Vitamin C plus rutin, in combination, shown to reduce oxidative stress markers in sciatic nerve. Vitamin C will be an aid in therapy to treat peripheral neuropathy.
Great article. Really shows the depth of the androgens and androgen metabolites in diabetes and diabetic complications. In this study, DHT and its metabolis 3-alpha androstanediol were shown to reduce inflammation and pain associated with diabetic neuropathy. Significant reduction in inflammation signaling (IL-1beta, TNF-alpha) was seen as was potential neurodegenerative processes (glutamate release and astrocyte immunoreactivity).
This study follows others: Diabetes associated with low Total Testosterone. The question is whether this is a cause and effect or merely an association?
This study also found age, income, BMI, and diabetic neuropathy as risk for low Testosterone.
alpha lipoic acid shown to reduce diabetic neuropathy in this review of 15 clinical trials. The trials included both IV and oral administration of alpha lipoic acid. Both routes of administration revealed positive reduction of neuropathic symptoms.
Case report of 3 cases finds improvement in diabetic foot complications, including neuropathy, in men treated with Testosterone. This makes sense as the Testosterone will improve insulin function, improve HgbA1c and reduce inflammation in these men.
both obesity and low testosterone are linked with promotion of inflammatory pathways [70–72] and exert harmful actions on the central [73–75] and peripheral [29,76] nervous systems
In general, obesity-related changes were worsened by low testosterone and improved by testosterone treatment; however, this relationship was not statistically significant in several instances. Further, our data suggest that a common pathway that may contribute to obesity and testosterone effects is regulation of inflammation
fasting blood glucose levels were independently and additively increased by GDX-induced testosterone depletion and high-fat diet
testosterone treatment significantly reduced fasting glucose under both the normal and high-fat diets, demonstrating potential therapeutic efficacy of testosterone supplementation
fasting insulin, insulin resistance (HOMA index), and glucose tolerance, low testosterone tended to exacerbate and or testosterone treatment improved outcomes.
testosterone status did not significantly affect body weight
testosterone’s effects likely do not indicate an indirect result on adiposity but rather regulatory action(s) on other aspects of metabolic homeostasis
Prior work in rodents has shown diet-induced obesity induces insulin resistance in rat brain [63] and that testosterone replacement improves insulin sensitivity in obese rats [64]. Our findings are consistent with the human literature, which indicates that (i) testosterone levels are inversely correlated to insulin resistance and T2D in healthy [30,65] as well as obese men [66], and (ii) androgen therapy can improve some metabolic measures in overweight men with low testosterone
it has been shown that TNFα has inhibitory effects on neuron survival, differentiation, and neurite outgrowth
Our data demonstrate that low testosterone and obesity independently increased cerebrocortical mRNA levels of both TNFα and IL-1β
Testosterone status also affected metabolic and neural measures
many beneficial effects of testosterone, including inhibition of proinflammatory cytokine expression
neuroprotection [80,81], are dependent upon androgen receptors, the observed effects of testosterone in this study may involve androgen receptor activation
testosterone can be converted by the enzyme aromatase into estradiol, which is also known to exert anti-inflammatory [82] and neuroprotective [83] actions
glia are the primary sources of proinflammatory molecules in the CNS
poorer survival of neurons grown on glia from mice maintained on high-fat diet
Since testosterone can affect glial function [86] and improve neuronal growth and survival [87–89], it was unexpected that testosterone status exhibited rather modest effects on neural health indices with the only significant response being an increase in survival in the testosterone-treated, high-fat diet group
significantly increased expression of TNFα and IL-1β in glia cultures derived from obese mice
testosterone treatment significantly lowered TNFα and IL-1β expression to near basal levels even in obese mice, indicating a protective benefit of testosterone across diet conditions
IL-1β treatment has been shown to induce synapse loss and inhibit differentiation of neurons
Testosterone status and diet-induced obesity were associated with significant regulation of macrophage infiltration
testosterone prevented and/or restored thermal nociception in both diet groups
a possible mechanism by which obesity and testosterone levels may affect the health of both CNS and PNS
Study points to obesity and low Testosterone contribution of neuroinflammation. No effect of body weight was seen with TRT. This animal model found similar positive effects of TRT in insulin sensitivity. Obesity and low T increase inflammatory cytokine production: this study found an increase in TNF-alpha and IL-1beta and TRT reduced TNF-alpha and IL-1beta to near base-line. Testosterone is neuroprotective and this study reviewed the small volume of evaded that pointed to benefit from estradiol. Testosterone's effect on glial survival was positive but not significant. Obesity and low T were found to be associated with increased macrophage infiltration in the PNS with increased TNF-alpha and IL-1beta. Testosterone therapy improved peripheral neuropathy via its positive effects on nocicieption.