high aromatase activity and conversion of testosterone to estrogen conversion plays a role in lupus and RA. Inflammatory cytokines are shown to increase aromatase activity.
increased testosterone to estrogen conversion, in part, stimulated by inflammatory cytokines: TNF, and IL-6. They propose aromatase inhibition to decrease testosterone to estrogen conversion. This study looked at individuals with HIV.
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
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.
Study finds that higher protein to carbohydrate intake has a positive effect on inflammatory cytokines, oxidative stress, improves insulin sensitivity and improves Beta cell function in premenopausal, non diabetic obese women.
inflammation negatively associated with SHBG in post menopause women. Interestingly, Estradiol was found to be positively associated. The inflammatory cytokines evaluated were CRP and IL-6.
study shows that progesterone directly inhibits pro-inflammatory cytokine signaling in rat dendritic cells. Progesterone here shows to be directly involved in a anti-inflammatory effect.
alpha lipoic acid found to improve insulin sensitivity and reduce oxidative stress and inflammatory markers. In this study, IV ALA was given daily for 2 weeks, and the result was reduced oxidized LDL and all other lipids, improved insulin sensitivity, reduced TNF-alpha, IL-6, and 8-iso-prostaglandin, and increased adiponectin.
Interesting study finds hyperandrogenism stimulates excessive inflammatory response to glucose intake. This study was done in otherwise healthy women not in women with PCOS. The inflammatory cytokine production was via NF-KappaB activation.
Again, this has negative implications in women being doped with Testosterone.
IR also indirectly induces DNA damage by stimulating reactive oxygen species (ROS) production
IR is known to induce EMT in vitro
p53 is activated in response to IR-induced DNA damage
IR paradoxically also promotes tumour recurrence and metastasis
DNA double-strand breaks (DSBs)
cancer cells undergoing EMT acquire invasive and metastatic properties
changes in the tumour microenvironment (TME)
IR seems to induce EMT and CSC phenotypes by regulating cellular metabolism
EMT, stemness, and oncogenic metabolism are known to be associated with resistance to radiotherapy and chemotherapy
Hanahan and Weinberg proposed ten hallmarks of cancer that alter cell physiology to enhance malignant growth: 1) sustained proliferation, 2) evasion of growth suppression, 3) cell death resistance, 4) replicative immortality, 5) evasion of immune destruction, 6) tumour-promoting inflammation, 7) activation of invasion and metastasis, 8) induction of angiogenesis, 9) genome instability, and 10) alteration of metabolism
EMT is a developmental process that plays critical roles in embryogenesis, wound healing, and organ fibrosis
IR is known to induce stemness and metabolic alterations in cancer cells
transforming growth factor-β [TGF-β], epidermal growth factor [EGF]) and their associated signalling proteins (Wnt, Notch, Hedgehog, nuclear-factor kappa B [NF-κB], extracellular signal-regulated kinase [ERK], and phosphatidylinositol 3-kinase [PI3K]/Akt
activate EMT-inducing transcription factors, including Snail/Slug, ZEB1/δEF1, ZEB2/SIP1, Twist1/2, and E12/E47
Loss of E-cadherin is considered a hallmark of EMT
IR has been shown to induce EMT to enhance the motility and invasiveness of several cancer cells, including those of breast, lung, and liver cancer, and glioma cells
IR may increase metastasis in both the primary tumour site and in normal tissues under some circumstance
sublethal doses of IR have been shown to enhance the migratory and invasive behaviours of glioma cells
ROS are known to play an important role in IR-induced EMT
High levels of ROS trigger cell death by causing irreversible damage to cellular components such as proteins, nucleic acids, and lipids, whereas low levels of ROS have been shown to promote tumour progression—including tumour growth, invasion, and metastasis
hypoxia-inducible factor-1 (HIF-1) is involved in IR-induced EMT
Treatment with the N-acetylcysteine (NAC), a general ROS scavenger, prevents IR-induced EMT, adhesive affinity, and invasion of breast cancer cells
Snail has been shown to play a crucial role in IR-induced EMT, migration, and invasion
IR activates the p38 MAPK pathway, which contributes to the induction of Snail expression to promote EMT and invasion
NF-κB signalling that promotes cell migration
ROS promote EMT to allow cancer cells to avoid hostile environments
HIF-1 is a heterodimer composed of an oxygen-sensitive α subunit and a constitutively expressed β subunit.
Under normoxia, HIF-1α is rapidly degraded, whereas hypoxia induces stabilisation and accumulation of HIF-1α
levels of HIF-1α mRNA are enhanced by activation of the PI3K/Akt/mammalian target of rapamycin (mTOR)
IR is known to increase stabilisation and nuclear accumulation of HIF-1α, since hypoxia is a major condition for HIF-1 activation
IR induces vascular damage that causes hypoxia
ROS is implicated in IR-induced HIF-1 activation
IR causes the reoxygenation of hypoxic cancer cells to increase ROS production, which leads to the stabilisation and nuclear accumulation of HIF-1
IR increases glucose availability under reoxygenated conditions that promote HIF-1α translation by activating the Akt/mTOR pathway
The stabilised HIF-1α then translocates to the nucleus, dimerizes with HIF-1β, and increases gene expression— including the expression of essential EMT regulators such as Snail—to induce EMT, migration, and invasion
TGF-β signalling has been shown to play a crucial role in IR-induced EMT
AP-1 transcription factor is involved in IR-induced TGF-β1 expression
Wnt/β-catenin signalling is also implicated in IR-induced EMT
Notch signalling is known to be involved in IR-induced EMT
IR also increases Notch-1 expression [99]. Notch-1 is known to induce EMT by upregulating Snail
PAI-1 signalling is also implicated in IR-induced Akt activation that increases Snail levels to induce EMT
EGFR activation is known to be associated with IR-induced EMT, cell migration, and invasion by activating two downstream pathways: PI3K/Akt and Raf/MEK/ERK
ROS and RNS are also implicated in IR-induced EGFR activation
IR has also been shown to activate Hedgehog (Hh) signalling to induce EMT
IR has been shown to induce Akt activation through several signalling pathways (EGFR, C-X-C chemokine receptor type 4 [CXCR4]/C-X-C motif chemokine 12 [CXCL12], plasminogen activator inhibitor 1 [PAI-1]) and upstream regulators (Bmi1, PTEN) that promote EMT and invasion
CSCs possess a capacity for self-renewal, and they can persistently proliferate to initiate tumours upon serial transplantation, thus enabling them to maintain the whole tumour
Conventional cancer treatments kill most cancer cells, but CSCs survive due to their resistance to therapy, eventually leading to tumour relapse and metastasis
identification of CSCs, three types of markers are utilised: cell surface molecules, transcription factors, and signalling pathway molecules
CSCs express distinct and specific surface markers; commonly used ones are CD24, CD34, CD38, CD44, CD90, CD133, and ALDH
Transcription factors, including Oct4, Sox2, Nanog, c-Myc, and Klf4,
signalling pathways, including those of TGF-β, Wnt, Hedgehog, Notch, platelet-derived growth factor receptor (PDGFR), and JAK/STAT
microRNAs (miRNAs), including let-7, miR-22, miR-34a, miR-128, the miR-200 family, and miR-451
Non-CSCs can be reprogrammed to become CSCs by epigenetic and genetic changes
EMT-inducing transcription factors, such as Snail, ZEB1, and Twist1, are known to confer CSC properties
Signalling pathways involved in EMT, including those of TGF-β, Wnt, and Notch, have been shown to play important roles in inducing the CSC phenotype
TGF-β1 not only increases EMT markers (Slug, Twist1, β-catenin, N-cadherin), but also upregulates CSC markers (Oct4, Sox2, Nanog, Klf4) in breast and lung cancer cells
some CSC subpopulations arise independently of EMT
IR has been shown to induce the CSC phenotype in many cancers, including breast, lung, and prostate cancers, as well as melanoma
Genotoxic stress due to IR or chemotherapy promotes a CSC-like phenotype by increasing ROS production
IR has been shown to induce reprogramming of differentiated cancer cells into CSCs
In prostate cancer patients, radiotherapy increases the CD44+ cell population that exhibit CSC properties
IR also induces the re-expression of stem cell regulators, such as Sox2, Oct4, Nanog, and Klf4, to promote stemness in cancer cells
EMT-inducing transcription factors and signalling pathways, including Snail, STAT3, Notch signalling, the PI3K/Akt pathway, and the MAPK cascade, have been shown to play important roles in IR-induced CSC properties
STAT3 directly binds to the Snail promoter and increases Snail transcription, which induces the EMT and CSC phenotypes, in cisplatin-selected resistant cells
Other oncogenic metabolic pathways, including glutamine metabolism, the pentose phosphate pathway (PPP), and synthesis of fatty acids and cholesterol, are also enhanced in many cancers
metabolic reprogramming
HIF-1α, p53, and c-Myc, are known to contribute to oncogenic metabolism
metabolic reprogramming
tumour cells exhibit high mitochondrial metabolism as well as aerobic glycolysis
occurring within the same tumour
CSCs can be highly glycolytic-dependent or oxidative phosphorylation (OXPHOS)-dependen
mitochondrial function is crucial for maintaining CSC functionality
cancer cells depend on mitochondrial metabolism and increase mitochondrial production of ROS that cause pseudo-hypoxia
HIF-1 then enhances glycolysis
CAFs have defective mitochondria that lead to the cells exhibiting the Warburg effect; the cells take up glucose, and then secrete lactate to 'feed' adjacent cancer cells
Epithelial cancer cells express MCT1, while CAFs express MCT4. MCT4-positive, hypoxic CAFs secrete lactate by aerobic glycolysis, and MCT1-expressing epithelial cancer cells then uptake and use that lactate as a substrate for the tricarboxylic acid (TCA) cycle
MCT4-positive cancer cells depend on glycolysis and then efflux lactate, while MCT1-positive cells uptake lactate and rely on OXPHOS
metabolic heterogeneity induces a lactate shuttle between hypoxic/glycolytic cells and oxidative/aerobic tumour cells
bulk tumour cells exhibit a glycolytic phenotype, with increased conversion of glucose to lactate (and enhanced lactate efflux through MCT4), CSC subsets depend on oxidative phosphorylation; most of the glucose entering the cells is converted to pyruvate to fuel the TCA cycle and the electron transport chain (ETC), thereby increasing mitochondrial ROS production
the major fraction of glucose is directed into the pentose phosphate pathway, to produce redox power through the generation of NADPH and ROS scavengers
HIF-1α, p53, and c-Myc, are known to contribute to oncogenic metabolism
regulatory molecules involved in EMT and CSCs, including Snail, Dlx-2, HIF-1, STAT3, TGF-β, Wnt, and Akt, are implicated in the metabolic reprogramming of cancer cells
HIF-1 induces the expression of glycolytic enzymes, including the glucose transporter GLUT, hexokinase, lactate dehydrogenase (LDH), and MCT, resulting in the glycolytic switch
HIF-1 represses the expression of pyruvate dehydrogenase kinase (PDK), which inhibits pyruvate dehydrogenase (PDH), thereby inhibiting mitochondrial activity
STAT3 has been implicated in EMT-induced metabolic changes as well
TGF-β and Wnt play important roles in the metabolic alteration of cancer cells
Akt is also implicated in the glycolytic switch and in promoting cancer cell invasiveness
EMT, invasion, metastasis, and stemness
pyruvate kinase M2 (PKM2), LDH, and pyruvate carboxylase (PC), are implicated in the induction of the EMT and CSC phenotypes
decreased activity of PKM2 is known to promote an overall shift in metabolism to aerobic glycolysis
LDH catalyses the bidirectional conversion of lactate to pyruvate
High levels of LDHA are positively correlated with the expression of EMT and CSC markers
IR has been shown to induce metabolic changes in cancer cells
IR enhances glycolysis by upregulating GAPDH (a glycolysis enzyme), and it increases lactate production by activating LDHA, which converts pyruvate to lactate
IR enhances glycolysis by upregulating GAPDH (a glycolysis enzyme), and it increases lactate production by activating LDHA, which converts pyruvate to lactate
IR also elevates MCT1 expression that exports lactate into the extracellular environment, leading to acidification of the tumour microenvironment
IR increases intracellular glucose, glucose 6-phosphate, fructose, and products of pyruvate (lactate and alanine), suggesting a role for IR in the upregulation of cytosolic aerobic glycolysis
Lactate can activate latent TGF-
lactate stimulates cell migration and enhances secretion of hyaluronan from CAF that promote tumour metastasis
promote tumour survival, growth, invasion, and metastasis; enhance the stiffness of the ECM; contribute to angiogenesis; and induce inflammation by releasing several growth factors and cytokines (TGF-β, VEGF, hepatocyte growth factor [HGF], PDGF, and stromal cell-derived factor 1 [SDF1]), as well as MMP
tumours recruit the host tissue’s blood vessel network to perform four mechanisms: angiogenesis (formation of new vessels), vasculogenesis (de novo formation of blood vessels from endothelial precursor cells), co-option, and modification of existing vessels within tissues.
immunosuppressive cells such as tumour-associated macrophages (TAM), MDSCs, and regulatory T cells, and the immunosuppressive cytokines, TGF-β and interleukin-10 (IL-10)
immunosuppressive cells such as tumour-associated macrophages (TAM), MDSCs, and regulatory T cells, and the immunosuppressive cytokines, TGF-β and interleukin-10 (IL-10)
intrinsic immunogenicity or induce tolerance
cancer immunoediting’
three phases: 1) elimination, 2) equilibrium, and 3) escape.
The third phase, tumour escape, is mediated by antigen loss, immunosuppressive cells (TAM, MDSCs, and regulatory T cells), and immunosuppressive cytokines (TGF-β and IL-10).
IR can elicit various changes in the TME, such as CAF activity-mediated ECM remodelling and fibrosis, cycling hypoxia, and an inflammatory response
IR activates CAFs to promote the release of growth factors and ECM modulators, including TGF-β and MMP
TGF-β directly influences tumour cells and CAFs, promotes tumour immune escape, and activates HIF-1 signalling
IR also promotes MMP-2/9 activation in cancer cells to promote EMT, invasion, and metastasis
IR-induced Snail increases MMP-2 expression to promote EMT
Radiotherapy has the paradoxical side-effect of increasing tumour aggressiveness
IR promotes ROS production in cancer cells, which may induce the activation of oncogenes and the inactivation of tumour suppressors, which further promote oncogenic metabolism
Metabolic alterations
oncogenic metabolism
elicit various changes in the TME
Although IR activates an antitumour immune response, this signalling is frequently suppressed by tumour escape mechanisms
play a role during the initial chemotactic response of neutrophils shortly after infection
following vitamin C supplementation, a 20% increase in neutrophil chemotactic activity was observed
also contributes to the phagocytosis and killing of microbes by neutrophils
low levels of vitamin C occurring in high-stress situations
maturation, proliferation, and viability of T cells have all been shown to be upregulated by the presence of normal physiologic concentrations of vitamin C
Vitamin C has been shown to directly affect the number of Igs released from B cells
vitamin C among healthy young adult males showed a significant increase in serum levels of IgA, IgG, and IgM
effects of high-dose vitamin C on cytokine levels in cancer patients, finding decreased amounts of the cytokines Interleukin-1 alpha (IL-1 alpha), IL-2, IL-8, and tumor necrosis factor-alpha (TNF-alpha) after high-dose vitamin C infusion
when vitamin C was supplemented with vitamin E in healthy adults, it increased the production of cytokines IL-1 beta and TNF-alpha
vitamin C acts to modulate the levels of cytokines to prevent them from fluctuating in either direction
vitamin C also acts as an important antioxidant to the cells of the immune system.
human leukocytes, neutrophils, in particular, possess the ability to transport the oxidized form of vitamin C across its membrane to use as a defense mechanism against ROS produced during an immune response
Vitamin C also can recover other endogenous antioxidants in the body such as vitamin E and glutathione, returning them to their active state
vitamin C can decrease the activation of NF-kB
can reduce harmful nitrogen-based compounds such as N-nitrosamines and nitrosamides, both of which are carcinogenic
subjects taking oral vitamin C supplementation saw a 60% to 90% reduction in oxidative stress compared to a placebo control
subjects infused with vitamin C alone had a 516% increase in glutathione levels compared to subjects not provided the 500 mg daily supplementation
hydroxylating proline and lysine
mature and stabilize the tissue of a healing wound
healing
oral surgery
improved soft tissue regeneration
vitamin C increases the mRNA levels of type I and type III collagen in the human dermis
Studies have demonstrated that those with low levels of vitamin C are at a significantly higher risk of respiratory infection compared to those with normal levels
viral cold duration was reduced by about 8% in adults and 13.5% in children using prophylactic daily doses of 200 mg of oral vitamin C
prophylactically supplementing vitamin C decreases the risk of infection with respiratory viruses such as the common cold
combined with probiotics, oral vitamin C supplementation showed a 33% decrease in the incidence of respiratory tract infections in preschool-age children [
high-dose oral supplementation of vitamin C managed to prevent or reduce symptoms if taken before or just after the onset of cold- or flu-like symptoms
improvements in oxygen saturation and decreased IL-6 levels (a marker of inflammation) in the treatment group compared to the control group
8 g doses of oral vitamin C
there is a negative correlation between age and serum levels of vitamin C
Patients with COVID-19 will likely also experience depletion in serum levels of vitamin C as a direct result of the upregulation of the immune system to combat the infection
Colunga et al. suggested that oral vitamin C can be combined with oral Quercetin, an antiviral flavonoid, to improve Quercetin’s ability to block viral membrane fusion of SARS-CoV-2
high doses of 1-2 g/day of oral vitamin C could prevent other upper respiratory infections
It appears vitamin C supplementation by itself does not provide a striking benefit in preventing COVID-19 infection for those without a deficiency
Flawed statement. What is normal? Vitamin D.
Many variables effect levels and dose, including the two compartment kinetics and absorption.
Hiedra et al. were able to show decreases in inflammatory biomarkers, such as D-dimer and ferritin
some evidence to support that prophylactic use of vitamin C helps reduce the severity of respiratory infection symptoms once a subject has already been infected
oral vitamin C in combination with zinc provided the largest amount of antibody titers 42 days
linear relationship between days of vitamin C therapy and survival duration
other studies were unable to find any definitive improvement concerning therapy with vitamin C
Either these studies are designed to fail or the authors are lacking some basic understanding of pharmacokinetics and pharmacodynamics with vitamin C.
Fowler et al. aimed to see if a high-dose vitamin C infusion would benefit patients affected by ARDS, but they were unable to conclude that vitamin C infusion, compared to a placebo, could decrease vascular inflammation and damage in ARDS
They are kind of make the point from my earlier note.
continuous vitamin C infusion at a rate of 60 mg/kg/day for four days decreased the need for mechanical ventilation and vasopressor use but had no significant effect on overall mortality
Again, designed to fail or ignorance designed the study which failed
Carr et al. suggested that high-dose IV vitamin C is most effective when treating sepsis as septic patients receiving the normal daily recommendations through diet still showed decreased vitamin C levels
High-dose IV vitamin C treatment has also been shown by Kakodkar et al. to decrease syndecan-1, an endothelial glycocalyx that contributes to mortality in septic patients
combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
reduced overall mortality
reduced overall mortality
propose the use for high-dose vitamin C to aid in the treatment of septic shock-induced hypotension
treatment of severe sepsis using a high dose (up to 200 mg/kg/day) of IV vitamin C was explored in phase I, a double-blind, randomized, placebo-controlled trial by Fowler et al. [75]. Their findings included a reduction in SOFA scores and decreased vascular injury compared to a placebo control group, all while showing minimal adverse side effects
Extensive research within the past two decades has shown that curcumin mediates its anti-inflammatory effects through the downregulation of inflammatory transcription factors (such as nuclear factor κB), enzymes (such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6)
Stimulation of TLRs initiates intracellular signaling cascades resulting in downstream NF-B and mitogen-activated protein kinase activation and production of proinflammatory chemokines associated with mechanisms of metabolic dysfunction and cardiovascular disease progression.
Elevated fatty acids levels associated with obesity activate TLR4 signaling in fat cells and macrophages, and induce insulin resistance in murine models
Study finds that Testosterone provided a small anti-inflammatory effect in post-menopausal women and men, whereas Estrogen increased macrophage cytokine production in post-menopausal women with elevated LDL. Now, this study did not differentiate PCOS versus non-PCOS, nor did it look at the effects of adiposity in these hormonal effects in women. Both of which, will effect the outcome.
CoQ10 reduced inflammatory cytokines IL-6 and TNF-alpha. CoQ10 also increased SOD, catalase, and glutathione perioxidase. The duration of therapy was quite short--12 weeks. The patients included in the study had pre-existing CAD.
study finds prolonged exposure to estrogen associated with increased colorectal cancer risk in postmenopausal women. So many unanswered questions. What was the ER status of these patients? What was the weight of these patients? One cannot simply compare estrogen exposure to colorectal cancer risk and say aha! What is the environment of the individual(s)?!Thanks
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Skeletal muscles are much more than just about contraction. There produce inflammatory cytokines and other signals that have endocrine-like effects. This article calls them myokines. A decrease in physical activity would leave an altered myokine response effecting the liver, adipose tissue, immune system and pancreatic function.
increased inflammatory markers associated with increased hot flash severity in menopausal women. This is also associated with increased cardiovascular disease. Interesting that progesterone has anti-inflammatory properties. So, therapy to reduce hot flashes should include inflammation reduction.