Weight and Inflammation Part 3
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In part 1 Dr. Zed Zha discussed a patient experience that elucidated the issues that happen when assumptions are made about the relationships between weight and health. In part 2 she began a discussion of four conditions that must be met to rigorously prove the theorem that weight loss lowers inflammation - “weight ↓ → inflammation ↓”. In part 3 of this 4-part series, she’ll discuss the third and fourth conditions.
Content note: These pieces are extensively referenced, please be aware that the references cited contain weight stigma.
Condition 1: Clearly define what constitutes "inflammation" and establish a valid, measurable method for quantifying it.
Condition 2: Measure inflammation both before and after weight loss in the same individuals, ensuring the data show a statistically significant reduction in inflammation.
Condition 3: Demonstrate that weight loss (weight ↓) is not associated with a “paradoxical” increase in inflammation (inflammation ↑), i.e., weight ↓ --/--> inflammation ↑.
Condition 4: If the first three conditions cannot be satisfied, a desperate alternative —proof by contradiction—can be employed: Show that the opposite is not true, specifically, that an increase in inflammation (inflammation ↑) does not correlate with an increase in weight (weight ↑), i.e., inflammation ↑ --/--> weight ↑.
3.Showing weight loss doesn’t increase inflammation (weight ↓ ≠ inflammation ↑.)
In a 2017 study following patients after bariatric surgery, patients’ inflammatory markers and adipose tissue (AT) pro-inflammatory markers not only remained unchanged, but there was also a 15-20 fold spike of AT neutrophils – the most abundant type of white blood cells in the immune system. And this flooding of AT by neutrophils was sustained for at least 12-months.19
And what I haven’t mentioned is, like the male mice study, in the above 2009 European study, the researchers actually found an initial increase in the gene expression of macrophage markers during the 1st month – the very low caloric diet phase.15 Interestingly, four years after this study, the same group recruited another 23 fat women to undergo an even longer restrictive diet period, this time 5-6 months. Before and after another 10kg average significant weight loss, their belly fat was biopsied and analyzed, again. Guess what they found? The precursor fat cells were more likely to become fat cells after this weight loss. The researchers were “tempted to speculate” that this meant weight loss made the cells more eager to store lipids, preventing the accumulation of these lipids in the rest of the body.20 But really, the more logical conclusion should be this: weight loss from restrictive diets pushes the body to make more fat cells whenever possible, which might be one of the reasons why weight cycling is the most common outcome of weight loss attempts.
In conclusion, I’ve got some bad news for the diet and weight loss industry: weight loss measures can cause significant stress on the body. And, as we’ll explore more in part 4, stress is very inflammatory. Condition 3: disproven.
4. Proving it’s not true that inflammation leads to weight gain. (Inflammation ↑ ≠ weight ↑.)
When you type in “inflammation and weight gain” on scholarly search engines, almost every study that comes up swaps “weight gain” to “ob*sity” as a disease. This is because medical research currently operates under the dogma that ob*sity is an illness and therefore must be the chicken. And inflammation, by default, is the egg. Any of my fat patients struggling with an inflammatory illness can tell you: it’s probably the opposite. And as their physician, I stand with them in this suspicion (and in general).
In 2014, researchers from UCLA and Vanderbilt set out to prove us right. (Tip of the hat to them!) They manipulated the genes of mice to make their blood vessels produce more reactive oxygen species, which trigger inflammation. These mice not only had moderate weight gain, but with high-fat feeding, their body mass increased out of proportion. Additionally, they had reduced activity level and energy expenditure, which was believed to be from skeletal muscle dysfunction caused by oxidative stress. Compared to the mice that had the opposite genetic manipulation, high-fat diet did not make them gain weight, and their AT had reduced inflammatory cells. They concluded, logically, that oxidative stress (which happened first) induced weight gain (which happened subsequently).26
In addition to proving that “ob*sity” can be a result of stress/inflammation, the study also elegantly showed two other important points: 1) what the mice ate wouldn’t have caused weight gain if no genetic predisposition to gaining weight was present in the first place, and 2) the ability to exercise and actually spend stored energy were also heavily influenced by genetic makeups. So, were these fat mice “overeaters” or “lazy,” or are those just rodent-blaming terms we used to pathologize fatness?
Ok, I might be getting ahead of myself here because this was a mouse study, not a human experiment. The problem with duplicating such data in humans is that we cannot sufficiently control inflammation or oxidative stress in a study environment. Genetically manipulating humans for medical experimentation is unethical; so is purposely inducing inflammation or stress in human subjects for the sake of measuring weight.
What do we do? Well, it turns out, there is plenty of data readily available to show that inflammation induces weight gain already. We just refuse to believe them.
In 2023, researchers from China used national survey data of over 20,000 patients to study the relationship between weight and arthritis over a 20-year period. Because for those who gained weight over time, their arthritis overlapped with their weight gain in life, the researchers concluded that ob*sity and weight gain increased the risks of arthritis. Even though the study itself admitted that time overlap didn’t mean causality, it still went on to suggest that “weight management throughout adulthood” can be a strategy for preventing arthritis.27 Notably, the study looked at both osteoarthritis – the wear and tear type – and rheumatoid arthritis (RA) – an autoimmune inflammatory disease. The etiology of osteoarthritis might be debatable. But RA has a well-established genetic basis in its cause. And up to 65% of seropositive RA is inherited.28 Therefore, unless “weight management” can alter genetics, it’s entirely plausible that the patients who had RA had RA-related inflammation first (because of their genetics), and the weight gain followed second.
Additionally, if you really investigate the data of this study, you will see that it actually found a “U” shaped association between absolute weight change and the risks of developing arthritis: the arthritic risks went up for both people who gained weight and lost weight over time. Plus, among those who went from “ob*se” to “non-ob*se” over 20 years, their arthritic risk did not change, at all. To me, these two results contradicted each other. The first said that losing weight can increase the risks of arthritis. Yet the second said when the weight loss is significant enough for a person to drop BMI categories, their arthritic risk didn’t change. That’s interesting: because either weight loss induces arthritis, or it doesn’t have anything to do with arthritis. But they can’t both be true! Unless…arthritis happens regardless of weight change, or BMI is a bad measure of weight. Or both.
In conclusion, it is not beyond reason to believe that first there was inflammation, and lo, from it arose weight gain thereafter. Condition 4, refuted.
It gives me more satisfaction than solving for x to say this, dear readers: I rest my case. Argument complete, theorem disproven, and no variables left to solve!
In part 4, we’ll look at two possible causes of inflammation that are too-often left out of the research and subsequent conversations on weight and inflammation.
(Scroll down for reference list)
Want to learn how to analyze research? I’m doing a workshop with Marci Evans, RD to teach just that. In an age when a lot of weight-science research is industry-funded and/or conducted by people with significant conflicts of interest, those of us who hope to understand and/or provide ethical, evidence-based care must be able to read the research with a critical eye. You can find details and registration at https://marcird.com/workshop/ There is a recording for those who can’t make it live and a pay-what-you-can option so that money isn’t a barrier to this information!
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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
19. Hagman DK, Larson I, Kuzma JN, et al. The short-term and long-term effects of bariatric/metabolic surgery on subcutaneous adipose tissue inflammation in humans. Metabolism. 2017;70:12-22.
20. Rossmeislová L, Mališová L, Kračmerová J, et al. Weight Loss Improves the Adipogenic Capacity of Human Preadipocytes and Modulates Their Secretory Profile. Diabetes. 2013;62(6):1990-1995. doi:10.2337/db12-0986
21. Verhaegen AA, Van Gaal LF. Drugs That Affect Body Weight, Body Fat Distribution, and Metabolism. In: Feingold KR, Anawalt B, Blackman MR, et al, eds. Endotext. MDText.com, Inc.Copyright © 2000-2024, MDText.com, Inc.; 2000.
22. Ma Y, Xiang Q, Yan C, Liao H, Wang J. Relationship between chronic diseases and depression: the mediating effect of pain. BMC Psychiatry. 2021/09/06 2021;21(1):436. doi:10.1186/s12888-021-03428-3
23. Mueller J, Ahern AL, Jones RA, et al. The relationship of within-individual and between-individual variation in mental health with bodyweight: An exploratory longitudinal study. PLOS ONE. 2024;19(1):e0295117. doi:10.1371/journal.pone.0295117
24. health.gov. Poverty. US Department of Health and Human Services. Accessed October 28, 2024. https://odphp.health.gov/healthypeople/priority-areas/social-determinants-health/literature-summaries/poverty#:~:text=Across%20the%20lifespan%2C%20residents%20of,mortality%2C%20and%20lower%20life%20expectancy.&text=Children%20make%20up%20the%20largest%20age%20group%20of%20those%20experiencing%20poverty.
25. Chastain R. Who Says Dieting Fails Most Of The Time? A research timeline of the epic failure of weight loss interventions. Weight and Healthcare blog. October 28, 2021. https://weightandhealthcare.substack.com/p/who-says-dieting-fails-the-majority?s=w
26. Youn J-Y, Siu KL, Lob HE, Itani H, Harrison DG, Cai H. Role of vascular oxidative stress in obesity and metabolic syndrome. Diabetes. 2014;63(7):2344-2355.
27. Nan K, Zhang M, Hu S, et al. Relationship of weight change patterns from young to middle adulthood with incident rheumatoid arthritis and osteoarthritis: a retrospective cohort study. Frontiers in Endocrinology. 2024;14:1308254.
28. Chauhan K, Jandu JS, Brent LH, Al-Dhahir MA. Rheumatoid Arthritis. StatPearls. StatPearls Publishing
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