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Nathan Goodyear

Caloric restriction increases adiponectin expression by adipose tissue and prevents the... - 0 views

www.jnutbio.com/...abstract

calorie restriction adiponectin insulin resistance adipocytes fat tissue cells overweight obesity

shared by Nathan Goodyear on 31 Jul 12 - No Cached
  • Nathan Goodyear on 31 Jul 12
     
    Calorie restriction increases adiponectin secretion from adipocytes.  Another plus of calorie restriction.  Remember, adiponectin and insulin are inversely associated.  Granted, this is in a rat model, but still supporting the overall health benefits of calorie restriction.
Nathan Goodyear

Protein Restriction, Epigenetic Diet, Intermittent Fasting as New Approaches for Preven... - 0 views

www.ncbi.nlm.nih.gov/...PMC6036773

Cancer "calorie restriction" protein nutrition diet "amino amino acids

shared by Nathan Goodyear on 15 Mar 19 - No Cached
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  • Nathan Goodyear on 15 Mar 19
     
    Calorie restriction and protein restriction inhibit IGF-1, insulin, AkT, PI3K, and mTOR. In addition, those with protein intake >20%, compared to 10%, was associated with a 4 fold increase in cancer death risk and a 75% increase in overall mortality. Protein restriction inhibits tumor growth, associated with a 30-70% reduction in IGF-1, reduced the accumulation of oxidized proteins. The restriction of tryptophan alone reduced inflammation.
Nathan Goodyear

PLOS ONE: Telomerase Reverse Transcriptase Synergizes with Calorie Restriction to Incre... - 0 views

www.plosone.org/...journal.pone.0053760

calorie restriction calorie restriction health Longevity telomere telomeres

shared by Nathan Goodyear on 19 Feb 13 - No Cached
  • Nathan Goodyear on 19 Feb 13
     
    calorie restriction, though not malnutrition, is associated with longevity as determined by increased telomerase reverse transcriptase and a reduction in aged related diseases.  Granted this was a mouse model.
Nathan Goodyear

Press-pulse: a novel therapeutic strategy for the metabolic management of cancer | Nutr... - 0 views

nutritionandmetabolism.biomedcentral.com/...s12986-017-0178-2

ketogenic diet ketogenic press-pulse hyperbaric oxygen therapy HBOTnutrition diet cancer HBOT IVC IV vitamin C DCA dichloracetic acid cancer therapy cancer treatment alternative cancer treatment

shared by Nathan Goodyear on 09 Jul 17 - No Cached
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  • A “press” disturbance was considered a chronic environmental stress on all organisms in an ecological community
  • “pulse” disturbances were considered acute events that disrupted biological communities to produce high mortality
  • Neoplasia involving dysregulated cell growth is the biological endpoint of the disease
  • ...84 more annotations...
  • Data from the American Cancer Society show that the rate of increase in cancer deaths/year (3.4%) was two-fold greater than the rate of increase in new cases/year (1.7%) from 2013 to 2017
  • cancer is predicted to overtake heart disease as the leading cause of death in Western societies
  • cancer can also be recognized as a metabolic disease.
  • glucose is first split into two molecules of pyruvate through the Embden–Meyerhof–Parnas glycolytic pathway in the cytosol
  • Aerobic fermentation, on the other hand, involves the production of lactic acid under normoxic conditions
  • persistent lactic acid production in the presence of adequate oxygen is indicative of abnormal respiration
  • Otto Warburg first proposed that all cancers arise from damage to cellular respiration
  • The Crabtree effect is an artifact of the in vitro environment and involves the glucose-induced suppression of respiration with a corresponding elevation of lactic acid production even under hyperoxic (pO2 = 120–160 mmHg) conditions associated with cell culture
  • the Warburg theory of insufficient aerobic respiration remains as the most credible explanation for the origin of tumor cells [2, 37, 51, 52, 53, 54, 55, 56, 57].
  • The main points of Warburg’s theory are; 1) insufficient respiration is the predisposing initiator of tumorigenesis and ultimately cancer, 2) energy through glycolysis gradually compensates for insufficient energy through respiration, 3) cancer cells continue to produce lactic acid in the presence of oxygen, and 4) respiratory insufficiency eventually becomes irreversible
  • Efraim Racker coined the term “Warburg effect”, which refers to the aerobic glycolysis that occurs in cancer cells
  • Warburg clearly demonstrated that aerobic fermentation (aerobic glycolysis) is an effect, and not the cause, of insufficient respiration
  • all tumor cells that have been examined to date contain abnormalities in the content or composition of cardiolipin
  • The evidence supporting Warburg’s original theory comes from a broad range of cancers and is now overwhelming
  • respiratory insufficiency, arising from any number mitochondrial defects, can contribute to the fermentation metabolism seen in tumor cells.
  • data from the nuclear and mitochondrial transfer experiments suggest that oncogene changes are effects, rather than causes, of tumorigenesis
  • Normal mitochondria can suppress tumorigenesis, whereas abnormal mitochondria can enhance tumorigenesis
  • In addition to glucose, cancer cells also rely heavily on glutamine for growth and survival
  • Glutamine is anapleurotic and can be rapidly metabolized to glutamate and then to α-ketoglutarate for entry into the TCA cycle
  • Glucose and glutamine act synergistically for driving rapid tumor cell growth
  • Glutamine metabolism can produce ATP from the TCA cycle under aerobic conditions
  • Amino acid fermentation can generate energy through TCA cycle substrate level phosphorylation under hypoxic conditions
  • Hif-1α stabilization enhances aerobic fermentation
  • targeting glucose and glutamine will deprive the microenvironment of fermentable fuels
  • Although Warburg’s hypothesis on the origin of cancer has created confusion and controversy [37, 38, 39, 40], his hypothesis has never been disproved
  • Warburg referred to the phenomenon of enhanced glycolysis in cancer cells as “aerobic fermentation” to highlight the abnormal production of lactic acid in the presence of oxygen
  • Emerging evidence indicates that macrophages, or their fusion hybridization with neoplastic stem cells, are the origin of metastatic cancer cells
  • Radiation therapy can enhance fusion hybridization that could increase risk for invasive and metastatic tumor cells
  • Kamphorst et al. in showing that pancreatic ductal adenocarcinoma cells could obtain glutamine under nutrient poor conditions through lysosomal digestion of extracellular proteins
  • It will therefore become necessary to also target lysosomal digestion, under reduced glucose and glutamine conditions, to effectively manage those invasive and metastatic cancers that express cannibalism and phagocytosis.
  • Previous studies in yeast and mammalian cells show that disruption of aerobic respiration can cause mutations (loss of heterozygosity, chromosome instability, and epigenetic modifications etc.) in the nuclear genome
  • The somatic mutations and genomic instability seen in tumor cells thus arise from a protracted reliance on fermentation energy metabolism and a disruption of redox balance through excess oxidative stress.
  • According to the mitochondrial metabolic theory of cancer, the large genomic heterogeneity seen in tumor cells arises as a consequence, rather than as a cause, of mitochondrial dysfunction
  • A therapeutic strategy targeting the metabolic abnormality common to most tumor cells should therefore be more effective in managing cancer than would a strategy targeting genetic mutations that vary widely between tumors of the same histological grade and even within the same tumor
  • Tumor cells are more fit than normal cells to survive in the hypoxic niche of the tumor microenvironment
  • Hypoxic adaptation of tumor cells allows for them to avoid apoptosis due to their metabolic reprograming following a gradual loss of respiratory function
  • The high rates of tumor cell glycolysis and glutaminolysis will also make them resistant to apoptosis, ROS, and chemotherapy drugs
  • Despite having high levels of ROS, glutamate-derived from glutamine contributes to glutathione production that can protect tumor cells from ROS
    • Nathan Goodyear
      Nathan Goodyear on 08 Feb 18
       
      reason to eliminate glutamine in cancer patients and even GSH with cancer patients
  • It is clear that adaptability to environmental stress is greater in normal cells than in tumor cells, as normal cells can transition from the metabolism of glucose to the metabolism of ketone bodies when glucose becomes limiting
  • Mitochondrial respiratory chain defects will prevent tumor cells from using ketone bodies for energy
  • glycolysis-dependent tumor cells are less adaptable to metabolic stress than are the normal cells. This vulnerability can be exploited for targeting tumor cell energy metabolism
  • In contrast to dietary energy reduction, radiation and toxic drugs can damage the microenvironment and transform normal cells into tumor cells while also creating tumor cells that become highly resistant to drugs and radiation
  • Drug-resistant tumor cells arise in large part from the damage to respiration in bystander pre-cancerous cells
  • Because energy generated through substrate level phosphorylation is greater in tumor cells than in normal cells, tumor cells are more dependent than normal cells on the availability of fermentable fuels (glucose and glutamine)
  • Ketone bodies and fats are non-fermentable fuels
  • Although some tumor cells might appear to oxidize ketone bodies by the presence of ketolytic enzymes [181], it is not clear if ketone bodies and fats can provide sufficient energy for cell viability in the absence of glucose and glutamine
  • Apoptosis under energy stress is greater in tumor cells than in normal cells
  • A calorie restricted ketogenic diet or dietary energy reduction creates chronic metabolic stress in the body
  • . This energy stress acts as a press disturbance
  • Drugs that target availability of glucose and glutamine would act as pulse disturbances
  • Hyperbaric oxygen therapy can also be considered another pulse disturbance
  • The KD can more effectively reduce glucose and elevate blood ketone bodies than can CR alone making the KD potentially more therapeutic against tumors than CR
  • Campbell showed that tumor growth in rats is greater under high protein (>20%) than under low protein content (<10%) in the diet
  • Protein amino acids can be metabolized to glucose through the Cori cycle
  • The fats in KDs used clinically also contain more medium chain triglycerides
  • Calorie restriction, fasting, and restricted KDs are anti-angiogenic, anti-inflammatory, and pro-apoptotic and thus can target and eliminate tumor cells through multiple mechanisms
  • Ketogenic diets can also spare muscle protein, enhance immunity, and delay cancer cachexia, which is a major problem in managing metastatic cancer
  • GKI values of 1.0 or below are considered therapeutic
  • The GKI can therefore serve as a biomarker to assess the therapeutic efficacy of various diets in a broad range of cancers.
  • It is important to remember that insulin drives glycolysis through stimulation of the pyruvate dehydrogenase complex
  • The water-soluble ketone bodies (D-β-hydroxybutyrate and acetoacetate) are produced largely in the liver from adipocyte-derived fatty acids and ketogenic dietary fat. Ketone bodies bypass glycolysis and directly enter the mitochondria for metabolism to acetyl-CoA
  • Due to mitochondrial defects, tumor cells cannot exploit the therapeutic benefits of burning ketone bodies as normal cells would
  • Therapeutic ketosis with racemic ketone esters can also make it feasible to safely sustain hypoglycemia for inducing metabolic stress on cancer cells
    • Nathan Goodyear
      Nathan Goodyear on 08 Feb 18
       
      Ketones are much more than energy adaptabilit, but actually are therapeutic.
  • ketone bodies can inhibit histone deacetylases (HDAC) [229]. HDAC inhibitors play a role in targeting the cancer epigenome
  • Therapeutic ketosis reduces circulating inflammatory markers, and ketones directly inhibit the NLRP3 inflammasome, an important pro-inflammatory pathway linked to carcinogenesis and an important target for cancer treatment response
  • Chronic psychological stress is known to promote tumorigenesis through elevations of blood glucose, glucocorticoids, catecholamines, and insulin-like growth factor (IGF-1)
  • In addition to calorie-restricted ketogenic diets, psychological stress management involving exercise, yoga, music etc. also act as press disturbances that can help reduce fatigue, depression, and anxiety in cancer patients and in animal models
  • Ketone supplementation has also been shown to reduce anxiety behavior in animal models
  • This physiological state also enhances the efficacy of chemotherapy and radiation therapy, while reducing the side effects
  • lower dosages of chemotherapeutic drugs can be used when administered together with calorie restriction or restricted ketogenic diets (KD-R)
  • Besides 2-DG, a range of other glycolysis inhibitors might also produce similar therapeutic effects when combined with the KD-R including 3-bromopyruvate, oxaloacetate, and lonidamine
    • Nathan Goodyear
      Nathan Goodyear on 08 Feb 18
       
      oxaloacetate is a glycolytic inhibitor, as is doxycycline, and IVC.
  • A synergistic interaction of the KD diet plus radiation was seen
  • It is important to recognize, however, that the radiotherapy used in glioma patients can damage the respiration of normal cells and increase availability of glutamine in the microenvironment, which can increase risk of tumor recurrence especially when used together with the steroid drug dexamethasone
  • Poff and colleagues demonstrated that hyperbaric oxygen therapy (HBOT) enhanced the ability of the KD to reduce tumor growth and metastasis
  • HBOT also increases oxidative stress and membrane lipid peroxidation of GBM cells in vitro
  • The effects of the KD and HBOT can be enhanced with administration of exogenous ketones, which further suppressed tumor growth and metastasis
  • Besides HBOT, intravenous vitamin C and dichloroacetate (DCA) can also be used with the KD to selectively increase oxidative stress in tumor cells
  • Recent evidence also shows that ketone supplementation may enhance or preserve overall physical and mental health
  • Some tumors use glucose as a prime fuel for growth, whereas other tumors use glutamine as a prime fuel [102, 186, 262, 263, 264]. Glutamine-dependent tumors are generally less detectable than glucose-dependent under FDG-PET imaging, but could be detected under glutamine-based PET imaging
  • GBM and use glutamine as a major fuel
  • Many of the current treatments used for cancer management are based on the view that cancer is a genetic disease
  • Emerging evidence indicates that cancer is a mitochondrial metabolic disease that depends on availability of fermentable fuels for tumor cell growth and survival
  • Glucose and glutamine are the most abundant fermentable fuels present in the circulation and in the tumor microenvironment
  • Low-carbohydrate, high fat-ketogenic diets coupled with glycolysis inhibitors will reduce metabolic flux through the glycolytic and pentose phosphate pathways needed for synthesis of ATP, lipids, glutathione, and nucleotides
  • Nathan Goodyear on 09 Jul 17
     
    Cancer is a mitochondrial disease? So says the well published Dr Seyfried. Glucose and glutamine drive cancer growth.
Nathan Goodyear

Evaluation of the effect of caloric restriction on... [Endocrine. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...19012000

BDNF obesity calorie restriction calorie-restriction neuroplasticity neurogenesis

shared by Nathan Goodyear on 25 Jun 12 - No Cached
  • Nathan Goodyear on 25 Jun 12
     
    In this study, weight loss through a calorie restriction diet, resulted in  an increase in BDNF.  The implications here is that obesity decreases BDNF, which is very important in neuroplasticity and neurogenesis.  Take home, obesity has negative effects on your brain. Remember that old commercial: "this is your brain on drugs".  Well, this is your brain with obesity.
Nathan Goodyear

Caloric Restriction Increases Serum Testoster... [Horm Metab Res. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24198220

low T Testosterone calorie restriction calorie restriction obesity aromatase men male hormone hormones

shared by Nathan Goodyear on 19 Feb 14 - No Cached
  • Nathan Goodyear on 19 Feb 14
     
    Calorie restriction increases serum Testosterone levels in obese men.  This fits with other research that weight reduction in obese men can resolve low T.  The obvious proposed mechanisms are a reduction in aromatase activity due to a loss of adiposity, a decrease in inflammatory cytokine production thus negatively effecting the HPA, improved HPA signaling and thus improved Testicular production of Testosterone.
fitspresso

https://www.thefastleanpro.us/ - 0 views

www.thefastleanpro.us

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shared by fitspresso on 27 Sep 23 - No Cached
  • fitspresso on 27 Sep 23
     
    Fast Lean Pro™ (official) | weight lose Formula thefastleanpro.us · by Fast Lean Pro Fast Lean Pro Only $49/Bottle Limited Time Offer! Fast Lean Pro Special Deal + Special 51% Discount Save $300 + 180 Days Money Back Guarantee FastLeanPro The #1 Solution To natural metabolism booster helps you lose weight quickly without starving yourself. Fast Lean Pro is a natural powder supplement for weight loss that has recently been developed by Japanese scientists. Regular Price: $99/per bottle Only for: $49/per bottle What Is Fast Lean Pro? Fast Lean Pro is a powdered dietary powdery supplement designed to aid in weight loss. It contains a unique combination of ingredients that are believed to activate the body's "fasting switch" to optimize results. This product focuses not only on weight loss but also on promoting cellular rejuvenation, fasting, and a healthy metabolism. The concept behind Fast Lean Pro is that incorporating fasting into one's lifestyle can lead to positive outcomes irrespective of individual food choices and eating habits. To comprehend the mechanism of the Fast Lean Pro process, it is necessary to delve into its specific details. One of the few weight loss pills on the market that contains Fibersol is Fast Lean Pro. This safe, specialized fiber adds bulk to its weight when combined with water, curbing your appetite before it throws off your meal plan. If you're trying to lose weight or curb your appetite, Fast Lean Pro can help. Supporting substances such as niacin and chromium contribute to this. The body can further benefit from these nutrients, such as through improved metabolic regulation. Fast lean Pro is non-GMO, vegan friendly, and contains no artificial ingredients or stimulants. Fast Lean Pro is a weight loss product that promotes the body's natural self-feeding process. The body naturally removes old, damaged cells through a process known as autophagy to encourage cell regeneration and repair. Recent studies by a group
Nathan Goodyear

An adaptive response to uncertainty can lead to weight gain during dieting attempts - 0 views

emph.oxfordjournals.org/...369.full

weight loss nutrition diet weight obesity overweight dieting

shared by Nathan Goodyear on 03 Jan 17 - No Cached
  • dieting attempts cause weight gain via providing (misleading) information about the environment to the subconscious systems that control body mass
  • Our model predicts that energy reserves should respond to repeated attempts to diet by weight cycling and becoming greater from one cycle to the next
  • the very conditions that cause weight gain initially—a glut of food—causes further weight gain once cyclical dieting begins
  • ...1 more annotation...
  • There is evidence that among weight cycling, people those who switch between dieting and binge-eating more frequently gain more weight
  • Nathan Goodyear on 03 Jan 17
     
    yo-yo dieting leads to weight gain, in part, due to increase food intake in between the calorie restriction phases.  The calorie restriction suppresses metabolic rate and results in muscle loss; both of which contribute to the rebound weight gain seen by so many.
Nathan Goodyear

THE NEUROPROTECTIVE PROPERTIES OF CALORIE RESTRICTION, THE KETOGENIC DIET, AND KETONE B... - 0 views

www.ncbi.nlm.nih.gov/...PMC2649682

calorie restriction ketogenic diet NF-KappaB BDNF neuroprotection SIRT1 mitochondria glutamate excitotoxicity inflammation antioxidants

shared by Nathan Goodyear on 25 Jun 12 - No Cached
  • Nathan Goodyear on 25 Jun 12
     
    Fantastic read on the biochemical benefits of calorie restriction and a ketogenic diet.
Nathan Goodyear

Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation,... - 0 views

jama.ama-assn.org/...1539.full

overweight weight loss obesity calorie restriction metabolism

shared by Nathan Goodyear on 11 Jul 11 - No Cached
  • Nathan Goodyear on 11 Jul 11
     
    prolonged calorie restriction results in loss of muscle mass, which results in decreased metabolism
Nathan Goodyear

Long-term effects of calorie restriction on serum sex hormone concentrations in men - 0 views

www.ncbi.nlm.nih.gov/...PMC3569090

calorie restriction Testosterone low T low Testosterone male hormones' nutrition diet

shared by Nathan Goodyear on 27 Sep 16 - No Cached
  • Nathan Goodyear on 27 Sep 16
     
    long term calorie restriction resulted in a decrease in total Testosterone and free Testosterone; an increase in SHBG was found.
Nathan Goodyear

Alterations in male sexual behaviour, attractiveness and testosterone levels induced by... - 0 views

www.ncbi.nlm.nih.gov/...18367259

nutrition diet male hormones' men hormones Testosterone low t Testosterone calorie restriction

shared by Nathan Goodyear on 27 Sep 16 - No Cached
  • Nathan Goodyear on 27 Sep 16
     
    animal study found that calorie restriction lowers Testosterone.
Nathan Goodyear

Caloric restriction modulates Mcl-1 expression and sensitizes lymphomas to BH3 mimetic ... - 0 views

bloodjournal.hematologylibrary.org/...blood-2013-01-478651

calorie restriction cancer

shared by Nathan Goodyear on 28 Aug 13 - No Cached
  • Nathan Goodyear on 28 Aug 13
     
    Calorie restriction aids fight against cancer on several fronts.  Granted this is a mouse study, but Cancer should be attacked through nutrition just as through surgery and chemo/radiation.
Nathan Goodyear

Caloric restriction delays age-related methylation drift | Nature Communications - 0 views

www.nature.com/...s41467-017-00607-3

calorie restriction epigenetics

shared by Nathan Goodyear on 27 Feb 18 - No Cached
  • Nathan Goodyear on 27 Feb 18
     
    How does calorie restriction work? Epigenetics.
Nathan Goodyear

Reduction of Chronic Hyperinsulinemia (Insulin Resistance) for the Prevention and Treat... - 0 views

fasting calorie restriction insulin resistance hyperinsulinemia cancer

shared by Nathan Goodyear on 10 Jan 21 - No Cached
  • Nathan Goodyear on 10 Jan 21
     
    Fasting and calorie restriction are a means to attack hyperinsulinemia and insulin resistance.
Nathan Goodyear

Caloric restriction improves memory in elderly humans - 0 views

www.pnas.org/...0808587106.full.pdf+html

calorie restriction calorie-restriction memory elderly

shared by Nathan Goodyear on 25 Jun 12 - No Cached
  • Nathan Goodyear on 25 Jun 12
     
    30% caloric restriction significantly improved memory/cognitive function in elderly.
Nathan Goodyear

Fuel metabolism in starvation - 0 views

www.med.upenn.edu/...ewArticleTIMM2008-9Lazar-1.pdf

metabolism fasting calorie restriction

shared by Nathan Goodyear on 01 Jul 13 - No Cached
  • Nathan Goodyear on 01 Jul 13
     
    Great review of the metabolic changes that the body undergoes during calorie restriction/fasting
Nathan Goodyear

Energy Intake and Prostate Tumor Growth, Angiogenesis, and Vascular Endothelial Growth ... - 0 views

jnci.oxfordjournals.org/...512.long

prostate cancer tumor angiogenesis calorie restriction

shared by Nathan Goodyear on 02 Jul 13 - No Cached
  • Nathan Goodyear on 02 Jul 13
     
    Granted, this is prostate tumor rat model.  But, a calorie restriction of 20-40% resulted in reduced tumor growth through inhibition of angiogenesis.
Nathan Goodyear

Ketoacids? Good medicine? - 0 views

www.ncbi.nlm.nih.gov/...tacca00002-0213.pdf

Beta-hydroxybutyrate brain neurology neuroplasticity neurogenesis inflammation calorie restriction ketosis ketoacids

shared by Nathan Goodyear on 25 Jun 12 - No Cached
  • Nathan Goodyear on 25 Jun 12
     
    Great, great read on how biochemistry effects brain function. Beta-hydroxybutyrate is an alternative fuel source for the brain in times of calorie restriction. This promotes neuroplasticity and neurogenesis without the inflammatory effects of glucose and insulin.
Nathan Goodyear

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

www.frontiersin.org/...full

press-pulse therapy hyperbaric ketogenic metabolic therapy cancer ketogenic diet Glioblastoma glioblastoma multiforme HBOT nutrition

shared by Nathan Goodyear on 01 Apr 18 - No Cached
  • 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
  • ...30 more annotations...
  • 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
      Nathan Goodyear on 21 May 18
       
      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
  • Nathan Goodyear on 01 Apr 18
     
    Case study of Glioblastoma treated with ketogenic metabolic therapy as an adjuct to modified standard therapy.
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