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Nathan Goodyear

Fructose: A Key Factor in the Development of Metabolic Syndrome and Hypertension - 0 views

www.ncbi.nlm.nih.gov/...PMC3677638

fructose phosphofructokinase MetS metabolic syndrome metabolic syndrome insulin resistance ATP mitochondria uric acid

shared by Nathan Goodyear on 01 Oct 13 - No Cached
  • Nathan Goodyear on 01 Oct 13
     
    Fructose intake increases MetS and hypertension.  The high fructose intake upregulates phosphofructokinase which increases triglyceride production, bypassing central regulation.  This results in ATP depletion with reduced capacity to recover.  Thus attempts by the cells to increase ATP through AMP deaminase results in uric acid production.
Nathan Goodyear

Metabolic management of brain cancer - 0 views

www.sciencedirect.com/...S0005272810006857

brain cancer

shared by Nathan Goodyear on 17 Jun 13 - No Cached
  • Glutamine is a major metabolic fuel for both brain tumor cells and tumor-associated macrophages (TAMs)
  • the malignant phenotype of brain tumor cells that survive radiotherapy is often greater than that of the cells from the original tumor.
  • Conventional chemotherapy has faired little better than radiation therapy for the long-term management of malignant brain cancer
  • ...37 more annotations...
  • most conventional radiation and brain cancer chemotherapies can enhance glioma energy metabolism and invasive properties, which would contribute to tumor recurrence and reduced patient survival [34].
  • We contend that all cancer regardless of tissue or cellular origin is a disease of abnormal energy metabolism
  • complex disease phenotypes can be managed through self-organizing networks that display system wide dynamics involving oxidative and non-oxidative (substrate level) phosphorylation
  • As long as brain tumors are provided a physiological environment conducive for their energy needs they will survive; when this environment is restricted or abruptly changed they will either grow slower, growth arrest, or perish [8] and [19]
  • New information also suggests that ketones are toxic to some human tumor cells and that ketones and ketogenic diets might restrict availability of glutamine to tumor cells [68], [69] and [70].
  • The success in dealing with environmental stress and disease is therefore dependent on the integrated action of all cells in the organism
  • Tumor cells survive in hypoxic environments not because they have inherited genes making them more fit or adaptable than normal cells, but because they have damaged mitochondria and have thus acquired the ability to derive energy largely through substrate level phosphorylation
  • Cancer cells survive and multiply only in physiological environments that provide fuels (mostly glucose and glutamine) subserving their requirement for substrate level phosphorylation
  • Integrity of the inner mitochondrial membrane is necessary for ketone body metabolism since β-hydroxybutyrate dehydrogenase, which catalyzes the first step in the metabolism of β-OHB to acetoacetate, interacts with cardiolipin and other phospholipids in the inner membrane
  • the mitochondria of many gliomas and most tumors for that matter are dysfunctional
  • Cardiolipin is essential for efficient oxidative energy production and mitochondrial function
  • Any genetic or environmental alteration in the content or composition of cardiolipin will compromise energy production through oxidative phosphorylation
  • The Crabtree effect involves the inhibition of respiration by high levels of glucose
  • the Warburg effect involves elevated glycolysis from impaired oxidative phosphorylation
  • the Crabtree effect can be reversible, the Warburg effect is largely irreversible because its origin is with permanently damaged mitochondria
  • The continued production of lactic acid in the presence of oxygen is the metabolic hallmark of most cancers and is referred to as aerobic glycolysis or the Warburg effect
  • We recently described how the retrograde signaling system could induce changes in oncogenes and tumor suppressor genes to facilitate tumor cell survival following mitochondrial damage [48].
  • In addition to glycolysis, glutamine can also increase ATP production under hypoxic conditions through substrate level phosphorylation in the TCA cycle after its metabolism to α-ketoglutarate
  • mitochondrial lipid abnormalities, which alter electron transport activities, can account in large part for the Warburg effect
  • targeting both glucose and glutamine metabolism could be effective for managing most cancers including brain cancer
  • The bulk of experimental evidence indicates that mitochondria are dysfunctional in tumors and incapable of generating sufficient ATP through oxidative phosphorylation
  • Cardiolipin defects in tumor cells are also associated with reduced activities of several enzymes of the mitochondrial electron transport chain making it unlikely that tumor cells with cardiolipin abnormalities can generate adequate energy through oxidative phosphorylation
  • The Crabtree effect involves the inhibition of respiration by high levels of glucose
  • Warburg effect involves elevated glycolysis from impaired oxidative phosphorylation
  • TCA cycle substrate level phosphorylation could therefore become another source of ATP production in tumor cells with impairments in oxidative phosphorylation
  • Caloric restriction, which lowers glucose and elevates ketone bodies [63] and [64], improves mitochondrial respiratory function and glutathione redox state in normal cells
  • DR naturally inhibits glycolysis and tumor growth by lowering circulating glucose levels, while at the same time, enhancing the health and vitality of normal cells and tissues through ketone body metabolism
  • DR is anti-angiogenic
  • DR also reduces angiogenesis in prostate and breast cancer
  • We suggest that apoptosis resistance arises largely from enhanced substrate level phosphorylation of tumor cells and to the genes associated with elevated glycolysis and glutaminolysis, e.g., c-Myc, Hif-1a, etc, which inhibit apoptosis
  • Modern medicine has not looked favorably on diet therapies for managing complex diseases especially when well-established procedures for acceptable clinical practice are available, regardless of how ineffective these procedures might be in managing the disease
  • More than 60 years of clinical research indicates that such approaches are largely ineffective in extending survival or improving quality of life
  • The process is rooted in the well-established scientific principle that tumor cells are largely dependent on substrate level phosphorylation for their survival and growth
  • Glucose and glutamine drive substrate level phosphorylation
  • targeting the glycolytically active tumor cells that produce pro-cachexia molecules, restricted diet therapies can potentially reduce tumor cachexia
  • It is important to recognize, however, that “more is not better” with respect to the ketogenic diet
  • Blood glucose ranges between 3.0 and 3.5 mM (55–65 mg/dl) and β-OHB ranges between 4 and 7 mM should be effective for tumor management
  • Nathan Goodyear on 17 Jun 13
     
    Dr Seyfriend presents his metabolic approach to the treatment of brain cancer.
Nathan Goodyear

Higher dietary fructose is associated with impaired hepatic adenosine triphosphate home... - 0 views

onlinelibrary.wiley.com/...34FD9FE5A86A5E9B8BE0490.d03t04

fructose uric acid ATP metabolic syndrome

shared by Nathan Goodyear on 17 Sep 13 - No Cached
  • Nathan Goodyear on 17 Sep 13
     
    uric acid used as marker for impaired ATP production in those with high fructose intake.
Nathan Goodyear

Higher dietary fructose is associated with impaired hepatic adenosine triphosphate home... - 0 views

onlinelibrary.wiley.com/...7A09FEEBBB7F7951B7A9695.f03t01

fructose uric acid nutrition ATP diabetes mitochondria

shared by Nathan Goodyear on 01 Oct 13 - No Cached
  • Nathan Goodyear on 01 Oct 13
     
    uric acid used to monitor liver's response to fructose.  Some have called it fructose toxicity.  The point, is that a high uric acid points to poor ATP recovery (mitochondria) in the fact of fructose.
Nathan Goodyear

Uric acid induces hepatic steatosis by generatio... [J Biol Chem. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23035112

uric acid mitochondria non-alcoholic fatty liver fructose triglyceride oxidative stress fatty liver liver ATP

shared by Nathan Goodyear on 01 Oct 13 - No Cached
  • Nathan Goodyear on 01 Oct 13
     
    Elevated uric acid levels up regulate fructose metabolism to triglycerides and fatty liver.  This study finds that liver mitochondrial oxidative stress is also evident.  This mitochondrial dysfunction also leads to compromised ATP production and fat accumulation specifically through inhibition of aconitase..
Nathan Goodyear

Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflamm... - 0 views

www.cell.com/...S0092-8674(16)31162-X

inflammation LPS macrophages lipopolysaccharide mitochondria energy ATP ROS

shared by Nathan Goodyear on 12 Oct 16 - No Cached
  • Nathan Goodyear on 12 Oct 16
     
    Fascinating study: inflammation via LPS induces pro-inflammatory move by macrophages that induces a change in mitochondria to increase inflammation and decrease ATP production.
Nathan Goodyear

T3 increases mitochondrial ATP production in oxidative muscle despite increased express... - 0 views

ajpendo.physiology.org/...E761.long

T3 hypothyroid hypothyroidism cancer oxidative phosphorylation mitochondria thyroid hormone hormones atp

shared by Nathan Goodyear on 29 Jun 13 - No Cached
  • Nathan Goodyear on 29 Jun 13
     
    This study finds that T3 increases enzymes in the oxidative phosphorylation pathways and not in the glycolytic pathways in mitochondria.  This has enormous health implications, especially in cancer.  This also casts doubt on the current traditional medical dogma of hypothyroid evaluation and management which gives no regard to T3 in testing or therapy.
Nathan Goodyear

NAD+ and Vitamin B3: From Metabolism to Therapies - 0 views

jpet.aspetjournals.org/...883.full

NAD NADH Niacin vitamin B3

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • Nathan Goodyear on 21 Jan 14
     
    NAD+ is very important in ATP production and as a means to counter free radicals.  This is a nice discussion of NAD metabolism.  
Nathan Goodyear

JISSN | Full text | International Society of Sports Nutrition position stand: creatine ... - 0 views

www.jissn.com/6

creatine sports nutrition exercise

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • the energy supplied to rephosphorylate adenosine diphosphate (ADP) to adenosine triphosphate (ATP) during and following intense exercise is largely dependent on the amount of phosphocreatine (PCr) stored in the muscle
  • Creatine is chemically known as a non-protein nitrogen
  • It is synthesized in the liver and pancreas from the amino acids arginine, glycine, and methionine
  • ...26 more annotations...
  • Approximately 95% of the body's creatine is stored in skeletal muscle
  • About two thirds of the creatine found in skeletal muscle is stored as phosphocreatine (PCr) while the remaining amount of creatine is stored as free creatine
  • The body breaks down about 1 – 2% of the creatine pool per day (about 1–2 grams/day) into creatinine in the skeletal muscle
  • The magnitude of the increase in skeletal muscle creatine content is important because studies have reported performance changes to be correlated to this increase
  • "loading" protocol. This protocol is characterized by ingesting approximately 0.3 grams/kg/day of CM for 5 – 7 days (e.g., ≃5 grams taken four times per day) and 3–5 grams/day thereafter [18,22]. Research has shown a 10–40% increase in muscle creatine and PCr stores using this protocol
  • Additional research has reported that the loading protocol may only need to be 2–3 days in length to be beneficial, particularly if the ingestion coincides with protein and/or carbohydrate
  • A few studies have reported protocols with no loading period to be sufficient for increasing muscle creatine (3 g/d for 28 days)
  • Cycling protocols involve the consumption of "loading" doses for 3–5 days every 3 to 4 weeks
  • Most of these forms of creatine have been reported to be no better than traditional CM in terms of increasing strength or performance
  • Recent studies do suggest, however, that adding β-alanine to CM may produce greater effects than CM alone
  • These investigations indicate that the combination may have greater effects on strength, lean mass, and body fat percentage; in addition to delaying neuromuscular fatigue
  • creatine phosphate has been reported to be as effective as CM at improving LBM and strength
  • Green et al. [24] reported that adding 93 g of carbohydrate to 5 g of CM increased total muscle creatine by 60%
  • Steenge et al. [23] reported that adding 47 g of carbohydrate and 50 g of protein to CM was as effective at promoting muscle retention of creatine as adding 96 g of carbohydrate.
  • It appears that combining CM with carbohydrate or carbohydrate and protein produces optimal results
  • Studies suggest that increasing skeletal muscle creatine uptake may enhance the benefits of training
  • Nearly 70% of these studies have reported a significant improvement in exercise capacity,
  • Long-term CM supplementation appears to enhance the overall quality of training, leading to 5 to 15% greater gains in strength and performance
  • Nearly all studies indicate that "proper" CM supplementation increases body mass by about 1 to 2 kg in the first week of loading
  • short-term adaptations reported from CM supplementation include increased cycling power, total work performed on the bench press and jump squat, as well as improved sport performance in sprinting, swimming, and soccer
  • Long-term adaptations when combining CM supplementation with training include increased muscle creatine and PCr content, lean body mass, strength, sprint performance, power, rate of force development, and muscle diameter
  • subjects taking CM typically gain about twice as much body mass and/or fat free mass (i.e., an extra 2 to 4 pounds of muscle mass during 4 to 12 weeks of training) than subjects taking a placebo
  • The gains in muscle mass appear to be a result of an improved ability to perform high-intensity exercise via increased PCr availability and enhanced ATP synthesis, thereby enabling an athlete to train harder
  • there is no evidence to support the notion that normal creatine intakes (< 25 g/d) in healthy adults cause renal dysfunction
  • no long-term side effects have been observed in athletes (up to 5 years),
  • One cohort of patients taking 1.5 – 3 grams/day of CM has been monitored since 1981 with no significant side effects
  • Nathan Goodyear on 27 Jan 14
     
    Nice review of the data, up to the publication date, on creatine.
Nathan Goodyear

Anticancer efficacy of the metabolic blocker ... [Anticancer Res. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23267123

3-bromopyruvate 3-BrPA cancer

shared by Nathan Goodyear on 11 Sep 13 - No Cached
  • Nathan Goodyear on 11 Sep 13
     
    3-bromopyruvate to target glycolysis and shut down ATP production in cancer cells.
Nathan Goodyear

3-Bromopyruvate (3BP) a fast acting, pro... [J Bioenerg Biomembr. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...22382780

cancer 3-bromopyruvate 3-BrPA

shared by Nathan Goodyear on 11 Sep 13 - No Cached
  • Nathan Goodyear on 11 Sep 13
     
    Just the abstract of this article is available.  3-Bromopyruvate useful in cancer treatments to stunt cancer ATP production.
Nathan Goodyear

Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin indu... - 0 views

www.ncbi.nlm.nih.gov/...PMC4639773

ivermectin cancer breast cancer

shared by Nathan Goodyear on 20 Mar 18 - No Cached
  • ATP can function as a prototypical danger signal that activates a potent immune response, but can also promote cancer progression
  • tumor growth and survival appears to critically
  • our findings indicate that Ivermectin may kill cancer cells though a mechanism combining apoptosis and necrosis/pyroptosis
  • ...1 more annotation...
  • Ivermectin has recently been shown to have anti-tumor properties that we hereby link to its ability to augment P2X4/P2X7/Pannexin-1 signaling and caspase-1 activation, which is also associated with cancer cells’ elevated expression of P2X4/P2X7 receptors
  • Nathan Goodyear on 20 Mar 18
     
    Ivermectin shown to induce apoptosis, necrosis, and autophagy in shows syngergist activity with chemotherapy.  This was shown in triple negative breast cancer cell lines which are more resistent to therapy.
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

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer - 0 views

www.ncbi.nlm.nih.gov/...PMC2567082

cancer dichloroacetate dichloracetic acid DCA

shared by Nathan Goodyear on 07 Nov 18 - No Cached
  • The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis
  • The most important reason for the poor performance of cancer drugs is the remarkable heterogeneity and adaptability of cancer cells. The molecular characteristics of histologically identical cancers are often dissimilar and molecular heterogeneity frequently exists within a single tumour.
  • Because GO is far more efficient in generating ATP compared with GLY (producing 36 vs 2 ATP per glucose
  • ...9 more annotations...
  • molecule), cancer cells upregulate glucose receptors and significantly increase glucose uptake in an attempt to ‘catch up
  • early carcinogenesis often occurs in a hypoxic microenvironment, the transformed cells have to rely on anaerobic GLY for energy production.
  • Hypoxia-inducible factor (HIF) is activated in hypoxic conditions
  • evidence suggests that transformation to a glycolytic phenotype offers resistance to apoptosis
  • non-small cell lung cancer, breast cancer and glioblastoma
  • Dichloroacetate activated the pyruvate dehydrogenase, which resulted in increased delivery of pyruvate into the mitochondria
  • DCA increased GO and depolarised the mitochondria, returning the membrane potential towards the levels of the non-cancer cells, without affecting the mitochondria of non-cancerous cells
  • induction of apoptosis by DCA in non-small cell lung cancer, breast cancer and glioblastoma cell lines
  • DCA was shown to induce apoptosis in endometrial (Wong et al, 2008) and prostate (Cao et al, 2008) cancer cells
  • Nathan Goodyear on 07 Nov 18
     
    DCA as targeted therapy in cancer.
Nathan Goodyear

T3 increases mitochondrial ATP production in oxidative muscle despite increased express... - 0 views

ajpendo.physiology.org/...E761.full.pdf

T3 hypothyroid hypothyroidism Cancer

shared by Nathan Goodyear on 28 Jun 13 - No Cached
  • Nathan Goodyear on 28 Jun 13
     
    T3 increases mitochondrial oxidative phosphorylation. This has huge impacts on which hypothyroidism is currently managed (only evaluate TSH and T4) and disease implication. We know that decoupling of oxidative phosporylation and a shift to glycolysis and glutaminolysis (substrate-level phosphorylation) results in genomic mutability and cancer, then a low T3 has implications in cancer prevention
Nathan Goodyear

Pathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells - 0 views

www.jbc.org/...21767.full

NAD mitochondria ATP

shared by Nathan Goodyear on 07 Jun 16 - No Cached
  • Nathan Goodyear on 07 Jun 16
     
    review of mammalian mitochondrial NAD pathways.
Nathan Goodyear

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3 | ... - 0 views

embomolmed.embopress.org/...721.full

NAD nicotinamide riboside mitochondria vitamin B3 ATP disease

shared by Nathan Goodyear on 07 Jun 16 - No Cached
  • Nathan Goodyear on 07 Jun 16
     
    NAD in the form of nicotinamide riboside found to be effective in treating mitochondrial myopathy in animal model.
Nathan Goodyear

Atorvastatin treatment reduces exercise capac... [J Appl Physiol. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21852406

statin mitochondria energy ATP muscle damage performance exercise

shared by Nathan Goodyear on 16 Mar 12 - No Cached
  • Nathan Goodyear on 16 Mar 12
     
    statin therapy damages mitochondria. Mitochondria are the powerhouses of the cell: they are the energy producers of the cell.  It is no surprise that damage to the cells capacity to make energy will in turn decrease the capacity of muscle to perform.
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