From Biotics

Vitamin D, Chronic Pain and Hypersensitivity

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: 1609-1618

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Vitamin D and Metastatic Colorectal Cancer Survival!

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)

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Niacin for Parkinson’s Disease?

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):34-8

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How to Diagnose Non-Celiac Gluten Sensitivity

Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease (CD) or wheat allergy (WA). Although NCGS is triggered by gluten-containing cereals, the offending dietary protein has not been identified yet, and could include other components such as amylase-trypsin inhibitors (ATIs). Indirect evidence suggests that NCGS is more common than CD. Using a self-administered evaluation incorporating a modified Gastrointestinal Symptom Rating Scale, the patient identifies 1 to 3 main symptoms that are quantitatively assessed using a Numerical Rating Scale ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict gluten free diet (GFD) and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. A variation of 30% of 1 to 3 main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. Note that NCGS may be transient, therefor gluten tolerance needs to be re-assessed in patients with NCGS.

Carlo Catassi, et al. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria. Nutrients. 2015 June; 7(6): 4966-4977.

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Zinc Supplementation for Depression?

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-e39

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Chondroitin Sulfate – Better than Celecoxib for Knee Osteoarthritis!

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).

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Vitamin D for Crohn’s Disease!

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) 294-302

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Vitamin D for Alzheimer’s and Dementia?

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

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Severe MTHFR deficiency treatment with TMG!

Researchers investigated the effect of trimethylglycine (TMG-also known as betaine) treatment on development and survival in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency. Deficiency of (5,10)-MTHFR is a frequent remethylation disorder, and clinical consequences vary greatly depending on the degree of enzyme deficiency. Carriers of the prevalent mild thermolabile variant are at risk for moderate hyperhomocysteinemia, but do not have neurological symptoms. On the other hand, severe MTHFR is rare, and presentation is in infancy or early childhood. The inability to remethylate homocysteine to methionine induces profoundly elevated homocysteine and decreased methionine concentrations in blood. Untreated patients either die or, if they survive, exhibit severe developmental delay and a life-long dependence on care. Researchers identified 15 case reports and case series totaling 36 patients with severe MTHFR deficiency, and compared the outcomes in treated vs. untreated patients, and early vs. late-treated patients. The main outcons and measures was survival and psychomotor development. Results showed that 11 of 36 patients died (31%), all of which occurring in patients who did not receive treatment or in whom treatment was delayed. In contrast, all 5 early-treated patients survived. Additionally, psychomotor development in surviving patients receiving treatment was normal in all 5 early-treated patients, but in none of the surviving patients with delayed treatment. Researchers concluded that early treatment prevents mortality and allows normal psychomotor development in patients with severe MTHFR deficiency, highlighting the importance of timely recognition through newborn screening.

EF Diekman, et al. Survival and Psychomotor Development with Early Betaine Treatment in Patients with Severe Methylenetetrahydrofolate Reductase Deficiency. JAMA Neurol. Feb 2014, Vol 71, No. 2

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Vitamin A Directs Immune Cells to the Intestines!

We know that vitamin A deficiencies lead to increased susceptibility to disease and low concentrations of immune cells in the mucosal barrier lining the intestines. Researchers from Purdue University found that the vitamin A metabolite retinoic acid (RA), is necessary for two of the three types of innate immune cells residing in the intestine (ILC1 and ILC3) to find their proper place. Innate lymphoid cells (ILCs), which are present in barrier tissues, gather in the lymph nodes where RA activates specific receptors upon two of the three subsets, acting as homing devices for the intestines. These immune cells then travel through the circulatory system, the receptor grab onto and bind to molecules in the intestines and keep the cells in place. They need to be concentrated in mucosal barrier tissues, because they are the point of entry from many infections from bacteria, viruses and parasites. These innate immune cells reside under the epithelial cell barrier that lines the intestine in a healthy system. When a pathogen penetrates the epithelial barrier, innate immune cells respond, attacking the pathogen to keep it from penetrating farther into the tissue or reaching the bloodstream. Researchers concluded that distinct programs regulate the migration of ILC subsets to the intestine for regulation of innate immunity. Interestingly, Vitamin D has been shown to work in a similar way to guide immune cells to the skin.

MH Kin, EJ Taparowsky, CH Kim. Retinoic acid differentially regulates the migration of innate lymphoid cell subsets to the gut. Immunity Vol 43, Issue 1, p107-119, 21 July 2015
Purdue study finds vitamin A directs immune cells to the intestines. July 9, 2015. http://www.purdue.edu

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