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Nathan Goodyear

Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde... - 0 views

www.hindawi.com/...360438

MDA malondialdehyde peroxidation oxidative stress free radicals

shared by Nathan Goodyear on 05 Dec 17 - No Cached
  • Hydroxyl radicals cause oxidative damage to cells because they unspecifically attack biomolecules [22] located less than a few nanometres from its site of generation and are involved in cellular disorders such as neurodegeneration [23, 24], cardiovascular disease [25], and cancer [26, 27].
  • It is generally assumed that in biological systems is formed through redox cycling by Fenton reaction, where free iron (Fe2+) reacts with hydrogen peroxide (H2O2) and the Haber-Weiss reaction that results in the production of Fe2+ when superoxide reacts with ferric iron (Fe3+)
  • other transition-metal including Cu, Ni, Co, and V can be responsible for formation in living cells
  • ...20 more annotations...
  • The hydroperoxyl radical () plays an important role in the chemistry of lipid peroxidation
  • The is a much stronger oxidant than superoxide anion-radical
  • Lipid peroxidation can be described generally as a process under which oxidants such as free radicals or nonradical species attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs) that involve hydrogen abstraction from a carbon, with oxygen insertion resulting in lipid peroxyl radicals and hydroperoxides as described previously
  • under medium or high lipid peroxidation rates (toxic conditions) the extent of oxidative damage overwhelms repair capacity, and the cells induce apoptosis or necrosis programmed cell death
  • The overall process of lipid peroxidation consists of three steps: initiation, propagation, and termination
  • Once lipid peroxidation is initiated, a propagation of chain reactions will take place until termination products are produced.
  • The main primary products of lipid peroxidation are lipid hydroperoxides (LOOH)
  • Among the many different aldehydes which can be formed as secondary products during lipid peroxidation, malondialdehyde (MDA), propanal, hexanal, and 4-hydroxynonenal (4-HNE) have been extensively studied
  • MDA has been widely used for many years as a convenient biomarker for lipid peroxidation of omega-3 and omega-6 fatty acids because of its facile reaction with thiobarbituric acid (TBA)
  • MDA is one of the most popular and reliable markers that determine oxidative stress in clinical situations [53], and due to MDA’s high reactivity and toxicity underlying the fact that this molecule is very relevant to biomedical research community
  • 4-HNE is considered as “second toxic messengers of free radicals,” and also as “one of the most physiologically active lipid peroxides,” “one of major generators of oxidative stress,” “a chemotactic aldehydic end-product of lipid peroxidation,” and a “major lipid peroxidation product”
  • MDA is an end-product generated by decomposition of arachidonic acid and larger PUFAs
  • Identifying in vivo MDA production and its role in biology is important as indicated by the extensive literature on the compound (over 15 800 articles in the PubMed database using the keyword “malondialdehyde lipid peroxidation” in December 2013)
  • MDA reactivity is pH-dependent
  • When pH decreases MDA exists as beta-hydroxyacrolein and its reactivity increases
  • MAA adducts are shown to be highly immunogenic [177–181]. MDA adducts are biologically important because they can participate in secondary deleterious reactions (e.g., crosslinking) by promoting intramolecular or intermolecular protein/DNA crosslinking that may induce profound alteration in the biochemical properties of biomolecules and accumulate during aging and in chronic diseases
  • MDA is an important contributor to DNA damage and mutation
  • This MDA-induced DNA alteration may contribute significantly to cancer and other genetic diseases.
  • Dietary intake of certain antioxidants such as vitamins was associated with reduced levels of markers of DNA oxidation (M1dG and 8-oxodG) measured in peripheral white blood cells of healthy subjects, which could contribute to the protective role of vitamins on cancer risk
  • 4-HNE is an extraordinarily reactive compound
  • Nathan Goodyear on 05 Dec 17
     
    Great review of lipid peroxidation
Nathan Goodyear

A pyrazole curcumin derivative restores membrane homeostasis disrupted after brain trauma - 0 views

www.ncbi.nlm.nih.gov/...PMC3225197

brain trauma TBI curcumin lipid peroxidation

shared by Nathan Goodyear on 01 Nov 13 - No Cached
  • Nathan Goodyear on 01 Nov 13
     
    TBI associated with increased  4-Hydroxynonenal.  This is associated with increased lipid per oxidation.  Curcumin protects against this lipid peroxidation per this study.
Nathan Goodyear

Adherence to a Mediterranean diet and plasma concentrations of lipid peroxidation in pr... - 0 views

www.ncbi.nlm.nih.gov/...PMC2980970

mediterranean diet mediterranean nutrition diet lipid peroxidation oxidation oxidative stress

shared by Nathan Goodyear on 17 Oct 16 - No Cached
  • Nathan Goodyear on 17 Oct 16
     
    Mediterranean diet associated with reduced lipid peroxidation.
Nathan Goodyear

Inhibition of lipid peroxidation and pr... [Biochim Biophys Acta. 2006] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...16236451

lipid peroxidation curcumin

shared by Nathan Goodyear on 03 Nov 13 - No Cached
  • Nathan Goodyear on 03 Nov 13
     
    Animal model finds that curcumin inhibits lipid peroxidation.
Nathan Goodyear

JAMA Network | Archives of Neurology | Damage to Lipids, Proteins, DNA, and RNA in Mild... - 0 views

archneur.jamanetwork.com/article.aspx

neurodegenerative disease free-radicals Alzheimer's disease Alzheimer's oxidative stress oxidative damage lipid peroxides isoprostanes 8-hydroxy-2-deoxyguanosine neurology

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  • Nathan Goodyear on 13 Jun 12
     
    oxidative damage found to be present in early Alzheimer's disease.  This early mild cognitive impairment is the time for treatment to delay disease progression.  As this study points out, most studies up to this point have been done on individuals with late Alzheimer's disease.  This show that oxidative damage plays a prominent role in disease development.  This study found oxidative damage through several markers: lipid peroxides,isoprostanes, 8-hydroxy-2-deoxyguanosine...
Nathan Goodyear

Effect of systemic vitamin C on free fatty ac... [Diabetes Metab. 2004] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15671911

vitamin C lipid peroxidation antioxidant vitamin

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  • Nathan Goodyear on 05 Jun 13
     
    Vitamin C shown to improve endothelial function, but not shown to decrease lipid peroxidation marker.
Nathan Goodyear

Apolipoprotein E allele-dependent antioxidant activity in brains with Alzheimer's disease - 0 views

www.neurology.org/...2319.abstract

antioxidant alzheimer disease brains neurology brain TBARS oxidative stress lipid peroxidation

shared by Nathan Goodyear on 13 Jun 12 - No Cached
  • Nathan Goodyear on 13 Jun 12
     
    TBARS were found elevated in Alzheimer's individuals.  TBARS are the result of oxidative stress.  Thus TBARS can be used to evaluate lipid peroxidation (oxidative damage) in the brain.
Nathan Goodyear

DHA dietary supplementation enhances the effects of exercise on synaptic plasticity and... - 0 views

www.ncbi.nlm.nih.gov/...PMC3208643

DHA n-3 omega 3 omega-3 fish oil cognition memory hippocampus exercise neuroplasticity BDNF brain derived neurotrophic factor lipid peroxidation

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  • Nathan Goodyear on 01 Nov 13
     
    DHA enriched diet plus exercis improved cognition through a increase in brain derived neurotrophic factor (BDNF).  The result was increased neuroplasticity.  Additionally, they were shown to reduce hippocampal lipid peroxidation.
Nathan Goodyear

Curcumin improves spatial memory and decrease... [Biogerontology. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23609199

memory curcumin turmeric brain cognition lipid peroxidation oxidative stress damage

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  • Nathan Goodyear on 01 Nov 13
     
    curcumin shown to improve cognitive function through a decrease in lipid peroxidation in the brain of rats.
Nathan Goodyear

SpringerLink - Indian Journal of Clinical Biochemistry, Volume 23, Number 1 - 0 views

www.springerlink.com/...m05p1164qk33475h

glutathione PIH antioxidants pregnancy

shared by Nathan Goodyear on 23 Feb 11 - No Cached
  • Our study clearly indicates a relationship between elevated lipid peroxidation, decreased non-enzymatic antioxidant in PIH.
  • Nathan Goodyear on 23 Feb 11
     
    decreased antioxidants, glutathione, and elevated lipid peroxidation as predictors of PIH
Nathan Goodyear

Implications of free radicals and antioxidant levels in carcinoma of the breast: A neve... - 0 views

www.indianjcancer.com/article.asp

SOD superoxide disumutase catalase antioxidants antioxidant breast cancer cancer malondialdehyde MDA lipid peroxides oxidative stress inflammation

shared by Nathan Goodyear on 10 Nov 14 - No Cached
  • Experimental investigations as well as clinical and epidemiological findings have provided evidence supporting the role of reactive oxygen metabolites or free radicals such as singlet oxygen O 2 - , superoxide anions (O 2 ), hydrogen peroxide (H­2 O2 ) and hydroxyl radical in the etiology of cancer.
  • Certain aldehydes such as Malonyldialdehyde (MDA), the end product of lipid peroxidation arising from free radical degeneration of polyunsaturated fatty acids can cause cross linking in lipids, proteins and nucleic acids leading to cellular damage.
  • In this study, patients with cancer exhibited higher levels of MDA, both in tissues and serum (p<0.001) compared to the control group [Table 1]. In tissue, the MDA level in stage IV was significantly higher as compared to stage I indicating increased free radical activity with increasing severity of cancer
  • ...6 more annotations...
  • From these observations, it can be concluded that MDA levels play an important role in assessing the outcome of cancer
  • SOD and CAT are considered primary antioxidant enzymes, since they are involved in direct elimination of reactive oxygen metabolites. [13-16] They also act as anti-carcinogens and inhibitors at initiation and promotion/transformation stage in carcinogenesis
  • In our study, SOD and CAT levels were found to be low in all cancer patients as compared to controls
  • Fridovich and Tayarani have demonstrated in their respective studies that the reduction in SOD activity increases the toxic effects of O2 - and this might lead to severe cellular damage.
  • Mehrotra et al. in their study also observed high levels of MDA and low levels of SOD and CAT in patients of cancer cervix which is in sync with our observations.
  • strong evidence regarding the definitive role of free radicals in breast malignancy.
  • Nathan Goodyear on 10 Nov 14
     
    This study finds a strong correlation between advancing breast cancer, decreased catalase and SOD with increasing MDA.  The authors of this study conclude this is a key factor in carcinogenesis and not a by-product of cancer.  This flies in the face of traditional medicines fear of antioxidant therapy in cancer.
Nathan Goodyear

Lipid peroxidation in hemodialysis patients: ef... [Clin Biochem. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18194672

IV vitamin C vitamin C lipid perioxidation antioxidants

shared by Nathan Goodyear on 05 Jun 13 - No Cached
  • Nathan Goodyear on 05 Jun 13
     
    IV vitamin C shown to reduce AGE and lipid hydroperoxide levels post IV vitamin C when compared prior and controls.
Nathan Goodyear

Oxidative Stress and Its Relationship With Adenosine Deaminase Activity in Various Stag... - 0 views

www.ncbi.nlm.nih.gov/...PMC3547448

Adenosine Deaminase ADA cancer breast cancer superoxide disumutase glutathione peroxidase oxidative stress inflammation

shared by Nathan Goodyear on 10 Nov 14 - No Cached
  • Reduced SOD activity might be responsible for excessive accumulation of superoxide anions leading to increased free radical mediated injury. Increased free radical production has been shown to be responsible for chromosomal damage leading to mutagenecity, cell proliferation and carcinogenesis. SOD activity showed marked improvement after mastectomy indicating the lowering of oxidative stress.
  • The increased production of reactive oxygen species causes oxidative stress leading to cell proliferation and hence increased inflammatory conditions
  • Superoxide dismutase is an important antioxidant enzyme which decomposes the harmful superoxide anions into hydrogen peroxide thus protects the body from the action of free radicals
  • ...20 more annotations...
  • Females suffering from breast cancer had significantly decreased Superoxide dismutase (SOD) and reduced glutathione (GSH) levels in comparison to normal females
  • ADA seems to be a promising marker of inflammation in breast cancer thereby suggesting that it can be used as a diagnostic tool to detect the stage of breast cancer along with cytopathological studies
  • In conclusion, our study confirmed the role of oxidative stress in the pathogenesis of breast cancer.
  • Another potent antioxidant molecule is reduced glutathione. It acts as reductant which converts hydrogen peroxide into water and reduces lipid peroxidation products into their corresponding alcohols and thus mediates protective action.
  • In the present study, significantly low SOD activity has been observed in female patients suffering from carcinoma breast both pre as well as post operative in comparison to healthy females.
  • We observed significantly decreased SOD activity and GSH levels in patients belonging to clinical stage 4 as compared to those having stages 1, 2 or 3 of breast cancer.
  • Increased ADA activity in breast cancer patients has also been reported
  • The compromised antioxidant defence system produces the oxidative stress which in turn creates the inflammatory response shown by concomitant increased adenosine deaminase (ADA) activity in female patients.
  • Experimental and epidemiological evidences implicate the involvement of oxygen derived free radical in the pathogenesis of breast cancer.
  • Antioxidant status was highly depressed in advanced stages of breast cancer as compared to initial stage.
  • In the present study, significantly low GSH levels were observed in female patients of carcinoma breast as compared to normal females
  • Walia et al. (1995) reported increased ADA activity in breast cancer patients as compared to age matched normal subjects.
  • These free radicals are able to cause damage to membrane, mitochondria and macromolecules including proteins, lipids and DNA and actively take part in cell proliferation. This cascade in turn generates the inflammatory response and causes the progression of the disease.
  • increased oxidative stress gives rise to inflammation which could further aggravates the disease
  • Breast carcinoma involves a cascade of events that are highly inflammatory.
  • Marked oxidative stress in stage 4 of breast cancer indicated advancement of the disease, hence checking oxidative stress at initial stage could be helpful for controlling the progression of the disease.
  • They concluded that ADA is a better probable parameter for detection of breast cancer
  • Adenosine deaminase enzyme (ADA) catalyzes the conversion of adenosine to inosine which finally gets converted to uric acid
  • serum ADA activity tends to increase with advancing age,
  • Prevalence of oxidative stress gives rise to inflammation.
  • Nathan Goodyear on 10 Nov 14
     
    Study finds a reduction in SuperOxide Dismutase and Glutathione Perioxidase in advancing breast cancer.  Cancer is a high oxidative stress disease that results in inflammation, mitochondrial dysfunction and proliferation.  Adenosine Deaminase (ADA) is proposed to be another biomarker to assess tumor stage.  
Nathan Goodyear

[Malondialdehyde (MDA) as a lipid peroxidation marker]. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15765761

MDA malondialdehyde oxidative stress peroxidation free radicals

shared by Nathan Goodyear on 05 Dec 17 - No Cached
  • Nathan Goodyear on 05 Dec 17
     
    Only abstract her and it is an older article.  Malondialdehyde (MDA) is a great marker of oxidative stress.  Specifically, MDA is an end product of polyunsaturated fat peroxidation.
Nathan Goodyear

Time-level relationship for lipid peroxidation and the protective effect of alpha-tocop... - 0 views

www.ncbi.nlm.nih.gov/...9696087

vitamin E TBI traumatic brain injury brain injury brain

shared by Nathan Goodyear on 21 Feb 16 - No Cached
  • Nathan Goodyear on 21 Feb 16
     
    Animal study: vitamin E (alpha tocopherol only therapy) protected against lipid oxidation in mild and severe TBI.
Nathan Goodyear

Oxidant stress, ant... [Prostaglandins Leukot Essent Fatty Acids. 1997] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...9089797

SLE lupus EPA DHA n-3 omega 3 omega-3 fish oil fish oil fatty acids

shared by Nathan Goodyear on 30 Oct 13 - No Cached
  • Nathan Goodyear on 30 Oct 13
     
    low EPA and DHA found in patients with Lupus.  The authors of this article went so far as to say that lipid peroxides, NO, and anti-oxidants should be a part of the work up for patients with Lupus.
Nathan Goodyear

Ozone therapy: A clinical review - 0 views

www.ncbi.nlm.nih.gov/...PMC3312702

cancer Ozone

shared by Nathan Goodyear on 13 Apr 20 - No Cached
  • Its basic function is to protect humans from harmful effects of UV radiation
  • Its effects are proven, consistent and with minimal side effects
  • Medical O3, used to disinfect and treat disease, has been around for over 150 years
  • ...11 more annotations...
  • O3 not only remedied infection, but also had hemodynamic and anti-inflammatory properties
  • Stimulation of oxygen metabolism
  • In fungi, O3 inhibits cell growth at certain stages
  • With viruses, the O3 damages the viral capsid and upsets the reproductive cycle by disrupting the virus-to-cell contact with peroxidation.
  • Inactivation of bacteria, viruses, fungi, yeast and protozoa: Ozone therapy disrupts the integrity of the bacterial cell envelope through oxidation of the phospholipids and lipoproteins
  • Activation of the immune system
  • 30 and 55 μg/cc
  • production of interferon and the greatest output of tumor necrosis factor and interleukin-2
  • Mechanism of action of O3 on the human lung
  • cascade of reactions like peroxidation of lipids leading to changes in membrane permeability,[41] lipid ozonation products (LOP) act as signal transducer molecules
  • Dietary antioxidants or free radical scavengers like vitamin E, C, etc., can prevent aforementioned effects of O3
  • Nathan Goodyear on 13 Apr 20
     
    Ozone therapy review
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

EDTA chelation therapy, without added vitamin C, decreases oxidative DNA damage and lip... - 0 views

www.altmedrev.com/...56.pdf

EDTA EDTA chelation vitamin C IV vitamin C CVD cardiovascular disease Diabetes

shared by Nathan Goodyear on 05 Jun 13 - No Cached
  • Nathan Goodyear on 05 Jun 13
     
    This study found that the elimination of hight dose vitamin C in EDTA chelation removed the pro oxidant effect. This provided an antioxidant effect only from EDTA chelation, which is beneficial in the oxidative damage diseases like CVD and Diabetes
Nathan Goodyear

Experimental study on the effect of vitamin C administration on lipid peroxidation and ... - 0 views

www.scopemed.org/?mno=30116

vitamin C vitamin antioxidant

shared by Nathan Goodyear on 05 Jun 13 - No Cached
  • Nathan Goodyear on 05 Jun 13
     
    Rat model shows that vitamin C reduces oxidative damage from lead.  Thus, vitamin C provides antioxidant effect.
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