONS: Body FM through augmenting IR as well as another mechanism(s) markedly influences optimal fitness in seemingly normal healthy, non-diabetic volunteers. Maintaining the lowest reasonable levels of IR or body FM should bring one closer to long-term, ideal health, but improving the two jointly is an even better option.

Alzheimer's Disease and Parkinson's Disease: A Nutritional Toxicology Perspective of the Impact of Oxidative Stress, Mitochondrial Dysfunction, Nutrigenomics and Environmental Chemicals.

Introduction: Alzheimer's disease is primarily a dementia-related disorder from progressive cognitive deterioration and memory impairment, while Parkinson's disease is primarily a movement disorder illness having movement disorder symptoms, bradykinesia (slowness of movements), hypokinesia (reduction of movement amplitude), and akinesia (absence of normal unconscious movements) along with muscle rigidity and tremor at rest. While aging is the main risk factor, epidemiological evidence suggests that the exposure to environmental toxicants, mainly pesticides, metals and solvents could increase the risk of developing neurodegenerative conditions.Oxidative stress in neurodegenerative diseases: Mitochondria function impacts cell respiratory processes, metabolism, energy production, intracellular signaling, free radical production, and apoptosis. In neurodegenerative diseases, mitochondrial dysfunction is associated with a compromised energy production, impaired calcium buffering, activation of proteases and phospholipases, and increased oxidative stress. Oxidative stress induced microglial cells activation, protein aggregation, neuroinflammation and mitochondrial dysfunction lead to neuronal deaths in these disorders.Role of nutrition: Neurodegenerative disease is not curable, but treatment is available to manage the symptoms and slow down the disease progression. The drugs for treating these diseases only reduce the cognitive impairment and behavioral problems, but do not stop the progression of neurodegeneration. Healthy diet, lifestyle improvement and nutraceuticals targeting of oxidative stress, inflammation, abnormal mitochondrial dynamics and the mitochondrial interaction with abnormal disease-related proteins and assessment of impact of environmental contaminants including occupational exposures to pesticides, can be a promising approach in the treatment of neurodegenerative diseases.Conclusion: These innovations can be benchmarked on firm understanding of nutrigenomics and the personalized management of individuals at risk.

Personalized Nutrition: Translating the Science of NutriGenomics Into Practice: Proceedings From the 2018 American College of Nutrition Meeting.

Adverse reactions to foods and adverse drug reactions are inherent in product defects, medication errors, and differences in individual drug exposure. Pharmacogenetics is the study of genetic causes of individual variations in drug response and pharmacogenomics more broadly involves genome-wide analysis of the genetic determinants of drug efficacy and toxicity. The similarity of nutritional genomics and pharmacogenomics stems from the innate goal to identify genetic variants associated with metabolism and disease. Thus, nutrigenomics can be thought of as encompassing gene-diet interactions involving diverse compounds that are present in even the simplest foods. The advances in the knowledge base of the complex interactions among genotype, diet, lifestyle, and environment is the cornerstone that continues to elicit changes in current medical practice to ultimately yield personalized nutrition recommendations for health and risk assessment. This information could be used to understand how foods and dietary supplements uniquely affect the health of individuals and, hence, wellness. The individual's gut microbiota is not only paramount but pivotal in embracing the multiple-functional relationships with complex metabolic mechanisms involved in maintaining cellular homeostasis. The genetic revolution has ushered in an exciting era, one in which many new opportunities are expected for nutrition professionals with expertise in nutritional genomics. The American College of Nutrition's conference focused on "Personalized Nutrition: Translating the Science of NutriGenomics Into Practice" was designed to help to provide the education needed for the professional engagement of providers in the personalized medicine era.

A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

OBJECTIVE: The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. RESULTS: Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. CONCLUSION: These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

Fermented papaya preparation modulates the progression of N-methyl-N-nitrosourea induced hepatocellular carcinoma in Balb/c mice.

AIM AND MAIN METHOD: The medicinal properties of fermented papaya preparation (FPP) derived from Carica papaya fruit was investigated in order to determine its ability to modulate the progression of N-methyl-N-nitrosourea induced hepatocellular carcinoma in Balb/c mice. KEY FINDINGS: As well as reducing the physical symptoms associated with N-methyl-N-nitrosourea (MNU)-induced hepatocellular carcinoma, supplementation of Balb/c mice with 500mg FPP/kg BW for 92days normalized the blood cell count, led to an increased activity of several key antioxidant enzymes (SOD: +20%, CAT: +81%, GPx: +66.1%, GR: +54.4%; P<0.001 vs. MNU control), increased the ferrous reducing antioxidant potential (+36.7%, P<0.001 vs. MNU control) and reduced the extent of lipid peroxidation in the liver by 44.3% (P<0.001 vs. MNU control). SIGNIFICANCE: Results demonstrated the ability of FPP to preserve the integrity of liver against oxidative damage and protect hepatocytes against irreversible DNA structural modifications induced by MNU, highlighting its potential role as an immune-defense modulator during hepatocarcinoma.

Diabetes as a risk factor to cancer: functional role of fermented papaya preparation as phytonutraceutical adjunct in the treatment of diabetes and cancer.

Oncologists and diabetologists quote scientific data from epidemiological and in vitro studies to show that high levels of insulin and glucose, in combination with oxidative stress and chronic inflammation, can heighten the risk of developing cancer amongst patients with diabetes. Although the cancers that have been consistently associated with type 2 diabetes include pancreatic, colorectal, breast and liver cancer, the preponderance of the disease risk factors such as obesity, inflammation, hyperglycemia, hyperinsulinaemia (as a result of insulin resistance and oxidative ß-cell damage) and the indirect influence of anti-diabetic medications are increasingly being defined. Fermented papaya preparation (FPP) has defined antioxidant and immune-modulating potentials. The ability of FPP influence signaling cascades associated with cell growth and survival presents a rational for chemopreventive adjunct that can be used in combination with traditional redox based therapies that target oxidative stress in the cancer micro environment. It is further suggested that the demonstrated efficacy FPP to control blood glucose, excessive inflammation and modulate free radical-induced oxidative damage which are triggers of liver, bladder, breast and prostate cancers in type 2 diabetics, may favorably mitigate the side effects of ensuing diabetes and cancer therapy. What remains paramount is early cancer detection and early determination of propensity risks for diabetes. The education of patients, proper dietary management and compliance with therapeutic regime directed at cancer and diabetes encapsulate challenges of global magnitude.

Mechanistic perspectives on cancer chemoprevention/chemotherapeutic effects of thymoquinone.

The bioactive natural products (plant secondary metabolites) are widely known to possess therapeutic value for the prevention and treatment of various chronic diseases including cancer. Thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone; TQ), a monoterpene present in black cumin seeds, exhibits pleiotropic pharmacological activities including antioxidant, anti-inflammatory, antidiabetic and antitumor effects. TQ inhibits experimental carcinogenesis in a wide range of animal models and has been shown to arrest the growth of various cancer cells in culture as well as xenograft tumors in vivo. The mechanistic basis of anticancer effects of TQ includes the inhibition of carcinogen metabolizing enzyme activity and oxidative damage of cellular macromolecules, attenuation of inflammation, induction of cell cycle arrest and apoptosis in tumor cells, blockade of tumor angiogenesis, and suppression of migration, invasion and metastasis of cancer cells. TQ shows synergistic and/or potentiating anticancer effects when combined with clinically used chemotherapeutic agents. At the molecular level, TQ targets various components of intracellular signaling pathways, particularly a variety of upstream kinases and transcription factors, which are aberrantly activated during the course of tumorigenesis.

Relationship between fermented papaya preparation supplementation, erythrocyte integrity and antioxidant status in pre-diabetics.

Erythrocytes and their membranes are favorable models to study the relationship between diabetes and susceptibility of erythrocytes to oxidative stress damage. The recommendation for the use of fermented papaya preparation (FPP) as a functional food for dietary management of type 2 diabetes was evaluated by assessing its effect on the human antioxidant status and erythrocyte integrity on a multi-ethnical pre-diabetic population. The in vivo effect of FPP was compared with its in vitro free radical scavenging potentials. FPP exhibited potent in vitro free radical scavenging activities thought to be attributed to residual phenolic or flavonoid compounds. Low doses of FPP significantly reduced the susceptibility of human erythrocytes to undergo free radical-induced hemolysis. The intake of 6g FPP/day for a period of 14weeks was observed to significantly reduce the rate of hemolysis and accumulation of protein carbonyls in the blood plasma of pre-diabetics. That FPP consumption on a daily basis can strengthen the antioxidant defense system in vivo was clearly demonstrated by the marked increase of total antioxidant status in the FPP-supplemented pre-diabetics. That FPP maintains the integrity of erythrocytes could benefit the strategies to improve the quality of future blood products.

Effectiveness of green tea in a randomized human cohort: relevance to diabetes and its complications.

Epidemiological studies have argued that green tea could mitigate diabetes and its complications. This study investigated the phytophenolic profile of Mauritian green tea and its antioxidant propensity. The effect of green tea on the risk factors: waist-hip ratio, glucose level, arterial pressure, antioxidant status, and alanine aminotransferase (ALT) in prediabetics was assessed. The experimental group consumed 3 cups of green tea daily for 14 weeks followed by a 2-week washout period. The control group followed a water regimen. Green tea contained high level of phenolics related to its antioxidant power. Green tea suppressed waist-hip ratio of women from a significant increase and suppressed mean arterial pressure of men and women from a significant decrease after week 14. It reduced ALT level in women by 13.0% (P < 0.1) while increasing the antioxidant potential of men and women sera by 2.7% (P < 0.1) and 5.1% (P < 0.1). The study timescale may have been too short to enable demonstration of effects on fasting plasma glucose and HbA1c outcomes. Green tea regimen could form part of a healthy lifestyle that might ameliorate features of metabolic syndrome and subsequent risks for diabetes and its complications. This trial is registered with ClinicalTrials.gov NCT01248143.

Effect of Aegle marmelos leaf extract on N-methyl N-nitrosourea-induced hepatocarcinogensis in Balb/c mice.

CONTEXT AND OBJECTIVE: Tobacco smoke and nitrostable foods containing N-methyl N-nitrosourea (MNU) are among the primary causes of liver cancer. To substantiate the beneficial claims ascribed to Aegle marmelos (L.) Corrêa (Rutaceae), the hepatoprotective potential of its leaf extract was studied using an MNU-induced hepatocarcinogenesis model in Balb/c mice. MATERIALS AND METHODS: After dose selection, 40 mice were randomly assigned to 4 groups: I (control), II (intraperitoneally (i.p.) primed with 50 mg/kg MNU), III (100 mg/kg A. marmelos hydroalcoholic extract (HEAM) i.p.) and IV (MNU + HEAM, i.p.). Inflammatory (IL-1ß, IL-6), anti-inflammatory (IL-4) cytokine expression, apoptosis (Bcl-2) and tumor-related (p53, c-jun) genes were assessed at mRNA level. HEAM effects on hematological parameters were examined. RESULTS AND DISCUSSION: HEAM treatment decreased IL-1ß, IL-6, Bcl-2 and c-jun respectively expressions by 90, 25, 53 and 30%, respectively. p53 and IL-4 expression was up-regulated by 1.5- and 2-fold. MNU decreased hemoglobin concentration (25%), lymphocyte count (42%) and increased leukocyte (100%), platelet (4-fold), neutrophil (43%), monocyte (10-fold) and eosinophil (10-fold) counts in Group II mice while HEAM modulated the same parameters by -7%, -21%, +24%, +3-fold, +12%, +3-fold and +4-fold, respectively, in MNU-induced mice compared to control. HEAM protective effect was confirmed by Raman spectroscopy where the MNU-induced peak at 1252 cm(-1) was normalized. DNA fragmentation data suggest apoptosis as one of the protective mechanisms of HEAM. CONCLUSION: The hepatoprotective, anti-carcinogenic and immunomodulatory effects of A. marmelos extract indicate potential beneficial effects in cancer therapy.

The inhibitory effect of a fermented papaya preparation on growth, hydrophobicity, and acid production of Streptococcus mutans, Streptococcus mitis, and Lactobacillus acidophilus: its implications in oral health improvement of diabetics.

Fermented papaya preparation (FPP) is a "natural health product." The high incidence of dental caries, gingivitis, periodontitis, and oral microbial infection cases among patients with diabetes mellitus continues to prevail. The potential role of FPP against common oral microbiota (Streptococcus mutans, Streptococcus mitis, and Lactobacillus acidophilus) isolated from the human oral cavity was investigated using in vitro simulation models of dental plaque and caries. FPP showed an inhibitory effect against the growth (at 0.05 mg/mL: S. mutans: -6.9%; S. mitis: -4.47%, P < 0.05), acid production (at 0.05 mg/mL: S. mutans: +6.38%; L. acidophilus: +2.25%), and hydrophobicity (at 50 mg/mL: S. mutans: 1.01%, P < 0.01; S. mitis: 7.66%, P < 0.05) of tested microbiota. The results of this study suggest that low doses of FPP may be a suitable complement to good oral hygiene practice for the effective prevention of dental caries, plaque, and gingivitis. The functional application of FPP as a constituent of a balanced diet and active lifestyle can make a positive contribution to the oral health status and well-being of patients with diabetes.

Functional benefits of ergothioneine and fruit- and vegetable-derived nutraceuticals: overview of the supplemental issue contents.

For good reason, there is increasing interest in assessing the clinical efficacy of dietary supplements, naturally occurring compounds, and nutraceuticals intended for improving health and reducing disease. This is also a pressing interest in mitigating the effects of age-dependent chronic diseases. This opportunity argues for the need to develop a clear understanding of the basic molecular mechanisms responsible for the actions of dietary biofactors that can contribute to the slowing or preventing of diseases and the possibility of enhancing these improvements by coupling them with healthy lifestyle changes.

Effects of a short term supplementation of a fermented papaya preparation on biomarkers of diabetes mellitus in a randomized Mauritian population.

OBJECTIVE: Clinical evidence and cellular models have shown an inverse relationship between the intakes of plant and fruit based diets and oxidative stress, suggesting the suitability of natural antioxidants in the management of diabetes mellitus and its complications. METHOD: A randomized controlled clinical trial was conducted at the Cardiac Centre, SSRN Hospital, Pamplemousses, (Mauritius) to determine the effect of a short term supplementation of a fermented papaya preparation (FPP®) on biomarkers of diabetes and antioxidant status in a multi-ethnical neo-diabetic population from November 2010 to March 2011. RESULT: Supplementation of 6g FPP®/day for a period of 14 weeks could improve the general health status of several organs targeted by oxidative stress during diabetes. When comparing experimental to control groups with independent samples t-test, C-reactive protein levels significantly decreased (P=0.018), LDL/HDL ratio was considerably changed (P=0.042), and uric acid levels were significantly improved (P=0.001). ANOVA results also validated the same findings with significant differences in C-reactive protein, LDL/HDL ratio, uric acid and in serum ferritin levels. CONCLUSION: FPP® may present a novel, economically feasible nutraceutical supplement for the management of diabetes and for those at risk for cardiovascular disease, neurological disease and other conditions worsened by overt inflammation and oxidative stress.