Weight loss vs fitness for health risks

Hello JULES,
Weight loss vs fitness for health risks

Executive summary

* A paper has just been published, which examined the benefits of increasing fitness and physical activity vs weight loss for reducing health risks.

* The paper focused on evidence for all-cause mortality and cardiovascular disease (CVD).

* It argued a number of interesting points: activity can largely mitigate obesity risk; and activity can improve cardio health. Conversely, weight loss does not necessarily improve mortality risk; and ‘yo-yo dieting’, which often happens, is unhealthy.

* The paper serves as an excellent summary of evidence for the mortality and CVD benefits of activity.

* It presented a compelling case for the benefits of exercise. The case for exercise being better than weight loss was less compelling, but this could be due to the absence of data on head-to-head comparisons between exercise and weight loss for mortality.

* The paper noted from the outset that the prevalence of obesity has increased over the past 40 years, as has the prevalence of weight loss attempts. Maybe exercise can be presented as better because the weight loss bar is so low.


Many thanks to two people for spotting the paper being featured in this week’s note. Dr Peter Brukner was one and Mats Lederhausen was the other. The paper was called “Obesity treatment: Weight loss versus increasing fitness and physical activity for reducing health risks” (Ref 1). The paper was published in iScience and it was written by two authors: Gaesser and Angadi.

The paper summary was compelling from the outset. The opening sentence argued for a weight-neutral strategy for obesity treatment (i.e., don’t try to lose weight). That statement jolts the reader into a sense of ‘this can’t be right – surely obesity needs to be addressed with weight loss?’ The rationale for this statement was then presented in five bullet points:

1) the mortality risk associated with obesity is largely attenuated or eliminated by moderate-to-high levels of cardiorespiratory fitness (CRF) or physical activity (PA);

2) most cardiometabolic risk markers associated with obesity can be improved with exercise training independent of weight loss and by a magnitude similar to that observed with weight-loss programs;

3) weight loss, even if intentional, is not consistently associated with lower mortality risk;

4) increases in CRF or PA are consistently associated with greater reductions in mortality risk than is intentional weight loss; and

5) weight cycling (what we might call yo-yo dieting) is associated with numerous adverse health outcomes including increased mortality.

The paper (25 pages long with 6-7 pages of references) then set out the case for this summary.

The introduction to the paper presented data for the increase in the prevalence of obesity over the past 40 years – in parallel with the increase in the prevalence of weight loss attempts. “In sum, multiple surveys demonstrate a high prevalence of weight loss attempts over the past 40 years, during which, obesity prevalence has increased approximately 3-fold. Thus, the intense focus on weight loss has not prevented excessive weight gain in recent decades.” i.e., weight loss hasn’t worked. Some individuals will have lost weight during that time, but, at the population level, it cannot be disputed that weight loss has not been achieved.

This Gaesser and Angadi review thus set out to address two questions: (1) What is the magnitude of mortality risk reduction associated with intentional weight loss compared to that associated with increasing either PA or CRF? and (2) What is the magnitude of cardiovascular disease (CVD) risk marker reduction associated with weight loss interventions compared with that of PA interventions?

My approach to this paper was as follows: first I reviewed the evidence for the five bullet points, as summarised above. I assumed that the totality of evidence was presented (i.e., no cherry picking). The authors focused on meta-analyses (pooling together) of studies, so I was reassured by the approach. There was one (important) paper missing, which I happened to know about from a previous Monday note. At the end, I will reflect and consider were the right health risks focused upon? Has the case been made that cardiorespiratory fitness (CRF) or physical activity (PA) are better than weight loss for health risks?

The paper chose to focus on mortality and CVD risk markers for its examination of which is better for health risks – weight loss or activity? Mortality and CVD risk markers are the big two, but the paper did not examine cancer, diabetes, dementia, and other aspects of physical health or mental health. We can proceed knowing that we are looking at a narrow – albeit the most important – focus of health risks.

1) The BMI-mortality relationship

The first bullet point argued that the mortality risk associated with obesity is largely attenuated or eliminated by moderate-to-high levels of cardiorespiratory fitness (CRF) or physical activity (PA).

The opening to this section of the paper reminded us that it is often assumed that higher BMI means higher mortality risk, but the evidence for this is inconsistent. Gaesser and Angadi cited meta-analyses from the past 10 years, which have come to different conclusions about the relationship between BMI and mortality. Flegal et al was one of many papers cited (Ref 2). I recall this paper well, as it found that the overweight category (BMI of 25-<30) was associated with lower mortality risk than the normal BMI range (18.5-<25). It also found that Grade 1 obesity (BMI 30-<35) was not associated with increased mortality risk. The evidence is more consistent that obesity at BMI levels of 35 or higher is associated with higher mortality risk.

This section then needed to show that the mortality risk associated with high obesity is largely attenuated or eliminated by moderate-to-high levels of cardiorespiratory fitness (CRF) or physical activity (PA).

This is the first example of the question being answered being different to the claimed research question. Showing that fitness or activity reduces the mortality risk associated with obesity is not the same as showing that fitness is better than weight loss.

This section did present a case for fitness or activity reducing the mortality risk associated with obesity; it didn’t present a case for fitness being better than weight loss.

One lead author was relied upon to demonstrate the benefits of CRF or PA. Barry et al (2014) (Ref 3) showed that CRF could eliminate the mortality risk associated with high BMI and Barry et al (2018) (Ref 4) showed that CRF could greatly attenuate the mortality risk. Barry et al 2014 found that low CRF (being unfit) was associated with a 2-2.5-fold higher risk of all-cause mortality regardless of BMI. Barry et al 2018 found that CRF did not eliminate the CVD mortality risk associated with high BMI, but it did show that low CRF is more hazardous than is high BMI.

Gaesser and Angadi also reviewed the literature for physical activity and muscular fitness, which I won’t go through here, as there is much to cover. In summary, evidence was provided to show that physical activity and muscular fitness attenuated some of the mortality associated with higher BMI.

This section didn’t look at the case for weight loss and mortality – that was covered in bullet point three.

The Flegal et al paper could be used as a comparison, with caveats. Flegal et al found that, relative to normal weight, the (relative) risk for all obesity was 18% higher and the relative risk for grade 2 (BMI 35-<40) and grade 3 obesity (BMI 40 or greater) combined was 29% higher (Ref 5).

This might suggest that, if someone with a BMI above 35 could lose weight and achieve a BMI of below 35, they could reduce their risk of mortality significantly. However, this can’t be assumed. The mortality risk of having a BMI of (say) 27 is different to the mortality risk of having had a BMI of (say) 40 and losing weight to achieve a BMI of 27. Having never been obese (a BMI of 27 throughout adulthood) will have a different mortality risk to having been obese for many years and then losing weight. The method of weight loss would also have an influence on health risk or improvement.

The relative risk ratios in the 2018 Barry et al paper were in the range of 25-42%. This might suggest that cardiorespiratory fitness is as good as, or better than weight loss albeit only comparing these two studies.

The evidence presented in this section (albeit relying on one lead author) has shown that the mortality risks of obesity can be at least attenuated with CRF. However, I don’t think evidence has been presented to show that CRF/activity is better than weight loss – the head-to-head on this does not seem to have been done.

2) Cardiometabolic health improvement: physical activity vs weight loss

This section opened with the acknowledgement that weight loss is associated with many improvements in cardiometabolic risk markers for CVD and type 2 diabetes. Eight meta-analyses were cited as evidence. The authors then claimed that “the improvements in cardiometabolic risk markers associated with weight loss interventions are generally no greater than exercise training interventions without a specific weight loss target.” Evidence was provided for systolic blood pressure reductions of approximately 2.5-5.7 mmHg from exercise training vs reductions of approximately 1-5 mmHg from weight reduction.

Evidence presented for blood lipids was not decisive either way. Evidence presented for vascular function (flow-mediated dilation – FMD) concluded that “improvements in FMD reported in exercise training studies are comparable to those observed with weight-loss interventions.”

The evidence presented under (2) was comparable between weight loss and exercise, rather than exercise being better. The bigger issue in this section was that Gaesser and Angadi omitted to cite a paper by Valenzuela et al, which I reviewed earlier this year (Ref 6). The Valenzuela et al research letter concluded that, at all three weight levels (normal BMI, overweight and obese), it was better to be active than insufficiently active and it was better to be insufficiently active than inactive but being active did not counter the impact of overweight and particularly obesity. Some of the risk ratios were large – an obese (BMI >30) but active person had approximately five times the risk of hypertension as a normal weight active person and an obese but active person had approximately four times the risk of diabetes as a normal weight active person. This paper alone would suggest that weight loss is far more important than exercise in mitigating diabetes and hypertension – the two most significant cardiometabolic markers.

3) Intentional weight loss and mortality

This section was split into meta-analyses of observational studies and meta-analyses of randomised controlled trials (RCTs).

The seminal meta-analysis of observation studies reported an interesting finding: “intentional weight loss was associated with a 13% lower risk for individuals classified as unhealthy (4 studies), and a 16% lower risk among unhealthy adults with obesity (4 studies). However, intentional weight loss was associated with an 11% higher mortality risk among healthy individuals (8 studies) and a 9% higher risk among mostly healthy adults without obesity (5 studies). Among healthy adults with obesity, intentional weight loss was not associated with a lower mortality risk” (Ref 7). I.e., the value of weight loss depends on the starting weight; that makes sense.

Gaesser and Angadi found four meta-analyses of RCTs on the effect of intentional weight loss on mortality. Only one showed a significantly lower mortality risk associated with intentional weight loss and even this should be treated with caution because of the very limited mortality data. The one meta-analysis of RCTs, which focused on CVD mortality, showed no benefit of intentional weight loss. “In the most recent meta-analysis, which included 31 RCT lifestyle interventions (Singh et al., 2019), intentional weight loss among adults with overweight or obesity was not associated with a statistically significant reduction in all-cause mortality.”

4) Increasing physical activity or cardiorespiratory fitness: consistent reductions in mortality risk

This section presented numerous studies which examined increases in either physical activity or cardiorespiratory fitness and reductions in all-cause and CVD mortality. The conclusions from review of all the studies was “With few exceptions, increasing PA is associated with an approximately 15%–50% reduction in all-cause mortality and an approximately 15%–40% reduction in CVD mortality or cardiovascular events. Greater reductions in all-cause mortality risk are typically observed with increases in CRF. When the improvement in CRF is expressed as moving from ‘unfit’ or ‘low fit’’ to a higher fitness category, the reduction in all-cause mortality is in the range of 30%–60%.”

To be fair this section also questioned whether weight loss could explain the reduced mortality risk associated with improvements in physical activity or CRF i.e., did people do exercise and then lose weight and then reduce health risks? The authors lamented that most studies about CRF and PA did not report on weight changes and those that did indicated that weight loss was not a significant contributing factor. They concluded that the activity -> weight loss -> health benefits pathway would be unlikely not least because “increasing PA typically results in little, if any, weight loss.” i.e., we can’t outrun a bad diet – I agree!

5) The adverse effects of weight loss: Weight cycling

The authors noted (correctly and with evidence) that weight loss is rarely sustained. They also noted that there is no standard definition of weight cycling and studies have differed on whether it poses a health risk. The largest and most recent of three meta-analyses looking at weight cycling and mortality reported that weight cycling was associated with a 41% higher risk of all-cause mortality and a 36% higher risk of CVD mortality but was not related to cancer mortality (Ref 8).

The authors conclusion

The author conclusion reiterated the fact that the increased prevalence of weight loss attempts has coincided with the increased prevalence of obesity. “Thus, a weight-centric approach to obesity treatment and prevention has been largely ineffective.” This would be difficult to dispute.

The authors then argued that a weight-neutral approach to treating obesity-related health conditions may be as, or more, effective than a weight-loss-centered approach, and such an approach could avoid the pitfalls associated with repeated weight loss failure. This is a reasonable position to take.

My reflections

This was a very interesting paper and it serves as an excellent reference for the collective pool of evidence for the benefits of CRF and PA. It focused on all-cause mortality and CVD mortality, which are the big two health issues. However, the condition arguably most impacted by weight loss and health benefits – type 2 diabetes (T2D) – was not addressed. Mortality with T2D would be captured in all-cause mortality but the increase in the incidence of T2D may not have reached the mortality figures yet. It has undoubtedly reached the hospital resources and quality of life stage. Evidence from the Virta and DiRECT trials make compelling cases for the health benefits of weight loss interventions, independent of exercise (Ref 9).

In the current environment, Covid-19 may have been an important omission – the data may not be fully available yet. However, as early as April 2020, data from New York informed us that, when risk factors were prioritised, having a BMI of over 40 was the most serious characteristic beyond age for having a bad outcome with Covid-19 (hospitalisation, ICU or death) (Ref 10). Faced with these odds, weight loss could be life saving as Covid-19 is now endemic.

Focusing on BMI as a measure of obesity and mortality reminds us that the relationship between BMI and mortality is not clear cut. Being overweight, rather than normal weight, is helpful (especially as we age) as we tend to lose weight quickly with serious illness and some excess weight can be a life saver. All obesity is not the same either. Having a BMI of over 40 is more serious than having a BMI of between 30 and 35. How long we have had that obesity and how often we have tried to diet will also impact health outcomes.

We also need to recognise that many? most? people don’t try to lose weight because they have examined mortality risk data. They want to move more easily, feel better about themselves, look good for an upcoming function etc. and just generally not to be judged by a judgmental society. Showing their pragmatism, the authors acknowledged that “focusing on PA and CRF without establishing a specific weight-loss target is a challenging proposition when nearly three-fourths of women and more than half of men desire to weigh less” (Ref 11). And that’s the fact – no matter how often we have failed to lose weight in the past, we will continue to try. This is why I think the approach to weight loss is so important. Just because eat less has failed, it doesn’t mean that eat better can’t succeed.

This review made a good case for CRF or PA reducing all-cause/CVD mortality risks. The case for this being better than weight loss was not as convincing. However, part of this was due to the fact that head-to-head comparisons have not been done. The paper did make a good case for challenging the view that all weight loss is healthy. It depends on the starting weight. It depends on how the weight was lost (the long paper also reviewed liposuction and bariatric surgery – which have their own health risks – as well as weight cycling).

My final observation is that data exist at population levels. Data were either from observational studies (many people) or randomised controlled trials (enough people to compare). The collective data may be more compelling for exercise than diet, but at the individual level weight loss will invariably have significant positive benefits. There may also be something in the opening to the introduction – the fact that weight loss has proved extremely elusive over the past 40 years. Maybe the collective data for weight loss is so poor that the bar for exercise to beat is not high?

On reflection, the paper should not surprise me (or us). I have often said that exercise is good for everything other than weight loss – I’ve just not wondered if exercise were better than weight loss for everything else!

Until the next time

All the best – Zoë


Ref 1: Gaesser & Angadi. Obesity treatment: Weight loss versus increasing fitness and physical activity for reducing health risks. iScience (2021). https://doi.org/10.1016/j.isci.2021.102995
Ref 2: Flegal et al. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013.
Ref 3: Barry et al. Fitness vs. fatness on all-cause mortality: a meta-analysis. Prog. Cardiovasc. Dis. 2014.
Ref 4: Barry et al. The joint association of fitness and fatness on cardiovascular disease mortality: a meta-analysis. Prog. Cardiovasc. Dis. 2018.
Ref 5: Flegal et al found that, relative to normal weight, the Hazard Ratio (HR) for all obesity was 1.18 (95% CI, 1.12–1.25) and the HR for grade 2 (BMI 35-<40) and grade 3 obesity (BMI 40 or greater) combined was 1.29 (95% CI, 1.18–1.41).
Ref 6: https://www.zoeharcombe.com/2021/02/the-fat-but-fit-debate/
Ref 7: Harrington et al. A review and meta-analysis of the effect of weight loss on all-cause mortality risk. Nutr. Res. Rev. 2009.
Ref 8: Zou et al. Body-weight fluctuation was associated with increased risk for cardiovascular disease, all-cause and cardiovascular mortality: a systematic review and meta-analysis. Front Endocrinol. 2019.
Ref 9: https://www.zoeharcombe.com/2020/09/low-calorie-vs-low-carbohydrate-for-t2d-remission-direct-vs-virta/
Ref 10: https://www.zoeharcombe.com/2020/04/covid-19-risk-factors/
Ref 11: Yaemsiri et al. Perceived weight status, overweight diagnosis, and weight control among US adults: the NHANES 2003-2008 Study. Int. J. Obes. 2011.

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