Literature search

Four electronic databases (Medline, Embase, PsycInfo and CINAHL) were used to identify relevant studies according to the search strategy which was developed in collaboration with two librarians (see online supplementary material 2). The databases were searched from inception to February 2018. As there is no standardised terminology to describe the exposure of interest (light incidental physical activity 1.5–3 METs), we expected difficulties to fully capture the literature comprehensively using a set of keywords. Consequently, a thorough secondary manual search strategy was conducted to ensure completeness of records (see online supplementary material 1 for full search strategy). The reference lists of all selected articles were also screened for eligible records. In turn, the reference lists of any article identified this way were screened as well. This process was repeated until no new eligible articles were identified (three rounds).

Inclusion criteria

Articles reporting experimental or observational studies investigating the relationship between LIPA and cardiometabolic health markers or all-cause and cardiovascular disease mortality in adults (aged ≥18years) and published in English were eligible for inclusion. To be included, studies had to measure (either subjectively or objectively) or elicit experimentally LIPA, defined as any physical activity above 1.5 METs and below 3 METs.

Exclusion criteria

As the focus of the review was on the primary prevention, we excluded studies which investigated cardiac rehabilitation programmes and secondary cardiovascular disease prevention trials and longitudinal studies. For the same reason, we also excluded studies which investigated only populations with diagnosed cardiovascular diseases or patients with cancer.

Study selection

The title and abstract of retrieved articles were screened for eligibility by two independent reviewers randomly assigned to each article from a pool of five reviewers (SFMC, MDC, JVC, KDC, LP). At this stage, studies were excluded solely if the available information in the title or the abstract made it clear that the article did not meet the criteria. Full texts were retrieved for all remaining articles and were assessed for inclusion by two randomly assigned reviewers to each article from a pool of five reviewers (SFMC, MDC, JVC, KDC, LP) who read the articles independently. Reasons for exclusion were recorded by each reviewer. SFMC collated all information and in the case of disagreement, consensus was reached via discussion between SFMC and the reviewers.

Study quality assessment

Included studies were rated independently by pairs of reviewers from a pool of six coauthors (LP, JVC, MDC, PD, KDC) using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields QUALSYST tool.¹² This tool was selected as it allows appraising quality and assessing potential for bias over a wide variety of research designs from experimental to observational. SFMC collated all information and in the case of disagreement, consensus was reached via discussion.

Data extraction

Study characteristics and data describing the relationship between LIPA and cardiometabolic outcomes and mortality were extracted using different pro forma for experimental and observational studies. Each study was assigned randomly a pair of reviewers from a pool of five coauthors (SFMC, LP, JVC, MDC, KDC) to extract the information.

Study quality

Quality scores for each study are given in online supplementary tables S1–S4. Overall quality scores were normally distributed with a mean of 65% in each type of study. The majority of controlled studies used quasiexperimental or crossover designs rather than randomised controlled trials. Among the acute mechanistic studies, articles reporting experiments conducted in free-living conditions scored lower than those conducted in controlled laboratory settings. For physical activity programme intervention studies, small sample sizes and lack of an appropriate control group were the most common reasons for lower quality scores. The range of scores was wider for observational studies mostly due to small sample sizes and inadequately justified analytic approaches.

Acute mechanistic studies

Twenty crossover studies investigated the acute effect through the course of a day of exposure to bouts of LIPA. Four studies investigated the effect of a single continuous bout of LIPA,^14–17 while 12 studies examined the effect of a set sequence of short bouts in laboratory settings,^18–29 and 4 studies examined the effect of the natural sequence of bouts of LIPA in free living conditions.^30–33 Among all mechanistic studies, 13 investigated the effect on glycaemia,^{17 20 22–26 28 30 32–34} 6 on triglycerides,^{19 20 24 32 33 35} 5 on cholesterol,^{17 23 30 32 33} 5 on blood pressure^{21 23 29 33 36} and 1 specifically on inflammatory markers.¹⁵ Sample sizes ranged from 10²⁶ to 34²⁸ participants, either healthy or drawn from convenience samples of metabolically impaired populations.

Meta-analysis was possible for studies investigating the effect of frequent short bouts of LIPA on plasma glucose, insulin and triglycerides (figure 2). Overall, acute mechanistic studies resulted in a statistically significant reduction in postprandial glucose (−17.48%; 95% CI −31.74 to –8.42) induced by bouts of LIPA as short as 2min and interrupting sedentary behaviour at least every 20min (figure 2A). Subgroup analysis showed that the effects on glucose outcomes were only significant both in metabolically impaired individuals. However, heterogeneity was significant (p<0.001) and high (I²=95%). This heterogeneity was driven by the inclusion of studies conducted both in the laboratory and in free-living conditions.^{30 32 33} If these studies were excluded, the four studies on metabolically impaired participants were homogeneous (I²=0%) and statistically insignificant (p=0.54). Sensitivity analysis showed that when the lowest quality study conducted in free-living conditions was removed from the analysis, results for healthy individual became significant (p=0.0005). There was no statistical difference in effect between groups but the effect appears larger in metabolically impaired individuals. Among laboratory studies, short bouts of LIPA reduced postprandial glucose by 20.07% (95% CI −37.18 to –2.96) for normal individual and by −28.72% (95% CI −33.92 to –23.52) in impaired individuals.

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Figure 2

Forest plot for inverse-variance meta-analysis of acute mechanistic studies showing the effect of frequent short bouts of light activity on (A) postprandial glucose level, (B) postprandial insulin level and (C) triglyceride levels, expressed as percentage change compared with the control condition consisting of a whole day (>7hours) sitting without interruptions.

For insulin (figure 2B), experimental studies displayed a statistically significant difference in postprandial insulin level (−25.05; 95% CI −31.76 to −18.33) with no difference in effect between groups. These results persisted in subsequent sensitivity analyses where lower quality or free-living studies were removed from the analysis. In addition, two studies^{16 37} also reported that the beneficial effect of LIPA on glycaemia persisted until the following day. Heterogeneity was high and significant (p<0.001; I²=89%) and was not modified by the sensitivity analysis.

For triglycerides (figure 2C), there was no significant effect (−0.31%;95% CI −5.62 to 5.01). Subgroup analysis showed no difference between healthy and metabolically impaired individuals. Heterogeneity was high and statistically significant (p<0.001; I²=83%). The sensitivity analysis did not alter any of the results but did reduce the heterogeneity, I²=27%.

Finally, three out of four studies investigating blood pressure reported significant positive effects of LIPA^{19 21 31} while one reported no significant effects.³⁸ There were no significant effects of LIPA on inflammatory markers.¹⁵

Physical activity programme intervention studies

Seven studies investigated the effect of participating in a long-term physical activity programme of LIPA on fitness (n=1), lipidaemia (n=4), adiposity (n=4), glycaemia (n=5) and blood pressure (n=4). There were not enough studies with outcomes data that could be pooled to conduct a meta-analysis and only a narrative synthesis was possible. LIPA was delivered in the form of walking programmes, cycling or yoga for 12–16 weeks at a volume ranging from 90 to 300min/week. Three studies were quasiexperimental^39–41 with small sample sizes ranging from 8 to 15 participants, and four were randomised controlled trials^42–44 with larger sample sizes ranging from 25 to 171 participants. Quasiexperimental studies reported significant improvements in fitness (increase of 5.5% in VO_2max ³⁹), blood pressure (reduction of around 10% in systolic and diastolic blood pressure),⁴¹ glycaemia (33% increase in glucose effectiveness^{39 40}), adiposity (reduction of 6.1% in body fat⁴¹) and lipidaemia (reduction of 6% in total cholesterol⁴¹) as a result of engaging in LIPA structured programmes. However, these results were not systematically replicated in larger scale randomised trials. Only Paoli et al ⁴² reported a significant improvement in adiposity (reduction of 9.7% in fat mass), blood pressure (decrease of 8% in systolic blood pressure and 2.5 in diastolic blood pressure) and lipidaemia (decrease of 2.5% in total cholesterol) after 12 weeks of 150min/week of LIPA delivered as a light-intensity circuit training programme. The other three studies^43–45 showed no effect, but the volume of LIPA delivered was considerably lower at 90min/week of LIPA.

Cross-sectional observational studies

Twenty-eight articles included in this review reported results of cross-sectional analyses, including nine articles of the 2003–2006 waves of the National Health and Nutrition Examination Survey (NHANES) and another 19 other epidemiological studies (online supplementary table S3). There was substantial heterogeneity in outcome measures and analytic procedures to enable meta-analysis. Among those, 17 studies reported associations with adiposity markers, 14 with lipidaemia markers, 19 with glycaemia markers, 3 with cardiophysical fitness, 7 with inflammatory markers, 9 with blood pressure and 5 with metabolic syndrome. Sample sizes ranged from n=50to 11000. Most articles (n=17) were based on objectively measured LIPA. There were consistent reports across studies of an association between time spent in LIPA and adiposity markers, lipidaemia markers (particularly triglyceride levels) and inflammatory markers. Generally, the reported effect sizes were small and were consistently stronger with the increased absolute intensity of LIPA considered. Evidence concerning associations with glycaemia was equivocal. Five separate analyses of NHANES data systematically reported beneficial associations between time spent in LIPA and glucose or insulin levels. This strongly suggests that in this study this cross-sectional association is indeed present, but this was not replicated in all other studies which mostly reported non-significant for association between time spent in LIPA and glycaemia. Equivocal findings were also found for outcomes such as fitness, the metabolic syndrome and composite metabolic scores. For blood pressure, the evidence was particularly inconsistent, even between separate analyses of NHANES data.

Prospective studies

Eligible articles included 17 prospective studies (online supplementary table S4). The majority of those (n=12) reported associations between LIPA and all-cause mortality, including four different analyses of the NHANES data set.^46–50 Five articles studied the association between LIPA and incidence of cardiometabolic diseases (type 2 diabetes and metabolic syndrome), one investigated change in glycaemia and one studied the change in adiposity. No relationship was found between time spent in LIPA and metabolic syndrome.⁵¹ Mekary et al showed a small decrease in body weight to be associated with increase in time spent in LIPA.⁵² A significant reduction in risk of developing type 2 diabetes (HR 0.60;95% CI 0.40 to 0.91) was reported with higher time spent in LIPA in a study of over 14 000 Finnish men and women,⁵³ but no significant longitudinal improvements in glycaemia and insulin resistance were found in a much smaller study of n=192 participants.⁵⁴ In contrast with these mixed results, studies with all-cause mortality as the outcome overwhelmingly reported significant beneficial associations. Results from five mortality studies could be pooled into a meta-analysis. The results presented in figure 3 show a pooled 29% reduction (95% CI −17% to –38%) in HR of mortality for longer time spent in LIPA (equivalent to a 29% reduction in HR for doubling the time spent in LIPA). Sensitivity analysis of the meta-analysis revealed that this result was robust. The results heterogeneity was moderate but significant (p=0.05; I²=57%). The heterogeneity can be traced to the two studies which used self-reported LIPA time^{55 56} rather than objective measures in the other three. It should be noted that three potentially eligible studies^46–48 were not included in the meta-analysis. Three of them were excluded^46–48 because they used the same NHANES data set as Matthews et al’s study⁵⁰ which scored higher in terms of quality rating. These three studies showed different results^46–48 for the same data set suggesting that conclusions are sensitive to different analytical approaches.

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Figure 3

Forest plot for inverse variance meta-analysis of prospective studies showing the association between time spent in light activity and all-cause mortality expressed as HR between highest and lowest amount of time reported in the studies. This corresponds to about a doubling of the time spent in light activity daily.

Biological mechanisms

The results of our review should be viewed through the limited mechanistic information explaining any observed associations and effects of LIPA in humans. A previously proposed animal-based mechanism stated that, compared with muscular inertia, there is substantial increase in lipoprotein lipase activity during light ambulation, suggesting that LIPA might be facilitating better metabolism of circulating lipids.⁵⁸ This mechanism was proposed in 2003⁵⁸ but has not been verified in humans and as such it is unknown if it can explain the epidemiological and experimental literature findings on the whole. Sedentary behaviour-focused paradigms that could lend mechanistic insights of the vascular, cellular and metabolic LIPA pathways of action are also still at hypothesis level.⁵⁸

Implications for practice

Increase in LIPA can occur through activities of daily living at work, home and during transportation and could potentially be achieved with less onus on the individual by promoting a physical environment and culture conducive to movement and activity. Our review suggests that maintaining or/and increasing daily levels of LIPA may have health-promoting potential. With very few exceptions,⁵⁹ current guidelines^{5 6} do not explicitly recommend LIPA because at the time of their development there was a near absence of evidence. Our review provides the first synthesis consolidating evidence from different studies on the potential of the largest time component of daily physical activity for primary prevention. However, the evidence remains currently limited.

Implications for research

Our results showed that LIPA may have beneficial health effects but also highlighted important gaps of the evidence base. Ascertaining the dose–response relationships between volume of LIPA and different health outcomes will require careful long-term experimentation to provide targets for intervention and policy. Greater attention needs to be directed to interactions with time spent in other components of the 24-hour physical activity continuum, such as MVPA and sleep sedentary behaviours. This may require novel analytical approaches capable of dealing with the compositional nature of the whole 24hours.⁶⁰ The body of evidence of acute experimental trials showing consistent effects of LIPA bouts on insulin and glucose (figure 2) provides useful direction for future mechanistic studies. Advances in objective physical activity measures and more accurate activity type classification and recognition are likely to improve substantially our understanding on health attributes of LIPA in the near future.

The authors acknowledge Juan Pablo Rey-López for his input and help developing this manuscript. KDC is supported by a postdoctoral fellowship of the Research Foundation Flanders (FWO11/PDO/097). JVC is supported by a postdoctoral fellowship of the Research Foundation Flanders (FWO 12I1117N). MH acknowledges support from the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University and the University of Leicester. ES is supported by the National Health and Medical Research Council through a Senior Research Fellowship, and by a University of Sydney SOAR Fellowship.