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Nathan Goodyear

The influence of diet on anti-cancer immune responsiveness - 0 views

    I can't wait to read this article.
Nathan Goodyear

The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for ... - 0 views

  • The ‘Glucose Ketone Index’ (GKI) was created to track the zone of metabolic management for brain tumor management
  • The GKI is a biomarker that refers to the molar ratio of circulating glucose over β-OHB, which is the major circulating ketone body.
  • We present evidence showing that the GKI can predict success for brain cancer management in humans and mice using metabolic therapies that lower blood glucose and elevate blood ketone levels
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  • The GKI can be useful in determining the success of dietary therapies that shift glucose- and lactate-based metabolism to ketone-based metabolism
  • Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, chronic inflammatory disease, and epilepsy
  • The zone of metabolic management is likely entered with GKI values between 1 and 2 for humans
  • Optimal management is predicted for values approaching 1.0, and blood glucose and ketone values should be measured 2–3 hours postprandial, twice a day if possible
    • Nathan Goodyear
      check GKI 2-3 hr postprandial twice daily
  • Preclinical studies have demonstrated a clear linkage between GKI and therapeutic efficacy
  • the Warburg effect (aerobic fermentation of glucose) is a common metabolic malady expressed in nearly all neoplastic cells of these and other malignant tumors
  • Aerobic fermentation (Warburg effect) is necessary to compensate for the insufficiency of mitochondrial oxidative phosphorylation in the cells of most tumors
  • Normal brain cells gradually transition from the metabolism of glucose to the metabolism of ketone bodies (primarily β-hydroxybutyrate and acetoacetate) for energy when circulating glucose levels become limiting
  • Ketone bodies bypass the glycolytic pathway in the cytoplasm and are metabolized directly to acetyl CoA in the mitochondria
  • Tumor cells are less capable than normal cells in metabolizing ketone bodies for energy due to their mitochondrial defects
  • daily activities and emotional stress can cause blood glucose levels to vary making it difficult for some people to enter the predicted zone of metabolic management
  • a clear association of the GKI to the therapeutic action of calorie restriction against distal invasion, proliferation, and angiogenesis in the VM-M3 model of glioblastoma
  • The results suggest that GKI levels that approach 1.0 are therapeutic for managing brain tumor growth
  • Therapeutic efficacy of the KD or calorie restriction is greater with lower GKI values than with higher values
    The glucose ketone index shown to predict dietary metabolic success. In humans with brain cancer-- the target is 1.  The glucose and ketone (betahydroxybutyrate) should be measured 2-3 hours postprandial twice daily.
Nathan Goodyear

Frontiers | Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic M... - 0 views

  • The SOC for GBM was modified in this patient to initiate KMT prior to surgical resection, to eliminate steroid medication, and to include HBOT as part of the therapy
  • the greatest therapeutic benefit for patients (near 1.0)
  • The observed reduction in blood glucose in our patient would reduce lactic acid fermentation in the tumor cells, while the elevation of ketone bodies would fuel normal cells thus protecting them from hypoglycemia and oxidative stress
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  • Previous studies showed that GBM survival and tumor growth was correlated with blood glucose levels
  • Evidence indicates that glioma cells cannot effectively use ketone bodies for energy due to defects in the number, structure, and function of their mitochondria
  • The accuracy of the GKI as a predictor for therapeutic efficacy, however, is better when ketone bodies are measured from the blood than when measured from the urine
  • A reduction of glucose-driven lactic acid fermentation would not only increase tumor cell apoptosis, but would also reduce inflammation and edema in the tumor microenvironment thus reducing tumor cell angiogenesis and invasion
  • Besides serving as a metabolic fuel for GBM, glutamine is also an essential metabolite for normal immune cells
  • therapies that inhibit glutamine availability and utilization must be strategically employed to avoid inadvertent impairment of immune cell functions
  • we used the non-toxic green tea extract, EGCG, and chloroquine in an attempt to limit glutamine availability to the tumor cells
  • EGCG is thought to target the glutamate dehydrogenase activity that facilitates glutamine metabolism in GBM cells
  • Chloroquine, on the other hand, will inhibit lysosomal digestion thus restricting fermentable amino acids and carbohydrates from phagocytosed materials in the tumor microenvironment
  • HBOT to increase oxidative stress in the tumor cells
  • As glucose and glutamine fermentation protect tumor cells from oxidative stress, reduced availability of these metabolites under ketosis could enhance the therapeutic action of HBOT, as we recently described
  • Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast
  • Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day
  • KD (increased to 1,500 kcal/day at day 22
  • the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA)
  • Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D
  • This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies
  • Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers
  • less than 20% of younger adults generally survive beyond 24 months
  • glucose and glutamine are the primary fuels that drive the rapid growth of most tumors including GBM
  • Glucose drives tumor growth through aerobic fermentation (Warburg effect), while glutamine drives tumor growth through glutaminolysis
  • The fermentation waste products of these molecules, i.e., lactic acid and succinic acid, respectively, acidify the tumor microenvironment thus contributing further to tumor progression
  • Glucose and glutamine metabolism is also responsible for the high antioxidant capacity of the tumor cells thus making them resistant to chemo- and radiotherapies
  • The reliance on glucose and glutamine for tumor cell malignancy comes largely from the documented defects in the number, structure, and function of mitochondria and mitochondrial-associated membranes
  • These abnormalities cause the neoplastic GBM cells to rely more heavily on substrate level phosphorylation than on oxidative phosphorylation for energy
  • dexamethasone not only increases blood glucose levels but also increases glutamine levels through its induction of glutamine synthetase activity
    • Nathan Goodyear
      use mannitol instead
  • Calorie restriction and restricted KD are anti-angiogenic, anti-inflammatory, anti-invasive, and also kill tumor cells through a proapoptotic mechanism
  • Evidence also shows that therapeutic ketosis can act synergistically with several drugs and procedures to enhance cancer management improving both progression free and overall survival
  • hyperbaric oxygen therapy (HBOT) increases oxidative stress on tumor cells especially when used alongside therapies that reduce blood glucose and raise blood ketones
  • The glutamine dehydrogenase inhibitor, epigallocatechin gallate (EGCG) is also proposed to target glutamine metabolism
    Case study of Glioblastoma treated with ketogenic metabolic therapy as an adjuct to modified standard therapy.
Nathan Goodyear

Dietary carbohydrate modification induces alterations in gene expression in abdominal s... - 0 views

    Nutrition and Epigenetics.  Study finds diffenet carb sources in diet effect different genetic expression.
Nathan Goodyear

Low carbohydrate diets improve atherogenic dyslipidemia even in the absence of weight loss - 0 views

    low carb diet found to benefit atherosclerosis and lipid abnormalities (Triglycerides, HDL, and LDL particle size).  Interesting enough, no significant weight loss was seen.
Nathan Goodyear

Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism - 0 views

    Very good review on the ketogenic diet in cancer.
Nathan Goodyear

The role of nutrition related genes and nutrigenetics in understanding the pathogenesis... - 0 views

    good review article on nutrition, epigenetics, and cancer
Nathan Goodyear

Effect of Distinct Lifestyle Interventions on Mobilization of Fat Storage Pools: The CE... - 0 views

    low carb mediterranean nutrition out performs low fat diet; but both are not served by following weight number.  MRI shows that fat mobilization of the superior low carb mediterranean nutrition plan is not adequately reflected in weight measurement. 
Nathan Goodyear

Cross-kingdom inhibition of breast cancer growth by plant miR159 - 0 views

  • MicroRNAs (miRNAs), a major family of small RNAs, are ∼23 nt-long single strands of RNA that bind to mRNA transcripts to inhibit their translation
  • A recent study by Zhang et al. reported that plant-derived miRNAs can be found in human serum.
  • The group demonstrates that the plant miRNA miR168 may be taken up through dietary intake to inhibit the expression of its target low-density lipoprotein receptor 1 in the liver, providing the first evidence that miRNA in food may influence gene expression in mammalian organs.
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  • A more recent finding by the same group shows that a plant miRNA from honeysuckle is able to inhibit Influenza A replication, indicating that plant miRNAs may be useful for treating human diseases.
  • We found that plant miR159 could be detected in human sera and its levels were inversely correlated with BC incidence and progression.
  • We further identified TCF7 as a mammalian target for miR159 and showed the anti-proliferative function of miR159 in BC cells using in vitro and in vivo models, demonstrating for the first time that a plant miRNA is able to influence BC cell growth.
  • certain dietary miRNAs from plants and other species may serve as highly affordable and powerful means of treatment with minimal inconvenience to patients.
  • miR159 which (using a synthetic mimic) targets TCF7 to inhibit the proliferation of cells whose growth is dependent on TCF7 such as the BC cells MDA-MB-231
  • our study using a BC model clearly indicates the anti-tumor effect of orally administered synthetic miR159 in its naturally existing form with the plant-specific 2'-O-methylation, suggesting the feasibility of using synthetic forms of plant miRNAs as dietary supplements in the treatment of human cancers, including those outside of the GI track
    Plant microRNA found to exist in human serum from gut absorption to then alter genetic expression in in-vitro and in vivo studies.
Nathan Goodyear

Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-l... - 0 views

    study finds very low calorie diet reversed diabetes. The greatest weight loss was associated with greatest remission of diabetes at 86% with >15 kg weight loss.
Nathan Goodyear

Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi - 0 views

  • Plant miRNA miR168a was found to present in the sera of mammals including human and regulate human gene LDLRAP1
  • plant miRNAs can present within human circulating system through dietary intake and regulate human gene expression emerged. Broccoli sourced miR159 was found in human sera and proved to inhibit breast cancer growth through targeting the gene TCF7
  • This miRNA, with same 6mer and 7mer-A1 target seed sequence as hsa-miR-4259 and hsa-miR-4715-5p, was predicted to target human JAK-STAT signaling pathway gene SPRY4 and transcription regulation genes through miRTar
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  • plant miRNAs present in human circulating system were proven to be able to target human genes
    Plant microRNA found in human serum.  Previous studies have shown that these plant microRNA's can interact with the human genome.
Nathan Goodyear

Nutrigenomics of extra-virgin olive oil: A review - Piroddi - 2016 - BioFactors - Wiley... - 0 views

    Great review on the nutrigenomics of Olive oil.
Nathan Goodyear

Alternatives for macronutrient intake and chronic disease: a comparison of the OmniHear... - 0 views

    Great review of the macronutrient make up of many popular diets
Nathan Goodyear

From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key... - 0 views

    epigenetics is the key to customizing lifestyle choices to optimize health potential.  It all begins with matching nutrition with epigenetics to limit inflammation.
Nathan Goodyear

Lipid metabolism is associated with developmental epigenetic programming | Scientific R... - 0 views

    maternal diet alters metabolism of offspring via epigenetics.
Nathan Goodyear

Postnatal diet remodels hepatic DNA methylation in metabolic pathways established by a ... - 0 views

    Only abstract available here.  Maternal nutrition, high fat diet in this study, altered genetic expression of offspring to increase future disease risk.  This study would have been better served if they had differentiated fats i.e. PUFA, MUFA, SF, TF....
Nathan Goodyear

Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras | Nature Communi... - 0 views

  • glucose deprivation triggers apoptosis47 and vitamin C treatment kills RAS-oncogene expressing tumor cells, but not wild-type RAS containing cells, by inhibition of GAPDH
    New study out of the UK supports the role of glucose in cancer growth and aggressiveness.  This research found that high influx of glucose into the glycolysis pathway upregulated the RAS oncogene via accumulation of the Fructose 1,6 bisphosphonate through the enzyme phosphofructokinase..
Nathan Goodyear

The emerging role of nutrition in Parkinson's disease - 0 views

    Good review of the current data on the role of nutrition in Parkinson's disease.  Take home, a lot of data is conflicting.  But the figure at the end does well to summarize: diet rich in polyphenols in fruits/veggies, carotenoids, resveratrol, Vitamin C, D, E, and MUFA and PUFA are neuroprotective compared to dairy being neurodegenerative.
Nathan Goodyear

Persistent epigenetic differences associated with prenatal exposure to famine in humans - 0 views

    Epigenetic as a result of famine exposure prenatally.
Nathan Goodyear

Epigenetics: A New Bridge between Nutrition and Health - 0 views

    7 year old study, though very much still relevant.  Nutrition effects epigenetics.
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