Abstract Background The association between diets that focus on plant foods and restrict animal products and cardiovascular disease (CVD) is inconclusive. We investigated whether cumulative intake of a plant‐centered diet and shifting toward such a diet are associated with incident CVD. Methods and Results Participants were 4946 adults in the CARDIA (Coronary Artery Risk Development in Young Adults) prospective study. They were initially 18 to 30 years old and free of CVD (1985–1986, exam year [year 0]) and followed until 2018. Diet was assessed by an interviewer‐administered, validated diet history. Plant‐centered diet quality was assessed using the A Priori Diet Quality Score (APDQS), in which higher scores indicate higher consumption of nutritionally rich plant foods and limited consumption of high‐fat meat products and less healthy plant foods. Proportional hazards models estimated hazard ratios of CVD associated with both time‐varying average APDQS and a 13‐year change in APDQS score (difference between the year 7 and year 20 assessments). During the 32‐year follow‐up, 289 incident CVD cases were identified. Both long‐term consumption and a change toward such a diet were associated with a lower risk of CVD. Multivariable‐adjusted hazard ratio was 0.48 (95% CI, 0.28–0.81) when comparing the highest quintile of the time‐varying average ADPQS with lowest quintiles. The 13‐year change in APDQS was associated with a lower subsequent risk of CVD, with a hazard ratio of 0.39 (95% CI, 0.19–0.81) comparing the extreme quintiles. Similarly, strong inverse associations were found for coronary heart disease and hypertension‐related CVD with either the time‐varying average or change APDQS. Conclusions Consumption of a plant‐centered, high‐quality diet starting in young adulthood is associated with a lower risk of CVD by middle age.
Visceral obesity increases risk of cognitive decline in humans, but subcutaneous adiposity does not. Here, we report that beige adipocytes are indispensable for the neuroprotective and anti-inflammatory effects of subcutaneous fat. Mice lacking functional beige fat exhibit accelerated cognitive dysfunction and microglial activation with dietary obesity. Subcutaneous fat transplantation also protects against chronic obesity in wildtype mice via beige fat-dependent mechanisms. Beige adipocytes restore hippocampal synaptic plasticity following transplantation, and these effects require the anti-inflammatory cytokine interleukin-4 (IL4). After observing beige fat-mediated induction of IL4 in meningeal T-cells, we investigated the contributions of peripheral lymphocytes in donor fat. There was no sign of donor-derived lymphocyte trafficking between fat and brain, but recipient-derived lymphocytes were required for the effects of transplantation on cognition and microglial morphology. These findings indicate that beige adipocytes oppose obesity-induced cognitive impairment, with a potential role for IL4 in the relationship between beige fat and brain function.
Although animal protein is usually considered to be a more potent stimulator of muscle protein synthesis than plant protein, the effect of protein source on lean mass and muscle strength needs to be systematically reviewed. This study aimed to examine potential differences in the effect of animal vs. plant protein on lean mass and muscle strength, and the possible influence of resistance exercise training (RET) and age. The following databases were searched: PubMed, Embase, Scopus and CINAHL Plus with Full Text, and 3081 articles were screened. A total of 18 articles were selected for systematic review, of which, 16 were used for meta-analysis. Total protein intakes were generally above the recommended dietary allowance at the baseline and end of intervention. Results from the meta-analyses demonstrated that protein source did not affect changes in absolute lean mass or muscle strength. However, there was a favoring effect of animal protein on percent lean mass. RET had no influence on the results, while younger adults (
Background Coffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant. Objectives We examined whether habitual coffee consumption is associated with differences in brain volumes or the odds of dementia or stroke. Methods We conducted prospective analyses of habitual coffee consumption on 398,646 UK Biobank participants (age 37–73 years), including 17,702 participants with MRI information. We examined the associations with brain volume using covariate adjusted linear regression, and with odds of dementia (4,333 incident cases) and stroke (6,181 incident cases) using logistic regression. Results There were inverse linear associations between habitual coffee consumption and total brain (fully adjusted β per cup −1.42, 95% CI −1.89, −0.94), grey matter (β −0.91, 95% CI −1.20, −0.62), white matter (β −0.51, 95% CI −0.83, −0.19) and hippocampal volumes (β −0.01, 95% CI −0.02, −0.003), but no evidence to support an association with white matter hyperintensity (WMH) volume (β −0.01, 95% CI −0.07, 0.05). The association between coffee consumption and dementia was non-linear (Pnon-linearity = 0.0001), with evidence for higher odds for non-coffee and decaffeinated coffee drinkers and those drinking >6 cups/day, compared to light coffee drinkers. After full covariate adjustment, consumption of >6 cups/day was associated with 53% higher odds of dementia compared to consumption of 1–2 cups/day (fully adjusted OR 1.53, 95% CI 1.28, 1.83), with less evidence for an association with stroke (OR 1.17, 95% CI 1.00, 1.37, p = 0.055). Conclusion High coffee consumption was associated with smaller total brain volumes and increased odds of dementia.
Very-low-carbohydrate diet triggers the endogenous production of ketone bodies as alternative energy substrates. There are as yet unproven assumptions that ketone bodies positively affect human immunity. We have investigated this topic in an in vitro model using primary human T cells and in an immuno-nutritional intervention study enrolling healthy volunteers. We show that ketone bodies profoundly impact human T-cell responses. CD4+, CD8+, and regulatory T-cell capacity were markedly enhanced, and T memory cell formation was augmented. RNAseq and functional metabolic analyses revealed a fundamental immunometabolic reprogramming in response to ketones favoring mitochondrial oxidative metabolism. This confers superior respiratory reserve, cellular energy supply, and reactive oxygen species signaling. Our data suggest a very-low-carbohydrate diet as a clinical tool to improve human T-cell immunity. Rethinking the value of nutrition and dietary interventions in modern medicine is required.
Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disorder. Impaired neuronal bioenergetics and neuroinflammation are thought to play key roles in the progression of AD, but their interplay is not clear. Nicotinamide adenine dinucleotide (NAD+) is an important metabolite in all human cells in which it is pivotal for multiple processes including DNA repair and mitophagy, both of which are impaired in AD neurons. Here, we report that levels of NAD+ are reduced and markers of inflammation increased in the brains of APP/PS1 mutant transgenic mice with beta-amyloid pathology. Treatment of APP/PS1 mutant mice with the NAD+ precursor nicotinamide riboside (NR) for 5 mo increased brain NAD+ levels, reduced expression of proinflammatory cytokines, and decreased activation of microglia and astrocytes. NR treatment also reduced NLRP3 inflammasome expression, DNA damage, apoptosis, and cellular senescence in the AD mouse brains. Activation of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) are associated with DNA damage and senescence. cGAS–STING elevation was observed in the AD mice and normalized by NR treatment. Cell culture experiments using microglia suggested that the beneficial effects of NR are, in part, through a cGAS–STING-dependent pathway. Levels of ectopic (cytoplasmic) DNA were increased in APP/PS1 mutant mice and human AD fibroblasts and down-regulated by NR. NR treatment induced mitophagy and improved cognitive and synaptic functions in APP/PS1 mutant mice. Our findings suggest a role for NAD+ depletion-mediated activation of cGAS–STING in neuroinflammation and cellular senescence in AD.
Highlights •We performed a meta-analysis on vegetarian diet and depression scores. •49889 participants (8057 vegetarians and 41832 non-vegetarian controls) were included. •Vegetarians showed higher depression scores than non-vegetarians. Abstract Background Several studies have suggested an association between vegetarian diet and higher depression scores. However, some studies have also shown an effect in the opposite direction, indicating lower depression scores in vegetarians. Given this discrepancy in the literature, this meta-analysis was aimed to determine whether there is a significant association between vegetarian diet and depression scores across different published studies. Methods A keyword search in major databases was conducted. Studies reporting depression scores in vegetarians and a non-vegetarian control group were included. Meta-analysis following a conditional random-effects procedure was conducted in R. Results After duplicates were removed and studies were analyzed for inclusion criteria, k=13 studies with an overall n of 49889 participants (8057 vegetarians and 41832 non-vegetarian controls) were included in the analysis. Random-effects meta-analysis revealed a significant difference between vegetarians and non-vegetarians, with vegetarians showing higher depression scores than non-vegetarians. Limitations The heterogeneity between studies was high and geographical variation in study location was low, limiting cross-cultural insights. Conclusions Vegetarians show higher depression scores than non-vegetarians. However, due to high heterogeneity of published studies, more empirical research is needed before any final conclusions can be drawn. Also, empirical studies from a higher number of different countries would be desirable.
This article presents an overview of the Jerusalem artichoke and its potential uses in consumer food products. Jerusalem artichoke, native to North America, is characterized by its sunflower-like appearance and carbohydrate-rich tubers. For centuries, Jerusalem artichoke tubers were a food source for Aboriginal Canadians and early European settlers. Today, Jerusalem artichoke is used to obtain inulin for addition into food products. Inulin is a polysaccharide that provides several health benefits when consumed. Due to its unique structure of fructose and glucose molecules, inulin is indigestible by the human digestive system. Its benefits are realized when it enters the large intestine and is fermented by microorganisms. This process stimulates prebiotic and dietary fibre effects that improve the growth of beneficial bacteria and promote greater digestive health. Additionally, inulin can act as a sugar or fat substitute in foods, and even facilitates the absorption of minerals in the large intestine. Currently, the use of Jerusalem artichoke inulin in commercial food products is limited. However, trends focusing on healthy living and supporting local industry indicate that Canadian consumers will positively view products made with Canadian-grown Jerusalem artichoke. The advantage that Jerusalem artichoke has over other inulin-rich products is that it can grow on poor land and is also more resistant to extreme weather conditions relative to corn and/or sugar beet; this is significant in the Canadian context. Given these trends and supplementary market data, the potential market size for Jerusalem artichoke-enriched products has been determined. Additionally, prices of currently available inulin-enriched products have been used as guidelines to determine total market potential. Market potential for baked goods, particularly muffins, was found to be CAD8,721,788whilemarketpotentialforbeverages,namelysoda,wasfoundtobeCAD 11,707,098. These numbers, though imperfect, indicate that there is strong potential for Jerusalem artichoke-enriched products to be marketed to Canadian consumers.
Social interactions among animals mediate essential behaviours, including mating, nurturing, and defence1,2. The gut microbiota contribute to social activity in mice3,4, but the gut–brain connections that regulate this complex behaviour and its underlying neural basis are unclear5,6. Here we show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone, which is primarily produced by activation of the hypothalamus–pituitary–adrenal (HPA) axis. Adrenalectomy, antagonism of glucocorticoid receptors, or pharmacological inhibition of corticosterone synthesis effectively corrects social deficits following microbiome depletion. Genetic ablation of glucocorticoid receptors in specific brain regions or chemogenetic inactivation of neurons in the paraventricular nucleus of the hypothalamus that produce corticotrophin-releasing hormone (CRH) reverse social impairments in antibiotic-treated mice. Conversely, specific activation of CRH-expressing neurons in the paraventricular nucleus induces social deficits in mice with a normal microbiome. Via microbiome profiling and in vivo selection, we identify a bacterial species, Enterococcus faecalis, that promotes social activity and reduces corticosterone levels in mice following social stress. These studies suggest that specific gut bacteria can restrain the activation of the HPA axis, and show that the microbiome can affect social behaviours through discrete neuronal circuits that mediate stress responses in the brain.
Obesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HTDRN) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HTDRN to hypothalamic arcuate nucleus (5-HTDRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT2C and 5-HT1B receptors, whereas activation of 5-HTDRN to ventral tegmental area (5-HTDRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HTDRN neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HTDRN neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.