Weight and Inflammation Part 4

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In part 1 of this series, Dr. Zed Zha shared a patient story of the harm that can happen when assumptions are made about the relationships between weight and inflammation. In parts 2 and 3, Dr. Zha examined common beliefs around inflammation, weight, and weight loss. In the final installment of this series, I’ll look at two possible confounding variables that may be at the root of associations between weight and inflammation.

Content note: These pieces are extensively referenced, please be aware that the references cited contain weight stigma.

A major issue with the current research that attempts to blame inflammation, and any related disease risk, on being higher weight (ie “overwe*ight and ob*sity”) is that it typically fails to mention, let alone address, weight cycling and weight stigma as possible confounding variables, despite a body of evidence suggesting otherwise.

Weight Cycling as a Potential Cause of Inflammation

Weight cycling refers to the loss and regain of weight. Research from the last century finds that it is, by far, the most common outcome of weight loss attempts.^{1,2,3,4,5,6,7}

Weight cycling has repeatedly been linked to inflammation in multiple studies, and this is not new information. In 2010, Strohacker and McFarlin found that weight cycling may “enhance the inflammatory capacity” of adipose tissue.⁸

And in their 2011 article in the Nutrition Journal, Bacon and Aphramor explain that

“Attempts to lose weight typically result in weight cycling, and such attempts are more common among ob*se individuals. Weight cycling results in increased inflammation, which in turn is known to increase risk for many ob*sity-associated diseases. Other potential mechanisms by which weight cycling contributes to morbidity include hypertension, insulin resistance and dyslipidemia. Research also indicates that weight fluctuation is associated with poorer cardiovascular outcomes and increased mortality risk. Weight cycling can account for all of the excess mortality associated with ob*sity in both the Framingham Heart Study and the National Health and Nutrition Examination Survey (NHANES). It may be, therefore, that the association between weight and health risk can be better attributed to weight cycling than adiposity itself.” ⁹

Just this year, Wang et al. published The Impact of Weight Cycling on Health and Ob*sity, which found that weight cycling “enhanced the inflammatory response of adipose tissue, macrophages infiltrated into adipose tissue, and increased the production of pro-inflammatory mediators in adipocytes.” ¹⁰

Given the prevalence of weight cycling in a world where it is the most common outcome of weight loss attempts and where repeated weight loss attempts are recommended for higher-weight people beginning at age two (not a typo)¹¹, there is a vast potential for negative impacts of weight cycling on inflammation and its associated risk factors across the lifespan of higher-weight people. And in a world, including healthcare and health research, rife with weight bias, there is a vast potential for the negative impacts of weight cycling to be blamed on being higher-weight, and for the ensuing recommendation to be attempted weight loss which is likely to result in weight cycling. This is viscous cycle harms higher-weight people at every point.

Weight Stigma as a Potential Cause of Inflammation

Weight stigma occurs when people experience different/worse treatment due to their size. More than 40% of people in the US report having experienced weight stigma.¹² Stigma has been linked to increased inflammation in marginalized communities including through racism,¹³ homophobia,^14,15 and transphobia.¹⁶

Much of this link has been seen through impacts of stigma on cortisol response. The Cleveland Clinic explains that nearly all body tissues have glucocorticoid receptors, and thus cortisol has the potential to impact almost every one of the body’s organ systems. Cortisol is a double-edged sword. While short burst exposure can reduce inflammation,. long-term exposure to high cortisone levels can create chronic inflammation. Chronically high cortisone levels have been associated with high blood sugar and high blood pressure.¹⁷

Research has found that experience, or even perception of the experience, of weight stigma can both decrease the short-term benefit of cortisol and increase the harm through long-term exposure.

For example, in finding that “experiencing weight stigma was stressful for participants who perceived themselves as heavy, regardless of their BMI”, Himmelstein et al. point out that “These results are important because stress and cortisol are linked to deleterious health outcomes.”¹⁸

In 2014, Tomiyama et al. found that “Independent of abdominal fat, weight stigma was significantly related to measures of cortisol…as well as higher levels of oxidative stress.” They concluded that “it is possible that weight stigma may contribute to poor health underlying some forms of ob*sity.”¹⁹

Finally, in 2019, McCleary-Gaddy et al. found that study participants who were “overw*ight” based on the BMI scale or who considered themselves to be “overw*ight” showed a blunted cortisol response in the presence of weight-stigma which was not found in “lean” participants in the same conditions. They concluded that “people who experience the chronic stress of being stigmatized due to their weight show blunted cortisol responses just as other chronically stressed people do.”²⁰

Here again, creating a “war on ob*sity” in which higher-weight people receive constant messages from every area of their lives, including healthcare and public health, that their bodies are wrong, bad, and diseased foments weight stigma that may well be driving health issues that are subsequently blamed on being higher-weight. This “war” makes higher-weight people into enemy combatants and casualties.

It should also be noted that in addition to inflammation, weight cycling and weight stigma have been linked to negative physical and psychological health outcomes including high blood pressure, type 2 diabetes, cardiovascular disease, suicidality, overall mortality and more.^21,22

Frustratingly, even among the above-cited studies, many still recommend or credit weight loss with lowing the risks associated with inflammation. This is despite research finding that the 5-10% weight loss, (the result for weight loss interventions, prior to the almost inevitable weight cycling) was found in correlational analysis to have “no clear relationship” to “health outcomes related to hypertension, diabetes or cholesterol” suggesting that behaviors were more likely to have created any positive effect, rather than weight change.²³ This is further supported by research showing that those with shared behaviors have similar health outcomes regardless of weight, ^{24, 25,26, 27}and that weight changes without behavior changes do not produce health changes²⁸.

In the absence of more definitive research that adequately addresses these variables, the truth is that health issues that are commonly called “weight-related” or “ob*sity-related” may, in fact, be weight cycling related and/or weight stigma related. Further, given that the vast majority of weight loss attempts end in weight cycling, the continued recommendation of these interventions and the stigma that comes with pathologizing body size and calling for the eradication of higher-weight people may very well be doing untold harm to higher-weight people. It creates a vicious cycle wherein, instead of following the data, healthcare and public health research and practice create weight stigma and weight cycling, then blame the negative outcomes that result on higher-weight bodies, then use those same negative outcomes to justify additional and greater weight stigma and weight cycling. Higher-weight patients often experience this as medical gaslighting.

To stop this cycle, we could move to a weight-neutral paradigm in which the focus is on supporting the health of people of all sizes without the intention to manipulate their weight or “help” them become thinner people. Campaigns to end weight stigma (and, critically, not a campaign from the weight loss industry and the non-profit astroturf “patient advocacy groups” they fund that co-opt the idea of weight stigma to sell weight loss) are urgently needed to create a world that affirms and accommodates people of all sizes.

Check out Dr. Zha’s substack here
(Scroll down for reference list)

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More research and resources:
https://haeshealthsheets.com/resources/

*Note on language: I use “fat” as a neutral descriptor as used by the fat activist community, I use “ob*se” and “overw*ight” to acknowledge that these are terms that were created to medicalize and pathologize fat bodies, with roots in racism and specifically anti-Blackness. Please read Sabrina Strings’ Fearing the Black Body – the Racial Origins of Fat Phobia and Da’Shaun Harrison’s Belly of the Beast: The Politics of Anti-Fatness as Anti-Blackness for more on this.

References

¹Albert Stunkard and Mavis McLaren-Hume, “The Results of Treatment for Obesity: A Review of the Literature and Report of a Series,” A.M.A. Archives of Internal Medicine 103, no. 1 (January 1, 1959): 79–85, https://doi.org/10.1001/archinte.1959.00270010085011.

² W. C. Miller, “How Effective Are Traditional Dietary and Exercise Interventions for Weight Loss?,” Medicine and Science in Sports and Exercise 31, no. 8 (August 1999): 1129–34, https://doi.org/10.1097/00005768-199908000-00008.

³ Traci Mann et al., “Medicare’s Search for Effective Obesity Treatments: Diets Are Not the Answer,” The American Psychologist 62, no. 3 (April 2007): 220–33, https://doi.org/10.1037/0003-066X.62.3.220.

⁴ Lucy Aphramor, “Validity of Claims Made in Weight Management Research: A Narrative Review of Dietetic Articles,” Nutrition Journal 9, no. 1 (July 20, 2010): 30, https://doi.org/10.1186/1475-2891-9-30.

⁵ Alison Fildes et al., “Probability of an Obese Person Attaining Normal Body Weight: Cohort Study Using Electronic Health Records,” American Journal of Public Health 105, no. 9 (September 2015): e54-59, https://doi.org/10.2105/AJPH.2015.302773.

⁶ A. Janet Tomiyama, Britt Ahlstrom, and Traci Mann, “Long-Term Effects of Dieting: Is Weight Loss Related to Health?,” Social and Personality Psychology Compass 7, no. 12 (2013): 861–77, https://doi.org/10.1111/spc3.12076.

⁷ Nathan R. Weeldreyer et al., “Cardiorespiratory Fitness, Body Mass Index and Mortality: A Systematic Review and Meta-Analysis,” British Journal of Sports Medicine, November 13, 2024, bjsports-2024-108748, https://doi.org/10.1136/bjsports-2024-108748.

⁸ K. Strohacker and Brian K. McFarlin, “Influence of Obesity, Physical Inactivity, and Weight Cycling on Chronic Inflammation,” Frontiers in Bioscience (Elite Edition) 2, no. 1 (January 1, 2010): 98–104, https://doi.org/10.2741/e70.

⁹ Linda Bacon and Lucy Aphramor, “Weight Science: Evaluating the Evidence for a Paradigm Shift,” Nutrition Journal 10, no. 1 (January 24, 2011): 9, https://doi.org/10.1186/1475-2891-10-9.

¹⁰ Huan Wang et al., “The Impact of Weight Cycling on Health and Obesity,” Metabolites 14, no. 6 (June 2024): 344, https://doi.org/10.3390/metabo14060344.

¹¹ Sarah E. Hampl et al., “Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity,” Pediatrics 151, no. 2 (January 9, 2023): e2022060640, https://doi.org/10.1542/peds.2022-060640.

¹² Zara Abrams, “The Burden of Weight Stigma,” https://www.apa.org, 2022, https://www.apa.org/monitor/2022/03/news-weight-stigma.

¹³ April D Thames et al., “Experienced Discrimination and Racial Differences in Leukocyte Gene Expression,” Psychoneuroendocrinology 106 (August 1, 2019): 277–83, https://doi.org/10.1016/j.psyneuen.2019.04.016.

¹⁴ Robert-Paul Juster et al., “Sexual Orientation Modulates Endocrine Stress Reactivity,” Biological Psychiatry 77, no. 7 (April 1, 2015): 668–76, https://doi.org/10.1016/j.biopsych.2014.08.013.

¹⁵ Magdalena Mijas et al., “Dysregulated by Stigma: Cortisol Responses to Repeated Psychosocial Stress in Gay and Heterosexual Men,” Psychoneuroendocrinology 131 (September 1, 2021): 105325, https://doi.org/10.1016/j.psyneuen.2021.105325.

¹⁶ L. Zachary DuBois et al., “Gender Minority Stress and Diurnal Cortisol Profiles among Transgender and Gender Diverse People in the United States,” Hormones and Behavior 159 (March 1, 2024): 105473, https://doi.org/10.1016/j.yhbeh.2023.105473.

¹⁷ Cleveland Clinic, “Cortisol: What It Is, Function, Symptoms & Levels,” Cleveland Clinic, 2021, https://my.clevelandclinic.org/health/articles/22187-cortisol.

¹⁸ Mary S. Himmelstein, Angela C. Incollingo Belsky, and A. Janet Tomiyama, “The Weight of Stigma: Cortisol Reactivity to Manipulated Weight Stigma,” Obesity 23, no. 2 (2015): 368–74, https://doi.org/10.1002/oby.20959.

¹⁹ A. Janet Tomiyama et al., “Associations of Weight Stigma with Cortisol and Oxidative Stress Independent of Adiposity,” Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association 33, no. 8 (August 2014): 862–67, https://doi.org/10.1037/hea0000107.

²⁰ Asia T McCleary-Gaddy et al., “Weight Stigma and Hypothalamic–Pituitary–Adrenocortical Axis Reactivity in Individuals Who Are Overweight,” Annals of Behavioral Medicine: A Publication of the Society of Behavioral Medicine 53, no. 4 (June 16, 2018): 392–98, https://doi.org/10.1093/abm/kay042.

²¹ Ragen Chastain, “The Harm of Weight Cycling,” Substack newsletter, Weight and Healthcare (blog), February 9, 2022, https://weightandhealthcare.substack.com/p/the-harm-of-intentional-weight-loss.

²² Ragen Chastain, “The Harm of Weight Stigma,” Substack newsletter, Weight and Healthcare (blog), March 8, 2023, https://weightandhealthcare.substack.com/p/the-harm-of-weight-stigma.

²³ Tomiyama, Ahlstrom, and Mann, “Long-Term Effects of Dieting.”

²⁴ Ming Wei et al., “Relationship between Low Cardiorespiratory Fitness and Mortality in Normal-Weight, Overweight, and Obese Men,” JAMA 282, no. 16 (October 27, 1999): 1547–53, https://doi.org/10.1001/jama.282.16.1547.

²⁵ Eric M. Matheson, Dana E. King, and Charles J. Everett, “Healthy Lifestyle Habits and Mortality in Overweight and Obese Individuals,” The Journal of the American Board of Family Medicine 25, no. 1 (January 1, 2012): 9–15, https://doi.org/10.3122/jabfm.2012.01.110164.

²⁶ Glenn A. Gaesser and Siddhartha S. Angadi, “Obesity Treatment: Weight Loss versus Increasing Fitness and Physical Activity for Reducing Health Risks,” iScience 24, no. 10 (October 22, 2021): 102995, https://doi.org/10.1016/j.isci.2021.102995.

²⁷ Weeldreyer, N. R., De Guzman, J. C., Paterson, C., Allen, J. D., Gaesser, G. A., & Angadi, S. S. (2024). Cardiorespiratory fitness, body mass index and mortality: A systematic review and meta-analysis. British Journal of Sports Medicine, bjsports-2024-108748. https://doi.org/10.1136/bjsports-2024-108748

²⁸ Klein, S., Fontana, L., Young, V. L., Coggan, A. R., Kilo, C., Patterson, B. W., & Mohammed, B. S. (2004). Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. The New England Journal of Medicine, 350(25), 2549–2557. https://doi.org/10.1056/NEJMoa033179