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Nathan Goodyear

Toxicity of the spike protein of COVID-19 is a redox shift phenomenon: A novel therapeu... - 0 views

www.sciencedirect.com/...S0891584923005014

COVID19 COVID-19 cancer inflammation SARS-CoV-2 spike proteins COVID spikeopathy

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • ...88 more annotations...
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • infection by Covid-19 follows a similar pattern
  • chronic inflammation
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • infection by Covid-19 follows a similar pattern
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • chronic inflammation
  • chronic inflammation
  • infection by Covid-19 follows a similar pattern
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • almost every disease presents an increased anabolism
  • almost every disease presents an increased anabolism
  • cell division is the most sophisticated way to release entropy
  • cell division is the most sophisticated way to release entropy
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
  • transition from catabolism to anabolism is driven by a redox shift
  • transition from catabolism to anabolism is driven by a redox shift
  • viral spike protein binds to ACE2 receptor of the host cell [22,23].
  • redox signaling plays an important role in regulating immune function and inflammation, and disruptions in this signaling can lead to excessive cytokine production and immune system activation
  • Aging is associated with a poor control of the redox balance
  • thiol/disulfide homeostasis
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • Redox signaling tightly modulates the inflammatory response and oxidative stress has been reported in acute Covid-19
  • People at high risk are the elderly, patients suffering from metabolic syndrome such as obesity, or those suffering from chronic diseases such as cancer or inflammation
  • COVID-19 patients with severe disease have higher levels of oxidative stress markers and lower antioxidant levels
  • oxidative stress can activate the NLRP3 inflammasome, which is a protein complex that plays a key role in the cytokine storm
  • inflammation leads to the formation of ROS and RNS, while redox iMeBalance results in cellular damage, which in turn triggers an inflammatory response
  • persistently elevated mtROS triggers endothelial dysfunction and inflammation, which results in a vicious loop involving ROS, inflammation, and mitochondrial dysfunction
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • reduced environment during the cytokine storm
  • IL-2 is highly up-regulated in Covid-19 patients [37], and IL-2 is known to significantly stimulate the generation of NO in patients
  • Nitric acid is also the key mediator of IL-2-induced hypotension and vascular leak syndrome
  • mitochondrial dysfunction has been linked to the pathogenesis of Covid-19
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • As catabolism is decreased, entropy is released through anabolism
  • Elevated levels of lactate, a characteristic of the Warburg effect, were also reported in the high-risk Covid-19
  • elevated levels of ventricular lactic acid consistent with oxidative stress
  • A decrease of ΔΨm is implicated in several inflammation-related diseases
  • decrease in ΔΨm in leucocytes from Covid-19 patients
  • vaccinated with RNA or DNA vaccines triggering the synthesis of the viral spike protein in human cells
  • viral reactivation in varicella-zoster virus [55] or hepatitis [56], coagulopathy and resulting stroke and myocarditis following both DNA-based vaccines [57] and RNA-based vaccines
  • Covid-19, mitochondrial impairment
  • characteristic of the Warburg effect is present in almost every disease and appears to be a central feature in most of the hallmarks of cancer
  • inflammation, mitochondrial dysfunction and increased lactate concentrations in the extracellular fluid
  • In Covid-19, like any inflammation, there is a metabolic rewiring where cells rely on glycolysis
  • As the mitochondria are impaired, the infected cell cannot catabolize efficiently. It will release lactic acid in the blood stream
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Mitochondrial impairment
  • Striking similarities are seen between cancer, Alzheimer's disease and Covid-19, all related to the Warburg effect
  • Cancer, inflammation, Alzheimer's, and Parkinson's diseases share a common peculiarity, the inability of the cell to export entropy outside the body in the harmless form of heat
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Entropy: lack of order or predictability; gradual decline into disorder.
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • It has been shown that Covid-19-patients treated with MEB, have a significant reduction in hospital stay duration and mortality
  • MeB is an acceptor-donor molecule
  • MeB + can take a pair of electrons (of H atoms) and MeBH can release this pair easily, so that MeB is partially recycled like a catalyst
  • MeB acts as an electron bridge between a donor (FADH2, FMNH, NADH) and an acceptor (complex IV of ETC or oxygen itself)
  • As a coenzyme of pyruvate dehydrogenase (PDH), alpha-lipoic acid (ALA) initiates the formation of acetyl-CoA to feed the TCA cycle
  • ALA enhances the catabolism of carbon. cycle and therefore may reduce the Warburg effect and consequently, lactate production
  • Methylene Blue plays a similar role after the TCA cycle, by carrying electrons to complex IV of the electron transport chain
  • Drugs such as lipoic acid and MeB, which target the metabolism, decrease the redox shift by increasing catabolism
Nathan Goodyear

Seasonal variation of salivary testosterone in... [Physiol Behav. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21802437

seasonal variation testosterone hormone hormones

shared by Nathan Goodyear on 15 Oct 12 - No Cached
  • Nathan Goodyear on 15 Oct 12
     
    interesting study that showed that testosterone levels in men and women fluctuate seasonally.  The highest levels are found in the fall for both sexes, but lowest during the summer.  Interestingly, birth control eliminated these seasonal variations and resulted in a "flatter seasonal testosterone profile".   So, maybe mean cycle, but on a much different time scale?  Interesting thought.
Nathan Goodyear

Colocalization of progesterone receptors A and B by dual immunofluourescent histochemis... - 0 views

jcem.endojournals.org/...2963.full.pdf

progesterone receptor progesterone receptors PR-A PR-B progesterone receptor receptors

shared by Nathan Goodyear on 24 Nov 12 - No Cached
  • Nathan Goodyear on 24 Nov 12
     
    PR-A and PR-B and regulation of the human menstural cycle.
Nathan Goodyear

Oestrogen receptor α and β mRNA expression in human endometrium throughout th... - 0 views

molehr.oxfordjournals.org/...559.full

endometrium ER-alpha ER-beta estrogen receptor alpha estrogen receptor beta estrogen receptor estrogen receptors estrogen receptor receptors alpha beta menstrual cycle human

shared by Nathan Goodyear on 07 Dec 12 - No Cached
  • Nathan Goodyear on 07 Dec 12
     
    Estrogen receptors alpha and beta show dominance in the proliferative phases, with alpha isoform predominating.  In the secretory phase, less expression of ER was present. ER alpha was predominantly expressed in the epithelial and stromal cells in the proliferative phase.  ER beta was predominantly expressed in glandular cells in the same proliferative phase.   in the luteal phase, ER alpha expression declined in the funtionalis layers.  ER alpha in the basalis remained unchanged.  ER beta in the functionalis layers also declined in the luteal phase.   No relative change was found in the weak expression of ER alpha/beta in the myometrium.
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

Orexin/Hypocretin: A Neuropeptide at the Interface of Sleep, Energy Homeostasis, and Re... - 0 views

pharmrev.aspetjournals.org/...162.full

orexin orexins sleep energy

shared by Nathan Goodyear on 02 Jan 13 - No Cached
  • Nathan Goodyear on 02 Jan 13
     
    great read on orexins!  Orexins play a role in feeding and in sleep/wake cycle. Orexins interact with the limbic system to play a role in reward.
Nathan Goodyear

Glioblastoma Cells Require Glutamate Dehydrogenase to Survive Impairments of Glucose Me... - 0 views

cancerres.aacrjournals.org/...7986.full.pdf

cancer Glioblastoma EGCG glutamine glucose

shared by Nathan Goodyear on 29 Jun 13 - No Cached
  • Nathan Goodyear on 29 Jun 13
     
    This article describes how important glutamine is as an alternative energy source in Glioblastoma. Cancer is a substrate-level dependent energy production disease. If one disrupts glycolysis as a source of energy, then many cancers will use glutamine through glutaminolysis. The cancer cells will do this through glutamate dehydrogenase and glutamate production. This will increase alpha-ketoglutarate which will then feed the substrate-level phosphorylation through the TCA cycle. This study mentioned that EGCG is a way to naturally inhibit glutamate dehydrogenase.
Nathan Goodyear

Effects of androgens on insulin actio... [Diabetes Metab Res Rev. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18615851

insulin resistance androgen testosterone DHT DHEA women PCOS hormones hormone

shared by Nathan Goodyear on 17 Oct 12 - No Cached
  • Nathan Goodyear on 17 Oct 12
     
    elevated insulin associated with insulin resistance causes elevated male hormones in women.  Whether it is in PCOS or postmenopausal over-aggressive replacement, Testosterone also turns right around and contributes to insulin resistance.  Vicious cycle.
Nathan Goodyear

urn:nbn:se:umu:diva-124842 : Training and hormones in physically active women : with an... - 0 views

umu.diva-portal.org/...record.jsf

resistance training exercise women hormones training female

shared by Nathan Goodyear on 27 Sep 16 - No Cached
  • Nathan Goodyear on 27 Sep 16
     
    Only abstract available: resistance training in first half of female cycle found to increase muscle mass and strength beyond that of the last 2 weeks.  No difference was found in the use of OCPs.
Nathan Goodyear

Dietary factors and luteal phase deficiency in healthy eumenorrheic women - 0 views

www.ncbi.nlm.nih.gov/...PMC4507331

hormones female hormones diet nutrition progesterone estrogen women

shared by Nathan Goodyear on 15 Feb 17 - No Cached
  • Nathan Goodyear on 15 Feb 17
     
    great read and review of diet and hormones in cycling women.
Nathan Goodyear

The Effect of High-Intensity Intermittent Exercise on Body Composition of Overweight Yo... - 0 views

www.hindawi.com/...480467

HIT high intensity intermittent training high intensity training exercise obesity weight-loss training overweight

shared by Nathan Goodyear on 13 Jul 12 - No Cached
  • Nathan Goodyear on 13 Jul 12
     
    High intensity training results in effective fat loss.  This study followed individuals over a 12 week cycle.  They performed HIT at 20 mins 3 x weekly.  Fat loss was statistically significant when compared to control group.
Nathan Goodyear

Adipose Tissue Inflammation in Obesity and Metabolic Syndrome - - Satoshi Nishimura - D... - 0 views

www.discoverymedicine.com/...obesity-and-metabolic-syndrome

inflammation obesity metabolic syndrome fat adipose tissue innate immune system humoral

shared by Nathan Goodyear on 21 Dec 11 - No Cached
  • Activation of inflammatory pathways in adipocytes impairs triglyceride storage and increases release of free fatty acids, an excess of which is known to induce insulin resistance in muscle and liver
  • recent studies have shown that large numbers of macrophages infiltrate obese adipose tissue,
  • It has been postulated that a paracrine loop involving free fatty acids and inflammatory cytokines establishes a vicious cycle between adipocytes and macrophages that propagates the inflammation
  • ...5 more annotations...
  • not only does interrupting the accumulation of macrophages within obese adipose tissue suppresses adipose inflammation in various animal models, it also ameliorates systemic insulin resistance and metabolic abnormalities, suggesting macrophages are key effector cells involved in adipose inflammation
  • activation of the leukocyte adhesion cascade, a hallmark of inflammation
  • Thus, obese visceral adipose tissue is clearly a site of chronic inflammation
  • CD8+ T cells within obese adipose tissue induce activation and migration of monocytes/macrophages, and in cooperation with the adipose tissue, they also induce macrophage differentiation. At the same time, obese adipose tissue activates CD8+ T cells, creating a vicious cycle involving CD8+ T cells, macrophages, and obese adipose tissue that propagates local inflammation
  • In obese adipose tissue there is a shift to dominance of CD8+ and TH1 T cells, which appears to propagate inflammation
  • Nathan Goodyear on 21 Dec 11
     
    fascinating read how the immune system and resultant inflammation results in obesity.
Nathan Goodyear

Investigations on oxidativ... [Eur Arch Psychiatry Clin Neurosci. 1999] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10654103

AGE advanced glycation end products neurodegenerative disease free radicals Alzheimer's Parkinson's disease antioxidants inflammation

shared by Nathan Goodyear on 13 Jun 12 - No Cached
  • Nathan Goodyear on 13 Jun 12
     
    This study finds that AGE, advanced glycation end products, play a significant role in free radical generation and neurodegenerative disease. Quote: "... pharmacologoical approaches which break the vicious cycle of oxidative stress and neurodegeneration offer new opportunities for the treatment of AD. These approaches include AGE- inhibitors, antioxidants, and anti-inflammatory substances which prevent radical production." They focus on the pharmacological, how about the natural first?
Nathan Goodyear

Estrogen Receptor-Related Receptor α Mediates Up-Regulation of Aromatase Expr... - 0 views

mend.endojournals.org/...1175.abstract

ER-alpha estrogen receptors aromatase prostate men male PGE2 hormone hormones

shared by Nathan Goodyear on 18 Sep 12 - No Cached
  • Nathan Goodyear on 18 Sep 12
     
    ER alpha increases aromatase expression in the prostate.  PGE2 increased the ER alpha receptor.  Vicious cycle in men.  Increased aromatase activity increases estrogen production which increases ER alpha (pro growth) and further aromatase activity.
Nathan Goodyear

Lowered testosterone in male obesity: Mechanisms, morbidity and management Tang Fui MN,... - 0 views

www.ajandrology.com/article.asp

Testosterone male obesity overweight men hormone hormones low T Low T

shared by Nathan Goodyear on 15 Jan 14 - No Cached
  • The number of overweight people is expected to increase from 937 million in 2005 to 1.35 billion in 2030
  • Similarly the number of obese people is projected to increase from 396 million in 2005 to 573 million in 2030
  • By 2030, China alone is predicted to have more overweight men and women than the traditional market economies combined
  • ...37 more annotations...
  • diacylglycerol O-acyltransferase 2 (DGAT2), mechanistically implicated in this differential storage, [10] is regulated by dihydrotestosterone, [11] suggesting a potential role for androgens to influence the genetic predisposition to either the MHO or MONW phenotype.
  • bariatric surgery achieves 10%-30% long-term weight loss in controlled studies
  • The fact that obese men have lower testosterone compared to lean men has been recognized for more than 30 years
  • Reductions in testosterone levels correlate with the severity of obesity and men
  • epidemiological data suggest that the single most powerful predictor of low testosterone is obesity, and that obesity is a major contributor of the age-associated decline in testosterone levels.
  • healthy ageing by itself is uncommonly associated with marked reductions in testosterone levels
  • obesity blunts this LH rise, obesity leads to hypothalamic-pituitary suppression irrespective of age which cannot be compensated for by physiological mechanisms
  • Reductions in total testosterone levels are largely a consequence of reductions in sex hormone binding globulin (SHBG) due to obesity-associated hyperinsulinemia
  • although controversial, measurement of free testosterone levels may provide a more accurate assessment of androgen status than the (usually preferred) measurement of total testosterone in situations where SHBG levels are outside the reference range
  • SHBG increases with age
  • marked obesity however is associated with an unequivocal reduction of free testosterone levels, where LH and follicle stimulating hormone (FSH) levels are usually low or inappropriately normal, suggesting that the dominant suppression occurs at the hypothalamic-pituitary level
  • adipose tissue, especially when in the inflamed, insulin-resistant state, expresses aromatase which converts testosterone to estradiol (E 2 ). Adipose E 2 in turn may feedback negatively to decrease pituitary gonadotropin secretion
  • diabetic obesity is associated with decreases in circulatory E 2
  • In addition to E 2 , increased visceral fat also releases increased amounts of pro-inflammatory cytokines, insulin and leptin; all of which may inhibit the activity of the HPT axis at multiple levels
  • In the prospective Massachusetts Male Aging Study (MMAS), moving from a non-obese to an obese state resulted in a decline of testosterone levels
  • weight loss, whether by diet or surgery, increases testosterone levels proportional to the amount of weight lost
  • fat is androgen-responsive
  • low testosterone may augment the effects of a hypercaloric diet
  • In human male ex vivo adipose tissue, testosterone decreased adipocyte differentiation by 50%.
  • Testosterone enhances catecholamine-induced lipolysis in vitro and reduces lipoprotein lipase activity and triglyceride uptake in human abdominal adipose tissue in vivo
  • in men with prostate cancer receiving 12 months of androgen deprivation therapy, fat mass increased by 3.4 kg and abdominal VAT by 22%, with the majority of these changes established within 6 months
  • severe sex steroid deficiency can increase fat mass rapidly
  • bidirectional relationship between testosterone and obesity
  • increasing body fat suppresses the HPT axis by multiple mechanisms [30] via increased secretion of pro-inflammatory cytokines, insulin resistance and diabetes; [19],[44] while on the other hand low testosterone promotes further accumulation of total and visceral fat mass, thereby exacerbating the gonadotropin inhibition
  • androgens may play a more significant role in VAT than SAT
  • men undergoing androgen depletion for prostate cancer show more marked increases in visceral compared to subcutaneous fat following treatment
    • Nathan Goodyear
      Nathan Goodyear on 16 Jan 14
       
      Interesting: low T increases VAT, yet T therapy does not reduce VAT, yet T therapy reduces SAT.
  • irisin, derived from muscle, induces brown fat-like properties in rodent white fat
  • androgens can act via the PPARg-pathway [37] which is implicated in the differentiation of precursor fat cells to the energy-consuming phenotype
  • low testosterone may compound the effect of increasing fat mass by making it more difficult for obese men to lose weight via exercise
  • pro-inflammatory cytokines released by adipose tissue may contribute to loss of muscle mass and function, leading to inactivity and further weight gain in a vicious cycle
  • Sarcopenic obesity, a phenotype recapitulated in men receiving ADT for prostate cancer, [55] may not only be associated with functional limitations, but also aggravate the metabolic risks of obesity;
  • observational evidence associating higher endogenous testosterone with reduced loss of muscle mass and crude measures of muscle function in men losing weight
  • genuine reactivation of the HPT axis in obese men requires more substantial weight-loss
  • A number of intervention studies have confirmed that both diet- and surgically-induced weight losses are associated with increased testosterone, with the rise in testosterone generally proportional to the amount of weight lost
  • men, regardless of obesity level, can benefit from the effect of weight loss.
  • inconsistent effect of testosterone on VAT
  • Nathan Goodyear on 15 Jan 14
     
    to be read
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

Breast Cancer Research | Full text | Endogenous sex steroids in premenopausal women and... - 0 views

breast-cancer-research.com/...R46

Testosterone breast cancer risk hormone hormones women female free

shared by Nathan Goodyear on 20 Mar 14 - No Cached
  • Nathan Goodyear on 20 Mar 14
     
    The literature on Testosterone and breast cancer is confusing at best, but just like therapy in men, it needs to be individualized.  This prospective case study found a significant increased odds of breast cancer in women with higher levels of free Testosterone.  Statistical significance was not found with Total Testosterone.  These were endogenous hormones.  The women in this study had "regular menstrual cycles" suggesting these women lacked PCOS.
Nathan Goodyear

Reproducibility of Plasma Steroid Hormones, Prolactin, and Insulin-like Growth Factor L... - 0 views

cebp.aacrjournals.org/...972.long

hormone hormones androgens Testosterone DHEAS IGF-1 prolactin IGFBP-3 women female

shared by Nathan Goodyear on 21 Mar 14 - No Cached
  • Nathan Goodyear on 21 Mar 14
     
    Very interesting study finds that a single value assessment of androgens, DHEAS, prolactin, IGF-1 and IGFBP-3 can be used to assess 3 year average in pre-menopause women.  Estrogen and progesterone need to be assessed through the cycle.
Nathan Goodyear

Uric Acid Stimulates Fructokinase and Accelerates Fructose Metabolism in the Developmen... - 0 views

www.ncbi.nlm.nih.gov/...PMC3480441

non-alcoholic fatty liver fatty liver fructose uric acid

shared by Nathan Goodyear on 01 Oct 13 - No Cached
  • Nathan Goodyear on 01 Oct 13
     
    Vicious cycle.  High fructose intake increases uric acid production.  Hyperuricemia then leads to further Fructose metabolism.  This study finds that hyperuricemia upregulates the fructokinase enzyme that is the first step in fructose metabolism.  This upregulation will increase fructose metabolism and increase fat accumulation in the liver.
Nathan Goodyear

Endocrine and clinical effects of myo-ino... [Gynecol Endocrinol. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23336594

myo-inositol PCOS insulin polycystic ovarian syndrome

shared by Nathan Goodyear on 20 Dec 13 - No Cached
  • Nathan Goodyear on 20 Dec 13
     
    Myo-inositol improves PCOS.  Specifically, myo-inositol improved insulin sensitivity, reduced insulin levels and restored HPA function.  IN these women with amenorrhea and oligomenorrhea, menestrual cycle regularity was restored.
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