Vitamin D has key impact in performance of soldiers. low vitamin D has been shown to be associated with increased risk for muscle/bone injury, weakness, and poor healing. Low vitamin D has been associated with low Testosterone. Low vitamin D has also been associated with poor cognition, depression and less than optimal recovery after TBI. This follows recent publication that normalization of vitamin D levels increases Testosterone levels.
Higher serum 25(OH)D concentrations were associated with lower fatality rates in patients with breast cancer
Patients with
the highest concentration of 25(OH)D had approximately half the fatality rate compared to those with the lowest concentration
According to this hypothesis, the growth of a
tumor may be arrested at almost any point in the DINOMIT model by restoring a high serum 25(OH)D concentration in the organism,
resulting in up-regulation of E-cadherin and restoration of a well-differentiated state
Laboratory studies have demonstrated anticancer effects of vitamin D metabolites on three critical phases in the development
of breast tumors: differentiation, apoptosis, and angiogenesis
Higher vitamin D levels associated with lower death rates from breast cancer. In fact, people with the highest levels of vitamin D had death rates cut in half. The authors point to 3 ares that vitamin D has a positive effect against cancer: differentiation, apoptosis, and angiogenesis.
Good article on the immunomodulation effect of vitamin D. The importance of vitamin D goes back to pregnancy. Vitamin D deficiencies during pregnancy inhibit appropriate invariant Natrual killer cells, which play important regulatory effect in autoimmune disease. Even with restoration of vitamin D levels with replacement, the full positive effects of vitamin D are not seen due to limited iNKT potential.
The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
This increase was even more pronounced at 44 d, at 33%
We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial,
which occurred as early as 14 d and was maintained until the end of the trial at 44 d
We first investigated testosterone production after 24 and 48 h of ibuprofen
exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent
(β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time
The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early
as 14 d of administration
Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen
administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production
of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection
except in one experiment with DHEA
Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory
effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine
cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of
steroidogenesis.
Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence,
expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
A previous study reported
androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of
every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
the changes in gene expression indicate that the transcriptional machinery behind the endocrine action
of Leydig cells was most likely impaired by ibuprofen exposure.
Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
The decrease in the free testosterone/LH ratio resulted primarily
from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen
exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted
from ibuprofen’s direct antiandrogenic action
AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from
gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the
Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
a chemical compound, through its effects on the signaling
compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in
the adult human
The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise
response in muscles by repressing transcription
Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates
(41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes
in peritubular cells was also affected
short-term
exposure
In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated
hypogonadism (4), an entity associated with all-cause mortality
compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
an inverse relationship was recently reported between endurance exercise training and male sexual libido
AMH concentrations are lower in seminal plasma from patients with azoospermia than
from men with normal sperm levels
inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical
compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
after administration of 600 mg of ibuprofen to healthy
volunteers
Fascinating link between vitamin D and mitochondria function in skeletal muscle. Vitamin D replacement was found to improve mitochondrial function, improve post exercise discomfort in those with vitamin D deficiency. Obviously, this provides support for a link between vitamin D and mitochondrial function. This could provide an important tool in the recovery phase in athletes.
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.
Good review of data on vitamin D, Vitamin D receptors and cancer risk. Studies have shown that low Vitamin D levels are associated with increased cancer risk and that higher vitamin D levels are associated with reduced cancer risk. The ability to fully map out vitamin Ds role in the physiology is probably difficult due to the heterogeneity of cancer development and physiology.
lower 25(OH)D level was significantly associated with lower total T, E2, SHBG, LH and FSH levels after adjusting for age, residence area, economic status and current smoker
association between 25(OH)D status and hypogonadism in Chinese men and confirms that this relationship is present in a large population
Hypercalcemia of malignancy occurs as the result of direct bone metastasis and via humoral mechanisms such as parathyroid hormone-related protein (PTHrP) or 1,25-dihydroxyvitamin D mediated pathways
ectopic secretion of parathyroid hormone (PTH) has been implicated
Hypercalcemia due to osteolytic bone lesions is common in multiple myeloma, leukemia, and breast cancer
Humoral hypercalcemia is predominant in squamous cell, renal cell and ovarian cancers, and lymphomas are associated with 1,25-dihydroxyvitamin D mediated hypercalcemia
20% of cases of hypercalcemia of malignancy and is frequently encountered in multiple myeloma, metastatic breast cancer, and to a lesser extent in leukemia and lymphoma
Physiologic bone turnover requires the complementary activity of osteoblasts – mesenchymal stem cell-derived bone-forming cells – and bone-resorbing cells of monocyte and macrophage lineage known as osteoclasts
In local osteolytic hypercalcemia, the RANKL/RANK interaction results in excessive osteoclast activation leading to enhanced bone resorption and thus hypercalcemia
In addition, osteoclast activation is also mediated by malignancy secreted cytokines, including interleukin-1, initially termed “osteoclast stimulating factor”
Macrophage inflammation protein 1-alpha (MIP 1-alpha)
hypercalcemia is through extra-renal 1,25-dihydroxyvitamin D (calcitriol) production
1% of cases
increased production of 1,25-dihydroxyvitamin D occurs nearly exclusively in Hodgkin and non-Hodgkin lymphoma with case reports of the same in ovarian dysgerminoma
1-α-hydroxylase in the kidney, a process regulated by PTH
in 1,25-dihydroxyvitamin D induced hypercalcemia, malignant cells likely recruit and induce adjacent macrophages to express 1-α-hydroxylase, converting endogenous calcidiol into calcitriol.31 Calcitriol then binds to receptors in the intestine leading to heightened enteric calcium reabsorption with resultant hypercalcemia
this mechanism of disease is best conceptualized as an absorptive form of hypercalcemia
Ectopic production of PTH by malignant cells has been described in a handful of cases involving cancer of the ovary and lung, as well as neuroendocrine tumors and sarcoma
primary hyperparathyroidism and malignancy comprising nearly 90% of cases of hypercalcemia
an initial panel consisting of PTH, PTHrP, phosphorus, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D should be obtained
Lymphoma, a hypercalcemia due to 1,25-dihydroxyvitamin D mediated pathways, is implied by elevations in 1,25-dihydroxyvitamin D without concomitant elevations in 25-hydroxyvitamin D. In such cases, PTH is low and PTHrP undetectable
Treatment of hypercalcemia of malignancy is aimed at lowering the serum calcium concentration by targeting the underlying disease, specifically by inhibiting bone resorption, increasing urinary calcium excretion, and to a lesser extent by decreasing intestinal calcium absorption
mildly symptomatic disease
marked symptoms
hydration with isotonic fluid (if admitted), avoidance of thiazide diuretics, and a low-calcium diet
denosumab
Denosumab is an RANKL antibody that inhibits osteoclast maturation, activation, and function
Vitamin D supplementation in those individuals with SLE found to benefit these patients. Vitamin D found to reduce TH1 and Th17 activity. It also was found to decrease memory B cells and auto-antibodies. Also of note is the level of vitamin D after therapy-only at 51.4 at 2 months and 41.5 at 6 months.
Low vitamin D levels or the receptors for vitamin D appear to result in an increase in Th17 cells. An increase in Th17 cells will lead to an imbalance with Treg cells and this imbalance is associated with Lupus and other autoimmune processes. Vitamin D inhibits Th17 cell activation.
Dose dependent vitamin D impact on fat. Low vitamin D concentrations associated with fat adipogenesis. Higher vitamin D concentrations inhibited adipogenesis.
d-chiro-inositol levels shown to be low in diabetics. Thus, d-chiro-inositol would prove to be helpful in diabetes management. D-chiro-inositol is a secondary messenger in insulin signaling
A large body of evidence exists to associate low vitamin D with cardiovascular disease. However, this review finds no causal relationship. Is vitamin D an indicator of poor health? Or is it the cause of poor health. Yet to be determined. Is vitamin D safe? Yes.
Alzheimer's model finds that amyloid-beta supresses vitamin D receptor. This study found that vitamin D therapy protected neurons by up regulating vitamin D receptors. This prevented cytotoxicity and cell death.
vitamin D in those with vitamin D deficiency and insulin resistance have improved insulin sensitivity. The doses used in the case studies presented are low. This article highlights the fact that vitamin D outperforms metformin in improved insulin sensitivity.
vitamin D deficiency predisposes children to the respiratory problems commonly found in the winter months. Vitamin D shown to reduce the incidence of such respiratory infections (cold, flu...)