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
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. 23
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
High breast density has been identified as a strong risk factor for breast cancer. Researchers tested the association between vitamin D intake, but not circulating vitamin D levels, and mammographic breast density among women. They conducted a cross-sectional study of 165 screening mammography patients at Nashville General Hospital’s Breast Health Center. Dietary and total (dietary plus supplementation) vitamin D, and calcium intakes were estimated by the AFFQ and blood samples were analyzed for 25(OH)D3. Average percent breast density for the left and right beast combined was estimated from digitized films. After statistical adjustment for age, race and body mass index, the result revealed there were significant trends of decreasing breast density with increasing vitamin D and calcium intake among premenopausal (but not postmenopausal) women.
AM Fair, et al. Increased vitamin D and calcium intake associated with reduced mammographic breast density among premenopausal women. Nutrition Research. Published online July 31, 20150
Melatonin is a hormone produce by the pineal gland and enterochromaffin cells which control sleep and gastrointestinal motility. Low melatonin levels lead to gastroesophageal reflux disease (GERD). Most patients with GERD have a sleep disorder, and low melatonin levels are a main cause of insomnia. It has an inhibitory action on gastric acid secretion and seems to control the lower esophageal sphincter.(1) Additionally, melatonin has been found to protect the gastrointestinal mucosa from oxidative damage caused by reactive oxygen species in different experimental ulcer models, where is has been shown to prevent acute ethanol-induced gastric injury from ethanol-induced via its antioxidant activity.(2) Another clinical study showed oral melatonin has a role in the prevention of GERD, and is effective in relieving epigastric pain and heartburn.(3)
1) J Dulce, et al. Which is the best choice for gastroesophageal disorders: Melatonin or proton pump inhibitors. World J Gastrointest Pharmcol Ther. 2010 Oct 6, 1(5): 102-106
2) D.Bilici, et al. Melatonin Prevents Ethanol-Induced Gastric Mucosal Damage Possibly Due to Its Antioxidant Effect. Digestive Diseases and Sciences. Apr 2002, Vol. 47, Issue 4. Pp 856-861.
3) TS Kandil, et al. The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease. BMC Gastroenterol. 2010 Jan 18;10:7. doi: 10.1186/1471-230X-10-7.
Vitamin D is known for its effects on bone mineralization, inflammatory processes and immunomodulatory properties, which positively influences human health, but in-vivo data on its effects on human gut microbiome are missing. Researchers conducted an open-label, interventional pilot study to investigate the effects of oral vitamin D3 on the human mucosa-associated and stool microbiome as well as CD8+ T cells in healthy volunteers. Sixteen participants were endoscopically examined to access a total of 7 sites, and researchers sampled stomach, small bowel, colon, and stools before and after 8 weeks of vitamin D3 supplementation. Weeks 1-4 participants took a weekly dose representing 140 IU/Kg body weight per day up to a max of 68,600 IU/week (9,800 IU/day). The following 4 weeks they took half the amount (70 IU/Kg body weight per day up to 34,300 IU/week (4,900 IU/day). Supplementation changed the gut microbiome in the upper GI tract (gastric corpus, antrum and duodenum). Researchers found a decreased relative abundance of Gammaproteobacteria including Pseudomonas spp., Escherichia/Shigella spp. and increased bacterial richness. No major changes occurred in the terminal ileum, appendiceal orifice, ascending colon, and sigmoid colon or in stool, but the CD8+ T cell fraction was significantly increased in the terminal ileum. They concluded that vitamin D3 modulates the gut microbiome of the upper GI tract which might explain its positive influence on GI diseases such as inflammatory bowel disease or bacterial infections. Local effects demonstrate pronounce regional differences in the response of the GI microbiome to external factors.
M Bashir, et al. Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract. Eur J Nutr. 2015 Jul 1. [Epub ahead of print]0