Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression.

AIM: Treatment-resistant depression patients are more likely to suffer from comorbid physical and mental disorders, experience marked and protracted functional impairment, and incur higher health-care costs than non-affected individuals. Magnesium sulfate is a treatment option that may offer great potential for patients with treatment-resistant depression based on prior work in animals and humans. METHODS: Twelve subjects with mild or moderate treatment-resistant depression were randomized into a double-blind crossover trial to receive an infusion of 4 g of magnesium sulfate in 5% dextrose or placebo infusion of 5% dextrose with a 5-day washout in between the 8-day intervention period. Subjects were assessed before and after the intervention for serum and urine magnesium, lipid panel, the Hamilton Rating Scale for Depression, and the Patient Health Questionnaire-9. RESULTS: We found a difference in serum magnesium from day 2 to 8 (pre-infusion) (P < 0.002) and from baseline to day 8 (P < 0.02). No changes were noted on the Hamilton Rating Scale for Depression or the Patient Health Questionnaire-9 24 h post-treatment, but as serum magnesium increased from baseline to day 7, the Patient Health Questionnaire-9 decreased from baseline to day 7 (P = 0.02). CONCLUSION: Magnesium sulfate did not significantly affect depression 24 h post-infusion, but other results were consistent with the literature. The association between changes in serum magnesium and the Patient Health Questionnaire-9 supports the idea that magnesium sulfate may be used to address treatment-resistant depression, an ongoing medical challenge.

RETRACTED ARTICLE: The Novel Effects of a Hydrolyzed Polysaccharide Dietary Supplement on Immune, Hepatic, and Renal Function in Adults with HIV in a Randomized, Double-Blind Placebo-Control Trial.

The primary objective of the study was to evaluate the effects of a hydrolyzed polysaccharide, rice bran arabinoxylan compound (RBAC), on immune, hepatic, and renal function in HIV + individuals. A six-month randomized double-blind placebo-controlled trial was utilized to conduct the intervention. Forty-seven HIV + participants on stable antiretroviral therapy were enrolled and randomly assigned to one of the two study conditions (n = 22 RBAC and n = 25 placebo) and consumed 3 gram/day of either compound for six months. Participants were assessed at baseline and 3 and 6 months follow-up for CD4+ and CD8+, liver enzymes, and kidney function. No side effects were reported, and liver and kidney markers nearly remained completely within normal limits. The percentage change in CD4+ was similar for the placebo (+2.2%) and RBAC (+3.1%) groups at 6 months follow-up. The percentage change in CD8+ count significantly decreased from baseline to 6 months in the RBAC group (-5.2%), whereas it increased in the placebo group (+57.8%; p = 0.04). The CD4+/CD8+ ratio improved clinically in the RBAC group from 0.95 (SD =0.62) at baseline to 1.07 (SD =0.11) at 6 months, whereas it declined in the placebo group from 0.96 (SD =0.80) at baseline to 0.72 (SD =0.59) at 6 months. Our results showed a statistically significant decrease in CD8+ count and a clinically significant increase in CD4+/CD8+ ratio for the RBAC group compared to the placebo group. Thus, the results of this study suggest that the immunomodulatory and antisenescent activities of RBAC are promising for the HIV population.

The Effect of Broad-Spectrum Dietary Supplementation on Quality of Life, Symptom Severity, and Functioning in Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive neurodegenerative disease that exerts a significant quality-of-life toll on patients. According to the literature, broad-spectrum dietary supplementation including a variety of nutrients, polysaccharides, and compounds may improve the quality of life, functionality, and symptom severity in people with MS. Individuals (n = 15) diagnosed with relapsing-remitting MS (RRMS) for an average of 12.4 years (SD = 7.4; R = 2, 25) were enrolled in a one-year open-label clinical trial in which they consumed a broad-spectrum dietary supplement regimen three times daily. Participants were assessed at baseline and at 3, 6, 9, and 12 months with the following: (1) Functional Assessment of MS (FAMS), (2) the EQ-5D-3L, (3) Beck Depression Inventory-II (BDI), (4) Health Conditions Discomfort Scale (HCDS), and (5) Self-Assessment of Severity of MS Symptoms Scale (SASMSSS). Participants included seven females and eight males (M age = 51.3 years; SD = 7.2; R = 38, 65). Few minor gastrointestinal effects were reported. At the end of the intervention, participants showed significant improvements in all outcome measures, particularly functionality on the FAMS, overall quality of life on the EQ-5D-3L, fewer depressive symptoms on the BDI, and improved severity of symptoms on the HCDS and the SASMSSS. Our results suggest that dietary supplementation containing a variety of nutrients can improve the quality of life, severity of disease symptoms, and functionality in MS patients. These findings are clinically promising for MS patients, given the lack of treatment options geared toward improving quality of life in this population.

The Effect of a Polysaccharide-Based Multinutrient Dietary Supplementation Regimen on Infections and Immune Functioning in Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive neurodegenerative disease associated with increased infection rates, chronic inflammation, and premature death. Optimization of nutritional status via dietary supplementation may improve immune function in people suffering from MS and lead to decreased rates of infection. Fifteen individuals with a diagnosis of relapsing-remitting MS for an average of 12.4 years (SD =7.4; R = 2, 25) were enrolled in a one-year open-label clinical trial. Participants consumed a broad-spectrum dietary supplement regimen containing polysaccharides, phytochemicals, antioxidants, vitamins, and minerals three times per day. The occurrence of infections and a panel of cytokines, growth factors, and T- and B-cell subsets were assessed at baseline and 12 months. Seven female and 8 male participants with an average age of 51.3 years (SD =7.2; R = 38, 65) completed the study. At the end of the intervention, participants had fewer total infections (M = 7.9, SD =8.1 at baseline and M = 2.5, SD =4.3 at 12-month follow-up). At 12 months, IL-2, TNF-α, EGF, and CD95 + CD34+ significantly increased, while IL-1ß significantly decreased. No major adverse effects were reported; only mild gastrointestinal intolerance was reported in four cases. A decreased occurrence of infection was observed in MS patients treated with 12 months of a polysaccharide-based multinutrient dietary supplement. Significant changes were also noted in several key biomarkers that would be physiologically favorable to the MS population. Thus, the results of this study suggest an immunomodulatory effect of the dietary supplement regimen studied.

The Novel Effects of a Hydrolyzed Polysaccharide Dietary Supplement on Immune, Hepatic, and Renal Function in Adults with HIV in a Randomized, Double-Blind, Placebo-Control Trial.

The primary objective of the study was to evaluate the effects of a hydrolyzed polysaccharide, rice bran arabinoxylan compound (RBAC), on immune, hepatic, and renal function in HIV + individuals. A 6-month randomized double-blind placebo-controlled trial was utilized to conduct the intervention. Forty-seven HIV + individuals on stable antiretroviral therapy were enrolled and randomly assigned to one of the 2 study conditions (n = 22 RBAC and n = 25 placebo) and consumed 3 gram/day of either compound for 6 months. Participants were assessed at baseline and 3 and 6 months follow-up for CD4+ and CD8+, liver enzymes, and kidney function. No side effects were reported, and liver and kidney markers remained nearly completely within normal limits. The percentage change in CD4+ was similar for the placebo (+2.2%) and RBAC (+3.1%) groups at 6 months follow-up. The percentage change in CD8+ count significantly decreased from baseline to 6 months in the RBAC group (-5.2%), whereas it increased in the placebo group (+57.8%; p = 0.04). The CD4+/CD8+ ratio improved clinically in the RBAC group from 0.95 (SD = 0.62) at baseline to 1.07 (SD = 0.11) at 6 months, whereas it declined in the placebo group from 0.96 (SD = 0.80) at baseline to 0.72 (SD = 0.59) at 6 months. Our results showed a statistically significant decrease in CD8+ count and a clinically significant increase in CD4+/CD8+ ratio for the RBAC group compared to the placebo group. Thus, the results of this study suggest that the immunomodulatory and antisenescent activities of RBAC are promising for the HIV population.

Cardiovascular, endothelial function, and immune markers in response to treatment with a polysaccharide in HIV+ adults in a randomized, double-blind placebo-controlled trial.

BACKGROUND AND AIM: Given the ongoing problems of hypertension and endothelial dysfunction in the HIV population, the primary objective of the study was to assess the cardiovascular, endothelial function, and immune markers in response to rice bran arabinoxylan compound (RBAC) treatment in a sample of HIV+ adults on antiretroviral therapy (ART). STUDY DESIGN: A randomized, double-blind placebo-controlled trial of 6 months was used to execute the study. MATERIALS AND METHODS: Forty-seven subjects were enrolled and randomly assigned to one of two study conditions (n=22 RBAC and n=25 placebo) for 6 months with assessments at baseline and 3 and 6 months. A multivariate repeated measures analysis of variance model was used to assess the differences between RBAC and placebo groups in cardiovascular (systolic blood pressure), endothelial function (skin blood flow in response to nitric oxide), and immune (CD4+ cell count) markers from baseline to 6 months. RESULTS: The effect of treatment (RBAC versus placebo) was significant (Wilks' λ=0.92, F[3, 102]=3.07, P=0.03). The effect of time was significant (Wilks' λ=0.10, F[2, 103]=474.6, P<0.001). The overall interaction between treatment and time was significant (Wilks' λ=0.92, F[2, 103]=4.58, P=0.01). Time contrasts showed that a difference in the overall dependent variable did not occur from baseline to 3 months (F[1, 104]=2.7, P=0.10), marginally occurred from baseline to 6 months (F[1, 104]=3.2, P=0.08), and was significant from 3 to 6 months (F[1, 104]=6.43, P=0.01). CONCLUSIONS: The overall significant interaction suggests varying responses in the dependent variables between RBAC and placebo over time, which is being driven by systolic blood pressure, as it decreased in the RBAC group, but increased in the placebo group. In addition, CD4+ manifested a non-significant increase from baseline to 3 months then decreased from 3 to 6 months in the RBAC group, whereas it decreased at 3 months followed by a slight increase at 6 months in the placebo group. Skin blood flow in response to nitric oxide improved non-significantly overall in both groups, but worsened from 3 to 6 months in the placebo group. Thus, RBAC treatment may contribute to modest short-term improvements in systolic blood pressure, endothelial function, and CD4+ cell count, which could help improve the overall health profile of HIV+ adults. RELEVANCE FOR PATIENTS: Persons with HIV on ART suffer disproportionately from hypertension and endothelial dysfunction compared to the non-infected population, and conventional medical therapy does not alleviate these issues. RBAC is a safe, low-risk alternative that may help to improve the overall quality of life of these patients through modest improvements in these biomarkers plus CD4+ cell count.

Anti-cancer effects of aloe-emodin: a systematic review.

BACKGROUND: Anthraquinones are a possible treatment option for oncological patients due to their anti-cancer properties. Cancer patients often exhaust a plethora of resources that ultimately fail to provide fully curative measures. Alternative treatments are subsequently sought in the hope of finding a therapeutic remedy. Po¬tential regimens include aloe-emodin and its related derivatives. This review therefore summarizes the effects of aloe-emodin and other aloe components in light of their anti-proliferative and anti-carcinogenic properties. METHODS: A systematic search was performed in PubMed for aloe-emodin and cancer in humans. Sixty abstracts of in vitrostudies were selected and reviewed with subsequent screening of the full text. Thirty-eight articles were summarized. RESULTS: Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule. The most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death; mitochondrial membrane and redox perturbations; and modulation of immune signaling. The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type. CONCLUSIONS: On the basis of this systematic review, the multiple consistent effects of aloe-emodin in hu¬man-derived cancer cell lines suggest that aloe-emodin is a potential anti-cancer agent that acts on cancer cells in a pleiotropic manner. RELEVANCE FOR PATIENTS: Cancer patients often utilize alternative therapies as a result of suboptimal efficacy of conventional treatments. Aloe-emodin might become a therapeutic option for cancer patients if the basic research is confirmed in clinical trials.

A double-blind, randomized trial on the effect of a broad-spectrum dietary supplement on key biomarkers of cellular aging including inflammation, oxidative stress, and DNA damage in healthy adults.

Background and Aim: Nutritional approaches that ameliorate cellular senescence may have the potential to counteract the effects of chronic disease. This study will investigate the effect of the Healthycell dietary supplement on markers of inflammation, oxidative stress, and DNA damage. Methods: Thirty adults between the ages of 18 and 55 were enrolled and randomly assigned to one of the two study conditions (n = 15 Healthycell and n = 15 placebo). Subjects participated in a four-week intervention and were assessed at baseline, four weeks, and six weeks (after a two-week washout period). Results: Pro-inflammatory cytokine interleukin (IL)-1α (t = 2.033; mean difference = -3.97 pg/ml; SE = 2.0; 95% CI: -8.0, -0.3; Cohen's d = 0.77; p = 0.05) decreased, while soluble cytokine receptors sTNFR-I (t = 2.057; mean difference = 52.39 pg/mL; SE = 18.5; 95% CI: 5.2, 99.6; Cohen's d = 0.53; p = 0.03) and sTNFR-II (t = 1.739; mean difference = 208.71 pg/ml; SE = 72.0; 95% CI: 24.4, 393.0; Cohen's d = 0.61; p = 0.02) increased in the treatment group versus control. C-reactive protein also rose in the Healthycell group during the trial (t = 2.568; mean difference = 1.41 mg/dL; SE = 0.4; 95% CI: 0.3, 2.5; Cohen's d = 0.66; p < 0.01), without accompanying increases in IL-6 and TNF-α. Additionally, cortisol levels decreased in the Healthycell group (t = 0.575; mean difference = -0.31 ug/dL; SE=0.1; 95% CI: -0.6, -0.03; Cohen's d = 0.88; p = 0.03). When groups were split by age (< 35 years vs. ≥ 35 years), 8-hydroxydeoxyguanosine, a marker of DNA damage, decreased in the older Healthycell group compared to placebo (t = 1.782; mean difference = -7.09 ng/mL; SE = 3.0; 95% CI: -13.3, -0.9; Cohen's d = 0.63; p = 0.03). Significant changes were also found for sTNFR-I, sTNFR-II, and IL-5 in the older group. All results were obtained from t tests by post-hoc analysis. Conclusions: Our findings show an improved inflammatory profile and decreased DNA damage. Additionally, the efficacy of Healthycell was primarily in older adults, where the processes that cause or are associated with cell senescence are more predominant. Relevance for patients: Healthycell may help to counteract the inflammatory effects of aging that lead to both cell senescence and the multitude of age-related chronic diseases.