Vitamin D Supplementation for the Treatment of Depressive Symptoms in Women with Type 2 Diabetes: A Randomized Clinical Trial.

Aim: To determine the efficacy and safety of vitamin D3 supplementation in reducing depressive symptoms in women with type 2 diabetes (T2D), depression, and low vitamin D. Methods: In this double-blind randomized active comparator-controlled trial, women with significant depressive symptoms as assessed by the Center for Epidemiologic Studies Depression (CES-D) scale received weekly oral vitamin D3 supplementation (50,000 IU) or an active comparator (5,000 IU) for 6 months. Assessments of vitamin D, 25-hydroxyvitamin D [25 (OH) D], and depression were measured at baseline, 3 months, and 6 months. Results: A total of 129 women were randomized, from which 119 completed the study (57 in lower dose and 62 in higher dose). Participants had an average 25 (OH) D and HbA1c of 20.8 ng/mL and 7.8%, respectively, at baseline. They were diverse (48% Black) and had a mean age of 50 and T2D for about 8 years. Upon completion of vitamin D3 supplementation, serum 25 (OH) D levels increased with 50,000 IU (+34 ng/mL) and 5,000 IU (+10 ng/mL). There was no difference in CES-D scores by treatment dose. Overall, depressive symptoms significantly improved over time with an average CES-D decline of 12.98 points (95% CI: -15.04 to -10.93; p < 0.001). Among women with moderate baseline depressive symptoms, those receiving the lower dose had nominally lower depression scores at follow-up than those in the higher dose cohort. Among women with severe baseline depressive symptoms, the improvement in follow-up depression scores was the same regardless of dose. Conclusions: There was no difference in the dosing effect of vitamin D3 supplementation for the treatment of depressive symptoms in women with T2D who present with significant symptoms and low vitamin D. Regardless of the dose, participants' mood improved over time. Further study of vitamin D to target depressive symptoms in comorbid populations is needed.

Vitamin D Supplementation and Cognition in People with Type 2 Diabetes: A Randomized Control Trial.

AIM: Type 2 diabetes increases the risk of cognitive decline which adversely impacts self-management of the disease. Evidence also supports a relationship between low serum 25(OH)D levels and poor cognition. The purpose of this trial was to assess vitamin D supplementation on cognitive executive functioning in persons living with type 2 diabetes. METHODS: This was a double-blinded RCT where participants were randomized to receive either weekly vitamin D3 supplementation (50,000 IUs) or a matching comparator (5,000 IUs) for three months. The primary outcome was a battery of neuropsychological tests. Serum 25(OH)D was measured by liquid chromatography/tandem mass spectrometry. Repeated assessments of cognitive measures were collected over 12 weeks using alternative testing forms to minimize practice effects. RESULTS: Thirty participants were randomized to either the low-dose allocation (n = 15) or the high-dose allocation (n = 15). Most participants were female (83%) and identified as Black (57%). For all cognition measures, there was no statistically significant finding between participants who received high-dose vitamin D supplementation and those who received low-dose supplementation. However, when assessing cognitive function in both groups over time, minimal improvement on the Symbol-Digits, the Stroop Interference Test, and the Trail Making Test Part B was observed. CONCLUSIONS: To our knowledge, this is the first randomized control trial to examine the effects of vitamin D supplementation on cognitive function in people with type 2 diabetes. However, no significant differences in cognitive outcomes between participants who received high-dose therapy and those who received low dose were found.

Vitamin D Supplementation Improves Mood in Women with Type 2 Diabetes.

OBJECTIVE: The aim of this study was to determine the effect of vitamin D supplementation on improving mood (depression and anxiety) and health status (mental and physical) in women with type 2 diabetes mellitus (T2DM). METHODS: Fifty women with T2DM and significant depressive symptomology were enrolled into the "Sunshine Study," where weekly vitamin D supplementation (ergocalciferol, 50,000 IU) was given to all participants for six months. The main outcomes included (1) depression (Center for Epidemiologic Studies Depression, CES-D, and Patient Health Questionnaire, PHQ-9), (2) anxiety (State-Trait Anxiety), and (3) health status (Short Form, SF-12). RESULTS: Forty-six women (92%) completed all visits. There was a significant decrease in depression (CES-D and PHQ-9, p < 0.001) and anxiety (state and trait, p < 0.001). An improvement in mental health status (SF-12, p < 0.001) was also found. After controlling for covariates (race, season of enrollment, baseline vitamin D, baseline depression (PHQ-9), and body mass index), the decline in depression remained significant (CES-D, p < 0.001). There was a trend for a better response to supplementation for women who were not taking medications for mood (antidepressants or anxiolytics) (p = 0.07). CONCLUSIONS: Randomized trials to confirm that vitamin D supplementation can improve mood and health status in T2DM women are needed.

BIOTIN INTERFERENCE WITH ROUTINE CLINICAL IMMUNOASSAYS: UNDERSTAND THE CAUSES AND MITIGATE THE RISKS.

OBJECTIVE: The objectives of this report are to review the mechanisms of biotin interference with streptavidin/biotin-based immunoassays, identify automated immunoassay systems vulnerable to biotin interference, describe how to estimate and minimize the risk of biotin interference in vulnerable assays, and review the literature pertaining to biotin interference in endocrine function tests. METHODS: The data in the manufacturer's "Instructions for Use" for each of the methods utilized by seven immunoassay system were evaluated. We also conducted a systematic search of PubMed/MEDLINE for articles containing terms associated with biotin interference. Available original reports and case series were reviewed. Abstracts from recent scientific meetings were also identified and reviewed. RESULTS: The recent, marked, increase in the use of over-the-counter, high-dose biotin supplements has been accompanied by a steady increase in the number of reports of analytical interference by exogenous biotin in the immunoassays used to evaluate endocrine function. Since immunoassay methods of similar design are also used for the diagnosis and management of anemia, malignancies, autoimmune and infectious diseases, cardiac damage, etc., biotin-related analytical interference is a problem that touches every area of internal medicine. CONCLUSION: It is important for healthcare personnel to become more aware of immunoassay methods that are vulnerable to biotin interference and to consider biotin supplements as potential sources of falsely increased or decreased test results, especially in cases where a lab result does not correlate with the clinical scenario. ABBREVIATIONS: FDA = U.S. Food & Drug Administration FT3 = free tri-iodothyronine FT4 = free thyroxine IFUs = instructions for use LH = luteinizing hormone PTH = parathyroid hormone SA/B = streptavidin/biotin TFT = thyroid function test TSH = thyroid-stimulating hormone.

Vitamin E prevents ethanol-induced inflammatory, hormonal, and cytotoxic changes in reproductive tissues.

Ethanol causes decreased function of the hypothalamic-pituitary-gonadal (HPG) axis. Ethanol resulted in inflammatory changes in HPG manifested by increased concentrations of pro-inflammatory cytokines. Since, such cytokines have deleterious effects on functions of HPG, it seemed possible that ethanol's suppressive action could be due, at least in part, to this inflammation. Since oxidative stress can cause inflammation, we have used the antioxidant vitamin E to test, whether reducing inflammation might protect reproductive functions from ethanol. Rats were fed an ethanol diet or pair fed identically without ethanol for a 3-week period. For the last 10 days, animals were given 30 IU/kg or 90 IU/kg or vehicle. Ethanol significantly increased hypothalamic, pituitary and testicular TNF-alpha and IL-6, all changes prevented by the higher dose of vitamin E. Also, ethanol induced changes in LHRH, LH, testosterone, and testicular germ cell apoptosis were similarly prevented by vitamin E. These data strikingly show that vitamin E protects the HPG from deleterious effects of ethanol and suggests that the mechanism of this protection might be both anti-inflammatory and antioxidant.

Effects of chronic ethanol (EtOH) administration on pro-inflammatory cytokines of the hypothalamic-pituitary-gonadal (HPG) axis in female rats.

We and others have investigated the effects of acute and chronic ethanol (EtOH) administration on function of the hypothalamic-pituitary-gonadal (HPG) axis in female rats, consistently finding EtOH to be detrimental. There are now substantial data that pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6), have anti-reproductive effects. If EtOH increased levels of these cytokines, such data would be consistent with, though not necessarily prove, a cytokine mediated mechanism for EtOH's deleterious effects on reproduction. Young adult female Sprague Dawley rats were used. In the experiment reported here, the Lieber DeCarli diet was used, with animals fed a 36% EtOH containing diet or pair fed an identical diet which contained dextrimaltose instead of EtOH. This was done for 4 to 6 weeks. TNFalpha and IL-6 were measured in the hypothalamus, pituitary, and ovary by ELISA. EtOH exposure resulted in significant increases in TNFalpha and IL-6 in hypothalami, pituitaries, and ovaries. The data reported here are the first to show consistent stimulatory effects of EtOH exposure on cytokines in the reproductive axis of female rats. Because the effects of these cytokines are generally anti-reproductive, these data provide a rational for more rigorous testing of the notion that part of EtOH's deleterious HPG effects may be due to such immuno-endocrine interactions.

The impact of burn injury and ethanol on the cytokine network of the mouse hypothalamus: reproductive implications.

Nearly 50% of the patients admitted to hospitals for burn injuries have detectable levels of alcohol (EtOH) in their circulation. In fact, EtOH is often a causal factor in their injury. It is well known that EtOH as well as burn injury disrupt function of the hypothalamic-pituitary-gonadal (HPG) axis. The cellular mechanisms by which EtOH and/or burn impacts on the HPG are not entirely understood. In the studies reported here, we tested the hypothesis that these injuries mediated their effects by local hypothalamic inflammation. Young adult male mice were subjected to either a 15% total body surface area, full thickness scald, to EtOH, or to both and compared to appropriate controls. They were sacrificed 48 h later. EtOH and burn, as well as the combined injury, consistently and impressively reduced serum testosterone, while increasing hypothalamic concentrations of all three of the pro-inflammatory cytokines, TNFalpha, IL-1beta, and IL-6. In general, the increases induced by burn were greater than those caused by EtOH and the effect of the combined insult was not additive. Hypothalamic concentrations of LHRH were also increased. The data are consistent with the idea that EtOH and/or burn, as models of critical illness, medicate their hypothalamic suppressive effects via increase in pro-inflammatory cytokines.