Table 2.

Biological, lifestyle, and mind-body medicines for mental health disorders and physical co-morbidities (Can be an appendices if required)

Therapy	Supporting evidence for effectiveness—mental health disorders	Supportive evidence for effectiveness—physical health
Exercise	A recent meta-review of exercise for the European Psychiatric Association’s guidelines confirmed significant symptomatic improvements for those with major depression or psychotic disorders, when used as an adjunctive treatment [118] Exercise may also provide effective first-line treatment for those with moderate depression [69] and may act as a preventative intervention; as physical activity significantly reduces the risk of developing depression or anxiety disorders [119, 120]	Exercise is associated with reduced risk of 26 difference types of cancer including breast, colorectal, esophageal, liver, and lung cancer [121]. Exercise training results in improvements in physical functioning, quality of life and cancer fatigue in several cancer survivor groups [122] Sedentary behavior is associated with greater risk for cardiovascular disease, cancer and type 2 diabetes [123] Exercise reduces the risk of cardiovascular disease and stroke in men and women by 20–30% and 10–20% respectively [124], of type 2 diabetes by 35% [125] and of all-cause and Alzheimer’s dementia by 10% and 13% respectively [126]
Mindfulness-based interventions (MBIs)	MBIs are more effective than treatment as usual, no treatment, non-specific active controls and specific active controls for common mental disorders, and similar in effectiveness to other active control conditions such as cognitive behavioural therapy [127, 128]. Effects in severe mental illness yet to be assessed. It should be noted that methodological quality of some studies in this field are poor, and overly enthusiastic conclusions may need to be tempered Yoga as an example: Moderate evidence for short-term effects for depression severity compared to usual care, limited evidence compared to relaxation, aerobic exercise [129] A 2013 meta analysis reported no evidence for any effect on positive or negative symptoms of schizophrenia, and moderate evidence for short-term effects on quality of life in high risk of bias studies [130]. A 2017 Cochrane Review reported Minimal differences between yoga and non-standard care (exercise), with the evidence too weak to draw any conclusions [131]	May help with adherence to lifestyle interventions. A number of meta-analyses suggest that mindfulness-based interventions may be beneficial in weight loss and in reducing obesity-related eating behaviours [72–75] Mindfulness-based interventions may be beneficial for people with diabetes by reducing depression, anxiety and distress symptoms, but their effect on physiological outcomes is mixed [132] Low quality evidence suggests mindfulness may have a small effect on improving chronic pain [133] Mindfulness-based interventions are beneficial for anxiety and depression symptoms in people with cancer [134] Randomised controlled trials have reported that mindfulness based interventions improve fatigue [135, 136] sleep quality [137] enhance psychosocial adjustment and quality of life [138] in women with breast cancer Promising evidence for cardiometabolic health (small changes in BP, lipids, BMI) [139] Reduces HbA1c by 0.39% compared to physical exercise in people with T2D [140] Recommended by the American Society of Clinical Oncology for anxiety, stress reduction, depression, mood disturbance, and improved quality of life in people with cancer [141] Improve health-related quality of life in individuals with substance abuse disorders [142], more effective than waitlist control for reducing consumption of illicit substances and alcohol although findings are limited by small sample sizes, inconsistent results [143]
Diet	Meta-analyses of RCTs confirm the benefits of dietary improvement for reducing symptoms of depression across the population [70]. In particular, three recent clinical trials have also reported the benefits of Mediterranean diet interventions on depression and depressive symptoms [144–146]	An umbrella review of observational studies and randomised controlled trials reported that greater adherence to the Mediterranean diet reduces risk for overall mortality, cardiovascular diseases, coronary heart disease, myocardial infarction, overall cancer incidence, neurodegenerative diseases and diabetes [147] Other examples include: An observational study suggests high adherence to the DASH, Mediterranean or a hybrid DASH-Mediterranean (MIND) diet may reduce risk of Alzheimer’s disease [148] Flavonol intake improves CV risk factors [149] Healthful plant-based diets reduce diabetes risk by 30% in a meta-analysis of observational studies [150] Vegetarian diets reduced HbA1c by -0.39% in a meta-analysis of six RCTs [151] in people with T2D Mediterranean diet was associated with better glycemic control and cardiovascular risk factors than control diets, including lower fat diets, in people with T2D [152] and shows strong and consistent beneficial effects on cardiovascular outcomes including clinically meaningful reductions in rates of coronary heart disease, ischemic stroke and total cardiovascular disease [153]
Nutraceuticals/phytoceuticals	Nutraceuticals: Recent meta-reviews [108] have found evidence supporting the use of: (i) omega-3 s as an adjunctive treatment for major depression or ADHD, (ii) bioactive forms of folic acid (i.e. l-methylfolate) in the treatment of psychotic disorders and major depression, (iii) N-acetyl cysteine for managing peripheral symptoms of severe mental illness, across a range of conditions Phytoceuticals: A systematic search identified 9 relevant meta-analyses of RCTs, with primary analyses including outcome data from 5,927 individuals. Supportive meta-analytic evidence was found for St John’s wort for major depressive disorder (MDD); curcumin and saffron for MDD or depression symptoms, and ginkgo for total and negative symptoms in schizophrenia. Kava was not effective in treating diagnosed anxiety disorders (Sarris 2020, in submission ENP)	CVD: Supplementing with tomato products (lycopene) has beneficial effects on BP, lipids and endothelial function [154]. Calcium may have a modest benefit for BP [155]. Moderate to low quality evidence supports the use of some nutrients for prevention of cardiovascular events (folic acid, B-vitamins) [156]. The use of omega-3 s for prevention of cardiovascular events has been controversial however the most recent meta-analysis of 127,477 participants demonstrates lower risk of cardiovascular events including AMI, CHD death, and total CVD death [157] with marine omega-3 supplementation. Coenzyme Q10 may be beneficial in heart failure [158] T2D: Zinc [159], curcumin [160], Coenzyme Q10 [161], probiotics [162, 163], and chromium [164] have been demonstrated to have beneficial effects on glycemic control and cardiovascular risk factors in meta-analyses in people with T2D