Testosterone shown to improve GLUT 4 and IRS-1 expression with low dose short term therapy; in contrast, high dose, prolonged therapy shown to down regulate IRS-1 and GLUT 4 expression. This shows the importance of using saliva for evaluation versus serum. Serum testing routinely leads to over treatment with high dosages of testosterone.
This study reveals CFS to be low adrenal cortisol output problem. In this study, low dose cortisol (hydrocortisone) therapy improved symptoms of fatigue and improved the CRH adrenal stimulation of adrenal cortisol production.
Master's thesis reviews Testosterone therapy in women. The evidence is poor. What is seen is that low SHBG and increasing Testosterone in the long term appears to be associated with adverse CV effects. Otherwise, the effects of Testosterone are negligible if negative at all. High dose studies did find increased CVD in women. The dosing here was at 40 mg.
Study looked at aromatase activity in androgen production in older men. The study found that aromatase inhibition with arimidex increased Testosterone production. PSA was also monitored and PSA increased in the smaller dose group versus the high dose group.
Another ill conceived conclusion by the authors. IF you are going to study something, know everything about it. They authors make a major statement about vitamin D, yet they seem to understand a basic understanding of vitamin dosing. The authors stated that dosing 2,000 IU of vitamin D in those with levels < 50 provided no benefit. That is of course correct, because 2,000 IU daily won't hold any levels stable, let alone increase levels to 70-80 where they need to be. The authors of this study are stuck in the traditional RDC thinking here.
What is interesting is that low vitamin D was associated with CVD, MS, dyslipidemia, inflammation, glucose dysmetabolism, infections, mood disorders, decline in cognition, impaired physical functioning, and all-cause mortality, But, vitamin D supplementation is only good for bones. The authors of this study make a mockery of medicine.
Hypogonadism may be defined either as serum concentration of T (either total T, bioavailable T or free T) or as low T plus symptoms of hypogonadism
The Baltimore Longitudinal Study on Aging reported the incidence of total serum T < 325 ng/dL to be 20% for men in their 60s, 30% for men in their 70s and 50% for men over 80
The Massachusetts Aging Male Study reported that 12.3% of men aged 40 to 70 had a total serum T of < 200 ng/dL with 3 or more symptoms of hypogonadism
The Boston Area Community Health Study reported that 5.6% of men aged 30 to 70 were hypogonadal, as defined by total serum T < 300 ng/dL; or, free serum T < 5 ng/dL plus 3 or more symptoms of hypogonadism
In a health screening project among 819 men in Taiwan, the prevalence of hypogonadism (total serum T < 300 ng/dL) ranged from 16.5% for men in their 40s, 23.0% for men in their 50s, 28.9% for men in their 60s, and 37.2% for men older than 70 years of age
The prevalence of hypogonadism among men in Taiwan is higher than the prevalence reported in the Massachusetts Male Aging Study
CAG repeat sequence, within the androgen receptor (AR). Rajender et al[12] reviewed over 30 studies on the AR trinucleotide repeat and infertility
suggestion that CAG repeat length may determine androgen responsiveness, this issue is not clearly settled
reported prevalence of low T in older men range from 5.6% to 50%
Those in the hypogonadal group (n = 4269) had direct health care costs, that exceeded the eugonadal group (n = 4269) by an average of $7100 over the course of the observation window
higher economic burden and presence of co-morbidities for hypogonadism
minor to moderate improvements in lean mass and muscle strength
increased bone mineral density
modest enhancement in sexual function
reduced adiposity
lessening of depressive symptoms
Meta-analyses of clinical TRT trials as of 2010 have identified three major adverse events resulting from TRT: (1) polycythemia; (2) an increase in prostate-related events; and (3) and a slight reduction in serum high-density lipoprotein (HDL) cholesterol
polycythemia (> 3.5-fold increase in risk
TRT produced a 40% prostate enlargement in older hypogonadal male Veterans over 12 mo
no published analysis has reported measurable increases in prostate cancer risk or Gleason score in men undergoing TRT, or in hypogonadal men with a history of prostate cancer undergoing TRT
the prostate which highly expresses the type II 5α-reductase enzyme. Inhibition of this enzyme via finasteride (a type II 5α-reductase inhibitor) or dutasteride (a dual type I and II 5α-reductase inhibitor) reduces circulating DHT 50%-75% and > 90%, respectively[47], and reduces prostate mass[48] and prostate cancer risk
Normally estradiol partially regulates testosterone levels, at the hypothalamus, blunting LH and FSH release from the pituitary. As a selective estrogen receptor modulator, CC interrupts this pathway, and consequently there is a greater stimulation for the production of testosterone in Leydig cells
In this study of men with low TT levels and without prior MI or stroke, normalization of TT levels using TRT is associated with lower all-cause mortality, fewer MIs, and ischaemic strokes.
retrospective study
significant benefit is observed only if the dose is adequate to normalize the TT levels
the mechanisms for these effects remain speculative
It can be postulated that the beneficial effect of normal T levels on adipose tissue, insulin sensitivity, and lipid profiles or by its anti-inflammatory and anticoagulant properties, as reported by other investigators, might have contributed to our findings
off-label use of TRT remains a concern
Recent FDA analyses suggest that currently only half of the men on TRT had been diagnosed with hypogonadism
25% of users did not have their T concentrations tested prior to initiating therapy
21% of those prescribed TRT did not have their levels tested at any time during treatment
two very recent meta-analyses suggested a lack of convincing evidence posed by TRT.
men without a history of previous MI or stroke who have low TT levels, TRT might be associated with decreased risks of MI, ischaemic stroke, and all-cause mortality in long-term follow-up
TRT should aim for doses resulting in normalization of TT level as this was shown to be associated with reduction in adverse CV events
Study of 209 men > 65 on Testosterone therapy was stopped early due to increase cardiovascular adverse events The likely reason was the amazingly high dosing. The men in this study were just doped. The dosing was 100 mg + which is in stark contrast to the 5-10 mg daily production of a young man at 22.
DCA can penetrate into the traditional chemotherapy sanctuary sites. Interestingly, it was reported that DCA could penetrate across the BBB,30 exhibiting the potential activity for brain therapy.
Clinical studies of DCA have shown reduced lactate levels
It has been reported that DCA activates the PDH by inhibition of PDK in a dose-dependent manner, and results in increased delivery of pyruvate into the mitochondria
The antitumor activity of DCA on nonsmall cell lung cancer, breast cancer, glioblastomas, and endometrial and prostate cancer cells has been demonstrated
It is well known that many chemotherapeutic agents have a low therapeutic index in brain tumors.
The most common metabolic hallmark of cancer cells is their propensity to metabolize glucose to lactic acid at a high rate even in the presence of oxygen
Pyruvate dehydrogenase kinase (PDK) is a gate-keeping enzyme that regulates the flux of carbohydrates (pyruvate) into the mitochondria
In the presence of activated PDK, pyruvate dehydrogenase (PDH), a critical enzyme that converts pyruvate to acetyl-CoA instead of lactate in glycolysis, is inhibited, limiting the entry of pyruvate into the mitochondria.
the level of Hsp70 was significantly decreased
DCA can penetrate the BBB
It has been reported that DCA treatment resulted in an increase in the proportion of tumor cells in the S phase, showing a decrease in proliferation as well as the induction of apoptosis
Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport, and/or stabilization by acting as a molecular chaperone, leading to the inhibition of apoptosis by both caspase-dependent and/or independent pathways
HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, and metastasis
Considering the fact that high expression of HSPs is essential for cancer survival, the inhibition of HSPs is an important strategy of anticancer therapy.
In addition, after 5 years of continued treatment with oral DCA at a dose of 25 mg/kg, the serum DCA levels are only slightly increased compared with the levels after the first several doses, also showing its safety for oral administration at this dose.
DCA can enter the circulation rapidly after oral administration and then generate the stimulation of PDH activity generally within minutes.
Our in vivo results in tumor tissues indicated that DCA significantly induced ROS production and decreased MMP in tumor tissues
The numbers of microvessels in the DCA treatment groups were significantly decreased, suggesting the potential antiangiogenic effect of DCA
Under hypoxic conditions, hypoxia-inducible factor (HIF-1α) is activated and induces angiogenesis
In addition, HIF-1α can also induce the expression of PDK,48 which can inhibit the activity of PDH
The inhibition effect of DCA on HIF-1α would decrease vascular endothelial growth factor and inhibit angiogenesis
the antiangiogenic effect in the 25 mg/kg treatment group was lower than that in 75 mg/kg or 125 mg/kg treatment groups
In conclusion, DCA induces the apoptosis of C6 cells through the activation of the mitochondrial pathway, arresting the cell cycle of C6 cells in S phase and down-regulating Hsp70 expression.
DCA significantly induced the ROS production and decreased the MMP in tumor tissues. Our in vivo antitumor activity results also indicated that DCA has an antiangiogenic effect