Intestinal immune regulatory signals govern gut homeostasis and is tightly controlled by the interaction of gut microbial gene products with pattern recognition receptors. The breakdown of such regulatory mechanisms may result in inflammatory bowel disease (IBD). Lactobacillus acidophilus contains unique surface layer proteins (Slps), including SlpA, SlpB, SlpX and lipoteichoic acid (LTA), which interact with pattern recognition receptors to mobilize immune responses. To demonstrate the role of SlpA in protective immune regulation, a strain of Lactobacillus acidophilus which solely expressed SlpA was generated. They demonstrated that its purified SlpA bind to the C-type lectin SIGNR3 to exert regulatory signals that result in mitigation of colitis, maintenance of healthy gastrointestinal microbiota, and protected gut mucosal barrier function. Interestingly, such protection was not observed in Slgnr3-/- mice, suggesting that the SlpA/SIGNR3 interaction plays a key regulatory role in colitis.
Lightfoot YL, et al. SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis. The EMBO Journal (2015) 34, 881-8950
Researchers wishing to evaluate the safety profile and characterize the immunologic effects of high dose vs low dose cholecalciferol (vitamin D3) supplementation in patients with MS, conducted a double-blind, randomized study of 40 patients with relapsing-remitting MS. Patients received 10,400 IU or 800 IU of D3 daily for 6 months. Assessments were conducted at baseline, 3 and 6 months. Results showed a mean increase of 25(OH)D levels was greater in the high dose group vs the low dose group. In the high dose group only, they found a reduction in the proportion of interleukin-17+CD4+ T cells, CD161+CD4+ T cells, and effector memory CD4+ T cells with concomitant increase in central memory CD4+ T cells and naïve CD4+ T cells. In other words, as the levels of vitamin D increased, there was a corresponding decrease in the levels of CD4+ T cells and interleukin-17, a protein they create which is pro-inflammatory. The researchers concluded that vitamin D3 supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS.
Sotirchos ES, et al. Safety and immunologic effects of high-vs low-dose cholecalciferol in multiple sclerosis. Neurology. 20150
Researchers from Bern University Hospital and the University of Bern in Switzerland studied 174 patients with chronic pain. Serum 25(OH)D measurements revealed 71% of patients were vitamin D deficient with 25(OH)D levels <50 nmol/L); another 21% had insufficient vitamin D levels with 25(OH)D <75 nmol/L. Researchers found a significant inverse association between continuously scaled 25(OH)D levels and mechanical pain sensitivity, a finding that is in agreement with experimental animal work on provoked pain sensitivity. They concluded that in patients with chronic pain, lowered vitamin D levels are associated with elevated central hypersensitivity, namely increased mechanical pain sensitivity and severity of somatic symptoms. As the prevalence of vitamin D deficiency/insufficiency is high in this population, it may seem good clinical practice to screen for 25(OH)D levels below 75 nmol/L and consider vitamin D supplementation. Von Kanel, et al. Vitamin D and Central Hypersensitivity in Patients with Chronic Pain. Pain Medicine 2014; 15: 1609-16180
Prospective epidemiologic data suggests higher levels of vitamin D are associated with improved survival in patients with colorectal cancer (CRC), however the relationship between 25(OH)D (vitamin D status) and outcome in metastatic CRC specifically is unknown. Researchers prospectively assessed the association between plasma 25(OH)D and overall survival (OS) in previously untreated metastatic CRC patients enrolled in CALGB 80505, a randomized phase III trial of chemotherapy + bevacizumab, cetuximab, or both, prior to the KRAS WT amendment. Among 1,043 patients, median plasma 25(OH)D was 17.2 ng/mL. Patients in the highest quintile of 25(OH)D had significantly improved overall survival (OS) compared to those in the lowest after adjusting for pathologic and clinical prognostic factors. Increasing concentrations of 25(OH)D were also associated with improved progression-free survival (PFS). Results were consistent across subgroups of patient characteristics, including KRAS status. The researchers concluded that higher concentrations of plasma 25(OH)D are associated with significantly improved survival in metastatic CRC patients treated with chemotherapy and biologics.
Kimmie, Ng, et al. Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance). 2015 Gastrointestinal Cancers Symposium. J Clin Oncol 33, 2015 (suppl 3; abstr 507)0
Anecdotal animal and human studies have implicated the symptomatic and neuroprotective roles of niacin in Parkinson’s disease (PD). Niacin has a high affinity for GPR109A, an anti-inflammatory receptor. Researchers hypothesize that GPR109A message and expression are up-regulated in individuals with PD. Niacin is a precursor for NDA-NADH which is needed for dopamine production, therefor niacin may serve three purposes: reduce inflammation through GPR109A-related mechanisms, increase dopamine synthesis in the striatum through NADPH supply, and increase NAD/NADH ratio to boost mitochondrial functions. GPR109A and its agonists are known to exert anti-inflammatory actions in the skin, gut and retina, but these roles are neither anticipated nor established in the central nervous system (CNS). These researchers, for the first time propose the roles of GPR109A and its agonist including niacin in CNS pathology, Moreover they predict that the neuroprotective roles of either niacin or butyrates in CNS occur via GPR109A.
Wakade C, Chong R. A novel treatment target for Parkinson’s disease. J Neurol Sci. 2014 Dec 15;347(1-2):34-81
Depression, a mental disorder associated with decreased productivity, poor psychosocial outcomes, and decreased quality of life, is a significant public health problem affecting millions of people in the US and elsewhere. Epidemiological studies have examined the association of low zinc (Zn) status with depression, but clinical trials on the effect of Zn supplementation in depression are limited. Researchers from Australia and Poland conducted a review of randomized controlled trials with a comparison group that examined Zn supplementation as the intervention, and depressive symptoms as the primary outcome. Four randomized controlled trials met inclusion criteria. In studies that examined the effects of Zn supplementations as an adjunct to antidepressants, Zn (7 to 25 mg/day for 10-12 wks) significantly lowered depressive symptom scores of depressed patients. In addition to depressive symptoms, researchers also examined the effect of Zn on other mood states such as anger, anxiety and tension. Results showed improvement in all mood states with Zn supplementation. Researchers concluded that the evidence suggests significant benefits from Zn supplementation, as a stand-alone intervention or as an adjunct to conventional drug therapy for reducing depressive symptoms in clinically depressed patients.
J Lai, et al. The efficacy of zinc supplementation in depression: Systematic review of randomized controlled trials. J of Affective Disorders 136 (2012) e31-e390
Canadian Researchers from nine different research institutions participated in a two-year randomized, controlled, double-blind clinical study to measure the disease modifying effect of chondroitin sulfate (CS) vs. Celecoxib (CE) on cartilage volume loss (CVL) in knee osteoarthritis (OA), and compare the effects of CS and CE on the symptoms of knee OA. Patients were treated with CS (1200 mg each day) or CE (200 mg each day) for 24 months. MRI was performed at baseline, 12 and 24 months. CVL, bone marrow lesion (BML) size, and synovial membrane thickness were evaluated using qMRI, and presence of joint swelling and effusion were clinically evaluated. Clinical symptoms were also assessed by validated questionnaires. The results showed the patients treated with CS had a reduction in CVL at 12 and 24 month in the medial tibiofemoral compartment and global knee at 12 and 24 months compared to CE. Both groups experienced similar reductions in disease symptoms (WOMAC total pain, function, and VAS pain) over time. Researchers concluded that this trial demonstrated CS is as effective as CE at reducing the symptoms of knee OA, and the superiority of CS over CE at reducing the long term progression of knee OA structural changes.
Pelletier JP, et al. In a Two-Year Double-Blind Randomized Controlled Multicenter Study, Chondroitin Sulfate Was Significantly Superior to Celecoxib at Reducing Cartilage Loss with Similar Efficacy at Reducing Disease Symptoms in Knee Osteoarthritis Patients. Arthritis Rheumatol. 2015; 67 (suppl 10).0
Researchers conducted a double-blind randomized placebo-controlled study, assigning 27 Crohn’s disease (CD) patients in remission to 2000 IU/day of vitamin D3 or placebo for 3 months. They determined intestinal permeability (IP), plasma-cathelicidin (LL-37), human-beta-defensin-2 (hBD2), disease activity [Crohn’s Disease Activity Index (CDAI)], c-reactive protein (CRP), fecal calprotectin, Quality of Life (QoL) and serum vitamin d (25(OH)D) at 0 and 3 months. Results showed that at 3 months, 25(OH)D concentrations were significantly higher in the treated group, and intra-group analysis showed increased LL-37 [an antimicrobial peptide (AMP) of the innate immune system expressed by the gastrointestinal epithelium] concentrations, and maintenance of IP measures. In contrast, in the placebo group, the small bowel and gastro-duodenal permeability increased from baseline. At 3 months, patients with 25(HO)D levels ≥ 75 nmol/L had significantly lower CRP, higher QoL, higher LL-37 concentrations and lower CDAI scores compared to those with lower 25(OH)D levels.
T Raftery, et al. Effects of vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn’s disease: Results from a randomized double-blind placebo-controlled study. United Euro Gastro Journal 2015, Vol. 3(3) 294-3020
Researchers from UC Davis Alzheimer’s Disease Center and Rutgers University wished to assess associations between Vitamin D (VitD) status and trajectories of change in subdomains of cognitive function. They conducted a cohort study of 382 ethnically diverse, older participants in an outpatient clinic (Feb. 2002-Aug. 2010) with baseline assessment and yearly follow-up visits. Serum 25-OHD levels were measured and categorized as deficient (< 12mg/mL), adequate (20 -49 ng/mL) or high (50 ng/mL or higher). Note: to convert to nanomoles per liter, multiply by 2.496. Subdomains of cognitive function were assessed using the Neuropsychological Assessment Scales. Associations were evaluated between 25-OHD levels (as continuous and categorical [deficient, insufficient or adequate]) and trajectories of cognitive decline. Low VitD status was associated with accelerated decline in cognitive function. According to Joshua Miller, professor in the Dept. of Pathology and Laboratory Medicine at the time the research was conducted (currently professor & chair of the Dept. of Nutritional Sciences at Rutgers University), VitD insufficiency was associated with significantly faster declines in both episodic memory and executive function performance. The researchers found that with over five years of follow-up, VitD deficient individuals experienced cognitive declines that were 2 to 3 times faster than those with adequate VitD levels.
JW Miller, et al. Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults. JAMA Neurology Publishes online Sept 142015 doi:10.1001/jama-neurol.2015.2115
Neuroscience News Sept 14, 2015