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Journal of Research and Health

2024، Volume 14، Number 3

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• A Bibliometric Analysis of Publications on Obesity and Hypertension Yanuan Ben Olina, Suparman Suparman, Budi Santosa, Satriya Pranata
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• Effects of a Mindfulness-based Education Program on Mindfulness, Emotional Regulation, Interoceptive Awareness, and University-life Adjustment for Korean University Freshmen Namgi Lee, Mijung Kim, Mijung Jung
• Perceived Life Outcomes of Indian Children During the Early Phase of the COVID-19 Lockdown: The Protective Roles of Joint and Nuclear Families Gyanesh Kumar Tiwari, Raghavendra Prasad Tiwari, Rakesh Pandey, Bablu Ray, Abhigyan Dwivedi, Devaki Nandan Sharma, Pankaj Singh, Ajay Kumar Tiwari, Ajit Kumar Singh
• Effect of Mindfulness-based Stress Reduction Intervention on Job Stress Among Primary School Teachers in Nigeria Osita Victor Ossai
• Spiritual Health, Nursing Stress, Compassion Fatigue, and COVID-19: A Descriptive Correlational Study Roya Vafaeinia, Tahereh Baloochi Beydokhti, Leila Moghadam Abbaspour, Hosein Ajamzibad
• Comparative Effects of Parent Management Training Combined With ACT and Mindful Parenting on Parent-child Relationship Farzaneh Kosari, Parviz Sabahi, Shahrokh Makvand Hosseini
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Associations between Nature Exposure and Health: A Review of the Evidence

Marcia p. jimenez.

1 Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02215, USA

2 Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA 02215, USA; ude.dravrah.hpsh@semajp

Nicole V. DeVille

3 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02215, USA; ude.dravrah.hpsh@ttoillee (E.G.E.); ude.dravrah.gninnahc@hcjer (J.E.H.)

Elise G. Elliott

4 Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02215, USA; ude.dravrah.hpsh@ffihcsj (J.E.S.); ude.dravrah.g@tliwg (G.E.W.)

Jessica E. Schiff

Grete e. wilt, jaime e. hart, peter james.

There is extensive empirical literature on the association between exposure to nature and health. In this narrative review, we discuss the strength of evidence from recent (i.e., the last decade) experimental and observational studies on nature exposure and health, highlighting research on children and youth where possible. We found evidence for associations between nature exposure and improved cognitive function, brain activity, blood pressure, mental health, physical activity, and sleep. Results from experimental studies provide evidence of protective effects of exposure to natural environments on mental health outcomes and cognitive function. Cross-sectional observational studies provide evidence of positive associations between nature exposure and increased levels of physical activity and decreased risk of cardiovascular disease, and longitudinal observational studies are beginning to assess long-term effects of nature exposure on depression, anxiety, cognitive function, and chronic disease. Limitations of current knowledge include inconsistent measures of exposure to nature, the impacts of the type and quality of green space, and health effects of duration and frequency of exposure. Future directions include incorporation of more rigorous study designs, investigation of the underlying mechanisms of the association between green space and health, advancement of exposure assessment, and evaluation of sensitive periods in the early life-course.

1. Introduction

The “biophilia hypothesis” posits that humans have evolved with nature to have an affinity for nature [ 1 ]. Building on this concept, two major theories—Attention Restoration Theory and Stress Reduction Theory—have provided insight into the mechanisms through which spending time in nature might affect human health. Attention Restoration Theory (ART) posits that the mental fatigue associated with modern life is associated with a depleted capacity to direct attention [ 2 ]. According to this theory, spending time in natural environments enables people to overcome this mental fatigue and to restore the capacity to direct attention [ 3 ]. The Stress Reduction Theory (SRT) describes how spending time in nature might influence feelings or emotions by activating the parasympathetic nervous system to reduce stress and autonomic arousal because of people’s innate connection to the natural world [ 4 , 5 ]. Further, proponents of the biophilia hypothesis postulate that green spaces provide children with opportunities such as discovery, creativity, risk taking, mastery, and control, which positively influence different aspects of brain development [ 6 ]. Beyond the biophilia hypothesis, there are a number of other pathways through which nature may affect health, including but not limited to increasing opportunities for social engagement and space for physical activity, while mitigating harmful environmental exposures (e.g., air pollution, noise, heat) [ 7 , 8 , 9 , 10 ]. Though evidence is inconsistent, physical activity may serve as an important mechanistic pathway to beneficial health outcomes by providing increased opportunities for outdoor exercise (e.g., walking) and play [ 7 , 8 , 9 ]. Facilitation of social contact is a promising mechanism emerging from recent literature, where natural environments and green space provide an avenue for increased contact with others and a greater sense of community [ 9 , 10 ]. The mechanism’s underlying associations between nature exposure and health outcomes are many, not completely understood, and could act in isolation or synergistically [ 11 ].

While the study of exposure to nature and health outcomes has expanded substantially over recent years, there remain many understudied relationships, mechanisms, and populations. For instance, there is a much more expansive evidence base for associations between nature and health, particularly with experimental studies, in adults than in children. This narrative review synthesizes recent scientific literature on associations between nature and health, highlighting studies conducted among children and youth where possible, published throughout August 2020 and based on: (1) randomized experimental studies of short-term exposure to nature and acute responses; and (2) observational studies of exposure to nature.

A narrative review synthesizes the results of quantitative studies that employ diverse methodologies and/or theoretical frameworks without a focus on the statistical significance of the studies’ results [ 12 , 13 ]. We conducted a keyword search-based review using PubMed Advanced Search on 31 August 2020 for studies published in the last ten years with titles or abstracts containing “greenness”, “green space” or “NDVI” (i.e., normalized difference vegetation index) as the exposure, and “health, “children’s health” or “youth health” as the outcome (National Library of Medicine, Bethesda, MD, USA). Using World Health Organization definitions, we categorized a child as a person younger than 10 years and youth from 10 to 24 years inclusive [ 14 ]. We limited this narrative review to research on human subjects only and included English-language-based, international peer-reviewed articles (e.g., primary research, reviews), online reports, electronic books, and press releases. We included both experimental and observational studies and applied snowballing search methodology using the references cited in the articles identified in the literature search. Each identified item was assessed for relevance by a member of the study team. This review is not comprehensive but is intended to summarize recent literature on nature exposure and health.

In retrieving literature on associations of nature and health, we reviewed a range of research from multiple health-related disciplines, geographic regions, and study populations. Evidence from the experimental and observational studies presented below represents more recent literature (e.g., the last decade) on nature exposure and health, primarily from Western countries.

3.1. Experimental Studies

We found a substantial body of research on natural environment interventions to evaluate the effects of nature on health from an experimental approach. The interventions consisted of active engagement in the natural environment (e.g., walking, running, or other activities), passive engagement (e.g., resting outside or living with a view), or virtual exposure (e.g., watching videos or viewing images of nature) [ 15 , 16 ]. The majority of experimental studies assessed mental health and neurologic outcomes. Results from experimental studies suggested a protective effect of exposure to natural environments on mental health outcomes and cognitive function.

3.1.1. Stress

Several experimental studies have examined perceived stress and other subjective measures of stress, such as sleep quality. A recent systematic review of more than 40 experimental studies indicates that measures of heart rate, blood pressure, and perceived stress provide the most convincing evidence that exposure to nature or outdoor environments may reduce the negative effects of stress [ 17 ]. The results from perceived or reported stress after exposure to natural environments were more consistent than findings from studies using physiological stress measurements (e.g., cortisol levels) among adults. A recent meta-analysis found evidence suggesting that exposure to natural environments may reduce cortisol levels, one of the most frequently studied biological markers of stress. Song et al. [ 18 ] reviewed 52 articles from Japan that examined the physiological effects of nature therapy. There was overwhelming evidence that cortisol levels decreased when participants were exposed to a natural environment. In numerous studies, salivary cortisol levels decreased after mild to moderate exercise in a natural environment compared with an urban environment [ 18 ].

Although many studies have observed significant decreases in measured salivary cortisol levels after exposure to natural environments, others have not observed any significant differences in salivary cortisol levels before and after exposure to natural environments [ 17 , 19 ]. However, a key limitation of using cortisol as a biomarker of stress in experimental studies is the fluctuation of cortisol over a 24-h period. Diurnal cortisol levels need to be taken into account in order to make a fair comparison, and most of the literature on exposure to nature and stress have only studied cortisol levels before and after exposure [ 17 ].

Experimental studies focusing on children or youth are sparse [ 20 , 21 ]. One quasi-experimental study conducted in 10–12 year-olds in a school setting examined the influence of natural environments on stress response [ 22 ]. The researchers observed higher tonic vagal tone, a measure of heart rate variability, in natural environments but found no associations with event or phasic vagal tone.

3.1.2. Affective State

Exposure to natural environments has also been studied in relation to the self-reported affective state, or the underlying experience of feeling, emotion or mood. Although study measures vary, studies among adults have generally observed relationships between exposure to natural environments and affective state, with positive associations with positive emotions and negative associations with negative emotions [ 16 , 22 , 23 ]. A study randomly assigned sixty adults to a 50-min walk in either a natural or an urban environment in Palo Alto, California, and found that compared to urban experience, nature experience led to affective benefits (decreased anxiety, rumination, and negative affect, and preservation of positive affect) as well as cognitive benefits (increased working memory performance) [ 23 ]. In a study investigating forest bathing, or shinrin-yoku, researchers found that time spent in forests was associated with a reduction in reported feelings of hostility, depression, and anxiety among adults with acute and chronic stress [ 24 ]. Another study examining walking in different environments observed the largest and most consistent improvements in psychological states associated with forest walks [ 25 ]. Forest bathing may play an important role in health promotion and disease prevention. However, the lack of studies focused on children or youth limits the generalizability of these findings across a wide age range [ 26 ].

3.1.3. Anxiety and Depressive Mood

Exposure to natural environments has been linked with decreases in anxiety and rumination, which are associated with negative mental health outcomes, such as depression and anxiety [ 23 , 27 ]. Nature-based health interventions (NBI) are interventions that aim to engage people in nature-based experiences with the goal of improving health and wellness outcomes [ 28 ]. One study evaluated a wetland NBI in Gloucestershire, UK, that was designed to facilitate engagement with nature as a treatment for individuals diagnosed with anxiety and/or depression. The study found that the wetland site provided a sense of escape from participants’ everyday environments, facilitating relaxation and reductions in stress [ 27 ]. A recent systematic review and meta-analysis found a reduction in depressive mood following short-term exposure to natural environments [ 21 ]. However, the authors noted that the reviewed studies were generally of low quality due to a lack of blinding of study participants and a lack of information on randomization quality among randomized trials.

3.1.4. Cognitive Function

Experimental studies have examined the impact of brief nature experiences and cognition among adults, investigating cognitive function related to exposure to natural environments, and are consistent with the results from studies among school-aged children. A growing number of studies have found that exposure to natural environments compared with urban environments is associated with improved attention, executive function, and perceived restorativeness [ 16 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. These studies have found statistically significant associations with positive cognitive outcomes, even after short periods of time spent in natural environments. Additionally, an emerging area of research is virtual reality (VR), using eye-tracking and wearable biomonitoring sensors to measure short-term physiological and cognitive responses to different biophilic indoor environments. These studies have found consistent physiological and cognitive benefits in indoor environments with diverse biophilic design features [ 38 , 39 ].

3.1.5. Brain Activity

Exposure to nature has been associated with alterations in brain activity in the prefrontal cortex, an area of the brain that plays an important role in emotional regulation [ 18 , 19 ]. One experimental study among female university students in Japan investigated physiological and psychological responses to looking at real plants compared with images of the same plants [ 40 ]. Although participants reported feelings of comfort and relaxation after seeing either real plants or images of the same plants, a physiological response was observed only after seeing real plants. Seeing real plants was associated with increased oxy-hemoglobin concentrations in the prefrontal cortex, suggesting that real plants may have physiological benefits for brain activity not replicated by images of plants.

3.1.6. Blood Pressure

Two meta-analyses [ 18 , 41 ] found evidence suggesting that exposure to a natural environment reduced blood pressure. Song et al. [ 18 ] reviewed the research in Japan from 52 studies on the physiological effects of nature therapy and found overwhelming evidence that blood pressure levels decreased when participants were exposed to a natural environment. Decreases in both systolic and diastolic blood pressure levels were observed across young healthy populations, as well as populations with hypertension. This suggests that forest walking may lead to a state of physiological relaxation [ 18 ]. Ideno et al. [ 41 ] conducted another systematic review and meta-analysis to synthesize the effects of forest bathing on blood pressure, including 20 trials involving 732 participants including high-school and college-aged youth. The authors found that both systolic and diastolic blood pressure taken in the forest environment were significantly lower than in non-forest environments [ 41 ].

3.1.7. Immune Function

In Japan, forest bathing has been positively associated with human immune function [ 42 ]. A study was conducted in which subjects experienced a 3-day/2-night bathing trip to forest areas, and blood and urine were sampled on days 2 and 3 of the trip. On days 7 and 30 after the trip, it was found that the mean values of natural killer (NK) cells (which play a major role in the immune system) and NK activity were higher on forest bathing days compared with control days [ 43 ]. This effect persisted for 30 days after the trip. A potential pathway for improved immune function is exposure to phytoncides (a substance emitted by plants and trees to protect themselves from harmful insects and germs), which could decrease stress hormones in the human body and increase NK cell activity. Additionally, the findings indicated that a day trip to a forest park also increased the levels of intracellular anti-cancer proteins [ 43 ].

3.1.8. Postoperative Recovery

While there is limited research on the effect of nature on postoperative recovery, a seminal study by Ulrich [ 4 ] investigated recovery after a cholecystectomy on patients with and without a room with a window view of a natural setting. Patients with a view of a natural setting had shorter hospital stays, received fewer negative evaluative comments in the nurse’s notes section of their charts, and took fewer potent analgesics (e.g., opiates) than those patients whose windows faced a brick building wall [ 4 ]. More recent research has successfully replicated the concept that plants and foliage in the hospital environment may have beneficial impacts on surgical recovery in randomized trials [ 44 , 45 ].

3.2. Observational Studies

Cross-sectional observational studies have shown evidence of positive associations between exposure to nature, higher levels of physical activity, and lower levels of cardiovascular disease. Increasingly, longitudinal observational studies have started to examine the long-term effects of exposure to nature on depression, anxiety, cognitive function, and chronic disease. Below, we summarize the key findings on mental health, physical activity, obesity, sleep, cardiovascular disease, diabetes, cancer, mortality, birth outcomes, asthma and allergies, and immune function.

3.2.1. Mental Health

A recent systematic review found limited evidence suggesting a beneficial association with mental well-being in children and depressive symptoms in adolescents and young adults [ 21 ]. However, access to green space has been linked with improved mental well-being, overall health, cognitive development in children [ 46 ], and lower psychological distress in teens [ 47 ]. A study that examined the restorative benefits associated with frequency of use of different types of green space among US-based students found that students who engaged with green spaces in active ways ≥15 min four or more times per week reported a higher quality of life, better overall mood, and lower perceived stress [ 48 ]. Research in the U.S.-based Growing Up Today Study (GUTS) found that increased exposure to greenness measured around the home was associated with a lower risk of high depressive symptoms cross-sectionally (as measured with the McKnight Risk Factor Survey) and a lower incidence of depression longitudinally [ 49 ]. The investigators observed stronger associations in more densely populated areas and among younger adolescents [ 49 ]. Similarly, a study in four European cities (Barcelona, Spain; Doetinchem, The Netherlands; Kaunas, Lithuania; and Stoke-on-Trent, UK) that evaluated childhood nature exposure and mental health in adulthood showed that adults with low levels of childhood nature exposure had, when compared with adults with high levels of childhood nature exposure, significantly worse mental health, assessed through self-reports of nervousness or depression [ 50 ]. Another study of approximately one million Danes over 28 years of follow-up found that high levels of continuous green space presence during childhood were associated with lower risk of a wide spectrum of psychiatric disorders later in life [ 51 ]. A study based in the UK tracked individuals’ residential trajectories for five consecutive years and showed that individuals who moved to greener areas had better mental health than before moving [ 52 ]. Collectively, these studies suggest that implementation of environmental policies to increase urban green space may have sustainable public health benefits.

Novel research has examined green outdoor settings as potential treatment for mental and behavioral disorders, such as attention-deficit/hyperactivity disorder (ADHD). One study demonstrated associations between green space exposure and improvement in behaviors and symptoms of ADHD and higher standardized test scores [ 46 ]. A recent systematic review found significant evidence for an inverse relationship between green space exposure and emotional and behavioral problems in children and adolescents [ 21 ]. Research has also shown that more and better quality residential green spaces are favorable for children’s well-being [ 53 ] and health-related quality of life [ 54 ]. Furthermore, the quality of green space appears to be more important as children age, as associations between green space quality and well-being are stronger in 12–13 year-olds compared with 4–5 year-olds [ 53 ]. In addition, natural features near schools, including forests, grasslands, and tree canopies, are associated with early childhood development, preschoolers’ improvement in socio-emotional competencies [ 55 ], and a decrease in autism prevalence [ 56 ].

Exposure to nature during adulthood also appears to be important for mental health. A study of 94,879 UK adults indicated a consistent protective effect of greenness on depression risk that was more pronounced among women, participants younger than 60 years, and participants residing in areas with low neighborhood socioeconomic status or high urbanicity [ 57 ]. Other innovative studies are starting to examine quantifiable time of exposure to evaluate the duration of time spent in nature that is associated with mental health benefits. For example, using a nationally representative sample of American adults, Beyer et al. [ 58 ] found that individuals who spent 5–6 or 6–8 h outdoors during weekends had lower odds of being at least mildly depressed, compared with individuals who spent less than 30 min outdoors on weekends. Another study from the UK suggested that lower levels of depression were associated with spending five hours or more weekly in a private garden [ 59 ]. Other studies are focused on uncovering which characteristics of green space are the determinants of mental health benefits. A UK study examined neighborhood bird abundance during the day and found inverse associations with prevalence of depression, anxiety, and stress [ 60 ].

The collective results from these studies suggest that nearby nature is associated with quantifiable mental health benefits, with the potential for lowering the physical and financial costs related to poor mental health. Most of these studies are cross-sectional, and reverse causation is possible. However, researchers are employing novel designs to examine the relationship between green space and mental health. For example, in a study of twins enrolled in the University of Washington Twin Registry, increased greenness was associated with decreased risk of self-reported depression, stress, or anxiety; however, only the results for depression were robust in within-twin pair analyses, suggesting the effect of green space on depression cannot be explained by genetics alone [ 61 ]. Finally, it is important to note that technological advancements have yielded improvements in assessments of exposure to nature and mental health. For instance, one study among adults 18–75 years of age used smartphones equipped with ecological momentary assessment applications to track location, physical activity, and mood for consecutive days, and found positive associations with feeling happy and restored or relaxed within 10 min of exposure to natural outdoor environments [ 62 ]. More novel studies such as these will bolster the evidence behind exposure to nature and mental health among children and/or youth.

3.2.2. Physical Activity

An extensive body of literature documents the impacts of access to green spaces or surrounding greenness on physical activity in children and adults. Proximity to green spaces may promote physical activity by providing a space for walking, running, cycling, and other activities. Although the bulk of the literature is cross-sectional, most studies (in both children and adults) have observed higher levels of physical activity in areas with more access to green space. For example, a study in Bristol, UK, evaluated associations between accessibility to green space and the odds of respondents achieving a recommended 30 min or more of moderate activity five times a week; respondents who lived closest to the type of green space classified as a formal park were more likely to achieve the physical activity recommendation [ 63 ]. Another study of adults in the UK found that people living in greenest compared with least-green areas were more likely to meet recommended daily physical activity guidelines [ 64 ]. However, another UK-based study did not find associations between road distance to nearest green space, number of green spaces, area of green space within a 2-km radius of residence, or green space quality and physical activity [ 65 ].

Almanza et al. [ 66 ] used GPS and accelerometry data among 208 children in California and found that greenness was associated with higher odds of moderate to vigorous physical activity, when comparing those in the 90th and 10th percentiles of greenness. Additionally, they found that children with >20 min daily green space exposure had nearly 5 times the daily rate of moderate to vigorous physical activity compared with those with nearly zero daily exposure [ 66 ]. Another study of Australian children illustrated that time spent outdoors at baseline positively predicted the amount of physical activity three years later [ 67 ]. In a review of youth health outcomes related to exercising in nature (i.e., “green exercise”), the results of fourteen studies (5 in the UK, 5 in the U.S., 2 in Australia, and 1 in Japan) indicated little evidence that green exercise is more beneficial than physical activity conducted in other locations, although any physical activity was beneficial across settings [ 68 ].

More recent studies have employed more sophisticated study designs to determine whether exposure to greenness increases physical activity. In studies that objectively assessed physical activity via accelerometers, individuals exposed to more greenness tended to be more physically active. For example, in a study of 15-year-olds in Germany, increases in greenness around the home address were associated with increased moderate-to-vigorous physical activity among youth in rural, but not urban, areas [ 69 ]. Another study of children in the UK evaluated momentary green space exposure based on GPS-derived location and contemporaneous physical activity measured by an accelerometer and found higher odds of physical activity in green space (versus outdoor non-green space) for boys but not girls [ 70 ].

3.2.3. Obesity

Green space may influence overweight or obesity through a physical activity pathway [ 71 ]. Some studies have shown that exposure to green space is associated with lower rates of obesity in children [ 67 ] and adults [ 72 ]; however, the results are conflicting. As with physical activity, many early studies were cross-sectional, and findings were more mixed for children than for adults. Some studies reported U-shaped associations with obesity [ 73 ], while other studies reported no association after adjustment for respondent characteristics [ 63 ] or neighborhood socioeconomic status [ 74 ]. Some studies demonstrate effect modification by gender [ 72 ]. Further, one cross-sectional UK-based study found that living in the greenest areas was associated with an increase in risk of being overweight and obese [ 75 ].

In one study of U.S. children, increasing greenness was associated with lower BMI z-scores and lower odds of increasing BMI z-scores between two follow-up times [ 76 ]. Another study of schoolchildren in Spain found that greenness and forest proximity were associated with lower prevalence of being overweight or obese [ 77 ]. One study found that street tree density was associated with lower obesity prevalence in New York City (U.S.) children; however, no association was found with park areas [ 78 ]. In an Australian study, the prevalence of being overweight was 27–41% lower in girls and boys who spent more time outdoors at the study baseline than those who spent less time outdoors [ 67 ]. Another study found that greenness was associated with decreased risk of being overweight but only among those in areas with a greater population density [ 79 ].

3.2.4. Sleep

Exposure to green space may influence sleep duration and quality. For instance, surrounding greenness may serve as a buffer for noise, which would disturb sleep. To date, only a handful of studies have examined these associations, and to our knowledge, even fewer have explored this association in children. A recent systematic review provided evidence of an association between green space exposure and improved sleep quality among adults [ 80 ]. A study of Australian adults who lived in areas with greater than 80% green space demonstrated lower risk of short sleep duration, even after adjustment for other predictors of sleep [ 81 ]. Among U.S. adults participating in the Behavioral Risk Factor Surveillance System survey, natural amenities (e.g., green space, lakes, and oceans) were associated with lower reporting of insufficient sleep, and greenness was especially protective among men and individuals over 65 years of age [ 82 ]. In the Survey of Health in Wisconsin Study, increased tree canopy at the Census block group level was associated with lower odds of short sleep duration on weekdays and suggestive of an association with lower odds of short sleep duration on weekends, although there was no association between tree canopy and self-reported sleep quality [ 83 ]. A nationally representative study of Australian and German children and adolescents found no evidence of significant associations between residential green space and insufficient sleep or poor sleep quality [ 84 ].

3.2.5. Cardiovascular Disease

Exposure to green space may affect levels of physical activity, stress, and high blood pressure that drive cardiovascular disease risk. Recent reviews have found consistent evidence that exposure to residential green space is associated with decreased cardiovascular disease incidence [ 85 , 86 ]. Participants living in areas with lower greenness have higher levels of mortality following a stroke [ 87 ], higher cardiovascular disease mortality [ 88 , 89 ], and higher coronary heart disease [ 90 ]. A study from the UK found that associations between exposure to nature and cardiovascular outcomes differed by gender, where male cardiovascular disease and respiratory disease mortality rates decreased with increasing green space, and no associations were found for women [ 88 ]. Furthermore, the relationships between exposure to greenspace and cardiovascular outcomes may be modified by urbanicity. A recent Australian study showed significantly lower odds of high blood pressure among adults in an urban population when reported green space visits were an average of 30 min or more [ 91 ].

3.2.6. Diabetes

Although limited, evidence regarding the association between green space and type 2 diabetes highlights green space as a possible route for diabetes prevention. There are a few cross-sectional studies that have reported that green space is inversely related to type 2 diabetes among adults [ 92 , 93 ]. Few studies have examined the relationship between green space and diabetes in children. Cross-sectional studies of children found inverse associations between time spent in green spaces and fasting blood glucose levels [ 77 ] and insulin resistance [ 94 ]. A recent longitudinal study conducted on US children found no associations between residential exposure to green space and insulin resistance [ 95 ].

3.2.7. Cancer

Research on the link between green space and cancer is limited and may vary depending on the type of cancer. A recent case-control study examined whether residential green space exposure was related to prostate cancer incidence and found that higher residential greenness was associated with lower risk of prostate cancer [ 96 ], and a separate study of U.S. men demonstrated inverse associations between neighborhood greenness and lethal prostate cancer [ 97 ]. Another study examined the association between green space and several cancer types and found that green space was protective for mouth, throat, and non-melanoma skin cancers but was not associated with colorectal cancer [ 98 ]. A U.S.-based nationwide study of nurses found that residential greenness was inversely associated with breast cancer mortality [ 99 ]. Conversely, another systematic review that evaluated evidence on the association between residential green spaces and lung cancer mortality found no benefits of residential greenness [ 85 ].

3.2.8. Mortality

Many early mortality studies relied on cross-sectional data and could not estimate nature exposure over time [ 100 ], whereas others could not account for important potential confounding by race/ethnicity, individual-level smoking, and area-level socioeconomic factors, such as median home value [ 101 , 102 ]. A UK-wide ecological study found that all-cause mortality was higher in greener cities [ 89 ]. An analysis of greenness and mortality in male and female stroke survivors living in Boston (U.S.) found that greater exposure to greenness was associated with higher survival rates [ 87 ]. Another U.S.-based nationwide study of nurses found a consistent protective relationship between residential greenness and non-accidental mortality [ 103 ]. The greenness–mortality relationship was explained primarily by a mental health pathway, and the relationship was strongest among those who had high levels of physical activity [ 103 ]. A study of 4.2 million adults in the Swiss National Cohort assessed the relationship between residential greenness and mortality, while mutually considering socioeconomic status, air pollution, and transportation noise exposure, and found that higher exposure to green space was associated with lower rates of death from natural causes, respiratory disease, and cardiovascular disease [ 104 ]. Protective effects were stronger in younger individuals and in women and, for most outcomes, in urban (versus rural) and in the highest (versus lowest) socioeconomic quartile. Effect estimates did not change after adjustment for air pollution and transportation noise, suggesting that the protective effect of exposure to nature persists in the absence of pollution sources. Finally, a systematic review and meta-analysis of cohort studies on green space and mortality assessed findings from nine studies, comprising 8.3 million individuals from seven countries across the globe [ 105 ]. Seven of the nine studies demonstrated an inverse relationship between green space exposure and mortality, and the authors recommended wide-scale interventions to increase and manage green spaces in order to improve public health outcomes.

3.2.9. Birth Outcomes

The relationship between exposure to nature and birth outcomes has been studied extensively in analyses across multiple countries. Findings of positive associations between greenness and birth weight and decreased risk of low birth weight are consistent, with stronger associations observed among those of a lower socioeconomic status [ 106 ]. Banay et al. [ 107 ] reviewed studies that examined the association between greenness and maternal or infant health. While the majority of studies were cross-sectional, many studies found evidence for positive associations between greenness and birth weight. Fewer studies demonstrated consistent evidence for an association between greenness and gestational age, preeclampsia, or gestational diabetes. These studies also found that effects were stronger among those of a lower socioeconomic status. A more recent review highlighted the evolving literature showing that higher levels of residential greenness were associated with lower risk of preterm birth, low birth weight, and small gestational-age babies [ 108 ]. Akaraci et al. [ 109 ] conducted a systematic review and meta-analysis of 37 studies on residential green and blue spaces and pregnancy outcomes. Increases in residential greenness were associated with higher birthweight and lower odds of being small for gestational age; however, no significant associations between residential blue spaces and birth outcomes were found.

3.2.10. Asthma/Allergies

Several studies have examined the relationship between greenspace and atopic outcomes, including asthma and allergies. Mechanistically, trees and plants are a source of allergens and respiratory irritants [ 110 ]. However, the biodiversity created by green space could be protective against inflammatory conditions [ 111 , 112 ]. The literature reflects these contrasting hypotheses with mixed findings. Some studies have shown no association between the normalized difference vegetation index (NDVI) or tree canopy cover and asthma [ 113 ], while other studies have shown that living close to forests and parks was positively associated with allergic rhinoconjunctivitis and asthma [ 77 ]. Another study of greenspace and allergies in Germany demonstrated positive associations in urban areas and negative associations in rural areas [ 114 ]. The same investigators examined data from seven birth cohorts across Sweden, Australia, the Netherlands, Canada, and Germany and found that the relationship between residential NDVI and allergic disease was positive in some countries and negative in others [ 115 ]. A study in Spain found proximity to residential greenness to be protective of bronchitis in the Mediterranean region of Spain and protective of wheezing for children in the Euro-Siberian region of Spain [ 116 ]. One study conducted in China examined the relationship between exposure to greenness and parks and asthma and allergies among middle-school-aged children [ 117 ]. The researchers observed no associations between residential greenness exposure and self-reported doctor-diagnosed asthma, pneumonia, rhinitis, and eczema; however, living farther away from a park was associated with decreased odds of currently or ever having asthma. In sum, the relationship between exposure to nature and asthma and allergies is inconsistent, with associations varying in magnitude and direction by geography. One review of fourteen studies suggested an association between early life exposure to urban greenness and allergic respiratory diseases (e.g., asthma, bronchitis, allergic symptoms) in childhood; however, there were inconsistencies among study results, likely due to variability in study design, exposure assessment, outcome ascertainment, and geographic region [ 118 ].

3.3. Natural Experiments/Randomized Controlled Trials of Chronic Outcomes

Beyond smaller experimental studies of short-term outcomes and observational epidemiologic studies of chronic outcomes, there are a few natural experiments and randomized controlled trials that add substantial evidence to the relationship between exposure to nature and health. These quasi-experimental and randomized trials have lower potential for confounding bias to explain observed associations between nature and health. One important study capitalized on a natural experiment when an invasive tree pest, the emerald ash borer, killed over 100 million ash trees in the Midwestern United States [ 119 ]. The investigators found that living in a county infested with the emerald ash borer was associated with a 41% increased risk of cardiovascular disease, and these results were only consistent when looking in metropolitan areas where they could adjust for socioeconomic status. Another innovative study examined the greening of vacant lots in Philadelphia [ 120 ]. This citywide study used a three-arm randomized trial approach to randomize 110 vacant lots to either no intervention, cleaning but no greening, or cleaning and greening. The study found that those living around lots that were greened had substantial decreases in reports of depression, poor mental health, and feelings of worthlessness compared with lots that had no intervention. Those living around lots that were cleaned but not greened showed no difference compared with no intervention. Another ongoing longitudinal study in Sydney, Australia, is evaluating the effects of large-scale investment in green space (e.g., public access points, advertising billboards, walking and cycle tracks, BBQ stations, and children’s playgrounds) on physical activity, mental health, and cardiometabolic outcomes [ 121 ]. This natural experiment utilizes proximity to different areas of the Western Sydney Parklands to define treatment and control groups.

Looking to the future, there are a few randomized trials in progress that will provide fundamental evidence to understand whether adding green pace to cities benefits health. The Green Heart Project in Louisville, Kentucky, will assess risk of diabetes and heart disease, stress levels, and the strength of social ties in 700 participants [ 122 ]. The team will take baseline measurements of air pollution levels and will plant as many as 8000 trees, plants, and shrubs throughout Louisville neighborhoods to create an urban ecosystem that promotes physical activity while simultaneously decreasing noise, stress, and air pollution. During five years of follow-up, participants will receive annual check-ups to evaluate how the increasing greenery has affected their physical and mental health and social ties. A second randomized trial is the ‘Productive Green Infrastructure for Post-industrial Urban Regeneration’ or ProGIreg, a multi-city study examining the potential effects of green infrastructure [ 123 ]. This project is based in Dortmund (Germany), Turin (Italy), Zagreb (Croatia) and Ningbo (China) where Living Labs are hosted and nature-based solutions are developed, tested, and implemented. Although health is not the main focus of this study, researchers are hoping to incorporate health metrics into the study design to examine pre- and post-intervention outcome data. Collectively, these randomized trials, natural experiments, and pre-post study designs will establish crucial data on whether interventions to incorporate nature into cities can measurably improve health.

3.4. Effect Modification/Susceptible Populations

Inequitable distribution of green spaces could exacerbate health inequalities if people who are already at greater health risks (e.g., people with lower socioeconomic status) have limited access. Many studies have indicated that disadvantaged populations have decreased access to nature and greenspace [ 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ]. At the same time, evidence suggests that exposure to nature disproportionately benefits disadvantaged populations, a phenomenon known as the equigenic effect of green space, which upends the expected association between lower socioeconomic status and greater risk of poor health outcomes [ 133 ]. Based on the theory of equigenic environments, one study showed that populations exposed to the greenest environments also had the lowest levels of health inequality related to income deprivation, suggesting that green space might be an important factor in reducing socioeconomic health disparities [ 89 ]. A review of 90 studies on green space and health outcomes demonstrated that individuals of lower socioeconomic status showed more beneficial effects than those of higher socioeconomic status; the authors found no significant differences in the protective effects of green space on health outcomes among different racial/ethnic groups [ 134 ]. The evidence is inconsistent, and more work is needed to elucidate potential mechanisms.

Conversely, improvements in access to green space may lead to “green gentrification,” an increase in property values that displaces low-income residents from their neighborhoods [ 129 , 135 , 136 , 137 ]. This process needs to be studied and understood so that its adverse effects can be prevented. Other cultural and contextual factors may affect nature preferences and experience of nature. For instance, there is evidence that the legacy of forced labor, lynching, and other violence may evoke deeply disturbing associations with trees, fields, and forests among some African Americans [ 138 , 139 ]. Similarly, some people may prefer open fields for sports, while others prefer picnic facilities for socializing.

4. Discussion

The purpose of this narrative review was to summarize recent experimental and observational literature on associations between nature exposure and health in adults and children/youth. While some associations between nature and health outcomes are well-studied, our review highlights the lack of studies, particularly experimental, among child/youth and other susceptible populations. We found evidence for associations between exposure to nature and improved cognitive function, brain activity, blood pressure, mental health, physical activity, and sleep. Results from experimental studies indicated protective effects of nature exposure on mental health and cognitive function. Cross-sectional observational studies provide evidence of positive associations between nature exposure, higher levels of physical activity and lower levels of cardiovascular disease. Observational studies, natural experiments, and randomized controlled trials are starting to assess the longitudinal effects of exposure to nature on depression, anxiety, cognitive function, chronic disease, and other health outcomes. Our review synthesizes recent literature, primarily from Western countries; thus, a limitation of this review is that we may not have captured all relevant literature from outside our publication range or across all geographic regions.

4.1. Data Gaps and Limitations

There are several limitations in the literature on exposure to nature and health. First, definitions of nature are inconsistent across studies. Further, the impacts of the quality of green space, duration of exposure to nature, frequency of exposure, or type of nature exposure on health outcomes are not well understood. Second, methods for measuring exposure to nature (e.g., percentage of residential greenness versus distance to the closest park) or defining the relevant geographic area of exposure (e.g., 500 m away from our home versus 1 km or 10 km) are inconsistent [ 140 , 141 ]. We must also develop methods to elucidate thresholds for dose and duration of nature exposure to achieve a given health effect. Although some studies have determined potential estimates of relevant doses [ 142 ], this area of research is nascent. In addition, standard approaches towards nature exposure assessment do not capture the variations in how people experience nature differentially (e.g., smell, touch, etc.) and have low reproducibility across studies (e.g., inconsistent land-use measures). Third, critical time windows of exposure during the life course that might have the greatest impact on health are also understudied (e.g., early life exposure, childhood exposure). Fourth, mechanistic pathways are understudied. Further, the dynamic relationship between green space, air pollution, noise, temperature, and neighborhood walkability also warrant further exploration, as these factors could be both mediators or moderators of the nature–health relationship [ 143 , 144 ]. We also know little about the potential harms of exposure to nature, most commonly observed in studies of asthma and allergies.

4.2. Future Directions

There are ample promising future directions for nature and health research. First, future research should employ rigorous study designs (e.g., longitudinal studies, randomized controlled trials) and investigate the underlying mechanisms of observed associations between exposure to nature and health outcomes. Although cross-sectional studies dominate the literature, there is increasing evidence emerging from prospective studies, which are essential to investigating causal relationships [ 108 ]. Novel designs, such as quasi-experimental studies and randomized trials, will provide further detail on how nature influences health [ 119 ]. Furthermore, studies should thoroughly evaluate potential biases, such as confounding by socioeconomic status, that may threaten the validity of studies on nature and health. Researchers should rigorously examine factors that may modify the effects of exposure to nature (e.g., socioeconomic status, gender, or race) to determine the subpopulations that might benefit most from exposure to nature. A life-course approach to examining associations between green space and health is also essential. We need to better understand vulnerable time windows in the early life-course where access or exposure to nature may have stronger impacts on health than in other time periods. Similarly, additional research assessing dose-response relationships (e.g., duration of time in nature or quantity of vegetation) is crucial to determine the minimum amount of exposure to green space needed to yield health benefits or if the relevant dosage varies across the life-course or across different countries/settings [ 142 ].

Second, future studies should make use of novel datasets and computational approaches that may provide rapid advances in exposure assessment. Emergence of advanced satellite and aerial photos combined with machine learning to develop tree canopy measures and other more specific metrics of nature provide information on specific species on the ground. Google Street View and other ubiquitous geocoded imagery, when combined with machine learning, also provide scalable approaches to estimate specific natural features from the on the ground perspective as human beings experience them [ 145 ]. Combined with geocoded residential addresses or GPS data and health or behavioral data, these approaches may unveil novel insights on how nature exposure affects health. Leveraging smartphones with GPS and accelerometry enable fine-scale information on exposure and physical activity. Ecological momentary assessment (EMA) or micro-surveys administered through smartphones can be used to ask about processes for how and why people interact with nature [ 62 ]. EMA can also be applied to estimate mental health outcomes in real time, and these responses can be geo-tagged and linked to spatial measures of natural environments. In addition, consumer wearable devices (e.g., FitBit) provide objective information on physical activity patterns, heart rate, sleep, and other biometrics down to the second level [ 146 ]. These data will prove crucial to better understand the behavioral mechanisms through which nature exposure impacts health. We should also capitalize on geo-located social media data (Flickr, Twitter, Facebook) and other data sources to understand exposure to nature [ 147 ]. Innovative metrics of mental health, such as skin conductivity, cortisol (stress), heart rate variability, brain activity through EEG, and functional MRI, can also provide information on stress processes when individuals encounter natural environments [ 148 ]. Such measures of nature exposure and time spent in nature should be incorporated into large federal data collection efforts, such as the Behavioral Risk Factor Surveillance System (BRFSS), National Health Interview Survey (NHIS), and National Health and Nutrition Examination Survey (NHANES) in the United States or the Health Survey for England (HSE) in the United Kingdom. These recommendations cannot be accomplished without also considering the impacts climate change is currently having and will have on exposures to nature, and how climate change may alter the relationship individuals have with nature.

Third, future studies on nature and mental health should focus more on positive health—happiness, purpose, flourishing—instead of just the absence of negative mental health outcomes. Further, more research is required on natural water features, or blue space [ 149 ], as well as other natural environments.

Fourth, the overwhelming majority of research on nature and health is on urban study populations in North America, Europe, and Australia. Researchers should also focus on different geographic areas, low-income and middle-income settings, and vulnerable or historically marginalized populations where nature benefits might be greatest. Researchers should also work together with communities as they conduct their research to ensure their work addresses the needs of community members.

Finally, we must also recognize the potential unintended consequences of adding green infrastructure in cities. Adding green amenities to cities may entice high-income populations, and the resulting increased property values shape a new conundrum, embodied in the exclusion and displacement associated with so-called green gentrification [ 135 ]. Results from this type of research should also be considered for policies, urban planning, and designing cities.

5. Conclusions

The purpose of this review was to examine recent literature on exposure to nature and health, highlighting studies on children and youth where possible. We assessed the strength of evidence from experimental and observational studies and found evidence for associations between exposure to nature and improved cognitive function, brain activity, blood pressure, mental health, physical activity, and sleep. Evidence from experimental studies suggested protective effects of exposure to natural environments on mental health outcomes and cognitive function. Cross-sectional observational studies provide evidence of positive associations between exposure to nature, higher levels of physical activity and lower levels of cardiovascular disease. Longitudinal observational studies are starting to assess the long-term effects of exposure to nature on depression, anxiety, cognitive function, and chronic disease. Limitations and gaps in studies of nature exposure and health include inconsistent measures of exposure to nature, knowledge of the impacts of the type and quality of green space, and the health effects of the duration and frequency of exposure among different populations (e.g., adults, children, historically marginalized). Future research should incorporate more rigorous study designs, investigate the underlying mechanisms of the association between green space and health, advance exposure assessment, and evaluate sensitive periods throughout the life-course.

Author Contributions

Conceptualization, M.P.J., N.V.D., J.E.H. and P.J.; methodology, M.P.J., N.V.D., J.E.H. and P.J.; writing—original draft preparation, M.P.J., N.V.D., E.G.E., J.E.S., G.E.W., J.E.H. and P.J.; writing—review and editing, M.P.J., N.V.D., E.G.E., J.E.S., G.E.W., J.E.H. and P.J.; supervision, J.E.H. and P.J.; project administration, N.V.D.; funding acquisition, P.J. All authors have read and agreed to the published version of the manuscript.

This research was funded by The National Geographic Society, and NIH grants R00 CA201542, R01 HL150119, T32 {"type":"entrez-nucleotide","attrs":{"text":"ES007069","term_id":"164015192","term_text":"ES007069"}} ES007069 , K99 AG066949, R01 ES028712 and P30 ES000002.

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Sumibcay JRC , Kunichoff D , Bassett MT. Racial and Ethnic Disparities in COVID-19 Mortality. JAMA Netw Open. 2024;7(5):e2411656. doi:10.1001/jamanetworkopen.2024.11656

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Racial and Ethnic Disparities in COVID-19 Mortality

• 1 FXB Center for Health and Human Rights, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
• 2 Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
• Invited Commentary Health Equity for US Asian, Native Hawaiian, and Pacific Islander Populations Naoko Muramatsu, PhD; Marshall H. Chin, MD, MPH JAMA Network Open

In May 2023, the United States ended the federal COVID-19 Public Health Emergency (PHE) with more than 1.1 million reported deaths. 1 American Indian or Alaska Native and Native Hawaiian or Pacific Islander individuals represent numerically small populations (constituting 1.3% and 0.3% of the total US population, 2 respectively). Their high mortality rates have minimal impact on national rates and may receive little attention. 3 To uncover these disparities, we analyzed separately the racial and ethnic mortality trends during the PHE, focusing on surge periods.

This cross-sectional analysis used publicly available COVID-19 mortality data from the National Center for Health Statistics 4 from February 2020 to September 2023 for 6 defined racial and ethnic groups: Hispanic, non-Hispanic American Indian or Alaska Native, non-Hispanic Asian, non-Hispanic Black, non-Hispanic Native Hawaiian or Pacific Islander, and non-Hispanic White. We added an additional category combining non-Hispanic Asian and non-Hispanic Native Hawaiian or Pacific Islander to examine the effect of the historical Asian–Pacific Islander grouping. 3 Cumulative age-adjusted mortality rates per 100 000 individuals were calculated for each racial group over 4 periods (February to June 2020, October 2020 to March 2021, June to October 2021, and November 2021 to March 2022), selected to correspond to the surges of COVID-19 mortality. We computed rate ratios with 95% CIs for each specified period, using non-Hispanic White individuals as the reference group. All analyses were performed using R version 4.2.2 (R Core Team 2022). Additional details are provided in the eMethods in Supplement 1 . This study was deemed not human participant research by the Harvard Longwood Campus institutional review board at Harvard University; therefore, the requirement for informed consent was waived. We followed the STROBE reporting guidelines.

During the examined period, the number of COVID-19 deaths equaled 172 129 for Hispanic individuals, 12 113 for non-Hispanic American Indian or Alaska Native individuals, 35 392 for non-Hispanic Asian individuals, 157 072 for non-Hispanic Black individuals, 2321 for non-Hispanic Native Hawaiian or Pacific Islander individuals, and 758 221 for non-Hispanic White individuals; the corresponding population sizes were 60.6 million, 2.4 million, 19.7 million, 41.9 million, 0.6 million, and 196.8 million, respectively ( Table ). Non-Hispanic Black, Hispanic, non-Hispanic American Indian or Alaska Native, and non-Hispanic Native Hawaiian or Pacific Islander groups experienced higher mortality than non-Hispanic White individuals, with disparities widening during surges. Non-Hispanic American Indian or Alaska Native and non-Hispanic Native Hawaiian or Pacific Islander groups consistently exhibited higher mortality rates compared with all other racial and ethnic groups during the second, third, and fourth periods ( Figure ). Throughout, non-Hispanic American Indian or Alaska Native individuals experienced the highest mortality rates, and Hispanic, non-Hispanic Native Hawaiian or Pacific Islander, and non-Hispanic Black populations followed closely ( Table ). Non-Hispanic Native Hawaiian or Pacific Islander individuals had the highest mortality rate among all groups during the third time interval, yielding the largest rate ratio when compared with non-Hispanic White individuals ( Table ). In contrast, non-Hispanic Asian individuals displayed the lowest mortality rates during the second, third, and fourth periods, with the second-lowest rates during the first period ( Table ). Non-Hispanic Asian and non-Hispanic Native Hawaiian or Pacific Islander groups combined exhibited similar results to the non-Hispanic Asian group alone ( Table ).

This analysis underscores the persistently high mortality risk for American Indian or Alaska Native and Native Hawaiian or Pacific Islander individuals during the PHE, exacerbated by the emergence of new variants of COVID-19. Limitations, such as data gaps, underreporting, and the misclassification of race and ethnicity (eg, death records), may lead to underestimating rates for specific groups like American Indian or Alaska Native, Native Hawaiian or Pacific Islander, and multiracial populations. 5 Encouraging consistent use and examination of racial and ethnic disaggregated data are critical to elucidating disparities. Combining Native Hawaiian or Pacific Islander individuals with Asian individuals, a group with lower mortality, masked Native Hawaiian or Pacific Islander persistent mortality risk, cautioning against the Asian–Pacific Islander categorization. The absence of further granular data limited the assessment of within-group differences. Aggregated data hamper the identification of crucial patterns, hindering the development of targeted interventions, such as financial resources and community-driven, culturally sensitive initiatives. It is noteworthy that 2 groups (American Indian or Alaska Native, Native Hawaiian or Pacific Islander) with persistently high COVID-19 mortality represent Indigenous populations subjected to racism and colonialism, suggesting the influence of historical trauma and genocidal policies. 6 Investigating the unique and upstream factors influencing mortality is critical to producing accurate epidemiological accounts of smaller groups with greater risk.

Accepted for Publication: March 13, 2024.

Published: May 21, 2024. doi:10.1001/jamanetworkopen.2024.11656

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2024 Sumibcay JRC et al. JAMA Network Open .

Corresponding Author: Jake Ryann C. Sumibcay, DrPH, MPH, FXB Center for Health and Human Rights, Harvard T.H. Chan School of Public Health, 651 Huntington Ave, Boston, MA 02115 ( [email protected] ).

Author Contributions: Mr Kunichoff had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: Sumibcay, Kunichoff.

Drafting of the manuscript: All authors.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Sumibcay, Kunichoff.

Obtained funding: Sumibcay.

Administrative, technical, or material support: Sumibcay.

Supervision: Sumibcay, Bassett.

Conflict of Interest Disclosures: Dr Sumibcay reported receiving grants from JPB Foundation outside the submitted work. No other disclosures were reported.

Data Sharing Statement: See Supplement 2 .

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• Volume 3, Issue 1
• Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study
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• Ge Chen 1 ,
• Zhengmin (Min) Qian 2 ,
• Junguo Zhang 1 ,
• Shiyu Zhang 1 ,
• http://orcid.org/0000-0002-7003-6565 Zilong Zhang 1 ,
• Michael G Vaughn 3 ,
• Hannah E Aaron 2 ,
• Chuangshi Wang 4 ,
• Gregory YH Lip 5 , 6 and
• http://orcid.org/0000-0002-3643-9408 Hualiang Lin 1
• 1 Department of Epidemiology , Sun Yat-Sen University , Guangzhou , China
• 2 Department of Epidemiology and Biostatistics, College for Public Health and Social Justice , Saint Louis University , Saint Louis , Missouri , USA
• 3 School of Social Work, College for Public Health and Social Justice , Saint Louis University , Saint Louis , Missouri , USA
• 4 Medical Research and Biometrics Centre , Fuwai Hospital, National Centre for Cardiovascular Diseases, Peking Union Medical College , Beijing , China
• 5 Liverpool Centre for Cardiovascular Science , University of Liverpool and Liverpool Heart and Chest Hospital , Liverpool , UK
• 6 Department of Clinical Medicine , Aalborg University , Aalborg , Denmark
• Correspondence to Dr Hualiang Lin, Department of Epidemiology, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; linhualiang{at}mail.sysu.edu.cn

Objective To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death.

Design Prospective cohort study.

Setting UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years).

Participants 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study.

Main outcome measures Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage).

Results Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99).

Conclusions Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

• Health policy
• Nutritional sciences
• Public health

Data availability statement

Data are available upon reasonable request. UK Biobank is an open access resource. Bona fide researchers can apply to use the UK Biobank dataset by registering and applying at http://ukbiobank.ac.uk/register-apply/ .

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/ .

https://doi.org/10.1136/bmjmed-2022-000451

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WHAT IS ALREADY KNOWN ON THIS TOPIC

Findings of the effects of omega 3 fatty acids or fish oil on the risk of cardiovascular disease are controversial

Most previous studies focused on one health outcome and did not characterise specific cardiovascular disease outcomes (eg, atrial fibrillation, myocardial infarction, stroke, heart failure, and major adverse cardiovascular events)

Whether fish oil could differentially affect the dynamic course of cardiovascular diseases, from atrial fibrillation to major adverse cardiovascular events, to other specific cardiovascular disease outcomes, or even to death, is unclear

WHAT THIS STUDY ADDS

In people with no known cardiovascular disease, regular use of fish oil supplements was associated with an increased relative risk of atrial fibrillation and stroke

In people with known cardiovascular disease, the beneficial effects of fish oil supplements were seen on transitions from atrial fibrillation to major adverse cardiovascular events, atrial fibrillation to myocardial infarction, and heart failure to death

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE, OR POLICY

Regular use of fish oil supplements might have different roles in the progression of cardiovascular disease

Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements

Introduction

Cardiovascular disease is the leading cause of death worldwide, accounting for about one sixth of overall mortality in the UK. 1 2 Fish oil, a rich source of omega 3 fatty acids, containing eicosapentaenoic acid and docosahexaenoic acid, has been recommended as a dietary measure to prevent cardiovascular disease. 3 The UK National Institute for Health and Care Excellence recommends that people with or at high risk of cardiovascular disease consume at least one portion of oily fish a week, and the use of fish oil supplements has become popular in the UK and other western countries in recent years. 4 5

Although some epidemiological and clinical studies have assessed the effect of omega 3 fatty acids or fish oil on cardiovascular disease and its risk factors, the findings are controversial. The Agency for Healthcare Research and Quality systematically reviewed 37 observational studies and 61 randomised controlled trials, and found evidence indicating the beneficial effects of higher consumption of fish oil supplements on ischaemic stroke, whereas no beneficial effect was found for atrial fibrillation, major adverse cardiovascular events, myocardial infarction, total stroke, or all cause death. 6 In contrast, the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) reported a decreased risk of major adverse cardiovascular events with icosapent ethyl in patients with raised levels of triglycerides, regardless of the use of statins. 7 Most of these findings, however, tended to assess the role of fish oil at a certain stage of cardiovascular disease. For example, some studies restricted the study population to people with a specific cardiovascular disease or at a high risk of cardiovascular disease, 8 9 whereas others evaluated databases of generally healthy populations. 10 All of these factors might preclude direct comparison of the effects of omega 3 fatty acids on atrial fibrillation events or on further deterioration of cardiovascular disease. Few studies have fully characterised specific cardiovascular disease outcomes or accounted for differential effects based on the complex disease characteristics of participants. Hence, in this study, we hypothesised that fish oil supplements might have harmful, beneficial, or no effect on different cardiovascular disease events in patients with varying health conditions.

Most previous studies on the association between fish oil and cardiovascular diseases generally focused on one health outcome. Also, no study highlighted the dynamic progressive course of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). Clarifying this complex pathway in relation to the detailed progression of cardiovascular diseases would provide substantial insights into the prevention or treatment of future disease at critical stages. Whether fish oil could differentially affect the dynamic course of cardiovascular disease (ie, from atrial fibrillation to major adverse cardiovascular events, to other specific cardiovascular disease outcomes, or even to death) is unclear.

To deal with this evidence gap, we conducted a longitudinal cohort study to estimate the associations between fish oil supplements and specific clinical cardiovascular disease outcomes, including atrial fibrillation, major adverse cardiovascular events, and all cause death in people with no known cardiovascular disease or at high risk of cardiovascular disease for the purpose of primary prevention. We also assessed the modifying effects of fish oil supplements on the disease process, from atrial fibrillation to other outcomes, in people with known cardiovascular disease for the purpose of secondary prevention.

The UK Biobank is a community based cohort study with more than half a million UK inhabitants aged 40-69 years at recruitment. 11–13 Participants were invited to participate in this study if they were registered with the NHS and lived within 35 km of one of 22 Biobank assessment centres. Between 1 March 2006 and 31 July 2010, a baseline survey was conducted, based on a touch screen questionnaire and face-to-face interviews, to collect detailed personal, socioeconomic, and lifestyle characteristics, and information on diseases. 11–13

We excluded patients who had a diagnosis of atrial fibrillation (n=8326), heart failure (n=2748), myocardial infarction (n=11 949), stroke (n=7943), or cancer (n=48 624) at baseline; who withdrew from the study during follow-up (n=1299); or who had incomplete or outlier data for the main information (n=11 748). Because we focused only on a specific sequence of progression of cardiovascular disease (ie, from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death), we excluded 1983 participants with other transition patterns. The remaining 415 737 participants were included in this analysis ( figure 1 ).

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Flowchart of selection of participants in study. The count of diagnosed diseases does not equate to the total number of individuals, because each person could have multiple diagnoses

Determining use of fish oil supplements

Information on regular use of fish oil supplements was collected from a self-reported touchscreen questionnaire during the baseline survey. 14 15 Each participant was asked whether they regularly used any fish oil supplement. Trained staff conducted a verbal interview with participants, asking if they were currently receiving treatments or taking any medicines, including omega 3 or fish oil supplements. Based on this information, we classified participants as regular users of fish oil supplements and non-users.

Follow-up and outcomes

Participants were followed up from the time of recruitment to death, loss to follow-up, or the end date of follow-up (31 March 2021), whichever came first. Incident cases of interest, including atrial fibrillation, heart failure, stroke, and myocardial infarction, were identified by linkage to death registries, primary care records, and hospital inpatient records. 11 Information on deaths was obtained from death registries of the NHS Information Centre, for participants in England and Wales, and from the NHS Central Register Scotland, for participants in Scotland. 11 Outcomes were defined by a three character ICD-10 (international classification of diseases, 10th revision) code. In this study, atrial fibrillation was defined by ICD-10 code I48, and major adverse cardiovascular events was determined by a combination of heart failure (I50, I11.0, I13.0, and I13.2), stroke (I60-I64), and myocardial infarction (I21, I22, I23, I24.1, and I25.2) codes.

We collected baseline data on age (<65 years and ≥65 years), sex (men and women), ethnic group (white and non-white), Townsend deprivation index (with a higher score indicating higher levels of deprivation), smoking status (never, previous, and current smokers), and alcohol consumption (never, previous, and current drinkers). Data for sex were taken from information in UK Biobank rather than from patient reported gender. Baseline dietary data were obtained from a dietary questionnaire completed by the patient or by an interviewer. The questionnaire was established for each nation (ie, England, Scotland, and Wales) to assess an individual's usual food intake (oily fish, non-oily fish, vegetables, fruit, and red meat). Diabetes mellitus was defined by ICD-10 codes E10-E14, self-reported physician's diagnosis, self-reported use of antidiabetic drugs, or haemoglobin A1c level ≥6.5% at baseline. Hypertension was defined by ICD-10 code I10 or I15, self-reported physician's diagnosis, self-reported use of antihypertensive drugs, or measured systolic and diastolic blood pressure ≥130/85 mm Hg at baseline. Information on other comorbidities (obesity (ICD-10 code E66), chronic obstructive pulmonary disease (J44), and chronic renal failure (N18)) was extracted from the first occurrence (UKB category ID 1712). Information on the use of drugs, including antihypertensive drugs, antidiabetic drug, and statins, was extracted from treatment and drug use records. Biochemistry markers were measured immediately at the central laboratory from serum samples collected at baseline. Binge drinking was defined as consumption of ≥6 standard drinks/day for women or ≥8 standard drinks/day for men. Detailed information on alcohol consumption and binge drinking in the UK Biobank was reported previously. 16

Statistical analysis

Characteristics of participants are summarised as number (percentages) for categorical variables and mean (standard deviation (SD)) for continuous variables. Comparisons between regular users of fish oil supplements and non-users were made with the χ 2 test or Student's t test.

We used a multi-state regression model to assess the role of regular use of fish oil supplements in the temporal disease progression from healthy status to atrial fibrillation, to major adverse cardiovascular events, and subsequently to death. The multi-state model is an extension of competing risks survival analysis. 17–19 The model allows simultaneous estimation of the role of risk factors in transitions from a healthy state to atrial fibrillation (transition A), healthy state to major adverse cardiovascular events (transition B), healthy state to death (transition C), atrial fibrillation to major adverse cardiovascular events (transition D), atrial fibrillation to death (transition E), and major adverse cardiovascular events to death (transition F) (transition pattern I, figure 2 ). The focus on these six transitions rather than on all possible health state transitions was preplanned and evidence based. If participants entered different states on the same date, we used the date of the theoretically previous state as the entry date of the latter state minus 0.5 days.

Numbers of participants in transition pattern I, from baseline to atrial fibrillation, major adverse cardiovascular events, and death

We further examined the effects of regular use of fish oil supplements on other pathways. For example, we divided major adverse cardiovascular events into three individual diseases (heart failure, stroke, and myocardial infarction), resulting in three independent pathways (transition patterns II, III, and IV, online supplemental figures S1–S3 ). All models were adjusted for age, sex, ethnic group, Townsend deprivation index, consumption of oily fish, consumption of non-oily fish, smoking status, alcohol consumption, obesity, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, chronic renal failure, and use of statins, antidiabetic drugs, and antihypertensive drugs.

Supplemental material

We conducted several sensitivity analyses for the multi-state analyses of transition pattern A: additionally adjusting for setting (urban and rural), body mass index (underweight, normal, overweight, and obese), and physical activity (low, moderate, and high) in the model; adjusting for binge drinking rather than alcohol consumption; additionally adjusting for other variables of dietary intake (consumption of vegetables, fruit, and red meat); calculating participants' entry date into the previous state with different time intervals (0.5 years, one year, and two years); excluding participants who entered different states on the same date; excluding events occurring in the first two years of follow-up; restricting the follow-up date to 31 March 2020 to evaluate the influence of the covid-19 pandemic; and the use of the inverse probability weighted method to deal with biases between the regular users and non-users of fish oil supplements. Also, we conducted grouped analyses for sex, age group, ethnic group, smoking status, consumption of oily fish, consumption of non-oily fish, hypertension, and drug use, to examine effect modification. The interactions were tested with the likelihood ratio test. All analyses were carried out with R software (version 4.0.3), and the multi-model analysis was performed with the mstate package. A two tailed P value <0.05 was considered significant.

Patient and public involvement

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Participants were involved in developing the ethics and governance framework for UK Biobank and have been engaged in the progress of UK Biobank through follow-up questionnaires and additional assessment visits. UK Biobank keeps participants informed of all research output through the study website ( https://www.ukbiobank.ac.uk/explore-your-participation ), participant events, and newsletters.

A total of 415 737 participants (mean age 55.9 (SD 8.1) years; 55% women), aged 40-69 years, were analysed, and 31.4% (n=1 30 365) of participants reported regular use of fish oil supplements at baseline ( figure 1 ). Table 1 shows the characteristics of regular users (n=130 365) and non-users (n=285 372) of fish oil supplements. In the group of regular users of fish oil supplements, we found higher proportions of elderly people (22.6% v 13.9%), white people (95.1% v 94.2%), and women (57.6% v 53.9%), and higher consumption of alcohol (93.1% v 92.0%), oily fish (22.1% v 15.4%), and non-oily fish (18.0% v 15.4%) than non-users. The Townsend deprivation index (mean −1.5 (SD 3.0) v −1.3 (3.0)) and the proportion of current smokers (8.1% v 11.4%) were lower in regular users of fish oil supplements. Online supplemental table S1 provides more details on patient characteristics and online supplemental table S2 compares the basic characteristics of included and excluded people.

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Baseline characteristics of study participants grouped by use of fish oil supplements

Over a median follow-up time of of 11.9 years, 18 367 participants had atrial fibrillation (transition A) and 17 826 participants had major adverse cardiovascular events (transition B); 14 902 participants died without having atrial fibrillation or major adverse cardiovascular events (transition C). Among patients with incident atrial fibrillation, 4810 developed major adverse cardiovascular events (transition D) and 1653 died (transition E). Among patients with incident major adverse cardiovascular events, 5585 died during follow-up (transition F, figure 2 ). In separate analyses for individual diseases (transition patterns II, III, and IV, online supplemental figures S1–S3 ), in patients with atrial fibrillation, 3085 developed heart failure, 1180 had a stroke, and 1415 had a myocardial infarction. During follow-up, 2436, 2088, and 2098 deaths occurred in patients with heart failure, stroke, and myocardial infarction, respectively.

Multi-state regression results

Table 2 shows the different roles of regular use of fish oil supplements in transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For individuals in the primary stage (healthy status), we found that the use of fish oil supplements had a harmful effect on the transition from health to atrial fibrillation, with an adjusted hazard ratio of 1.13 (95% CI 1.10 to 1.17, transition A). The hazard ratio for transition B (from health to major adverse cardiovascular events) was 1.00 (95% CI 0.97 to 1.04) and for transition C (from health to death) was 0.98 (0.95 to 1.02).

Hazard ratios (95% confidence intervals) for each transition, for different transition patterns for progressive cardiovascular disease by regular use of fish oil supplements

For individuals in the secondary stage (atrial fibrillation) at the beginning of the study, regular use of fish oil supplements decreased the risk of major adverse cardiovascular events (transition D, hazard ratio 0.92, 95% CI 0.87 to 0.98), and had a borderline protective effect on the transition from atrial fibrillation to death (transition E, 0.91, 0.82 to 1.01). For transition F, from major adverse cardiovascular events to death, after adjusting for covariates, the hazard ratio was 0.99 (0.94 to 1.06, transition pattern I, table 2 ).

We divided major adverse cardiovascular events into three individual diseases (ie, heart failure, stroke, and myocardial infarction) and found that regular use of fish oil supplements was marginally associated with an increased risk of stroke in people with a healthy cardiovascular state (hazard ratio 1.05, 95% CI 1.00 to 1.11), whereas a protective effect was found in transitions from healthy cardiovascular states to heart failure (0.92, 0.86 to 0.98). For patients with atrial fibrillation, we found that the beneficial effects of regular use of fish oil supplements were for transitions from atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and from atrial fibrillation to death (0.88, 0.81 to 0.95) for transition pattern IV. For patients with heart failure, we found a protective effect of regular use of fish oil supplements on the risk of mortality (0.91, 0.84 to 0.99) (transition patterns II, III, and IV, table 2 ).

Stratified and sensitivity analyses

We found that age, sex, smoking, consumption of non-oily fish, prevalent hypertension, and use of statins and antihypertensive drugs modified the associations between regular use of fish oil supplements and the transition from healthy states to atrial fibrillation ( online supplemental figure S4 ). We found that the association between regular use of fish oil supplements and risk of transition from healthy states to major adverse cardiovascular events was greater in women (hazard ratio 1.06, 95% CI 1.00 to 1.11, P value for interaction=0.005) and non-smoking participants (1.06, 1.06 to 1.11, P value for interaction=0.001) ( online supplemental figure S4 ). The protective effect of regular use of fish oil supplements on the transition from healthy states to death was greater in men (hazard ratio 0.93, 95% CI 0.89 to 0.98, P value for interaction=0.003) and older participants (0.91, 0.86 to o 0.96, P value for interaction=0.002) ( online supplemental figures S5 and S6 ). The results were not substantially changed in the sensitivity analyses ( online supplemental table S3 ).

Principal findings

Our study characterised the regular use of fish oil supplements on the progressive course of cardiovascular disease, from a healthy state (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). In this prospective analysis of more than 400 000 UK adults, we found that regular use of fish oil supplements could have a differential role in the progression of cardiovascular disease. For people with a healthy cardiovascular profile, regular use of fish oil supplements, a choice of primary prevention, was associated with an increased risk of atrial fibrillation. For participants with a diagnosis of atrial fibrillation, however, regular use of fish oil supplements, as secondary prevention, had a protective effect or no effect on transitions from atrial fibrillation to major adverse cardiovascular events, atrial fibrillation to death, and major adverse cardiovascular events to death. When we divided major adverse cardiovascular events into three individual diseases (ie, heart failure, stroke, and myocardial infarction), we found associations that could suggest a mildly harmful effect between regular use of fish oil supplements and transitions from a healthy cardiovascular state to stroke, whereas potential beneficial associations were found between regular use of fish oil supplements and transitions from atrial fibrillation to myocardial infarction, atrial fibrillation to death, and heart failure to death.

Comparison with other studies

Primary prevention.

The cardiovascular benefits of regular use of fish oil supplements have been examined in numerous studies but the results are controversial. Extending previous reports, our study estimated the associations between regular use of fish oil supplements and specific clinical cardiovascular disease outcomes in people with no known cardiovascular disease. Our findings are in agreement with the results of several previous randomised controlled trials and meta-analyses. The Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridaemia (STRENGTH) reported that consumption of 4 g/day of marine omega 3 fatty acids was associated with a 69% higher risk of new onset atrial fibrillation in people at high risk of cardiovascular disease. 20 A meta-analysis of seven randomised controlled trials showed that users of marine omega 3 fatty acids supplements had a higher risk of atrial fibrillation events, with a hazard ratio of 1.25 (95% CI 1.07 to 1.46, P=0.013). 21 The Vitamin D and Omega-3 Trial (VITAL Rhythm study), a large trial of omega 3 fatty acids for the primary prevention of cardiovascular disease in adults aged ≥50 years, however, found no effects on incident atrial fibrillation, major adverse cardiovascular events, or cardiovascular disease mortality among those treated with 840 mg/day of marine omega 3 fatty acids compared with placebo. 10 22

One possible explanation for the inconsistent results in these studies is that adverse effects might be related to dose and composition. Higher doses of omega 3 fatty acids used in previous studies might have had an important role in causing an adverse effect on atrial fibrillation. 21 One study found that high concentrations of fish oil altered cell membrane properties and inhibited Na-K-ATPase pump activity, whereas a low concentration of fish oil minimised peroxidation potential and optimised activity. 23 In another study, individuals with atrial fibrillation or flutter had higher percentages of total polyunsaturated fatty acids, and n-3 and n-6 polyunsaturated fatty acids, on red blood cell membranes than healthy controls. 24

In terms of composition of omega 3 fatty acids, a recent meta-analysis showed that eicosapentaenoic acid alone can be more effective at reducing the risk of cardiovascular disease than the combined effect of eicosapentaenoic acid and docosahexaenoic acid. 25 Similar outcomes were reported in the INSPIRE study, which showed that higher levels of docosahexaenoic acid reduced the cardiovascular benefits of eicosapentaenoic acid when given as a combination. 26 Another possible explanation is that age, sex, ethnic group, smoking status, dietary patterns, and use of statins and antidiabetic drugs by participants might modify the effects of regular use of fish oil supplements on cardiovascular disease events. Despite these differences in risk estimates, our findings do not support the use of fish oil or omega 3 fatty acid supplements for the primary prevention of incident atrial fibrillation or other specific clinical cardiovascular disease events in generally healthy individuals. Caution might be warranted when fish oil supplements are used for primary prevention because of the uncertain cardiovascular benefits.

Secondary prevention

Our large scale cohort study assessed the role of regular use of fish oil supplements on the disease process, from atrial fibrillation to more serious cardiovascular disease stages, to death, in people with known cardiovascular disease. Contrary to the observations for primary prevention, we found associations that could suggest beneficial effects between regular use of fish oil supplements and most cardiovascular disease transitions. No associations were found between regular use of fish oil supplements and transitions from atrial fibrillation to death, or from major adverse cardiovascular events to death.

Consistent with our hypothesis, the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI) Prevenzione study reported an association between administration of low dose prescriptions of n-3 polyunsaturated fatty acids and reduced cardiovascular events in patients with recent myocardial infarction. 27 A meta-analysis of 16 randomised controlled trials also reported a tendency towards a greater beneficial effect for secondary prevention in patients with cardiovascular disease. 28 Why patients with previous atrial fibrillation benefit is unclear. These findings indicate that triglyceride independent effects of omega 3 fatty acids might in part be responsible for the benefits in cardiovascular disease seen in previous trials. 29–31 No proven biological mechanism for this explanation exists, however, and the dose and formulation of omega 3 fatty acids used in clinical practice are not known.

For the disease process, from cardiovascular disease to death, our findings are consistent with the results of secondary prevention trials of omega 3 fatty acids, which have mostly shown a weak or neutral preventive effect in all cause mortality with oil fish supplements. The GISSI heart failure trial (GISSI-HF), conducted in 6975 patients with chronic heart failure, reported that supplemental omega 3 fatty acids reduced the risk of all cause mortality by 9% (hazard ratio 0.91, 95% CI 0.833 to 0.998, P=0.041). 32 Zelniker et al showed that omega 3 fatty acids were inversely associated with a lower incidence of sudden cardiac death in patients with non-ST segment elevation acute coronary syndrome. 33 A meta-analysis found that use of omega 3 supplements of ≤1 capsule/day was not associated with all cause mortality, but among participants with a risk of cardiovascular disease, taking a higher dose was associated with a reduction in cardiac death and sudden death. 28 Individuals who might benefit the most from fish oil or omega 3 fatty acid supplements are possibly more vulnerable individuals, such as those with previous cardiovascular diseases and those who can no longer live in the community. How fish oil supplements stop further deterioration of cardiovascular disease is unclear, but the theory that supplemental omega 3 fatty acids might protect the coronary artery is biologically plausible, suggesting that omega 3 fatty acids have anti-inflammatory and anti-hypertriglyceridaemia effects, contributing to a reduction in thrombosis and improvement in endothelial function. 34–41 Nevertheless, the effects of omega 3 fatty acids vary according to an individual's previous use of statins, which might partly explain the different effects of fish oil supplements in people with and without cardiovascular disease.

Many studies of omega 3 fatty acids, including large scale clinical trials and meta-analyses, have not produced entirely consistent results. 21 25 42 Our study mainly explored the varied potential effects of regular use of fish oil supplements on progression of cardiovascular disease, offering an initial overview of this ongoing discussion. Our findings suggest caution in the use of fish oil supplements for primary prevention because of the uncertain cardiovascular benefits and adverse effects. Further studies are needed to determine whether potential confounders modify the effects of oil fish supplements and the precise mechanisms related to the development and prognosis of cardiovascular disease events.

Strengths and limitations of this study

The strengths of our study were the large sample size, long follow-up period, which allowed us to analyse clinically diagnosed incident diseases, and complete data on health outcomes. Another strength was our analytical strategy. The multi-state model gives less biased estimates than the conventional Cox model, and distinguished the effect of regular use of fish oil supplements on each transition in the course of cardiovascular disease.

Our study had some limitations. Firstly, as an observational study, no causal relations can be drawn from our findings. Secondly, although we adjusted for multiple covariates, residual confounding could still exist. Thirdly, information on dose and formulation of the fish oil supplements was not available in this study, so we could not evaluate potential dose dependent effects or differentiate between the effects of different fish oil formulations. Fourthly, the use of hospital inpatient data for determining atrial fibrillation events could have excluded some events triggered by acute episodes, such as surgery, trauma, and similar conditions, resulting in underestimation of the true risk because undiagnosed atrial fibrillation is a common occurrence. 43 Fifthly, most of the participants in this study were from the white ethnic group and whether the findings can be generalised to other ethnic groups is not known. Finally, our study did not consider behavioural changes in populations with different cardiovascular profiles because of limited information, and variations in outcomes for different cardiovascular states merits further exploration.

Conclusions

This large scale prospective study of a UK cohort suggested that regular use of fish oil supplements might have differential roles in the course of cardiovascular diseases. Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for disease progression, from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine whether potential confounders modify the effects of oil fish supplements and the precise mechanisms for the development and prognosis of cardiovascular disease events.

Ethics statements

Patient consent for publication.

Consent obtained directly from patients.

Ethics approval

The UK Biobank study obtained ethical approval from the North West Multicentre Research ethics committee, Information Advisory Group, and the Community Health Index Advisory Group (REC reference for UK Biobank 11/NW/0382). Participants gave informed consent to participate in the study before taking part.

Acknowledgments

This study was conducted with UK Biobank Resource (application No: 69550). We appreciate all participants and professionals contributing to UK Biobank.

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Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

• Data supplement 1
• Data supplement 2

GYL and HL are joint senior authors.

Contributors HL supervised the whole project and designed the work. GC and HL directly accessed and verified the underlying data reported in the manuscript. GC contributed to data interpretation and writing of the report. ZQ, SZ, JZ, ZZ, MGV, HEA, CW, and GYHL contributed to the discussion and data interpretation, and revised the manuscript. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. HL is the guarantor. Transparency: The lead author (guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Funding This work was supported by the Bill and Melinda Gates Foundation (grant No INV-016826). Under the grant conditions of the foundation, a creative commons attribution 4.0 generic license has already been assigned to the author accepted manuscript version that might arise from this submission. The funder had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.

Competing interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Bill and Melinda Gates Foundation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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• Pedestrian safety on the road to net zero: cross-sectional study of collisions with electric and hybrid-electric cars in Great Britain
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• http://orcid.org/0000-0003-4431-8822 Phil J Edwards ,
• Siobhan Moore ,
• Craig Higgins
• London School of Hygiene & Tropical Medicine , London , UK
• Correspondence to Dr Phil J Edwards, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK; phil.edwards{at}LSHTM.ac.uk

Background Plans to phase out fossil fuel-powered internal combustion engine (ICE) vehicles and to replace these with electric and hybrid-electric (E-HE) vehicles represent a historic step to reduce air pollution and address the climate emergency. However, there are concerns that E-HE cars are more hazardous to pedestrians, due to being quieter. We investigated and compared injury risks to pedestrians from E-HE and ICE cars in urban and rural environments.

Methods We conducted a cross-sectional study of pedestrians injured by cars or taxis in Great Britain. We estimated casualty rates per 100 million miles of travel by E-HE and ICE vehicles. Numerators (pedestrians) were extracted from STATS19 datasets. Denominators (car travel) were estimated by multiplying average annual mileage (using National Travel Survey datasets) by numbers of vehicles. We used Poisson regression to investigate modifying effects of environments where collisions occurred.

Results During 2013–2017, casualty rates per 100 million miles were 5.16 (95% CI 4.92 to 5.42) for E-HE vehicles and 2.40 (95%CI 2.38 to 2.41) for ICE vehicles, indicating that collisions were twice as likely (RR 2.15; 95% CI 2.05 to 2.26) with E-HE vehicles. Poisson regression found no evidence that E-HE vehicles were more dangerous in rural environments (RR 0.91; 95% CI 0.74 to 1.11); but strong evidence that E-HE vehicles were three times more dangerous than ICE vehicles in urban environments (RR 2.97; 95% CI 2.41 to 3.7). Sensitivity analyses of missing data support main findings.

Conclusion E-HE cars pose greater risk to pedestrians than ICE cars in urban environments. This risk must be mitigated as governments phase out petrol and diesel cars.

• WOUNDS AND INJURIES
• CLIMATE CHANGE

Data availability statement

Data are available in a public, open-access repository. Numerator data (numbers of pedestrians injured in collisions) are publicly available from the Road Safety Data (STATS19) datasets ( https://www.data.gov.uk/dataset/cb7ae6f0-4be6-4935-9277-47e5ce24a11f/road-safety-data ). Denominator data (100 million miles of car travel per year) may be estimated by multiplying average annual mileage by numbers of vehicle registrations (publicly available from Department for Transport, https://www.gov.uk/government/statistical-data-sets/veh02-licensed-cars ). Average annual mileage for E-HE and ICE vehicles may be estimated separately for urban and rural environments using data that may obtained under special licence from the National Travel Survey datasets ( http://doi.org/10.5255/UKDA-Series-2000037 ).

https://doi.org/10.1136/jech-2024-221902

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WHAT IS ALREADY KNOWN ON THIS TOPIC

Electric cars are quieter than cars with petrol or diesel engines and may pose a greater risk to pedestrians.

The US National Highway Transportation Safety Agency found that during 2000–2007 the odds of an electric or hybrid-electric car causing a pedestrian injury were 35% greater than a car with a petrol or diesel engine.

The UK Transport Research Laboratory found the pedestrian casualty rate per 10 000 registered electric or hybrid-electric vehicles during 2005–2007 in Great Britain was lower than the rate for petrol or diesel vehicles.

WHAT THIS STUDY ADDS

In Great Britain during 2013–2017, pedestrians were twice as likely to be hit by an electric or hybrid-electric car than by a petrol or diesel car; the risks were higher in urban areas.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

The greater risk to pedestrian safety posed by electric or hybrid-electric cars needs to be mitigated as governments proceed to phase out petrol and diesel cars.

Drivers of electric or hybrid-electric cars must be cautious of pedestrians who may not hear them approaching and may step into the road thinking it is safe to do so, particularly in towns and cities.

Introduction

Many governments have set targets to reach net-zero emissions to help mitigate the harms of climate change. Short-term health benefits of reduced emissions are expected from better air quality with longer-term benefits from reduced global temperatures. 1

Transition to electric and hybrid-electric (E-HE) cars

One such target is to phase out sales of new fossil fuel-powered internal combustion engine (ICE) vehicles and replace these with E-HE vehicles. 2 3

Pedestrian safety

Road traffic injuries are the leading cause of death for children and young adults. 4 A quarter of all road traffic deaths are of pedestrians. 5 Concerns have been raised that E-HE cars may be more hazardous to pedestrians than ICE cars, due to being quieter. 6 7 It has been hypothesised that E-HE cars pose a greater risk of injury to pedestrians in urban areas where background ambient noise levels are higher. 8 However, there has been relatively little empirical research on possible impacts of E-HE cars on pedestrian road safety. A study commissioned for the US National Highway Transportation Safety Agency based on data from 16 States found that the odds of an E-HE vehicle causing a pedestrian injury were 35% greater than an ICE vehicle. 9 In contrast, a study commissioned by the UK Department for Transport found pedestrian casualty rates from collisions with E-HE vehicles during 2005–2007 were lower than for ICE vehicles. 10 Possible reasons for these conflicting results are that the two studies used different designs and estimated different measures of relative risk—the first used a case–control design and estimated an OR, whereas the second used a cross-sectional study and estimated a rate ratio. ORs will often differ from rate ratios. 11 Other reasons include differences between the USA and the UK in the amount and quality of walking infrastructure. 12

Aim and objectives

We aimed to add to the evidence base on whether E-HE cars pose a greater injury risk to pedestrians than ICE cars by analysing road traffic injury data and travel survey data in Great Britain.

We sought to improve on the previous UK study by using distance travelled instead of number of registered vehicles as the measure of exposure in estimation of collision rates.

The objectives of this study were:

To estimate pedestrian casualty rates for E-HE and ICE vehicles and to compare these by calculating a rate ratio;

To assess whether or not the evidence supports the hypothesis that casualty rate ratios vary according to urban or rural environments. 8

Study design

This study was an analysis of differences in casualty rates of pedestrians per 100 million miles of E-HE car travel and rates per 100 million miles of ICE car travel.

This study was set in Great Britain between 2013 and 2017.

Participants

The study participants were all pedestrians reported to have been injured in a collision with a car or a taxi.

The exposure was the type of propulsion of the colliding vehicle, E-HE or ICE. E-HE vehicles were treated as a single powertrain type, regardless of the mode of operation that a hybrid vehicle was in at the time of collision (hybrid vehicles typically start in electric mode and change from battery to combustion engine at higher speeds). 13

The outcome of interest was a pedestrian casualty.

Effect modification by road environment

We used the urban–rural classification 14 of the roads on which the collisions occurred to investigate whether casualty rate ratios comparing E-HE with ICE vehicles differed between rural and urban environments.

Data sources/measurement

Numerator data (numbers of pedestrians injured in collisions) were extracted from the Road Safety Data (STATS19) datasets. 15

Denominator data (100 million miles of car travel per year) were estimated by multiplying average annual mileage by numbers of vehicle registrations. 16 Average annual mileage for E-HE and ICE vehicles was estimated separately for urban and rural environments using data obtained under special licence from the National Travel Survey (NTS) datasets. 17 We estimated average annual mileage for the years 2013–2017 because the NTS variable for the vehicle fuel type did not include ‘hybrid’ prior to 2013 and data from 2018 had not been uploaded to the UK data service due to problems with the archiving process (Andrew Kelly, Database Manager, NTS, Department for Transport, 23 March 2020, personal communication). Denominators were thus available for the years 2013–2017.

Data preparation

The datasets for collisions, casualties and vehicles from the STATS19 database were merged using a unique identification number for each collision.

Statistical methods

We calculated annual casualty rates for E-HE and ICE vehicles separately and we compared these by calculating a rate ratio. We used Poisson regression models to estimate rate ratios with 95% CIs and to investigate any modifying effects of the road environment in which the collisions occurred. For this analysis, our regression model included explanatory terms for the main effects of the road environment, plus terms for the interaction between type of propulsion and the road environment. The assumptions for Poisson regression were met in our study: we modelled count data (counts of pedestrians injured), traffic collisions were independent of each other, occurring in different places over time, and never occurring simultaneously. Data preparation, management and analyses were carried out using Microsoft Access 2019 and Stata V.16. 18

Sensitivity analysis

We conducted an extreme case analysis where all missing propulsion codes were assumed to be ICE vehicles (there were over a 100 times more ICE vehicles than E-HE vehicles on the roads in Great Britain during our study period, 16 so missing propulsion is more likely to have been ICE).

The sample size for this study included all available recorded road traffic collisions in Great Britain during the study period. We estimated that for our study to have 80% power at the 5% significance level to show a difference in casualty rates of 2 per 100 miles versus 5.5 per 100 miles, we would require 481 million miles of vehicle travel in each group (E-HE and ICE); whereas to have 90% power at the 1% significance level to show this difference, 911 million miles of vehicle travel would be required in each group. Our study includes 32 000 million miles of E-HE vehicle travel and 3 000 000 million miles of ICE vehicle travel and therefore our study was sufficiently powered to detect differences in casualty rates of these magnitudes.

Between 2013 and 2017, there were 916 713 casualties from reported road traffic collisions in Great Britain. 120 197 casualties were pedestrians. Of these pedestrians, 96 285 had been hit by a car or taxi. Most pedestrians—71 666 (74%) were hit by an ICE car or taxi. 1652 (2%) casualties were hit by an E-HE car or taxi. For 22 829 (24%) casualties, the vehicle propulsion code was missing. Most collisions occurred in urban environments and a greater proportion of the collisions with E-HE vehicles occurred in an urban environment (94%) than did collisions with ICE vehicles (88%) ( figure 1 ).

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Flow chart of pedestrian casualties in collisions with E-HE or ICE cars or taxis from reported road traffic collisions in Great Britain 2013–2017. E-HE, electric and hybrid-electric; ICE, internal combustion engine.

Main results

During the period 2013 to 2017, the average annual casualty rates of pedestrians per 100 million miles were 5.16 (95% CI 4.92 to 5.42) for E-HE vehicles and 2.40 (95% CI 2.38 to 2.41) for ICE vehicles, which indicates that collisions with pedestrians were on average twice as likely (RR 2.15 (95% CI 2.05 to 2.26), p<0.001) with E-HE vehicles as with ICE vehicles ( table 1 ).

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Pedestrian casualties due to collisions with cars or taxis from reported road traffic collisions in Great Britain 2013–2017—by vehicle propulsion type

In our extreme case analysis, the 22 829 pedestrian casualties where vehicle propulsion was missing were all assumed to have been struck by ICE vehicles. In this case, average casualty rates of pedestrians per 100 million miles were 3.16 (95% CI 3.14 to 3.18) for ICE vehicles, which would indicate that collisions with pedestrians were on average 63% more likely (RR 1.63 (95% CI 1.56 to 1.71), p<0.001) with E-HE vehicles than with ICE vehicles ( table 2 ).

Extreme case sensitivity analysis—pedestrian casualties due to collisions with cars or taxis from reported road traffic collisions in Great Britain 2013–2017 by vehicle propulsion type where 22 829 missing vehicle propulsion codes are assumed to be ICE vehicles

Relative risks according to road environment

Casualty rates were higher in urban than rural environments ( tables 3 and 4 ).

Pedestrian casualties due to collisions with cars or taxis from reported road traffic collisions in Great Britain 2013–2017—by vehicle propulsion type in urban road environments

Pedestrian casualties due to collisions with cars or taxis from reported road traffic collisions in Great Britain 2013–2017—by vehicle propulsion type in rural road environments

Urban environments

Collisions with pedestrians in urban environments were on average over two and a half times as likely (RR 2.69 (95% CI 2.56 to 2.83, p<0.001) with E-HE vehicles as with ICE vehicles ( table 3 ).

The extreme case sensitivity analysis showed collisions with pedestrians in urban environments were more likely with E-HE vehicles (RR 2.05; 95% CI 1.95 to 2.15).

Rural environments

Collisions with pedestrians in rural environments were equally likely (RR 0.91; 95% CI 0.74 to 1.11) with E-HE vehicles as with ICE vehicles ( table 4 ).

The extreme case sensitivity analysis found evidence that collisions with pedestrians in rural environments were less likely with E-HE vehicles (RR 0.68; 95% CI 0.55 to 0.83).

Results of Poisson regression analysis

Our Poisson regression model results ( table 5 ) showed that pedestrian injury rates were on average 9.28 (95% CI 9.07 to 9.49) times greater in urban than in rural environments. There was no evidence that E-HE vehicles were more dangerous than ICE vehicles in rural environments (RR 0.91; 95% CI 0.74 to 1.11), consistent with our finding in table 4 . There was strong evidence that E-HE vehicles were on average three times more dangerous than ICE vehicles in urban environments (RR 2.97; 95% CI 2.41 to 3.67).

Results of Poisson regression analysis of annual casualty rates of pedestrians per 100 million miles by road environment and the interaction between vehicle propulsion type and environment

Statement of principal findings

This study found that in Great Britain between 2013 and 2017, casualty rates of pedestrians due to collisions with E-HE cars and taxis were higher than those due to collisions with ICE cars and taxis. Our best estimate is that such collisions are on average twice as likely, and in urban areas E-HE vehicles are on average three times more dangerous than ICE vehicles, consistent with the theory that E-HE vehicles are less audible to pedestrians in urban areas where background ambient noise levels are higher.

Strengths and weaknesses of the study

There are several limitations to this study which are discussed below.

The data used were not very recent. However, ours is the most current analysis of E-HE vehicle collisions using the STATS19 dataset.

Before we can infer that E-HE vehicles pose a greater risk to pedestrians than ICE vehicles, we must consider whether our study is free from confounding and selection bias. Confounding occurs when the exposure and outcome share a common cause. 19 Confounders in this study would be factors that may both cause a traffic collision and also cause the exposure (use of an E-HE car). Younger, less experienced drivers (ie, ages 16–24) are more likely to be involved in a road traffic collision 20 and are also more likely to own an electric car. 21 Some of the observed increased risk of electric cars may therefore be due to younger drivers preferring electric cars. This would cause positive confounding, meaning that the true relative risk of electric cars is less than we have estimated in our study. Regarding selection bias, it is known that the STATS19 dataset does not include every road traffic casualty in Great Britain, as some non-fatal casualties are not reported to the police. 22 If casualties from collisions are reported to the police differentially according to the type of vehicle propulsion, this may have biased our results; however, there is no reason to suspect that a pedestrian struck by a petrol or diesel car is any more or less likely to report the collision to the police than one struck by an electric car.

We must also address two additional concerns as ours is a cross-sectional study: The accuracy of exposure assignment (including the potential for recall bias) and the adequacy of prevalence as a proxy for incidence. 23 First, the accuracy of exposure assignment and the potential for recall bias are not issues for this study, as the exposure (type of propulsion of the colliding vehicle, E-HE or ICE), is assigned independently of the casualties by the UK Department for Transport who link the vehicle registration number (VRN) of each colliding vehicle to vehicle data held by the UK Driver Vehicle and Licensing Agency (DVLA). 10 Second, we have not used prevalence as a proxy for incidence but have estimated incidence using total distance travelled by cars as the measure of exposure.

We may therefore reasonably infer from our study results that E-HE vehicles pose a greater risk to pedestrians than ICE vehicles in urban environments, and that part of the risk may be due to younger people’s preference for E-HE cars.

A major limitation of the STATS19 road safety dataset used in this study was that it did not contain a vehicle propulsion code for all vehicles in collisions with pedestrians. We excluded these vehicles from our primary analysis (a complete case analysis) and we also conducted an extreme case sensitivity analysis. We will now argue why imputation of missing vehicle propulsion codes would not have added value to this study. Vehicle propulsion data are obtained for the STATS19 dataset by the UK Department for Transport who link the VRN of each colliding vehicle recorded in STATS19 to vehicles data held by the UK DVLA. The STATS19 data on reported collisions and casualties are collected by a Police Officer when an injury road accident is reported to them; Most police officers write details of the casualties and the vehicles involved in their notebooks for transcription onto the STATS19 form later at the Police station. 24 The VRN is one of 18 items recorded on each vehicle involved in a collision. Items may occasionally be missed due to human error during this process. Where a VRN is missing, vehicle propulsion will be missing in the STATS19 dataset. The chance that any vehicle-related item is missing will be independent of any characteristics of the casualties involved and so the vehicle propulsion codes are missing completely at random (MCAR). As the missing propulsion data are very likely MCAR, the set of pedestrians with no missing data is a random sample from the source population and hence our complete case analysis for handling the missing data gives unbiased results. The extreme case sensitivity analysis we performed shows a possible result that could occur, and it demonstrates our conclusions in urban environments are robust to the missing data. Lastly, to impute the missing data would require additional variables which are related to the likelihood of a VRN being missing. Such variables were not available and therefore we do not believe a useful multiple imputation analysis could have been performed.

Strengths and weaknesses in relation to other studies

Our study uses hundreds of millions of miles of car travel as the denominators in our estimates of annual pedestrian casualty rates which is a more accurate measure of exposure to road hazards than the number of registered vehicles, which was used as the denominator in a previous study in the UK. 10 Our results differ to this previous study which found that pedestrian casualty rates from collisions with E-HE vehicles during 2005–2007 were lower than those from ICE vehicles. Our study has updated this previous analysis and shows that casualty rates due to E-HE vehicle collisions exceed those due to ICE vehicle collisions. Similarly, our study uses a more robust measure of risk (casualty rates per miles of car travel) than that used in a US study. 9 Our study results are consistent with this US study that found that the odds of an E-HE vehicle causing a pedestrian injury were 35% greater than an ICE vehicle. Brand et al 8 hypothesised, without any supporting data, that “hybrid and electric low-noise cars cause an increase in traffic collisions involving vulnerable road users in urban areas” and recommended that “further investigations have to be done with the increase of low-noise cars to prove our hypothesis right.” 8 We believe that our study is the first to provide empirical evidence in support of this hypothesis.

Meaning of the study: possible explanations and implications for clinicians and policymakers

More pedestrians are injured in Great Britain by petrol and diesel cars than by electric cars, but compared with petrol and diesel cars, electric cars pose a greater risk to pedestrians and the risk is greater in urban environments. One plausible explanation for our results is that background ambient noise levels differ between urban and rural areas, causing electric vehicles to be less audible to pedestrians in urban areas. Such differences may impact on safety because pedestrians usually hear traffic approaching and take care to avoid any collision, which is more difficult if they do not hear electric vehicles. This is consistent with audio-testing evidence in a small study of vision-impaired participants. 10 From a Public Health perspective, our results should not discourage active forms of transport beneficial to health, such as walking and cycling, rather they can be used to ensure that any potential increased traffic injury risks are understood and safeguarded against. A better transport policy response to the climate emergency might be the provision of safe, affordable, accessible and integrated public transport systems for all. 25

Unanswered questions and future research

It will be of interest to investigate the extent to which younger drivers are involved in collisions of E-HE cars with pedestrians.

If the braking distance of electric cars is longer, 26 and electric cars are heavier than their petrol and diesel counterparts, 27 these factors may increase the risks and the severity of injuries sustained by pedestrians and require investigation.

As car manufacturers continue to develop and equip new electric cars with Collision Avoidance Systems and Autonomous Emergency Braking to ensure automatic braking in cases where pedestrians or cyclists move into the path of an oncoming car, future research can repeat the analyses presented in this study to evaluate whether the risks of E-HE cars to pedestrians in urban areas have been sufficiently mitigated.

Conclusions

E-HE vehicles pose a greater risk to pedestrians than petrol and diesel powered vehicles in urban environments. This risk needs to be mitigated as governments proceed to phase out petrol and diesel cars.

Ethics statements

Patient consent for publication.

Not applicable.

Ethics approval

This study involves human participants and was approved by the LSHTM MSc Research Ethics Committee (reference #16400). The study uses the anonymised records of people injured in road traffic collisions, data which are routinely collected by UK police forces. The participants are unknown to the investigators and could not be contacted.

Acknowledgments

We thank Rebecca Steinbach for her advice on analysis of National Travel Survey data, Jonathan Bartlett for his advice on missing data, and Ben Armstrong for his advice on Poisson regression. We are grateful to the reviewers and to Dr C Mary Schooling, Associate Editor, whose comments helped us improve the manuscript. We are grateful to Jim Edwards and Graham Try for their comments on earlier versions of this manuscript.

• H Baqui A ,
• Benfield T , et al
• Gilchrist J
• ↵ WHO factsheet on road traffic injuries . Available : https://www.who.int/news-room/fact-sheets/detail/road-traffic-injuries#:~:text=Approximately%201.19%20million%20people%20die,adults%20aged%205%E2%80%9329%20years [Accessed 14 Apr 2024 ].
• ↵ Reported road casualties great Britain, annual report . 2022 . Available : https://www.gov.uk/government/statistics/reported-road-casualties-great-britain-annual-report-2022 [Accessed 14 Apr 2024 ].
• Maryland General Assembly
• Haas P , et al
• Morgan PA ,
• Muirhead M , et al
• Greenland S
• Buehler R ,
• Alternative Fuels Data Center
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• Hernán MA ,
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Contributors CH and PJE developed the idea for this study and supervised SM in performing the literature search, downloading, managing and analysing the data. SM wrote the first draft of the manuscript, which was the dissertation for her MSc in Public Health. PJE prepared the first draft of the manuscript for the journal. All authors assisted in editing and refining the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. PJE (guarantor) accepts full responsibility for the work and the conduct of the study, had access to the data and controlled the decision to publish.

Funding This study was conducted in part fulfilment of the Masters degree in Public Health at the London School of Hygiene & Tropical Medicine. The second author was self-funded for her studies for this degree.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

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Pharmacists prove effective, less costly care option for minor illnesses

SPOKANE, Wash. – Greater use of pharmacists to treat minor illnesses could potentially save millions of dollars in health care costs, according to new research led by Washington State University. The findings also indicate a way to improve healthcare access by expanding availability of pharmacists’ clinical services including prescribing medications, amid an ongoing shortage of primary care providers.

The study found that care for a range of minor health issues – including urinary tract infections, shingles, animal bites and headaches – costs an average of about $278 less when treated in pharmacies compared to patients with similar conditions treated at “traditional sites” of primary care, urgent care or emergency room settings. Follow-ups with pharmacy patients showed that almost all their illnesses had resolved after the initial visit with a pharmacist.

Notably, if all of the illnesses in the three-year study that were treated at a traditional site of care had been treated by community pharmacists, it would have saved an estimated $23 million in health care expenses.

“The findings show that pharmacists, especially in the outpatient community setting, are a viable solution to part of our patient access to care problem in our state and country,” said lead author Julie Akers, a WSU pharmacy researcher. “Pharmacists are trained and qualified to do this work, and unfortunately in many settings, highly underutilized. And they could have a huge impact on how fast patients access care, which can minimize the complexity and the progression of their condition.”

For this study, published in the journal ClinicoEconomics and Outcomes Research , Akers’ research team analyzed data of nearly 500 patients who received care from 175 pharmacists at 46 pharmacies across the state of Washington from 2016 to 2019. The team also followed up with the patients 30 days after their pharmacy visits to assess treatment effectiveness. They then compared these cases with insurance data of patients from the same time period with conditions of the same type and level who had sought care at a doctor’s office, urgent care facility or emergency room.

The researchers found that for almost every minor illness in the study, pharmacy care was not only effective but cost much less, sometimes dramatically so. For instance, the study found that for an uncomplicated case of urinary tract infection, normally treated with antibiotics, a first visit to an emergency room cost on average $963, a primary care physician’s office, $121 – at the pharmacy, the average was $30.

The study was conducted by a team of pharmacy researchers in coordination with an advisory board of physicians. The findings highlight the advantages of expanding the physician-pharmacist collaboration that allows some pharmacists to directly prescribe medications.

Washington state was the first in the nation to enact the “prescribing authority” in 1979 which enables a licensed prescriber such as a physician to delegate a pharmacist to prescribe and administer certain drugs.

As part of their education, pharmacists are trained in clinical evaluation of common illnesses, and as Akers pointed out, they already regularly make recommendations for conditions that can be treated with over-the-counter medications. The prescribing authority allows them to take their current practice to the next level if over-the-counter medicines are not enough.

Pharmacists also often refer patients to different providers for conditions that are complex, need further testing or cannot be resolved through medication alone. For less serious conditions, this study shows that pharmacists with prescribing authority can help fill a gap in care, especially in rural areas or at times of the day when there are few options available, Akers said.

“We’ve seen over time, more and more patients struggle to get access to care,” she said. “Over the past couple of decades, we’ve seen inappropriate use of urgent cares and emergency departments for things that really didn’t need go to that level of service.”

There is more work to do to be able to expand this treatment at pharmacies, Akers added. This includes creating greater public awareness, so people expect this type of service at pharmacies as they now do with vaccinations. Pharmacies also need to address the financial sustainability of providing these expanded patient care services, and Akers hopes the team’s next project will involve helping pharmacies transition to medical billing, which could greatly increase access to care for patients without the ability to pay out of pocket for care.

The current study was supported by a grant from the National Association of Chain Drug Stores Foundation. Additional co-authors include Jennifer Miller, Linda MacLean, Bidisha Mandal and Clark Hogan of WSU as well as Brandy Seignemartin of Idaho State University.  

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By the numbers: There are now more daily marijuana users in the US than daily alcohol users

FILE - A man smokes marijuana in lower Manhattan outside the first legal dispensary for recreational marijuana in New York on Thursday, Dec. 29, 2022. Daily and near-daily marijuana use is now more common than similar levels of high-frequency drinking in the U.S., according to an analysis of survey data over four decades, according to research published Wednesday, May 22, 2024, in the journal Addiction. (AP Photo/Ted Shaffrey, File)

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New research based on data from the National Survey on Drug Use and Health, published Wednesday in the journal Addiction, compares Americans’ use of cannabis and alcohol over the past 40 years. Here are some of the findings and other notable numbers.

— An estimated 17.7 million people reported using marijuana daily or near-daily in 2022, up from less than 1 million in 1992.

— An estimated 14.7 million used used alcohol daily or near daily in 2022, up from about 9 million in 1992.

— 42% of people who say they’ve used marijuana in the past month say they do so daily or near daily.

— 11% of alcohol users drink daily or near daily.

— 62 million Americans, about 20% of the U.S. population ages 12 and older, reported using marijuana at least once in the past year, according to the survey .

— About 3 in 10 people who use cannabis have cannabis use disorder , according to the U.S. Centers for Disease Control and Prevention.

— 177 million Americans reported that they drank in the past year .

— 29.5 million Americans had an alcohol use disorder as of 2022.

— Recreational marijuana is legal in 24 U.S. states .

Teens who use marijuana are more likely to suffer psychotic disorders, study finds

Teenagers who used cannabis within the last year had a dramatically higher rate of developing a psychotic disorder, according to a study published Wednesday. 

The study, led by researchers from the University of Toronto, found an 11 times higher risk of developing a psychotic disorder among teenagers who used cannabis compared with those who did not. When the analysis was limited to just emergency room visits and hospitalizations, there was a 27-fold increase in psychotic disorders in teenagers who had used the drug. 

“When I see youths with psychotic symptoms, they’re almost always using lots of cannabis,” said Dr. Leslie Hulvershorn, a child psychiatrist and chair of the psychiatry department at Indiana University who was not involved with the study. “It would be unusual to see someone present with psychotic symptoms to a hospital and not have smoked cannabis.”

The paper adds to the growing body of research that links cannabis to an increased risk of psychotic disorders, particularly in adolescence. Use of marijuana, particularly higher-potency products, has been linked to a variety of mental health disorders, including schizophrenia, anxiety and depression .

“I think that there’s enough evidence out there for us to give recommendations that teens probably shouldn’t be using cannabis,” said the study’s lead author, Andre McDonald, a postdoctoral research fellow at McMaster University in Hamilton, Ontario. “If we can somehow ask teens to delay their use until their brain has developed a little further, I think that would be good for public health.”

While most teenagers who use cannabis will not develop psychotic disorders, McDonald said, the findings are concerning given how debilitating these conditions can be. 

The new study, like previous research on marijuana and psychosis, does not directly prove that marijuana is causing psychotic disorders. While it’s possible that teens who were prone to develop psychotic disorders could have also been more likely to use cannabis, it’s unlikely because of how striking the association was, Hulvershorn said. 

“The magnitude of the effect here is just hard to believe that it’s not related to cannabis,” Hulvershorn said. 

There was no association between cannabis use and psychotic disorders in people ages 20 to 33. 

“There’s something about that stage of brain development that we haven’t yet fully characterized — where there’s a window of time where cannabis use may increase the risk of psychosis,” said Dr. Kevin Gray, a professor of psychiatry and director of addiction sciences at the Medical University of South Carolina who was not involved with the study. “This study really puts a fine point on delaying cannabis use until your 20s may mitigate one of the most potentially serious risks.”

The Biden administration has been moving toward rescheduling marijuana from Schedule I to the less dangerous Schedule III, which would also acknowledge its medical benefits at the federal level. While the potential change is expected later this year, cannabis is currently legal in 24 states for recreational use.

Marijuana use among high school students has remained steady in recent years. Nearly 1 in 3 12th graders reported using it in the previous year, according to the 2023 Monitoring the Future Survey, an annual survey that measures drug and alcohol use among adolescent students nationwide. 

The new research, published in the respected journal Psychological Medicine, includes data from over 11,000 teens and young adults who were ages 12 to 24 at the beginning of the study.

The authors pulled from the annual Canadian Community Health Survey, focusing on 2009 to 2012. Participants were then followed for up to nine years after the initial survey to track any visits they may have had to doctors or emergency rooms or any times they were admitted to hospitals.. 

Of the teens who were hospitalized or visited emergency rooms for psychotic disorders, roughly 5 in 6 had reported previous cannabis use.

“We see this replicated over and over again that there’s this developmental window of adolescence that’s very high-risk,” Gray said. 

It’s not completely clear why, he added, but one theory is that disruptions to the endocannabinoid system in adolescence may make psychotic symptoms more likely. The endocannabinoid system is a complex signaling system in the brain that marijuana targets. That could make it harder to distinguish reality from what is going on inside the head, leading to symptoms such as hallucinations. 

The authors did not specifically look at how the potency of marijuana products affected the risk of mental disorders, although previous research has found an increased risk .

Akshay Syal, M.D., is a medical fellow with the NBC News Health and Medical Unit.