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Nathan Goodyear

Testosterone physiology in resistance exercise an... [Sports Med. 2010] - PubMed - NCBI - 0 views

  • testosterone stimulates protein synthesis
  • promotion of muscle hypertrophy by testosterone
  • intracellular androgen receptor (AR)
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  • In general, testosterone concentration is elevated directly following heavy resistance exercise in men
  • Findings on the testosterone response in women are equivocal with both increases and no changes observed in response to a bout of heavy resistance exercise
  • Age also significantly affects circulating testosterone concentrations.
  • Aging beyond 35-40 years is associated with a 1-3% decline per year in circulating testosterone concentration in men
  • aging results in a reduced acute testosterone response to resistance exercise in men.
  • In women, circulating testosterone concentration also gradually declines until menopause, after which a drastic reduction is found.
  • acute increases in testosterone can be induced by resistance exercise
  • testosterone is an important modulator of muscle mass in both men and women
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    Resistance training to increase endogenous Testosterone production: more specific, the exercise must be high rep or as the authors call it--high volume.  To do this, the weight needs to be light.
Nathan Goodyear

Testosterone, SHBG and differential white blood cell count in middle-aged and older men... - 0 views

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    higher endogenous total Testosterone associated with decline in WBC.  Simply a cross sectional analysis.  No association with low free Testosterone.
Nathan Goodyear

Changes in the immune system during menopause and aging. - PubMed - NCBI - 0 views

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    Menopause is associated with a decline in CD4 T and B cells and well as a decrease in NK cells.  This is a set up for disease, particularly cancer.
Nathan Goodyear

Nutrients | Free Full-Text | Vitamin C Status Correlates with Markers of Metabolic and ... - 0 views

  • vitamin C deficiency is the fourth most prevalent nutrient deficiency reported in the United States
  • Hypovitaminosis C (defined as a plasma concentration ≤23 µmol/L)
  • The CHALICE (Canterbury Health, Ageing and Lifecourse) study is a unique New Zealand study comprising a comprehensive database of determinants of health
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  • The CHALICE cohort of 404 individuals aged 50 years had an average vitamin C intake of ~110 mg/day, which should provide adequate plasma concentrations [14]. Despite this, a significant proportion of the participants had inadequate plasma vitamin C status
  • inadequate plasma vitamin C concentrations (i.e., <50 µmol/L)
  • adequate plasma levels (i.e., >50 µmol/L)
  • Higher plasma vitamin C status was associated with lower weight, BMI and waist circumference
  • plasma vitamin C was negatively associated with blood triglycerides, HbA1c and insulin, and positively associated with HDL levels.
  • No correlation was found between plasma vitamin C and the two indicators of heart health; blood pressure and cardiovascular risk score.
  • 2.4% of 50-year-olds were deficient in vitamin C (i.e., <11 µmol/L)
  • hypovitaminosis C (i.e., <23 µmol/L)
  • A high proportion (63%) of our participants had inadequate plasma vitamin C concentrations (i.e., <50 µmol/L)
  • The association of low vitamin C with obesity in this study replicates results in the literature [35,40,41,42,43,44], and it is apparent that individuals with higher weight require higher intakes of vitamin C to reach adequate vitamin C status
  • higher plasma vitamin C status is associated with lower circulating levels of blood triglycerides, insulin and HbA1c
  • A role for vitamin C in the prevention or management of diabetes and/or metabolic syndrome has been suggested
  • In this study, we also demonstrate lower levels of mild cognitive impairment in those with high vitamin C status
  • The odds of mild cognitive impairment were twice as high for those below 23 μmol/L plasma vitamin C concentration.
  • Vitamin C is present at very high concentrations in the brain
  • animal models have shown that the brain is the last organ to be depleted of the vitamin during prolonged deficiency
  • A recent animal study has shown that moderate vitamin C deficiency may play a role in accelerating amyloid plaque accumulation in Alzheimer’s disease
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    New study: vitamin C levels correlate with cognitive and metabolic health. What is your vitamin C level? Despite the adequate levels of vitamin C intake, a large % of the individuals had inadequate vitamin C levels which points to a demand issue.  Higher oxidative stress, chronic inflammation... would drive demand for vitamin C higher. Lower vitamin C levels were associated with more metabolic disease, ie. DM, and more cognitive decline.
Nathan Goodyear

Mediterranean diet, cognitive function, and dementia: a systematic review. - PubMed - NCBI - 0 views

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    review finds Mediterranean diet may slow cognitive decline and decrease risk of Alzheimer's disease.
Nathan Goodyear

Mediterranean Diet, Cognitive Function, and Dementia: A Systematic Review of the Evidence - 0 views

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    review finds Mediterranean diet associated with improved cognitive function and possible delay in cognitive decline.
Nathan Goodyear

Effect of acute DHEA administration on free testosterone in middle-aged and young men f... - 0 views

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    Decline in free Testosterone, especially in physically unfit men, blunted by oral 50 mg DHEA night before exercise.  Total Testosterone and DHEA remained significantly low up to 24 hours post HIIT.
Nathan Goodyear

Changes in the rate of PSA progression and the level of alkaline phosphatase during hig... - 0 views

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    Brief read...will re-read, but IV vitamin C (albeit relatively low doses) correlate with decline in psa and alkP.
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https://www.sightcare-co.com/ - 0 views

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LeanBiome™ (Official) | Get Save UpTo $540 Today Only! - 0 views

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Nathan Goodyear

The endocrinology of sexual arousal - 0 views

  • A number of age-related changes may be relevant: altered negative feedback of testosterone and hence less increase in luteinizing hormone (LH) with falling testosterone levels, increased sex hormone binding globulin (SHBG) and hence relatively reduced free testosterone and the likelihood of an age-related decline in testosterone receptor sensitivity
  • In the older male, the picture is complicated by various aging effects, including altered hypothalamo–pituitary feedback, increased testosterone binding and reduced receptor sensitivity
  • The neurophysiological basis of NPT is still disputed, but one plausible explanation is that REM sleep is associated with a ‘switching off’ of the noradrenergic cells in the locus coeruleus
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  • the impact of testosterone on the emergence of sexual arousability is less clear
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    Good discussion of the arousal/sexual response differences between men and women from a physiological perspective.  
Nathan Goodyear

Waist-to-height ratio as a predictor of serum testosterone in ageing men with symptoms ... - 0 views

  • WHt ratio was calculated by dividing waist (cm) by height (cm)
  • nverse relationships of BMI and WC with TT and cFT have been previously documented in unselected cohorts of adult men
  • over the age of 54 years
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  • adjusting WC for height (WHt ratio) improves the prediction of TT and cFT compared with either BMI or WC alone
  • there were inverse correlations between cFT, TT and either BMI or WC
  • for each unit increase in BMI, there was a 2% fall in TT and cFT
  • for each 10 cm increment in WC, TT and cFT levels declined by 7%.
  • The magnitude of this relationship between increasing BMI and decreasing TT is similar to that described in the Massachusetts Male Ageing Study
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    waist to height ratio reliable predictor of low T in men.
Nathan Goodyear

Gender and sex hormones in multiple sclerosis pathology and therapy - 0 views

  • It is now well recognized that the disease manifestation is reduced in pregnant women with relapsing-remitting MS
  • This occurs particularly during the third trimester when levels of estrogens (estradiol and estriol) and progesterone (see Table 2) are elevated up to about 20 times
  • This seems well correlated with a decrease in active white matter lesions detected by MRI
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  • This clinical improvement is however followed by temporary rebound exacerbations at post-partum, when the hormone levels decline
  • a shift from Th1 to Th2 immune response, expansion of suppressive regulatory T lymphocytes and decrease in the number of circulating CD16+ natural killer (NK)-cells
  • Th1 lymphocytes secrete proinflammatory cytokines (e.g. IL-2, IFNgamma, lymphotoxin) while Th2 cells secrete anti-inflammatory cytokines (e.g. IL-4, IL-5, IL-10), which favor humoral-mediated responses
  • Th2 cytokines are associated with down-regulation of Th1 cytokines and this Th2 shift is believed to provide protection from allograft rejection during pregnancy as well as from Th1-mediated autoimmune disease
  • it is worth noting that the levels of other hormones with anti-inflammatory activity (1,25-dihydroxy-vitamin D3, norepinephrine, cortisol) also increase by 2 to 4 times during late pregnancy
  • 1,25-dihydroxy vitamin D3 induces regulatory T-cell function important for development of self-tolerance
  • breast-feeding does not alter the relapse rate in women with MS
  • Leptin is a pleiotropic hormone produced primarily by adipocytes but also by T lymphocytes and neurons
  • Several lines of evidence indicate that leptin contributes to EAE/MS pathogenesis, influencing its onset and clinical severity, by acting as a proinflammatory cytokine which promotes regulatory T cell (Treg) anergy and hyporesponsiveness, resulting in increased Th1 (TNFalpha, INFgamma) and reduced Th2 (IL-4) cytokine production
  • circulating leptin levels are increased in relapsing-remitting MS patients (men and women analyzed together) while the CD4+CD25+Treg population decreases
  • As the leptin plasma concentrations are proportional to the amount of fat tissue, obese/overweight individuals produce higher levels of leptin
  • Nielsen et al found that estradiol and progesterone exert neuroprotection against glutamate neurotoxicity, while MPA antagonizes the neuroprotective effect of estradiol and exacerbated neuron death induced by glutamate excitotoxicity
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    very good review of the differences in MS and hormones between the sexes.
Nathan Goodyear

Cardiorespiratory fitness is associated with white matter integrity in aging - Hayes - ... - 0 views

  • CRF impacts cognition and the brain during childhood, exerts minimal influence during young adulthood when indicators of neural structure and function are typically at their lifetime peak, but may again positively impact brain structure and function in OA as cognitive decline begins in later adulthood.
  • enhanced white matter microstructure in high-fit children relative to low-fit children
  • current results support the notion that CRF contributes to successful brain aging
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  • there is regional specificity in the associations between peak VO2 and FA
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    Physical fitness associated with improved brain aging as the body ages.
Nathan Goodyear

Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurode... - 0 views

  • The starting dose was 500 mg/day and if no toxicity was noted, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. There was no treatment-related toxicity up to 8 g/day but the bulky volume of the drug was unacceptable to the patients beyond 8 g/day.
  • The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of curcumin and gradually declined within 12 hours
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    Great article on the benefits of curcumin in therapy for inflammation and disease.
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Nathan Goodyear

Study Suggests Coenzyme Q10 Slows Functional Decline in Parkinson's Disease: National I... - 0 views

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    high dose CoQ10 shown to slow disease progression in Parkinson's disease.  A similar study had shown the same finding in Huntington's disease.  Both are excitotoxic diseases
Nathan Goodyear

Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 di... - 0 views

  • up to 40% of men with T2DM have testosterone deficiency
  • Among diabetic patients, a reduction in sex hormone binding globulin levels induced by insulin resistance leads to a further decline of testosterone levels
  • low bioavailable testosterone concentration was related to decreased lean body mass and muscle strength
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  • Testosterone deficiency has a high prevalence in men with T2DM, and it is also associated with impaired insulin sensitivity, increased percentage body fat, central obesity, dyslipidemia, hypertension and cardiovascular diseases (CVD)
  • A meta-analysis of four randomized controlled trials (RCTs) showed that TRT seemed to improve glycemic control as well as fat mass in T2DM subjects with low testosterone levels and sexual dysfunction.
  • testosterone administration could increase muscle mass and strength
  • Insulin stimulates glucose uptake into muscle and adipose tissue via the Glut4 glucose transporter isoform. When insulin activates signaling via the insulin receptor, Glut4 interacts with insulin receptor substrate 1 to initialize intracellular signaling and facilitate glucose transportation into the cell
  • The benefits of TRT on glucose metabolism can mainly be explained by its influence on the insulin signaling pathway
  • Insulin resistance as assessed by, which is calculated from the equation (If*Gf/22.5, where If is fasting insulin and Gf is fasting glucose), was definitely improved by TRT after testosterone administration in three studies
  • Testosterone was observed to elevate the expression levels and stimulate translocation of Glut4 in cultured skeletal muscle cells and to upregulate Glut4 by activating insulin receptor signaling pathways in neonatal rats
  • These effects were inhibited by a dihydrotestosterone (DHT) blocker, indicating that glucose uptake may correlate with conversion of testosterone to DHT and activation of the androgen receptor.
  • TRT reduced triglyceride levels
  • TRT has been reported to have a positive effect in the decrease of total and LDL cholesterol levels and triglycerides in hypogonadal men
  • a recent meta-analysis showed that statins could significantly lower testosterone concentrations.
  • Epidemiological studies have found a negative relationship between testosterone levels and typical cardiovascular risk markers, such as body mass index, waist circumference, visceral adiposity and carotid intima-media thickness.
  • Testosterone treatment was shown to raise hemoglobin, hematocrit and thromboxane, all of which might give rise to CVD
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    Low Testosterone is a very significant problem in men with type II Diabetes.  Estimated to reach 40%, likely much higher.  They based these estimates only on T levels and sexual symptoms. Testosterone improves glycemic control primarily through Increased transcription and transloction of GLUT4 insulin receptors to the cell surface.  Inflammation reduction is also a mechanism.  Testosteorne lowers Triglycerides in the traditional lipid profile.  Studies are mixed on the other aspects of  lipids.  
Nathan Goodyear

Testosterone and glucose metabolism in men: current concepts and controversies - 0 views

    • Nathan Goodyear
       
      80% of E2 production in men, that will cause low T in men, comes from SQ adiposity.  This leads to increase in visceral adiposity.
  • Only 5% of men with type 2 diabetes have elevated LH levels (Dhindsa et al. 2004, 2011). This is consistent with recent findings that the inhibition of the gonadal axis predominantly takes place in the hypothalamus, especially with more severe obesity
  • Metabolic factors, such as leptin, insulin (via deficiency or resistance) and ghrelin are believed to act at the ventromedial and arcuate nuclei of the hypothalamus to inhibit gonadotropin-releasing hormone (GNRH) secretion
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  • kisspeptin has emerged as one of the most potent secretagogues of GNRH release
  • Consistent with the hypothesis that obesity-mediated inhibition of kisspeptin signalling contributes to the suppression of the HPT axis, infusion of a bioactive kisspeptin fragment has been recently shown to robustly increase LH pulsatility, LH levels and circulating testosterone in hypotestosteronaemic men with type 2 diabetes
  • Figure 4
  • Interestingly, a recent 16-week study of experimentally induced hypogonadism in healthy men with graded testosterone add-back either with or without concomitant aromatase inhibitor treatment has in fact suggested that low oestradiol (but not low testosterone) may be responsible for the hypogonadism-associated increase in total body and intra-abdominal fat mass
    • Nathan Goodyear
       
      This does not fit with the research on receptors, specifically estrogen receptors.  These studies that the authors are referencing are looking at "circulating" levels, not tissue levels.
  • A smaller study with a similar experimental design found that acute testosterone withdrawal reduced insulin sensitivity independent of body weight, whereas oestradiol withdrawal had no effects
  • Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al. 2012b) are important contributors to the suppression of the HPT axis
  • This is supported by observational studies showing that weight gain and development of diabetes accelerate the age-related decline in testosterone
  • Weight loss can reactivate the hypothalamic–pituitary–testicular axis
  • The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen receptor modulators in obese men
  • Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men with type 2 diabetes
  • Several observational and randomised studies reviewed in Grossmann (2011) have shown that weight loss, whether by diet or surgery, leads to substantial increases in testosterone, especially in morbidly obese men
  • This suggests that weight loss can lead to genuine reactivation of the gonadal axis by reversal of obesity-associated hypothalamic suppression
  • There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
  • in those men in whom glycaemic control worsened, testosterone decreased
  • successful weight loss combined with optimisation of glycaemic control may be sufficient to normalise circulating testosterone levels in the majority of such men
  • weight loss, optimisation of diabetic control and assiduous care of comorbidities should remain the first-line approach.
    • Nathan Goodyear
       
      This obviously goes against marketing-based medicine
  • In part, the discrepant results may be due to the fact men in the Vigen cohort (Vigen et al. 2013) had a higher burden of comorbidities. Given that one (Basaria et al. 2010), but not all (Srinivas-Shankar et al. 2010), RCTs in men with a similarly high burden of comorbidities reported an increase in cardiovascular events in men randomised to testosterone treatment (see section on Testosterone therapy: potential risks below) (Basaria et al. 2010), testosterone should be used with caution in frail men with multiple comorbidities
  • The retrospective, non-randomised and non-blinded design of these studies (Shores et al. 2012, Muraleedharan et al. 2013, Vigen et al. 2013) leaves open the possibility for residual confounding and multiple other sources of bias. These have been elegantly summarised by Wu (2012).
  • Effects of testosterone therapy on body composition were metabolically favourable with modest decreases in fat mass and increases in lean body mass
  • This suggests that testosterone has limited effects on glucose metabolism in relatively healthy men with only mildly reduced testosterone.
  • it is conceivable that testosterone treatment may have more significant effects on glucose metabolism in uncontrolled diabetes, akin to what has generally been shown for conventional anti-diabetic medications.
  • the evidence from controlled studies show that testosterone therapy consistently reduces fat mass and increases lean body mass, but inconsistently decreases insulin resistance.
  • Interestingly, testosterone therapy does not consistently improve glucose metabolism despite a reduction in fat mass and an increase in lean mass
  • the majority of RCTs (recently reviewed in Ng Tang Fui et al. (2013a)) showed that testosterone therapy does not reduce visceral fat
    • Nathan Goodyear
       
      visceral and abdominal adiposity are biologically different and thus the risks associated with the two are different.
    • Nathan Goodyear
       
      yet low T is associated with an increase in visceral adiposity--confusing!
  • testosterone therapy decreases SHBG
  • testosterone is inversely associated with total cholesterol, LDL cholesterol and triglyceride (Tg) levels, but positively associated with HDL cholesterol levels, even if adjusted for confounders
  • Although observational studies show a consistent association of low testosterone with adverse lipid profiles, whether testosterone therapy exerts beneficial effects on lipid profiles is less clear
  • Whereas testosterone-induced decreases in total cholesterol, LDL cholesterol and Lpa are expected to reduce cardiovascular risk, testosterone also decreases the levels of the cardio-protective HDL cholesterol. Therefore, the net effect of testosterone therapy on cardiovascular risk remains uncertain.
  • data have not shown evidence that testosterone causes prostate cancer, or that it makes subclinical prostate cancer grow
  • compared with otherwise healthy young men with organic androgen deficiency, there may be increased risks in older, obese men because of comorbidities and of decreased testosterone clearance
  • recent evidence that fat accumulation may be oestradiol-, rather than testosterone-dependent
Nathan Goodyear

The molecular basis of neurodegeneration in multiple sclerosis - 0 views

  • Inflammation is the most predominant feature during the early (relaping) phases of the disease and declines with aging of the patients and disease duration
  • in the process of oligodendrocyte destruction and demyelination in MS lesions iron is liberated from its intracellular ferritin bound stores into the extracellular space, where it is taken up by microglia and macrophages and again stored together with ferritin. When this happens in MS lesions in an environment, where free radicals are produced by oxidative burst, iron can be liberated from ferritin and transformed into reactive Fe++[114], which reacts with hydrogen peroxide to generate highly reactive hydroxyl radicals [36] and thus amplifies oxidative damage and associated cellular injury
  • anti-inflammatory or immunomodulatory treatments are effective in the relapsing stage, but the benefit is lost when the patients have entered the progressive phase
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  • Inflammation will remain a key target, since the data suggest that microglia activation and oxidative burst is driven by inflammation throughout all stages of the disease.
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    Very nice review of the neurodegenerative process in MS.  
Nathan Goodyear

Therapy in the Early Stage: Incretins - 0 views

  • Increased resistance to insulin action in the skeletal muscle and liver associated with enhanced hepatic glucose output and impaired insulin secretion due to a progressive decline of β-cell function are long-recognized core defects
  • in addition, other mechanisms/organs are involved, augmenting the pathological pathways: adipocytes (altered fat metabolism due to insulin resistance), gastrointestinal tract (incretin deficiency and/or resistance), pancreatic α-cells (hyperglucagonemia and increased hepatic sensitivity to glucagon), kidneys (enhanced glucose reabsorption), and central nervous system (insulin resistance)
  • β-cell failure
    • Nathan Goodyear
       
      and studies have shown that a reduction in insulin function will decrease LH production and thus lead to a decrease in Testosterone production in men.
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  • Incretins are gut-derived hormones, members of the glucagon superfamily, released in response to nutrient ingestion (mainly glucose and fat)
  • They exert a wide range of effects, including stimulation of pancreatic insulin secretion in a glucose-dependent manner and play an important role in the local gastrointestinal and whole-body physiology
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    good discussion on incretins and their role in glucose homeostasis. 
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