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Despite abundant cross-sectional evidence that low vitamin D status is associated with risk of cognitive decline in ageing, interventional evidence for benefits of vitamin D supplementation is lacking. This study was a 6 month randomised, double-blinded placebo-controlled clinical trial of the effects of vitamin D3 (D3), enhanced vitamin D2 in a mushroom matrix (D2M), standard mushroom (SM) and placebo (PL) on cognition and mood in n = 436 healthy older male (49%) and female volunteers aged ≥ 60 years. Primary end points were change in serum vitamin D metabolites (25-OH-D, 25-OH-D2 and 25-OH-D3), cognitive performance, and mood over 24 weeks. Levels of total 25-OH-D and 25-OH-D3 were maintained in the D3 arm but decreased significantly (p < 0.05) in the remaining arms (D2M, SM and PL). Analysis also revealed differential changes in these metabolites depending on total vitamin D status at baseline. There were no significant effects of treatment on any of the measures of cognitive function or mood. Overall, the results show that daily supplementation of ~600 IU of vitamin D3 was sufficient to maintain 25-OH-D throughout winter months, but in contrast to existing cross-sectional studies there was no support for benefit of vitamin D supplementation for mood or cognition in healthy elderly people.

Results indicate that WPI consumption improves active B and folate status. Unlike SPI, WPI consumption may prevent increase in MMA, HCY, and genome instability in older Australians with low vitamin B status.

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Endocannabinoids (ECs) mediate effects via cannabinoid receptor types 1 and 2 (CB1 and 2) and transient receptor potential channel-vanilloid subfamily member 1 (TRPV1) channels. In high-fat diet (HFD)-induced obese mice overactivity of the EC system and inhibition of CB1 increase skeletal muscle glucose uptake. We explored the role of TRPV1. Male TRPV1+/+(WT) and TRPV1−/−(KO)-mice were fed (20 wk) a standard laboratory diet (SLD) or HFD. An intraperitoneal glucose tolerance test was performed. RT-PCR was performed to measure mRNA of genes involved in glucose/lipid metabolism and the EC system in soleus (SOL) and extensor digitorum longus (EDL) muscles. Cultured L6 cells were used to measure glucose uptake in skeletal muscle. HFD mice weighed more and had higher insulin levels than SLD mice, with no genotype differences. Basal and peak glucose were higher in HFD mice irrespective of genotype, but glucose cleared faster in HFD WT vs. HFD KO-mice. 2-Arachidonoylglycerol augmented insulin-induced glucose uptake in skeletal L6-cells, an effect blocked by the TRPV1 antagonist SB-366791. In EDL, fatty acid amide hydrolase (FAAH) mRNA was increased in KO vs. WT mice, irrespective of diet. Pyruvate dehydrogenase kinase isozyme 4 (PDK4) and mitochondrial uncoupling protein 3 (UCP3) were elevated and FA desaturase 2 (FADS2) mRNA lower in HFD mice, irrespective of genotype. CB1 and stearoyl-CoA desaturase 1 (SCD1) were lower in HFD WT mice only. In SOL, PDK4, UCP3, hormone-sensitive lipase (LIPE), fatty acid translocase (CD36), and carnitine palmitoyl transferase 2 (CPT2) were elevated and SCD1, FAAH, FADS2, and Troponin 1 (TNNC1) mRNA lower in HFD mice, irrespective of genotype. In conclusion, TRPV1 regulates glucose disposal in HFD mice. We propose that TRPV1 plays a role in coordinating glucose metabolism in EDL under conditions of metabolic stress.

Background: Cross-sectional evidence suggests a positive relationship between vitamin D status and cognitive performance and mood; however, interventional clinical evidence is lacking. Vitamin D deficiency is prevalent in the elderly. If justified, supplementation offers a potentially cost-effective approach for maintaining cognitiondependent quality of life in aging populations. Exposure to UV light elevates the vitamin D content of mushrooms, which represent a novel and convenient source of dietary vitamin D (D2). Here we present the protocol for a study to determine whether increasing vitamin D status improves cognitive function, mood and depressive symptoms in healthy older subjects. Methods:The study is a double blind, placebo-controlled clinical trial with 400 healthy male and female subjects aged 60-90 years old. Subjects pre-screened for confounders of cognition but not vitamin D status, are randomised across four groups, receiving daily supplement treatments in parallel over six months; either: vitamin D2-enriched mushroom solids, vitamin D3 alone, standard mushroom solids, or placebo. Primary endpoints are: changes in serum 25-OH-D2 and 25-OH-D3 metabolites and general cognitive performance. Secondary endpoints include mood and depressive symptoms. Data analysis will adjust for covariate measures. Blood samples taken at the three clinic visits (baseline, 5 weeks and 6 months) will be stored. Citation: Zajac I, Cavuoto P, Danthiir V, Wittert GA, Krause D, Lawson L, Noakes M, Syrette J, Weaver J, Bennett L (2016) Study protocol: a randomised, double blinded, placebo-controlled clinical trial testing the effects of a vitamin D-enriched mushroom supplement on cognitive performance and mood in healthy elderly adults. Healthy Aging Research 5:5.