Hypogonadism and MetS are strongly associated [12, 13, 16], having even been demonstrated that with the increasing number of MetS parameters there is a proportional raise in the incidence of hypogonadism
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Vitamin B6 supplementation can improve peripheral polyneuropathy in patients ... - 0 views
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Vitamin B6 pyrodoxine P5P pyridoxal-5-phosphate neuropathy peripheral neuropathy vitamin
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Sensory Neuropathy from Pyridoxine Abuse - NEJM - 0 views
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JAMA Network | JAMA: The Journal of the American Medical Association | Effect of Homocy... - 0 views
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Folic acid folate vitamin B12 B6 CVD cardiovascular events homocysteine The swiss heart study
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Impact of vitamin B6 status on psychological distress in a longitudinal study of HIV-1 ... - 0 views
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Cambridge Journals Online - Abstract - Vitamin B6: a challenging link between nutrition... - 0 views
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Decreased Rate of Coronary Restenosis after Lowering of Plasma Homocysteine Levels - NEJM - 0 views
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Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease - NEJM - 0 views
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Hormonal Modulation in Aging Patients with Erectile Dysfunction and Metabolic Syndrome - 0 views
www.ncbi.nlm.nih.gov/...PMC3888699
low T Testosterone hypogonadism MetS metabolic syndrome men male hormone hormones
shared by Nathan Goodyear on 05 Feb 14
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the presence of MetS did not prove to be a significant determinant of hypogonadism, as it did not lead to a decline in T levels, in MetS patients with already established hypogonadism, the increasing number of MetS features was associated with further decline in T
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In the setting of MetS, hypertriglyceridemia and increased WC have been reported as the most important determinants of hypogonadism
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recent literature consistently associates obesity not only with higher risk of hypogonadism [4, 6, 27] but also with lower T levels
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Visceral adiposity has been particularly related with reduction of T and SHBG levels (independent of other metabolic disorders)
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WC was one of the MetS parameters with the greatest influence in T levels decrease, presenting itself as a strong risk factor for hypogonadism development
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MetS-related T decline was not accompanied by an increase in pituitary LH levels, suggesting impairment in gonadotropin secretion
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The molecules behind this smoothing compensatory effect of GnRH/LH are still unknown, but estrogens and insulin, as well as leptin, TNF-α, and other adipokines, were proposed candidates
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fat stores undertake an increase aromatization of androgens, therefore raising estrogen levels [9, 15], which in turn decrease LH secretion
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our data contradicts the concept that estradiol exerts a negative feedback on hypothalamic GnRH secretion
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taking into account that high estradiol levels have already been described as the only abnormality in a subset of patients with ED, the hypothesis that the later might not only be caused by androgen deficiency is becoming increasingly evident
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it has been reported that the chronic exposure to phosphodiesterase type 5 inhibitors (PDE5i), widely used for the treatment of ED, may influence serum estradiol levels
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thyroid disorders (specially hyperthyroidism) have been related to ED and hypogonadism, and so must be considered in a sexual-dysfunction setting
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It is clear from the current literature that collecting a more thorough hormonal panel might be a wise approach to further uncover hormonal relations
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We concluded that in ED patients with hypogonadism and MetS, the attenuated response of HPG axis (normal or low LH levels) might not always be due to an underlying adiposity-dependent estrogen-raising effect.
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our findings indicate that ED, aging, and estradiol might have a stronger connection than what is currently described in the literature.
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Targeting Synaptic Dysfunction in Alzheimer's Disease by Administering a Specific Nutri... - 0 views
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The central role of magnesium deficiency in Tourette's syndrome: causal relationships b... - 0 views
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http://jpmph.org/upload/pdf/jpmph-45-387.pdf - 0 views
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Testosterone level in men with type 2 diabetes mellitus and related metabolic... - 0 views
www.ncbi.nlm.nih.gov/...PMC4364844
low T low Testosterone Diabetes Testosterone men male hormones metabolic syndrome
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defined by consistent symptoms and signs of androgen deficiency, and an unequivocally low serum testosterone level
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the threshold serum testosterone level below which adverse clinical outcomes occur in the general population is not known
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most population-based studies use the serum testosterone level corresponding to the lower limit, quoted from 8.7 to 12.7 nmol/L, of the normal range for young Caucasian men as the threshold
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Researchers tried to examine whether serum total or free testosterone would be a better/more reliable choice when studying the effect of testosterone. The results were mixed. Some reported significant associations of both serum total and free testosterone level with clinical parameters25, whereas others reported that only serum free testosterone26 or only serum total testosterone6 showed significant associations.
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−0.124 nmol/L/year in serum total testosterone
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In experimental studies, androgen receptor knockout mice developed significant insulin resistance rapidly
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In mouse models, testosterone promoted differentiation of pluripotent stem cells to the myogenic lineage
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testosterone decreased insulin resistance by enhancing catecholamine induced lipolysis in vitro, and reducing lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo
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testosterone regulated skeletal muscle genes involved in glucose metabolism that led to decreased systemic insulin resistance
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In the liver, hepatic androgen receptor signaling inhibited development of insulin resistance in mice
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independent and inverse association of testosterone with hepatic steatosis shown in a cross-sectional study carried out in humans
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Although a low serum testosterone level could contribute to the development of obesity and type 2 diabetes through changes in body composition, obesity might also alter the metabolism of testosterone
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In obese men, the peripheral conversion from testosterone to estrogen could attenuate the amplitude of luteinizing hormone pulses and centrally inhibit testosterone production
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leptin, an adipokine, has been shown to be inversely correlated with serum testosterone level in men
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Leydig cells expressed leptin receptors and leptin has been shown to inhibit testosterone secretion, suggesting a role of obesity and leptin in the pathogenesis of low testosterone
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Baltimore Longitudinal Study of Aging (BLSA) cohort made up of 3,565 middle-class, mostly Caucasian men from the USA, the incidence of low serum total testosterone increased from approximately 20% of men aged over 60 years, 30% over 70 years, to 50% over 80 years-of-age
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As the binding of testosterone to albumin is non-specific and therefore not tight, the sum of free and albumin-bound testosterone is named bioavailable testosterone, which reflects the hormone available at the cellular level
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alterations in SHBG concentration might affect total serum testosterone level without altering free or bioavailable testosterone
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A significant, independent and longitudinal effect of age on testosterone has been observed with an average change of −0.124 nmol/L/year in serum total testosterone28. The same trend has been shown in Europe and Australia
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Asian men residing in HK and Japan, but not those living in the USA, had 20% higher serum total testosterone than in Caucasians living in the USA, as shown in a large multinational observational prospective cohort of the Osteoporotic Fractures in Men Study
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subjects with chronic diseases consistently had a 10–15% lower level compared with age-matched healthy subjects
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In Caucasians, the mean serum total testosterone level for men in large epidemiological studies has been reported to range from 15.1 to 16.6 nmol/L
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Chinese middle-aged men reported a similar mean serum testosterone level of 17.1 nmol/L in 179 men who had a family history of type 2 diabetes and 17.8 nmol/L in 128 men who had no family history of type 2 diabetes
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HK involving a cohort of 1,489 community-dwelling men with a mean age of 72 years, a mean serum total testosterone of 19.0 nmol/L was reported
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pro-inflammatory factors, such as tumor necrosis factor-α in the testes, could locally inhibit testosterone biosynthesis in Leydig cells47, and testosterone treatment in men was shown to reduce the level of tumor necrosis factor-α
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In Asians, a genetic deletion polymorphism of uridine diphosphate-glucuronosyltransferase UGT2B17 was associated with reduced androgen glucuronidation. This resulted in higher level of active androgen in Asians as compared to Caucasians, as Caucasians' androgen would be glucuronidated into inactive forms faster.
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Compared with Caucasians, the frequency of this deletion polymorphism of UGT2B17 was 22-fold higher in Asian subjects
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Other researchers have suggested that environmental, but not genetic, factors influenced serum total testosterone
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The basal and ligand-induced activity of the AR is inversely associated with the length of the CAG repeat chain
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In the European Male Aging Study, increased estrogen/androgen ratio in association with longer AR CAG repeat was observed
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a smaller number of AR CAG repeat had been shown to be associated with benign prostate hypertrophy and faster prostate growth during testosterone treatment
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the odds of having a short CAG repeat (≤17) were substantially higher in patients with lymph node-positive prostate cancer than in those with lymph node-negative disease or in the general population
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assessing the polymorphism at the AR level could be a potential tool towards individualized assessment and treatment of hypogonadism.
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In elderly men, there was reduced testicular response to gonadotropins with suppressed and altered pulsatility of the hypothalamic pulse generator
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a significant, independent and longitudinal effect of age on serum total testosterone level had been observed
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A significant graded inverse association between serum testosterone level and insulin levels independent of age has also been reported in Caucasian men
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most studies showed that changes in serum testosterone level led to changes in body composition, insulin resistance and the presence of MES, the reverse might also be possible
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MES predicted a 2.6-fold increased risk of development of low serum testosterone level independent of age, smoking and other potential confounders
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Other prospective studies have shown that development of MES accelerated the age-related decline in serum testosterone level
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In men with type 2 diabetes, changes in serum testosterone level over time correlated inversely with changes in insulin resistance
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weight loss by either diet control or bariatric surgery led to a substantial increase in total testosterone, especially in morbidly obese men, and the rise in serum testosterone level was proportional to the amount of weight lost
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To date, published clinical trials are small, of short duration and often used pharmacological, not physiological, doses of testosterone
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In the population-based Osteoporotic Fractures in Men Study cohort from Sweden, men in the highest quartile of serum testosterone level had the lowest risk of cardiovascular events compared with men in the other three quartiles (hazard ratio [HR] 0.70
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low serum total testosterone was associated with a significant fourfold higher risk of cardiovascular events when comparing men from the lowest testosterone tertile with those in the highest tertile
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Shores et al. were the first to report that low serum testosterone level, including both serum total and free testosterone, was associated with increased mortality
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low serum total testosterone increased all-cause (HR 1.35, 95% CI 1.13–1.62, P < 0.001) and cardiovascular mortality (HR 1.25
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European Association for the Study of Diabetes 2013 suggested there was an inverse relationship between serum testosterone level and acute myocardial infarction
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Diabetic men in the highest quartile of serum total testosterone had a significantly reduced risk of acute MI when compared with those in the lower quartiles
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serum total testosterone level in the middle two quartiles at baseline predicted reduced incidence of death compared with having the highest and lowest levels
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Nice review of Testosterone levels and some of the evidence linking Diabetes with low T. However, the conclusion by the authors regarding what is causing the low T in men with Diabetes is baffling. The literature does not point to one cause, it is clearly multifactorial--obesity, inflammation, high aromatase activity...I would suggest the authors continue their readings in the manner.
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Anticancer mechanisms of cannabinoids - 0 views
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modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival
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cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals
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of the approximately 108 cannabinoids produced by C. sativa, Δ9-tetrahydrocannabinol (thc) is the most relevant because of its high potency and abundance in plant preparations
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Tetrahydrocannabinol exerts a wide variety of biologic effects by mimicking endogenous substances—the endocannabinoids anandamide3 and 2-arachidonoylglycerol4,5—that engage specific cell-surface cannabinoid receptors
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the cb2 receptor was initially described to be present in the immune system6, but was more recently shown to also be expressed in cells from other origins
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Most of the effects produced by cannabinoids in the nervous system and in non-neural tissues rely on cb1 receptor activation
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cannabinoid receptors and their endogenous ligands are both generally upregulated in tumour tissue compared with non-tumour tissue
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cb2 promotes her2 (human epidermal growth factor receptor 2) pro-oncogenic signalling in breast cancer
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pharmacologic stimulation of cb receptors is, in most cases, antitumourigenic. Nonetheless, a few reports have proposed a tumour-promoting effect of cannabinoids
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most prevalent effect is the induction of cancer cell death by apoptosis and the inhibition of cancer cell proliferation
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thc and other cannabinoids induce the apoptotic death of glioma cells by cb1- and cb2-dependent stimulation
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Autophagy is primarily a cytoprotective mechanism, although its activation can also lead to cell death
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the effect of cannabinoids in hormone- dependent tumours might rely, at least in part, on the ability to interfere with the activation of growth factor receptors
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glioma cells), pharmacologic blockade of either cb1 or cb2 prevents cannabinoid-induced cell death with similar efficacy
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other types of cancer cells (pancreatic48, breast24, or hepatic43 carcinoma cells, for example), antagonists of cb2 but not of cb1 inhibit cannabinoid antitumour actions
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cannabidiol (cbd), a phytocannabinoid with a low affinity for cannabinoid receptors15, and other marijuana-derived cannabinoids57 have also been proposed to promote the apoptotic death of cancer cells acting independently of the cb1 and cb2 receptors
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In cancer cells, cannabinoids block the activation of the vascular endothelial growth factor (vegf) pathway, an inducer of angiogenesi
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In vascular endothelial cells, cannabinoid receptor activation inhibits proliferation and migration, and induces apoptosis
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cb1 or cb2 receptor agonists (or both) reduce the formation of distant tumour masses in animal models of both induced and spontaneous metastasis, and inhibit adhesion, migration, and invasiveness of glioma64, breast65,66, lung67,68, and cervical68 cancer cells in culture
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the ceramide/p8–regulated pathway plays a general role in the antitumour activity of cannabinoids targeting cb1 and cb2
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cbd, by acting independently of the cb1 and cb2 receptors, produces a remarkable anti-tumour effect—including reduction of invasiveness and metastasis
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recent observations suggest that the combined administration of cannabinoids with other anticancer drugs acts synergistically to reduce tumour growth
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combined administration of gemcitabine (the benchmark agent for the treatment of pancreatic cancer) and various cannabinoid agonists synergistically reduced the viability of pancreatic cancer cells
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Other reports indicated that anandamide and HU-210 might also enhance the anticancer activity of paclitaxel89 and 5-fluorouracil90 respectively
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Combined administration of thc and cbd enhances the anticancer activity of thc and reduces the dose of thc needed to induce its tumour growth-inhibiting activity
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Preclinical animal models have yielded data indicating that systemic (oral or intraperitoneal) administration of cannabinoids effectively decreases tumour growth
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Combinations of cannabinoids with classical chemotherapeutic drugs such as the alkylating agent temozolomide (the benchmark agent for the management of glioblastoma80,84) have been shown to produce a strong anticancer action in animal models
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pharmacologic inhibition of egfr, erk83, or akt enhances the cell-death-promoting action of thc in glioma cultures (unpublished observations by the authors), which suggests that targeting egfr and the akt and erk pathways could enhance the antitumour effect of cannabinoids
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Vitamin-Dependent Methionine Metabolism and Alcoholic Liver Disease - 0 views
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methionine metabolism Alcoholic liver disease vitamin B12 Folate B6 transmethylation methylation pathway
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Vitamins and regulation of angiogenesis: [A, B1, B2, B3, B6, B9, B12, C, D, E, K] - Sci... - 0 views
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The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A... - 0 views
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White blood cells, including neutrophils and monocytes, accumulate concentrations of vitamin C up to 100 times greater than that of plasma
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Vitamin C is a crucial component of both the innate (nonspecific) and adaptive (specific) portions of the immune system
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maturation, proliferation, and viability of T cells have all been shown to be upregulated by the presence of normal physiologic concentrations of vitamin C
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vitamin C among healthy young adult males showed a significant increase in serum levels of IgA, IgG, and IgM
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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
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when vitamin C was supplemented with vitamin E in healthy adults, it increased the production of cytokines IL-1 beta and TNF-alpha
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vitamin C acts to modulate the levels of cytokines to prevent them from fluctuating in either direction
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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
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Vitamin C also can recover other endogenous antioxidants in the body such as vitamin E and glutathione, returning them to their active state
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can reduce harmful nitrogen-based compounds such as N-nitrosamines and nitrosamides, both of which are carcinogenic
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subjects taking oral vitamin C supplementation saw a 60% to 90% reduction in oxidative stress compared to a placebo control
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subjects infused with vitamin C alone had a 516% increase in glutathione levels compared to subjects not provided the 500 mg daily supplementation
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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
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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
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prophylactically supplementing vitamin C decreases the risk of infection with respiratory viruses such as the common cold
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combined with probiotics, oral vitamin C supplementation showed a 33% decrease in the incidence of respiratory tract infections in preschool-age children [
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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
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improvements in oxygen saturation and decreased IL-6 levels (a marker of inflammation) in the treatment group compared to the control group
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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
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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
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It appears vitamin C supplementation by itself does not provide a striking benefit in preventing COVID-19 infection for those without a deficiency
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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
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other studies were unable to find any definitive improvement concerning therapy with vitamin C
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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
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in a sample of 67 COVID-19-positive ICU patients, 82% of them displayed plasma vitamin C levels below 0.4 mg/dL
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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
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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
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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
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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
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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
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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
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Maintaining a daily intake of 75 and 100 mg for men and women, respectively, as recommended by the U.S. Institute of Medicine