Abstract Title: Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells. Abstract Source: J Cell Physiol. 2018 Feb ;233(2):1202-1212. Epub 2017 Jul 11. PMID: 28471474 Abstract Author(s): Oriana Lo Re, Concetta Panebianco, Stefania Porto, Carlo Cervi, Francesca Rappa, Stefano Di Biase, Michele Caraglia, Valerio Pazienza, Manlio Vinciguerra Article Affiliation: Oriana Lo Re Abstract: Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. A 24 hr fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cytometry. Expression of lypolysaccharide (LPS)-induced activation markers (vimentin, αSMA) was evaluated by qPCR and immunoblotting. Liver fibrosis and inflammation were evaluated in a mouse model of steatohepatitis exposed to cycles of fasting, by histological and biochemical analyses. A 24 hr fasting-induced changes were also analyzed on the proliferation/viability/glucose uptake of human HCC cells exposed to Sorafenib. An expression panel of genes involved in survival, inflammation, and metabolism was examined by qPCR in HCC cells exposed to fasting and/or Sorafenib. Fasting decreased the proliferation and the activation of HSC. Repeated cycles of short term starvation were safe in mice but did not improve fibrosis. Fasting synergized with Sorafenib in hampering HCC cell growth and glucose uptake. Finally, fasting normalized the expression levels of genes which are commonly altered by Sorafenib in HCC cells. Fasting or fasting-mimicking diet diets should be evaluated in preclinical studies as a mean to potentiate the activity of Sorafenib in clinical use. Article Published Date : Jan 31, 2018

Abstract Title: Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. Abstract Source: JBI Database System Rev Implement Rep. 2018 Feb ;16(2):507-547. PMID: 29419624 Abstract Author(s): Leanne Harris, Sharon Hamilton, Liane B Azevedo, Joan Olajide, Caroline De Brún, Gillian Waller, Vicki Whittaker, Tracey Sharp, Mike Lean, Catherine Hankey, Louisa Ells Article Affiliation: Leanne Harris Abstract: OBJECTIVE: To examine the effectiveness of intermittent energy restriction in the treatment for overweight and obesity in adults, when compared to usual care treatment or no treatment. INTRODUCTION: Intermittent energy restriction encompasses dietary approaches including intermittent fasting, alternate day fasting, and fasting for two days per week. Despite the recent popularity of intermittent energy restriction and associated weight loss claims, the supporting evidence base is limited. INCLUSION CRITERIA: This review included overweight or obese (BMI≥25 kg/m) adults (≥18 years). Intermittent energy restriction was defined as consumption of ≤800 kcal on at least one day, but no more than six days per week. Intermittent energy restriction interventions were compared to no treatment (ad libitum diet) or usual care (continuous energy restriction ∼25% of recommended energy intake). Included interventions had a minimum duration of 12 weeks from baseline to post outcome measurements. The types of studies included were randomized and pseudo-randomized controlled trials. The primary outcome of this review was change in body weight. Secondary outcomes included: i) anthropometric outcomes (change in BMI, waist circumference, fat mass, fat free mass); ii) cardio-metabolic outcomes (change in blood glucose and insulin, lipoprotein profiles and blood pressure); and iii) lifestyle outcomes: diet, physical activity, quality of life and adverse events. METHODS: A systematic search was conducted from database inception to November 2015. The following electronic databases were searched: MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, ISRCTN registry, and anzctr.org.au for English language published studies, protocols and trials. Two independent reviewers evaluated the methodological quality of included studies using the standardized critical appraisal instruments from the Joanna Briggs Institute. Data were extracted from papers included in the review by two independent reviewers using the standardized data extraction tool from the Joanna Briggs Institute. Effect sizes were expressed as weighted mean differences and their 95% confidence intervals were calculated for meta-analyses. RESULTS: Six studies were included in this review. The intermittent energy restriction regimens varied across studies and included alternate day fasting, fasting for two days, and up to four days per week. The duration of studies ranged from three to 12 months. Four studies included continuous energy restriction as a comparator intervention and two studies included a no treatment control intervention. Meta-analyses showed that intermittent energy restriction was more effective than no treatment for weight loss (-4.14 kg; 95% CI -6.30 kg to -1.99 kg; p ≤ 0.001). Although both treatment interventions achieved similar changes in body weight (approximately 7 kg), the pooled estimate for studies that investigated the effect of intermittent energy restriction in comparison to continuous energy restriction revealed no significant difference in weight loss (-1.03 kg; 95% CI -2.46 kg to 0.40 kg; p = 0.156). CONCLUSIONS: Intermittent energy restriction may be an effective strategy for the treatment of overweight and obesity. Intermittent energy restriction was comparable to continuous energy restriction for short term weight loss in overweight and obese adults. Intermittent energy restriction was shown to be more effective than no treatment, however, this should be interpreted cautiously due to the small number of studies and future research is warranted to confirm the findings of this review. Article Published Date : Jan 31, 2018

Abstract Title: Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats. Abstract Source: Exp Biol Med (Maywood). 2018 Feb ;243(4):334-343. Epub 2018 Jan 7. PMID: 29307281 Abstract Author(s): Bae Kun Shin, Suna Kang, Da Sol Kim, Sunmin Park Article Affiliation: Bae Kun Shin Abstract: Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused withβ-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared tothe Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly, cortisol levels were increased by Alzheimer's disease but decreased by intermittent fasting. Intermittent fasting improved dyslipidemia and liver damage index compared to ad libitum. Alzheimer's disease lowered low-density lipoprotein cholesterol and serum triglyceride levels compared to Non-Alzheimer's disease. In conclusion, Alzheimer's disease impaired not only cognitive function but also disturbed energy, glucose, lipid, and bone metabolism in ovariectomized rats. Intermittent fasting protected against the deterioration of these metabolic parameters, but it exacerbated bone mineral density loss and insulin resistance at fasting in Alzheimer's disease-induced estrogen-deficient rats. Impact statement Intermittent fasting was evaluated for its effects on cognitivefunction and metabolic disturbances in a rat model of menopause and Alzheimer's disease. Intermittent fasting decreased skin temperature and fat mass, and improved glucose tolerance with decreasing food intake. Intermittent fasting also prevented memory loss: short-term and special memory loss. Therefore, intermittent fasting may prevent some of the metabolic pathologies associated with menopause and protect against age-related memory decline. Article Published Date : Jan 31, 2018

Abstract Title: Intermittent Fasting Alleviates the Increase of Lipoprotein Lipase Expression in Brain of a Mouse Model of Alzheimer's Disease: Possibly Mediated byβ-hydroxybutyrate. Abstract Source: Front Cell Neurosci. 2018 ;12:1. Epub 2018 Jan 17. PMID: 29386999 Abstract Author(s): Jingzhu Zhang, Xinhui Li, Yahao Ren, Yue Zhao, Aiping Xing, Congmin Jiang, Yanqiu Chen, Li An Article Affiliation: Jingzhu Zhang Abstract: Intermittent fasting has been demonstrated to protect against Alzheimer's disease (AD), however, the mechanism is unclear. Histone acetylation and lipoprotein lipase (LPL) are involved in AD progression. Importantly, LPL has been documented to be regulated by histone deacetylases (HDACs) inhibitors (increase histone acetylation level) in adipocyte and mesenchymal stem cells, or by fasting in adipose and muscle tissues. In brain, however, whether histone acetylation or fasting regulates LPL expression is unknown. This study was designed to demonstrate intermittent fasting may protect against AD through increasingβ-hydroxybutyrate, a HDACs inhibitor, to regulate LPL. We also investigated microRNA-29a expression associating with regulation of LPL and histone acetylation. The results showed LPL mRNA expression was increased and microRNA-29a expression was decreased in the cerebral cortex of AD model mice (APP/PS1), which were alleviated by intermittent fasting. No significant differences were found in the total expression of LPL protein (brain-derived and located in capillary endothelial cells from peripheral tissues) in the cerebral cortex of APP/PS1 mice. Further study indicated that LPL located in capillary endothelial cells was decreased in the cerebral cortex of APP/PS1 mice, which was alleviated by intermittent fasting. LPL and microRNA-29a expression were separately increased and down-regulated in 2 μM Aβ-exposed SH-SY5Y cells, but respectively decreased and up-regulated in 10μM Aβ-exposed cells, which were all reversed byβ-hydroxybutyrate. The increase of HDAC2/3 expression and the decrease of acetylated H3K9 and H4K12 levels were alleviated in APP/PS1 mice by intermittent fasting treatment, as well in 2 or 10 μM Aβ-exposed cells byβ-hydroxybutyrate treatment. These findings above suggested the results from APP/PS1 mice were consistent with those from cells treated with 2 μM Aβ. Interestingly, LPL expression was reduced (0.2-folds) and microRNA-29a expression was up-regulated (1.7-folds) in HDAC2-silenced cells, but respectively increased (1.3-folds) and down-regulated (0.8-folds) in HDAC3-silenced cells. Furthermore, LPL expression was decreased in cells treated with microRNA-29a mimic and increased with inhibitor treatment. In conclusion, intermittent fasting inhibits the increase of brain-derived LPL expression in APP/PS1 mice partly throughβ-hydroxybutyrate-mediated down-regulation of microRNA-29a expression. HDAC2/3 may be implicated in the effect of β-hydroxybutyrate on microRNA-29a expression. Article Published Date : Dec 31, 2017

Abstract Title: Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota. Abstract Source: Cell Metab. 2017 Oct 3 ;26(4):672-685.e4. Epub 2017 Sep 14. PMID: 28918936 Abstract Author(s): Guolin Li, Cen Xie, Siyu Lu, Robert G Nichols, Yuan Tian, Licen Li, Daxeshkumar Patel, Yinyan Ma, Chad N Brocker, Tingting Yan, Kristopher W Krausz, Rong Xiang, Oksana Gavrilova, Andrew D Patterson, Frank J Gonzalez Article Affiliation: Guolin Li Abstract: While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases. Article Published Date : Oct 02, 2017

Abstract Title: Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages. Abstract Source: Oncotarget. 2017 Sep 26 ;8(43):74649-74660. Epub 2017 Aug 16. PMID: 29088814 Abstract Author(s): Pengfei Sun, Huihui Wang, Zhiyong He, Xiangyuan Chen, Qichao Wu, Wankun Chen, Zhirong Sun, Meilin Weng, Minmin Zhu, Duan Ma, Changhong Miao Article Affiliation: Pengfei Sun Abstract: Dietary restriction has been recognized as a healthy and natural therapy for cancer. It is reported that different forms of dietary restriction can promote anti-tumor immunity. However, it is not clear how fasting affects tumor-associated macrophages (TAMs). This study aims to investigate the relationship between fasting and antitumor immunity in terms of tumor-associated macrophages. In vivo, the results showed that alternate day fasting for 2 weeks inhibitted the tumor growth of mice without causing a reduction of body weight. Meanwhile, M2 polarization of tumor-associated macrophages in tumor tissues of alternate day fasting group was also decreased. In vitro, fasting induced the autophagy of CT26 cells, decreased the generation of extracellular adenosine by supressing the expression of CD73 in CT26 cells. Decreasing adenosine inhibitted M2 polarization of RAW264.7 cells through inactivating JAK1/STAT3 signal pathway in fasting condition. Eventually, the proliferation of CT26 cancer cells declined on account of fasting-facilitated antitumor immunity. These results suggested that fasting suppressed M2 polarization of tumor-associated macrophages to inhibit tumor growth through decreasing the level of adenosine in the tumor microenvironment both in vivo and in vitro. This process was associated with increasing autophagy of tumor cells. Article Published Date : Sep 25, 2017

Abstract Title: Intermittent fasting prompted recovery from dextran sulfate sodium-induced colitis in mice. Abstract Source: J Clin Biochem Nutr. 2017 Sep ;61(2):100-107. Epub 2017 Jul 28. PMID: 28955126 Abstract Author(s): Toshihiko Okada, Takeshi Otsubo, Teruki Hagiwara, Fumika Inazuka, Eiko Kobayashi, Shinji Fukuda, Takuya Inoue, Kazuhide Higuchi, Yuki I Kawamura, Taeko Dohi Article Affiliation: Toshihiko Okada Abstract: Fasting-refeeding in mice induces transient hyperproliferation of colonic epithelial cells, which is dependent on the lactate produced as a metabolite of commensal bacteria. We attempted to manipulate colonic epithelial cell turnover with intermittent fasting to prompt recovery from acute colitis. Acute colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium in the drinking water for 5 days. From day 6, mice were fasted for 36 h and refed normal bait, glucose powder, or lactylated high-amylose starch. On day 9, colon tissues were subjected to analysis of histology and cytokine expression. The effect of lactate on the proliferation of colonocytes was assessed by enema in vivo and primary culture in vitro. Intermittent fasting resulted in restored colonic crypts and less expression of interleukin-1β and interleukin-17 in the colon than in mice fed ad libitum. Administration of lactate in the colon at refeeding time by enema or by feeding lactylated high-amylose starch increased the number of regenerating crypts. Addition of lactate but not butyrate or acetate supported colony formation of colonocytes in vitro. In conclusion, intermittent fasting in the resolution phase of acute colitis resulted in better recovery of epithelial cells and reduced inflammation. Article Published Date : Aug 31, 2017

Abstract Title: Intermittent Fasting Preserves Beta-Cell Mass in Obesity-induced Diabetes via the Autophagy-Lysosome Pathway. Abstract Source: Autophagy. 2017 Aug 30:0. Epub 2017 Aug 30. PMID: 28853981 Abstract Author(s): Haiyan Liu, Ali Javaheri, Rebecca J Godar, John Murphy, Xiucui Ma, Nidhi Rohatgi, Jana Mahadevan, Krzysztof Hyrc, Paul Saftig, Connie Marshall, Michael L McDaniel, Maria S Remedi, Babak Razani, Fumihiko Urano, Abhinav Diwan Article Affiliation: Haiyan Liu Abstract: Obesity-induced diabetes is characterized by hyperglycemia, insulin resistance, and progressive beta cell failure. In islets of mice with obesity-induced diabetes, we observe increased beta cell death and impaired autophagic flux. We hypothesized that intermittent fasting, a clinically sustainable therapeutic strategy, stimulates autophagic flux to ameliorate obesity-induced diabetes. Our data show that despite continued high-fat intake, intermittent fasting restores autophagic flux in islets and improves glucose tolerance by enhancing glucose-stimulated insulin secretion, beta cell survival, and nuclear expression of NEUROG3, a marker of pancreatic regeneration. In contrast, intermittent fasting does not rescue beta-cell death or induce NEUROG3 expression in obese mice with lysosomal dysfunction secondary to deficiency of the lysosomal membrane protein, LAMP2 or haplo-insufficiency of BECN1/Beclin-1, a protein critical for autophagosome formation. Moreover, intermittent fasting is sufficient to provoke beta cell death in non-obese lamp2 null mice, attesting to a critical role for lysosome function in beta cell homeostasis under fasting conditions. Beta cells in intermittently-fasted LAMP2- or BECN1-deficient mice exhibit markers of autophagic failure with accumulation of damaged mitochondria and upregulation of oxidative stress. Thus, intermittent fasting preserves organelle quality via the autophagy-lysosome pathway to enhance beta cell survival and stimulates markers of regeneration in obesity-induced diabetes. Article Published Date : Aug 29, 2017

Abstract Title: Fasting as possible complementary approach for polycystic ovary syndrome: Hope or hype? Abstract Source: Med Hypotheses. 2017 Aug ;105:1-3. Epub 2017 Jun 23. PMID: 28735644 Abstract Author(s): Benito Chiofalo, Antonio Simone Laganà, Vittorio Palmara, Roberta Granese, Giacomo Corrado, Emanuela Mancini, Salvatore Giovanni Vitale, Helena Ban Frangež, Eda Vrtačnik-Bokal, Onofrio Triolo Article Affiliation: Benito Chiofalo Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation. Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role on aging and metabolic homeostasis. Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women. Article Published Date : Jul 31, 2017

Abstract Title: Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition. Abstract Source: Metabolism. 2017 Jun ;71:70-82. Epub 2017 Mar 9. PMID: 28521881 Abstract Author(s): Albert E Towers, Maci L Oelschlager, Jay Patel, Stephen J Gainey, Robert H McCusker, Gregory G Freund Article Affiliation: Albert E Towers Abstract: BACKGROUND: Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. METHODS: Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. RESULTS: A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. CONCLUSIONS: Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. Article Published Date : May 31, 2017

Abstract Title: Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion. Abstract Source: J Nutr. 2017 May 17. Epub 2017 May 17. PMID: 28515159 Abstract Author(s): Yuan Hu, Ying Yang, Miao Zhang, Min Deng, Jun-Jian Zhang Article Affiliation: Yuan Hu Abstract: Background: Whether intermittent fasting (IF) pretreatment can prevent vascular cognitive dysfunction remains unknown to our knowledge.Objective: We investigated the effects and underlying mechanisms of IF pretreatment on cognitive dysfunction in a permanent 2-vessel occlusion (2VO) vascular dementia rat model.Methods: Male Wistar rats weighing 200 g were subjected to either IF or ad libitum feeding for 12 wk before 2VO surgery. Rats in the IF protocol underwent alternative-day feed deprivation (FD). Memory of the animals was assessed by using the Morris water maze (MWM) and the novel object recognition (NOR) test 6 wk after the surgery. After behavioral testing, malondialdehyde and glutathione concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein concentrations, and microglia density were determined in the hippocampus of rats.Results: 2-vessel occlusion operation ad libitum (2VO-AL) rats had significantly longer escape latencies on day 4 of the training phase and spent a lower percentage of time in the target quadrant (25% compared with 38% and 41%) in the MWM, and had lower discrimination ratios (47% compared with 65% and 67%) in the NOR test than 2-vessel operation and alternate-day feed deprivation (2VO-FD) and sham operation ad libitum (Sham-AL) rats, respectively (P<0.05). This indicates that IF helps to prevent vascular cognitive deficits. 2VO-AL rats also had higher malondialdehyde (3.54 compared with 2.15 and 1.66 nmol/mg protein) and lower glutathione concentrations (53.25 compared with 66.41 and 91.71 nmol/mg protein), lower SOD activity (100.1 compared with 133.3 and 138.5 U/mg protein), lower gene expression of antioxidative enzymes, higher expression of inflammatory proteins, and higher microglia density in the hippocampus than 2VO-FD and Sham-AL rats, respectively (P<0.05). This suggests that IF has antioxidative and anti-inflammatory effects.Conclusions: IF pretreatment provided sustained neuroprotection in a rat model of vascular dementia. These effects were associated with reduced oxidative stress and neuroinflammation. Article Published Date : May 16, 2017

Abstract Title: Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways. Abstract Source: Biogerontology. 2017 May 6. Epub 2017 May 6. PMID: 28478492 Abstract Author(s): Harpal Singh, Taranjeet Kaur, Shaffi Manchanda, Gurcharan Kaur Article Affiliation: Harpal Singh Abstract: Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1β, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen. Article Published Date : May 05, 2017

Abstract Title: Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. Abstract Source: World J Diabetes. 2017 Apr 15 ;8(4):154-164. PMID: 28465792 Abstract Author(s): Terra G Arnason, Matthew W Bowen, Kerry D Mansell Article Affiliation: Terra G Arnason Abstract: AIM: To determine the short-term biochemical effects and clinical tolerability of intermittent fasting (IF) in adults with type 2 diabetes mellitus (T2DM). METHODS: We describe a three-phase observational study (baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements (using the Yale Physical Activity Survey) were taken at the end of each phase. Participants reported morning, afternoon and evening self-monitored blood glucose (SMBG) and fasting duration on a daily basis throughout all study stages, in addition to completing a remote food photography diary three times within each study phase. Fasting blood samples were collected on the final days of each study phase. RESULTS: At baseline, the ten participants had a confirmed diagnosis of T2DM and were all taking metformin, and on average were obese [mean body mass index (BMI) 36.90 kg/m(2)]. We report here that a short-term period of IF in a small group of individuals with T2DM led to significant group decreases in weight (-1.395 kg, P = 0.009), BMI (-0.517, P = 0.013), and at-target morning glucose (SMBG). Although not a study requirement, all participants preferentially chose eating hours starting in the midafternoon. There was a significant increase (P<0.001) in daily hours fasted in the IF phase (+5.22 h), although few attained the 18-20 h fasting goal (mean 16.82± 1.18). The increased fasting duration improved at-goal (<7.0 mmol/L) morning SMBG to 34.1%, from a baseline of 13.8%. Ordinal Logistic Regression models revealed a positive relationship between the increase in hours fasted and fasting glucose reaching target values (χ(2) likelihood ratio = 8.36, P = 0.004) but not for afternoon or evening SMBG (all P>0.1). Postprandial SMBGs were also improved during the IF phase, with 60.5% readings below 9.05 mmol/L, compared to 52.6% at baseline, and with less glucose variation. Neither insulin resistance (HOMA-IR), nor inflammatory markers (C-reactive protein) normalized during the IF phase. IF led to an overall spontaneous decrease in caloric intake as measured by food photography (Remote Food Photography Method). The data demonstrated discernable trends during IF for lower energy, carbohydrate, and fat intake when compared to baseline. Physical activity, collected by a standardized measurement tool (Yale Physical Activity Survey), increased during the intervention phase and subsequently decreased in the follow-up phase. IF was well tolerated in the majority of individuals with 6/10 participants stating they would continue with the IF regimen after the completion of the study, in a full or modified capacity (i.e., every other day or reduced fasting hours). CONCLUSION: The results from this pilot study indicate that short-term daily IF may be a safe, tolerable, dietary intervention in T2DM patients that may improve key outcomes including body weight, fasting glucose and postprandial variability. These findings should be viewed as exploratory, and a larger, longer study is necessary to corroborate these findings. Article Published Date : Apr 14, 2017

Abstract Title: Effects of A One-week Fasting Therapy in Patients with Type-2 Diabetes Mellitus and Metabolic Syndrome - A Randomized Controlled Explorative Study. Abstract Source: Exp Clin Endocrinol Diabetes. 2017 Apr 13. Epub 2017 Apr 13. PMID: 28407662 Abstract Author(s): Chenying Li, Badri Sadraie, Nico Steckhan, Christian Kessler, Rainer Stange, Michael Jeitler, Andreas Michalsen Article Affiliation: Chenying Li Abstract: There is increasing experimental evidence for beneficial effects of calorie restriction and intermittent fasting in type 2 diabetes mellitus (T2DM). In humans, prolonged fasting is established as a health-promoting complementary treatment in Europe and claimed to improve metabolism by a complex hormetic response. We aimed to investigate effects of a one-week fasting period compared to usual care in T2DM by means of a pilot trial. Patients with manifest T2DM medically treated with oral hypoglycemic agents and/or insulin were randomly assigned to a 7-day fasting program followed by dietary advice or to usual care and dietary advice only. Fasting was performed according to the method of Buchinger with a nutritional energy intake of 300kcal/day by liquids only and stepwise re-introduction of solid food thereafter. Outcomes were assessed baseline and after 4 months. Of 46 enrolled participants, 32 (n=16 each group) completed the trial and were included for final analyses. Fasting was well accepted, there were no serious adverse events. After 4 months mean weight decreased by 3.5 kg and 2.0 kg in the fasting vs. control group (p=0.03) paralleled by greater reduction of abdominal circumference (p=0.001). Fasting led to a significant decrease of systolic/diastolic blood pressure (p=0.01; p=0.003) and increased quality-of-life (p=0.04), while for HbA1c, insulin and HOMA-index only non-significant improvements were observed. Results of this study suggest that prolonged fasting is feasible and might have beneficial clinical effects. The effectiveness of fasting should be proved in larger confirmatory trials that include intermittent fasting in follow-ups to enable morepronounced and long-term effects. Article Published Date : Apr 12, 2017

Abstract Title: Positive effects of intermittent fasting in ischemic stroke. Abstract Source: Exp Gerontol. 2017 Mar ;89:93-102. Epub 2017 Jan 20. PMID: 28115234 Abstract Author(s): David Yang-Wei Fann, Gavin Yong Quan Ng, Luting Poh, Thiruma V Arumugam Article Affiliation: David Yang-Wei Fann Abstract: Intermittent fasting (IF) is a dietary protocol where energy restriction is induced by alternate periods of ad libitum feeding and fasting. Prophylactic intermittent fasting has been shown to extend lifespan and attenuate the progress and severity of age-related diseases such as cardiovascular (e.g. stroke and myocardial infarction), neurodegenerative (e.g. Alzheimer's disease and Parkinson's disease) and cancerous diseases in animal models. Stroke is the second leading cause of death, and lifestyle risk factors such as obesity and physical inactivity have been associated with elevated risks of stroke in humans. Recent studies have shown that prophylactic IF may mitigate tissue damage and neurological deficit following ischemic stroke by a mechanism(s) involving suppression of excitotoxicity, oxidative stress, inflammation and cell death pathways in animal stroke models. This review summarizes data supporting the potential hormesis mechanisms of prophylactic IF in animal models, and with a focus on findings from animal studies of prophylactic IF in stroke in our laboratory. Article Published Date : Feb 28, 2017

Abstract Title: Dietary Regulation of Adult Stem Cells. Abstract Source: Curr Stem Cell Rep. 2017 Mar ;3(1):1-8. Epub 2017 Feb 8. PMID: 28966904 Abstract Author(s): Miyeko D Mana, Elaine Yih-Shuen Kuo, Ömer H Yilmaz Article Affiliation: Miyeko D Mana Abstract: PURPOSE OF REVIEW: Dietary intake is a critical regulator of organismal physiology and health. Tissue homeostasis and regeneration are dependent on adult tissue stem cells that self-renew and differentiate into the specialized cell types. As stem cells respond to cues from their environment, dietary signals and nutrients influence tissue biology by altering the function and activity of adult stem cells. In this review, we highlight recent studies that illustrate how diverse diets such as caloric restriction, fasting, high fat diets, and ketogenic diets impact stem cell function and their microenvironments. RECENT FINDINGS: Caloric restriction generally exerts positive effects on adult stem cells, notably increasing stem cell functionality in the intestine and skeletal muscle as well as increasing hematopoietic stem cell quiescence. Similarly, fasting confers protection of intestinal, hematopoietic, and neuronal stem cells against injury. High fat diets induce intestinal stem cell niche independence and stem-like properties in intestinal progenitors, while high fat diets impair hematopoiesis and neurogenesis. SUMMARY: Caloric restriction and fasting are generally beneficial to adult stem cell function, while high fat diets impair stem cell function or create opportunities for tumorigenesis. However, the effects of each diet on stem cell biology are complex and vary greatly between tissues. Given the recent interest in developing dietary interventions or mimetics as therapeutics, further studies, including on ketogenic diets, will be essential to understand how adult stem cells respond to diet-induced signals and physiology. Article Published Date : Feb 28, 2017

Abstract Title: Metabolic effects of fasting on human and mouse blood in vivo. Abstract Source: Autophagy. 2017 Jan 6:0. Epub 2017 Jan 6. PMID: 28059587 Abstract Author(s): Federico Pietrocola, Yohann Demont, Francesca Castoldi, David Enot, Sylvère Durand, Michaela Semeraro, Elisa Elena Baracco, Jonathan Pol, Jose Manuel Bravo-San Pedro, Chloé Bordenave, Sarah Levesque, Juliette Humeau, Alexis Chery, Didier Métivier, Frank Madeo, M Chiara Maiuri, Guido Kroemer Article Affiliation: Federico Pietrocola Abstract: Starvation is a strong physiological stimulus of macroautophagy/autophagy. In this study, we addressed the question as to whether it would be possible to measure autophagy in blood cells after nutrient deprivation. Fasting of mice for 48 h (which causes ∼20% weight loss) or starvation of human volunteers for up to 4 days (which causes<2% weight loss) provokes major changes in the plasma metabolome, yet induces only relatively minor alterations in the intracellular metabolome of circulating leukocytes. White blood cells from mice and human volunteers responded to fasting with a marked reduction in protein lysine acetylation, affecting both nuclear and cytoplasmic compartments. In circulating leukocytes from mice that underwent 48-h fasting, an increase in LC3B lipidation (as assessed by immunoblotting and immunofluorescence) only became detectable if the protease inhibitor leupeptin was injected 2 h before drawing blood. Consistently, measurement of an enhanced autophagic flux was only possible if white blood cells from starved human volunteers were cultured in the presence or absence of leupeptin. Whereas all murine leukocyte subpopulations significantly increased the number of LC3B(+) puncta per cell in response to nutrient deprivation, only neutrophils from starved volunteers showed signs of activated autophagy (as determined by a combination of multi-color immunofluorescence, cytofluorometry and image analysis). Altogether, these results suggest that white blood cells are suitablefor monitoring autophagic flux. In addition, we propose that the evaluation of protein acetylation in circulating leukocytes can be adopted as a biochemical marker of organismal energetic status. Article Published Date : Jan 05, 2017

Abstract Title: Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation. Abstract Source: Nat Med. 2017 Jan ;23(1):79-90. Epub 2016 Dec 12. PMID: 27941793 Abstract Author(s): Zhigang Lu, Jingjing Xie, Guojin Wu, Jinhui Shen, Robert Collins, Weina Chen, Xunlei Kang, Min Luo, Yizhou Zou, Lily Jun-Shen Huang, James F Amatruda, Tamra Slone, Naomi Winick, Philipp E Scherer, Cheng Cheng Zhang Article Affiliation: Zhigang Lu Abstract: New therapeutic approaches are needed to treat leukemia effectively. Dietary restriction regimens, including fasting, have been considered for the prevention and treatment of certain solid tumor types. However, whether and how dietary restriction affects hematopoietic malignancies is unknown. Here we report that fasting alone robustly inhibits the initiation and reverses the leukemic progression of both B cell and T cell acute lymphoblastic leukemia (B-ALL and T-ALL, respectively), but not acute myeloid leukemia (AML), in mouse models of these tumors. Mechanistically, we found that attenuated leptin-receptor (LEPR) expression is essential for the development and maintenance of ALL, and that fasting inhibits ALL development by upregulation of LEPR and its downstream signaling through the protein PR/SET domain 1 (PRDM1). The expression of LEPR signaling-related genes correlated with the prognosis of pediatric patients with pre-B-ALL, and fasting effectively inhibited B-ALL growth in a human xenograft model. Our results indicate that the effects of fasting on tumor growth are cancer-type dependent, and they suggest new avenues for the development of treatment strategies for leukemia. Article Published Date : Dec 31, 2016

Abstract Title: Intermittent Fasting Protects against Alzheimer's Disease Possible through Restoring Aquaporin-4 Polarity. Abstract Source: Front Mol Neurosci. 2017 ;10:395. Epub 2017 Nov 29. PMID: 29238290 Abstract Author(s): Jingzhu Zhang, Zhipeng Zhan, Xinhui Li, Aiping Xing, Congmin Jiang, Yanqiu Chen, Wanying Shi, Li An Article Affiliation: Jingzhu Zhang Abstract: The impairment of amyloid-β (Aβ) clearance in the brain plays a causative role in Alzheimer's disease (AD). Polarity distribution of aquaporin-4 (AQP4) is important to remove Aβ from brain. AQP4 polarity can be influenced by the ratio of two AQP4 isoforms M1 and M23 (AQP4-M1/M23), however, it is unknown whether the ratioof AQP4-M1/M23 changes in AD. Histone deacetylase 3 has been reported to be significantly increased in AD brain. Moreover, evidence indicated that microRNA-130a (miR-130a) possibly mediates the regulation of histone deacetylase 3 on AQP4-M1/M23 ratio by repressing the transcriptional activity of AQP4-M1 in AD. This study aimed to investigate whether intermittent fasting (IF), increasing the level of an endogenous histone deacetylases inhibitor β-hydroxybutyrate, restores AQP4 polarity via miR-130a mediated reduction of AQP4-M1/M23 ratio in protection against AD. The results showed that IF ameliorated cognitive dysfunction, prevented brain from Aβ deposition, and restored the AQP4 polarity in a mouse model of AD (APP/PS1 double-transgenic mice). Additionally, IF down-regulated the expression of AQP4-M1 and histone deacetylase 3, reduced AQP4-M1/M23 ratio, and increased miR-130a expression in the cerebral cortex of APP/PS1 mice.,β-hydroxybutyrate was found to down-regulate the expression of AQP4-M1 and histone deacetylase 3, reduce AQP4-M1/M23 ratio, and increase AQP4-M23 and miR-130a expression in 2 μM Aβ-treated U251 cells. Interestingly, on the contrary to the result observed in 2 μM Aβ-treated cells, AQP4 expression was obviously decreased in cells exposed to 10 μM Aβ. miR-130a mimic decreased the expression of AQP4-M1 and the ratio of AQP4-M1/M23, as well as silencing histone deacetylase 3 caused the up-regulation of AQP4 and miR-130a, and the reduction of AQP4-M1/M23 ratio in U251 cells. In conclusion, IFexhibits beneficial effects against AD. The mechanism may be associated with recovery of AQP4 polarity, resulting from the reduction of AQP4-M1/M23 ratio. Furthermore, β-hydroxybutyrate may partly mediate the effect of IF on the reduction of AQP4-M1/M23 ratio in AD, in which miR-130a and histone deacetylase 3 may be implicated. Article Published Date : Dec 31, 2016

Abstract Title: Caloric restriction - A promising anti-cancer approach: From molecular mechanisms to clinical trials. Abstract Source: Biochim Biophys Acta. 2016 Nov 19 ;1867(1):29-41. Epub 2016 Nov 19. PMID: 27871964 Abstract Author(s): Gelina S Kopeina, Vyacheslav V Senichkin, Boris Zhivotovsky Article Affiliation: Gelina S Kopeina Abstract: Cancer is the second leading cause of death worldwide and the morbidity is growing in developed countries. According to WHO,>14 million people per year are diagnosed with cancer and about 8 million die. Anti-cancer strategy includes chemo-, immune- and radiotherapy or their combination. Unfortunately, these widely used strategies often have insufficient efficacy and significant toxic effects on healthy cells. Consequently, the improvement of treatment approaches is an important goal. One of promising schemes to enhance the effect of therapy is the restriction of calorie intake or some nutrients. The combination of caloric restriction or its chemical mimetics along with anti-cancer drugs may suppress growth of tumor cells and enhance death of cancer cells. That will allow the dose of therapeutic drugs to be decreased and their toxic effects to be reduced. Here the possibility of using this combinatory therapy as well as the molecular mechanisms underlying this approach will be discussed. Article Published Date : Nov 18, 2016

Abstract Title: Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing autophagic flux disturbance and inhibiting apoptosis. Abstract Source: Exp Ther Med. 2016 Nov ;12(5):3021-3028. Epub 2016 Oct 31. PMID: 27882110 Abstract Author(s): Ji Heun Jeong, Kwang Sik Yu, Dong Ho Bak, Je Hun Lee, Nam Seob Lee, Young Gil Jeong, Dong Kwan Kim, Jwa-Jin Kim, Seung-Yun Han Article Affiliation: Ji Heun Jeong Abstract: Previous studies have demonstrated that autophagy induced by caloric restriction (CR) is neuroprotective against cerebral ischemia. However, it has not been determined whether intermittent fasting (IF), a variation of CR, can exert autophagy-related neuroprotection against cerebral ischemia. Therefore, the neuroprotective effect of IF was evaluated over the course of two weeks in a rat model of focal cerebral ischemia, which was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). Specifically, the role of autophagy modulation as a potential underlying mechanism for this phenomenon was investigated. It was demonstrated that IF reduced infarct volume and brain edema, improved neurobehavioral deficits, and rescued neuronal loss after MCAO/R. Furthermore, neuronal apoptosis was decreased by IF in the rat cortex. An increase in the number of autophagosomes (APs) was demonstrated in the cortices of IF-treated rats, using immunofluorescence staining and transmission electron microscopy. Using immunoblots, an IF-induced increase was detected in microtubule-associated protein 1 light chain 3 (LC3)-II, Rab7, and cathepsin D protein levels, which corroborated previous morphological studies. Notably, IF reduced the accumulation of APs and p62, demonstrating that IF attenuated the MCAO/R-induced disturbance of autophagic flux in neurons. The findings of the present study suggest that IF-induced neuroprotection in focal cerebral ischemia is due, at least in part, to the minimization of autophagic flux disturbance and inhibition of apoptosis. Article Published Date : Oct 31, 2016

Abstract Title: Impact of intermittent fasting on health and disease processes. Abstract Source: Ageing Res Rev. 2016 Oct 31. Epub 2016 Oct 31. PMID: 27810402 Abstract Author(s): Mark P Mattson, Valter D Longo, Michelle Harvie Article Affiliation: Mark P Mattson Abstract: Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16-48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer's disease Parkinson's disease and stroke. Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging. Article Published Date : Oct 30, 2016

Abstract Title: Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Abstract Source: Cancer Cell. 2016 Jul 11 ;30(1):147-60. PMID: 27411589 Abstract Author(s): Federico Pietrocola, Jonathan Pol, Erika Vacchelli, Shuan Rao, David P Enot, Elisa E Baracco, Sarah Levesque, Francesca Castoldi, Nicolas Jacquelot, Takahiro Yamazaki, Laura Senovilla, Guillermo Marino, Fernando Aranda, Sylvère Durand, Valentina Sica, Alexis Chery, Sylvie Lachkar, Verena Sigl, Norma Bloy, Aitziber Buque, Simonetta Falzoni, Bernhard Ryffel, Lionel Apetoh, Francesco Di Virgilio, Frank Madeo, Maria Chiara Maiuri, Laurence Zitvogel, Beth Levine, Josef M Penninger, Guido Kroemer Article Affiliation: Federico Pietrocola Abstract: Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. Article Published Date : Jul 10, 2016

Abstract Title: Role of therapeutic fasting in women's health: An overview. Abstract Source: J Midlife Health. 2016 Apr-Jun;7(2):61-4. PMID: 27499591 Abstract Author(s): Pradeep M K Nair, Pranav G Khawale Article Affiliation: Pradeep M K Nair Abstract: Fasting is a therapeutic tool practiced since millennia by different cultures and medical systems heterogeneously. PubMed and Google Scholar search engines were searched using the keywords"fasting,""intermittent fasting,""calorie restriction,""women's health,""women's disorders,""fasting and aging,"and"fasting and health."All the animal and human studies which address women's health and disorders were included in the review. Fasting has shown to improve the reproductive and mental health. It also prevents as well as ameliorates cancers and musculoskeletal disorders which are common in middle-aged and elderly women. The present studies available have limitations such as majority of the studies are preclinical studies and human studies are with lesser sample size. Future studies should address this gap by designing medically supervised fasting techniques to extract better evidence. Nevertheless, fasting can be prescribed as a safe medical intervention as well as a lifestyle regimen which can improve women's health in many folds. Article Published Date : Mar 31, 2016

Abstract Title: Cinnamaldehyde supplementation prevents fasting-induced hyperphagia, lipid accumulation, and inflammation in high-fat diet-fed mice. Abstract Source: Biofactors. 2016 Mar-Apr;42(2):201-11. Epub 2016 Feb 19. PMID: 26893251 Abstract Author(s): Pragyanshu Khare, Sneha Jagtap, Yachna Jain, Ritesh K Baboota, Priyanka Mangal, Ravneet K Boparai, Kamlesh K Bhutani, Shyam S Sharma, Louis S Premkumar, Kanthi K Kondepudi, Kanwaljit Chopra, Mahendra Bishnoi Article Affiliation: Pragyanshu Khare Abstract: Cinnamaldehyde, a bioactive component of cinnamon, is increasingly gaining interest for its preventive and therapeutic effects against metabolic complications like type-2 diabetes. This study is an attempt to understand the effect of cinnamaldehyde in high-fat diet (HFD)-associated increase in fasting-induced hyperphagia and related hormone levels, adipose tissue lipolysis and inflammation, and selected cecal microbial count in mice. Cinnamaldehyde, at 40µM dose, prevented lipid accumulation and altered gene expression toward lipolytic phenotype in 3T3-L1 preadipocyte cell lines. In vivo, cinnamaldehyde coadministration prevented HFD-induced body weight gain, decreased fasting-induced hyperphagia, as well as circulating leptin and leptin/ghrelin ratio. In addition to that, cinnamaldehyde altered serum biochemical parameters related to lipolysis, that is, glycerol and free fatty acid levels. At transcriptional level, cinnamaldehyde increased anorectic gene expression in hypothalamus and lipolytic gene expression in visceral white adipose tissue. Furthermore, cinnamaldehyde also decreased serum IL-1β and inflammatory gene expression in visceral white adipose tissue. However, cinnamaldehyde did not modulate the population of selected gut microbial (Lactobacillus, Bifidibaceria, and Roseburia) count in cecal content. In conclusion, cinnamaldehyde increased adipose tissue lipolysis, decreased fasting-induced hyperphagia, normalized circulating levels of leptin/ghrelin ratio, and reduced inflammation in HFD-fed mice, which augurs well for its antiobesity role. Article Published Date : Feb 29, 2016

Abstract Title: Docosahexaenoic acid-supplementation prior to fasting prevents muscle atrophy in mice. Abstract Source: J Cachexia Sarcopenia Muscle. 2016 Feb 15. Epub 2016 Feb 15. PMID: 27239420 Abstract Author(s): Christiane Deval, Frédéric Capel, Brigitte Laillet, Cécile Polge, Daniel Béchet, Daniel Taillandier, Didier Attaix, Lydie Combaret Article Affiliation: Christiane Deval Abstract: BACKGROUND: Muscle wasting prevails in numerous diseases (e.g. diabetes, cardiovascular and kidney diseases, COPD,…) and increases healthcare costs. A major clinical issue is to devise new strategies preventing muscle wasting. We hypothesized that 8-week docosahexaenoic acid (DHA) supplementation prior to fasting may preserve muscle mass in vivo. METHODS: Six-week-old C57BL/6 mice were fed a DHA-enriched or a control diet for 8 weeks and then fasted for 48 h. RESULTS: Feeding mice a DHA-enriched diet prior to fasting elevated muscle glycogen contents, reduced muscle wasting, blocked the 55% decrease in Akt phosphorylation, and reduced by 30-40% the activation of AMPK, ubiquitination, or autophagy. The DHA-enriched diet fully abolished the fasting induced-messenger RNA (mRNA) over-expression of the endocannabinoid receptor-1. Finally, DHA prevented or modulated the fasting-dependent increase in muscle mRNA levels for Rab18, PLD1, and perilipins, which determine the formation and fate of lipid droplets, in parallel with muscle sparing. CONCLUSIONS: These data suggest that 8-week DHA supplementation increased energy stores that can be efficiently mobilized, and thus preserved muscle mass in response to fasting through the regulation of Akt- and AMPK-dependent signalling pathways for reducing proteolysis activation. Whether a nutritional strategy aiming at increasing energy status may shorten recovery periods in clinical settings remains to be tested. Article Published Date : Feb 14, 2016

Abstract Title: A Single Bout of Fasting (24 h) Reduces Basal Cytokine Expression and Minimally Impacts the Sterile Inflammatory Response in the White Adipose Tissue of Normal Weight F344 Rats. Abstract Source: Mediators Inflamm. 2016 ;2016:1698071. Epub 2016 Dec 18. PMID: 28077915 Abstract Author(s): Kristin J Speaker, Madeline M Paton, Stewart S Cox, Monika Fleshner Article Affiliation: Kristin J Speaker Abstract: Sterile inflammation occurs when inflammatory proteins are increased in blood and tissues by nonpathogenic states and is a double-edged sword depending on its cause (stress, injury, or disease), duration (transient versus chronic), and inflammatory milieu. Short-term fasting can exert a host of health benefits through unknown mechanisms. The following experiment tested if a 24 h fast would modulate basal and stress-evoked sterile inflammation in plasma and adipose. Adult male F344 rats were either randomized to ad libitum access to food or fasted for 24 h prior to 0 (control), 10, or 100, 1.5 mA-5 s intermittent, inescapable tail shocks (IS). Glucose, nonesterified free fatty acids (NEFAs), insulin, leptin, and corticosterone were measured in plasma and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and IL-10 in plasma, and subcutaneous, intraperitoneal, and visceral compartments of white adipose tissue (WAT). In control rats, a 24 h fastreduced all measured basal cytokines in plasma and visceral WAT, IL-1β and IL-6 in subcutaneous WAT, and IL-6 in intraperitoneal WAT. In stressed rats (IS), fasting reduced visceral WAT TNF-α, subcutaneous WAT IL-1β, and plasma insulin and leptin. Short-term fasting may thus prove to be a usefuldietary strategy for reducing peripheral inflammatory states associated with visceral obesity and chronic stress. Article Published Date : Dec 31, 2015

Abstract Title: Fasting-induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health. Abstract Source: EMBO Mol Med. 2016 ;8(6):654-69. Epub 2016 Jun 1. PMID: 27137487 Abstract Author(s): Jessica Fuhrmeister, Annika Zota, Tjeerd P Sijmonsma, Oksana Seibert, Şahika Cıngır, Kathrin Schmidt, Nicola Vallon, Roldan M de Guia, Katharina Niopek, Mauricio Berriel Diaz, Adriano Maida, Matthias Blüher, Jürgen G Okun, Stephan Herzig, Adam J Rose Article Affiliation: Jessica Fuhrmeister Abstract: Recent studies have demonstrated that repeated short-term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered"growth arrest and DNA damage-inducible"GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre-diabetes and type 2 diabetes, in both mice and humans. Using whole-body knockout mice as well as liver/hepatocyte-specific gain- and loss-of-function strategies, we revealed arole for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity-driven hyperglycaemia. In summary, fasting stress-induced GADD45β represents a liver-specific molecular event promoting adaptive metabolic function. Article Published Date : Dec 31, 2015

Abstract Title: Fasting and Caloric Restriction in Cancer Prevention and Treatment. Abstract Source: Recent Results Cancer Res. 2016;207:241-66. PMID: 27557543 Abstract Author(s): Sebastian Brandhorst, Valter D Longo Article Affiliation: Sebastian Brandhorst Abstract: Cancer is the second leading cause of death in the USA and among the leading major diseases in the world. It is anticipated to continue to increase because of the growth of the aging population and prevalence of risk factors such as obesity, smoking, and/or poor dietary habits. Cancer treatment has remained relatively similar during the past 30 years with chemotherapy and/or radiotherapy in combination with surgery remaining the standard therapies although novel therapies are slowly replacing or complementing the standard ones. According to the American Cancer Society, the dietary recommendation for cancer patients receiving chemotherapyis to increase calorie and protein intake. In addition, there are no clear guidelines on the type of nutrition that could have a major impact on cancer incidence. Yet, various forms of reduced caloric intake such as calorie restriction (CR) or fasting demonstrate a wide range of beneficial effectsable to help prevent malignancies and increase the efficacy of cancer therapies. Whereas chronic CR provides both beneficial and detrimental effects as well as major compliance challenges, periodic fasting (PF), fasting-mimicking diets (FMDs), and dietary restriction (DR) without a reduction in calories are emerging as interventions with the potential to be widely used to prevent and treat cancer. Here, we review preclinical and preliminary clinical studies on dietary restriction and fasting and their role in inducing cellular protection and chemotherapy resistance. Article Published Date : Dec 31, 2015

Abstract Title: Enhanced Therapeutic Efficacy in Cancer Patients by Short-term Fasting: The Autophagy Connection. Abstract Source: Front Oncol. 2016 ;6:242. Epub 2016 Nov 14. PMID: 27896219 Abstract Author(s): Gustav van Niekerk, Suzèl M Hattingh, Anna-Mart Engelbrecht Article Affiliation: Gustav van Niekerk Abstract: Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy toward cell maintenance and repair processes, rather than growth and proliferation. However, fasting is also known to upregulate autophagy, an evolutionarily conserved catabolic process that is upregulated in response to various cell stressors. Here, we review a number of mechanisms by which fasting-induced autophagy may have an impact on both chemo-tolerance and chemo-sensitization. First, fasting may exert a protective effect by mobilizing autophagic components prior to chemo-induction. In turn, the autophagic apparatus can be repurposed for removing cellular components damaged by chemotherapy. Autophagy also plays a key role in epitope expression as well as in modulating inflammation. Chemo-sensitization resulting from fasting may in fact be an effect of enhanced immune surveillance as a result of better autophagy-dependent epitope processing. Finally, autophagy is involved in host defense against viruses, and aspects of the autophagic process are also often targets for viral subversion. Consequently, altering autophagic flux by fasting may alter viral infectivity. These observations suggest that fasting-induced autophagy may have an impact on therapeutic efficacy in various oncological contexts. Article Published Date : Dec 31, 2015

Abstract Title: Safety and feasibility of fasting in combination with platinum-based chemotherapy. Abstract Source: BMC Cancer. 2016 ;16(1):360. Epub 2016 Jun 10. PMID: 27282289 Abstract Author(s): Tanya B Dorff, Susan Groshen, Agustin Garcia, Manali Shah, Denice Tsao-Wei, Huyen Pham, Chia-Wei Cheng, Sebastian Brandhorst, Pinchas Cohen, Min Wei, Valter Longo, David I Quinn Article Affiliation: Tanya B Dorff Abstract: BACKGROUND: Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients. METHODS: 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay.Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. RESULTS: The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. CONCLUSION: Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. TRIAL REGISTRATION: NCT00936364 , registered propectively on July 9, 2009. Article Published Date : Dec 31, 2015

Abstract Title: The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study. Abstract Source: BMC Cancer. 2015 Oct 5 ;15:652. Epub 2015 Oct 5. PMID: 26438237 Abstract Author(s): Stefanie de Groot, Maaike P G Vreeswijk, Marij J P Welters, Gido Gravesteijn, Jan J W A Boei, Anouk Jochems, Daniel Houtsma, Hein Putter, Jacobus J M van der Hoeven, Johan W R Nortier, Hanno Pijl, Judith R Kroep Article Affiliation: Stefanie de Groot Abstract: BACKGROUND: Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC). METHODS: Eligible patients had HER2-negative, stage II/III BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) were randomized to fast 24 h before and after commencing chemotherapy, or to eat according to the guidelines for healthy nutrition. Toxicity in the two groups was compared. Chemotherapy-induced DNA damage in peripheral blood mononuclear cells (PBMCs) was quantified by the level ofγ-H2AX analyzed by flow cytometry. RESULTS: Thirteen patients were included of whom seven were randomized to the STF arm. STF was well tolerated. Mean erythrocyte- and thrombocyte counts 7 days post-chemotherapy were significantly higher (P = 0.007, 95 % CI 0.106-0.638 and P = 0.00007, 95 % CI 38.7-104, respectively) in the STF group compared to the non-STF group. Non-hematological toxicity did not differ between the groups. Levels ofγ-H2AX were significantly increased 30 min post-chemotherapy in CD45 + CD3- cells in non-STF, but not in STF patients. CONCLUSIONS: STF during chemotherapy was well tolerated and reduced hematological toxicity of TAC in HER2-negative BC patients. Moreover, STF may reduce a transient increase in, and/or induce a faster recovery of DNA damage in PBMCs after chemotherapy. Larger studies, investigating a longer fasting period, are required to generate more insight into the possible benefits of STF during chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01304251 , March 2011. Article Published Date : Oct 04, 2015

Abstract Title: A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Abstract Source: Cell Metab. 2015 Jul 7 ;22(1):86-99. Epub 2015 Jun 18. PMID: 26094889 Abstract Author(s): Sebastian Brandhorst, In Young Choi, Min Wei, Chia Wei Cheng, Sargis Sedrakyan, Gerardo Navarrete, Louis Dubeau, Li Peng Yap, Ryan Park, Manlio Vinciguerra, Stefano Di Biase, Hamed Mirzaei, Mario G Mirisola, Patra Childress, Lingyun Ji, Susan Groshen, Fabio Penna, Patrizio Odetti, Laura Perin, Peter S Conti, Yuji Ikeno, Brian K Kennedy, Pinchas Cohen, Todd E Morgan, Tanya B Dorff, Valter D Longo Article Affiliation: Sebastian Brandhorst Abstract: Prolonged fasting (PF) promotes stress resistance, but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. In mice, 4 days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems, an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss. In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease, and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan. Article Published Date : Jul 06, 2015

Abstract Title: Regulation of energy metabolism by inflammation: a feedback response in obesity and calorie restriction. Abstract Source: Aging (Albany NY). 2010 Jun;2(6):361-8. PMID: 20606248 Abstract Author(s): Jianping Ye, Jeffrey N Keller Article Affiliation: Pennington Biomedical Research Center, Louisiana State University System, LA 70808, USA. Abstract: Caloric restriction (CR), in the absence of malnutrition, delays aging and prevents aging-related diseases through multiple mechanisms. A reduction in chronic inflammation is widely observed in experimental models of caloric restriction. The low inflammation status may contribute to the reduced incidence of osteoporosis, Alzheimer's disease, cardiovascular diseases and cancer in the aging subjects. The association of caloric restriction with low inflammation suggests a role of energy accumulation in the origin of the chronic inflammation. This point is enforced by recent advances in obesity research. Abundant literature on obesity suggests that chronic inflammation is a consequence of energy accumulation in the body. The emerging evidence strongly supports that the inflammatory response induces energy expenditure in a feedback manner to fight against energy surplus in obesity. If this feedback system is deficient (Inflammation Resistance), energy expenditure will be reduced and energy accumulation will lead to obesity. In this perspective, we propose that an increase in inflammation in obesity promotes energy expenditure with a goal to get rid of energy surplus. A decrease in inflammation under caloric restriction contributes to energy saving. Inflammation is a mechanism for energy balance in the body. Inflammation resistance will lead to obesity. We will review the recent literature in support of the viewpoints. Article Published Date : Jun 01, 2010

Abstract Title: Lemon detox diet reduced body fat, insulin resistance, and serum hs-CRP level without hematological changes in overweight Korean women. Abstract Source: Nutr Res. 2015 May ;35(5):409-20. Epub 2015 Apr 10. PMID: 25912765 Abstract Author(s): Mi Joung Kim, Jung Hyun Hwang, Hyun Ji Ko, Hye Bock Na, Jung Hee Kim Article Affiliation: Mi Joung Kim Abstract: The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes. Article Published Date : Apr 30, 2015

Abstract Title: Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. Abstract Source: J Clin Invest. 2015 ;2015. Epub 2015 Nov 3. PMID: 26529255 Abstract Author(s): Javier Traba, Miriam Kwarteng-Siaw, Tracy C Okoli, Jessica Li, Rebecca D Huffstutler, Amanda Bray, Myron A Waclawiw, Kim Han, Martin Pelletier, Anthony A Sauve, Richard M Siegel, Michael N Sack Article Affiliation: Javier Traba Abstract: BACKGROUND: Activation of the NLRP3 inflammasome is associated with metabolic dysfunction, and intermittent fasting has been shown to improve clinical presentation of NLRP3 inflammasome-linked diseases. As mitochondrial perturbations, which function as a damage-associated molecular pattern, exacerbate NLRP3 inflammasome activation, we investigated whether fasting blunts inflammasome activation via sirtuin-mediated augmentation of mitochondrial integrity. METHODS: We performed a clinical study of 19 healthy volunteers. Each subject underwent a 24-hour fast and then was fed a fixed-calorie meal. Blood was drawn during the fasted and fed states and analyzed for NRLP3 inflammasome activation. We enrolled an additional group of 8 healthy volunteers to assess the effects of the sirtuin activator, nicotinamide riboside, on NLRP3 inflammasome activation. RESULTS: In the fasting/refeeding study, individuals showed less NLRP3 inflammasome activation in the fasted state compared with that in refed conditions. In a human macrophage line, depletion of the mitochondrial-enriched sirtuin deacetylase SIRT3 increased NLRP3 inflammasome activation in association with excessive mitochondrial ROS production. Furthermore, genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in parallel with enhanced mitochondrial function in cultured cells and in leukocytes extracted from healthy volunteers and from refed individuals but not in those collected during fasting. CONCLUSIONS: Together, our data indicate that nutrient levels regulate the NLRP3 inflammasome, in part through SIRT3-mediated mitochondrial homeostatic control. Moreover, these results suggest that deacetylase-dependent inflammasome attenuation may be amenable to targeting in human disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT02122575 and NCT00442195. FUNDING: Division of Intramural Research, NHLBI of the NIH. Article Published Date : Dec 31, 2014

Abstract Title: Alpha lipoic acid induces hepatic fibroblast growth factor 21 expression via up-regulation of CREBH. Abstract Source: Biochem Biophys Res Commun. 2014 Dec 12 ;455(3-4):212-7. Epub 2014 Nov 5. PMID: 25449271 Abstract Author(s): Kwi-Hyun Bae, Ae-Kyung Min, Jung-Guk Kim, In-Kyu Lee, Keun-Gyu Park Article Affiliation: Kwi-Hyun Bae Abstract: Hepatic expression of fibroblast growth factor 21 (FGF21), one of the most promising therapeutic candidates for metabolic syndrome, is induced by multiple factors associated with fasting, including cyclic AMP response element-binding protein H (CREBH). Alpha lipoic acid (ALA), a naturally occurring thiol antioxidant, has been shown to induce metabolic changes that are similar to those induced by FGF21, including weight loss and increased energy expenditure. Here, we investigated the effect of ALA on hepatic FGF21 expression. ALA treatment enhanced CREBH and FGF21 mRNA expression and protein abundance in cultured hepatocytes. ALA increased FGF21 promoter activity by up-regulating CREBH expression and increasing CREBH binding to the FGF21 promoter, indicating that ALA up-regulates FGF21 at the transcriptional level. Moreover, inhibition of endogenous CREBH expression by siRNA attenuated ALA-induced FGF21 expression. Finally, treatment of mice with ALA enhanced fasting-induced up-regulation of CREBH and FGF21 in the liver and inhibited feeding-induced suppression of their expression. Consistently, ALA increased serum FGF21 levels in both fasted and fed mice. Collectively, these results indicate that ALA increases hepatic FGF21 expression via up-regulation of CREBH, identifying ALA as a novel positive regulator of FGF21. Article Published Date : Dec 11, 2014

Abstract Title: High-oleic peanuts: new perspective to attenuate glucose homeostasis disruption and inflammation related obesity. Abstract Source: Obesity (Silver Spring). 2014 Sep ;22(9):1981-8. Epub 2014 Jun 27. PMID: 24975522 Abstract Author(s): Raquel Duarte Moreira Alves, Ana Paula Boroni Moreira, Viviane Silva Macedo, Josefina Bressan, Rita de Cássia Gonçalves Alfenas, Richard Mattes, Neuza Maria Brunoro Costa Article Affiliation: Raquel Duarte Moreira Alves Abstract: OBJECTIVE: To evaluate the effects of acute and daily consumption of high-oleic peanuts (HOP) on inflammation and glucose homeostasis in overweight/obese men. METHODS: In a 4-week randomized clinical trial, males with body mass index of 29.8± 2.3 kg/m(2) and aged 18-50 years were assigned to the groups: control (CT, n = 22); conventional peanuts (CVP, n = 22); or HOP (n = 21). They followed a hypocaloric-diet with or without 56 g/day of CVP or HOP. Main outcomes were changes in fasting blood biomarkers and postprandial insulin, glucose, tumor necrosis factor-alfa (TNF-α), and interleukin-10 (IL-10) responses after acute peanut intake. RESULTS: At baseline, HOP showed significantly lower postprandial responses of glucose, insulin, and TNF-α than CVP and CT. Changes in fasting blood biomarkers did not differ between groups after the 4-week intervention. However, within groups, total cholesterol decreased in CT, and all groups reduced High-density lipoprotein (HDL-c). Triglycerides were reduced in HOP and CVP. IL-10 increased significantly in all groups while only the CT and CVP showed increased TNF-α after intervention. CONCLUSION: Acute high-oleic peanut consumption leads to stronger moderation of postprandial glucose, insulin, and TNF-α concentrations than CVP and control meal intake. Whether daily intake of high-oleic peanuts has additional benefits to CVP remains uncertain. Article Published Date : Aug 31, 2014

Abstract Title: Intermittent fasting attenuates inflammasome activity in ischemic stroke. Abstract Source: Exp Neurol. 2014 Jul ;257:114-9. Epub 2014 May 5. PMID: 24805069 Abstract Author(s): David Yang-Wei Fann, Tomislav Santro, Silvia Manzanero, Alexander Widiapradja, Yi-Lin Cheng, Seung-Yoon Lee, Prasad Chunduri, Dong-Gyu Jo, Alexis M Stranahan, Mark P Mattson, Thiruma V Arumugam Article Affiliation: David Yang-Wei Fann Abstract: Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Article Published Date : Jun 30, 2014

Abstract Title: The antidiabetic action of camel milk in experimental type 2 diabetes mellitus: an overview on the changes in incretin hormones, insulin resistance, and inflammatory cytokines. Abstract Source: Horm Metab Res. 2014 Jun ;46(6):404-11. Epub 2014 Mar 13. PMID: 24627103 Abstract Author(s): A A Korish Article Affiliation: A A Korish Abstract: Folk medicine stories accredited the aptitude of camel milk (CMK) as a hypoglycemic agent and recent studies have confirmed this in the diabetic patients and experimental animals. However, the mechanism(s) by which CMK influences glucose homeostasis is yet unclear. The current study investigated the changes in the glucose homeostatic parameters, the incretin hormones, and the inflammatory cytokines in the CMK-treated diabetic animals. A model of type 2 diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin 40 mg/kg/day for 4 repeated doses. Camel milk treatment was administered for 8 weeks. The changes in glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic peptide (GIP), glucose tolerance, fasting and glucose-stimulated insulin secretion, insulin resistance (IR), TNF-α, TGF-β1, lipid profile, atherogenic index (AI), and body weight were investigated. The untreated diabetic animals showed hyperglycemia, increased HOMA-IR, hyperlipidemia, elevated AI, high serum incretins [GLP-1 and GIP], TNF-α, and TGF-β1 levels and weight loss as compared with the control group. Camel milk treatment to the diabetic animals resulted in significant lowered fasting glucose level, hypolipidemia, decreased HOMA-IR, recovery of insulin secretion, weight gain, and no mortality during the study. Additionally, CMK inhibits the diabetes-induced elevation in incretin hormones, TNF-α and TGF-β1 levels. The increase in glucose-stimulated insulin secretion, decreased HOMA-IR, modulation of the secretion and/or the action of incretins, and the anti-inflammatory effect are anticipated mechanisms to the antidiabetic effect of CMK and suggest it as a valuable adjuvant antidiabetic therapy. Article Published Date : May 31, 2014

Abstract Title: Regular intake of high-oleic peanuts improves fat oxidation and body composition in overweight/obese men pursuing a energy-restricted diet. Abstract Source: Obesity (Silver Spring). 2014 Jun ;22(6):1422-9. Epub 2014 Mar 27. PMID: 24639419 Abstract Author(s): Raquel Duarte Moreira Alves, Ana Paula Boroni Moreira, Viviane Silva Macedo, Rita de Cássia Gonçalves Alfenas, Josefina Bressan, Richard Mattes, Neuza Maria Brunoro Costa Article Affiliation: Raquel Duarte Moreira Alves Abstract: OBJECTIVE: Evaluate the effect of high-oleic and conventional peanuts within a hypocaloric-diet on energy metabolism and body composition. METHODS: This 4-week randomized clinical trial included males with BMI of 29.7 ± 2.4 kg m(-2) and aged between 18 and 50 years. Participants were assigned to the groups: control (CT, n = 22) that followed a hypocaloric-diet; conventional peanuts (CVP, n = 22) or high-oleic peanuts (HOP, n = 21) that received the hypocaloric-diet including (not adding) 56 g day(-1) of peanuts. Glucose, fat oxidation, and body fatness and lean mass were the main outcomes. RESULTS: Body weight and composition did not differ between groups. However, within group total body fat (kg) reduced with CVP and HOP, with a significant decrease in body fat percentage in HOP. While total lean mass (kg) decreased in CT, total lean mass (%) increased in HOP. Truncal lean mass decreased in the CT. At baseline, HOP had greater postprandial fat oxidation than the CVP. After 4-weeks, fasting fat oxidation increased in CVP and HOP. Fat oxidation increased in CT and HOP during the 200 min after meal intake compared to the fasting condition. CONCLUSION: Regular peanut consumption, especially the high-oleic type, within a hypocaloric-diet increased fat oxidation and reduced body fatness in overweigh and obese men. Article Published Date : May 31, 2014

Abstract Title: Vitamin D supplementation and serum levels of magnesium and selenium in type 2 diabetes mellitus patients: gender dimorphic changes. Abstract Source: Int J Vitam Nutr Res. 2014 ;84(1-2):27-34. PMID: 25835233 Abstract Author(s): Nasser M Al-Daghri, Khalid M Alkharfy, Nasiruddin Khan, Hanan A Alfawaz, Abdulrahman S Al-Ajlan, Sobhy M Yakout, Majed S Alokail Article Affiliation: Nasser M Al-Daghri Abstract: The aim of our study was to evaluate the effects of vitamin D supplementation on circulating levels of magnesium and selenium in patients with type 2 diabetes mellitus (T2DM). A total of 126 adult Saudi patients (55 men and 71 women, mean age 53.6±10.7 years) with controlled T2DM were randomly recruited for the study. All subjects were given vitamin D3 tablets (2000 IU/day) for six months. Follow-up mean concentrations of serum 25-hydroxyvitamin D [25-(OH) vitamin D] significantly increased in both men (34.1±12.4 to 57.8±17.0 nmol/L) andwomen (35.7±13.5 to 60.1±18.5 nmol/L, p<0.001), while levels of parathyroid hormone (PTH) decreased significantly in both men (1.6±0.17 to 0.96±0.10 pmol/L, p=0.003) and women (1.6±0.17 to 1.0±0.14 pmol/L, p=0.02). In addition, there was a significant increase in serum levels of selenium and magnesium in men and women (p-values<0.001 and 0.04, respectively) after follow-up. In women, a significant correlation was observed between delta change (variables at six months-variable at baseline) of serum magnesium versus high-density lipoprotein (HDL)-cholesterol (r=0.36, p=0.006) and fasting glucose (r=-0.33, p=0.01). In men, there was a significant correlation between serum selenium and triglycerides (r=0.32, p=0.04). Vitamin D supplementation improves serum concentrations of magnesium and selenium in a gender-dependent manner, which in turn could affect several cardiometabolic parameters such as glucose and lipids. Article Published Date : Dec 31, 2013

Abstract Title: Chronic intake of onion extract containing quercetin improved postprandial endothelial dysfunction in healthy men. Abstract Source: J Am Coll Nutr. 2013 ;32(3):160-4. PMID: 23885989 Abstract Author(s): Hideki Nakayama, Nobuaki Tsuge, Hiroshi Sawada, Yukihito Higashi Article Affiliation: Hideki Nakayama Abstract: BACKGROUND: Epidemiologic studies have shown that dietary flavonoids reduce the risk of cardiovascular events. Onion is rich in quercetin, a strong antioxidant flavonoid. In some in vitro studies, quercetin improved endothelial function associated with atherosclerosis, a leading cause of cardiovascular events. OBJECTIVE: The aim of this study was to determine whether chronic onion extract intake would improve postprandial endothelial dysfunction induced by an oral maltose load in healthy men. METHODS: Healthy men (44±10 years, n=23) received 4.3 g of onion extract (containing 51 mg of quercetin) once a day for 30 days. Before and after the chronic onion extract intake, fasting and postprandial flow-mediated vasodilation (FMD) responses were measured. RESULTS: Maltose loading significantly decreased FMD both before and after chronic onion extract intake (p=0.000037 and p=0.0035, respectively). The chronic onion extract intake did not significantly affect fasting FMD (p=0.069) but improved the postprandial FMD significantly from 5.1%±2.2% to 6.7%±2.6% (p=0.00015). The chronic onion extract intake did not alter systemic and forearm hemodynamics. CONCLUSION: These findings suggest that chronic onion extract intake ameliorates postprandial endothelial dysfunction in healthy men and may be beneficial for improving cardiovascular health. Article Published Date : Dec 31, 2012

Abstract Title: Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Abstract Source: Nature. 2012 Sep 13 ;489(7415):318-21. PMID: 22932268 Abstract Author(s): Julie A Mattison, George S Roth, T Mark Beasley, Edward M Tilmont, April M Handy, Richard L Herbert, Dan L Longo, David B Allison, Jennifer E Young, Mark Bryant, Dennis Barnard, Walter F Ward, Wenbo Qi, Donald K Ingram, Rafael de Cabo Article Affiliation: Julie A Mattison Abstract: Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented inyoung and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate. Article Published Date : Sep 12, 2012

Abstract Title: Potentiation of dietary restriction-induced lifespan extension by polyphenols. Abstract Source: Biochim Biophys Acta. 2012 Jan 11 ;1822(4):522-526. Epub 2012 Jan 11. PMID: 22265987 Abstract Author(s): Daniel J Aires, Graham Rockwell, Ting Wang, Jennifer Frontera, Jo Wick, Wenfang Wang, Marija Tonkovic-Capin, Jianghua Lu, Lezi E, Hao Zhu, Russell H Swerdlow Article Affiliation: Division of Dermatology, University of Kansas, KS 66160, USA. Abstract: Dietary restriction (DR) extends lifespan across multiple species including mouse. Antioxidant plant extracts rich in polyphenols have also been shown to increase lifespan. We hypothesized that polyphenols might potentiate DR-induced lifespan extension. Twenty week old C57BL/6 mice were placed on one of three diets: continuous feeding (control), alternate day chow (Intermittent fed, IF), or IF supplemented with polyphenol antioxidants (PAO) from blueberry, pomegranate, and green tea extracts (IF+PAO). Both IF and IF+PAO groups outlived the control group and the IF+PAO group outlived the IF group (all p<0.001). In the brain, IF induced the expression of inflammatory genes and p38 MAPK phosphorylation, while the addition of PAO reduced brain inflammatory gene expression and p38 MAPK phosphorylation. Our data indicate that while IF overall promotes longevity, some aspects of IF-induced stress may paradoxically lessen this effect. Polyphenol compounds, in turn, may potentiate IF-induced longevity by minimizing specific components of IF-induced cell stress. Article Published Date : Jan 11, 2012

Abstract Title: The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. Abstract Source: Elife. 2012 ;1:e00065. Epub 2012 Oct 15. PMID: 23066506 Abstract Author(s): Yuan Zhang, Yang Xie, Eric D Berglund, Katie Colbert Coate, Tian Teng He, Takeshi Katafuchi, Guanghua Xiao, Matthew J Potthoff, Wei Wei, Yihong Wan, Ruth T Yu, Ronald M Evans, Steven A Kliewer, David J Mangelsdorf Article Affiliation: Yuan Zhang Abstract: Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic growth and causes bone loss. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting markers of NAD+ metabolism or AMP kinase and mTOR signaling. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used to extend lifespan in other species.DOI:http://dx.doi.org/10.7554/eLife.00065.001. Article Published Date : Dec 31, 2011

Abstract Title: Cardiovascular protection afforded by caloric restriction: essential role of nitric oxide synthase. Abstract Source: Geriatr Gerontol Int. 2011 Apr;11(2):143-56. Epub 2011 Jan 4. PMID: 21199236 Abstract Author(s): Ken Shinmura Article Affiliation: Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. Abstract: Caloric restriction is an established intervention, of which anti-aging effects are scientifically proven. It has pleiotropic effects on the cardiovascular system: vascular protection, improvement of myocardial ischemic tolerance and retardation of cardiac senescence. First, increasing evidence from both experimental and clinical studies supports the concept that "a man is as old as his arteries". Caloric restriction could prevent the progression of atherosclerosis and vascular aging through direct and indirect mechanisms. Second, the hearts of senescent animals are more susceptible to ischemia than those of young animals. We demonstrated that short-term and prolonged caloric restriction confers cardioprotection against ischemia/reperfusion injury in young and aged rodents. Furthermore, we showed that the increase in circulating adiponectin levels and subsequent activation of adenosine monophosphate-activated protein kinase are necessary for the cardioprotection afforded by short-term caloric restriction. In contrast, the mechanisms by which prolonged caloric restriction confers cardioprotection seem more complicated. Adiponectin, nitric oxide synthase and sirtuin may form a network of cardiovascular protection during caloric restriction. Recently, by using genetically engineered mice, we found that, in addition to endothelial nitric oxide synthase, neuronal nitric oxide synthase plays an essential role in the development of cardioprotection afforded by prolonged caloric restriction. Third, long-term caloric restriction has cardiac-specific effects that attenuate the age-associated impairment seen in left ventricular diastolic function. It is possible that long-term caloric restriction partially retards cardiac senescence by attenuating oxidative damage in the aged heart. Overall, we strongly believe that caloric restriction could reduce morbidity and mortality of cardiovascular events in humans. Geriatr Gerontol Int 2011; 11: 143-156. Article Published Date : Apr 01, 2011

Abstract Title: Comparative transcriptional pathway bioinformatic analysis of dietary restriction, Sir2, p53 and resveratrol life span extension in Drosophila. Abstract Source: Cell Cycle. 2011 Mar 15;10(6). Epub 2011 Mar 15. PMID: 21325893 Abstract Author(s): Michael Antosh, Rachel Whitaker, Adam Kroll, Suzanne Hosier, Chengyi Chang, Johannes Bauer, Leon Cooper, Nicola Neretti, Stephen L Helfand Article Affiliation: Brown University; Providence, RI USA. Abstract: A multiple comparison approach using whole genome transcriptional arrays was used to identify genes and pathways involved in calorie restriction/dietary restriction (DR) life span extension in Drosophila. Starting with a gene centric analysis comparing the changes in common between DR and two DR related molecular genetic life span extending manipulations, Sir2 and p53, lead to a molecular confirmation of Sir2 and p53's similarity with DR and the identification of a small set of commonly regulated genes. One of the identified upregulated genes, takeout, known to be involved in feeding and starvation behavior, and to have sequence homology with Juvenile Hormone (JH) binding protein, was shown to directly extend life span when specifically overexpressed. Here we show that a pathway centric approach can be used to identify shared physiological pathways between DR and Sir2, p53 and resveratrol life span extending interventions. The set of physiological pathways in common among these life span extending interventions provides an initial step toward defining molecular genetic and physiological changes important in life span extension. The large overlap in shared pathways between DR, Sir2, p53 and resveratrol provide strong molecular evidence supporting the genetic studies linking these specific life span extending interventions. Article Published Date : Mar 15, 2011

Abstract Title: Proposed biomolecular theory of fasting during fevers due to infection. Abstract Source: Am J Gastroenterol. 2011 Jan 11. Epub 2011 Jan 11. PMID: 11703168 Abstract Author(s): E Yarnell Abstract: The folk admonition to starve a fever may have a scientific basis. Fevers due to infectious organisms that produce neuraminidase (sialidase) may contribute to the pathophysiology of autoimmune conditions. Neuraminidase unmasks host cellular lectins that interact with food lectins and can induce human leukocyte antigen type II (HLA II) expression. HLA II can then bind food lectins and serve as targets for antibody production. Some of these antibodies can then cross-react and attack healthy tissue, inducing disease. The example of insulin-dependent diabetes mellitus is discussed, helping to explain why infectious organisms and dairy product ingestion appear to be linked to some cases of this disease. Genetic variants and other factors may contribute to disease pathogenesis, so this model does not explain all instances of autoimmune disease. Fasting as a way to avoid the process by not introducing food lectins is briefly reviewed. Neuraminidase inhibitors might be useful in preventing genesis of autoimmunity during infection, although this possibility has not been formally tested. Article Published Date : Jan 11, 2011

Abstract Title: Cognitive performances are selectively enhanced during chronic caloric restriction or resveratrol supplementation in a primate. Abstract Source: PLoS One. 2011;6(1):e16581. Epub 2011 Jan 31. PMID: 21304942 Abstract Author(s): Alexandre Dal-Pan, Fabien Pifferi, Julia Marchal, Jean-Luc Picq, Fabienne Aujard, Article Affiliation: Mécanismes Adaptatifs et Evolution, UMR 7179 Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, Brunoy, France. Abstract: Effects of an 18-month treatment with a moderate, chronic caloric restriction (CR) or an oral supplementation with resveratrol (RSV), a potential CR mimetic, on cognitive and motor performances were studied in non-human primates, grey mouse lemurs (Microcebus murinus).Thirty-three adult male mouse lemurs were assigned to three different groups: a control (CTL) group fed ad libitum, a CR group fed 70% of the CTL caloric intake, and an RSV group (RSV supplementation of 200 mg.kg(-1).day(-1)) fed ad libitum. Three different cognitive tests, two motor tests, one emotional test and an analysis of cortisol level were performed in each group.Compared to CTL animals, CR or RSV animals did not show any change in motor performances evaluated by rotarod and jump tests, but an increase in spontaneous locomotor activity was observed in both groups. Working memory was improved by both treatments in the spontaneous alternation task. Despite a trend for CR group, only RSV supplementation increased spatial memory performances in the circular platform task. Finally, none of these treatments induced additional stress to the animals as reflected by similar results in the open field test and cortisol analyses compared to CTL animals.The present data provided the earliest evidence for a beneficial effect of CR or RSV supplementation on specific cognitive functions in a primate. Taken together, these results suggest that RSV could be a good candidate to mimic long-term CR effects and support the growing evidences that nutritional interventions can have beneficial effects on brain functions even in adults. Article Published Date : Jan 01, 2011

Abstract Title: Preoperative dietary restriction reduces hepatic tumor load by reduced E-selectin-mediated adhesion in mice. Abstract Source: J Surg Oncol. 2010 Sep 15;102(4):348-53. PMID: 20672315 Abstract Author(s): Tessa M van Ginhoven, Jan Willem van den Berg, Willem A Dik, Jan N M Ijzermans, Ron W F de Bruin Article Affiliation: Department of Surgery, Erasmus MC, Rotterdam, The Netherlands. Abstract: BACKGROUND: Inflammatory responses facilitate metastasis by increasing expression of adhesion molecules. Dietary restriction (30% reduction in daily calorie intake) reduces the expression of adhesion molecules and protects against surgically induced inflammation. DR might therefore beneficially interfere with surgery-induced inflammation and subsequent adhesion of circulating tumor cells. METHODS: BALB/c mice were subjected to 2 weeks dietary restriction prior to inoculation with tumor cells. Intra-splenic injection of 5.0 x 10(4) C26-colon carcinoma cells was followed by splenectomy. Hepatic tumor load was scored after 10 days as a percentage (tumor surface/total liver surface) on H&E stained sections. Liver mRNA expression of adhesion molecules was determined and the effect of serum from dietary restriction mice on in vitro tumor growth and adhesion capacity was assessed. RESULTS: Preoperative dietary restriction significantly reduced mRNA expression levels of E-selectin (P = 0.0087) and hepatic tumor load (P = 0.036). Dietary restriction serum did not affect in vitro cell growth but reduced in vitro adhesion of C26 cells to endothelial cells (P = 0.0043). CONCLUSIONS: Preoperative dietary restriction reduces hepatic tumor load after injection with tumor cells. Reduced adhesion to endothelial cells and reduced mRNA expression of E-selectin suggest that dietary restriction reduces tumor load by lowering the adhesion of circulating tumor cells to hepatic vascular endothelium. Article Published Date : Sep 15, 2010

Abstract Title: Dietary methionine restriction improves colon tight junction barrier function and alters claudin expression pattern. Abstract Source: Am J Physiol Cell Physiol. 2010 Aug 25. Epub 2010 Aug 25. PMID: 20739626 Abstract Author(s): Arivudainambi Ramalingam, Xuexuan Wang, Melissa Gabello, M Carmen Valenzano, Alejandro P Soler, Akihiro Ko, Patrice J Morin, James M Mullin Article Affiliation: 1Lankenau Institute for Medical Research. Abstract: The beneficial effects of caloric restriction in increasing longevity and forestalling age-related diseases are well known. Dietary restriction of methionine also renders similar benefits. We recently showed in a renal epithelial cell culture system that reduction of culture medium methionine by 80% resulted in altered tight junctional (TJ) claudin composition and also improved epithelial barrier function (51). In the current study, we examined the effect of dietary restriction of methionine on TJ barrier function in rat gastrointestinal tissue in order to see if this phenomenon also holds true in a tissue model and for a different epithelial cell type. After 28 days on methionine-restricted (MR) diet, rats showed small but significant reductions in the plasma and (intracellular) colonocyte levels of methionine. Colon mucosal sheets from rats on MR diet showed increased transepithelial electrical resistance with concomitant decrease in paracellular diffusion of (14)C-D-mannitol suggesting improved barrier function relative to rats on control diet. This improved barrier function could not be explained by changes in colon crypt length or frequency. Neither was the colonocyte mitotic index nor the apoptotic frequency altered significantly. However, TJ composition/structure was being altered by the MR diet. RT-PCR and Western blot analysis showed an increase in the abundance of claudin-3 and an apparent change in the post-translational modification of occludin, data reinforcing a paracellular barrier alteration. Overall, our data suggest that reduction in dietary intake of methionine results in improved epithelial barrier function by inducing altered TJ protein composition. Article Published Date : Aug 25, 2010

Abstract Title: Ameliorative potential of resveratrol on proinflammatory cytokines, hyperglycemia mediated oxidative stress, and pancreatic beta-cell dysfunction in streptozotocin-nicotinamide-induced diabetic rats. Abstract Source: J Cell Physiol. 2010 Aug;224(2):423-32. PMID: 20333650 Abstract Author(s): P Palsamy, S Subramanian Article Affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India. Abstract: Chronic exposure of pancreatic beta-cells to supraphysiologic glucose causes adverse beta-cell dysfunction. Thus, the present study was aimed to investigate the hypothesis that oral administration of resveratrol attenuates hyperglycemia, proinflammatory cytokines and antioxidant competence and protects beta-cell ultrastructure in streptozotocin-nicotinamide-induced diabetic rats. Oral administration of resveratrol (5 mg/kg body weight) to diabetic rats for 30 days showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), TNF-alpha, IL-1beta, IL-6, NF-kappaB p65 unit and nitric oxide (NO) with concomitant elevation in plasma insulin. Further, resveratrol treated diabetic rats elicited a notable attenuation in the levels of lipid peroxides, hydroperoxides and protein carbonyls in both plasma and pancreatic tissues. The diminished activities of pancreatic superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione-S-transferase (GST) as well as the decreased levels of plasma ceruloplasmin, vitamin C, vitamin E and reduced glutathione (GSH) in diabetic rats were reverted to near normalcy by resveratrol administration. Based on histological and ultrastructural observations, it is first-time reported that the oral administration of resveratrol may effectively rescue beta-cells from oxidative damage without affecting their function and structural integrity. The results of the present investigation demonstrated that resveratrol exhibits significant antidiabetic potential by attenuating hyperglycemia, enhancing insulin secretion and antioxidant competence in pancreatic beta-cells of diabetic rats. Article Published Date : Aug 01, 2010

Abstract Title: Short-term fasting induces profound neuronal autophagy. Abstract Source: Autophagy. 2010 Aug ;6(6):702-10. Epub 2010 Aug 14. PMID: 20534972 Abstract Author(s): Mehrdad Alirezaei, Christopher C Kemball, Claudia T Flynn, Malcolm R Wood, J Lindsay Whitton, William B Kiosses Article Affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA. Abstract: Disruption of autophagy--a key homeostatic process in which cytosolic components are degraded and recycled through lysosomes--can cause neurodegeneration in tissue culture and in vivo. Upregulation of this pathway may be neuroprotective, and much effort is being invested in developing drugs that cross the blood brain barrier and increase neuronal autophagy. One well-recognized way of inducing autophagy is by food restriction, which upregulates autophagy in many organs including the liver; but current dogma holds that the brain escapes this effect, perhaps because it is a metabolically privileged site. Here, we have re-evaluated this tenet using a novel approach that allows us to detect, enumerate and characterize autophagosomes in vivo. We first validate the approach by showing that it allows the identification and characterization of autophagosomes in the livers of food-restricted mice. We use the method to identify constitutive autophagosomes in cortical neurons and Purkinje cells, and we show that short-term fasting leads to a dramatic upregulation in neuronal autophagy. The increased neuronal autophagy is revealed by changes in autophagosome abundance and characteristics, and by diminished neuronal mTOR activity in vivo, demonstrated by a reduction in levels of phosphorylated S6 ribosomal protein in Purkinje cells. The increased abundance of autophagosomes in Purkinje cells was confirmed using transmission electron microscopy. Our data lead us to speculate that sporadic fasting might represent a simple, safe and inexpensive means to promote this potentially therapeutic neuronal response. Article Published Date : Jul 31, 2010

Abstract Title: Beneficial effects of dietary restriction in type 2 diabetic rats: the role of adipokines on inflammation and insulin resistance. Abstract Source: Br J Nutr. 2010 Jul;104(1):76-82. Epub 2010 Feb 24. PMID: 20178670 Abstract Author(s): Joana Crisóstomo, Lisa Rodrigues, Paulo Matafome, Carmen Amaral, Elsa Nunes, Teresa Louro, Pedro Monteiro, Raquel Seiça Article Affiliation: Faculty of Medicine, Institute of Physiology, University of Coimbra, Coimbra, Portugal. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: Inflammation plays an important role in diabetes mellitus and its complications. In this context, the negative cross-talk between adipose tissue and skeletal muscle leads to disturbances in muscle cell insulin signalling and induces insulin resistance. Because several studies have shown that energy restriction brings some benefits to diabetes, the aim of the present study was to evaluate the effects of dietary restriction on systemic and skeletal muscle inflammatory biomarkers, such C-reactive protein, adipokines and cytokines, and in insulin resistance in Goto-Kakizaki rats. This is an animal model of spontaneous non-obese type 2 diabetes with strongly insulin resistance and without dyslipidaemia. Animals were maintained during 2 months of dietary restriction (50 %) and were killed at 6 months of age. Some biochemical determinations were done using ELISA and Western blot. Data from the present study demonstrate that in Goto-Kakizaki rats the dietary restriction improved insulin resistance, NEFA levels and adipokine profile and ameliorated inflammatory cytokines in skeletal muscle. These results indicate that dietary restriction in type 2 diabetes enhances adipose tissue metabolism leading to an improved skeletal muscle insulin sensitivity. Article Published Date : Jul 01, 2010

Abstract Title: FoxO1 is involved in the antineoplastic effect of calorie restriction. Abstract Source: Aging Cell. 2010 Jun;9(3):372-82. Epub 2010 Mar 6. PMID: 20222901 Abstract Author(s): Haruyoshi Yamaza, Toshimitsu Komatsu, Saori Wakita, Carole Kijogi, Seongjoon Park, Hiroko Hayashi, Takuya Chiba, Ryoichi Mori, Tatsuo Furuyama, Nozomu Mori, Isao Shimokawa Article Affiliation: Department of Investigative Pathology, Nagasaki University, Japan. Abstract: The FoxO transcription factors may be involved in the antiaging effect of calorie restriction (CR) in mammals. To test the hypothesis, we used FoxO1 knockout heterozygotic (HT) mice, in which the FoxO1 mRNA level was reduced by 50%, or less, of that in wild-type (WT) mouse tissues. The WT and HT mice were fed ad libitum (AL) or 30% CR diets from 12 weeks of age. Aging- and CR-related changes in body weight, food intake, blood glucose, and insulin concentrations were similar between the WT and HT mice in the lifespan study. The response to oxidative stress, induced by intraperitoneal injection of 3-nitropropionic acid (3-NPA), was evaluated in the liver and hippocampus at 6 months of age. Several of the selected FoxO1-target genes for cell cycle arrest, DNA repair, apoptosis, and stress resistance were up-regulated in the WT-CR tissues after 3-NPA injection, while the effect was mostly diminished in the HT-CR tissues. Of these gene products, we focused on the nuclear p21 protein level in the liver and confirmed its up-regulation only in the WT-CR mice in response to oxidative stress. The lifespan did not differ significantly between the WT and HT mice in AL or CR conditions. However, the antineoplastic effect of CR, as indicated by reduced incidence of tumors at death in the WT-CR mice, was mostly abrogated in the HT-CR mice. The present results suggest a role for FoxO1 in the antineoplastic effect of CR through the induction of genes responsible for protection against oxidative and genotoxic stress. Article Published Date : Jun 01, 2010

Abstract Title: The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction. Abstract Source: Age (Dordr). 2010 May 26. Epub 2010 May 26. PMID: 20502969 Abstract Author(s): Benjamin L Predmore, Maikel J Alendy, Khadija I Ahmed, Christiaan Leeuwenburgh, David Julian Article Affiliation: Department of Biology, University of Florida, Gainesville, FL, 32611, USA. Abstract: Hydrogen sulfide gas (H(2)S) is a putative signaling molecule that causes diverse effects in mammalian tissues including relaxation of blood vessels and regulation of perfusion in the liver, but the effects of aging on H(2)S signaling are unknown. Aging has negative impacts on the cardiovascular system. However, the liver is more resilient with age. Caloric restriction (CR) attenuates affects of age in many tissues. We hypothesized that the H(2)S signaling system is negatively affected by age in the vasculature but not in the liver, which is typically more resilient to age, and that a CR diet minimizes the age affect in the vasculature. To investigate this, we determined protein and mRNA expression of the H(2)S-producing enzymes cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS), H(2)S production rates in the aorta and liver, and the contractile response of aortic rings to exogenous H(2)S. Tissue was collected from Fisher 344 x Brown Norway rats from 8-38 months of age, which had been maintained on an ad libitum (AL) or CR diet. The results demonstrate that age and diet have differential effects on the H(2)S signaling system in aorta and liver. The aorta showed a sizeable effect of both age and diet, whereas the liver only showed a sizeable effect of diet. Aortic rings showed increased contractile sensitivity to H(2)S and increased protein expression of CSE and CBS with age, consistent with a decrease in H(2)S concentration with age. CR appears to benefit CSE and CBS protein in both aorta and liver, potentially by reducing oxidative stress and ameliorating the negative effect of age on H(2)S concentration. Therefore, CR may help maintain the H(2)S signaling system during aging. Article Published Date : May 26, 2010

Abstract Title: Targeting the autophagy pathway for cancer chemoprevention. Abstract Source: Curr Opin Cell Biol. 2010 Apr;22(2):218-25. Epub 2010 Jan 22. PMID: 20096553 Abstract Author(s): Meredith A Steeves, Frank C Dorsey, John L Cleveland Article Affiliation: Department of Cancer Biology, The Scripps Research Institute-Florida, 130 Scripps Way, Jupiter, FL 33458, United States. Abstract: Autophagy is crucial for maintaining cellular homeostasis, coping with metabolic stress, and limiting oxidative damage. Several autophagy-deficient or knockout models show increased tumor incidence, implicating autophagy as a tumor suppressor. Autophagy is involved in multiple processes that may curb transformation, including the control of oncogene-induced senescence (OIS), which can limit progression to full malignancy, and efficient antigen presentation, which is crucial for immune cell recognition and elimination of nascent cancer cells. Activation of the autophagy pathway may therefore hold promise as a chemoprevention strategy. Caloric restriction, bioactive dietary compounds, or specific pharmacological activators of the autophagy pathway are all possible avenues to explore in harnessing the autophagy pathway in cancer prevention. Article Published Date : Apr 01, 2010

Abstract Title: Prolonged fasting as a method of mood enhancement in chronic pain syndromes: a review of clinical evidence and mechanisms. Abstract Source: Curr Pain Headache Rep. 2010 Apr;14(2):80-7. PMID: 20425196 Abstract Author(s): Andreas Michalsen Article Affiliation: Immanuel Hospital Berlin, Department of Internal and Complementary Medicine, Institute of Social Medicine, Epidemiology and Health Economics, Charité-University Medical Centre, Germany. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: Periods of deliberate fasting with restriction to intake of solid food are practiced worldwide, mostly based on a traditional, cultural, or religious background. Recent evidence from clinical trials shows that medically supervised modified fasting (200-500 kcal nutritional intake/day) with periods from 7 to 21 days is efficacious in the treatment of rheumatic diseases and chronic pain syndromes. Here, fasting is frequently accompanied by increased alertness and mood enhancement. The beneficial claims of fasting are supported by experimental research, which has found fasting to be associated with increased brain availability of serotonin, endogenous opioids, and endocannabinoids. Fasting-induced neuroendocrine activation and mild cellular stress response with increased production of neurotrophic factors may also contribute to the mood enhancement of fasting. Fasting treatments may be useful as an adjunctive therapeutic approach in chronic pain patients. The mood-enhancing and pain-relieving effect of therapeutic fasting should be further evaluated in randomized clinical trials. Article Published Date : Apr 01, 2010

Abstract Title: Long-term effects of calorie restriction on serum sex-hormone concentrations in men. Abstract Source: Aging Cell. 2010 Apr;9(2):236-42. Epub 2010 Jan 20. PMID: 20096034 Abstract Author(s): Roberto Cangemi, Alberto J Friedmann, John O Holloszy, Luigi Fontana Article Affiliation: Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA. Abstract: Calorie restriction (CR) slows aging and consistently reduces circulating sex hormones in laboratory animals. However, nothing is known regarding the long-term effects of CR with adequate nutrition on serum sex-hormone concentration in lean healthy humans. In this study, we measured body composition, and serum total testosterone, total 17-beta-estradiol, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEA-S) concentrations in 24 men (mean age 51.5 +/- 13 years), who had been practicing CR with adequate nutrition for an average of 7.4 +/- 4.5 years, in 24 age- and body fat-matched endurance runners (EX), and 24 age-matched sedentary controls eating Western diets (WD). We found that both the CR and EX volunteers had significantly lower body fat than the WD volunteers (total body fat, 8.7 +/- 4.2%; 10.5 +/- 4.4%; 23.2 +/- 6.1%, respectively; P = 0.0001). Serum total testosterone and the free androgen index were significantly lower, and SHBG was higher in the CR group than in the EX and WD groups (P Article Published Date : Apr 01, 2010

Abstract Title: Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Abstract Source: Trends Pharmacol Sci. 2010 Feb;31(2):89-98. Epub 2010 Jan 25. PMID: 20097433 Abstract Author(s): Valter D Longo, Luigi Fontana Article Affiliation: The Andrus Gerontology Center, University of Southern California, Los Angeles, CA, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: An important discovery of recent years has been that lifestyle and environmental factors affect cancer initiation, promotion and progression, suggesting that many malignancies are preventable. Epidemiological studies strongly suggest that excessive adiposity, decreased physical activity, and unhealthy diets are key players in the pathogenesis and prognosis of many common cancers. In addition, calorie restriction (CR), without malnutrition, has been shown to be broadly effective in cancer prevention in laboratory strains of rodents. Adult-onset moderate CR also reduces cancer incidence by 50% in monkeys. Whether the antitumorigenic effects of CR will apply to humans is unknown, but CR results in a consistent reduction in circulating levels of growth factors, anabolic hormones, inflammatory cytokines and oxidative stress markers associated with various malignancies. Here, we discuss the link between nutritional interventions and cancer prevention with focus on the mechanisms that might be responsible for these effects in simple systems and mammals with a view to developing chemoprevention agents. Article Published Date : Feb 01, 2010

Abstract Title: Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Abstract Source: Cell Death Dis. 2010 Jan;1(1):e10. PMID: 21364612 Abstract Author(s): E Morselli, M C Maiuri, M Markaki, E Megalou, A Pasparaki, K Palikaras, A Criollo, L Galluzzi, S A Malik, I Vitale, M Michaud, F Madeo, N Tavernarakis, G Kroemer Article Affiliation: INSERM, U848, Villejuif F-94805, France. Abstract: Caloric restriction and autophagy-inducing pharmacological agents can prolong lifespan in model organisms including mice, flies, and nematodes. In this study, we show that transgenic expression of Sirtuin-1 induces autophagy in human cells in vitro and in Caenorhabditis elegans in vivo. The knockdown or knockout of Sirtuin-1 prevented the induction of autophagy by resveratrol and by nutrient deprivation in human cells as well as by dietary restriction in C. elegans. Conversely, Sirtuin-1 was not required for the induction of autophagy by rapamycin or p53 inhibition, neither in human cells nor in C. elegans. The knockdown or pharmacological inhibition of Sirtuin-1 enhanced the vulnerability of human cells to metabolic stress, unless they were stimulated to undergo autophagy by treatment with rapamycin or p53 inhibition. Along similar lines, resveratrol and dietary restriction only prolonged the lifespan of autophagy-proficient nematodes, whereas these beneficial effects on longevity were abolished by the knockdown of the essential autophagic modulator Beclin-1. We conclude that autophagy is universally required for the lifespan-prolonging effects of caloric restriction and pharmacological Sirtuin-1 activators. Article Published Date : Jan 01, 2010

Abstract Title: Beneficial effects of mild stress (hormetic effects): dietary restriction and health. Abstract Source: J Physiol Anthropol. 2010;29(4):127-32. PMID: 20686325 Abstract Author(s): Katsuyasu Kouda, Masayuki Iki Article Affiliation: Department of Public Health, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: Hormesis is defined as a dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition, and has been recognized as representing an overcompensation for mild environmental stress. The beneficial effects of mild stress on aging and longevity have been studied for many years. In experimental animals, mild dietary stress (dietary restriction, DR) without malnutrition delays most age-related physiological changes, and extends maximum and average lifespan. Animal studies have also demonstrated that DR can prevent or lessen the severity of cancer, stroke, coronary heart disease, autoimmune disease, allergy, Parkinson's disease and Alzheimer's disease. The effects of DR are considered to result from hormetic mechanisms. These effects were reported by means of various DR regimens, such as caloric restriction, total-nutrient restriction, alternate-day fasting, and short-term fasting. Mild dietary stress, including restriction of amount or frequency of intake, is the essence of DR. For more than 99% of their history, humans lived as hunter-gatherers and adapted to restrictions in their food supply. On the other hand, an oversufficiency of food for many today has resulted in the current global epidemic of obesity and obesity-related diseases. DR may be used, therefore, as a novel approach for therapeutic intervention in several diseases, when detailed information about effects of mild dietary stress on human health is obtained from clinical trials. Article Published Date : Jan 01, 2010

Abstract Title: Caloric restriction delays disease onset and mortality in rhesus monkeys. Abstract Source: Theriogenology. 2009 Sep 15;72(5):624-35. Epub 2009 Jul 14. PMID: 19590001 Abstract Author(s): Ricki J Colman, Rozalyn M Anderson, Sterling C Johnson, Erik K Kastman, Kristopher J Kosmatka, T Mark Beasley, David B Allison, Christina Cruzen, Heather A Simmons, Joseph W Kemnitz, Richard Weindruch Article Affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals. Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species. Article Published Date : Sep 15, 2009

Abstract Title: Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms. Abstract Source: Nutrition. 2009 Sep;25(9):964-72. Epub 2009 Mar 5. PMID: 12558961 Abstract Author(s): Mark P Mattson, Wenzhen Duan, Zhihong Guo Article Affiliation: Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, Baltimore, Maryland 21224, USA. Abstract: Although all cells in the body require energy to survive and function properly, excessive calorie intake over long time periods can compromise cell function and promote disorders such as cardiovascular disease, type-2 diabetes and cancers. Accordingly, dietary restriction (DR; either caloric restriction or intermittent fasting, with maintained vitamin and mineral intake) can extend lifespan and can increase disease resistance. Recent studies have shown that DR can have profound effects on brain function and vulnerability to injury and disease. DR can protect neurons against degeneration in animal models of Alzheimer's, Parkinson's and Huntington's diseases and stroke. Moreover, DR can stimulate the production of new neurons from stem cells (neurogenesis) and can enhance synaptic plasticity, which may increase the ability of the brain to resist aging and restore function following injury. Interestingly, increasing the time interval between meals can have beneficial effects on the brain and overall health of mice that are independent of cumulative calorie intake. The beneficial effects of DR, particularly those of intermittent fasting, appear to be the result of a cellular stress response that stimulates the production of proteins that enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic factors such as brain-derived neurotrophic factor (BDNF), protein chaperones such as heat-shock proteins, and mitochondrial uncoupling proteins. Some beneficial effects of DR can be achieved by administering hormones that suppress appetite (leptin and ciliary neurotrophic factor) or by supplementing the diet with 2-deoxy-d-glucose, which may act as a calorie restriction mimetic. The profound influences of the quantity and timing of food intake on neuronal function and vulnerability to disease have revealed novel molecular and cellular mechanisms whereby diet affects the nervous system, and are leading to novel preventative and therapeutic approaches for neurodegenerative disorders. Article Published Date : Sep 01, 2009

Abstract Title: Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and decrease levels of N-acylethanolamines in hippocampus. Abstract Source: Neurochem Int. 2009 Mar-Apr;54(3-4):199-204. Epub 2008 Nov 30. PMID: 19100800 Abstract Author(s): Suzanne L Hansen, Ane H Nielsen, Katrine E Knudsen, Andreas Artmann, Gitte Petersen, Uffe Kristiansen, Steen H Hansen, Harald S Hansen Article Affiliation: Department of Pharmacology and Pharmacotherapy, University of Copenhagen, Denmark. Abstract: The ketogenic diet (KD) is used for the treatment of refractory epilepsy in children, however, the mechanism(s) remains largely unknown. Also, the antiepileptogenic potential in animal models of epilepsy has been poorly addressed. Activation of cannabinoid type-1 receptor (CB(1)-R) upon seizure activity may mediate neuroprotection as may several N-acylethanolamines. It is unknown how the KD interfere with the endocannabinoid system. We investigated the antiepileptogenic potential of the KD in the pentylenetetrazole kindling model in young mice and measured the hippocampal levels of CB(1)-R by Western blot and of endocannabinoids and N-acylethanolamines by mass spectrometry. The KD significantly decreased incidence and severity of seizures, and significantly increased the latency to clonic convulsions. There were no changes in levels of endocannabinoids or CB(1)-R expression by either seizure activity or type of diet. The level of oleoylethanolamide as well as the sum of N-acylethanolamines were significantly decreased by the KD, but were unaffected by seizure activity. The study shows that the KD had clear antiepileptogenic properties in the pentylenetetrazole kindling model and does not support a role of endocannabinoids in this model. The significance of the decreased hippocampal level of oleoylethanolamide awaits further studies. Article Published Date : Mar 01, 2009

Abstract Title: Caloric restriction and aging: studies in mice and monkeys. Abstract Source: Toxicol Pathol. 2009;37(1):47-51. Epub 2008 Dec 15. PMID: 19075044 Abstract Author(s): Rozalyn M Anderson, Dhanansayan Shanmuganayagam, Richard Weindruch Article Affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: It is widely accepted that caloric restriction (CR) without malnutrition delays the onset of aging and extends lifespan in diverse animal models including yeast, worms, flies, and laboratory rodents. The mechanism underlying this phenomenon is still unknown. We have hypothesized that a reprogramming of energy metabolism is a key event in the mechanism of CR (Anderson and Weindruch 2007). Data will be presented from studies of mice on CR, the results of which lend support to this hypothesis. Effects of long-term CR (but not short-term CR) on gene expression in white adipose tissue (WAT) are overt. In mice and monkeys, a chronic 30% reduction in energy intake yields a decrease in adiposity of approximately 70%. In mouse epididymal WAT, long-term CR causes overt shifts in the gene expression profile: CR increases the expression of genes involved in energy metabolism (Higami et al. 2004), and it down-regulates the expression of more than 50 pro-inflammatory genes (Higami et al. 2006). Whether aging retardation occurs in primates on CR is unknown. We have been investigating this issue in rhesus monkeys subjected to CR since 1989 and will discuss the current status of this project. A new finding from this project is that CR reduces the rate of age-associated muscle loss (sarcopenia) in monkeys (Colman et al. 2008). Article Published Date : Jan 01, 2009

Abstract Title: In vitro cellular adaptations of indicators of longevity in response to treatment with serum collected from humans on calorie restricted diets. Abstract Source: PLoS One. 2008;3(9):e3211. Epub 2008 Sep 15. PMID: 18791640 Abstract Author(s): Joanne S Allard, Leonie K Heilbronn, Carolina Smith, Nicole D Hunt, Donald K Ingram, Eric Ravussin, , Rafael de Cabo Abstract: Calorie restriction (CR) produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF) and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL) animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals. Two pilot studies were undertaken to examine the effects of ADF and CR on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human hepatoma cells and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period). Cells cultured in serum from ADF participants, showed a 20% increase in Sirt1 protein which correlated with reduced triglyceride levels. ADF serum also induced a 9% decrease in proliferation and a 25% increase in heat resistance. Cells cultured in serum from CR participants induced an increase in Sirt1 protein levels by 17% and a 30% increase in PGC-1alpha mRNA levels. This first in vitro study utilizing human serum to examine effects on markers of health and longevity in cultured cells resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity. The use of this in vitro technique may be helpful for predicting the potential of CR, ADF and other dietary manipulations to affect markers of longevity in humans. Article Published Date : Jan 01, 2008

Abstract Title: Prevention of insulin resistance by ingesting aqueous extract of Ocimum sanctum to fructose-fed rats. Abstract Source: Horm Metab Res. 2008 Jan;40(1):44-9. Epub 2007 Dec 18. PMID: 18085503 Abstract Author(s): S S Reddy, R Karuna, R Baskar, D Saralakumari Article Affiliation: Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, Andhra Pradesh, India. Abstract: The study was aimed to examine if oral administration of the aqueous extract of the whole plant OCIMUM SANCTUM (OS) protects against the development of insulin resistance in fructose fed rats. Male Wister rats were randomly divided into four groups of eight animals each: group-S (starch diet), group-F (fructose diet), group-F+OS (fructose diet along with OCIMUM SANCTUM extract at a dose of 200 mg/kg), group-S+OS (starch diet along with OCIMUM SANCTUM). During the experimental period of 60 days body weight, plasma glucose, insulin, and triglycerides were measured at an interval of 15 days. Insulin sensitivity was assessed at the end of experimental period by measuring glucose-insulin index, which is the product of the areas under the curve of glucose and insulin during oral glucose tolerance test. The nontoxic nature of OS was revealed by unaltered body weight, plasma glucose, insulin, and triglyceride levels in group-S+OS when compared with group-S. A significant gain in body weight, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and insulin resistance were observed in group-F when compared with group-S. OS treatment prevented the observed fructose induced alterations in group-F+OS. In conclusion, our results suggests that oral administration of OS aqueous extract could delay the development of insulin resistance in rats and may be used as an adjuvant therapy for treating diabetic patients with insulin resistance. Article Published Date : Jan 01, 2008

Abstract Title: Fourteen weeks of treatment with Viscofiber increased fasting levels of glucagon-like peptide-1 and peptide-YY. Abstract Source: J Med Food. 2007 Dec;10(4):720-4. PMID: 18158848 Abstract Author(s): Frank Greenway, Carol E O'Neil, Laura Stewart, Jennifer Rood, Michael Keenan, Roy Martin Article Affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: Fermentable dietary fiber has been shown to cause fat loss and to increase peptide-YY (PYY) and glucagon-like peptide 1 (GLP-1) levels in rodents. In single meal tests, humans have an increase in PYY and GLP-1 to dietary fiber, but the response of these hormones to longer-term treatment is not known. Viscofiber (Cevena Bioproducts Inc., Edmonton, AB, Canada) is a high-viscosity fermentable dietary fiber made by a proprietary process from oats and barley. Seven healthy overweight and obese subjects were treated with a calorie-restricted diet, a lifestyle change program, and 4 g of Viscofiber/day for 16 weeks. Hunger, satiety, PYY, and GLP-1 were measured before and 1 hour after a standard meal test before and at week 14 of the study. Hunger and satiety were measured by Visual Analog Scales. PYY and GLP-1 were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Weight was reduced 3.07 +/- 3.13 kg (P<.05) over the 16 weeks. Fasting PYY increased 8.67 +/- 6.62 pg/mL (P<.05) and fasting GLP-1 increased 2.67 +/- 0.84 pmol/L (P<.01) at 14 weeks compared to baseline. Satiety increased 1.78 +/- 1.43 cm (P<.01) at the 1-hour post-meal time point on week 14 compared to the study baseline. We conclude that 14 weeks of treatment with Viscofiber at 4 g/day along with a lifestyle change program and diet causes weight loss and increases fasting PYY, fasting GLP-1, and satiety at 1 hour following a standard meal, which extends the single meal test observations in humans. Article Published Date : Dec 01, 2007

Abstract Title: [Fasting as part of a naturopathic treatment approach for polymyalgia rheumatica]. Abstract Source: Forsch Komplementmed. 2007 Aug;14(4):235-9. Epub 2007 Jul 20. PMID: 17848800 Abstract Author(s): Rainer Stange, Christine Pflugbeil Abstract: A 67-year-old woman with proven diagnosis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) was admitted to stationary treatment twice to receive a complex therapy with methods of natural medicine comprising fasting as its main treatment element. Both times, a discrepancy between the course of markers of the acute phase on the one hand, and subjective as well as objective clinical outcome on the other hand could be observed.This may point to special conditions of this chronic inflammatory disease as compared to e.g.rheumatoid arthritis, but also to specific problems in assessing possible effects of the treatments chosen, particularly fasting therapy, as compared to effects of conventional therapies. Article Published Date : Aug 01, 2007

Abstract Title: The antioxidant role of pterostilbene in streptozotocin-nicotinamide-induced type 2 diabetes mellitus in Wistar rats. Abstract Source: J Pharm Pharmacol. 2006 Nov;58(11):1483-90. PMID: 17132211 Abstract Author(s): M Amarnath Satheesh, L Pari Article Affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamilnadu, India. Abstract: The antioxidant effect of pterostilbene on streptozotocin-nicotinamide-induced diabetic rats has been assessed. The activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione was significantly decreased in liver and kidney of diabetic animals when compared with normal control. There were significant improvements in these activities after treatment with pterostilbene at a dose of 40 mg kg(-1) for six weeks. The increased levels of lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) in liver and kidney of diabetic rats were also normalized by treatment with pterostilbene. Chronic treatment of pterostilbene remarkably reduced the pathological changes observed in liver and kidney of diabetic rats. These results indicated the antioxidant property of pterostilbene. Article Published Date : Nov 01, 2006

Abstract Title: Serum leptin levels in childhood celiac disease. Abstract Source: J Clin Gastroenterol. 2006 Nov-Dec;40(10):906-9. PMID: 17063109 Abstract Author(s): Vildan Ertekin, Zerrin Orbak, Mukadder Ayse Selimoglu, Leyla Yildiz Article Affiliation: Divisions of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Faculty of Medicine, Ataturk University, Erzurum, Turkey. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: OBJECTIVE: Leptin has effects on growth and is also involved in immune regulation. We thought that with its intestinal histopathologic alterations due to immune mechanisms, and subsequent malnutrition and/or growth failure, celiac disease (CD) deserves interest regarding leptin status. METHOD: Serum leptin levels of 19 children with CD on admission and 1 year after gluten-free diet (GFD) and of 16 healthy children were determined. RESULTS: Mean age was 9.7+/-3.3 years. Mean serum leptin level of children with CD on admission and of healthy children were 1.60+/-0.63 ng/mL, and 3.98+/-1.49 ng/mL, respectively (P: 0.0001). Mean serum leptin level under GFD was 4.55+/-1.97 ng/mL. There was a statistical significant difference between serum levels determined before and 1 year after GFD (P: 0.001) and between those of under GFD and healthy children (P: 0.001). Of 19 patients with CD, 10 (52.6%) showed Marsh IIIc, other 9 (47.4%) showed Marsh IIIa histologic lesions. Mean serum leptin level of children with Marsh IIIc and Marsh IIIa were not different (1.70+/-0.73 ng/mL vs. 1.45+/-0.59 ng/mL). Leptin was correlated with body mass index in healthy children, and in CD both before and after GFD (P<0.001). Mean lumbar z score of the patients on admission and after GFD were 2.7+/-1.3 and 1.9+/-0.8, respectively (P: 0.048). Serum leptin level was not correlated with lumbar z score either before or after GFD. CONCLUSIONS: Serum leptin level is affected in childhood CD, it is not directly related to histopathologic findings, and is responsive to GFD. Further studies investigating its level in different clinical and histopathologic presentations might give clear clues about the role of leptin in CD. Article Published Date : Oct 31, 2006

Abstract Title: Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones. Abstract Source: J Clin Endocrinol Metab. 2006 Aug;91(8):3232-5. Epub 2006 May 23. PMID: 16720655 Abstract Author(s): Luigi Fontana, Samuel Klein, John O Holloszy, Bhartur N Premachandra Article Affiliation: Washington University School of Medicine, 4566 Scott Avenue, Campus Box 8113, St. Louis, MO 63110, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: CONTEXT: Caloric restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in T(3) hormone may increase life span by conserving energy and reducing free-radical production. OBJECTIVE: The objective of the study was to assess the relationship between long-term CR with adequate protein and micronutrient intake on thyroid function in healthy lean weight-stable adult men and women. DESIGN, SETTING, AND PARTICIPANTS: In this study, serum thyroid hormones were evaluated in 28 men and women (mean age, 52 +/- 12 yr) consuming a CR diet for 3-15 yr (6 +/- 3 yr), 28 age- and sex-matched sedentary (WD), and 28 body fat-matched exercising (EX) subjects who were eating Western diets. MAIN OUTCOME MEASURES: Serum total and free T(4), total and free T(3), reverse T(3), and TSH concentrations were the main outcome measures. RESULTS: Energy intake was lower in the CR group (1779 +/- 355 kcal/d) than the WD (2433 +/- 502 kcal/d) and EX (2811 +/- 711 kcal/d) groups (P<0.001). Serum T(3) concentration was lower in the CR group than the WD and EX groups (73.6 +/- 22 vs. 91.0 +/- 13 vs. 94.3 +/- 17 ng/dl, respectively) (P Article Published Date : Aug 01, 2006

Abstract Title: Effects of chili consumption on postprandial glucose, insulin, and energy metabolism. Abstract Source: Am J Clin Nutr. 2006 Jul;84(1):63-9. PMID: 16825682 Abstract Author(s): Kiran Dk Ahuja, Iain K Robertson, Dominic P Geraghty, Madeleine J Ball Article Affiliation: School of Human Life Sciences, University of Tasmania, Launceston, Australia. Abstract: BACKGROUND: Animal and some human studies have indicated that the consumption of chili-containing meals increases energy expenditure and fat oxidation, which may help to reduce obesity and related disorders. Because habitual diets affect the activity and responsiveness of receptors involved in regulating and transporting nutrients, the effects of regular consumption of chili on metabolic responses to meals require investigation. OBJECTIVE: The objective was to investigate the metabolic effects of a chili-containing meal after the consumption of a bland diet and a chili-blend (30 g/d; 55% cayenne chili) supplemented diet. DESIGN: Thirty-six subjects with a mean (+/-SD) age of 46 +/- 12 y and a body mass index (in kg/m2) of 26.3 +/- 4.6 participated in a randomized, crossover, intervention study with 2 dietary periods (chili and bland) of 4 wk each. The postprandial effects of a bland meal after a bland diet (BAB), a chili meal after a bland diet (CAB), and a chili meal after a chili-containing diet (CAC) were evaluated. Serum insulin, C-peptide, and glucose concentrations and energy expenditure (EE) were measured at fasting and up to 120 min postprandially. RESULTS: Significant heterogeneity was observed between the meals for the maximum increase in insulin and the incremental area under the curve (iAUC) for insulin (P = 0.0002); the highest concentrations were with the BAB meal and the lowest with the CAC meal. When separated at the median BMI (26.3), the subjects with a BMI>or = 26.3 also showed heterogeneity in C-peptide, iAUC C-peptide, and net AUC EE (P<0.02 for all); the highest values occurred after the BAB meal and the lowest after the CAC meal. Conversely, the C-peptide/insulin quotient (an indicator of hepatic insulin clearance) was highest after the CAC meal (P = 0.002). CONCLUSION: Regular consumption of chili may attenuate postprandial hyperinsulinemia. Article Published Date : Jul 01, 2006

Abstract Title: Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot-Marie-Tooth disease. Abstract Source: Ann Dermatol Venereol. 2006 May;133(5 Pt 1):425-8. PMID: 19320048 Abstract Author(s): Irina Madorsky, Katherine Opalach, Amanda Waber, Jonathan D Verrier, Chelsea Solmo, Thomas Foster, William A Dunn, Lucia Notterpek Article Affiliation: Department of Neuroscience, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. Abstract: Charcot-Marie-Tooth type 1A (CMT1A) neuropathies linked to the misexpression of peripheral myelin protein 22 (PMP22) are progressive demyelinating disorders of the peripheral nervous system. In this study we asked whether dietary restriction by intermittent fasting (IF) could alleviate the neuropathic phenotype in the Trembler J (TrJ) mouse model of CMT1A. Our results show that neuropathic mice kept on a five month long IF regimen had improved locomotor performance compared to ad libitum (AL) fed littermates. The functional benefits of this dietary intervention are associated with an increased expression of myelin proteins combined with a thicker myelin sheath, less redundant basal lamina, and a reduction in aberrant Schwann cell proliferation. These morphological improvements are accompanied by a decrease in PMP22 protein aggregates, and enhanced expression of cytosolic chaperones and constituents of the autophagy-lysosomal pathway. These results indicate that dietary restriction is beneficial for peripheral nerve function in TrJ neuropathic mice, as it promotes the maintenance of locomotor performance. Article Published Date : May 01, 2006

Abstract Title: Protective effect of melatonin and omeprazole against alendronat-induced gastric damage. Abstract Source: Dig Dis Sci. 2005 Aug;50(8):1506-12. PMID: 16110843 Abstract Author(s): Goksel Sener, Figen Onuk Goren, Nefise B Ulusoy, Yasemin Ersoy, Serap Arbak, Gül Ayanoglu Dülger Article Affiliation: School of Pharmacy, Department of Pharmacology, Marmara University, Haydarpasa, Istanbul, Turkey. Abstract: Alendronate causes serious gastrointestinal adverse effects. We aimed to investigate if free radicals have any role in the damage induced by alendronate and if melatonin or omeprazole is protective against this damage. Rats were administered 20 mg/kg alendronate by gavage for 4 days, either alone or following treatment with melatonin or omeprazole. On the last day, following drug administration, pilor ligation was performed, and 2 hr later rats were killed and stomachs were removed. Gastric acidity and tissue ulcer index values, lipid peroxidation, and myeloperoxidase and glutathione levels, as well as the histologic appearance of the stomach tissues, were determined. Chronic oral administration of alendronate induced significant gastric damage, increasing lipid peroxidation and myeloperoxidase activity, while tissue glutathione levels decreased. Treatment with omeprazole or melatonin prevented this damage as well as the changes in biochemical parameters, and melatonin appeared to be more efficient than omeprazole in protecting the mucosa. Intraperitoneal administration of alendronate did not cause much gastric irritation. Findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect and that melatonin and omeprazole are protective against this damage due to their antioxidant properties. Article Published Date : Aug 01, 2005

Abstract Title: [Anti-aging effects by caloric restriction]. Abstract Source: J Inorg Biochem. 2004 Dec;98(12):2063-70. PMID: 19591287 Abstract Author(s): Takahiko Shimizu, Takuji Shirasawa Article Affiliation: Research Team for Molecular Biomarkers, Tokyo Metropolitan Institute of Gerontology. Abstract: Caloric restriction (CR) in experimental animals shows to extend the lifespan of animals with the decreased frequency of age-related diseases. CR also produces beneficial health effects in monkeys and humans. These benefits include improved insulin sensitivity, enhanced stress resistance, decreased cancer incidence, and increased neuronal function and neurogenesis. Several important signal transduction pathways have been implicated in the regulation of the physiological processes of CR leading to increased lifespan. One of these pathways includes the Sirt1 pathway. Sirt1 deacetylates a large number of transcriptional factors and cofactors involved in cell growth, differentiation, stress resistance, oxidative damage, and metabolism. Recently, several studies report that resveratrol and other compounds exogenously activate Sirt1 protein and improve the obesity-associated pathology in mice. In this text, we introduce the recent topics of CR research and discuss the anti-aging effects by CR. Article Published Date : Dec 01, 2004

Abstract Title: Effect of green tea in the prevention and reversal of fasting-induced intestinal mucosal damage. Abstract Source: Nutrition. 2003 Jun;19(6):536-40. PMID: 12781855 Abstract Author(s): Sami Asfar, Suad Abdeen, Hussein Dashti, Mousa Khoursheed, Hilal Al-Sayer, Thazhumpal Mathew, Abdullatif Al-Bader Article Affiliation: Department of Surgery, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: OBJECTIVE: Epidemiologic studies have suggested that high consumption of green tea protects against the development of chronic active gastritis and decreases the risk of stomach cancer. The effect of green tea on the intestinal mucosa was not studied previously, so we examined the effects of green tea on the intestinal mucosa of fasting rats in a controlled experimental setting. METHODS: Two sets of experiments were performed. In the recovery set, rats were fasted for 3 d, after which they were allowed free access to water, black tea, green tea, or vitamin E for 7 d. On day 8, the animals were killed, and small bowels were removed for histologic examination. In the pretreatment set, rats were allowed a normal diet, but the water supply was replaced with green tea, black tea, or vitamin E for 14 d. They were subsequently fasted for 3 d. On day 4, the rats were killed, and small bowels were removed for histologic examination. RESULTS: In the recovery set, fasting for 3 d caused shortening of villi, atrophy, and fragmentation of mucosal villous architecture, with a significant (P<0.0001) reduction in the length and surface area of the villi. Ingestion of green tea and, to a lesser extent, vitamin E for 7 d helped in the recovery of villi to normal. In the pretreatment set, drinking green tea, black tea, or vitamin E for 14 d before fasting protected intestinal mucosa from damage. CONCLUSION: The mucosal and villous atrophy induced by fasting was reverted to normal by the ingestion of green tea and, to a lesser extent, vitamin E. Black tea ingestion had no effect. In addition, ingestion of black tea, green tea, and vitamin E before fasting protected the intestinal mucosa against atrophy. Article Published Date : Jun 01, 2003

Abstract Title: Serum vitamin D and risk of bladder cancer. Abstract Source: Biol Trace Elem Res. 2002 Nov;89(2):105-10. PMID: 20978193 Abstract Author(s): Alison M Mondul, Stephanie J Weinstein, Satu Männistö, Kirk Snyder, Ronald L Horst, Jarmo Virtamo, Demetrius Albanes Article Affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: Vitamin D may protect against several cancers, but data about the association between circulating vitamin D and bladder cancer are limited. Within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a randomized controlled trial conducted to determine the effects ofα-tocopherol and β-carotene supplements on cancer incidence in male smokers, 250 bladder cancer cases were randomly sampled by month of blood collection. Controls were matched 1:1 to cases on age at randomization and date of blood collection. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer by a priori categories of baseline serum 25-hydroxyvitamin D [25(OH)D; i.e.,<25, 25 to<37.5, 37.5 to<50,≥50 nmol/L] and by season-specific quartiles. After multivariable adjustment, we found that lower 25(OH)D was associated with a statistically significantly increased risk of bladder cancer (versus ≥50 nmol/L;<25 nmol/L: OR, 1.73; 95% CI, 1.03-2.91; 25 to<37.5 nmol/L: OR, 1.81; 95% CI, 1.05-3.14; 37.5 to<50 nmol/L: OR, 1.76; 95% CI, 1.02-3.02; P trend=0.04). Similarly, increased risks for the lowest vitamin D category were observed when season-specific quartiles were used (Q1 versus Q4: OR, 1.63; 95% CI, 0.96-2.75; P trend=0.03). In this prospective study of male smokers, lower serum 25(OH)D was associated with an increased risk of bladder cancer. Future studies should examine the association in other populations, especially nonsmokers and women. Article Published Date : Nov 01, 2002

Abstract Title: Effects of Aronia melanocarpa juice as part of the dietary regimen in patients with diabetes mellitus. Abstract Source: Folia Med (Plovdiv). 2002 ;44(3):20-3. PMID: 12580526 Abstract Author(s): Simeon B Simeonov, Nikolai P Botushanov, Eksapet B Karahanian, Maria B Pavlova, Haralambos K Husianitis, Dimitar M Troev Article Affiliation: Simeon B Simeonov Abstract: The low calorie juice Aronia melanocarpa (sugar free, with artificial sweeteners) could be a valuable adjunct to the complex therapy of patients with diabetes mellitus. In this study no increased blood glucose levels were established 60 min. following ingestion of 200 ml Aronia juice. On the contrary, lower fasting blood glucose concentrations were measured in 16 patients with insulin dependent diabetes and in 25 patients with non-insulin dependent diabetes (25 women and 16 men, 3 to 62 years of age, median age 38.8 +/- 4.7) with duration of the disease from 1 month to 13 years. Serial blood glucose measurements showed: 14.23 +/- 1.32 mmol/l at baseline and 11.4 +/- 0.89 mmol/l blood glucose level after 60 min., the difference being statistically significant (p<0.05). The ingestion of 200 ml Aronia juice combined with a standard breakfast produced similar results (the basal concentration of glucose was 13.43 +/- 1.12 mmol/l; it decreased to 11.94 +/- 1.02 mmol/l at 60 min., the difference did not reach statistical significance. The daily intake of 200 ml Aronia juice over a period of 3 months was effective in lowering fasting blood glucose levels from 13.28 +/- 4.55 mmol/l to 9.10 +/- 3.05 mmol/l (p<0.001) in 21 patients with non-insulin dependent diabetes--13 women and 8 men aged from 42 to 62 (median age 53.6 +/- 3.65) with disease duration from 6 to 17 years. Aronia had a beneficial effect on HbA1c, total cholesterol and lipid levels. They dropped from 9.39 +/- 2.16% to 7.49 +/- 1.33% (p<0.001), from 6.45 +/- 1.59 mmol/l to 5.05 +/- 0.96 mmol/l (p<0.001) and from 2.92 +/- 2.15 mmol/l to 1.7 +/- 1.07 mmol/l (p<0.001), respectively. Results were compared with those obtained in 23 patients with non-insulin dependent diabetes (15 women and 8 men aged from 48 to 67 years, median age 54.9 +/- 3.34) with disease duration from 6 to 17 years. The above mentioned parameters remained unchanged in these patients. Accumulated data illustrated the hypoglycemic potential of Aronia juice. The precise mechanism of its action is unknown but its beneficial effects and good taste make it a valuable adjunct to the dietary treatment of patients with diabetes mellitus. Article Published Date : Dec 31, 2001

Abstract Title: Neuroprotective signaling and the aging brain: take away my food and let me run. Abstract Source: Brain Res. 2000 Dec 15;886(1-2):47-53. PMID: 11119686 Abstract Author(s): M P Mattson Article Affiliation: Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, 5600 Nathan Shock Drive, 21224-6825, Baltimore, MD, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: It is remarkable that neurons are able to survive and function for a century or more in many persons that age successfully. A better understanding of the molecular signaling mechanisms that permit such cell survival and synaptic plasticity may therefore lead to the development of new preventative and therapeutic strategies for age-related neurodegenerative disorders. We all know that overeating and lack of exercise are risk factors for many different age-related diseases including cardiovascular disease, diabetes and cancers. Our recent studies have shown that dietary restriction (reduced calorie intake) can increase the resistance of neurons in the brain to dysfunction and death in experimental models of Alzheimer's disease, Parkinson's disease, Huntington's disease and stroke. The mechanism underlying the beneficial effects of dietary restriction involves stimulation of the expression of 'stress proteins' and neurotrophic factors. The neurotrophic factors induced by dietary restriction may protect neurons by inducing the production of proteins that suppress oxyradical production, stabilize cellular calcium homeostasis and inhibit apoptotic biochemical cascades. Interestingly, dietary restriction also increases numbers of newly-generated neural cells in the adult brain suggesting that this dietary manipulation can increase the brain's capacity for plasticity and self-repair. Work in other laboratories suggests that physical and intellectual activity can similarly increase neurotrophic factor production and neurogenesis. Collectively, the available data suggest the that dietary restriction, and physical and mental activity, may reduce both the incidence and severity of neurodegenerative disorders in humans. A better understanding of the cellular and molecular mechanisms underlying these effects of diet and behavior on the brain is also leading to novel therapeutic agents that mimick the beneficial effects of dietary restriction and exercise. Article Published Date : Dec 15, 2000

Abstract Title: The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Abstract Source: Diabetes Care. 1998 May;21(5):682-6. PMID: 9589224 Abstract Author(s): M de Lordes Lima, T Cruz, J C Pousada, L E Rodrigues, K Barbosa, V Canguçu Abstract: OBJECTIVE: Hypomagnesemia occurs in 25-38% of patients with type 2 diabetes. Several studies have suggested an association between magnesium (Mg) depletion and insulin resistance and/or reduction of insulin secretion in these cases. Our purpose was to evaluate if Mg supplementation (as magnesium oxide [MgO]) would improve metabolic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 128 patients with type 2 diabetes (32 men, 96 women, aged 30-69 years), treated by diet or diet plus oral antidiabetic drugs, in the Bahia Federal University Hospital, Brazil. Patients at risk for hypomagnesemia or with reduced renal function were excluded. This study was a clinical randomized double-blind placebo-controlled trial. Patients received either placebo, 20.7 mmol MgO, or 41.4 mmol MgO daily (elementary Mg) for 30 days. Mg concentrations were measured in plasma, in mononuclear cells, and in 24-h urine samples. Fasting blood glucose, HbA1, and fructosamine were used as parameters of metabolic control. RESULTS: Of the patients, 47.7% had low plasma Mg, and 31.1% had low intramononuclear Mg levels. Intracellular Mg in patients with diabetes was significantly lower than in the normal population (62 blood donors; 1.4 +/- 0.6 vs. 1.7 +/- 0.6 micrograms/mg of total proteins). No correlation was found between plasma and intracellular Mg concentrations (r = -0.179; P = 0.15) or between Mg concentrations and glycemic control (r = -0.165; P = 0.12). Intracellular Mg levels were lower in patients with peripheral neuropathy than in those without (1.2 +/- 0.5 vs. 1.5 +/- 0.6 micrograms/mg). Similar findings were observed in patients with coronary disease (1.0 +/- 0.5 vs. 1.5 +/- 0.6 micrograms/mg). In the placebo and in the 20.7 mmol Mg groups, neither a change in plasma and intracellular levels nor an improvement in glycemic control were observed. Replacement with 41.4 mmol Mg tended to increase plasma, cellular, and urine Mg and caused a significant fall (4.1 +/- 0.8 to 3.8 +/- 0.7 mmol/l) in fructosamine (normal, 1.87-2.87 mmol/l). CONCLUSIONS: Mg depletion is common in poorly controlled patients with type 2 diabetes, especially in those with neuropathy or coronary disease. More prolonged use of Mg in doses that are higher than usual is needed to establish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications. Article Published Date : May 01, 1998

Abstract Title: Effects of duration of fast and animal age on the gastrointestinal absorption of plutonium. Abstract Source: Radiat Res. 1986 Jul;107(1):73-82. PMID: 3737878 Abstract Author(s): M H Bhattacharyya, R P Larsen, R D Oldham, E S Moretti, M I Spaletto Abstract: The fraction of plutonium absorbed after oral administration of Pu(VI) to 24-h-fasted mice was 19 X 10(-4), 13-fold higher than in fed mice, 1.4 X 10(-4). We have investigated the relevance of the high gastrointestinal (GI) absorption value for the 24-h-fasted animals in setting drinking water standards for humans. When fasting was initiated at the beginning of the active phase of the mouse's daily activity cycle (when they would normally eat), plutonium GI absorption rose from 2.8 X 10(-4) at zero-time to a level typical of the 24-h-fasted mouse after only 2 h of fasting. In contrast, in mice allowed to eat for 4 h into their active phase prior to initiation of the fast (meal-fed mice), 8 h of fasting were required before GI absorption rose to a level similar to that of the 24-h-fasted mouse. The fraction of plutonium retained after gavage administration of Pu(VI) to 1-day-old rats was 74 X 10(-4), 70-fold higher than the value for fed adults. Retention after GI absorption in neonates remained 30- to 70-fold higher than in adults until weaning. One week after weaning, the fraction absorbed and retained by fed weanling rats was the same as that for fed adults, 1 X 10(-4). Drinking water standards for plutonium have been set based on GI absorption values for fed adult animals. The 10- to 100-fold increases in plutonium absorption in young and fasted animals reported by ourselves and others, and the rapid rise to fasted levels of absorption at the start of the animal's active phase, indicate that consideration should be given to elevated levels of plutonium absorption in young and fasted individuals. Article Published Date : Jul 01, 1986