*3.9. Vegetables and Fruit*

The results of the studies related to vegetables and fruit were largely positive (Figure 12). The majority (64%, *n* = 60) of the studies were conducted in animal models. These trials involved the administration of single fruits or vegetables and 58 of 60 reported a reduction in anxiety symptom severity. The most commonly studied foods included citrus fruits (*n* = 13), grape (*n* = 7), berries (*n* = 6), pomegranate (*n* = 6), fennel (*n* = 4), and lettuce (*n* = 4) with a wide variety of vegetables and fruits used in the remaining studies. Several observational studies reported an association between higher fruit and vegetable intake and lower levels of anxiety symptoms or disorder prevalence. A small number of intervention studies increased intake of individual vegetable or fruits; studies delivering cherries, tomato juice, orange juice, and fennel reported reduction of anxiety symptom severity. Three experimental studies delivered interventions aimed at increasing intake of vegetable and/or fruit servings consumed by participants [46–48]. Two reported a decrease in anxiety symptoms. None of the human experimental studies involved participants with anxiety disorders.

**Figure 12.** Studies assessing vegetables and/or fruit and anxiety. ■ Higher intake or levels associated with decreased anxiety. ■ No association between intake or levels and anxiety. ■ Higher intake or levels associated with increased anxiety.

#### *3.10. Phytochemicals*

A large number of studies have explored the effects of caffeine on anxiety symptoms (Figure 13). Many of these animal (*n* = 37) and human experimental (*n* = 33) studies administered caffeine as a supplement or provided energy drinks to subjects. While the animal studies reported a mixture of anxiogenic and anxiolytic effects, the observational and human experimental studies were more likely to report worsening anxiety symptoms with higher intake of caffeine. Several animal and human experimental studies assessed the impact of green tea and its constituents epigallocatechin-3-gallate (EGCG) and l-theanine on anxiety levels. The studies reported primarily anti-anxiety effects; however, a meta-analysis of trials delivering L-theanine and EGCG failed to detect a significant benefit [49].

Anti-anxiety effects have been reported in animal studies assessing a wide range of plants and plant constituents that may be found in the North American diet with primarily anxiolytic findings reported. These included culinary herbs (rosemary, cinnamon, coriander, basil, and nigella), herbal teas (chamomile, hibiscus, and rose tea), the phytonutrients curcumin (found in turmeric), quercetin (found in various vegetables and fruits), resveratrol (found in grapes), saffron and its constituents, soy and its constituents and other phytoestrogenic foods, nut and seed extracts, chocolate and cocoa and a variety of flavonoids, polyphenols, and carotenoids. Additionally, human experimental studies delivering green tea, curcumin, saffron, chamomile, and soy also reported anti-anxiety effects. Meta-analyses of experimental studies using chamomile [50], saffron [51], and curcumin [52,53] found a decrease in anxiety symptoms, while the meta-analysis of studies administering resveratrol reporting a non-significant improvement [54]. A small number of the human experimental studies involved participants with anxiety disorders including

three studies using chamomile [55–57], two using saffron [58,59], one using curcumin [60], and one using l-theanine [61]. All trials, with the exception of the l-theanine study [61], reported a reduction in anxiety symptoms severity.


**Figure 13.** Studies assessing phytochemicals and anxiety \* Culinary Herbs: rosemary, cinnamon, coriander, basil, nigella; Herbal tea: chamomile, hibiscus, rose tea. ■ Higher intake or levels associated with decreased anxiety. ■ No association between intake or levels and anxiety. ■ Higher intake or levels associated with increased anxiety.

#### *3.11. Food Allergy and Intolerance*

A small body of evidence, primarily observational in nature, suggests a possible connection between food allergy or intolerance and anxiety symptoms (Figure 14). Eleven of thirteen studies found higher levels of anxiety symptoms in participants with celiac disease or a food allergy. Consumption of a gluten-free diet or avoidance of other food allergens was associated with improved anxiety symptoms in observational studies and two case reports. Seven experimental studies have assessed these diet interventions with three reporting benefit. Participants were predominantly irritable bowel syndrome sufferers; none included individuals with anxiety disorders.


**Figure 14.** Studies assessing food allergies or sensitivities and anxiety. ■ Higher intake or levels associated with decreased anxiety. ■ No association between intake or levels and anxiety. ■ Higher intake or levels associated with increased anxiety.

#### *3.12. Gut Microbiome*

A number of studies have assessed the impact of probiotic and prebiotic supplementation in animals and humans (Figure 15). Animal trials have reported significant improvement in anxiety symptoms with supplementation of *Lactobacillus* strains, *Bifidobacterium* strains, combinations of *Lactobacillus* and *Bifidobacterium* strains, prebiotics, and synbiotics (combinations of prebiotics and probiotics). Interventions aimed at increasing

microbiome diversity or addition of fermented foods or fiber were associated with decreased anxiety symptom severity. Administration of pathogenic organisms and antibiotics were associated with worsening anxiety symptom severity.


**Figure 15.** Studies assessing the microbiome and anxiety. ■ Higher intake or levels associated with decreased anxiety. ■ No association between intake or levels and anxiety. ■ Higher intake or levels associated with increased anxiety.

> Among the human studies, predominantly positive findings were reported by trials administering *Bifidobacterium* strains and multi-strain probiotics while trials administering *Lactobacillus* strains, combinations of *Lactobacillus* and *Bifidobacterium* strains, and prebiotics reported either positive findings or no effect. Two trials involved participants with anxiety disorders [62,63]; one reported a benefit [63]. Three meta-analyses have pooled the trials assessing anxiety outcomes following probiotic supplementation [64–66]; one of three reported a significant improvement [65].
