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The Association between Mushroom Consumption and Mild Cognitive Impairment: A Community-Based Cross-Sectional Study in Singapore
Abstract
We examined the cross-sectional association between mushroom intake and mild cognitive impairment (MCI) using data from 663 participants aged 60 and above from the Diet and Healthy Aging (DaHA) study in Singapore. Compared with participants who consumed mushrooms less than once per week, participants who consumed mushrooms >2 portions per week had reduced odds of having MCI (odds ratio = 0.43, 95% CI 0.23-0.78, p = 0.006) and this association was independent of age, gender, education, cigarette smoking, alcohol consumption, hypertension, diabetes, heart disease, stroke, physical activities, and social activities. Our cross-sectional data support the potential role of mushrooms and their bioactive compounds in delaying neurodegeneration.
... In a community cross-sectional study in Singapore, human participants over the age of 60, who self-reportedly consumed more than two portions of various varieties of mushrooms per week, had a 43% reduced risk of acquiring mild cognitive impairment (MCI). Additionally, mushrooms were shown to correlate with faster performance during cognitive examinations in those aged 60 and older [14]. ...
... Additionally, this indicates that WBM supplementation could be ameliorative when administered for longer periods of time. Potentially, WBMs may be incorporated therapeutically in patients with the present symptoms of cognitive impairment, as mushrooms have already been shown to reduce risk of mild cognitive impairments in older individuals [14]. Future studies could assess anxiety through Elevated Zero Maze (EZM) and Open Field Testing (OFT). ...
... Feng et al. [14] showed that in humans, at least three weekly servings of WBMs mitigated MCI in elderly patients. Our study shows these benefits in mice when consumption begins at an early age (4 weeks) throughout middle age (32 weeks). ...
Alzheimer’s Disease (AD) is characterized by cognitive impairment and the presence of amyloid-β (Aβ) plaques and tau tangles. This study was conducted to assess the effects of white button mushroom (WBM) supplementation on spatial memory and plaque formation in mice with mutations in amyloid (Aβ). Mice with amyloid precursor protein (hAPP) mutations and their wildtype (WT) littermates were fed a 10% white button mushroom (WBM) feed ad libitum three times per week, in addition to their normal diet. Morris water maze (MWM) was conducted at 14 and 32 weeks of age to assess spatial memory and Aβ plaque pathology in the hippocampus was analyzed. Our results showed that hAPP mice on the WBM diet were faster in reaching the platform in the MWM compared to hAPP mice on the control diet at 32 weeks (p < 0.05). Significantly fewer plaque deposits were found in the hippocampi of hAPP mice on the WBM diet compared to those on the control diet at 32 weeks (p < 0.05). Overall, hAPP mice on the WBM diet had improved spatial memory at 32 weeks of age compared to those on the control diet and exhibited fewer amyloid plaques.
... Epidemiological findings from our group and others suggested that mushroom consumption is associated with a lower risk of chronic diseases, including some cancers (12) , depression, (13) the metabolic syndromes (14) , cognitive impairment (15,16) and dementia (17) . A study conducted in Norway found that high mushroom intake in the elderly was associated with better cognitive performance than those with very low or no intake (18) . ...
... Because individuals 80 and over are top-coded at 80 years of age in the NHANES in order to protect participants' confidentiality, thus age groupings were created as follows: age (60 to < 70 years, 70 to < 80 years and ≥ 80 years). These covariates were selected because they have shown to be associated with both cognitive functioning and mushroom intake (13,15,25) . A previous study indicated that mushroom consumers in the US were more likely to be non-Hispanic White (34) . ...
... Another prospective cohort study conducted in the Netherlands showed that higher mushroom intake was associated with better cognitive function at baseline (44) . A recent community-based cross-sectional study conducted in Singapore showed that people who consumed more than two portions of mushrooms per week had lower odds of mild cognitive impairment (15) . The authors of this study suggested that the bioactive compounds in mushrooms have the potential to delay neurodegeneration (15) . ...
Emerging evidence has suggested that mushrooms, which are a rich source of the potent antioxidants ergothioneine and glutathione as well as vitamin D, may have neuroprotective properties. This study investigated the association between mushroom consumption and cognitive performance in a nationally representative sample of US older adults. We analyzed data from older adults aged ≥ 60 years from the 2011-2014 National Health and Nutrition Examination Survey. Mushroom intake was measured using up to two 24-hour dietary recalls and was categorized into three groups (lowest, middle, and highest). Cognitive function tests included the Animal Fluency Test (AF); Consortium to Establish a Registry for Alzheimer's Disease Delayed Recall (CERAD-DR) and Word Learning (CERAD-WL); and Digit Symbol Substitution Test (DSST). Multivariable linear regression models were developed, adjusting for socio-demographics, major lifestyle factors, self-reported chronic diseases, and dietary factors, including the Healthy Eating Index-2015 score and total energy. The study included 2,840 participants. Compared with the lowest category of mushroom intake, participants in the highest category (median intake = 13.4 g /1000 kcal/d) had higher scores for DSST (β = 3.87; 95% confidence interval [CI] 0.30, 7.45; P for trend=0.03) and CERAD-WL (β = 1.05; 95% CI: 0.0003, 2.10; P for trend=0.04). Similar non-significant trends were observed for AF (β = 0.24; 95% CI: -2.26, 2.73; P for trend=0.92) but not for the CERAD-DR. Greater mushroom intake was associated with certain cognitive performance tests, suggesting regular mushroom consumption may reduce the risk of cognitive decline. More research is needed to explore these associations further.
... Interestingly, two studies have reported that the supplementation of L. edodes derived β-glucan for consecutive 28 days can improve gut microbiome dysbiosis in aged mice [18], and thereby improve insulin resistance in insulin-deficient type 2 diabetic rats [19]. Moreover, a recent cross-sectional study has shown that mushroom consumption had reduced the incidence rate of mild cognitive impairment in aged individuals in Singapore [20]. These findings suggest that the main ingredient of L. edodes, β-glucan, may have the potential to regulate gut microbiota and gut-brain axis. ...
... Collectively, these data demonstrated that L. edodes β-glucan ameliorated the cognitive deficits induced by chronic HF diet, and these neuroprotective effects potentially occurred through the improvement of the colon-microbiota-brain axis. Previously, edible mushrooms have shown beneficial effects on cognition in a cross-sectional study [20]. Here we reported that the main ingredient of edible mushroom, L. edodes β-glucan, improved the gut microbiota-brain axis. ...
... Here we reported that the main ingredient of edible mushroom, L. edodes β-glucan, improved the gut microbiota-brain axis. Therefore, the beneficial effects of β-glucan may contribute to the ability of mushroom in the improvement of cognitive function, as described previously in the human study [20]. ...
Background
Long-term high fat (HF) diet intake can cause neuroinflammation and cognitive decline through the gut-brain axis. (1, 3)/(1, 6)-β-glucan, an edible polysaccharide isolated from medical mushroom, Lentinula edodes ( L. edodes ), has the potential to remodel gut microbiota. However, the effects of L. edodes derived β-glucan against HF diet-induced neuroinflammation and cognitive decline remain unknown. This study aimed to evaluate the neuroprotective effect and mechanism of dietary L edodes β-glucan supplementation against the obesity-associated cognitive decline in mice fed by a HF diet.
Methods
C57BL/6J male mice were fed with either a lab chow (LC), HF or HF with L. edode s β-glucan supplementation diets for 7 days (short-term) or 15 weeks (long-term). Cognitive behavior was examined; blood, cecum content, colon and brain were collected to evaluate metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology.
Results
We reported that short-term and long-term L. edodes β-glucan supplementation prevented the gut microbial composition shift induced by the HF diet. Long-term L. edodes β-glucan supplementation prevented the HF diet-induced recognition memory impairment assessed by behavioral tests (the temporal order memory, novel object recognition and Y-maze tests). In the prefrontal cortex and hippocampus, the β-glucan supplementation ameliorated the alteration of synaptic ultrastructure, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits induced by HF diet. Furthermore, the β-glucan supplementation increased the mucosal thickness, upregulated the expression of tight junction protein occludin, decreased the plasma LPS level, and inhibited the proinflammatory macrophage accumulation in the colon of mice fed by HF diet.
Conclusions
This study revealed that L. edodes β-glucan prevents cognitive impairments induced by the HF diet, which may occur via colon-brain axis improvement. The finding suggested that dietary L. edodes β-glucan supplementation may be an effective nutritional strategy to prevent obesity-associated cognitive decline.
... This cohort study showed that frequent consumption of mushrooms was significantly associated with a decreased risk of incident dementia and might have a preventive effect on the risk of dementia [22]. The research team of the National University of Singapore, School of Medicine found that the elderly consuming at least two standard mushrooms (about 300 g) per week were found to reduce the risk of mild cognitive impairment (MCI) by 50% [23]. A study on the correlation between mushroom intake and cognitive ability in elderly Americans suggested that higher mushroom intake might reduce the risk of cognitive decline in older adults [24]. ...
... least two standard mushrooms (about 300 g) per week were found to reduce the risk of mild cognitive impairment (MCI) by 50% [23]. A study on the correlation between mushroom intake and cognitive ability in elderly Americans suggested that higher mushroom intake might reduce the risk of cognitive decline in older adults [24]. ...
Alzheimer’s disease (AD) stands as a prevailing neurodegenerative condition (NDs), leading to the gradual deterioration of brain cells and subsequent declines in memory, thinking, behavior, and emotion. Despite the intensive research efforts and advances, an effective curative treatment for the disease has not yet been found. Mushrooms, esteemed globally for their exquisite flavors and abundant nutritional benefits, also hold a wealth of health-promoting compounds that contribute to improving AD health. These compounds encompass polysaccharides, proteins, lipids, terpenoids, phenols, and various other bioactive substances. Particularly noteworthy are the potent neuroprotective small molecules found in mushrooms, such as ergothioneine, erinacine, flavonoids, alkaloids, ergosterol, and melanin, which warrant dedicated scrutiny for their therapeutic potential in combating AD. This review summarizes such positive effects of mushroom bioactive compounds on AD, with a hope to contribute to the development of functional foods as an early dietary intervention for this neurodegenerative disease.
... One interpretation of such data could be that die- 61 tary supplementation with ergothioneine in pregnancy may reduce pre-eclampsia risk, 62 and this is obviously now worth testing. 63 68 work, we leveraged calibration data available in the previous study to estimate the er-69 gothioneine blood levels (ng/mL) in 432 women of whom 335 did not develop PE, 23 suf-70 fered preterm PE, and 74 suffered from term PE. 71 72 In Figure 1 the distribution of ergothioneine levels in the study-subjects are plotted. The levels range from ~140 ng/ ml to 998 ng/ml, with a median level of ~260 ng/ml. ...
... Ergothioneine was also the metabolite associated with 157 the lowest hazard ratio for all-cause mortality [65], and had the third highest loading in a 158 signature collection of healthy metabolites [66]. Mushroom consumption is also strongly 159 associated with a lowering of all-cause mortality [67] and of the incidence of mild cogni-160 tive impairment [68]. Consequently, since certain aspects of the pre-eclampsia syndrome 161 share hallmarks of vascular disease [69][70][71], this study adds weight to the idea that it might 162 be a useful nutraceutical in the prevention of (cardio)vascular diseases more generally. ...
Ergothioneine, an antioxidant nutraceutical mainly at present derived from the dietary intake of mushrooms, has been suggested as a preventive for pre-eclampsia. We analysed early pregnancy samples for a cohort of 432 first time mothers as part of the Screening for Endpoints in Pregnancy (SCOPE, European branch) project to determine the concentration of ergothioneine in their plasma. There was a weak association between the ergothioneine levels and maternal age, but none for BMI. Of these 432 women, 97 went on to develop pre-term (23) or term (74) pre-eclampsia. If a threshold was set at the 90th percentile of the reference range in the control population (≥ 462 ng/mL), only one of these 97 women (1%) developed pre-eclampsia, versus 97/432 (22.5%) whose ergothioneine level was below this threshold. One possible interpretation of these findings, consistent with previous experiments in a reduced uterine perfusion model in rats, is that er-gothioneine may indeed prove protective against pre-eclampsia in humans. An intervention study of some kind now seems warranted.
... Outputs of food systems may contribute to improvement of well-being, a criterion of socio-culturally sustainable food systems, through consumption of nutritious and medicinal foods [80,94]. Evidence supports the contribution of human SCM consumption to a wide range of health benefits, including improved cognitive function, decreased risk of cancer, strengthening of the immune system, and decreased sodium intake [15,55,58,[95][96][97]. Many of the medicinal benefits linked to SCM consumption are not associated with A. bisporus consumption [98]. ...
... Increasing farm resilience has been shown to increase economic sustainability [4]. Farm resilience can be defined as the ability of a farm system to withstand disturbances while still providing stable and consistent levels of nutritious food to consumers [95]. Increasing diversification is a core strategy used to increase farm system resilience [112]. ...
Producing and consuming specialty cultivated mushrooms (SCMs), cultivated mushrooms outside of the Agaricus genus, has the potential to positively impact sustainable food systems. Few studies have examined consumer perceptions of SCMs and industry-wide trends of SCM production in the United States (US), despite the USD 66.1 million in SCM sales in the US during 2020. This study looked at the barriers to and opportunities for cultivating, marketing, and consuming SCMs in the US by conducting a producer survey with SCM facilities in the US (n = 63). Survey results found diversification across products and practices within the SCM industry and on an individual business level. The most common place SCM growers sold their products was farmers’ markets (n = 63). The majority (53%) of growers (n = 60) used diverse (four or more) approaches to advertise their products. The majority of SCM growers (57%) indicated they had participated in a community outreach event in the past five years to help promote their SCM products (n = 63). Findings indicate there are opportunities for greater SCM business owner diversity. Our results indicate that production of SCMs may support economic, environmentally, and socio-culturally sustainable food systems and that there is further room for increased sustainability across the industry.
... Table 1 lists the EGT level in the human blood of healthy and subjects with neurodegenerative diseases. In addition, as mushrooms are known to be the richest source of EGT, cross-sectional studies were conducted in Singapore (Feng et al., 2019), Japan (S. and Western Norway (Nurk et al., 2010) to investigate the association between mushroom consumption and cognitive impairment among community-living elderly. Their results revealed that mushroom consumers had a lower incidence of cognitive impairment or dementia, suggesting that consuming 2 portions of mushrooms per week is ideal for healthy ageing (Feng et al., 2019). ...
... In addition, as mushrooms are known to be the richest source of EGT, cross-sectional studies were conducted in Singapore (Feng et al., 2019), Japan (S. and Western Norway (Nurk et al., 2010) to investigate the association between mushroom consumption and cognitive impairment among community-living elderly. Their results revealed that mushroom consumers had a lower incidence of cognitive impairment or dementia, suggesting that consuming 2 portions of mushrooms per week is ideal for healthy ageing (Feng et al., 2019). However, Sotgia et al. (2014) reported that EGT is unlikely to be used to measure health index as there was no significant difference between the serum EGT concentrations in healthy and unhealthy subjects among the Australian elderly population although EGT concentrations declined with age (Sotgia et al., 2014). ...
Healthy ageing is a crucial process that needs to be highlighted as it affects the quality of lifespan. An increase in oxidative stress along with ageing is the major factor related to the age-associated diseases, especially neurodegenerative disorders. An antioxidant-rich diet has been proven to play a significant role in the ageing process. Targeting ageing mechanisms could be a worthwhile approach to improving health standards. Ergothioneine (EGT), a hydrophilic compound with specific transporter known as OCTN1, has been shown to exert anti-ageing properties. In addition to its antioxidant effect, EGT has been reported to have anti-senescence, anti-inflammatory and anti-neurodegenerative properties. This review aims to define the pivotal role of EGT in major signalling pathways in ageing such as insulin/insulin-like growth factor (IGF) signalling (IIS), sirtuin 6 (SIRT6) and mammalian target of rapamycin complex (mTOR) pathways. The review further discusses evidence of EGT on neurodegeneration in its therapeutic context in various model organisms, providing new insights into improving health. In conclusion, an ergothioneine-rich diet may be beneficial in preventing age-related diseases, resulting in a healthy ageing population.
... In humans, several cross-sectional observational studies have revealed a significant decline in ET levels in patients with MCI, AD, VaD, and other neurocognitive disorders [11,27,28,45,46]. Corroborating the observations from animal studies, several cohort studies have shown improvements in cognitive functions and reduced risk of developing cognitive impairments with dietary intake of mushrooms, known as one of the richest sources of ET [13,[47][48][49][50][51]. Only one clinical study based in France has reported evidence of a link between peripheral ET and longitudinally assessed global cognitive decline [31]; however, this is the first study to comprehensively analyze the association between peripheral ET levels and individual cognitive domains as well as with known risk factors of cognitive decline (e.g., CeVD and , and hippocampus volume (C) are reported when there was a statistically significant mediation, as estimated by the difference between the total (path c) and direct (path c') effect of plasma ET on cognitive change (c-c ). ...
... In humans, several crosssectional observational studies have revealed a significant decline in ET levels in patients with MCI, AD, VaD, and other neurocognitive disorders [11,27,28,45,46]. Corroborating the observations from animal studies, several cohort studies have shown improvements in cognitive functions and reduced risk of developing cognitive impairments with dietary intake of mushrooms, known as one of the richest sources of ET [13,[47][48][49][50][51]. Only one clinical study based in France has reported evidence of a link between peripheral ET and longitudinally assessed global cognitive decline [31]; however, this is the first study to comprehensively analyze the association between peripheral ET levels and individual cognitive domains as well as with known risk factors of cognitive decline (e.g., CeVD and brain atrophy). ...
Low blood concentrations of the diet-derived compound ergothioneine (ET) have been associated with cognitive impairment and cerebrovascular disease (CeVD) in cross-sectional studies, but it is unclear whether ET levels can predict subsequent cognitive and functional decline. Here, we examined the temporal relationships between plasma ET status and cognition in a cohort of 470 elderly subjects attending memory clinics in Singapore. All participants underwent baseline plasma ET measurements as well as neuroimaging for CeVD and brain atrophy. Neuropsychological tests of cognition and function were assessed at baseline and follow-up visits for up to five years. Lower plasma ET levels were associated with poorer baseline cognitive performance and faster rates of decline in function as well as in multiple cognitive domains including memory, executive function, attention, visuomotor speed, and language. In subgroup analyses, the longitudinal associations were found only in non-demented individuals. Mediation analyses showed that the effects of ET on cognition seemed to be largely explainable by severity of concomitant CeVD, specifically white matter hyperintensities, and brain atrophy. Our findings support further assessment of plasma ET as a prognostic biomarker for accelerated cognitive and functional decline in pre-dementia and suggest possible therapeutic and preventative measures.
... Some epidemiological studies have reported associations between mushroom consumption and low risks of chronic diseases, such as cancers [16,17], metabolic syndrome [18], cognitive impairment [19], and dementia [20] although some studies failed to observe significant associations [21][22][23][24][25]. However, whether the consumption of mushrooms is associated with better survival and low risk of premature mortality remains uncertain using large-scale epidemiologic studies. ...
... A study conducted by Zhang and colleagues showed that greater mushroom consumption was associated with a lower risk of dementia in elderly Japanese [20]. Furthermore, a study conducted in Singapore showed that mushroom intake was associated with lower odds of mild cognitive impairment [19]. However, several other epidemiological studies yield non-significant associations [21][22][23][24][25]. Furthermore, a previous systematic review and meta-analysis of fruit and vegetable intake and risk of mortality using 2 studies found no association between mushroom consumption and all-cause mortality [26]. ...
Background
Whether mushroom consumption, which is rich in several bioactive compounds, including the crucial antioxidants ergothioneine and glutathione, is inversely associated with low all-cause and cause-specific mortality remains uncertain. This study aimed to prospectively investigate the association between mushroom consumption and all-cause and cause-specific mortality risk.
Methods
Longitudinal analyses of participants from the Third National Health and Nutrition Examination Survey (NHANES III) extant data (1988–1994). Mushroom intake was assessed by a single 24-h dietary recall using the US Department of Agriculture food codes for recipe foods. All-cause and cause-specific mortality were assessed in all participants linked to the National Death Index mortality data (1988–2015). We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause and cause-specific mortality.
Results
Among 15,546 participants included in the current analysis, the mean (SE) age was 44.3 (0.5) years. During a mean (SD) follow-up duration of 19.5 (7.4) years , a total of 5826 deaths were documented. Participants who reported consuming mushrooms had lower risk of all-cause mortality compared with those without mushroom intake (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.73–0.98) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors including total energy. When cause-specific mortality was examined, we did not observe any statistically significant associations with mushroom consumption. Consuming 1-serving of mushrooms per day instead of 1-serving of processed or red meats was associated with lower risk of all-cause mortality (adjusted HR = 0.65; 95% CI: 0.50–0.84). We also observed a dose-response relationship between higher mushroom consumption and lower risk of all-cause mortality (P-trend = 0.03).
Conclusion
Mushroom consumption was associated with a lower risk of total mortality in this nationally representative sample of US adults.
... Although PASS online did not generate a Pa value for vitamin D 3 as a treatment for multiple sclerosis (Table 3), vitamin D 2 was active in multiple sclerosis treatment and anti-parkinsonian effects. Vitamin D 2 might be effective for some dementias, as mushroom intake correlates with reduced mild cognitive impairment risk [94]. Notably, the relationship of vitamin D 3 to antidiabetic (type 1) activity (Table 3) aligns with the sunlight exposure-type 1 diabetes connection [95,96]. ...
We previously examined the cellular uptake of six types of vitamin D in human intestinal Caco-2 cells. Since vitamins D5–D7 were commercially unavailable, we synthesized these compounds organically before studying them. This process led us to understand that new secosteroids could be generated as vitamin D candidates, depending on the sterol used as the starting material. We obtained two new secosteroids—compounds 3 and 4—from fucosterol in the current study. We investigated the intestinal absorption of these compounds using Caco-2 cells cultured in Transwells and compared the results with vitamin D3, a representative secosteroid. The intestinal absorption of compound 4 was comparable to that of vitamin D3. Compound 3 showed similar uptake levels but transported about half as much as vitamin D3. These compounds demonstrated intestinal absorption at the cellular level. Vitamin D is known for its diverse biological activities manifest after intestinal absorption. Using PASS online simulation, we estimated the biological activity of compound 3’s activated form. In several items indicated by PASS, compound 3 exhibited stronger biological activity than vitamins D2–D7 and was also predicted to have unique biological activities.
... Ergothioneine (see also above) is highly abundant in mushrooms and their consumption has been found to positively influence cognitive impairment in elderly people, confirming the importance of ergothioneine in healthy aging (Feng et al. 2019). ...
A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related factor 2 (Nrf2) and other processes. Increased levels of ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result in a harmful condition termed oxidative stress (“bad stress”). Although it is widely accepted, that many chronic diseases are multifactorial in origin, they share oxidative stress as a common denominator. Here we review the importance of oxidative stress and the mechanisms through which oxidative stress contributes to the pathological states of an organism. Attention is focused on the chemistry of ROS and RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl radicals, nitric oxide, peroxynitrite), and their role in oxidative damage of DNA, proteins, and membrane lipids. Quantitative and qualitative assessment of oxidative stress biomarkers is also discussed. Oxidative stress contributes to the pathology of cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s and Parkinson’s diseases, Down syndrome), psychiatric diseases (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, lung cancer), and aging. The concerted action of antioxidants to ameliorate the harmful effect of oxidative stress is achieved by antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), and small molecular weight antioxidants (vitamins C and E, flavonoids, carotenoids, melatonin, ergothioneine, and others). Perhaps one of the most effective low molecular weight antioxidants is vitamin E, the first line of defense against the peroxidation of lipids. A promising approach appears to be the use of certain antioxidants (e.g. flavonoids), showing weak prooxidant properties that may boost cellular antioxidant systems and thus act as preventive anticancer agents. Redox metal-based enzyme mimetic compounds as potential pharmaceutical interventions and sirtuins as promising therapeutic targets for age-related diseases and anti-aging strategies are discussed.
... Ergothioneine was also the metabolite associated with the lowest hazard ratio for all-cause mortality (70), and had the third highest loading in a signature collection of healthy metabolites (71). Mushroom consumption is also strongly associated with a lowering of all-cause mortality (72) and of the incidence of mild cognitive impairment (73). Consequently, since certain aspects of the preeclampsia syndrome share hallmarks of vascular disease (74)(75)(76), this study adds weight to the idea that it might be a useful nutraceutical in the prevention of (cardio)vascular diseases more generally. ...
Ergothioneine, an antioxidant nutraceutical mainly at present derived from the dietary intake of mushrooms, has been suggested as a preventive for pre-eclampsia. We analysed early pregnancy samples from a cohort of 432 first time mothers as part of the Screening for Endpoints in Pregnancy (SCOPE, European branch) project to determine the concentration of ergothioneine in their plasma. There was a weak association between the ergothioneine levels and maternal age, but none for BMI. Of these 432 women, 97 went on to develop pre-term (23) or term (74) pre-eclampsia. If a threshold was set at the 90th percentile of the reference range in the control population (≥ 462 ng/mL), only one of these 97 women (1%) developed pre-eclampsia, versus 96/397 (24.2%) whose ergothioneine level was below this threshold. One possible interpretation of these findings, consistent with previous experiments in a reduced uterine perfusion model in rats, is that ergothioneine may indeed prove protective against pre-eclampsia in humans. An intervention study of some kind now seems warranted.
... Even the slighter amounts of consumption resulted in delayed rate but promising decline in the mild cognitive impairment. Researchers believe this decline due to a bioactive compound i.e., the ergothioneine which possesses properties like antioxidation and anti-inflammation and naturally ergothioneine is not produced in the body rather have to be consumed from outside in diet (Feng et al., 2019). ...
Mushrooms are natural source of many bioactive compounds that serve as supplements for human health. Today a lot of natural products are being extracted from mushrooms and used to treat many human diseases. Mushrooms from ancient era are being exploited for its therapeutic uses, in treatments because of its anti-inflammatory, anti-diabetic, and anticancer properties. In Taiwan, Antrodia cinnamomea is known as ‘National Treasure of Taiwan’ and ‘Ruby in the Forest’ as it is a rare parasitic fungus with anti-tumour, anti-fatigue, anti-inflammatory, anti-oxidant and hepatoprotective functions. Mushrooms contain ample amounts of Vitamins, Minerals, Protein content, carbohydrate and oxalic acid as primary metabolites and contain anthraquinones, benzoic acid derivatives, steroids, triterpenes, terpenoids, terpenes, as secondary metabolites. Over 30 species of mushrooms are found to have anti-cancer properties and over 100 mushrooms are found to have medicinal effects on human health including anti-viral, anti-bacterial, anti-inflammatory, anti-parasitic and anti-tumour activity. Polysaccharides are considered most important constituent for medicines especially ɑ-Glucans and β-Glucans are considered best and versatile. The fruiting bodies of mushroom bear the bioactive compounds which can be glycosides, polysaccharides, proteins, minerals, alkaloids, volatile oils, terpenoids, phenols, flavonoids, carotenoids, folates, lectins, enzymes, ascorbic acid and organic acids. The effectiveness and the concentration of the bioactive compounds depend upon the cultivation environment, storage conditions, cooking method, type of mushrooms and age/developmental stage. This review focuses on different bioactive compounds found in mushrooms, their bioactivities and role in human health.
... However, it should be noted that there are still very few studies concerning the application of mushroom antioxidants on humans in the context of clinical trials on neuroprotection [197]. Furthermore, the few studies available in humans have been conducted on mushroom extracts/powders or whole mushrooms ingested with the diet [198][199][200][201] and not on isolated antioxidant compounds. Taking into account this aspect, future directions should be aimed towards conducting clinical studies in humans in order to evaluate the neuroprotective potential not only of whole mushrooms but also of the individual antioxidant compounds. ...
The last century has seen an increase in our life expectancy. As a result, various age-related diseases, such as neurodegenerative diseases (NDs), have emerged, representing new challenges to society. Oxidative stress (OS), a condition of redox imbalance resulting from excessive production of reactive oxygen species, represents a common feature that characterizes the brains of elderly people, thus contributing to NDs. Consequently, antioxidant supplementation or dietary intake of antioxidant-containing foods could represent an effective preventive and therapeutic intervention to maintain the integrity and survival of neurons and to counteract the neurodegenerative pathologies associated with aging. Food contains numerous bioactive molecules with beneficial actions for human health. To this purpose, a wide range of edible mushrooms have been reported to produce different antioxidant compounds such as phenolics, flavonoids, polysaccharides, vitamins, carotenoids, ergothioneine, and others, which might be used for dietary supplementation to enhance antioxidant defenses and, consequently, the prevention of age-related neurological diseases. In this review, we summarized the role of oxidative stress in age-related NDs, focusing on the current knowledge of the antioxidant compounds present in edible mushrooms, and highlighting their potential to preserve healthy aging by counteracting age-associated NDs.
... 72 Chocolate has also been associated with better overall cognitive function in a community based sample in the Maine-Syracuse Longitudinal Study. 73 Decreased risk of developing all-cause MCI has also been associated with greater consumption of mushrooms, 74 and a decreased risk of developing all-cause dementia has also been associated with mushroom consumption. 75 An 18-month double-blind, placebo-controlled trial of curcumin was found to result in improved memory and attention as well as decreased amyloid and tau accumulation on PET in non-demented adults. ...
As our population ages, there is interest in delaying or intervening in cognitive decline. While newer agents are under development, agents in mainstream use do not impact the course of diseases that cause cognitive decline. This increases interest in alternative strategies. Even as we welcome possible new disease-modifying agents, they are likely to remain costly. Herein, we review the evidence behind other complementary and alternative strategies for cognitive enhancement and prevention of cognitive decline.
... It is not easily obtained in pure form (though biotechnological processes are starting to make it [808][809][810][811][812][813][814][815][816][817]), but its availability via mushrooms can provide a convenient supply [818][819][820]. Indeed mushrooms themselves have been shown to be highly protective against mild cognitive impairment [821], as well as other diseases involving oxidative stress [787], and are themselves under consideration and trial as anti-COVID-19 agents [822,823]. ...
Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I-R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.
... Mushrooms contain wide range of bioactive molecules which have beneficial effects in the treatment of certain non-communicable diseases including hypertension (Sekiya et al., 2006), hypercholesterolemia (He et al., 2019), hyperlipidemia (Feng et al., 2019), diabetes (Ng et al., 2015), and cancer (Wong et al., 2020). Although over 1100 mushroom species are edible, certain mushroom species have economical and industrial importance (Afrin et al., 2016). ...
Eritadenine, a cholesterol lowering component, found significantly in a mushroom cultivar namely Lentinula edodes. Pressurized liquid extraction (PLE) technique provided higher results for eritadenine, total phenolics and antioxidant capacity than classical aqueous ethanol extraction. Three optimum extraction points giving the close results for eritadenine amount were determined by applying the principles of central composite design. Among the optimum points, 142 °C was selected as optimum extraction temperature and water was selected as extraction solvent. Five minute was enough in PLE to extract eritadenine, extending extraction time to 30 min had no positive or negative effects on eritadenine. One extraction cycle was enough to extract the eritadenine. Thermal degradation studies conducted between 140 and 170 °C indicated the striking thermal stability of eritadenine with a half-life-(t1/2) value of 9.29 h and decimal reduction time-(D) of 30.88 h at 170 °C. This indicated the suitability of eritadenine for enrichment of thermally treated foods.
... With an increased prevalence or incidence of MCI in Chinesespeaking populations around the world (approximately 14% prevalence of MCI in aged 60 years or older; Feng et al., 2019;Vanoh et al., 2017), it is of great importance to have a Chinese version of questionnaire inquiring SCD in MCI to study MCI in the Chinese communities. Based on such need, we translated the SCD-Q21 (see details in Supplementary Material S2). ...
Background
Subjective cognitive decline‐questionnaire 9 (SCD‐Q9) was developed to detect SCD complaints at risk of mild cognitive impairment (MCI). However, our previous findings indicated that its coverage might be insufficient. To test this hypothesis, we recently translated SCD‐Q21.
Objective
To examine the reliability and validity of this translated SCD‐Q21 and to explore its effectiveness for discriminating MCI from controls.
Methods
Item analysis was performed to understand its item discrimination and homogeneity. The Cronbach's α and Spearman‐Brown's split‐half coefficients were calculated to test its reliability. The Kaiser–Meyer–Olkin (KMO) value, Bartlett's sphericity test, and exploratory factor analysis (EFA) were used to examine its construct validity. The content validity was evaluated using five‐grade Likert scale. Finally, the SCD‐Q21 scores in MCI and controls were compared.
Results
The difference of each item between the extreme groups was significant. The Cronbach's α coefficient was .913 and Spearman‐Brown's split‐half coefficient was .894. When performing holding one‐out approach, the Cronbach's α coefficient ranged from .906 to .914. The KMO value was .929 and the difference of Bartlett's Sphericity test was significant. All experts scored 5 points when assessing its content. Finally, a significant difference of score was found between MCI and NC groups.
Conclusions
The reliability and validity of the SCD‐Q21 are good, which may pave a way for its application in a wider Chinese‐speaking population.
... The WFPB diet essentially consists of vegetables, whole grains, legumes, fruits, nuts and seeds, without restricting energy intake (see table 5). In addition, the regular consumption of specific foods Open access that have the potential to beneficially influence cognitive functions, based on current clinical evidence, is encouraged (eg, green leafy vegetables, 38 mushrooms, 39 citrus fruits, 40 soy products, 41 blueberries, 42 nuts, 43 turmeric, 44 green tea 45 and omega-3 fatty acids 46 ). Participants are instructed to exclude animal products from their diets because of the proinflammatory potential of animal products and to refrain from consuming highly processed foods. ...
Introduction
People with mild cognitive impairment (MCI) are at increased risk of decreasing cognitive functioning. Computerised cognitive training (CCT) and nutrition have been shown to improve the cognitive capacities of people with MCI. For each variable, we developed two kinds of interventions specialised for people with MCI (CCT: ‘individualised’ CCT; nutrition: a whole-food, plant-based diet). Additionally, there are two kinds of active control measures (CCT: ‘basic’ CCT; nutrition: a healthy diet following the current guidelines of the German Nutrition Society). The aim of this study is to investigate the effects of the two interventions on cognition in people with MCI in a 2×2 randomised controlled trial with German participants.
Methods and analysis
Participants will be community-dwelling individuals with a psychometric diagnosis of MCI based on the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination. With N=200, effects with an effect size of f ≥0.24 (comparable to Cohen’s d ≥0.48) can be detected. Screening, baseline, t6 and t12 testing will be conducted via a videoconferencing assessment, telephone, and online survey. Participants will be randomly allocated to one of four groups and will receive a combination of CCT and online nutritional counselling. The CCT can be carried out independently at home on a computer, laptop, or tablet. Nutrition counselling includes 12 online group sessions every fortnight for 1.5 hours. The treatment phase is 6 months with follow-ups after six and 12 months after baseline.
Ethics and dissemination
All procedures were approved by the Friedrich-Alexander-Universität Erlangen-Nürnberg Ethics Committee (Ref. 21-318-1-B). Written informed consent will be obtained from all participants. Results will be published in peer-reviewed scientific journals, conference presentations.
Trial registration number
ISRCTN10560738 .
... Indeed, ET has many neuroprotective properties [4,5,18,26,27], as reviewed in detail in this special issue [18,25,26]. Consistent with a key protective role of ET against the development of age-related diseases, higher dietary consumption of mushrooms, a rich source of ET [9], is associated with lower disease risk [28][29][30][31]. ...
... Participants from the study group showed a significantly better performance in cognitive function tests than participants from the placebo group after 16 weeks of therapy. Additionally, a survey of Singaporean residents showed an association between the amount of mushroom consumption and the incidence of age-related conditions, such as dementia or MCI [166], once again suggesting that the mushrooms contain a significant number of compounds that have the ability to slow the deterioration of cognitive functions. ...
Dietary supplements and nutraceuticals have entered the mainstream. Especially in the media, they are strongly advertised as safe and even recommended for certain diseases. Although they may support conventional therapy, sometimes these substances can have unexpected side effects. This review is particularly focused on the modulation of autophagy by selected vitamins and nutraceuticals, and their relevance in the treatment of neurodegenerative diseases, especially Parkinson’s disease (PD). Autophagy is crucial in PD; thus, the induction of autophagy may alleviate the course of the disease by reducing the so-called Lewy bodies. Hence, we believe that those substances could be used in prevention and support of conventional therapy of neurodegenerative diseases. This review will shed some light on their ability to modulate the autophagy.
... Accumulating research has provided evidence for the protective effects of mushrooms and cereal against various chronic diseases and neurodegeneration disorders. A community-based crosssectional study in Singapore demonstrates that participants who consumed mushrooms >2 portions per week have a reduced risk of mild cognitive impairment (17). Breakfast cereal consumption by children and adolescence is associated with greater cognitive performance (18,19). ...
Background:
Dietary fiber is fermented in the lower gastrointestinal tract, potentially impacting the microbial ecosystem and thus may improve elements of cognition and brain function via the gut-brain axis. β-glucans, soluble dietary fiber, have different macrostructures and may exhibit different effects on the gut-brain axis. This study aimed to compare the effects of β-glucans from mushroom, curdlan and oats bran, representing β-(1,3)/(1,6)-glucan, β-(1,3)-glucan or β-(1,3)/(1,4)-glucan, on cognition and the gut-brain axis.
Methods:
C57BL/6J mice were fed with either control diet or diets supplemented with β-glucans from mushroom, curdlan and oats bran for 15 weeks. The cognitive functions were evaluated by using the temporal order memory and Y-maze tests. The parameters of the gut-brain axis were examined, including the synaptic proteins and ultrastructure and microglia status in the hippocampus and prefrontal cortex (PFC), as well as colonic immune response and mucus thickness and gut microbiota profiles.
Results:
All three supplementations with β-glucans enhanced the temporal order recognition memory. Brain-derived neurotrophic factor (BDNF) and the post-synaptic protein 95 (PSD95) increased in the PFC. Furthermore, mushroom β-glucan significantly increased the post-synaptic thickness of synaptic ultrastructure in the PFC whilst the other two β-glucans had no significant effect. Three β-glucan supplementations decreased the microglia number in the PFC and hippocampus, and affected complement C3 and cytokines expression differentially. In the colon, every β-glucan supplementation increased the number of CD206 positive cells and promoted the expression of IL-10 and reduced IL-6 and TNF-α expression. The correlation analysis highlights that degree of cognitive behavior improved by β-glucan supplementations was significantly associated with microglia status in the hippocampus and PFC and the number of colonic M2 macrophages. In addition, only β-glucan from oat bran altered gut microbiota and enhanced intestinal mucus.
Conclusions:
We firstly demonstrated long-term supplementation of β-glucans enhanced recognition memory. Comparing the effects of β-glucans on the gut-brain axis, we found that β-glucans with different molecular structures exhibit differentia actions on synapses, inflammation in the brain and gut, and gut microbiota. This study may shed light on how to select appropriate β-glucans as supplementation for the prevention of cognitive deficit or improving immune function clinically.
... EGT has been found to promote the proliferation and differentiation of neuronal cells and relieve depressive symptoms in mice at a reasonable daily intake level (120 mg EGT/100 g diet) (Nakamichi et al., 2016). Recently, a communitybased cross-sectional in Singapore also found that eating mushrooms (more than 2 times a week) contributes to improving the cognitive level and extending the life of patients (Feng et al., 2019). However, in the elderly, especially in patients with neurodegenerative diseases, the level of EGT is significantly decreased in the brain and plasma (Cheah et al., 2016a). ...
L-Ergothioneine (EGT) is a natural antioxidant derived from microorganisms, especially in edible mushrooms. EGT is found to be highly accumulated in tissues that are susceptible to oxidative damage, and it has attracted extensive attention due to its powerful antioxidant activity and the tight relationships of this natural product with various oxidative stress-related diseases. Herein, we 1) introduce the biological source and in vivo distribution of EGT; 2) review the currently available evidence concerning the relationships of EGT with diabetes, ischemia-reperfusion injury-related diseases like cardiovascular diseases and liver diseases, neurodegenerative diseases, and other diseases pathogenically associated with oxidative stress; 3) summarize the potential action mechanisms of EGT against these diseases; 4) discuss the advantages of EGT over other antioxidants; and 5) also propose several future research perspectives for EGT. These may help to promote the future application of this attractive natural antioxidant.
... However, it is worth specifying that the aforementioned meta-analysis mostly considered patients with a diagnosed depression, while we opted for a brief screening tool, i.e., the Geriatric Depression Scale (GDS), for excluding major depression. The same can be noted for other well-known reliable protective/risk factors against/favoring developing MCI and dementia, such as, physical activity, smoking, alcohol consumption, and BMI, e.g., [69][70][71][72]. Regarding physical activity, we can speculate that the use of a single item, as in this study, may be insufficiently sensitive in capturing the variability within habits among our study participants. ...
Mild Cognitive Impairment (MCI) is a transition stage between normal aging and dementia and can be useful to monitor the cognitive status of people at risk of dementias. Our aims were to investigate the prevalence of amnestic and non-amnestic MCI in a South Italian elderly population, and to identify socio-demographic, clinical and lifestyle factors associated with MCI. A cross-sectional retrospective population study on 839 community-dwelling participants over 60 years of age was carried out. Elderly people were administered a brief neuropsychological screening to identify their cognitive and functional status, and a questionnaire to investigate several socio-demographic, clinical, and lifestyle factors. Prevalence estimate for MCI was 12.0% (95% CI: 10.0–14.5%), for amnestic MCI was 7.4% (95% CI: 5.8–9.4%), and for non-amnestic MCI was 4.6% (95% CI: 3.4–6.4%), for people older than 60 years of age. Logistic regression models, corrected for age, sex, and education, revealed a significant association of MCI with the following factors: age, education, intellectual activities, and topographical disorientation. On the other hand, education, clinical factors (e.g., depression level and perceived physical pain), lifestyle factors (e.g., smoking, alcohol, and leisure/productive activities), dietary habits, quality of life, and self-reported topographical disorientation were non-significantly associated with MCI. Prevalence estimates and the association of MCI and its subtypes with risk and protective factors were discussed in comparison with the most recent systematic reviews and meta-analyses.
... In humans, the enhancement effects on cognitive function associated with an increase in mushroom consumption evidenced the crucial role of ergothioneine in the brain. 78 Several studies demonstrated that this compound could promote neurogenesis and act against oxidative damage and neuroinflammation. 72,79−81 The precise role of selenoneine in this organ is not known so far. ...
... For humans, the main dietary source of ERG is mushrooms. Mushroom intake is associated with decreased risk of developing mild cognitive impairment (Feng et al., 2019) and decreased cancer risk (Ba et al., 2021). ERG was Abbreviations: ATP-PRT, ATP phosphoribosyltransferase; CDW, Cell dry weight; CoA, Coenzyme A; ERG, Ergothioneine; GAAC, General amino acid control; GFP, Green fluorescent protein; HCO, Hercynylcysteine sulfoxide; MTHFR, Methylenetetrahydrofolate reductase; NCR, Nitrogen catabolite repression; OCTN1, Organic cation transporter novel-type 1; SAM, S-adenosylmethionine; SC, Synthetic complete; TRA, β-(1,2,4-triazol-3-yl)-DL-alanine. ...
Ergothioneine (ERG) is an unusual sulfur-containing amino acid. It is a potent antioxidant, which shows great potential for ameliorating neurodegenerative and cardiovascular diseases. L-ergothioneine is rare in nature, with mushrooms being the primary dietary source. The chemical synthesis process is complex and expensive. Alternatively, ERG can be produced by fermentation of recombinant microorganisms engineered for ERG overproduction. Here, we describe the engineering of S. cerevisiae for high-level ergothioneine production on minimal medium with glucose as the only carbon source. To this end, metabolic engineering targets in different layers of the amino acid metabolism were selected based on literature and tested. Out of 28 targets, nine were found to improve ERG production significantly by 10%–51%. These targets were then sequentially implemented to generate an ergothioneine-overproducing yeast strain capable of producing 106.2 ± 2.6 mg/L ERG in small-scale cultivations. Transporter engineering identified that the native Aqr1 transporter was capable of increasing the ERG production in a yeast strain with two copies of the ERG biosynthesis pathway, but not in the strain that was further engineered for improved precursor supply. Medium optimization indicated that additional supplementation of pantothenate improved the strain's productivity further and that no supplementation of amino acid precursors was necessary. Finally, the engineered strain produced 2.39 ± 0.08 g/L ERG in 160 h (productivity of 14.95 ± 0.49 mg/L/h) in a controlled fed-batch fermentation without supplementation of amino acids. This study paves the way for the low-cost fermentation-based production of ergothioneine.
... In addition, decrease in ET levels has also been observed in vascular dementia and dementia (21,127). A study of subjects who consumed mushrooms, a rich source of ET, revealed an inverse correlation between mild cognitive impairment and mushroom intake, which was independent of age, gender, or lifestyle habits such as smoking or alcohol consumption (35). Oral administration of ET also promoted memory in rodents, as measured by the novel object recognition test (93). ...
Significance:
Ergothioneine (ET) is an unusual sulfur containing amino acid derived from histidine, acquired predominantly from the diet. Its depletion is associated with deleterious consequences in response to stress stimuli in cell culture models, prompting us to classify it as a vitamin in 2010, which was later supported by in vivo studies. ET is obtained from a variety of foods and is taken up by a selective transporter. ET possesses antioxidant and anti-inflammatory properties, which confers cytoprotection. ET crosses the blood brain barrier and has been reported to have beneficial effects in the brain. Here we discuss the cytoprotective and neuroprotective properties of ET, which may be harnessed for combating neurodegeneration and decline during aging. Recent Advances: The designation of ET as a stress vitamin is gaining momentum, opening a new field of investigation involving small molecules that are essential for optimal physiological functioning and maintenance of healthspan.
Critical issues:
Although ET was discovered more than a century ago, its physiological functions are still being elucidated, especially in the brain. As ET is present in most foods, toxicity associated with its deprivation has been difficult to assess.
Future directions:
Using genetically engineered cells and mice, it may now be possible to elucidate roles of ET. This coupled with advances in genomics and metabolomics may lead to identification of ET function. As ET is a stable antioxidant with anti-inflammatory properties, whose levels decline during aging, supplementing ET in the diet or consuming an ET-rich diet may prove beneficial.
... They have been considered a "forgotten source of nutrients" [29], making it hard to calculate their actual consumption and contribution to human health. Despite this limitation, accumulating evidence suggests that mushroom consumption may be associated with a lower risk of chronic diseases, including cancers [30], metabolic syndrome, [22] cognitive impairment, [31,32], and dementia [33]. A few epidemiological observational studies also have reported an inverse association between mushroom consumption and the risk of mortality [34,35]. ...
Background
Whether mushroom consumption, which is a rich source of potent antioxidants ergothioneine and glutathione, vitamins, and minerals (e.g., selenium & copper), is associated with a lower mortality risk is not well understood. This study aimed to examine the association between mushroom consumption and risk of mortality in a prospective cohort study and a meta-analysis of prospective cohort studies.
Methods
We followed 30,378 participants from the continuous National Health and Nutrition Examination Survey (NHANES) extant data (2003-2014). Dietary mushroom intake was assessed using up to two 24-h recalls. Mortality was evaluated in all participants linked to the National Death Index mortality data through December 31, 2015. We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). We also conducted a meta-analysis, including results from our present study and 4 other cohort studies.
Results
During a mean (SD) of 6.7 (3.4) years of follow-up, a total of 2855 death cases were documented among NHANES participants. In our analysis of continuous NHANES, we found a non-significant association between mushroom consumption and all-cause mortality (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.67-1.06) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors, including total energy. The meta-analysis of prospective cohort studies, including 601,893 individuals, showed that mushroom consumption was associated with a lower risk of all-cause mortality (pooled risk ratio: 0.94; 95% CI: 0.91, 0.98).
Conclusion
In a meta-analysis of prospective cohort studies, mushroom consumption was associated with a lower risk of all-cause mortality.
... A unique feature of ERGO compared to other antioxidants is that its distribution to the brain parenchyma is independent of the BBB, but rather mediated by OCTN1 receptors. Thus, it seems reasonably certain that there is a huge interest in assessing the protective role of ERGO in the brain 15,23,29 , particularly oxidative stress related to Alzheimer's disease [40][41][42] . In www.nature.com/scientificreports/ ...
Ergothioneine (ERGO) is a rare amino acid mostly found in fungi, including mushrooms, with recognized antioxidant activity to protect tissues from damage by reactive oxygen species (ROS) components. Prior to this publication, the biodistribution of ERGO has been performed solely in vitro using extracted tissues. The aim of this study was to develop a feasible chemistry for the synthesis of an ERGO PET radioligand, [11C]ERGO, to facilitate in vivo study. The radioligand probe was synthesized with identical structure to ERGO by employing an orthogonal protection/deprotection approach. [11C]methylation of the precursor was performed via [11C]CH3OTf to provide [11C]ERGO radioligand. The [11C]ERGO was isolated by RP-HPLC with a molar activity of 690 TBq/mmol. To demonstrate the biodistribution of the radioligand, we administered approximately 37 MBq/0.1 mL in 5XFAD mice, a mouse model of Alzheimer’s disease via the tail vein. The distribution of ERGO in the brain was monitored using 90-min dynamic PET scans. The delivery and specific retention of [11C]ERGO in an LPS-mediated neuroinflammation mouse model was also demonstrated. For the pharmacokinetic study, the concentration of the compound in the serum started to decrease 10 min after injection while starting to distribute in other peripheral tissues. In particular, a significant amount of the compound was found in the eyes and small intestine. The radioligand was also distributed in several regions of the brain of 5XFAD mice, and the signal remained strong 30 min post-injection. This is the first time the biodistribution of this antioxidant and rare amino acid has been demonstrated in a preclinical mouse model in a highly sensitive and non-invasive manner.
... People who incorporate mushrooms into their diets, even in small amounts (more than twice a week), seem to have a lower risk of mild cognitive impairment, usually preceding Alzheimer's disease [196]. Mushrooms contain many other substances whose exact role in brain health is not yet clear, but they include hericenones, erinacines terpenoids, scabronines, isoindolinones, sterols, and dictyophorines, which are a series of compounds that could contribute to the growth of nerve and brain cells [197]. ...
The defining characteristics of the traditional Sub-Saharan Africa (SSA) cuisine have been the richness in indigenous foods and ingredients, herbs and spices, fermented foods and beverages, and healthy and whole ingredients used. It is crucial to safeguard the recognized benefits of mainstream traditional foods and ingredients, which gradually eroded in the last decades. Notwithstanding poverty, chronic hunger, malnutrition, and undernourishment in the region, traditional eating habits have been related to positive health outcomes and sustainability. The research prevailed dealing with food availability and access rather than the health, nutrition, and diet quality dimensions of food security based on what people consume per country and on the missing data related to nutrient composition of indigenous foods. As countries become more economically developed, they shift to “modern” occidental foods rich in saturated fats, salt, sugar, fizzy beverages, and sweeteners. As a result, there are increased incidences of previously unreported ailments due to an unbalanced diet. Protein-rich foods in dietary guidelines enhance only those of animal or plant sources, while rich protein sources such as mushrooms have been absent in these charts, even in developed countries. This article considers the valorization of traditional African foodstuffs and ingredients, enhancing the importance of establishing food-based dietary guidelines per country. The crux of this review highlights the potential of mushrooms, namely some underutilized in the SSA, which is the continent’s little exploited gold mine as one of the greatest untapped resources for feeding and providing income for Africa’s growing population, which could play a role in shielding Sub-Saharan Africans against the side effects of an unhealthy stylish diet.
... Alzheimer's disease [222]. Mushrooms contain many other substances whose exact role in brain health is not yet clear. ...
In Sub-Saharan Africa, despite poverty, chronic hunger and food insecurity, traditional eating has been related to positive health outcomes and sustainability. There is little health research on diet quality based on what African people consume. The defining characteristics of the traditional African cuisine are the richness in herbs and spices, fermented foods and beverages, and healthy and whole ingredients used. However, as countries in this region become more economically developed, there is a shift to “modern” occidental foods rich in saturated fats, sugar and sweeteners. As a result, there are increased incidences of previously unreported ailments due to unbalanced diet. The regular practice of infinite international aid to the region to curb food insecurity has been unsustainable, ineffective and with no end in sight. Local increase in production and productivity is imperative. Protein rich foods in dietary guidelines enhance only those of animal or plant sources while rich protein sources such of mushroom, has been absent in these charts. This article considers the valorisation of traditional African foods and the importance of establishing an African Food-Based Dietary Guidelines (AFBDGs), an unprecedented Food Pyramid, along with the added emphasis on the potential of African mushrooms, which may play a role in shielding Sub-Saharan Africans against the side-effects of a western stylish diet and promote health. It enhances the preventive role of mushrooms in viral diseases and other disorders.
... Several studies investigated the putative health benefits of mushroom consumption. These include the association of increased mushroom consumption with decreased risks of dementia [133,134], cardiovascular disease, certain cancers (e.g. prostate and breast cancer) [135,136], IBD [137], metabolic syndrome [138], PD and other neurological disorders [139], viral infections [140] and many other conditions. ...
There has been a recent surge of interest in the unique low molecular weight dietary thiol/thione, ergothioneine. This compound can accumulate at high levels in the body from diet and may play important physiological roles in human health and development, and possibly in prevention and treatment of disease. Blood levels of ergothioneine decline with age and onset of various diseases. Here we highlight recent advances in our knowledge of ergothioneine.
... In 2019, a community-based cross-sectional study was conducted on 663 participants aged ≥60 years from the Diet and Healthy Aging study in Singapore (Feng et al., 2019). Individuals consuming >2 portions of mushrooms per week had reduced risk of mild cognitive impairment in the multiple-adjusted logistic regression model (OR: 0.48; 95%CI 0.26-0.89; ...
Background
mushrooms are traditionally used as a food ingredient and in folk medicine. Many in vitro and animal studies have reported their potential health effects, but without any clear application in human health. Although they have a worldwide history of use in dishes and folk medicine, mushroom extracts are commonly taken as supplements but need to be evaluated regarding clinical effects and safety, in particular among patients searching for further efficacy for their disease beside pharmacological treatments already prescribed.
Scope and approach
this review summarizes available data from the scientific literature about the nutritional and effects of mushrooms on human health by selecting clinical studies on humans in English. At the same time, the safety profile and unwanted effects were highlighted.
Key findings and conclusions
in spite of their wide use among populations, data on humans were scant and did not justify extensive use without more well-designed trials on mushroom efficacy. Overall, their use seems to be safe, but with some side effects, easily reversible after intake interruption. Nutritional use seems promising for coping with the energy surplus of the Western countries and could be useful for some nutritional aspects.
Background
The evidence concerning dietary diversity and cognitive function remains insufficient.
Objective
To investigate the association of dietary diversity score (DDS) with mild cognitive impairment (MCI) and cognitive performance in different domains.
Methods
Data from The Lifestyle and Healthy Aging of Chinese Square Dancer Study was used in this study. DDS was constructed based on the intake frequencies of 9 food groups assessed by a validated food frequency questionnaire. MCI was diagnosed by Petersen’s criteria. A neuropsychological test battery was used to assess the performance on cognitive domains, and test scores were standardized to Z scores. Multiple linear regression models and logistic regression models were used to estimate the β and odds ratios and their 95% CIs, respectively.
Results
Among 1,982 participants, the mean (SD) age was 63.37 (5.00) years, 1,778 (89.71%) were women, and 279 (14.08%) had MCI. Compared to the DDS quartile (0, 6], the multivariable-adjusted odds ratios (95% CI) were 0.74 (0.48, 1.15) for DDS quartile (6, 7], 0.65 (0.43, 0.97) for DDS quartile (7, 8], and 0.55 (0.37, 0.84) for DDS quartile (8, 9]. Furthermore, higher DDS was positively associated with better performance of cognitive domains, including global cognitive function (β= 0.20, 95% CI: 0.12, 0.30), episodic memory (β= 0.21, 95% CI: 0.07, 0.35), attention (β= 0.15, 95% CI: 0.03, 0.26), language fluency (β= 0.24, 95% CI: 0.10, 0.38), and executive function (β= – 0.24, 95% CI: – 0.38, – 0.10).
Conclusions
This study indicated that higher DDS was associated with better cognitive function among middle-aged and older Chinese people.
n recent years, growing awareness of the role of oxidative stress in brain health has prompted antioxidants, especially dietary antioxidants, to receive growing attention as possible treatments strategies for patients with neurodegenerative diseases (NDs). The most widely studied dietary antioxidants include active substances such as vitamins, carotenoids, flavonoids and polyphenols. Dietary antioxidants are found in usually consumed foods such as fresh fruits, vegetables, nuts and oils and are gaining popularity due to recently growing awareness of their potential for preventive and protective agents against NDs, as well as their abundant natural sources, generally non-toxic nature, and ease of long-term consumption. This review article examines the role of oxidative stress in the development of NDs, explores the ‘two-sidedness’ of the blood–brain barrier (BBB) as a protective barrier to the nervous system and an impeding barrier to the use of antioxidants as drug medicinal products and/or dietary antioxidants supplements for prevention and therapy and reviews the BBB permeability of common dietary antioxidant suplements and their potential efficacy in the prevention and treatment of NDs. Finally, current challenges and future directions for the prevention and treatment of NDs using dietary antioxidants are discussed, and useful information on the prevention and treatment of NDs is provided.
Background/Objectives: Bioactive compounds in mushrooms may protect the brain from neurodegeneration by inhibiting the production of amyloid-β and playing an antioxidant role. This study aimed to examine the associations of...
A growing number of studies is focusing on the pharmacology and feasibility of bioactive compounds as a novel valuable approach to target a variety of human diseases related to neurological degeneration. Among the group of the so-called medicinal mushrooms (MMs), Hericium erinaceus has become one of the most promising candidates. In fact, some of the bioactive compounds extracted from H. erinaceus have been shown to recover, or at least ameliorate, a wide range of pathological brain conditions such as Alzheimer’s disease, depression, Parkinson’s disease, and spinal cord injury. In a large body of in vitro and in vivo preclinical studies on the central nervous system (CNS), the effects of erinacines have been correlated with a significant increase in the production of neurotrophic factors. Despite the promising outcome of preclinical investigations, only a limited number of clinical trials have been carried out so far in different neurological conditions. In this survey, we summarized the current state of knowledge on H. erinaceus dietary supplementation and its therapeutic potential in clinical settings. The bulk collected evidence underlies the urgent need to carry out further/wider clinical trials to prove the safety and efficacy of H. erinaceus supplementation, offering significant neuroprotective applications in brain pathologies.
Dementia, a form of neurodegenerative disease, is a chronic brain disorder that affects memory and learning. Oxidative stress and inflammation are believed to contribute to the pathogenesis of dementia, as an imbalance of oxidant-antioxidant/pro-inflammatory-anti-inflammatory cytokines homeostasis causes neuroinflammation and an increased rate of reactive oxygen species generation. Natural, medicinal mushrooms, enriched with antioxidants and anti-inflammatory properties, are growing popular as agents to provide beneficial neuronal health effects, such as inhibiting oxidative stress, protecting neuronal excitotoxicity, and boosting the human immune response. Mushrooms such as Hericium erinaceus and Coriolus versicolor have been demonstrated to improve cognitive function and prevent and reduce Alzheimer’s and Parkinson’s disease. The bioactive compounds in these mushrooms include erinacines, polyphenols, polysaccharopeptides, and terpenoids. Erinacine A, one of the main bioactive components, effectively reduces neurodegeneration and dementia and has no known adverse side effects. The mycelia are safe for oral consumption over an extended period and can be supplemented in a diet. This chapter summarizes current scientific information on the health properties of H. erinaceus and C. versicolor to contribute to prophylactic and therapeutic findings regarding neuroprotection against dementia.KeywordsAlzheimer’s Disease
Coriolus versicolor
Dementia
Hericium erinaceus
MushroomsNeurodegeneration
Age-related loss of function brings age-related disease, and therefore it is of primary importance to search for interventions that can help minimize detrimental symptoms people deal with in old age. Fungi have always been given a great deal of attention and reverence in traditional medical practices for their ability to minimize harmful symptoms of diseases. More recently, the role of fungi in influencing healthspan and lifespan is being directly studied in the lab. To treat animal model organisms with fungi-derived molecules, extractions from different life cycle stages of fungi are performed. This includes mycelium (the vegetative stage), sporocarps (the reproductive stage), or spores (the end product of the reproductive stage), and each stage provides a variety of bioactive compounds. These bioactive compounds include glycoproteins, polysaccharides, triterpenoids, meroterpenoids, sesquiterpenoids, steroids, alkaloids, benzopyran derivatives, and benzoic acid derivatives, amongst others. In this work, we review evidence that fungal extracts from multiple species can have beneficial effects on the lifespan and healthspan of model organisms, such as C. elegans worms, D. melanogaster flies, and M. musculus mice. We cover extraction methods and lifespan effects of Ganoderma lucidum (i.e. Reishi), Lentinula edodes (i.e. Shiitake), the genus Auricularia (i.e. jelly ear mushrooms), the genera Cordyceps and Ophiocordyceps (e.g. the caterpillar fungi), Hericium erinaceus (i.e. Lion's mane), the mold genus Monascus, and also Inonotus obliquus (i.e. Chaga), Grifola frondosa (i.e. Maitake or hen-of-the-woods), the genus Pleurotus (e.g. oyster mushrooms), and Agaricus subrufescens (i.e. the almond mushroom). We propose that further research on fungal extracts will provide a greater picture of the role fungi-derived bioactive molecules can have in developing longevity and neuroprotective medicines for humans.
Ergothioneine (EGT) is a high-value natural sulfur-containing amino acid and has been shown to possess extremely potent antioxidant and cytoprotective activities. At present, EGT has been widely used in food, functional food, cosmetics, medicine, and other industries, but its low yield is still an urgent problem to overcome. This review briefly introduced the biological activities and functions of EGT, and expounded its specific applications in food, functional food, cosmetic, and medical industries, introduced and compared the main production methods of EGT and respective biosynthetic pathways in different microorganisms. Furthermore, the use of genetic and metabolic engineering methods to improve EGT production was discussed. In addition, the incorporation of some food-derived EGT-producing strains into fermentation process will allow the EGT to act as a new functional factor in the fermented foods.
This article reviews what is presently known about the biological roles of the diet-derived compound ergothioneine (ET). ET seems important to humans because it is rapidly taken up from the diet by a transporter largely or completely specific for ET, and once taken up it is retained within the body for weeks or months. The various possible functions of ET in vivo are explored. Much emphasis has been placed on the antioxidant properties of ET, but although these are well established in vitro, the evidence that antioxidant activity is the principal function of ET in vivo is weak. ET is not unique in this: The evidence for the antioxidant roles of vitamin C and polyphenols such as the flavonoids in vivo is also weak. By contrast, α-tocopherol has demonstrated in vivo antioxidant effects in humans.
Expected final online publication date for the Annual Review of Food Science and Technology, Volume 14 is March 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
We define copromycodiversity as all the morphological, physiological, functional, and ecological diversity of an assemblage of dung-inhabiting fungi, also known as coprophilous fungi. These fungi are represented by species of the phyla Ascomycota, Basidiomycota, and Mucoromycota in the sensu stricto of the Kingdom. Traditionally, other groups of organisms, such as some species of protists from the phylum Amoebozoa (Myxomycetes) can also be found associated with these substrates, being studied together with fungi, here in sensu lato. This fungal group is responsible for the maintenance of supporting ecosystem services, essential for life as we know it, acting in the cycling of matter and energy via dung decomposition. Despite this, there are still few studies involving these organisms. In this thesis, we seek to contribute to expanding scientific knowledge about dung-inhabiting fungi (sensu lato), whether in terms of their biology, ecology, or taxonomy. We begin by promoting a synthesis of knowledge as well as a scientometric analysis of the first studies in Brazil and in the world, in addition to an updated list of species and their geographic distribution, adding new occurrences. We compile data on the occurrence and applications of the genus Chaetomium, a fimicolous fungal genus, which means that its species are found associated with both dung and decaying plant debris, as well as developed a proposal for a life cycle for dung-inhabiting fungi, contemplating both the coprophilous and fimicolous cycles. We show how differences in the type of digestive tract of the animal that originated the dung can influence the taxonomic diversity and ecological profiles of species of fungi that inhabit this substrate. Furthermore, we evaluated, in a microcosm experiment, the durability, decomposition rate, and nutritional composition of cattle and equine dung as suitable substrates for the development of coprophilous organisms. Finally, we present the experience report on how we are using social media to communicate fungal biology to the public, developing media strategies to publicize different aspects of our research with dung-inhabiting fungi as well as other fungal groups to the general community. It is expected that the data presented here can contribute to the expansion of knowledge about these fungi, reducing the gap in knowledge about biology, ecology, distribution, and productivity, especially in Brazil. In addition, we hope to encourage the training of human resources as well as the development of additional studies that will contribute to an increasingly better understanding of copromycodiversity.
The potential of edible mushrooms as an unexploited treasure trove, although rarely included in known food guidelines, is highlighted. Their role in shielding people against the side effects of an unhealthy stylish diet is reviewed. Mushrooms complement the human diet with various bioactive molecules not identified or deficient in foodstuffs of plant and animal sources, being considered a functional food for the prevention of several human diseases. Mushrooms have been widely used as medicinal products for more than 2,000 years, but globally the potential field of use of wild mushrooms has been untapped. There is a broad range of edible mushrooms which remain poorly identified or even unreported which is a valuable pool as sources of bioactive compounds for biopharma utilization and new dietary supplements. Some unique elements of mushrooms and their role in preventative healthcare are emphasized, through their positive impact on the immune system. The potential of mushrooms as antiviral, anti-inflammatory, anti-neoplastic, and other health concerns is discussed. Mushrooms incorporate top sources of non-digestible oligosaccharides, and ergothioneine, which humans are unable to synthesize, the later a unique antioxidant, cytoprotective, and anti-inflammatory element, with therapeutic potential, approved by world food agencies. The prebiotic activity of mushrooms beneficially affects gut homeostasis performance and the balance of gut microbiota is enhanced. Several recent studies on neurological impact and contribution to the growth of nerve and brain cells are mentioned. Indeed, mushrooms as functional foods' nutraceuticals are presently regarded as next-generation foods, supporting health and wellness, and are promising prophylactic or therapeutic agents.
Objectives:
Cognitive impairment commonly occurs among older people worldwide. Although the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet was associated with better cognitive function and lower risk of cognitive impairment, it could not be applied to older Chinese due to the traditional dietary characteristics in China. We aimed to develop the Chinese version of the MIND (cMIND) diet and verify its association with cognitive impairment among older Chinese individuals.
Design:
A cross-sectional study.
Setting and participants:
We included a total of 11,245 participants from the Chinese Longitudinal Healthy Longevity Study (CLHLS) follow-up survey in 2018. The mean age of the participants at study baseline was 84.06 (±11.46) years.
Measurements:
We established the cMIND diet based on current evidence in the diet-cognition field, combined with Chinese dietary characteristics. The verification of its association with cognitive impairment was conducted using the data from the CLHLS follow-up survey. Adherence to the cMIND diet was assessed by the cMIND diet score, which was calculated from a food frequency questionnaire. Cognitive impairment was identified by the Mini-Mental State Examination. Instrumental activities of daily living (IADL) disability was defined according to the self-reported performance of eight activities.
Results:
The cMIND diet comprised 11 brain-healthy food groups and 1 unhealthy food group. The median cMIND diet score of all participants was 4.5 (from a total of 12 points) and the prevalence of cognitive impairment was 15.2%. Compared with the lowest tertile, the highest tertile score was associated with lower odds of cognitive impairment (odds ratio (OR)=0.60, 95% confidence interval (CI): 0.51-0.72) and IADL disability (OR=0.86, 95% CI: 0.75-0.98) in the full-adjusted model.
Conclusion:
We developed the cMIND diet that was suitable for older Chinese individuals, and our results suggested that higher adherence to the cMIND diet was associated with reduced odds of cognitive impairment and IADL disability. In view of the limitations of cross-sectional design in the study, further research is clearly warranted.
Memory is the ability of an individual to record the information and recall it whenever needed. A complex network of numerous nerve cells and cortex of brain helps us to store memory captured in the form of words/pictures/olfactory signals, etc. Hippocampus helps in converting short form of memory into long term. By continuous learning we memorize the things and in an accident or disease there is loss of memory, stress and anxiety can lead to depression and ill health. Just like herbs (i.e. tea—Camellia sinensis (L.) Kuntze) stimulates the nerves of our brain the use of certain mushrooms like Hericium, Ganoderma, Lentinula, Psilocybe helps in brain-boosting and cognitive impairments. Mushrooms and their bioactive compounds present in the mycelial extract help in lowering the blood pressure, change the mood and control the progression of Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS).Stressful conditions are often associated with loss of memory and other cognitive functions, which may lead to threats of schizophrenia and Alzheimer’s disease. In traditional or alternative system of medicine, numerous plants and fungi have been used to alleviate memory impairment both in healthy individuals and those with disease states which are now recognized as specific cognitive disorders. An ethno-mycological approach has provided leads to identify mushrooms and their bioactive compounds that may have potential to modulate cognitive abilities by different modes of action. A variety of therapeutic targets have been identified as relevant in the treatment of cognitive disorders, and neuroprotection against glutamate-induced overstimulation of N-methyl-d-aspartate (NMDA) receptors, by the use of NMDA receptor modulators.Other activities considered to be relevant in the alleviation of cognitive impairment include anti-inflammatory, antioxidant and estrogenic activities. Psychedelics produced by hallucinogenic mushrooms can cause physical changes in brain, even to the cellular as well as molecular levels, which is the primary component. These psychedelics when exposed to neuron cells help to create new outgrowths of the neuron network in the brain. These new connections help in brain functioning. Proactive compounds like hericenones (from mushroom) and erinacines (from mycelium) of lion’s mane, cordycepin from Cordyceps
, lentinan from Lentinula help in stress alleviation, induce sound sleep and enhance the memory by stimulating the brain and avoiding shrinking of neurons in the cortex.KeywordsMemoryMushroomsDietary supplements
Hericium
Ganoderma
Cordyceps
Ergothioneine (ERGO) is a potent antioxidant and anti-inflammatory amino acid that is highly bioavailable to humans from the diet. ERGO is now regarded by some as a "longevity vitamin" that has the potential to mitigate some chronic diseases of aging and thereby increase life expectancy when present in adequate amounts. However, only limited knowledge exists regarding ERGO content in the human diet. Since ERGO is produced primarily by fungi, mushrooms are known to be the leading dietary source, but ERGO is found in relatively low amounts throughout the food chain as a result of soil-borne fungi or bacteria passing it on to plants through their roots. Some conventional agricultural practices that negatively impact soil fungi, such as excessive soil disturbance (plowing), can significantly reduce ERGO content of food crops when compared to regenerative practices such as eliminating tillage of the soil (No-Till). This has led us to the concept that ERGO may be a definitive connection between soil health and human health.
Substantial studies have suggested that natural compounds rich in antioxidants can enhance the immune system and decrease oxidative stress. These substances facilitate in scavenging the reactive species that initiate the peroxidation, inhibit the formation of peroxides, breaking the autoxidative chain reaction, and quenching •O2⁻. The molecules with antioxidants properties such as low molecular weight antioxidant, glutathione, polyphenol, carotenoids, minerals, ascorbic acid, vitamin E, ubiquinone, organosulfur compounds, ergothioneine, betalains, and carnosine/anserine have demonstrated their potential in the alleviation of age-related diseases. However, the exact molecular mechanisms of these molecules involved in the prevention of age-related diseases are worth discussing further. In this chapter, we discussed the biological mechanism of molecules with antioxidant activity against age-related diseases. Overall, a better understanding of the mode of action of antioxidants involved in the redox imbalance in age-related diseases would provide a useful approach in mediating diseases.
Background
Diabetic cardiotoxicity is commonly associated with oxidative injury, inflammation, and endothelial dysfunction. L-ergothioneine (L-egt), a diet-derived amino acid, has been reported to decrease mortality and risk of cardiovascular injury, provides cytoprotection to tissues exposed to oxidative damage, and prevents diabetes-induced perturbation.
Objective
This study investigated the cardioprotective effects of L-egt on diabetes-induced cardiovascular injuries and its probable mechanism of action.
Methods
Twenty-four male Sprague-Dawley rats were divided into non-diabetic (n=6) and diabetic groups (n=18). Six weeks after the induction of diabetes, the diabetic rats were divided into three groups (n=6) and administered distilled water, L-egt (35mg/kg), and losartan (20mg/kg) by oral gavage for six weeks. Blood glucose and mean arterial pressure (MAP) were recorded pre-and post-treatment, while biochemical, ELISA, and Rt-PCR analyses were conducted to determine inflammatory, injury-related and antioxidant biomarkers in cardiac tissue after euthanasia. Also, an in-silico study, including docking and molecular dynamic simulations of L-egt toward the Keap1-Nrf2 protein complex, was done to provide a basis for the molecular antioxidant mechanism of L-egt.
Results
Administration of L-egt to diabetic animals reduced serum triglyceride, water intake, MAP, biomarkers of cardiac injury (CK-MB, LDH), lipid peroxidation, and inflammation. Also, L-egt increased body weight, antioxidant enzymes, upregulated Nrf2, HO-1, NQO1 expression, and decreased Keap1 expression. The in-silico study showed that L-egt inhibits Keap1-Nrf2 complex by binding to the active site of Nrf2 protein, thereby preventing its degradation.
Conclusion
L-egt protects against diabetes-induced cardiovascular injury via the upregulation of Keap1-Nrf2 pathway and its downstream cytoprotective antioxidants.
There is mounting evidence for the potential for the natural dietary antioxidant and anti-inflammatory amino acid l -Ergothioneine (ERGO) to prevent or mitigate chronic diseases of aging. This has led to the suggestion that it could be considered a ‘longevity vitamin.’ ERGO is produced in nature only by certain fungi and a few other microbes. Mushrooms are, by far, the leading dietary source of ERGO, but it is found in small amounts throughout the food chain, most likely due to soil-borne fungi passing it on to plants. Because some common agricultural practices can disrupt beneficial fungus–plant root relationships, ERGO levels in foods grown under those conditions could be compromised. Thus, research is needed to further analyse the role agricultural practices play in the availability of ERGO in the human diet and its potential to improve our long-term health.
Ergothioneine is a thiol/thione molecule synthesised only by some fungi and bacteria. Nonetheless, it is avidly taken up from the diet by humans and other animals through a transporter, OCTN1, and accumulates to high levels in certain tissues. Ergothioneine is not rapidly metabolised or excreted in urine and is present in many, if not all, human tissues and body fluids. Ergothioneine has powerful antioxidant and cytoprotective properties in vitro and there is evidence that the body may concentrate it at sites of tissue injury by raising OCTN1 levels. Decreased blood and/or plasma levels of ergothioneine have been observed in some diseases suggesting that a deficiency could be relevant to the disease onset or progression. This brief Review explores the possible roles of ergothioneine in human health and disease. This article is protected by copyright. All rights reserved.
The candidate vitamin ergothioneine (ET) is a unique antioxidant. Expression of the ergothioneine transporter (ETT) (gene symbol SLC22A4) in distinct cells is thought to signal intracellular ET activity, since we have previously shown that the ETT is highly selective for ET. Unfortunately, some continue to hold the ETT as a relevant drug transporter, using the misleading functional name OCTN1, novel organic cation transporter. The present study was provoked by 2 recent reports in which new ETT substrates were declared. Astonishingly, the transport efficiencies (TE) of ETT for saracatinib and some nucleoside drugs were as high as the TE for ET. Here we examined, based on regulated expression of ETT from human and rat in 293 cells and liquid chromatography-mass spectrometry quantification, the transport of several drugs. With the nucleosides cytarabine, gemcitabine, 2'-deoxycytidine, and 2'-deoxyadenosine, and the drugs saracatinib, ipratropium, metformin, and oxaliplatin, the uptake into cells expressing ETT was not increased over control cells. ETT-mediated uptake of gabapentin was detectable, but the TE was approximately 100-fold lower than the TE for ergothioneine (50 to 200 μl min-1 mg protein-1). In conclusion, the ETT remains highly specific for its physiological substrate ergothioneine. Our results contradict several reports on additional substrates. The ETT does not provide multiple substrate specificities and it is not a transporter of cationic drugs. Only compounds that are related to ET in substructure - for example gabapentin, carnitine, and tetraethylammonium - can be transported, but with very low efficiency. Thus, ETT persists as a specific molecular indicator of ET activity.
L-ergothioneine (ET) is a diet-derived amino acid that accumulates at high concentrations in animals and humans. Numerous studies have highlighted its antioxidant abilities in vitro, and possible cytoprotective capabilities in vivo. We investigated the uptake and distribution of ET in various organs by a highly sensitive and specific liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) technique, both before and after oral administration of pure ET (35 and 70 mg/kg/day for 1, 7, and 28 days) to male C57BL6J mice. ET primarily concentrates in the liver and whole blood, and also in spleen, kidney, lung, heart, intestines, eye, and brain tissues. Strong correlations were found between ET and its putative metabolites - hercynine, ET-sulfonate (ET-SO3H), and S-methyl ET. Hercynine accumulates in the brain after prolonged ET administration. This study demonstrates the uptake and distribution of ET and provides a foundation for future studies with ET to target oxidative damage in a range of tissues in human diseases.
Aim:
We investigated the uptake and pharmacokinetics of ergothioneine (ET), a dietary thione with free radical scavenging and cytoprotective capabilities, after oral administration to humans, and its effect on biomarkers of oxidative damage and inflammation.
Results:
Following oral administration, ET is avidly absorbed and retained by the body with significant elevations in plasma and whole blood concentrations, and relatively low urinary excretion (less than 4% of administered ET). ET levels in whole blood were highly correlated to levels of hercynine and S-methyl-ergothioneine, suggesting that they may be metabolites. After ET administration, some decreasing trends were seen on biomarkers of oxidative damage and inflammation, including allantoin (urate oxidation), 8-hydroxy-2-deoxyguanosine (DNA damage), 8-iso-PGF2α (lipid peroxidation), protein carbonylation, and C-reactive protein. However, most of the changes were non-significant.
Innovation:
This is the first study investigating the administration of pure ET to healthy human volunteers, and monitoring its uptake and pharmacokinetics. This compound is rapidly gaining attention due to its unique properties, and this study lays the foundation for future studies.
Conclusion:
The uptake and retention of ET by the body suggests an important physiological function. The decreasing trend of oxidative damage biomarkers is consistent with animal studies suggesting that ET may function as a major antioxidant but perhaps only under conditions of oxidative stress.
Abstract Mushrooms have long been used not only as food but also for the treatment of various ailments. Although at its infancy, accumulated evidence suggested that culinary-medicinal mushrooms may play an important role in the prevention of many age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Therefore, efforts have been devoted to a search for more mushroom species that may improve memory and cognition functions. Such mushrooms include Hericium erinaceus, Ganoderma lucidum, Sarcodon spp., Antrodia camphorata, Pleurotus giganteus, Lignosus rhinocerotis, Grifola frondosa, and many more. Here, we review over 20 different brain-improving culinary-medicinal mushrooms and at least 80 different bioactive secondary metabolites isolated from them. The mushrooms (either extracts from basidiocarps/mycelia or isolated compounds) reduced beta amyloid-induced neurotoxicity and had anti-acetylcholinesterase, neurite outgrowth stimulation, nerve growth factor (NGF) synthesis, neuroprotective, antioxidant, and anti-(neuro)inflammatory effects. The in vitro and in vivo studies on the molecular mechanisms responsible for the bioactive effects of mushrooms are also discussed. Mushrooms can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro evidence and clinical trials with humans are needed.
This study aimed to determine the stratified normative data by age and education for a modified version of the Mini-Mental State Examination (MMSE) test from a large sample of community-dwelling Chinese older adults in Singapore, and to examine the MMSE's value in detecting early cognitive impairment.
We studied 1,763 Chinese older adults with normal cognitive function and 121 Chinese older adults with early cognitive impairment (Clinical Dementia Rating global score 0.5). Normative MMSE values were derived for each of the 15 strata classified by age (three groups) and education level (five groups). Receiver operating characteristic curve analysis was conducted for the whole sample and each of the three education subgroups (no education, primary, secondary and above).
Education level and age significantly influenced the normative values of MMSE total scores in Chinese older adults with normal cognitive function. For the purpose of detecting early cognitive impairment, an optimal balance between sensitivity (Se) and specificity (Sp) was obtained at a cutoff score of 25, 27 and 29 for each of the three education groups, respectively. For the whole sample, the optimal cutoff point was 26 (Se 0.61, Sp 0.84, area under curve 0.78).
Age and education level must be taken into account in the interpretation of optimal cutoffs for the MMSE. Although widely used, the MMSE has limited value in detecting early cognitive impairment; tests with better performance should be considered in clinical practice.
Neuropsychological testing is key to diagnosing and assessing for dementia but there is a dearth of normative neuropsychological data for ethnic Chinese older persons, particularly for non-English-speaking individuals with low education. The aim of this study was to establish a set of age-specific, education-specific, and culture-appropriate norms on measures of cognitive function for a population of cognitively normal community-dwelling Chinese elderly, and explore the effects of age and education on test performance. Results showed decreasing test performances with increasing age and very poor performance in the most poorly educated strata. However, the age-associated decline in test performance was not uniform across different education groups, indicating a more complex association. The present findings highlight a need for normative data that are applicable to lower educated elderly people as this group makes up a substantial proportion of the Asian elderly.
To postpone cognitive decline and dementia in old age, primary prevention is required earlier in life during middle age. Dietary components may be modifiable determinants of mental performance. In the present study, habitual fruit and vegetable intake was studied in association with cognitive function and cognitive decline during middle age. In the Doetinchem Cohort Study, 2613 men and women aged 43-70 years at baseline (1995-2002) were examined for cognitive function twice, with a 5-year time interval. Global cognitive function and the domains memory, information processing speed and cognitive flexibility were assessed. Dietary intake was assessed with a semi-quantitative FFQ. In multivariate linear regression analyses, habitual fruit and vegetable intake was studied in association with baseline and change in cognitive function. Higher reported vegetable intake was associated with lower information processing speed (P = 0·02) and worse cognitive flexibility (P = 0·03) at baseline, but with smaller decline in information processing speed (P < 0·01) and global cognitive function (P = 0·02) at follow-up. Total intakes of fruits, legumes and juices were not associated with baseline or change in cognitive function. High intakes of some subgroups of fruits and vegetables (i.e. nuts, cabbage and root vegetables) were associated with better cognitive function at baseline and/or smaller decline in cognitive domains. In conclusion, total intake of fruits and vegetables was not or inconsistently associated with cognitive function and cognitive decline. A high habitual consumption of some specific fruits and vegetables may diminish age-related cognitive decline in middle-aged individuals. Further research is needed to verify these findings before recommendations can be made.
Fruits and vegetables are among the most nutritious and healthy of foods, and are related to the prevention of many chronic diseases. The aim of the study was to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Two thousand and thirty-one elderly subjects (aged 70-74 years; 55% women) recruited from the general population in Western Norway underwent extensive cognitive testing and completed a comprehensive FFQ. The cognitive test battery covered several domains (Kendrick Object Learning Test, Trail Making Test--part A, modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test). A validated and self-reported FFQ was used to assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake. The associations were strongest between cognition and the combined intake of fruits and vegetables, with a marked dose-dependent relationship up to about 500 g/d. The dose-related increase of intakes of grain products and potatoes reached a plateau at about 100-150 g/d, levelling off or decreasing thereafter, whereas the associations were linear for mushrooms. For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fibre bread were most pronounced. The only negative cognitive association was with increased intake of white bread. In the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner.
The relation between vitamin B-12 and cognitive function in older adults is unclear. Limited evidence suggests that the relation is modulated by apolipoprotein E epsilon4. Hence, it is important to further examine this gene-nutrient interaction.
The aim was to investigate the role of apolipoprotein E (APOE) epsilon4 as a genetic predisposing factor modulating the effect of vitamin B-12 on cognitive function.
A battery of neuropsychological tests, including the Mini-Mental State Examination (MMSE) for global cognition, was administered at the baseline assessment to 539 Chinese adults aged > or =55 y. The MMSE was repeated at a median 18 mo (n = 376) and a median of 38 mo (n = 247) after baseline. The interaction of vitamin B-12 and APOE epsilon4 on cognitive function was examined in a linear mixed-effects model for MMSE and in a multiple linear regression model for neuropsychological test scores.
APOE epsilon4 was associated with a lower MMSE score. Vitamin B-12 (natural log transformed) was positively related to MMSE score, and this association was much stronger in APOE epsilon4 carriers than in APOE epsilon4 noncarriers (P for interaction = 0.016). Significant interactions between natural log-transformed vitamin B-12 and APOE epsilon4 were also found for the Digit Span Backward Longest Sequence (P for interaction = 0.013) and Rey Auditory Verbal Learning Test immediate recall (P for interaction = 0.005). Better performance in these 2 tests was associated with vitamin B-12 in APOE epsilon4 carriers but not in APOE epsilon4 noncarriers.
The association between vitamin B-12 and cognitive function was moderated by APOE epsilon4 status.
Variants of the SLC22A4 gene are associated with susceptibility to rheumatoid arthritis and Crohn's disease. SLC22A4 codes for an integral membrane protein, OCTN1, that has been presumed to carry organic cations like tetraethylammonium across the plasma membrane. Here, we show that the key substrate of this transporter is in fact ergothioneine (ET). Human OCTN1 was expressed in 293 cells. A substrate lead, stachydrine (alias proline betaine), was identified by liquid chromatography MS difference shading, a new substrate search strategy. Analysis of transport efficiency of stachydrine-related solutes, affinity, and Na⁺ dependence indicates that the physiological substrate is ET. Efficiency of transport of ET was as high as 195 μl per min per mg of protein. By contrast, the carnitine transporter OCTN2 from rat did not transport ET at all. Because ET is transported >100 times more efficiently than tetraethylammonium and carnitine, we propose the functional name ETT (ET transporter) instead of OCTN1. ET, all of which is absorbed from food, is an intracellular antioxidant with metal ion affinity. Its particular purpose is unresolved. Cells with expression of ETT accumulate ET to high levels and avidly retain it. By contrast, cells lacking ETT do not accumulate ET, because their plasma membrane is virtually impermeable for this compound. The real-time PCR expression profile of human ETT, with strong expression in CD71⁺ cells, is consistent with a pivotal function of ET in erythrocytes. Moreover, prominent expression of ETT in monocytes and SLC22A4 polymorphism associations suggest a protective role of ET in chronic inflammatory disorders.
• erythrocyte
• inflammation
Objective:
To examine the association between long-term tea consumption and depressive and anxiety symptoms in community-living elderly.
Design:
Community based cross-sectional study.
Setting:
The Diet and Healthy Aging Study (DaHA), a prospective cohort study in Singapore.
Participants:
614 elderly aged 60 years and above, who were free of dementia and cognitive impairment.
Measurements:
Information on tea consumption was obtained through interviewer-administered questionnaire. Long-term tea drinking was defined as regular consumption for at least 15 years. Depressive and anxiety symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15) and the 20-item Geriatric Anxiety Inventory (GAI), respectively. A generalized structural equation model (gSEM) was applied to ascertain the association between long-term tea consumption and depressive and anxiety symptoms.
Results:
About 59% of the subjects had consumed tea for over 15 years. Long term tea consumption was significantly associated with a reduced odds of having depressive and anxiety symptoms, after adjusting for demographics (i.e., age, gender, education and ethnicity), comorbid conditions (i.e., heart disease, diabetes, stroke, hypertension and hyperlipidaemia) and long-term coffee consumption.
Conclusion:
There was evidence suggesting that long-term tea consumption was associated with reduced depressive and anxiety symptoms among community-living elderly. This suggests that it is worthwhile to further investigate the role of tea's bioactive compounds in promoting mental health in aging.
While mushrooms are the highest dietary source for the unique sulfur-containing antioxidant ergothioneine, little is known regarding levels of the major biological antioxidant glutathione. Thus, our objectives were to determine and compare levels of glutathione, as well as ergothioneine, in different species of mushrooms. Glutathione levels varied >20-fold (0.11 to 2.41 mg/g dw) with some varieties having higher levels than reported for other foods. Ergothioneine levels also varied widely (0.15 to 7.27 mg/g dw) and were highly correlated with those of glutathione (r=0.62, P<0.001). Both antioxidants were more concentrated in pileus than stipe tissues in selected mushrooms species. Agaricus bisporus harvested during the third cropping flush contained higher levels of ergothioneine and glutathione compared to the first flush, possibly as a response to increased oxidative stress. This study demonstrated that certain mushroom species are high in glutathione and ergothioneine and should be considered an excellent dietary source of these important antioxidants.
Background:
Both in vivo and in vitro studies have indicated that edible mushrooms may have preventive effects against cognitive impairment. However, few cohort studies have yet examined the relationship between mushroom consumption and incident dementia.
Objective:
We examined the relationship between mushroom consumption and incident dementia in a population of elderly Japanese subjects.
Design:
Prospective cohort study.
Setting:
Ohsaki Cohort 2006 Study.
Participants:
13,230 individuals aged ≥65 years living in Ohsaki City, northeastern Japan.
Measurements:
Daily mushroom consumption, other lifestyle factors, and dementia incidence.
Results:
The 5.7 years incidence of dementia was 8.7%. In comparison with participants who consumed mushrooms <1 time/wk, the multi-adjusted HRs (95% CI) for incident dementia among those did so 1-2 times/week and ≥3 times/week were 0.95 (0.81, 1.10) and 0.81 (0.69, 0.95), respectively (P-trend <.01). The inverse association persisted after excluding participants whose dementia event occurred in the first 2 years of follow-up and whose baseline cognitive function was lower. The inverse association did not differ statistically in terms of vegetable consumption (P-interaction = .10).
Conclusions:
This cohort study suggests that frequent mushroom consumption is significantly associated with a lower risk of incident dementia, even after adjustment for possible confounding factors.
There is an exponential increase in dementia in old age at a global level because of increasing life expectancy. The prevalence of neurodegenerative diseases such as dementia and Alzheimer's disease (AD) will continue to rise steadily, and is expected to reach 42 million cases worldwide in 2020. Despite the advancement of medication, the management of these diseases remains largely ineffective. Therefore, it is vital to explore novel nature-based nutraceuticals to mitigate AD and other age-related neurodegenerative disorders. Mushrooms and their extracts appear to hold many health benefits, including immune-modulating effects. A number of edible mushrooms have been shown to contain rare and exotic compounds that exhibit positive effects on brain cells both in vitro and in vivo. In this review, we summarize the scientific information on edible and culinary mushrooms with regard to their anti dementia/AD active compounds and/or pharmacological test results. The bioactive components in these mushrooms and the underlying mechanism of their activities are discussed. In short, these mushrooms may be regarded as functional foods for the mitigation of neurodegenerative diseases.
Ergothioneine (ET), a naturally occurring thione, can accumulate in the human body at high concentrations from diet. Following absorption via a specific transporter, OCTN1, ET may accumulate preferentially in tissues predisposed to higher levels of oxidative stress and inflammation. Given its potential cytoprotective effects, we examined how ET levels change with age. We found that whole blood ET levels in elderly individuals decline significantly beyond 60 years of age. Additionally, a subset of these subjects with mild cognitive impairment had significantly lower plasma ET levels compared with age-matched subjects. This decline suggests that deficiency in ET may be a risk factor, predisposing individuals to neurodegenerative diseases.
Objectives
To examine the relationships between tea consumption habits and incident neurocognitive disorders (NCD) and explore potential effect modification by gender and the apolipoprotein E (APOE) genotype. DesignPopulation-based longitudinal study. SettingThe Singapore Longitudinal Aging Study (SLAS). Participants957 community-living Chinese elderly who were cognitively intact at baseline. MeasurementsWe collected tea consumption information at baseline from 2003 to 2005 and ascertained incident cases of neurocognitive disorders (NCD) from 2006 to 2010. Odds ratio (OR) of association were calculated in logistic regression models that adjusted for potential confounders. ResultsA total of 72 incident NCD cases were identified from the cohort. Tea intake was associated with lower risk of incident NCD, independent of other risk factors. Reduced NCD risk was observed for both green tea (OR=0.43) and black/oolong tea (OR=0.53) and appeared to be influenced by the changing of tea consumption habit at follow-up. Using consistent nontea consumers as the reference, only consistent tea consumers had reduced risk of NCD (OR=0.39). Stratified analyses indicated that tea consumption was associated with reduced risk of NCD among females (OR=0.32) and APOE e4 carriers (OR=0.14) but not males and non APOE e4 carriers. Conclusion
Regular tea consumption was associated with lower risk of neurocognitive disorders among Chinese elderly. Gender and genetic factors could possibly modulate this association.
Ergothioneine (ET) is a diet-derived, thiolated derivative of histidine with antioxidant properties, at least in vitro. Although ET is produced only by certain fungi and bacteria, it can be found at high concentrations in certain human and animal tissues and is absorbed through a specific, high affinity transporter (OCTN1). In liver, heart, joint and intestinal injury, elevated ET concentrations have been observed in injured tissues. The physiological role of ET remains unclear. We thus review current literature to generate a specific hypothesis: that the accumulation of ET in vivo is an adaptive mechanism, involving the regulated uptake and concentration of an exogenous natural compound to minimize oxidative damage.
Decline in brain function during normal aging is partly due to the long-term effects of oxidative stress and inflammation. Several fruits and vegetables have been shown to possess antioxidant and anti-inflammatory properties. The present study investigated the effects of dietary mushroom intervention on mobility and memory in aged Fischer 344 rats. We hypothesized that daily supplementation of mushroom would have beneficial effects on behavioral outcomes in a dose-dependent manner. Rats were randomly assigned to receive a diet containing either 0%, 0.5%, 1%, 2%, or 5% lyophilized white button mushroom (Agaricus bisporus); after 8 weeks on the diet, a battery of behavioral tasks was given to assess balance, coordination, and cognition. Rats on the 2% or 5% mushroom-supplemented diet consumed more food, without gaining weight, than rats in the other diet groups. Rats in the 0.5% and 1% group stayed on a narrow beam longer, indicating an improvement in balance. Only rats on the 0.5% mushroom diet showed improved performance in a working memory version of the Morris water maze. When taken together, the most effective mushroom dose that produced improvements in both balance and working memory was 0.5%, equivalent to about 1.5 ounces of fresh mushrooms for humans. Therefore, the results suggest that the inclusion of mushroom in the daily diet may have beneficial effects on age-related deficits in cognitive and motor function.
This review summarizes the literature on the prevalence and incidence rates of dementia in Chinese populations, including survey results outside mainland China. We identified 15 prevalence studies and five incidence studies. The studies consistently reported sharply increased prevalence and incidence rates of dementia with increasing age. As estimated, there are at least 6,464,040 dementia patients in mainland China alone and we expect the number to rise in the coming decades. It is clear that dementia will be a new epidemic of the 21st century without major public health policies and preventive measures that target at the disease. We urge more research and hope that we will be able to prevent dementia or at least delay the onset in the near future with evidence-based measures.
Elevated homocysteine has emerged as a risk factor for cognitive impairment even in healthy elderly persons. Reduced brain volume and white matter hyperintensities also occur in healthy elderly as well, but the interrelationships between these have not been well studied. We report these interrelationships in non demented, relatively healthy, community-dwelling older adults from a single East Asian population.
Two hundred twenty-eight right-handed participants age 55 years and above were evaluated. Persons with medical conditions or neurological diseases other than well-controlled diabetes mellitus and hypertension were excluded. Participants underwent quantitative magnetic resonance imaging of the brain using a standardized protocol and neuropsychological evaluation. Plasma homocysteine, folate, vitamin B(12), and markers for cardiovascular risk: blood pressure, body mass index, fasting blood glucose, and lipid profile were measured.
Elevated homocysteine was associated with reduced global cerebral volume, larger ventricles, reduced cerebral white matter volume, and lower cognitive performance in several domains. Elevated homocysteine was associated with reduced white matter volume (β = -20.80, t = -2.9, df = 223, p = 0.004) and lower speed of processing (β = -0.38, t = -2.1, df = 223, p = 0.03), even after controlling for age, gender, and education. However, the association between homocysteine and lower speed of processing disappeared after controlling for white matter volume. Elevated homocysteine was not associated with white matter hyperintensity volume or with hippocampal volume. Although homocysteine and folate levels were correlated, their effects on white matter volume were dissociated.
In non demented, relatively healthy adults, elevated homocysteine is associated with lower cognitive scores and reduced cerebral white matter volume. These effects can be dissociated from those related to white matter hyperintensities or reduced folate level.
Introduction: Few studies have examined neuropsychiatric symptoms in community dwelling older adults with mild cognitive impairment (MCI). In the present study, we compared the prevalence of neuropsychiatric symptoms in older adults with normal cognition, MCI, and dementia in a population‐based sample.
Methods: Subjects were selected from the Singapore Longitudinal Ageing study. Normal cognitive function was defined as Clinical Dementia Rating (CDR) global score=0 and Mini‐Mental State Examination (MMSE) total score ≥24. MCI was defined as CDR global score=0.5, and dementia was defined as CDR global score ≥1. Neuropsychiatric Inventory (NPI) was administered on reliable informants for 293 subjects (136 normal, 133 MCI, and 24 dementia).
Results: The prevalence of neuropsychiatric symptoms (at lest one symptom) was 5.9% for normal cognition, 12.8% for MCI, and 50% for dementia. The most common neuropsychiatric symptoms in subjects with MCI were depression/dysphoria (6.8%), irritability/lability (3.8%), apathy/indifference (2.3%), and agitation/aggression (2.3%). NPI total score increased with increasing CDR global score ( P <0.001). The adjusted mean NPI total score was 0.07 (SEM=0.49) for normal cognition, 0.86 (SEM=0.46) for MCI, and 4.50 (SEM=0.82) for dementia.
Discussion: In community dwelling Asian older adults, we found an increasing prevalence of neuropsychiatric symptoms in subjects with normal cognition, MCI and dementia. Further studies with larger samples and strict criteria for MCI in an Asian population should be conducted.
Ergothioneine (ET) is a sulfur containing amino acid that functions as an antioxidant. Mushrooms are a primary source of ET containing from 0.4 to 2.0mg/g (dry-weight). The bioavailability of ET from mushrooms in humans remains unclear.
We evaluated the bioavailability of ET in healthy men (n=10) in a pilot study, using a randomized, cross-over, dose-response, postprandial time-course design, conducted at the General Clinical Research Center at Pennsylvania State University in 2009.
ET was administered through a mushroom test meal containing 8 g and 16 g of mushroom powder. Postprandial red blood cell concentrations of ET were measured. Plasma glucose, triglycerides, HDL, LDL and total cholesterol also were monitored. Biomarkers of inflammation and oxidative stress were evaluated using C-reactive protein and ORAC(total).
ET was bioavailable after consuming mushrooms and a trend in the postprandial triglyceride response indicated that there was a blunting effect after both the 8 g and 16 g ET doses were compared with the 0 g dose. Despite ET's antioxidant properties, ORAC(total) values decreased after the 8 g and 16 g mushroom meal.
Ergothioneine from A. bisporus mushrooms is bioavailable as assessed by red blood cell uptake postprandially, and consumption is associated with an attenuated postprandial TG response.
Since its discovery, the unique properties of the naturally occurring amino acid, L-ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine), have intrigued researchers for more than a century. This widely distributed thione is only known to be synthesized by non-yeast fungi, mycobacteria and cyanobacteria but accumulates in higher organisms at up to millimolar levels via an organic cation transporter (OCTN1). The physiological role of EGT has yet to be established. Numerous in vitro assays have demonstrated the antioxidant and cytoprotective capabilities of EGT against a wide range of cellular stressors, but an antioxidant role has yet to be fully verified in vivo. Nevertheless the accumulation, tissue distribution and scavenging properties, all highlight the potential for EGT to function as a physiological antioxidant. This article reviews our current state of knowledge. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.
A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly. Laboratory tests showed no adverse effect of Yamabushitake. The results obtained in this study suggest that Yamabushitake is effective in improving mild cognitive impairment.
The superoxide radical (O.2-) and nitric oxide (NO.) combine very rapidly to form peroxynitrite (ONOO-), a reactive tissue damaging nitrogen species thought to be involved in the pathology of several chronic diseases. The natural product ergothioneine protects against the nitration of tyrosine and the inactivation of alpha 1-antiproteinase by ONOO-. Ergothioneine merits further investigation as a biological and therapeutic antioxidant agent.
The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.