Phytochemicals and Mental Health

Flavonoids are dietary antioxidant and anti-inflammatory compounds. Previously, Holland et al. demonstrated the links between flavonoids and cognition. In this current study, the authors (2022) explored the links between cognitive performance (episodic memory, global cognition, visuospatial ability, semantic memory, working memory, and perceptual speed) and the dietary intake of flavonoids and flavonol constituents (isorhamnetin, kaempferol, myricetin, quercetin) in a sample of 961 participants of the Rush Memory and Aging Project, a 6.9-year prospective cohort study of adults aged between 60-100 years old. An annual cognitive evaluation was done using 19 standardized tests, while dietary intake was evaluated through a validated semi-quantitative food frequency questionnaire. Analysis of the results revealed that increased dietary intake of flavonols and flavonol constituents decreased the rate of decline in episodic memory, perceptual speed, semantic memory, visuospatial ability, working memory, and global cognition. Furthermore, out of individual flavonol constituents, only quercetin and kaempferol were associated with significant decreases in the rate of cognitive decline. The authors conclude that the dietary consumption of flavonols and flavonol constituents may help reduce the rate of decline in cognitive abilities and global cognition in a population of seniors. [NPID: Flavonols, dietary intake, seniors, global cognition, cognitive domains]

Flavonoids were found to exert several beneficial impacts on health, such as antioxidant, anticancer, anti-inflammatory, neuroprotective, antiviral and cardio-protective effects. Flavonoids may represent a feasible bioactive intervention, and their effects depend on the type of flavonoid, its bioavailability and mechanism of action. In this study by Ullah et al. (2020), the authors highlight the current findings regarding the beneficial effects of individual flavonoids, isolation and synthesis methods, and currently available animal and human models. [NPID: Antioxidative, flavonoids, neuroprotective, polyphenols, quercetin]

Despite the progress in the understanding of Alzheimer’s disease (AD) pathogenesis and clinical course, advancing AD treatment beyond symptomatic intervention remains lacking. AD is a chronic neurodegenerative disease, characterized by amyloid beta (Aβ) peptide depositions that construct neurofibrillary tangles (NFTs). Recent evidence points to flavonoids as potential dietary interventions for AD treatment owing to their anti-inflammatory, antioxidant, anticholinesterase, and particularly their anti-amyloidogenic properties, where flavonoids were shown to help clear Aβ proteins and inhibit mTOR/autophagy signaling. In this review by Uddin et al. (2020), the authors explore the potential mechanisms behind the beneficial impact of flavonoids on AD and their role as novel therapeutic modalities. [NPID: Alzheimer’s disease, PI3K/Akt signaling, MAPK signaling, mTOR, amyloid plaque, flavonoids, neurofibrillary tangles]

Current studies point to the intake of fruits and vegetables to help protect against oxidative stress, aging, and neuroinflammation, processes that are thought to be involved in the pathophysiology of Alzheimer’s disease (AD). AD affects millions around the world, however, the majority of available treatment modalities are pharmacologically based, and our understanding of the risk factors for developing AD remains insufficient. Fruits and vegetables are thought to exert their beneficial properties through contained antioxidant and antiinflammatory phytochemical compounds. This review by Hartman & Ross (2018) highlights the currently available experimental and epidemiological evidence on the use of phytochemicals in the treatment of AD. The authors conclude by recommending the addition of bioactive phytochemicals as part of the dietary intervention to ameliorate the neuropathic insults and age-related derangements underlying AD. [NPID: Alzheimer’s disease, phytochemicals, fruits, vegetables, dietary intake]

Cerebral injuries cause a cascade of inflammatory events, namely, tissue responses in the form of reactive gliosis and microgliosis, and the secretion of inflammatory substances like cytokines, proteases, reactive oxygen, and nitrogen species. This cascade is thought to play a critical role in post-traumatic systemic and neuroinflammatory states and associated cognitive impairments seen in several neurological disorders. Standard treatment guidelines involve the use of non-steroidal anti-inflammatory drugs (NSAIDs) to control inflammation, however, their poor safety profile makes long term use unlikely. The use of naturally-occurring compounds as therapeutic alternatives is gaining traction due to their feasibility and their wide range of physiological effects. In the holistic practice of Ayurveda, Ashwagandha (Withania somnifera, Winter cherry) is a shrub with notable immunomodulatory properties. Gupta & Kaur (2018) built on their previous in vitro experiments, and aimed to investigate the use of a water extract from the Ashwagandha leaves (ASH-WEX) to treat systemic LPS-induced neuroinflammation and subsequent behavioral complications seen in an in vivo rat model. During the eight weeks of the study, it was observed that oral ASH-WEX administration substantially treated the anxiety-like behavior seen in rats, where treated rats achieved better Elevated Plus Maze test scores. In addition, the treated rats demonstrated significantly lower markers of brain tissue injury, systemic inflammation, and oxidative stress. The authors attribute these findings to identifying several activated pathways related to inflammatory suppression in rats as a result of ASH-WEX treatment (NFκB, P38, and JNK MAPKs). The authors conclude that their study demonstrates pioneering evidence to the anti-neuroinflammatory properties of ASH-WEX against LPS-induced neuroinflammation and its behavioral complications, inferring that Ashwagandha leaves and their contained phytochemicals may present a favorable foundation to develop new anti-neuroinflammatory interventions. [NPID: Anxiety-like behavior, Ashwagandha, inflammatory cytokines, lipopolysaccharide, neuroinflammation, reactive gliosis]

Polyphenols are plant compounds with unique structural elements that have several effects on our well-being and have been shown to help combat obesity, hyperglycemia and hyperlipidemia. Polyphenols are found in many plants, and are a topic of growing interest for their beneficial impact on stress. In this review, Sakakibara & Shimoi (2020) present a summary of the physiological reactions to stress and the biomarkers used to evaluate these reactions in animal studies and human trials. They also look at popular animal models used to measure the efficacy of anti-stress interventions, and discuss the recent findings from investigating the mechanism of action and impact of polyphenols on stress in animal models and human trials. The authors highlight that these recent findings necessitate more studies and human trials to further understand the impact of polyphenols on stress and their possible use as preventative measures against health complications related to stress. [NPID: Stress, polyphenols, plants, animal models, human trials]

Recently, the links connecting the diet we consume to our risk of experiencing mental disorders has gained significant attention, especially during the days of COVID-19 preventative measures and lockdowns. In this review, Álvarez et al. (2022) summarizes studies from popular repositories (Scopus, PubMed, and Google Scholar) to salvage data relating to ancestral diets (containing flowers, seeds, herbaceous plants, fungi, leaves, and tree barks) and the promotion of mental health. In the past, ancestral diets were components of human dietary patterns and affected foraging behaviors across several ecosystems. The authors comment that our comprehension of ancestral diets has deteriorated across generations, and thus this work sought to highlight food matrices used for nutritional or curative reasons, endorsed for their anxiolytic and antidepressant properties, and outline the role of metabolism and gut microbiome in transforming bioactive compounds in diet, in particular, polyphenols. [NPID: Ancestral food, anxiety, depression, microbiota, polyphenols]

Depression is a globally prevalent and crippling disease, afflicting individuals across the world regardless of their age. Although research on depression produced variable results, a common denominator seen in studies is the rise in inflammatory markers and oxidative stress associated with depression, which invariably, were found to be linked to the etiology and onset of depression. In this review by Behl et al. (2022), the authors outline oxidative stress and inflammatory markers seen in depressive disorders and the relationship between them and current treatment interventions. Natural polyphenols were found to have an inhibitory effect on various cell signaling pathways, including oxidative stress and inflammatory pathways, which potentiates polyphenols in preventing and treating depressive disorders. The authors highlight the part polyphenols play in treating depressive disorders, and argue that conducting further work to outline their mechanism of action and identifying their key compounds is necessary to develop innovative interventions to prevent and treat depressive disorders. [NPID: Antidepressants, depression, inflammation, oxidative stress, psychiatric disorders]

Polyphenols are natural organic compounds found in many plants consumed in our diets and carry several health benefits, including antidepressant properties. Although readily absorbed in our small intestine, polyphenols have complicated structures, resulting in a low bioavailability with their arrival at the large intestine virtually unchanged. The gut microbiome, however, acts on polyphenols, breaking them down into absorbable beneficial metabolites, thus helping to increase their bioavailability and allowing for their antidepressant effects to take place via the microbiota-gut-brain (MGB) axis. In return, the gut microbiota use polyphenol substrates for their nutrition, allowing them to flourish and maintain the intestinal barrier. In this review by Zhou et al. (2020), the authors outline the crucial relationship between the gut microbiome and the processing of polyphenols and/or their metabolic products, and the resultant antidepressant effects. The authors comment that this postulates the potential use of the gut microbiome as a target for treating depression. [NPID: Antidepressant, depression, gut microbiota, polyphenols, the microbial-gut-brain axis]

In this study, Gan et al. (2019) investigated whether bamboo leaf flavonoids had an impact on depressive symptoms in type 2 diabetic rats, and attempted to understand the mechanism by which flavonoids exerted their antidepressant effects. Male Sprague-Dawley (SD) rats at eight weeks of age were divided into 5 groups: Two control groups including one for the study design, a group which received bamboo leaf flavonoid diluted in solvent, a solvent control group and a final control group of normal rats that received the bamboo leaf flavonoid intervention. Depression was induced in the rats via administration of streptozotocin (STZ), and bamboo leaf flavonoids were administered for 12 weeks. To evaluate depression, the rats underwent Tail Suspension Tests (TST) and Forced Swimming Tests (FST), in addition to evaluating markers of cellular stress, inflammation and brain neurons via Western blotting, enzyme-linked immunosorbent assay (ELISA), and Nissl staining of brain samples, respectively. The authors observed that, compared to control groups, 12 weeks of bamboo leaf flavonoids treatment had improved mobility parameters in TST and FST, healthier brain hippocampal tissue and reduced inflammatory and cellular stress markers in treated rats. In conclusion, the authors state that treatment with bamboo leaf flavonoids helps improve symptoms and signs of depression in diabetic rats, as evident by healthier brain tissue and a reduction in inflammatory markers, and by inhibition of cellular stress pathways in treated rats compared to controls. [NPID: Depression, diabetes mellitus, type 2, flavonoids, hippocampus, rats, animal]

Mental disorders grew to become an increasing concern for public health across the world. Current research has revealed the existence of a relationship between nutrition and disorders such as depression and anxiety, hinting at the role changes our diet and nutritional supplements may play in improving our mental health. Polyphenols, available in several plants consumed as part of our diet, were found to possess anti-inflammatory and antioxidant activities that can modify the physical changes seen in depression and anxiety. In their study, Lin et al. (2021) aimed to investigate the impact polyphenol supplements may have on depression, anxiety and Quality of Life (QoL). The authors conducted a systematic review and meta-analysis of randomized controlled trials that scored a “moderate” quality or higher (as per the Physiotherapy Evidence Database) and which employed polyphenols to target depression, anxiety and/or QoL. They ultimately selected 18 studies that investigated a total of 1,523 patients suffering from depression, finding that most literature supports a substantial improvement of symptoms of depression and depressive symptoms scores with polyphenol supplementation compared to controls. Furthermore, two out of five studies found substantial improvements in QoL, while in five out of six studies that investigated anxiety, the results showed a substantial improvement in depression scores. However, no differences were found in terms of anxiety symptoms with polyphenol supplementation compared to controls. Thus, the authors conclude that polyphenol supplementation may be a worthwhile treatment option for depression, while acknowledging that physical illnesses and their symptoms exert a notable impact on the course of depression and, hence, they may also benefit from using polyphenol supplements as a preventative measure. The authors comment that due to the various polyphenols available, certain polyphenols may be more effective than others depending on their application, and further work is necessary to identify how distinct varieties of depression could benefit from certain polyphenols compared to others. [NPID: Anxiety, depression, nutrition, polyphenol, quality of life]

Depression is a prevalent mental health disease that impacts over 350 million individuals across the globe. Current research postulates that dietary choices may protect against depression, with several studies highlighting the benefits of the Mediterranean diet (rich in vegetables and olive oil, and including moderate amounts of protein) on depression. A potential theory as to why the Mediterranean diet exerts these effects is due to boasting elevated levels of polyphenols. Thus, Bayes et al. (2020) conducted this systematic literature review to investigate the impact of polyphenols found in the Mediterranean diet on depression. By searching through several databases (PROQUEST, SCOPUS (Elsevier), MEDLINE (EBSCO), CINAHL, and EMBase, up to 18 February, 2019) and selecting 20 observational and 17 experimental studies that included adults ages 18-80 years and by assessing depression scores in relation to polyphenol intake from several sources (tea, coffee, citrus, nuts, soy, grapes, legumes, and spices), the authors found that 29 studies reported a substantial polyphenol impact on improving symptoms of depression. Furthermore, this review found links between consuming polyphenols and the odds of suffering from depression, in addition to a substantial relationship between consuming polyphenols and a reduction in the symptoms of depression. The authors conclude that their review discovered areas necessitating further studies to fully outline the beneficial part polyphenols may play in treating depressive symptoms in both young and adult male populations. [NPID: Depression, flavonoids, major depressive disorder, mental health, phytochemicals, polyphenols, Mediterranean diet]

Current literature has demonstrated that dietary patterns may be related to the onset and course of mental health disorders such as depression, specifically, diets rich in plants, herbal beverages and nutritional supplements, which contain a high concentration of flavonoids (natural phenolic compounds found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine). Ali et al. (2021) endeavored to drive a systematic review investigating how flavonoids in our diet can impact depressive symptoms. 46 studies were selected (36 interventional trials with a collective total of 2,788 participants and 10 observational studies) and their subsequent analysis showed that consuming flavonoids lead to a substantial reduction in the symptoms of depression experienced by the participants, which postulates that a high intake of flavonoids may be beneficial to individuals suffering from depressive symptoms. The authors conclude that further work is critical to further the understanding of the mechanisms driving the response to flavonoid consumption, including central nervous system responses. [NPID: Antioxidants, depression, diet, flavonoids, mental health, oxidative stress]

Depression is a critical mental health disorder that has a chronic course, and is prone to deterioration if treatment is not administered promptly. Recent literature demonstrated the relationship between the gut microbiome and the brain through the microbiome-gut-brain axis. In this study by Park et al. (2020), the authors investigated the results of flavonoid consumption on depression through evaluating alterations in gut microbiome and symptoms of depression following the administration of flavonoid-rich orange juice to young participants over the course of eight weeks. Depressive symptoms were evaluated via the Center for Epidemiological Studies Depression Scale (CES-D). The results showed that, compared to control participants, the consumption of flavonoid-rich orange juice lead to an increase of the Lachnospiraceae family of the gut microbiome, which relates to higher levels of brain-derived neurotrophic factor (BDNF; a neurotrophin that is involved in the therapeutic response to antidepressants). The authors conclude that these results present gut microbiome alteration using flavonoids as a new approach to treating depression in young adults. [NPID: Lachnospiraceae, depression, flavonoid treatment, microbiota]

The diets we consume play a critical part in the onset and course of depression. Carotenoids have substantial antioxidant and anti-inflammatory properties, however, the literature exploring the potential links between carotenoid consumption and symptoms of depression remains insufficient. Thus, Ge at al. (2020) conducted this cross-sectional study to investigate the relationship between carotenoids in diet and the odds of experiencing symptoms of depression in a population of adults (17,401 participants, 18-80 years) selected from the United States National Health and Nutrition Examination Survey between 2009 and 2016. The participants recorded their diets through two 24-h dietary recall interviews, and had their depressive symptoms evaluated via the Patients' Health Questionnaire-9 (PHQ-9). The results demonstrated that consumption of carotenoids in diet, especially alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin, are related to a substantial decrease in the risk of experiencing symptoms of depression, inferring that carotenoid consumption protects against depression. [NPID: NHANES, depressive symptoms, dietary carotenoid intakes, dose–response relationship, restricted cubic spline models, PHQ-9]

Spurred by a lack of sufficient studies investigating the impact of dietary carotenoids on depression, Lin & Shen (2021) conducted their study to explore the links between carotenoids found in diet and the pervasiveness of symptoms of depression. Selecting a population of 4,105 adults from the 2015-2016 United States National Health and Nutrition Examination Survey, the authors evaluated dietary consumption using two 24-h dietary recall interviews, and for symptoms of depression through the nine-item Patient Health Questionnaire (PHQ-9). The analyses revealed a significant decrease of symptoms of depression with intake of beta-cryptoxanthin above 110 ug/1000 Kcal, but no changes were observed with either alpha-carotene, beta-carotene, lycopene, or lutein/zeaxanthin. Thus, the authors conclude that consuming a diet rich in beta-cryptoxanthin may confer protection against symptoms of depression, and that further research is necessary to state informed dietary recommendations. [NPID: Beta-cryptoxanthin, carotenoids, depression, dose-response, NHANES, PHQ-9]

Phytochemicals are a class of biologically active nutrient compounds found in plants, and serve several nutritional and immunoprotective functions. Some phytochemicals possess antioxidant properties, such as flavonoids and carotenoids, which were found to protect against symptoms of depression when consumed in diet. Park et al. (2021) conducted this study to investigate the impact of flavonoid and carotenoid consumption on symptoms of depression in a population of adult females. Depression was investigated using the Beck Depression Inventory-II (BDI-II), while dietary intake of flavonoids and carotenoids was evaluated through a semi-quantitative food frequency questionnaire. The authors found that an intake of flavones, anthocyanins, individual phenolic compounds, lycopene, and zeaxanthin lead to a substantial decrease in symptoms of depression. To understand the nature of this finding further, the authors conducted an in silico analysis (pharmacological analysis using computational models) of the flavonoids, revealing that flavonoids had a high propensity to bind with monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB), which are two key enzymatic targets in the pathology of depression. This binding resulted in enhancing the activation of brain-derived neurotrophic factor (BDNF) by carotenoids. The authors conclude that these findings present the potential mechanism through which flavonoids and carotenoids impact symptoms of depression, and the promise they hold as prospective dietary modalities to treat symptoms of depression. [NPID: Carotenoids, depression, flavonoids, in silico]

Depression is a grave mental health disorder that elicits several complications, including poor quality of life, behavioral problems, and limitations of activities of daily living, in millions of patients globally. Identifying new therapeutic options to combat depression is an area of continuously growing interest, and more recently, the links between oxidative stress and the onset of depression. Flavonoids are naturally-occurring plant compounds that were found to induce antidepressant-like activity, amongst their several physiological and biochemical effects on the human body. Recent evidence on the use of antioxidant flavonoids as novel dietary interventions to treat symptoms of depression revealed substantial promise of their potential to herald creative antidepressant pharmacotherapeutic agents. In this review by Hritcu et al. (2017), the authors highlight the chemical and pharmacological mechanisms behind the antidepressant activity of flavonoids, and their impact on oxidative stress relative to the pathology of depression. [NPID: Depression, flavonoids, antidepressant, oxidative stress]

Depression and anxiety are prevalent mental health disorders that affect around 20% of the global population. Research aimed at creating innovative treatment interventions is ongoing, however, current pharmacological treatment for emotional disorders require a long treatment course (up to weeks) before they start eliciting a positive response on a patient’s emotional state, not to mention the significant side effects associated with such interventions. Flavonoids are plant-derived natural compounds (in sources such as fruits, vegetables, and medicinal herbs) that have beneficial therapeutic properties, and have been shown to hold promise in the treatment of emotional disorders, such as anxiety and depression, through several studies. In this review, Ko et al. (2020) look at the recent evidence highlighting flavonoids as promising vectors for the treatment of depression and anxiety, and their use in the development of new interventional pharmacotherapeutics. The authors compiled current works which investigated distinct flavonoid compounds, outlined their mechanism of action in emotion-related disorders, and discussed their behavioral, molecular, physiological, and neurochemical aspects, be it on a cellular level or on animal models. [NPID: Anxiety, depression, emotional disorders, flavonoids, mechanisms of action, therapeutic effects]

Flavonoids, which are biologically active chemicals found in plants, have been shown to have significant physiological functions that benefit our health, however, flavonoids are not readily absorbed in the intestine and require pre-processing through the intestinal gut microbiota. Flavonoids, in turn, influence the gut microbiome population by providing the microbiome with nutrients from their breakdown, and thus help in improving overall gut health. Studies have shown that the onset of mental health disorders such as depression is linked to changes in the gut microbiome that influence the gut-brain axis. Taking this into account, Zhao et al. (2021) present their work on how the relationship between flavonoids and the gut microbiome may be utilized to treat symptoms of depression. [NPID: Bioavailability, depression, flavonoids, intestinal microbiota]

Depression is one of the most prevalent mental health disorders, afflicting thought, emotional state, behavior, and the general welfare of patients. The WHO projects that depression would be the first suspect behind several other prevalent diseases by 2030. Currently available pharmacological therapy for depression is riddled with poor safety profiles, chronicity of treatment course, and poor response due to the complex nature of depressive disorders. Furthermore, pharmacotherapeutics cannot be administered until the patients suffer from significant impairment to activities of daily life, and have a narrow scope of physiologic action. In comparison, plant-occurring natural compounds, such as flavonoids, were shown to have a wide scope of physiologic action, interacting with several molecular and neuronal pathways to exert their antidepressant activity. Pannu et al. (2021) speculate that flavonoids would be beneficial in individuals who are on the precipice of developing clinical depression, and endeavored through their review to examine pre-clinical depression studies and the links between structure and action of flavonoids, and to outline recommendations for clinical trials aimed at developing flavonoid-based novel antidepressants. [NPID: Anti-depressants, anti-oxidant, depression, flavonoids, nutraceuticals]