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Intervention with Micronutrients and Long-Term Impact in Brazil-RECODISA

ABSTRACT: Intervention with Micronutrients and Long-Term Impact in Brazil-RECODISA

PROVIDER: PRJNA922669 | ENA |

REPOSITORIES: ENA

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Project description:Interventions: Participants will take 6 brazil nuts a day for four weeks. This four week intervention will be preceded by a 4 week run-in / wash out phase participants will be advised to exclude any selenium rich foods or green tea during the study This Pilot study will confirm the amount of Brazil Nuts we will use in the study comparing with green tea. This follow up study (Effects of combining Selenium (Se) and green tea on biomarkers for colorectal cancer prevention in human subjects). will be registered with ANZCTR in the near future’ At the initial interview dietary advice will be given. This will give an understanding of the nature of the volunteers diet and the likely influence of Se to the diet and suitability to become involved in the study (if intolerant to nuts volunteers will not participate in the study) We will ask participants not to consume, whenever possible, throughout the study:- Any selenium supplement Any selenium enriched foods, such as nuts, sea food (such as tuna or octopus) The Brazil nut is a large nut that comes from the castanheiro de para tree in Brazil’s rainforests. Each serving of about six to eight nuts contains 4 g of protein and 7 grams each of monosaturated and polysaturated fat. Brazil nuts (Berholletia excelas, family Lecythidaceae) are the richest known food source of selenium, with mean concentrations reported in the literature between 8-83 micrograms Se/g 6 Brazil nuts daily provides 48 micrograms Se/day - 53 micrograms Se/day Primary outcome(s): If supplementation of 6 Brazil nuts/day increases plasma Selenium (Se) levels A blood sample (5mls of whole blood taken on 2 occasions) will be collected at baseline and after intervention, testing for plasma Selenium levels[Blood samples collected at commencement of intervention (week 0) and at end of intervention (wk 4)] Study Design: Purpose: Prevention; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety

Project description:In Alzheimer’s disease, dysfunctional microglia possess abnormal immunometabolic features that cause neuronal/synaptic damage and aggravate pathology. A critical question is how to reverse or fine-tune abnormal microglial metabolism towards beneficial immunometabolic outcomes. A major metabolic intervention strategy to raise circulating ketone levels for health benefits, such as by consumption of a ketogenic diet 1, fasting, or other approaches collectively called ketotherapeutics, has raised a great deal of interest, but its effects on microglia are not well understood. Our previous in vitro study showed that β-hydroxybutyrate (BHB), a major ketone body, reverses multiple pathological features of amyloid-β oligomer (AβO)-activated human microglia. In the current study, we tested the in vivo effects of BHB on microglia and synaptic plasticity in the 5xFAD Alzheimer’s disease mouse model. To capture the metabolic impact of BHB on microglia, we employed a “subacute” 1-week regimen of daily intraperitoneal injection of BHB (250 mg/kg), which induced brief and mild episodic (daily) ketosis. This short regimen was able to mitigate pro-inflammatory microglia activation linked to NLRP3 inflammasome formation, and reduce brain amyloid-β deposition by enhancing phagocytosis. Remarkably, this regimen mitigated the deficits of hippocampal long-term depression but not long-term potentiation, and this effect was linked to suppression of the inflammasome-generated cytokine IL-1β. Our results suggest that short-term BHB treatment may ameliorate microglial abnormalities and microglia-regulated synaptic deficits in Alzheimer’s disease. Because beneficial results were achieved with mild episodic BHB elevation alone without diet restriction and without the need of feeding a KD, our results have significant implications to human ketotherapeutics. As KDs are known for poor compliance and low sustainability due to their restrictive nature, our study opens the possibility for alternative ketogenic approaches that are less restrictive, potentially safer, and easier for compliance than a KD, such as short-term BHB injections or dietary ketone esters, a translatable form of induced ketosis.

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Intervention with Micronutrients and Long-Term Impact in Brazil-RECODISA

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