Overweight and obesity are significant public health concerns, associated with increased morbidity and mortality. While the ideal range of body weights for optimal health remains a subject of debate, the question of whether weight loss extends longevity is crucial. This review examines the evidence supporting weight loss through diet and lifestyle changes as a means of prolonging life.
Introduction
Weight loss has been linked to improvements in cardiovascular disease (CVD) risk factors, such as blood pressure, lipid profiles, and glucose tolerance. Consequently, it might be expected that weight loss would lead to decreased mortality in the long term, particularly in obese individuals with serious medical complications or after substantial weight loss following surgical procedures. However, the long-term effects of more moderate weight loss for those who are not severely obese and do not have co-morbidities are less clear. Many prospective studies show conflicting results, while some recent studies indicate either excess or unchanged mortality following weight loss.
Inconsistent results might be due to failure to control for known confounding factors (for example, underlying disease, intention to lose weight). Also, many of the existing studies were not specifically designed to test the hypothesis that weight loss increases or decreases relative risk (RR) of all-cause mortality. Methodological problems have also been identified, for example, the method by which the weight loss was achieved has usually not been reported (although dietary energy restriction is likely to have been a major factor), while weight changes before and after the recording periods have usually not been determined.
Given the current obesity epidemic and the emphasis on encouraging individuals with a BMI above 25 kg/m2 to lose weight through diet and lifestyle modifications, it is essential to determine whether the long-term effects of weight loss benefit life expectancy. The aim of this study was to examine the available evidence of the impact of weight loss, as a lifestyle intervention, on the RR of all-cause mortality and to quantify this using meta-analysis. Data were pooled in a number of different ways in order to examine the influence of a number of possible confounders. Meta-analysis was used to provide a more objective appraisal of the evidence, integrating data from multiple prospective cohort studies to increase the power and precision of estimates of effect and reducing the likelihood of false negative results.
Methods
Search Strategy
A comprehensive literature search was conducted independently by two investigators to identify prospective cohort studies that evaluated the effect of weight loss as a lifestyle intervention on mortality risk. PubMed/Medline and ScienceDirect databases were searched for articles published between 1987 and 2008, limited to the English language. The search terms included ‘weight, BMI, loss, change, mortality, intentional, unintentional, relative risk, prospective and cohort’. Bibliographies of retrieved papers and linked articles were also hand-searched.
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Data Selection
Inclusion criteria were prospective studies in English of adults (men and/or women) with data on body weight and weight loss over more than 1 year. Studies needed to present RR of mortality and associated 95 % CI for the group that lost weight relative to a comparable reference group who lost minimal or no weight. Drug treatment studies and studies that measured weight loss following bariatric surgery were excluded, as the aim was to assess the effect of lifestyle interventions. Twenty-six publications were identified that met the inclusion criteria.
Data Extraction and Analysis
Data on RR of mortality and 95 % confidence limits were extracted for all subgroups presented by the authors (for example, men and women, intentional v. unintentional weight loss, obese v. overweight). Moderator variables such as baseline BMI (normal, overweight, obese), reason for weight loss (intentional, unintentional), baseline health status (healthy, unhealthy), method used to estimate weight loss (measured weight loss, reported weight loss) and physical activity adjustment (adjusted data, unadjusted data) were used to classify subgroups for separate analysis. For the subgroup analysis based on baseline BMI the ranges used in papers generally corresponded to those recommended by WHO.
Analysis was carried out using adjusted data because papers gave insufficient data on CI for unadjusted data. Although multivariable adjustment of the data varied from study to study, all adjusted for smoking. Results are shown in the form of schematic plots (Forest plots), which illustrate the size and direction of effect for each study and the weighted effect of all studies combined, with 95 % (lower and upper) CI. Meta-analysis uses a weighted average of the results, in which the larger and more precise studies have more influence than the smaller ones. Results are shown for the random effects model, which assumes the underlying effect may vary for each population. This is the most appropriate model where heterogeneity is present. Statistical significance of the overall pooled effect was based on P < 0·05.
Results
Study Characteristics
The study populations and subgroups' characteristics are summarized in Table 1. Sample sizes ranged from 34 to 5008 subjects, and the majority of the data was collected from white populations of US and UK origin. All of the studies were designed to investigate RR of mortality and weight change.
Quantitative Data Synthesis
Given the acknowledged importance of whether weight loss is intended or not, results are presented for (a) intentional, (b) unintentional and (c) weight loss not specified. For the main category of interest, i.e. intentional weight loss, sub-analyses are given for healthy v. unhealthy subjects. These have then been further analysed to examine the influence of moderators and confounders.
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Intentional Weight Loss
Overall, there was no significant effect of intentional weight loss on all-cause mortality (RR 1·01 (95 % CI 0·93, 1·09); P = 0·89).
Unintentional Weight Loss
Unintentional weight loss was associated with higher mortality (RR 1·22 (95 % CI 1·09, 1·37); P = 0·001), as has been shown in other studies.
Unknown or Unspecified Cause of Weight Loss
Where the cause of weight loss was unspecified, there was also excess mortality (RR 1·39 (95 % CI 1·29, 1·51); P < 0·001). Most of these studies were on ‘healthy’ subjects, but the subgroup who were unhealthy had even higher mortality associated with weight loss (RR 1·75 (95 % CI 1·24, 2·46); P = 0·001). Studies where weight loss intention was not explored may suffer from the same problem of confounding by illness as those in which weight loss was unintentional.
Subgroup Analyses of Intentional Weight Loss
Relative Weight at Baseline
Weight loss appeared to benefit obese weight losers who were also classified as unhealthy at baseline (RR 0·84 (95 % CI 0·73, 0·97); P = 0·018) but had no benefit for healthy obese (RR 1·02). Overall, there was no change in risk for the obese group (RR 0·94 (95 % CI 0·86, 1·04); P = 0·002). For intentional weight losers whose baseline BMI was within the normal to overweight range, or for mixed-weight populations, the RR of mortality was increased (RR 1·09 (95 % CI 1·02, 1·17); P = 0·008).
Method of Assessing Weight Loss
The majority of study groups with data on intentional weight loss (fifteen out of eighteen studies) relied on reported measurements of weight or weight loss. Among these, RR associated with weight loss was near unity. However, the three study groups with actual measurement had a net RR of 1·28 (95 % CI 1·07, 1·53).
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Physical Activity Adjustment
Adjustment for physical activity was made in most studies (fourteen out of eighteen studies) but there was essentially no difference in the RR according to whether the models had adjusted for activity or not (RR 0·98 v. 1·01 where adjusted for physical activity).
Discussion
Main Findings
This meta-analysis explored the effect of weight loss on mortality using sensitivity and subgroup analysis to explore some of the likely causes of heterogeneity, especially intentionality, health and baseline BMI. Whereas weight loss for unknown or unspecified reasons was clearly associated with excess mortality, intentional weight loss resulted in virtually no change in mortality overall. Importantly, we found opposing effects among healthy and unhealthy adults and between the obese and those with more moderate degrees of overweight or from the general population. The excess risk of weight loss in healthy adults was estimated to be of the order of 11 %. This was counterbalanced by a benefit of about 13 % among unhealthy adults (i.e. those with diabetes or obesity-related health conditions).
Comparison with Other Studies
The literature is equivocal on the risks and benefits of weight loss. Many prospective studies and reviews appear to show an increased mortality associated with weight loss, which runs counter to conventional wisdom relating to the adverse effects of obesity and the beneficial changes in risk factors associated with weight loss. It has been argued that methodological weaknesses explain much of this paradox, including failure to adjust for known confounders. In particular, it has been claimed that intentionality of weight loss is key but many studies fail to distinguish between intentional and unintentional weight loss, the latter being a cardinal sign of ill health and a predictor of increased mortality in old age.
Some clinical trials have demonstrated beneficial effects of weight loss with regard to morbidity in individuals suffering from either diabetes, obesity-related health conditions, cancer or other diseases. There are also an increasing number of favourable reports from bariatric surgery, such as the ‘Swedish obese subjects’ (SOS) study which has shown that substantial long-term weight reduction appreciably improves the cardiovascular risk profile of morbidly obese subjects, ultimately resulting in a decrease in overall mortality. Although such data may be encouraging, their success cannot necessarily be extrapolated to the public health setting where the weight losses normally achieved by diet are modest and difficult to sustain.
Time-Restricted Eating and Weight Loss
Although it is well established that caloric restriction (CR) is the primary driver of weight loss, circadian-driven metabolic benefits have been recognized as possibly enhancing the effects of CR. Studies involving a total of 1341 participants were analyzed. The results of main findings revealed that, in studies using non-isocaloric controls, the TRE group showed significant reductions in body weight (BW) (mean difference [MD]: -2.82 kg; 95% CI: -3.49, -2.15), fat mass (FM) (MD: -1.36 kg; 95% CI: -2.09, -0.63), and fat-free mass (FFM) (MD: -0.86 kg; 95% CI: -1.23, -0.49). In studies that used isocaloric control strategies, the TRE group showed significant reductions in BW (MD: -1.46 kg; 95% CI: -2.65, -0.26), FM (MD: -1.50 kg; 95% CI: -2.77, -0.24), and FFM (MD: -0.41 kg; 95% CI: -0.79, -0.
TRE yields favorable anthropometric and clinical outcomes, even when intake is isocaloric between the intervention and control groups.
Hidden Ingredients in Weight Loss Products
Consumers should also be aware of the potential dangers of weight loss products containing hidden drug ingredients. The Food and Drug Administration (FDA) has issued numerous public notifications regarding products marketed for weight loss that contain undeclared and potentially harmful substances.