Next Article in Journal
Rutin, a Flavonoid Compound Derived from Garlic, as a Potential Immunomodulatory and Anti-Inflammatory Agent against Murine Schistosomiasis mansoni
Next Article in Special Issue
Mixed Berry Juice and Cellulose Fiber Have Differential Effects on Peripheral Blood Mononuclear Cell Respiration in Overweight Adults
Previous Article in Journal
cMIND Diet, Indoor Air Pollution, and Depression: A Cohort Study Based on the CLHLS from 2011 to 2018
Previous Article in Special Issue
Quercetin Is An Active Agent in Berries against Neurodegenerative Diseases Progression through Modulation of Nrf2/HO1
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Nutrients
Volume 15
Issue 5
10.3390/nu15051204
nutrients-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Considerations for Optimizing Warfighter Psychological Health with a Research-Based Flavonoid Approach: A Review

by
Tanisha L. Currie
1,*,
Marguerite M. Engler
1,
Victor Krauthamer
2,
Jonathan M. Scott
3,
Patricia A. Deuster
3 and
Thomas P. Flagg
4
1
Graduate School of Nursing, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
2
Department of Biomedical Engineering, George Washington University, Washington, DC 20052, USA
3
Consortium for Health and Military Performance, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
4
Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
*
Author to whom correspondence should be addressed.
Nutrients 2023, 15(5), 1204; https://doi.org/10.3390/nu15051204
Submission received: 16 January 2023 / Revised: 13 February 2023 / Accepted: 23 February 2023 / Published: 27 February 2023
(This article belongs to the Special Issue Berries, Metabolism, Bioenergetics, and Cognition)
Browse Figure
Versions Notes

Abstract

:
Optimal nutrition is imperative for psychological health. Oxidative stress and inflammation are underlying etiologies for alterations in psychological health. Warfighters are at risk of health concerns such as depression due to increased stress in austere environments and family separation while deployed. Over the last decade, research has demonstrated the health benefits of flavonoids found in fruits and berries. Berry flavonoids have potent antioxidant and anti-inflammatory properties by inhibiting oxidative stress and inflammation. In this review, the promising effects of various berries rich in bioactive flavonoids are examined. By inhibiting oxidative stress, berry flavonoids have the potential to modulate brain, cardiovascular, and intestinal health. There is a critical need for targeted interventions to address psychological health concerns within the warfighter population, and a berry flavonoid-rich diet and/or berry flavonoid dietary supplement intervention may prove beneficial as an adjunctive therapy. Structured searches of the literature were performed in the PubMed, CINAHL, and EMBASE databases using predetermined keywords. This review focuses on berry flavonoids’ critical and fundamental bioactive properties and their potential effects on psychological health in investigations utilizing cell, animal, and human model systems.

1. Introduction

Depression is the fourth leading cause of disability, impacting more than 264 million people globally [1]. The COVID-19 pandemic also increased rates worldwide, with reports of a rise in depressive symptoms in American adults [2,3]. Economically, the U.S. spends approximately $1 trillion on mental health and treatments [1]. When left untreated, depression can lead to suicidal ideation and attempts [4,5].
Many occupational groups, including law enforcement, healthcare and social worker professionals, artists, academia and administration, food service industries, and the government, are impacted by depression [6]. The highly trained and agile warfighter community is a group that embodies strength and resiliency; however, this community is not immune to the wider societal issues of depression and other mental health disorders, and it has suffered rising rates of depression and suicide [7]. The Armed Forces are consistently faced with the challenges of high-stress work environments and multiple deployments, which have led to high incidences of post-traumatic stress disorder (PTSD), major depressive disorder (MDD), substance abuse, obesity and being overweight, and other comorbid illnesses [8]. According to the Health of the Force report, 18% of warfighters were obese, and 15% of this vulnerable population had at least one behavioral health diagnosis [9]. Depression is prevalent in the warfighter population due to the intense performance demands and requirement to stay operationally fit and ready [10,11]. In a recent Armed Forces surveillance report, 853,060 active component service members were diagnosed with at least one mental health disorder, including depression [12].
Mental health and well-being can be enhanced by improving mood [13]. Mood can be described as an actual psychological state that can arise in response to an event [14]. The impact of mood is profound and can shape how things are perceived to influence behavioral, mental, and physical health [13,14]. There are two components of mood: Positive Affect (PA) and Negative Affect (NA). PA is the extent to which a person feels enthusiastic, vigorous, and alert [15], whereas NA is the extent to which a person feels distressed, angry, nervous, or depressed [15]. Depression, a state of low mood, lack of vigor, and diminished quality of life [16], is one characteristic of mood that affects a large proportion of the population with cardiovascular disease.
Currently, cognitive-based therapies and pharmacological treatments address negative moods and depression. Pharmacological treatments may be limited in their effectiveness, as their uptake into the brain may be restricted [17]. Additionally, antidepressant pharmacological therapies such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs) often have side effects, such as weight gain, insomnia, hypertension, and stroke in some individuals [18,19]. Therefore, novel and safe solutions are needed as preventive and adjunctive therapies to reduce depression and improve mood.
Mounting evidence suggests that nutrition and, in particular, foods containing flavonoids can affect symptoms of depression [10,20,21]. Flavonoids are a diverse group of secondary metabolites produced by plants that contribute to pigmentation and protect against pathogens [22]. They are commonly found in food and beverages, such as fruit, vegetables, tea, red wine, and chocolate [22]. Flavonoids can be divided into five subclasses: flavanones, isoflavones, flavanols, flavan-3-ols, and anthocyanins [23]. We recently showed that berry extracts inhibit oxidative stress in both cardiomyocyte and microglial cell cultures [24], suggesting that flavonoids derived from plants may be a promising approach to scavenge free radicals and decrease oxidative stress to reduce cell injury [25]. Here, we review recent studies that illustrate the potential promise of berry-derived flavonoids to improve psychological health.

2. Data Collection and Database Construction

The following databases were searched on 21 January 2020 for relevant articles: PubMed, CINAHL, and EMBASE. The literature search included combinations of keywords and appropriate subject headings for each database to retrieve articles focused on the use of flavonoids such as blackcurrant on mood and depression. Results were limited to those in the English language. The search strategy identified a total of 661 articles, and after the removal of 415 duplicate articles, 246 articles were screened. A total of 86 articles were reviewed, and the most relevant studies were included within the literature review. To ensure each concept was fully represented for blackcurrant, mood, and depression, incorporated terms such as “Ribes nigrum”, “Ribes americanum”, “Black currant”, “blackcurrant”, “Grossulariaceae”, “mood”, “depression”, and “depressive disorder” were used.
In an effort to update the most current literature, a second search was conducted on 15 April 2021 using the following databases for relevant articles: PubMed, CINAHL, Web of Science, and EMBASE. The literature search included combinations of keywords and appropriate subject headings for each database that retrieved studies focused on the use of cell models in the investigations with berry flavonoids and their effects on oxidative stress in cardiomyocyte and microglial cell lines. Results were limited to those in English only. To ensure each concept was fully represented for berry flavonoids, terms such as “bilberry”, “cherry”, “blueberry”, “lingonberry”, “elderberry”, “strawberry”, “cranberry”, and “depression and berry flavonoids” were used. For the concept of cell models, the following terms were included: “microglia”, “bv-2”, “cardiac muscle cell”, “rat-atrial-cell”, “cardiac myocyte”, “oxidative stress”, and “inflammation”. The search strategy identified a total of 89 articles. After the removal of 39 duplicate articles that appeared in the search engine results more than once, a total of 50 articles were reviewed, and the most relevant studies were included in the literature review.

3. Depression, Oxidative Stress, and Berry Flavonoids

The Monoamine Hypothesis of Depression proposes that altered psychological health is an imbalance of neurotransmitters. Neurotransmitters are instrumental in regulating mood, learning, memory, appetite, sleep, and other executive functions [26]. Decreasing levels of monoamine neurotransmitters can lead to impaired psychological health, such as depression [27]. To mitigate these harmful psychological impacts, standard pharmacological therapies, such as MAOIs, SSRIs, and SNRIs, are typically prescribed by healthcare providers to treat the neurotransmitter imbalances [26]. These pharmacological therapies are often effective; however, dietary substances may interact and interfere with their efficacy or cause adverse effects. An example of this is the “cheese effect” that occurs when tyramine, an ingredient found in cheese, interacts with MAOIs, leading to the acute onset of hypertension that may lead to serotonin accumulation and neurotoxicity [28]. Moreover, these treatments do not address the root cause that led to the imbalance in the first place.
Depression is also associated with cardiovascular disease [1,29]. A “vascular depression hypothesis” was proposed to underscore the link between depression and vascular diseases, including coronary artery disease, hypertension, and peripheral vascular disease. Alterations in vascular structure and the expression of endothelial cell molecules, such as nitric oxide, have been reported in individuals with depression [30]. This suggests that there may be a common mechanism linking the altered function of these two distinct physiological systems. Oxidative stress that occurs when there is an overproduction of reactive oxygen species (ROS) or an imbalance of antioxidants and ROS [31] emerged as a potential common threat. Inflammation and oxidative stress have independently been linked to both impaired psychological health, such as negative mood [32,33], and cardiovascular disease [1,29].
Lifestyle and environmental or occupational factors can contribute to the development of oxidative stress and lead to impaired neuronal and cardiovascular function (Figure 1). Studies suggest that impaired brain health may be related to the increased production of ROS and induced nitric oxide synthase, elevated cytokines, and increased inflammatory processes [34,35]. Over the last decade, flavonoids have garnered significant interest for their role in bolstering neuroplasticity and dendritic branching, which are necessary processes for neuronal function and connectivity [36]. These bioactive compounds also seem to be neuroprotective, inhibiting apoptosis and downregulating oxidative stress [24,37,38]. Notably, berries such as elderberry, black chokeberry, and blackcurrant are rich in flavonoids called anthocyanins that provide fruits, vegetables, and flowers their color pigments of red, blue, and purple hues [39,40]. Cyanidin 3-glucoside (C3G), a common bioactive ingredient found in berries, is the most frequently detected phenolic compound (out of a total of 203 compounds) in human urine and plasma after the consumption of berries [41]. C3G was detected in 69% of human plasma samples and 58% in urine samples after berry consumption [41]. C3G was also detected in the vascular endothelium and the brain [41]. This suggests that C3G is absorbed and taken up into the body’s tissues, and that it can cross the highly selective blood–brain barrier. Flavonoids can counter the negative cellular effects of oxidative stress and inflammation by modulating cellular signaling pathways [24,38,42]. Although it can vary based on the origin, seasonal conditions, preparations, and primary ingredients, anthocyanins contained in berries generally have a higher antioxidant capacity than other flavonoids [43].
The mechanisms underlying the potential benefit of flavonoids may reflect the combination of many different actions on inflammatory processes, downregulation of oxidative stress, and antioxidant effects. The potential health benefits of berry flavonoids as a nutritional intervention for individual health are illustrated in Figure 1. Excess ROS can damage the mitochondrial energy balance in nervous system, leading to compromised psychological health. Over time, this may also affect brain function and performance. We propose that flavonoid-rich foods can positively affect the warfighter’s psychological health by decreasing ROS and oxidative stress in neural mitochondria.

4. Evidence for the Benefits of Berry Flavonoids in the Treatment of Depression

Several studies have investigated the effects of flavonoids on mood as well as cognition [44,45,46]. Depression was found to be increased in older adults who had low intakes of fruits and vegetables [21]. Several studies also demonstrated the benefits of flavonoid-rich diets or beverages in reducing depressive symptoms [47,48,49]. In a double-blind, placebo-controlled crossover study investigating the effect of wild blueberry (WBB) drinks in young adults and children, drinking the WBB drink resulted in significantly higher positive affect scores than sipping the placebo beverage compared to baseline in young adults [50]. A similar improvement in positive affect was observed in children [50]. Similarly, following a diet rich in flavonoids from fruits as well as berries, vegetables, and chocolate for eight weeks was found to decrease depressive symptoms and improve general mental health statuses in mildly hypertensive patients [51]. Moreover, Watson et al. found blackcurrant increases alertness and lowers fatigue in healthy adults [52]. The results of these studies show that flavonoids may improve memory, attention, and cognitive reaction time in both human and animal models [53,54,55]. In a recent article, Kontaogianni et al. randomized participants with hypertension to consume either a low polyphenol diet (LPD), which consisted of two or fewer portions of fruits and vegetables per day with no dark chocolate, or a high polyphenol diet (HPD), which consisted of six portions of fruits and vegetables per day plus dark chocolate, over the course of eight weeks with a washout period [51]. The findings show that the participants within the HPD had reduced depressive symptoms and overall improved well-being in comparison to the control group [51]. Taken together, these studies suggest that berry flavonoids have a promising role in psychological health.
Studies also suggest that the amelioration of depressive-like behaviors correlates with the antioxidant activities of whole berry extracts or constituent flavonoids [51,56,57,58,59]. For example, a recent study showed that Grewia asiatica extracts improved depressive symptoms while increasing antioxidant activity in a rat model [60]. Similarly, blueberry extract improved the antioxidant profile and depression symptoms in a mouse model of depression [57]. In a more recent study, Lycium barbarum berry (Lyc), commonly referred to as Goji berry, was orally administered for four weeks to eight-week-old male rats in an ionizing radiation-induced depression and spatial memory impairment rodent model. Results showed improved cognition, spatial memory, and depression symptoms [61]. Although the Goji berry has potent antioxidant activity, it is unclear whether the positive effects in this study were due to improvement of ROS because it was not assessed. Several studies also demonstrated an antioxidant effect in microglial cells, the resident immune cells in the central nervous system [24,37,62,63]. The potent antioxidative effects of berry flavonoids can be helpful in mitigating harmful processes, and collectively, these studies support the hypothesis that flavonoids and particularly berry extracts can reduce depression through antioxidant effects, act as neuromodulators, and promote cognitive health.
There are other possible mechanisms of the beneficial actions of berry flavonoids. Studies analyzing the relationship between flavonoids and mood suggest that berry flavonoids may modulate monoamine neurotransmitter activity in the CNS [20,32,53]. Acute supplementation with flavonoid-rich blackcurrant was shown to inhibit MAO-A and MAO-B enzymes that suppress dopamine and serotonin levels [64]. Consistent with the positive effect of berry-derived flavonoids on psychological health, blackcurrant extract drinks decreased mental fatigue and improved cognition and mood in healthy adults after a 3-day intervention [64]. This was associated with changes in blood biomarkers, including reduced platelet MAO-B activity. In another study of the effects of blackcurrant juice on mood and physiological biomarkers following treadmill exercise in healthy, sedentary adults, results showed that consuming blackcurrant juice one hour before a walking exercise resulted in a 90% decrease in platelet MAO-B activity (p < 0.001) and remained at 25% of baseline by the end [65]. Although this study did not demonstrate significant differences in mood between the blackcurrant and placebo groups, it did provide measures of MAO-B enzyme activity and a brain health marker. In addition, plasma anthocyanin concentrations, the major components in blackcurrant (cyanidin glucoside, delphinidin glucoside, and cyanidin rutinoside), significantly increased in those receiving the treatments compared to those who received the control beverage. Taken together, these studies suggest that blackcurrant or blackcurrant extracts may modulate or downregulate MAO-B activity.
Alternatively, Hritcu et al. highlighted the relationship of antidepressant-like flavonoids and neuropsychiatric disorders through the suggested modulation of a neurotrophin called brain-derived neurotrophic factor (BDNF) [58]. BDNF plays a critical role in brain health, as it ensures proper neurotransmission, neuronal growth, plasticity, and survival [58,66]. Evidence showed various flavonoids enhanced BDNF expression in the hippocampus of mice models, attenuated oxidative stress and inflammatory properties, mimicked anti-depressant actions, and inhibited monoamine oxidase activities and L-arginine-NO pathways [58]. Earlier reports triangulated a link between decreased BDNF expression, high cortisol levels, and atrophy of the hippocampus with depression [58,66]. Diets possessing appropriate sources of naturally occurring bioactive compounds found in strawberries, grapes, other berry polyphenols, nuts, and spices were shown to play a critical role in hippocampus neurogenesis [67]; conversely, diets that are high in fats and refined sugar lead to decreased hippocampus neurogenesis and decreased BDNF, which is an essential factor in neuroplasticity [67]. Another pathway that has gained greater attention is nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 is a nuclear transcription factor, and it plays a significant role in protecting against oxidative stress by regulating antioxidant defense and detoxifying gene expression [68], which contributes to cytoprotection [68]. In a recent review highlighting the role of Nrf2 and natural flavonoid activators by Zuo et al., flavonoids such as curcumin, quercetin, and resveratrol reportedly reduced oxidative stress and inflammation, upregulated glutathione levels in vitro, diminished depressive-like behaviors within a mouse model, and decreased malondialdehyde (MDA) levels, which are a by-product of lipid peroxidation through Nrf2 activation [68].
Studies also point to other possible anti-inflammatory and neuroprotective mechanisms. Ebenezer et al. showed that rodents with induced post-traumatic stress disorder (PTSD) demonstrated a significant decrease in proinflammatory cytokines, TLR4, and HMGB1 post-2% blueberry enriched diet through a suggested role of antioxidant defense compared to the control group [69]. Similarly, kaempferol-3-glucoside and narirutin may potentially modulate depressive-like effects in the offspring of a rodent model, whereas a high-sugar diet increased expression of an inflammatory protein marker, TBK1, in the hippocampus [59]. In a study of anxiety-like behavior post-myocardial infarction (MI) in rodents, epigallocatechin-3-gallate (EGCG), which is commonly found in green tea, reduced anxiety-like behavior, decreased inflammatory and apoptosis markers of IL-6 (specifically, caspase 3, 8, and 9 mRNA), and downregulated the STAT3 protein [70]. This study supports a mechanism of action in which EGCG mitigated anxiety-like behavior through suppression of inflammation and apoptosis within the hippocampus of rats post-MI. The observation that flavonoids can affect microglia [24,37,62,63] suggests that the anti-inflammatory activity of berry extracts may provide anti-depressant effects.
It was also suggested that cardiovascular dysfunction, particularly in older individuals, can lead to the development of depression. The “vascular depression hypothesis” suggests that white matter damage resulting from ischemia may contribute to the onset of depression and cognitive dysfunction [71]. Moreover, rates of depression are elevated following myocardial infarction [72]. Cardiovascular disease continues to be a leading cause of death of Americans [73], and the U.S. active-duty military force is not exempt from its occurrence [9]. One recent study demonstrated that several different classes of anti-hypertensive drugs were associated with a reduced incidence of depression [72]. Several studies have also shown that flavonoids and berry-derived flavonoids improve cardiovascular health [42,62,74,75,76]. Understanding the potential role of flavonoids in cardiovascular health may also help to shed further light on their relationship to psychological health. In a randomized, double-blind, placebo-controlled classic study conducted by Engler et al., young healthy participants during a two-week period were randomized into either a high-flavonoid dark chocolate group or a low-flavonoid dark chocolate group for daily consumption [77]. Cardiovascular and blood marker measures were performed, including investigating the study participants’ flow mediated dilation (FMD) measures. FMD is a non-invasive functional test used to assess arterial blood flow, and it was conducted within this study to measure the effects of dark chocolate consumption in participants randomized to either the high-flavonoid dark chocolate group or the low-flavonoid dark chocolate group. Interestingly, the results show that the high-flavonoid dark chocolate group (containing the higher concentration of epicatechin levels) significantly improved (FMD) levels or increased endothelium-dependent vasodilation in comparison to the control group [77]. Moreover, there were no significant effects on cardiovascular-related blood markers following the study; however, there were significantly higher epicatechin levels found within the high-flavonoid dark chocolate group in comparison to the control group [77]. Either way, this study indicates that the consumption of high-flavonoid dark chocolate with its bioactive compound of epicatechin has health-promoting cardiovascular effects. In another study, the effect of a berry flavonoid, blackcurrant, on vascular health was investigated in a six-week study, measuring FMD and oxidative stress blood markers (i.e., F2-isoprostanes) in a healthy adult population that routinely consumed low amounts of flavonoids [78]. Results showed significant increases in FMD, vitamin C levels, and a significant reduction in F2-isoprostane levels with 20% blackcurrant juice compared to 6.4% blackcurrant juice and flavored water placebo groups [78]. Similarly, the low (6.4%) blackcurrant group also showed a significant reduction in oxidative stress measures; however, the 20% blackcurrant group demonstrated the greatest cardioprotective effect in reduced oxidative stress and improved FMD measures. Both studies illustrate that moderate to high flavonoid consumption had greater cardiovascular health benefits, such as reduced oxidative stress and improved arterial blood flow outcomes, within these human trial investigations. Additionally, prior work in the literature linked flavonoids and berry flavonoid consumption with improved cardiovascular performance. For example, prior evidence has shown increased cerebral blood flow, enhanced psychological health, and cognitive function following flavonoid consumption [53,79]. Although there is some evidence adding to our scientific knowledge associated with peripheral and central blood flow and its connection to flavonoids and psychological health [79], greater clarity is warranted in understanding the several underlying mechanisms.
Finally, there is an apparent bidirectional association between obesity (defined as a body mass index (BMI) of 30 kg/m2 or higher) and depression [80,81,82,83]. Schvey et al. found in their study consisting of 119 active-duty service members of both male and female participants that obesity and being overweight are associated with depressive symptoms, weight stigma, and maladaptive behaviors and eating patterns [84]. Berry flavonoids as a targeted nutritional approach against obesity may provide anti-inflammatory and antioxidant health benefits. For example, in a prospective cohort study consisting of approximately 124,000 men and women that healthcare professionals conducted over 24 years, the results showed that participants who consumed a high flavonoid diet self-reported less weight gain [85]. Although the soluble fiber present in flavonoids has been linked to contributions to weight loss, there may be other underlying mechanisms at play. In reviews by Sandova et al. and Tsuda et al., the potential mechanisms influencing the role of flavonoids in anti-obesity effects include downregulation of lipid accumulation and inhibition of lipogenesis in the liver. Moreover, there was increased browning of white adipose tissue (WAT) and stimulation of brown adipose tissue (BAT), which is important for storing of energy, fat metabolism, and burning calories in the body through induced thermogenesis [86,87]. It is also increasingly recognized that the function of the gut microbiome contributes to overall human health, including brain health [88]. It is postulated that anthocyanins may have inhibitory effects on epithelial cell inflammation, thereby supporting intestinal health through modulation of the gastrointestinal microbiota [89]. Bioactive compounds commonly found in berry flavonoids and teas, such as anthocyanins, quercetin, resveratrol, and EGCG, have shown, individually and collectively, promising actions on increased lipolysis, adiponectin signaling, modulating of the gut microbiota, and influences on body weight reduction [86,87].

5. Summary

In summary, the evidence reviewed demonstrates that berries and berry flavonoids can improve psychological health and cognitive function. There has been much compelling research on flavonoids influence on brain aging, neurodegeneration, and memory over the last decade [90,91]. Collectively, the results show that various fruit sources of flavonoids, such as blackcurrant and WBB, may improve mood and decrease fatigue. It is apparent that berries and berry flavonoids possess anti-depressant and anxiolytic effects in both animal and human studies. Despite the increase in research in the field, discerning the mechanisms of the beneficial effects of berry flavonoids remains a difficult challenge.
The complex actions of berry flavonoids that include the antioxidative and cytoprotective effects that may influence cell signaling pathways involved in neurotransmitter breakdown, neuron survival and proliferation, and inflammation have all been implicated as possible mechanisms of action. The association of obesity and cardiovascular disease with depression likely provides an important clue. Cardiovascular disease, obesity, and depression are all associated with persistent inflammation [92,93]. Remaining in a chronic inflammatory state not only disrupts organ dysfunction [92], but it can also instigate depression [94]. Hence, inflammation is a major link to metabolic dysfunction in the form of obesity, and evidence suggests that being in a state of chronic inflammation can trigger further cytokine activity, which can disrupt cellular functioning and overall psychological health. This suggests that targeting oxidative stress and chronic inflammation may be an ideal way to treat depression. Because berries offer a rich source of flavonoids that provide antioxidant and anti-inflammatory activity, this could be an excellent dietary approach.
It should be noted that there are limitations across these studies that must be acknowledged. These include the need for varied study populations and for investigation of additional biomarker endpoints. Further research and clinical trials are needed to explore the potential mechanisms of action of berry flavonoids and their effects on psychological health as well as the optimal dosages for well-being. Another limitation is the consistency of berry composition. The constituent flavonoids vary from berry to berry and from cultivar to cultivar. Thus, more research into the actions of individual bioactive flavonoids may provide a means to develop dietary supplements that provide consistent and reproducible effects.
The increasing rate of depression is a societal problem, and the warfighter population is not immune [12]. This population is heavily burdened with arduous occupational tasks that require a high level of mental acuity, skill, and physical stamina to achieve optimal performance [95]. Identifying beneficial nutritional strategies for the warfighter by leveraging scientific methodologies from the bench to the clinical level may elucidate novel and targeted nutritional interventions and technologies. These new innovations would have the potential to address warfighter injury, recovery, nutrition climate-sensitive rations, and countermeasures for warfighters exposed to extreme hot or cold conditions in austere environments. Using research-based, flavonoid-rich dietary supplements in conjunction with a whole-food, plant-forward diet may also optimize psychological and cognitive health where a whole-food, plant-forward diet is limited. As nutritional science continues to evolve, we must ensure that our nation’s most acceptable human weapon system, our warfighters, is optimally fueled and nourished to meet any demand at a moment’s notice. Strategically, we must also equip and assist our leaders and healthcare professionals through education and bring the science within the ranks to capitalize on warfighter nutrition readiness and psychological health.
The evidence presented here indicates that a research-based dietary supplement and/or increased consumption of a high-flavonoid diet, including berry flavonoids, may prove beneficial in this population. As a flavonoid supplement approach, more rigorous research would need to be conducted concerning product temperature sustainability in austere environments, shelf life, and appropriate flavonoid dosage. Moreover, this may be a portable and feasible solution toward increasing flavonoid intake within this group during austere heat and cold environments. For example, a fruit chew and/or a powdered berry flavonoid drink within warfighter rations or Meals Ready to Eat (MRE) may be of interest within this warfighter population. Providing a berry flavonoid in a portable form in a population in which mental health stigma and psychological risk factors are prevalent is of concern, and it may prove feasible and easy to adapt within the warfighter’s lifestyle.

6. Conclusions

Collectively, the findings presented here demonstrate that an assortment of berry flavonoids, such as blackcurrant and their bioactive compounds, and general flavonoids exert various effects with improvements in mood, depression, anxiety, cognitive performance, and overall psychological health. Further research is needed to better understand the varied effects of dietary flavonoids, but evidence supports the conclusion that increasing flavonoid consumption may be an adjunctive therapy for improved psychological health in the warfighter population.

Author Contributions

Manuscript writing—original draft preparation, writing—review and editing, and resources, T.L.C.; writing—review and editing and supervision T.P.F.; writing—review and editing, M.M.E.; original draft preparation, review, and editing, J.M.S.; writing—review and editing, P.A.D.; writing—review and editing, V.K. All authors have read and agreed to the published version of the manuscript.

Funding

We are grateful for the generous financial support and research resources from the TriService Nursing Research Program funding N21-02GR in preparation of this manuscript.

Acknowledgments

We would like to thank Sofia Echelmeyer and Linda Culp from the Uniformed Services University of the Health Sciences for assistance with figure preparation. We would also like to sincerely acknowledge and thank both Barbara Shukitt-Hale (US Department of Agriculture and Tufts University) and Alyssa Brooks (National Institutes of Health) for their editing and mentorship support for this article.

Conflicts of Interest

There are no conflict of interest. The opinions and assertions expressed herein are those of the author(s) and do not reflect the official policy or position of the Brooke Army Medical Center, the Uniformed Services University, the U.S. Army Medical Department of the Army, the Department of the Defense, or the U.S. Government.

References

  1. World Health Organization. Depression and Other Common Mental Disorders: Global Health Estimates; World Health Organization: Geneva, Switzerland, 2017. [Google Scholar]
  2. Lee, Y.; Lui, L.M.W.; Chen-Li, D.; Liao, Y.; Mansur, R.B.; Brietzke, E.; Rosenblat, J.D.; Ho, R.; Rodrigues, N.B.; Lipsitz, O.; et al. Government response moderates the mental health impact of COVID-19: A systematic review and meta-analysis of depression outcomes across countries. J. Affect. Disord. 2021, 290, 364–377. [Google Scholar] [CrossRef]
  3. Zheng, J.; Morstead, T.; Sin, N.; Klaiber, P.; Umberson, D.; Kamble, S.; De Longis, A. Psychological distress in North America during COVID-19: The role of pandemic-related stressors. Soc. Sci. Med. 2021, 270, 113687. [Google Scholar] [CrossRef]
  4. Moradi, Y.; Dowran, B.; Sepandi, M. The global prevalence of depression, suicide ideation, and attempts in the military forces: A systematic review and Meta-analysis of cross sectional studies. BMC Psychiatry 2021, 21, 510. [Google Scholar] [CrossRef]
  5. Brådvik, L.A.-O. Suicide Risk and Mental Disorders. Int. J. Environ. Res. Public Health 2018, 15, 2028. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Woo, J.M.; Postolache, T.T. The impact of work environment on mood disorders and suicide: Evidence and implications. Int. J. Disabil. Hum. Dev. 2008, 7, 185–200. [Google Scholar] [CrossRef] [Green Version]
  7. Inoue, C.; Shawler, E.; Jordan, C.H.; Jackson, C.A. Veteran and Military Mental Health Issues. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2021. [Google Scholar]
  8. Lazar, S.G. The mental health needs of military service members and veterans. Psychodyn. Psychiatry 2014, 42, 459–478. [Google Scholar] [CrossRef]
  9. Department of Defense. DoD Health of the Force 2021; Department of Defense: Washington, DC, USA, 2021; p. 98. [Google Scholar]
  10. Kris-Etherton, P.M.; Petersen, K.S.; Hibbeln, J.R.; Hurley, D.; Kolick, V.; Peoples, S.; Rodriguez, N.; Woodward-Lopez, G. Nutrition and behavioral health disorders: Depression and anxiety. Nutr. Rev. 2021, 79, 247–260. [Google Scholar] [CrossRef]
  11. Watrous, J.R.; McCabe, C.T.; Jones, G.; Farrokhi, S.; Mazzone, B.; Clouser, M.C.; Galarneau, M.R. Low back pain, mental health symptoms, and quality of life among injured service members. Health Psychol. Off. J. Div. Health Psychol. Am. Psychol. Assoc. 2020, 39, 549–557. [Google Scholar] [CrossRef] [PubMed]
  12. Stahlman, S.; Oetting, A.A. Mental health disorders and mental health problems, active component, U.S. Armed Forces, 2007–2016. Msmr 2018, 25, 2–11. [Google Scholar] [PubMed]
  13. Bar, M. A cognitive neuroscience hypothesis of mood and depression. Trends Cogn. Sci. 2009, 13, 456–463. [Google Scholar] [CrossRef] [Green Version]
  14. McConville, C.; Simpson, E.E.; Rae, G.; Polito, A.; Andriollo-Sanchez, M.; Meunier, N.; Stewart-Knox, B.J.; O’Connor, J.M.; Roussel, A.M.; Cuzzolaro, M.; et al. Positive and negative mood in the elderly: The ZENITH study. Eur. J. Clin. Nutr. 2005, 59 (Suppl. 2), S22–S25. [Google Scholar] [CrossRef] [Green Version]
  15. Watson, D.; Clark, L.A.; Tellegen, A. Development and validation of brief measures of positive and negative affect: The PANAS scales. J. Personal. Soc. Psychol. 1988, 54, 1063–1070. [Google Scholar] [CrossRef] [PubMed]
  16. Blazer, D.G. Depression in Late Life: Review and Commentary. J. Gerontol. Ser. A 2003, 58, M249–M265. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. O’Brien, F.E.; Dinan, T.G.; Griffin, B.T.; Cryan, J.F. Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: Clinical significance of in vitro and in vivo findings. Br. J. Pharmacol. 2012, 165, 289–312. [Google Scholar] [CrossRef] [Green Version]
  18. Herraiz, T.; Guillen, H. Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant Extracts with Potential Antidepressant Actions. Biomed Res. Int. 2018, 2018, 4810394. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  19. Crawford, A.A.; Lewis, S.; Nutt, D.; Peters, T.J.; Cowen, P.; O’Donovan, M.C.; Wiles, N.; Lewis, G. Adverse effects from antidepressant treatment: Randomised controlled trial of 601 depressed individuals. Psychopharmacology 2014, 231, 2921–2931. [Google Scholar] [CrossRef] [Green Version]
  20. Nabavi, S.M.; Daglia, M.; Braidy, N.; Nabavi, S.F. Natural products, micronutrients, and nutraceuticals for the treatment of depression: A short review. Nutr. Neurosci. 2017, 20, 180–194. [Google Scholar] [CrossRef]
  21. Payne, M.E.; Steck, S.E.; George, R.R.; Steffens, D.C. Fruit, vegetable, and antioxidant intakes are lower in older adults with depression. J. Acad. Nutr. Diet. 2012, 112, 2022–2027. [Google Scholar] [CrossRef] [Green Version]
  22. Khan, J.; Deb, P.K.; Priya, S.; Medina, K.D.; Devi, R.; Walode, S.G.; Rudrapal, M. Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns. Molecules 2021, 26, 4021. [Google Scholar] [CrossRef]
  23. Al-Khayri, J.M.; Sahana, G.R.; Nagella, P.; Joseph, B.V.; Alessa, F.M.; Al-Mssallem, M.Q. Flavonoids as Potential Anti-Inflammatory Molecules: A Review. Molecules 2022, 27, 2901. [Google Scholar] [CrossRef]
  24. Currie, T.; Engler, M.; Olsen, C.; Krauthamer, V.; Scott, J.; Deuster, P.; Flagg, T. The Effects of Blackcurrant and Berry Extracts on Oxidative Stress in Cultured Cardiomyocytes and Microglial Cells. FASEB J. 2022, 36, R2805. [Google Scholar] [CrossRef]
  25. Pietta, P.G. Flavonoids as antioxidants. J. Nat. Prod. 2000, 63, 1035–1042. [Google Scholar] [CrossRef]
  26. Yeung, A.W.K.; Georgieva, M.G.; Atanasov, A.G.; Tzvetkov, N.T. Monoamine Oxidases (MAOs) as Privileged Molecular Targets in Neuroscience: Research Literature Analysis. Front. Mol. Neurosci. 2019, 12, 143. [Google Scholar] [CrossRef] [Green Version]
  27. Nutt, D.J. Relationship of neurotransmitters to the symptoms of major depressive disorder. J. Clin. Psychiatry 2008, 69 (Suppl. 1), 4–7. [Google Scholar]
  28. Finberg, J.P.; Rabey, J.M. Inhibitors of MAO-A and MAO-B in Psychiatry and Neurology. Front. Pharmacol. 2016, 7, 340. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  29. Ménard, C.; Hodes, G.E.; Russo, S.J. Pathogenesis of depression: Insights from human and rodent studies. Neuroscience 2016, 321, 138–162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  30. Baruah, J.; Vasudevan, A. The Vessels Shaping Mental Health or Illness. Open Neurol. J. 2019, 13, 1–9. [Google Scholar] [CrossRef] [Green Version]
  31. Liguori, I.; Russo, G.; Curcio, F.; Bulli, G.; Aran, L.; Della-Morte, D.; Gargiulo, G.; Testa, G.; Cacciatore, F.; Bonaduce, D.; et al. Oxidative stress, aging, and diseases. Clin. Interv. Aging 2018, 13, 757–772. [Google Scholar] [CrossRef] [Green Version]
  32. Sturza, A.; Popoiu, C.M.; Ionica, M.; Duicu, O.M.; Olariu, S.; Muntean, D.M.; Boia, E.S. Monoamine Oxidase-Related Vascular Oxidative Stress in Diseases Associated with Inflammatory Burden. Oxid. Med. Cell. Longev. 2019, 2019, 8954201. [Google Scholar] [CrossRef]
  33. Lau, F.C.; Shukitt-Hale, B.; Joseph, J.A. Nutritional intervention in brain aging: Reducing the effects of inflammation and oxidative stress. Subcell Biochem. 2007, 42, 299–318. [Google Scholar] [PubMed]
  34. Simonyi, A.; Chen, Z.; Jiang, J.; Zong, Y.; Chuang, D.Y.; Gu, Z.; Lu, C.H.; Fritsche, K.L.; Greenlief, C.M.; Rottinghaus, G.E.; et al. Inhibition of microglial activation by elderberry extracts and its phenolic components. Life Sci. 2015, 128, 30–38. [Google Scholar] [CrossRef] [Green Version]
  35. Solleiro-Villavicencio, H.; Rivas-Arancibia, S. Effect of Chronic Oxidative Stress on Neuroinflammatory Response Mediated by CD4+T Cells in Neurodegenerative Diseases. Front. Cell. Neurosci. 2018, 12, 114. [Google Scholar] [CrossRef] [Green Version]
  36. Cichon, N.; Saluk-Bijak, J.; Gorniak, L.; Przyslo, L.; Bijak, M. Flavonoids as a Natural Enhancer of Neuroplasticity—An Overview of the Mechanism of Neurorestorative Action. Antioxidants 2020, 9, 1035. [Google Scholar] [CrossRef]
  37. Shukitt-Hale, B.; Kelly, M.E.; Bielinski, D.F.; Fisher, D.R. Tart Cherry Extracts Reduce Inflammatory and Oxidative Stress Signaling in Microglial Cells. Antioxidants 2016, 5, 33. [Google Scholar] [CrossRef] [Green Version]
  38. Rutledge, G.A.; Fisher, D.R.; Miller, M.G.; Kelly, M.E.; Bielinski, D.F.; Shukitt-Hale, B. The effects of blueberry and strawberry serum metabolites on age-related oxidative and inflammatory signaling in vitro. Food Funct. 2019, 10, 7707–7713. [Google Scholar] [CrossRef]
  39. Khoo, H.E.; Azlan, A.; Tang, S.T.; Lim, S.M. Anthocyanidins and anthocyanins: Colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food Nutr. Res. 2017, 61, 1361779. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  40. Di Lorenzo, C.A.-O.; Colombo, F.; Biella, S.; Stockley, C.; Restani, P.A.-O. Polyphenols and Human Health: The Role of Bioavailability. Nutrients 2021, 13, 273. [Google Scholar] [CrossRef] [PubMed]
  41. Sandoval-Ramírez, B.A.; Catalán, Ú.; Fernández-Castillejo, S.; Pedret, A.; Llauradó, E.; Solà, R. Cyanidin-3-glucoside as a possible biomarker of anthocyanin-rich berry intake in body fluids of healthy humans: A systematic review of clinical trials. Nutr. Rev. 2020, 78, 597–610. [Google Scholar] [CrossRef] [PubMed]
  42. Engler, M.M.; Engler, M.B. The Cardioprotective Effects of Flavonoids. Int. J. Cardiovasc. Dis. Diagn. 2020, 5, 042046. [Google Scholar]
  43. Yang, M.; Koo, S.I.; Song, W.O.; Chun, O.K. Food matrix affecting anthocyanin bioavailability: Review. Curr. Med. Chem. 2011, 18, 291–300. [Google Scholar] [CrossRef]
  44. Hein, S.; Whyte, A.R.; Wood, E.; Rodriguez-Mateos, A.; Williams, C.M. Systematic Review of the Effects of Blueberry on Cognitive Performance as We Age. J. Gerontol. A Biol. Sci. Med. Sci. 2019, 74, 984–995. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Bell, L.; Lamport, D.J.; Butler, L.T.; Williams, C.M. A Review of the Cognitive Effects Observed in Humans Following Acute Supplementation with Flavonoids, and Their Associated Mechanisms of Action. Nutrients 2015, 7, 10290–10306. [Google Scholar] [CrossRef]
  46. Nehlig, A. The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. Br. J. Clin. Pharmacol. 2013, 75, 716–727. [Google Scholar] [CrossRef] [Green Version]
  47. de Oliveira, N.G.; Teixeira, I.T.; Theodoro, H.; Branco, C.S. Dietary total antioxidant capacity as a preventive factor against depression in climacteric women. Dement. Neuropsychol. 2019, 13, 305–311. [Google Scholar] [CrossRef]
  48. Godos, J.; Castellano, S.; Ray, S.; Grosso, G.; Galvano, F. Dietary Polyphenol Intake and Depression: Results from the Mediterranean Healthy Eating, Lifestyle and Aging (MEAL) Study. Molecules 2018, 23, 999. [Google Scholar] [CrossRef] [Green Version]
  49. Hintikka, J.; Tolmunen, T.; Honkalampi, K.; Haatainen, K.; Koivumaa-Honkanen, H.; Tanskanen, A.; Viinamäki, H. Daily tea drinking is associated with a low level of depressive symptoms in the Finnish general population. Eur. J. Epidemiol. 2005, 20, 359–363. [Google Scholar] [CrossRef]
  50. Khalid, S.; Barfoot, K.L.; May, G.; Lamport, D.J.; Reynolds, S.A.; Williams, C.M. Effects of Acute Blueberry Flavonoids on Mood in Children and Young Adults. Nutrients 2017, 9, 158. [Google Scholar] [CrossRef] [PubMed]
  51. Kontogianni, M.D.; Vijayakumar, A.; Rooney, C.; Noad, R.L.; Appleton, K.M.; McCarthy, D.; Donnelly, M.; Young, I.S.; McKinley, M.C.; McKeown, P.P.; et al. A High Polyphenol Diet Improves Psychological Well-Being: The Polyphenol Intervention Trial (PPhIT). Nutrients 2020, 12, 2445. [Google Scholar] [CrossRef] [PubMed]
  52. Watson, A.W.; Okello, E.J.; Brooker, H.J.; Lester, S.; McDougall, G.J.; Wesnes, K.A. The impact of blackcurrant juice on attention, mood and brain wave spectral activity in young healthy volunteers. Nutr. Neurosci. 2019, 22, 596–606. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. Jäger, A.K.; Saaby, L. Flavonoids and the CNS. Molecules 2011, 16, 1471–1485. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  54. Shukitt-Hale, B.; Cheng, V.; Joseph, J.A. Effects of blackberries on motor and cognitive function in aged rats. Nutr. Neurosci. 2009, 12, 135–140. [Google Scholar] [CrossRef] [PubMed]
  55. Scholey, A.B.; French, S.J.; Morris, P.J.; Kennedy, D.O.; Milne, A.L.; Haskell, C.F. Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort. J. Psychopharmacol. 2010, 24, 1505–1514. [Google Scholar] [CrossRef] [PubMed]
  56. Kelly, E.; Vyas, P.; Weber, J.T. Biochemical Properties and Neuroprotective Effects of Compounds in Various Species of Berries. Molecules 2017, 23, 26. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  57. Spohr, L.; Luduvico, K.P.; Soares, M.S.P.; Bona, N.P.; Oliveira, P.S.; de Mello, J.E.; Alvez, F.L.; Teixeira, F.C.; Felix, A.O.C.; Stefanello, F.M.; et al. Blueberry extract as a potential pharmacological tool for preventing depressive-like behavior and neurochemical dysfunctions in mice exposed to lipopolysaccharide. Nutr. Neurosci. 2022, 25, 857–870. [Google Scholar] [CrossRef]
  58. Hritcu, L.; Ionita, R.; Postu, P.A.; Gupta, G.K.; Turkez, H.; Lima, T.C.; Carvalho, C.U.S.; de Sousa, D.P. Antidepressant Flavonoids and Their Relationship with Oxidative Stress. Oxidative Med. Cell. Longev. 2017, 2017, 5762172. [Google Scholar] [CrossRef] [Green Version]
  59. de la Garza, A.A.; Garza-Cuellar, M.A.; Silva-Hernandez, I.A.; Cardenas-Perez, R.E.; Reyes-Castro, L.A.; Zambrano, E.; Gonzalez-Hernandez, B.; Garza-Ocañas, L.; Fuentes-Mera, L.; Camacho, A. Maternal Flavonoids Intake Reverts Depression-like Behaviour in Rat Female Offspring. Nutrients 2019, 11, 572. [Google Scholar] [CrossRef] [Green Version]
  60. Imran, I.; Javaid, S.; Waheed, A.; Rasool, M.F.; Majeed, A.; Samad, N.; Saeed, H.; Alqahtani, F.; Ahmed, M.M.; Alaqil, F.A. Grewia asiatica Berry Juice Diminishes Anxiety, Depression, and Scopolamine-Induced Learning and Memory Impairment in Behavioral Experimental Animal Models. Front. Nutr. 2020, 7, 587367. [Google Scholar] [CrossRef]
  61. Guo, L.; Du, Q.-Q.; Cheng, P.-Q.; Yang, T.-T.; Xing, C.-Q.; Luo, X.-Z.; Peng, X.-C.; Qian, F.; Huang, J.-R.; Tang, F.-R. Neuroprotective Effects of Lycium barbarum Berry on Neurobehavioral Changes and Neuronal Loss in the Hippocampus of Mice Exposed to Acute Ionizing Radiation. Dose Response 2021, 19, 15593258211057768. [Google Scholar] [CrossRef]
  62. Isaak, C.K.; Petkau, J.C.; Blewett, H.; O, K.; Siow, Y.L. Lingonberry anthocyanins protect cardiac cells from oxidative-stress-induced apoptosis. Can. J. Physiol. Pharmacol. 2017, 95, 904–910. [Google Scholar] [CrossRef] [Green Version]
  63. Shao, Z.H.; Xie, J.T.; Vanden Hoek, T.L.; Mehendale, S.; Aung, H.; Li, C.Q.; Qin, Y.; Schumacker, P.T.; Becker, L.B.; Yuan, C.S. Antioxidant effects of American ginseng berry extract in cardiomyocytes exposed to acute oxidant stress. Biochim. Biophys. Acta 2004, 1670, 165–171. [Google Scholar] [CrossRef]
  64. Watson, A.W.; Haskell-Ramsay, C.F.; Kennedy, D.O.; Cooney, J.M.; Trower, T.; Scheepens, A. Acute supplementation with blackcurrant extracts modulates cognitive functioning and inhibits monoamine oxidase-B in healthy young adults. J. Funct. Foods 2015, 17, 524–539. [Google Scholar] [CrossRef] [Green Version]
  65. Lomiwes, D.; Ha, B.; Ngametua, N.; Burr, N.S.; Cooney, J.M.; Trower, T.M.; Sawyer, G.; Hedderley, D.; Hurst, R.D.; Hurst, S.M. Timed consumption of a New Zealand blackcurrant juice support positive affective responses during a self-motivated moderate walking exercise in healthy sedentary adults. J. Int. Soc. Sport. Nutr. 2019, 16, 33. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  66. Krishnan, V.; Nestler, E.J. The molecular neurobiology of depression. Nature 2008, 455, 894–902. [Google Scholar] [CrossRef] [Green Version]
  67. Poulose, S.M.; Miller, M.G.; Scott, T.; Shukitt-Hale, B. Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function. Adv. Nutr. 2017, 8, 804–811. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  68. Zuo, C.; Cao, H.; Song, Y.; Gu, Z.; Huang, Y.; Yang, Y.; Miao, J.; Zhu, L.; Chen, J.; Jiang, Y.; et al. Nrf2: An all-rounder in depression. Redox Biol. 2022, 58, 102522. [Google Scholar] [CrossRef] [PubMed]
  69. Ebenezer, P.J.; Wilson, C.B.; Wilson, L.D.; Nair, A.R.; J, F. The Anti-Inflammatory Effects of Blueberries in an Animal Model of Post-Traumatic Stress Disorder (PTSD). PLoS ONE 2016, 11, e0160923. [Google Scholar] [CrossRef] [Green Version]
  70. Wang, J.; Li, P.; Qin, T.; Sun, D.; Zhao, X.; Zhang, B. Protective effect of epigallocatechin-3-gallate against neuroinflammation and anxiety-like behavior in a rat model of myocardial infarction. Brain Behav. 2020, 10, e01633. [Google Scholar] [CrossRef]
  71. Taylor, W.D.; Aizenstein, H.J.; Alexopoulos, G.S. The vascular depression hypothesis: Mechanisms linking vascular disease with depression. Mol. Psychiatry 2013, 18, 963–974. [Google Scholar] [CrossRef] [Green Version]
  72. Kessing, L.V.; Rytgaard, H.C.; Ekstrøm, C.T.; Torp-Pedersen, C.; Berk, M.; Gerds, T.A. Antihypertensive Drugs and Risk of Depression: A Nationwide Population-Based Study. Hypertension 2020, 76, 1263–1279. [Google Scholar] [CrossRef]
  73. Benjamin, E.J.; Muntner, P.; Alonso, A.; Bittencourt, M.S.; Callaway, C.W.; Carson, A.P.; Chamberlain, A.M.; Chang, A.R.; Cheng, S.; Das, S.R.; et al. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation 2019, 139, e56–e528. [Google Scholar] [CrossRef]
  74. Gopalan, A.; Reuben, S.C.; Ahmed, S.; Darvesh, A.S.; Hohmann, J.; Bishayee, A. The health benefits of blackcurrants. Food Funct. 2012, 3, 795–809. [Google Scholar] [CrossRef]
  75. Barnes, M.J.; Perry, B.G.; Hurst, R.D.; Lomiwes, D. Anthocyanin-Rich New Zealand Blackcurrant Extract Supports the Maintenance of Forearm Blood-Flow During Prolonged Sedentary Sitting. Front. Nutr. 2020, 7, 74. [Google Scholar] [CrossRef] [PubMed]
  76. Kalt, W.; Cassidy, A.; Howard, L.R.; Krikorian, R.; Stull, A.J.; Tremblay, F.; Zamora-Ros, R. Recent Research on the Health Benefits of Blueberries and Their Anthocyanins. Adv. Nutr. 2020, 11, 224–236. [Google Scholar] [CrossRef]
  77. Engler, M.B.; Engler, M.M.; Chen, C.Y.; Malloy, M.J.; Browne, A.; Chiu, E.Y.; Kwak, H.K.; Milbury, P.; Paul, S.M.; Blumberg, J.; et al. Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J. Am. Coll. Nutr. 2004, 23, 197–204. [Google Scholar] [CrossRef]
  78. Khan, F.; Ray, S.; Craigie, A.M.; Kennedy, G.; Hill, A.; Barton, K.L.; Broughton, J.; Belch, J.J. Lowering of oxidative stress improves endothelial function in healthy subjects with habitually low intake of fruit and vegetables: A randomized controlled trial of antioxidant- and polyphenol-rich blackcurrant juice. Free Radic. Biol. Med. 2014, 72, 232–237. [Google Scholar] [CrossRef]
  79. Rees, A.; Dodd, G.F.; Spencer, J.P.E. The Effects of Flavonoids on Cardiovascular Health: A Review of Human Intervention Trials and Implications for Cerebrovascular Function. Nutrients 2018, 10, 1852. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  80. Luppino, F.S.; de Wit, L.M.; Bouvy, P.F.; Stijnen, T.; Cuijpers, P.; Penninx, B.W.; Zitman, F.G. Overweight, obesity, and depression: A systematic review and meta-analysis of longitudinal studies. Arch. Gen. Psychiatry 2010, 67, 220–229. [Google Scholar] [CrossRef] [PubMed]
  81. Vogelzangs, N.; Kritchevsky, S.B.; Beekman, A.T.; Brenes, G.A.; Newman, A.B.; Satterfield, S.; Yaffe, K.; Harris, T.B.; Penninx, B.W. Obesity and onset of significant depressive symptoms: Results from a prospective community-based cohort study of older men and women. J. Clin. Psychiatry 2010, 71, 391–399. [Google Scholar] [CrossRef] [Green Version]
  82. Jung, S.J.; Woo, H.T.; Cho, S.; Park, K.; Jeong, S.; Lee, Y.J.; Kang, D.; Shin, A. Association between body size, weight change and depression: Systematic review and meta-analysis. Br. J. Psychiatry J. Ment. Sci. 2017, 211, 14–21. [Google Scholar] [CrossRef] [Green Version]
  83. Nigatu, Y.T.; Bültmann, U.; Reijneveld, S.A. The prospective association between obesity and major depression in the general population: Does single or recurrent episode matter? BMC Public Health 2015, 15, 350. [Google Scholar] [CrossRef] [Green Version]
  84. Schvey, N.A.; Barmine, M.; Bates, D.; Oldham, K.; Bakalar, J.L.; Spieker, E.; Maurer, D.; Stice, E.; Stephens, M.; Tanofsky-Kraff, M.; et al. Weight stigma among active duty U.S. military personnel with overweight and obesity. Stigma Health 2017, 2, 281–291. [Google Scholar] [CrossRef]
  85. Bertoia, M.L.; Rimm, E.B.; Mukamal, K.J.; Hu, F.B.; Willett, W.C.; Cassidy, A. Dietary flavonoid intake and weight maintenance: Three prospective cohorts of 124,086 US men and women followed for up to 24 years. BMJ 2016, 352, i17. [Google Scholar] [CrossRef] [Green Version]
  86. Sandoval, V.; Sanz-Lamora, H.; Arias, G.; Marrero, P.F.; Haro, D.; Relat, J. Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral. Nutrients 2020, 12, 2393. [Google Scholar] [CrossRef]
  87. Tsuda, T. Recent Progress in Anti-Obesity and Anti-Diabetes Effect of Berries. Antioxidants 2016, 5, 13. [Google Scholar] [CrossRef] [Green Version]
  88. Anand, N.; Gorantla, V.R.; Chidambaram, S.B. The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders. Cells 2023, 12, 54. [Google Scholar] [CrossRef] [PubMed]
  89. Tan, J.; Li, Y.; Hou, D.X.; Wu, S. The Effects and Mechanisms of Cyanidin-3-Glucoside and Its Phenolic Metabolites in Maintaining Intestinal Integrity. Antioxidants 2019, 8, 479. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  90. Thangthaeng, N.; Poulose, S.M.; Miller, M.G.; Shukitt-Hale, B. Preserving Brain Function in Aging: The Anti-glycative Potential of Berry Fruit. Neuromol. Med. 2016, 18, 465–473. [Google Scholar] [CrossRef] [PubMed]
  91. Carey, A.N.; Fisher, D.R.; Bielinski, D.F.; Cahoon, D.S.; Shukitt-Hale, B. Walnut-Associated Fatty Acids Inhibit LPS-Induced Activation of BV-2 Microglia. Inflammation 2020, 43, 241–250. [Google Scholar] [CrossRef] [PubMed]
  92. Kawai, T.; Autieri, M.V.; Scalia, R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am. J. Physiol. Cell Physiol. 2021, 320, C375–C391. [Google Scholar] [CrossRef]
  93. Zhang, Z.; Zhao, L.; Zhou, X.; Meng, X.; Zhou, X. Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets. Front. Immunol. 2022, 13, 1098725. [Google Scholar] [CrossRef] [PubMed]
  94. Beurel, E.; Toups, M.; Nemeroff, C.B. The Bidirectional Relationship of Depression and Inflammation: Double Trouble. Neuron 2020, 107, 234–256. [Google Scholar] [CrossRef] [PubMed]
  95. Henning, P.C.; Park, B.S.; Kim, J.S. Physiological decrements during sustained military operational stress. Mil. Med. 2011, 176, 991–997. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Nutrients 15 01204 g001 550
Figure 1. The Effects of Berry Flavonoids on Brain Health.
Figure 1. The Effects of Berry Flavonoids on Brain Health.
Nutrients 15 01204 g001
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Currie, T.L.; Engler, M.M.; Krauthamer, V.; Scott, J.M.; Deuster, P.A.; Flagg, T.P. Considerations for Optimizing Warfighter Psychological Health with a Research-Based Flavonoid Approach: A Review. Nutrients 2023, 15, 1204. https://doi.org/10.3390/nu15051204

AMA Style

Currie TL, Engler MM, Krauthamer V, Scott JM, Deuster PA, Flagg TP. Considerations for Optimizing Warfighter Psychological Health with a Research-Based Flavonoid Approach: A Review. Nutrients. 2023; 15(5):1204. https://doi.org/10.3390/nu15051204

Chicago/Turabian Style

Currie, Tanisha L., Marguerite M. Engler, Victor Krauthamer, Jonathan M. Scott, Patricia A. Deuster, and Thomas P. Flagg. 2023. "Considerations for Optimizing Warfighter Psychological Health with a Research-Based Flavonoid Approach: A Review" Nutrients 15, no. 5: 1204. https://doi.org/10.3390/nu15051204

APA Style

Currie, T. L., Engler, M. M., Krauthamer, V., Scott, J. M., Deuster, P. A., & Flagg, T. P. (2023). Considerations for Optimizing Warfighter Psychological Health with a Research-Based Flavonoid Approach: A Review. Nutrients, 15(5), 1204. https://doi.org/10.3390/nu15051204

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop