Inspraakbijdrage Groene Zorg Alliantie

The strongest associaIon was with PM2.5: an increase in concentraIon of 10 μg/m3 led to a staIsIcally significant increase in asthma-related emergency department visits on the same day or up to three days aherwards. Non-significant associaIons were observed with NO2, O3, sulphur dioxide (SO2), PM10 and carbon monoxide (CO). Increased exposure to all pollutants also led to increased hospital admissions, although the data did not reach significance across all Ime lags (116). A further meta-analysis linked short-term exposure to PM2.5,

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PM10, and SO2 to respiratory morbidity, with PM10-2.5 associated with an increased risk of asthma morbidity in the following hours (117). A scoping review looked at individual pollutants, finding that PM, O3, CO, SO2, and NO2 can all precipitate asthma exacerbaIons, leading to emergency department aWendance and hospital admissions, with PM2.5, NO2 and O3 associated with higher mortality in asthmaIcs (118). Amongst children in Southern California with asthma, symptoms (bronchiIs, phlegm and wheeze), medicaIon use, emergency department visits or hospitalisaIons, and school absences were negaIvely impacted by air polluIon exposure (108). Whilst not yet a major issue in the UK, the Thoracic Society of Australia and New Zealand have highlighted the impacts of wildfire (landscape fire smoke) on asthma exacerbaIons. InternaIonal data consistently demonstrate an increased risk of asthma exacerbaIons during wildfire periods, with the greatest risk in older adults (>65 years) and children (119). Epidemiological evidence supports a posiIve associaIon between wildfire smoke and emergency department aWendances due to asthma, and with increased asthma reliever inhaler use and oral steroid prescripIon. (120).

COPD The European Respiratory Society (ERS) reviewed several systemaIc reviews and meta-analyses on air polluIon and COPD in 2023, proposing mechanisIc pathways and producing recommendaIons for healthcare professionals. An increase in PM2.5 concentraIon of 10 μg/m3 was associated with an 18% increase in COPD incidence (121). PopulaIon-based data and cohort studies idenIfy a supralinear relaIonship of incident COPD with ambient concentraIons of PM2.5, NO2 and O3 (122,123). In a Taiwanese cohort of 285,000 paIents, lung funcIon trajectories and PM2.5 concentraIons were examined at their home addresses over two years. A higher PM2.5 concentraIon was associated with lower FEV1, FVC and FEV1/FVC raIo, with the risk of COPD over Ime increasing by approximately 40% for people living in the most polluted areas compared with the least (by quarIles) (124). The review highlights that data are more robust in supporIng the relaIonship between fine and ultrafine (PM2.5 and smaller) parIculate maWer and poor COPD outcomes, compared to other components such as NO2, SO2 and CO. A ERS report further notes that paIents with COPD experience more symptoms (such as wheezing, cough and breathlessness), and an acute decline in both FEV1 and FVC, when exposed to air polluIon such as that in London’s Oxford Street or a commercial road, when compared to Hyde Park (an urban park) (125).

A 2016 meta-analysis concluded that worse air quality is associated with COPD exacerbaIons, with the relaIonship strongest for parIculate maWer three days aher exposure and for gaseous pollutants on the first day of exposure (126). Medicare data of 11.5 million paIents in the USA demonstrated that a short-term increase of 10 μg/m3 in ambient PM2.5 concentraIon was associated with a 2.6-fold increased risk of COPD-related hospitalisaIon (127). Mortality data relaIng to COPD and air polluIon are less well established, especially in the UK. One meta-analysis assessing air polluIon and respiratory disease mortality demonstrated that a 10 μg/m3 increase in NO2 was associated with a relaIve risk of 1.03 for COPD mortality, with mixed results for O3 exposure (128). In 2016, the WHO esImated that approximately 25% of COPD deaths were aWributable to air polluIon (129). Respiratory Infec;on The link between air polluIon and respiratory infecIon has been most extensively studied in relaIon to COVID-19. A systemaIc review suggested that for an increase in PM2.5 concentraIon of 10 μg/m3, there was a 66% increase in infecIon, 127% increase in severity and 40% increase in mortality (130). Other studies corroborate the associaIon between air polluIon and respiratory infecIon, such as viral infecIon (131) and pneumonia (132) in children.

In this global meta-analysis of paediatric populaIons, the excess risk of pneumonia was greatest with SO2, with a 2.9% increase per 10 parts per billion (ppb) gaseous concentraIon rise, but the findings were also significant with PM2.5, O3, PM10 and NO2. In adults, a 10 μg/m3 increase in PM2.5 concentraIon led to a 1% increase in hospital admission or emergency department visits for pneumonia, while increases of 10 ppb in NO2 and SO2 led to a significant 3.2% and 2.4% increase in hospital presentaIon or admission with pneumonia

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respecIvely (133). The previously discussed meta-analysis of air polluIon and respiratory disease mortality idenIfied that a 10 μg/m3 increase in NO2 was associated with a relaIve risk of 1.06 for acute lower respiratory tract infecIon mortality, with mixed results for O3 exposure (128). Inters;;al Lung Disease (ILD) ILD is an umbrella term for inflammaIon and ohen irreversible fibrosis of the lung Issue, with idiopathic pulmonary fibrosis (IPF) being the most common form. Air polluIon has been postulated to have a causal role in iniIal IPF development, severity, and prognosis (134). A review of IPF iniIaIon and outcomes (134) highlights a retrospecIve study of over 2000 paIents with IPF in Northern Italy, concluding that there was an approximate 7% increase in IPF incidence per 10 μg/m3 in NO2 concentraIon, although with a non-significant confidence interval once confounders were accounted for (135). An addiIonal narraIve review has reported on the impact of air polluIon on intersIIal lung diseases (136). Of the referenced studies, results from an Indian cohort diagnosed with hypersensiIvity pneumoniIs (an inflammatory ILD) had a 7% greater chance of developing the condiIon for every 10 μg/m3 increase in PM2.5 concentraIon (137).

In a French cohort of 192 paIents with IPF followed for five years, an increase in the mean O3 concentraIon was associated with an increased risk of exacerbaIons, with mortality risk rising with cumulaIve PM2.5 and PM10 exposure (138). O3 and NO2 exposure have previously been shown to increase exacerbaIon risk in South Korea (139). Further research is required to determine the impact of pollutants on the natural history of ILDs; a single cohort study previously demonstrated a decline in FVC with increasing PM10 exposure but inconsistent results with PM2.5 and on six-minute walk tests (140). Pulmonary Embolism A single meta-analysis has examined air polluIon and pulmonary embolism risk (141). The nine studies included were mainly from developed countries and examined a range of pollutants. Increased NO2 exposure (and, to a lesser extent O3) were associated with an increased risk of pulmonary embolism. Obstruc;ve sleep apnoea A systemaIc review reported six studies which examined the relaIonship between airborne polluIon exposure and sleep-disordered breathing (142). Two idenIfied an associaIon of PM2.5 and NO2 exposure and sleep-disordered breathing measured via polysomnography (143,144).

Two more demonstrated an associaIon with PM10 (one with a worsening respiratory disturbance index (RDI) and sleep Ime spent in hypoxia (oxygen saturaIon <90%) (130), the other with worsening severity of obstrucIve sleep apnoea(OSA) (145)). One other reported a posiIve associaIon between the severity of OSA and CO exposure (146).

Diet The role of diet in the development of chronic respiratory disease is less established compared to air polluIon. Hypothesised mechanisms predominantly focus on nutriIon as an inflammatory mediator, idenIfying certain nutrients associated with the development and severity of allergic disease. Longitudinal cohort studies indicate that maternal and early childhood nutriIon is crucial in the development of allergic disease (147). While allergic diseases are beyond the scope of this review, studies on asthma are discussed here.

Asthma Diets high in calories, saturated fat, and protein, and low in fibre, are associated with an increased risk of asthma and allergic rhiniIs. In comparison, a Mediterranean diet high in vegetables, fruit, fibre, olive oil, and fish is associated with reduced risk (147,148). Cohort studies indicate that higher fruit and vegetable intake is correlated with lower risk of developing asthma, higher FEV1, and

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reduced wheeze in children, adolescents and adults (149). This is consistent with RCT evidence: aher a two-week period of following either a high or low fruit and vegetable diet, asthmaIc adults in the low intake group had more than double the risk of an asthma exacerbaIon and significantly lower spirometry values than the high intake group (150). Notably, the supplementaIon arm of the trial run in parallel found no difference in outcomes between lycopene supplementaIon and placebo, supporIng a whole-food approach. However, the European Academy of Allergy and Clinical Immunology find insufficient evidence to recommend increasing fruit and vegetables solely to reduce asthma risk (151). That said, obesity is an established risk factor for asthma and dietary intervenIons for weight loss are effecIve at improving asthma control in children (152). ObservaIonal evidence supports an inverse correlaIon between dairy intake and asthma incidence. An eight-week experimental study in asthmaIc children eliminaIng milk and eggs demonstrated a 22% improvement in peak expiratory flow rate in the intervenIon group, significantly different from the slight decrease seen in the control group (153). Further research is needed given the small study size and short follow up period. COPD Epidemiological studies report an inverse associaIon between consumpIon of the Mediterranean diet, and COPD incidence.

Higher adherence to the Mediterranean diet is associated with a lower risk of developing COPD (case-control evidence reports a 27% lower risk in those with middle to high adherence scores compared with low scores aher adjustment for educaIon level) (154). The Mediterranean diet typically contains less processed meat. A systemaIc review and meta-analysis of five prospecIve cohort studies reported a dose-response relaIonship with an 8% increased risk of COPD per 50g/week increase in processed meat consumpIon (155). Physical Ac&vity Research on the relaIonship between physical acIvity and respiratory disease focuses predominantly on pulmonary rehabilitaIon as a therapeuIc intervenIon, parIcularly for COPD paIents. The evidence discussed here considers first the effecIveness of supervised rehabilitaIon, then exercise and acIve travel. Pulmonary Rehabilita;on Pulmonary rehabilitaIon (PR) is a mulI-component intervenIon that includes exercise training, educaIon, and behavioural change. Literature reviews have examined the impact of PR on acute exacerbaIons, quality of life, exercise tolerance, respiratory muscle strength and mortality in COPD paIents (156–162).

Exercise-based PR is associated with improvements in walking distance, exercise capacity, and health-related quality of life in COPD paIents (including low-quality evidence supporIng the use of PR in those with severe COPD (158,160,161). Two reviews of RCTs focused on early PR (within four weeks) aher acute COPD exacerbaIons (159). Early PR was associated with a reduced length of hospital stay, reduced risk of hospital readmission, and lower mortality at the end of treatment (RR = 0.58; CI 0.35-0.98), although the long-term impact on mortality is unclear. PR has also been trialled in paIents with fibroIc ILD, and is associated with an improvement in six-minute walking distance with mixed effects on dyspnoea, and a trend towards significance in improving quality of life (163,164). Aerobic Exercise Aside from controlled exercise programmes, COPD paIents can also benefit from general increases in physical acIvity. Unsupervised physical acIvity, predominantly walking, is associated with improved walking distance as well as improved emoIonal funcIon, health-related quality of life, muscle strength, reduced faIgue, and symptoms of anxiety and depression (165). A review examining

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barriers to exercise in COPD paIents included anxiety about breathlessness, recommending light physical acIviIes such as walking as a more acceptable long-term approach (166). Aerobic exercise is beneficial for both asthma symptoms and fitness. A systemaIc review and metaanalysis of 11 RCTs showed that aerobic exercise improves asthma control and lung funcIon (but not markers of airway inflammaIon) (167). A second systemaIc review and meta-analysis found walking distance to also be improved, as might be expected (168). Intensive inpaIent exercise protocols have demonstrated significant improvements in walking distance in paIents with pulmonary arterial hypertension (aher medical opImisaIon), but are unlikely to be generalisable outside of clinical se•ngs (169). The greatest benefit was seen with intervenIons combining aerobic exercise, strength training and respiratory muscle exercises. However, outpaIent programmes that are feasible to follow long-term require further research. Commu;ng Concerns that air polluIon may miIgate or reverse the health benefits of acIve commuIng have been raised. A comprehensive systemaIc review found that higher levels of air polluIon mildly reduced the short-term benefits of walking or cycling on lung funcIon, with the strongest associaIons being with PM2.5 and ultrafine parIcle concentraIons (170).

However, evidence for modificaIon of the long-term health benefits of exercise is not clear, with many studies suggesIng that air polluIon does not reduce these benefits, and no significant impact of NO2 levels on chronic respiratory diseases (including lung cancer, asthma and COPD). It is also important for policymakers to consider that increasing numbers of acIve commuters can reduce air polluIon and the associated negaIve health effects (171). Electrically assisted, or e-, bikes provide powered assistance and can shih the choice of transport by providing a less exerIonal alternaIve to convenIonal cycling. E-bikes that require pedalling have been invesIgated to determine the health impact of these less intensive approaches. A review of experimental and observaIonal studies conducted a meta-analysis demonstraIng increased maximal oxygen consumpIon and power output compared to baseline (172). Two included studies, that used convenIonal cycling as a comparator, found no difference in improvements in VO2max or maximal power, suggesIng that e-bikes might provide equivalent health benefits. Cardiovascular Diseases Air pollu&on Air polluIon represents a complex mixture of parIcles and gases (such as CO, SO2, and NO) that are either not part of natural air or are present in abnormally high concentraIons (173).

Air polluIon is normally considered by locaIon: ambient (outdoor) or indoor exposure. Ambient air polluIon mainly stems from burning of fossil fuels. Indoor polluIon in high income countries also relates to the burning of gas in boilers and cooking stoves, but also from aerosol and candle use. Long-term (one to five year) exposure to increased PM2.5 concentraIons causes a 16-31% increase in annual IHD mortality (174). Even short-term exposure (hours to days) can increase the risk of cardiovascular-related death by <1%. Air polluIon also increases the risk of developing heart failure, and of atrial fibrillaIon and other cardiac arrhythmias (175). Short-term exposure to increased PM2.5 concentraIons increases systolic blood pressure by up to 10mmHg (176), while long-term exposure is associated with increased atheroscleroIc plaque formaIon, leh ventricular hypertrophy, and caroId inIma media thickness (177). The main physiological mechanism underlying the cardiovascular risk increases appears to be vascular inflammaIon and oxidaIve stress. Diet

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Plant-based diets reduce cardiovascular-associated mortality by up to 32% (178,179). AddiIonally, vegetarians (especially men) have lower BMI, blood pressure and circulaIng cholesterol concentraIons. Adherence to the Mediterranean diet reduces the risk of cardiovascular events (such as myocardial infarcIon, ischaemic stroke) or of peripheral vascular disease by more than one third (180). The physiological mechanism underlying these health benefits is not fully understood, but likely relates to reduced consumpIon of meat, saturated fat, refined sugar and refined starches, and possibly to increased subsItuIon with omega three faWy acids (181,182). Increasing evidence suggests that plant-based diets confer benefit via impacts on the gut microbiome (182,183). Physical Ac&vity The World Health OrganizaIon (WHO) defines physical acIvity (PA) as “any bodily movement produced by skeletal muscles that requires energy expenditure”. It reduces the risk of chronic diseases, including IHD and ischemic stroke (184). The WHO thus recommends a minimum exercise target of 600 metabolic equivalent minutes (METs) per week: approximately 150 minutes of total (brisk) walking Ime or 75 minutes of running per week. One MET is defined as the amount of oxygen consumed while a person is si•ng quietly (approximately 3.5 mL O2/kg body weight/minute).

Increases in daily step count lead to a non-linear reducIon in cardiovascular death risk: an increase in 500 steps per day can reduce cardiovascular-related mortality risk by 7%, but the extent of risk reducIon lessens with higher total step counts (185). Meta-analyses including other types of acIvity have come to similar conclusions (186). Increasing weekly METs from <600 to 4000-7999 can reduce the risk of ischaemic stroke by 19% and that of IHD by 23% (186). Conversely, higher daily si•ng Ime is associated with an increased risk of cardiovascular disease and diabetes. This relaIonship remains when adjusted for physical acIvity, albeit somewhat weakened for cardiovascular disease (187). Physical acIvity increases postprandial glucose and insulin responses, improves blood pressure (predominantly systolic) and lower limb vascular funcIon. If maintained for a longer Ime period, it also leads to improvements in body weight, waist circumference, body fat percentage, fasIng glucose, HbA1c and HDL concentraIons (188). While such improvements may appear incremental, the synergisIc effects lead to overall cardiovascular risk reducIon (189). Cancer Pollu&on Air polluIon exposure increases cancer risk (including that related to liver and colorectal cancers (190), breast and brain cancer (191,192)). Even pre-natal exposure is a risk (193).

The WHO thus lists PM2.5 parIculates as class 1 carcinogens (194) (perhaps through oxidaIve stress or other inflammatory processes (195,196)). Diet The western diet (typified by a high intake of ultra-processed foods, sucrose, fat and refined grains, but with liWle fresh fruit and vegetables or fibre) is strongly associated with risk of developing colorectal cancer (197). In contrast, the Mediterranean diet reduces all-cause cancer mortality, and risk of developing colorectal, head and neck, lung, gastric, bladder and liver cancers (198). This benefit might, in part, be mediated though impacts on obesity: 11% of European colorectal cancer (the third most diagnosed and second most lethal cancer globally) cases are due to obesity (199). However, the benefits of a Mediterranean diet on colorectal cancer risk persist in those of normal weight studies.

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ObservaIonal studies show that consumpIon of plant-based diets is associated with reduced (especially colorectal and breast) cancer risk (200). However, prospecIve RCTs are needed to confirm causality. Physical Ac&vity AcIve transport reduces cancer risk: ~150 minutes of walking or 90 minutes of cycling per week reduces the risk of endometrial, colorectal and breast cancers by up to 30%, with benefit increasing with greater exercise (201,202). Exercise also improves tolerance of cancer chemotherapy and radiotherapy (203), and of compleIng treatment courses (204). Different measures of physical strength have shown to predict mortality in paIents with cancer, such as the six minute walking test and grip strength (205). In a meta-analysis of 15 studies including 350 paIents, (cancer) pre-operaIve exercise training reduced the length of hospital stay by almost five days and decreased post-operaIve complicaIons (206). Exercise at the start of cancer treatment is thus endorsed by bodies such as Cancer Research UK. Endocrine Diseases Pollu&on While the impact of polluIon on cardiovascular and respiratory disease is well established, it also contributes to disease burden across the life course starIng in utero, including endocrine diseases. Early Life Exposures GestaIonal exposure to air polluIon is linked to adverse foetal, neonatal and maternal outcomes.

These include maternal gestaIonal diabetes mellitus (GDM), pre-eclampsia and hypertension, and neonatal low birthweight, preterm birth, and neonatal mortality. An umbrella review of studies examining PM2.5 found that these associaIons varied by trimester (207). A 2023 review of 31 cohort studies found that exposure to PM2.5, PM10, NO2, and SO2 was associated with increased risk of GDM predominantly in the first trimester (208). Analysis of specific PM components showed that black carbon exposure in the second trimester and NO3- exposure in the first trimester increase risk of GDM. Childhood and adolescence In childhood, ambient polluIon is associated with higher risk of being overweight and obese. A meta-analysis of 15 studies examined childhood exposure to air pollutants and found a posiIve associaIon between PM10, PM2.5, and PM0.1 with both obesity and BMI (209). A 2024 meta-analysis demonstrated that for every 10 μg/m3 increase in PM (PM1, PM2.5, and PM10), nitrogen oxide species, and O3, the odds of being overweight and obese in childhood and adolescence (<19 years) increased by 6-23% depending on the pollutant (210). Insulin sensiIvity and glucose tolerance were also reduced, and blood lipid concentraIons increased. Consistent with this, prenatal maternal exposure to PM2.5 was associated with an increased risk of childhood obesity (211).

Adulthood These associaIons persist in adulthood. A 10 μg/m3 increase in PM2.5 and PM10 concentraIon is associated with a 15.9% and 9.2% increase in obesity incidence respecIvely (211). Similar results are reported for NO2, SO2, and O3 (209). An increase of 5 μg/m3 in annual average PM2.5 or PM10 concentraIon was associated with 14% or 9% increases of metabolic syndrome (the presence of abdominal obesity, hypertension, hyperglycaemia, high triglycerides, and low HDL) risk, respecIvely (212). Several studies have linked air polluIon with T2DM. A study following 1.7 million US Medicare parIcipants reported a 15% increased risk of developing T2DM per 10 μg/m3 in long-term PM2.5 exposure, even aher controlling for individual and environmental confounders (213). Similarly, meta-

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analysis of studies in Europe and North America showed an increased risk of T2DM of 8-10% per 10 μg/m3 of PM2.5 or NO2 (214). MechanisIc evidence supports a causal relaIonship with insulin resistance in children and adults noted with even short periods of exposure to air polluIon (215). This appears to be consistent across PM2.5, PM10, NO2, and SO2. Studies exploring diabetes-related mortality demonstrate increased risk with increasing polluIon, even at low levels, and over short and long-term exposure periods (215). The American Cancer PrevenIon Study found an 18% increase in diabetes-related mortality per 10 μg/m3 increase in PM2.5. These studies provide convincing evidence of the impact of air polluIon on T2DM. A 2024 global burden of disease study esImated that 20% of all diabetes-related deaths and DALYs globally are aWributable to PM2.5 (216). Although Type 1 Diabetes (T1DM) is less studied than T2DM, a 2022 meta-analysis of six studies demonstrated a significantly increased risk of T1DM per 10 μg/m3 increase in O3 (OR 1.51; 95% CI 1.26-1.80) and a more modest increase in risk per 10 μg/m3 increase in PM2.5 (OR 1.03; 95% CI 1.01, 1.05) (217). Emerging evidence links air polluIon to increased disease risk of thyroid disease (studies predominantly focused on prenatal exposure (218), male and female inferIlity (219), and osteoporosis) (220).

Diet Evidence for the impact of diet on endocrine disease is predominantly focussed on weight loss and diabetes, with fewer studies examining bone fracture risk, or diabeIc complicaIons such as chronic kidney disease (CKD). Dietary variables in research can broadly be divided into paPerns (e.g. vegetarian, Mediterranean, Ketogenic) where the definiIon specifies the type and amounts of different foods, food groups (e.g. meat, dairy, legumes) or nutrients (e.g. fibre, protein, fats). AddiIonally, some studies examine the “healthiness” of dietary intake to create a composite score (e.g. the plant-based index). Obesity Obesity is a major risk factor for mulIple NCDs. Adherence to plant-based, vegetarian, and vegan diets are associated with lower weight and BMI. A meta-analysis of eleven trials found that vegan diets were associated with greater weight loss and reduced BMI compared to a range of control diets (including habitual diets and specified alternaIves such as the Mediterranean diet), with a mean difference of 4.1kg (p<0.001) and 1.38kg/m2 (p<0.001) respecIvely (221). Lipid profiles (including lower total cholesterol and LDL-C) also improved. This was consistent with other meta-analyses of vegetarian diets (222,223). Huang et al. (222) included twelve RCTs, and demonstrated a mean weight loss of 2kg compared with non-vegetarian diets.

Subgroup analysis demonstrated greater weight loss in vegans than lacto-ovo-vegetarians. A second meta-analysis of overweight or obese adults demonstrated significantly reduced LDL-C, total cholesterol and HbA1C in those consuming vegetarian diets (223). Evidence in adults combining vegetarian diets with aerobic exercise showed superior glycaemic control, and lower fasIng plasma glucose, waist circumference, BMI, and insulin resistance compared with either intervenIon alone (224). A limitaIon of many of these studies is the short duraIon of follow up. However, the AdvenIst Health Study 2 (a large cohort with a high proporIon of vegetarians followed since 2002) reveals a dose-response relaIonship, BMI falling with diet stringency: vegans have a mean BMI of 23.6kg/m2 compared with non-vegetarians (28.8 kg/m2) (225). A systemaIc review of nine cohort studies examining plant-based diets took food quality into account (226). Plant-based diets were associated with lower body adiposity than diets with higher animal-source foods, whilst healthier plant-based diets (using index scoring) were more strongly associated with weight loss than less healthy plant-based diets (which had either a null or adverse associaIon). There is a paucity of research on the health impact of poultry consumpIon, with most comparing red meat and plant-based foods.

No RCTs assessed processed poultry foods (227). A systemaIc review and meta-analysis of 21 trials studying the impact of pulse consumpIon on body

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weight found significant weight reducIon in pulse-containing diets even when matched for energy intake (p=0.03) (228). Increasing recogniIon of the dual benefits of plant-based diets for health and sustainability have led to several studies examining sustainable dietary paWers and weight. A meta-analysis of eight studies demonstrated that high adherence to sustainable diets (defined as diets that provided sustainability measures such as the EAT-Lancet diet) was associated with a reduced risk of overweight (RR 0.69) or obesity (RR = 0.61) (229). Lastly, intervenIonal research aiming to prevent life-long poor dietary habits has focused largely on childhood intervenIons. A systemaIc review of 137 intervenIons (72% aiming to increase fruit and vegetable consumpIon) found that behavioural insights were effecIve at improving children’s diets in 74% of the included intervenIons (230). Most effecIve approaches were using incenIves, changing defaults, and modifying the physical environment whereas providing informaIon in isolaIon was least effecIve. Children Childhood obesity has been an area of growing concern in the UK, where one in three children leave primary school overweight (231).

A meta-analysis of 15 studies in children, found that both diet only or ‘diet and exercise’ resulted in weight loss and metabolic profile improvement, with combinaIon intervenIons delivering greater changes (232). Dietary intervenIons predominantly focused on calorie restricIon although some increased dietary fibre or fruit and vegetable consumpIon. Increasing numbers of children are consuming plant-based, vegetarian or vegan diets with 8% of children in the UK reporIng to be vegan, 13% vegetarian, and 21% likely to become vegetarian (233). A systemaIc review of health outcomes in vegan or vegetarian children consistently found no evidence that vegetarian children had no difference in growth compared to omnivores, although iron, iodine and vitamin B12 levels did seem slightly lower (234). For vegans, growth, body fat, iron, iodine, vitamin B12 and bone health were all reduced, but a lower cardiovascular disease risk was also evident with more favourable lipid profiles. The impact of supplementaIon, varying risk by developmental stage, and long-term impact into adulthood require further research. Diabetes The relaIonship of several dietary paWerns with T2DM have been examined, including the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), Por{olio (cholesterol lowering), Nordic, and vegetarian diets. All improved HbA1c, fasIng glucose and fasIng insulin (235).

A metaanalysis of 17 studies found that high adherence to a plant-based diet reduced the risk of T2DM by 18% compared to low adherence with a stronger inverse associaIon seen when healthy plant-based foods were emphasised, such as vegetables, fruits, wholegrains and legumes (58). This is supported by evidence of lower risk with consumpIon of whole plant-based foods, while refined grains and sugar sweetened beverages are associated with higher risk of T2DM (236). Vegetarian diets are associated with mulIple health benefits. An umbrella review idenIfied 20 metaanalyses reporIng on 34 health outcomes and found beneficial effects for cholesterol, BMI, diabetes and ischaemic heart disease risk, and several cancers (237). A meta-analysis of 14 observaIonal studies reported lower risk of diabetes compared to non-vegetarians (238). A vegan diet is also associated with a lower T2DM prevalence and incidence, and improved glucose homeostasis in diabeIcs (239). These associaIons may result from the higher fibre content in plant-source foods: a meta-analysis of 359,167 parIcipants found a 19% lower risk of T2DM with high total fibre intake compared to low intake and a dose response relaIonship demonstraIng a 6% decreased risk of T2DM per 2g/day increment in fibre intake (240).

Given these reported benefits, studies have examined the impact of subsItuIng animal-source foods or proteins for plant-equivalents. Two 2023 systemaIc reviews focus on this approach. One systemaIc review and meta-analysis examined 24 prospecIve cohort studies (241). An inverse associaIon with T2DM incidence was found subsItuIng red meat with wholegrains or cereals or nuts and a larger reducIon in T2DM incidence when subsItuIng processed meat with nuts. AddiIonally, a lower T2DM incidence was seen when replacing poultry with wholegrains or replacing

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eggs with nuts or wholegrains. These findings were reported alongside beneficial effects on CVD and all-cause mortality when subsItuIng animal source meats, dairy, and eggs with plant-equivalents. A second systemaIc review examined subsItuIng protein from animal to plant sources (242). Included studies predominantly focused on protein isolates rather than whole foods. Conclusions were limited by high risk of bias but suggested a lower T2DM incidence subsItuIng animal protein for plant protein. Evidence supports the consumpIon of sustainable diets for reducing diabetes risk. The EAT-Lancet diet (plant-based, with an emphasis on whole foods and limited animal-based food and refined sugar intake), aims to provide a reference diet that can miIgate both malnutriIon and unsustainable agricultural pracIces for beWer human and planetary health. A systemaIc review examining the associaIon between the EAT-Lancet diet and diabetes in five studies (four focused exclusively on T2DM incidence) (243) idenIfied a decreased risk of T2DM onset (i.e. preventaIve role) and a doseresponse relaIonship (higher adherence associated with lower risk of T2DM). One study, following a UK Biobank cohort of individuals without a prior diagnosis of diabetes over 10 years, found that each incremental increase in adherence score was associated with a 6% decrease in risk of T2DM (244).

Analysis revealed that 44% of this associaIon was mediated by BMI. Gesta;onal Diabetes Maternal diets are important for foetal health. GestaIonal diabetes (GDM, diabetes during gestaIon that was not detected prior to pregnancy) can result in high risk of hypertension, caesarean secIon, neonatal hypoglycaemia and macrosomia (245). Furthermore, women diagnosed with GDM have more than seven Imes higher risk of T2DM compared with normoglycaemic women and children are more likely to develop insulin sensiIvity and pancreaIc beta-cell dysfuncIon in later life (246,247). A meta-analysis of ten prospecIve cohort studies found that plant-based dietary paWerns were associated with a lower risk of GDM (RR=0.85) (245). Data from two studies demonstrated that higher adherence to a plant-based diet was associated with a lower risk of GDM. Metabolic Syndrome Diets (such as the Mediterranean and DASH diets) associated with reduced risk of obesity and diabetes are likely to be associated with lower risk of metabolic syndrome (248). A 2024 review revealed beneficial effects of plant-based diets on individual metabolic syndrome components, although the diverse range of diets studies and variable supplement protocols limited the conclusions that could be drawn (249).

Fracture Risk While deficiency in vitamin B12 is easily remedied with supplementaIon, vegetarian and vegan diets are associated with 9% and 43% higher risk of bone fractures respecIvely compared with meat eaters in the EPIC-Oxford cohort (60). AdjusIng for dietary calcium only parIally accounted for this elevated risk, and some evidence suggests that adequate vitamin D, calcium and protein-rich foods in the diet may counteract this, highlighIng the need to provide adequate guidelines to those transiIoning to a plant-based diet (250). Physical Ac&vity Obesity and Diabetes Aerobic acIve transport uses oxygen to generate energy. Intense exercise (e.g. intense cycling) supplements this with anaerobic metabolism (derives energy without using oxygen). Low intensity aerobic exercise (and thus ‘gentle acIve commuIng’) is beneficial to health. Walking reduces lower body fat, BMI and cholesterol levels (251). A systemaIc review and meta-analysis of adult RCTs showed that walking decreased waist circumference, weight, body fat, and BMI (252). In children and adolescence, a consistent inverse associaIon is seen between walking step count and obesity (253). RCT evidence also supports walking as a means to reduce fasIng blood glucose,

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HbA1c, postprandial blood glucose and fasIng insulin (254). A dose-response relaIonship is reported with lower risk of T2DM with faster walking speeds (255). In prediabeIc paIents, meta-analysis of ten RCTs shows a significant reducIon in BMI, HbA1c and fasIng blood glucose levels with aerobic exercise compared to control (256). In overweight or obese paIents, moderate conInuous or high intensity training are equally effecIve in significantly reducing body fat and waist circumference (257). In sarcopenic obesity (low muscle mass and high body fat with higher metabolic risk) (258), aerobic exercise decreases body weight and fat mass. Similar benefits are seen for T2DM risk. Aune et al. (259) reported an inverse associaIon between physical acIvity and T2DM risk, noIng that this was consistent across light, moderate, and vigorous acIvity as well as resistance exercise. AcIve commuIng, by foot, bicycle or other non-motorised means has gained aWenIon as a low-cost, healthy, and climate friendly approach to daily travel. ObservaIonal research shows an associaIon between acIve commuIng and obesity and diabetes. A meta-analysis of 28 observaIonal studies showed a 12% and 18% reducIon in risk of obesity and diabetes respecIvely compared with inacIve commuIng (260).

Workplace environments have become increasingly sedentary and several intervenIonal studies have focused on increasing acIvity whilst working using treadmill, cycling, stepping or standing desks. A systemaIc review demonstrated improved glycaemic control and body weight with treadmill desk use (261). Gesta;onal Diabetes Mellitus (GDM) Insulin resistance is higher during pregnancy and some women develop GDM with higher risk of adverse neonatal outcomes and later development of T2DM. Exercise is an insulin sensiIser, but historical concerns around preterm birth have led to low levels of awareness amongst women on the safety of exercise in pregnancy. ObservaIonal studies show that physically demanding work including prolonged standing and heavy lihing were associated with higher risk of miscarriage and preterm delivery (262). However, evidence does not support these concerns for exercise with several systemaIc reviews of RCTs finding a reducIon in caesarean secIon rates and no change or even a lower risk in pre-term birth risk (263,264). Aerobic or resistance exercise reduce the risk of developing GDM, and reduce insulin requirements, fasIng glucose levels and HbA1c (264,265). Polycys;c Ovarian Syndrome (PCOS) PCOS is a common endocrine disorder characterised by reduced frequency or lack of ovulaIon, higher circulaIng androgens, and polycysIc ovaries visualised on ultrasound.

It is associated with reduced ferIlity, obesity and insulin resistance (266). Across seven RCTs, regular aerobic exercise improved menstrual paWerns, shihing from amenorrhea to oligomenorrhea or normal menstruaIon and an improvement in ovulaIon rate. Hyperandrogenism features improved, testosterone level reduced, and lower rates of anxiety and depression were found in the intervenIon groups. Small sample sizes, short intervenIon duraIon, and lack of standardised outcome measures prevent idenIficaIon of opImal duraIon, intensity or type of exercise for PCOS (266). Osteoporosis Physical acIvity is beneficial for bone health and osteoporosis prevenIon across the life-course. Exercise intervenIons increase bone mineral density (BMD) in prepubertal children (267) although, with acIve transport in mind, such benefits relate to weight bearing exercise such as walking/running (268). In adults aged >65 years, physical acIvity improves lumbar and hip bone mineral density (269). Higher doses of physical acIvity combining mulIple exercise types were most effecIve. Exercise also reduces the risk of osteoporoIc fractures (46). A meta-analysis of studies on post-menopausal women found similar associaIons between exercise training and BMD (270). More data is required to understand the impact on male osteoporosis risk (271). Mental Health Disorders Pollu&on

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Cogni;ve Impairment Evidence supports an associaIon between both short- and long-term exposures to ambient polluIon and cogniIve impairment. A systemaIc review and meta-analysis found that long-term PM2.5 exposure was associated with a significant increase in the risk of all-cause demenIa (pooled OR 1.3), Alzheimer’s (OR 1.65) and Parkinson’s disease (OR 1.17) (272). AddiIonally, PM10 exposure was associated with an increased risk of vascular demenIa (OR 1.12). Similar results have been reported for other pollutants including NOx, NO2, and O3 (273). For Alzheimer’s disease, a dose-response relaIonship has been noted with higher incidence of Alzheimer’s disease in regions with higher polluIon (274). Childhood Neurodevelopmental Disorders In utero exposure has also been linked to subsequent cogniIve impairment and behavioural changes in childhood, including inaWenIon, lower IQ scores, and symptoms of anxiety and depression (275). Prenatal exposure to pollutants is associated with increased risk of auIsm spectrum disorder (ASD) in epidemiological studies, with higher suscepIbility reported in boys. Plausible biological mechanisms include damage to the blood-placental barrier and transfer of PM to the immature foetal brain, increased neuroinflammaIon and oxidate stress (276).

Post-natal traffic-related polluIon exposure is similarly associated with structural brain changes in neuroimaging studies, as well as higher risk of ADHD and ASD (276). Higher polluIon exposure across childhood is associated with lower academic achievement and cogniIve performance. Mood Disorders A US study esImaIng exposure using residenIal address for children found that increased NOx exposure was associated with a significant increase in symptoms of anxiety and depression at age 18, even aher adjusIng for confounders including socioeconomic status (277). Both short- and long-term exposure to PM2.5 and NO2 are associated with an increased risk of depression (278). A meta-analysis of cohort studies on long-term exposure air polluIon included 23 arIcles on depression and five on anxiety in adults (279). Analysis of PM2.5 and risk of anxiety did not demonstrate a significantly increased risk, however PM2.5 and NO2 were associated with an increased relaIve risk of depression (PM2.5 (RR: 1.10, 95% CI [1.00, 1.20]) and NO2 (RR: 1.17, 95% CI [1.06, 1.31]). While no associaIons were found for CO, PM10, SO2 or O3 pollutants, short-term exposure to these pollutants has been shown to increase risk of depression (278).

An in-depth analysis of 30 studies on stress and anxiety disorders was consistent with Cao et al.’s (279) meta-analysis finding no significant increase in risk of anxiety or psychological stress with PM10, PM2.5 or NO2 (280). Furthermore, short-term increases in exposure to PM2.5 and PM10 of 10 μg/m3 are associated with 2% and 1% increases in risk of aWempted suicide respecIvely (281). In analysis of three cohorts, exposure to PM10 in the second trimester is associated with an increased odds of postpartum depression (OR 1.26) (282). Psychosis A meta-analysis of ten studies found a highly staIsIcally significant (albeit small effect size) increased risk of hospital admission for schizophrenia per 10 μg/m3 increase in short-term exposure to NO2 (RR 1.029, 95% CI 1.016-1.041 p<0.001) (283). Sleep Disorders We did not idenIfy any systemaIc review or meta-analysis on polluIon and sleep disorders, however a cross-secIonal study in the UK Biobank cohort found that PM2.5 was associated with an increased risk of sleep disorders (OR 2.39; 95% CI 1.64-3.48 per 10 μg/m3) (284). Both PM2.5 and PM10 were associated with a significant reducIon in sleep duraIon which remained aher adjusIng for co-variates including BMI, alcohol consumpIon, educaIon level, and residenIal noise level.

While these results should be interpreted with cauIon given the cross-secIonal study design, insomnia is associated with a 27% higher risk of cogniIve disorders (95% CI 1.16-1.39), providing a plausible

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biological mechanism for the reported associaIon between polluIon and cogniIve impairment (285). Diet NutriIonal psychiatry is a relaIvely recent field of research, emerging from several studies that link dietary paWerns to mental health. Emerging evidence suggests that the gut microbiome may modulate the ‘gut-brain axis’ - the two-way network connecIon between the central nervous system and the intesIne (286). Many foods contain molecules that may influence brain development and neural signalling (287). Recent intervenIonal studies provide evidence of the beneficial effect of plant-based diets, and diets with higher intake of fibre or polyphenols, on mental health. The epidemiological and experimental evidence is summarised below. Depression Epidemiological studies have idenIfied an associaIon between dietary paWerns such as the Mediterranean diet, plant-based diets and lower risk of depression. An umbrella review idenIfied sixteen meta-analyses of observaIonal studies and two meta-analyses of RCTs reporIng on the Mediterranean diet, DASH, vegetarian, Dietary Inflammatory Index (DII), Western diet, and low calorie or low fat diets (288). Higher adherence to the Mediterranean diet or a lower dietary inflammatory index (lower intake of inflammaIon-associated foods) was associated with lower risk of depression.

Weak or no evidence was found for the DASH, vegetarian, Western or other diets. O’Neil et al. (289) performed a systemaIc review of 12 cross-secIonal or prospecIve cohort studies that looked at children and adolescents (age range 4.5-18 years). Higher diet quality was associated with significantly beWer mental health, and unhealthy dietary paWerns were associated with worse mental health, although the predominantly cross-secIonal design of these studies cannot rule out reverse causality. In adults, a meta-analysis of 13 observaIonal studies demonstrated a significant associaIon between a healthy diet paWern (higher fruit, vegetable, fish and wholegrain intake) and reduced odds of depression (OR 0.84l 95% CI 0.76-0.92 p>0.001) (290). ObservaIonal studies on the Mediterranean diet have also been synthesised (291). High adherence to a Mediterranean diet was associated with reduced risk for depression (RR 0.68). IntervenIonal trials demonstrate that following a Mediterranean diet and/or adding Mediterraneanlike supplements can reduce the risk of depression, and improve depressive symptoms (292–295). A systemaIc review of RCTs on low carbohydrate and ketogenic diets found no evidence that either diet was superior to control in modifying mood, faIgue, or QoL (296).

An RCT with six-month follow up distributed food hampers and provided workshops to encourage a Mediterranean diet alongside fish oil supplements, while a control group aWended social group events (292). Authors reported a significantly higher consumpIon of fruit, vegetables, nuts, legumes, and wholegrains and less red meat and poultry in the intervenIon group at three months. The intervenIon group had significantly reduced depressive symptoms at three months, and this was sustained at six months (p=0.03). Secondary analyses demonstrated a correlaIon between reduced depression and increased Mediterranean diet adherence and increased consumpIon of vegetables and nuts. The SMILES trial was a 12-week RCT where 33 parIcipants with moderate to severe depression received either dietary support or social support sessions (293). Whilst criIcised for its reporIng of blinding and recruitment methods as well as its small sample size, it demonstrated a significant decrease in interviewer-determined depression symptoms and an increase in remission rates in those receiving nutriIonal counselling and advice compared to the control group with a number needed to treat of 4.1 (297).

Lastly, a 14-day RCT randomised young adults to receive either usual diet (control), prompted consumpIon (text reminders and fruit and vegetable voucher), or fruit and vegetable delivery with two addiIonal daily servings on top of their normal diet. Self-reported depression and anxiety symptoms improved in the fruit and vegetable delivery group (295).

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Cogni;ve Impairment Epidemiological evidence links dietary paWerns to cogniIve impairment. A meta-analysis of 22 observaIonal studies demonstrated that high adherence to a Mediterranean diet was consistently associated with a reduced risk of cogniIve impairment (RR 0.60 95% CI 0.43-0.83) (291). The evidence for dietary components of the EAT-Lancet reference diet on cogniIon have been summarised by Dalile et al. (298). They concluded that lack of evidence limits definiIve conclusions but that wholegrains, fruit and vegetables, and nuts may improve cogniIve funcIon. Longitudinal cohort studies support the beneficial relaIonship between fruit and vegetable intake and improved cogniIon (299). Two internaIonal trials provided an adult cohort of 27,860 parIcipants with high cardiovascular risk to examine diet quality (using a healthy eaIng index) and cogniIon (mini-mental state examinaIon score) (300). Healthier, higher scoring foods included vegetables, fruits, nuts, and soy proteins. During the 56 month follow up, those in the healthiest dietary quinIle had a significantly reduced risk of cogniIve decline compared with the unhealthiest quinIle (HR 0.76). Another study examined polyphenol dietary intake by measuring excreIon in urine (301).

The cross-secIonal study of 447 asymptomaIc elderly adults with high cardiovascular risk analysed food intake, urinary polyphenols, and cogniIve scores. They found that increased intake of anIoxidant-rich foods and in parIcular polyphenols, was associated with beWer cogniIve funcIon. This evidence has led to a proposed new dietary combinaIon known as the Mediterranean-DASH IntervenIon for NeurodegeneraIve Delay (MIND) – a mix of anI-hypertensive and Mediterranean diet paWerns that focuses on foods that might protect against neurodegeneraIon by increasing plant-based foods (vegetables, fruits, leafy greens, berries, nuts, beans, poultry, fish, olive oil) and reducing unhealthy foods (red meat and other foods high in saturated and trans-fat) (302). Greater adherence to it is associated with a slower rate of cogniIve decline across cogniIve domains (p<0.0001), even aher adjustment for cardiovascular disease risk factors, depression, obesity and age. This posiIve associaIon has been replicated in a 12-year longitudinal cohort study of Australian 60- to 64-year-olds, in whom high adherence to the MIND diet is associated with a lower odds of 12year cogniIve impairment (adjusted OR 0.47) compared to medium and low intake (303). These studies suggest that diet may play a role in both prevenIng and delaying the onset of demenIa.

ConducIng RCTs on whole dietary paWerns and long-term outcomes such as cogniIon can be challenging, and few such trials exist. Evidence is strongest for the Mediterranean diet. RCT evidence demonstrates the benefit of a Mediterranean diet on cogniIon compared to a low-fat control diet (304). Valls-Pedret et al. allocated parIcipants to consume the Mediterranean diet with either anIoxidant rich foods (extra virgin olive oil 1L/week) or mixed nuts (30g/day) or control (advice) in Spain. The Mediterranean diet and olive oil group scored beWer on composite frontal and global cogniIon scores compared with control (p=0.003 and p=0.005 respecIvely). The Mediterranean diet and nuts group performed significantly beWer compared with control for memory composite scores (p=0.04). The NU-AGE trial (running over a year in five European countries with 612 parIcipants (305)) found that adherence to a Mediterranean diet was correlated with changes in the gut microbiome, with increases in certain bacterial taxa that favour lower inflammatory markers and beWer cogniIon. Most RCTs are spread thinly across different foods or food-extracts including flavonoids, fruit extracts, cocoa, and nuts with weak or conflicIng results (299). A matched non-randomised control experiment included 23 overweight but otherwise healthy elderly parIcipants in each group (306).

Resveratrol, a plant-based polyphenol, was taken for 26 weeks versus placebo and demonstrated improved retenIon of words over 30 mins compared to baseline (p=0.038). In summary, diet is a modifiable risk factor for depression and cogniIve impairment. A paucity of intervenIonal research limits conclusions regarding causality. Epidemiological studies of dietary paWerns and food groups idenIfy the Mediterranean, MIND diet, and fruit and vegetable intake as superior to other diets or targeted nutriIonal approaches.

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Physical Ac&vity Depression There is strong evidence that exercise is an effecIve treatment for depression. A meta-analysis of RCTs idenIfied 218 studies and calculated pooled esImates by exercise type compared to acIve control as well as assessing the risk of dropouts to determine acceptability of the intervenIon (307). They found that exercise had a moderate effect on depression either alone or in combinaIon with pharmacotherapy or cogniIve behavioural therapy. The most effecIve modaliIes included jogging, and a dose-response relaIonship demonstrated greater benefit with increasing intensity. These results are supported by epidemiological evidence. A systemaIc review of 30 prospecIve longitudinal studies found that physical acIvity was associated with a lower risk of developing depression, even for brief duraIon, although increasing Ime spent exercising was associated with a greater reducIon in risk supporIng a preventaIve role (308). The role of physical acIvity in grief has also been reviewed, examining experimental and observaIonal studies (309). Physical acIvity was reported as beneficial in building and maintaining social relaIonships as well as reducing levels of depression, stress, loneliness and PTSD. Perinatal Period A meta-analysis of 48 RCTs showed that exercise was associated with significantly reduced perinatal depression scores compared to control (p<0.0001) (310).

Sub-group analyses demonstrated that exercise was effecIve at prevenIng and treaIng postpartum depression. Another RCT meta-analysis examined the effecIveness of exercise for treaIng postpartum depression: 12 RCTs including a total of 1260 women compared exercise to usual care (311). Exercise reduced depressive symptoms across all modaliIes compared with usual care. This included pram walking, yoga and supervised mixed exercise. Anxiety A systemaIc review and meta-analysis of 15 RCTs assessed the impact of exercise on individuals diagnosed with anxiety disorders or with heightened anxiety assessed using a validated scale (312). Aerobic exercise was found to reduce anxiety compared to waiIng list controls and higher intensity exercise was found to be more effecIve than low intensity although few studies followed up paIents long-term to determine persistence in effect. Other Mental Illness There is insufficient evidence on other mental health outcomes. A systemaIc review of eight studies examined individuals with schizophrenia, schizophrenia-like psychosis, schizoaffecIve disorders and bipolar affecIve disorder and found no evidence that exercise improved symptoms of schizophrenia or co-exisIng anxiety or depression (313).

Ac;ve Transport in Green Spaces In those aged 14-24, brief exposure to green spaces such as walking through parks improves mood and reduces anxiety in the short-term, although long-term evaluaIon is lacking (314). Studies also suggest mental health benefits for outdoor over indoor exercise, although data are sparse. A systemaIc review found seven studies of which only two reported a significant associaIon between acIve commuIng and reduced depression symptoms (315). Only one study was included from the UK (316). This longitudinal cohort study examined the difference in depressive symptoms in adults from the Biobank cohort. Adults without pre-exisIng depression who changed from inacIve to acIve commuIng reported significantly milder depressive symptoms compared to those who remained inacIve. Future acIve travel studies should evaluate mental health outcomes to determine the possible benefits and most effecIve modality or duraIon. Cogni;ve Impairment Physical acIvity may modify cogniIve funcIon. In healthy populaIons, repeated physical acIvity is associated with a small but significant improvement in memory test performance (317). A scoping

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review of RCTs on older adults with cogniIve frailty found that exercise (modaliIes included flexibility, resistance, or balance training, or walking or cycling) was associated with significant improvements in cogniIve funcIon, frailty, and depression (318). Similarly, a systemaIc review and meta-analysis of prospecIve cohort studies reported that high amounts of physical acIvity in older adults resulted in a 22% decrease in all-cause demenIa risk compared with those who were physical inacIve (p<0.05) (319). However, evidence is conflicIng for walking acIvity. A meta-analysis of RCTs reported that walking intervenIons did not result in a significant improvement in cogniIve funcIon in older adults with mild cogniIve impairment (320). A meta-analysis demonstrates that exercise significantly improves physical funcIon and neuropsychiatric symptoms in paIents with Alzheimer’s Disease (321). A non-significant trend was noted for cogniIve funcIon, and secondary analyses showed that aerobic exercise was significantly associated with improved MMSE test scores. A systemaIc review of quanItaIve and qualitaIve studies found a small but consistently posiIve effect of walking on depression, mood or other behavioural and psychological symptoms in paIents with demenIa, and reported posiIve experiences such as improved sleep, well-being, and maintaining “self-hood” (322).

Evidence also supports the use of exercise to improve physical strength, balance and mobility in paIents with demenIa (323). Sleep disorders are an important risk factor for depression, demenIa, diabetes and cardiovascular disease. RCT evidence suggests that physical acIvity (all types) is effecIve at improving sleep (324). People suffering with chronic faIgue syndrome (characterised by post-exerIonal faIgue and ohen severe cogniIve symptoms, pain and mental illness) may also benefit from physical acIvity to improve symptoms, especially faIgue. However, available evidence suggests this benefit is no greater than cogniIve behavioural therapy (325). In summary, physical acIvity is an effecIve treatment for depression, and may improve cogniIve funcIon and lower the risk of demenIa. Further research is required to determine the long-term impact of physical acIvity on anxiety. Combining physical acIvity with exposure to green spaces may provide addiIonal mental health benefits.