Navigating Obesity in Immune Dysfunction

Everyone’s awareness about comorbidities, especially overweight and obesity, is heightened due to COVID-19. And in two recent WebMD polls, up to 47% of women and 55% of men report gaining weight during the lockdown – no surprise there – but this may imply patients may be more interested in achieving weight loss goals as part of their overall health care than in previous times.

Except we know conventional weight loss programs that lead to a calorie deficit are woefully inadequate (even counterproductive), leading to poor resistance to infection and malnutrition, as Corey Schuler from Integrative Therapeutics explains in this blog below. Read on to learn about the immunometabolic changes brought about in obesity, how to counter them, and I for one, am super grateful Corey relays this encouraging fact: losing just 5% of body mass leads to significant benefits.

Such good news, and highly achievable! This is a challenge most patients and practitioners can rise to, especially with the concrete action steps outlined in this article. The obesity epidemic isn’t going anywhere unfortunately, but with a careful and thoughtful approach to weight loss, immunity, and nutrition, achieving a healthier body weight might just be one silver lining of the COVID-19 pandemic. ~DrKF

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Navigating Obesity in Immune Dysfunction

Obesity is a well-recognized risk for poor health, and, most notably, cardiovascular pathology and complications. Except in the circumstances of morbid and super morbid obesity accompanied by significant hypertension, that risk seems like several horizons away and often does not translate to action. What can a practitioner do, when a patient does not see the danger signs that are flashing all around them?

It can reasonably be argued that our food supply, environment, media, and general population-wide sedentary lifestyle are significant contributors and that policy-based and societal changes are required to change the course of obesity as a disease state. The trajectory is clearly on the rise with twelve states now reporting a prevalence of 35% or higher.¹ In 2017 six states had this prevalence and in 2018, nine states reported as such.² Furthermore, “obesity disproportionately impacts some racial and ethnic minority groups.”²

However, practitioners in both integrative and conventional medicine in a clinical setting, must assess and treat obesity on an individual basis to reduce the consequences of obesity which may be more near term than we ever realized. The Centers for Disease Control and Prevention suggests that “as BMI increases, the risk of death from COVID-19 increases” which draws from the published findings of a retrospective cohort study of Kaiser Permanente Southern California members diagnosed with COVID-19 between February 13^th and May 2^nd, 2020.³  In fact, patients with obesity may have 3x the risk of hospitalization which is the same risk factor as having diabetes or hypertension.⁴ The risks do not end there.  Mechanical ventilation may be more difficult and less effective in obese patients due to decreased lung capacity.⁵

With this, and accumulating data, patients may be viewing their battle with weight more urgently. Or, they may not…and it then becomes incumbent upon their practitioners to shine a light on this urgency without inciting unnecessary fear.

We know that obesity causes T lymphocyte dysfunction.⁶ T lymphocytes are important parts of the adaptive immune system responsible for directly killing infected host cells, activating other immune cells, producing cytokines, and regulating the immune response. Obesity also causes increases in Tumor Necrosis Factor-alpha (TNF-a), which is a marker of inflammation.⁶ The good news is that weight loss can restore these dysfunctions.⁶ TNF-α can be secreted from adipose tissue and tissue-localized macrophages, which are increased in obesity. It is a well-known pro-inflammatory cytokine that is essential for the acute phase reaction but also a fundamental initiating factor in insulin resistance. TNF-a activates additional proinflammatory cytokines which subsequently reduce the ability of muscles cells (myocytes) and fat cells (adipocytes) to uptake glucose at the level of the insulin receptors.⁷ Obesity causes excess production of inflammatory adipocytokines which results in changes in immunometabolism and ultimately both impairs protective immunity and increases risk of autoimmunity.⁸

On the flip side, malnutrition causes insufficient production of inflammatory adipocytokines which results in different but also unwanted changes in immunometabolism such as decreased cytotoxic (CD4+ and CD8+) T cell counts and decreases in M1 macrophages. M1 macrophages, also known as classically activated macrophages, are responsible for secreting pro-inflammatory cytokines and chemokines such as IL-6, IL-12 and TNF-a. These markers in excess can certainly be problematic, but when they are not sufficiently produced, pathogens that have penetrated barrier defenses are more likely to proliferate. Malnutrition also impairs protective immunity but confers protection against autoimmunity.⁸ At the crossroads of these effects is leptin. Generally, obesity results in elevated leptin levels while hypoleptinemia reflects the insufficiency status described above. Leptin is not only a commercially available marker that can be tracked by the practitioner, but it is functional and influential in the crosstalk of these important immune players.⁸

In 2016, published results of a small randomized control trial made headlines, and impacted clinical recommendations for many practitioners. That study suggested that patients begin seeing positive health benefits after losing just 5% of their body mass.⁹ This modest improvement in body composition was more achievable than attempting to reach a specific population-based BMI goal such as less than 30 kg/m².  More recently, a large retrospective study out of the UK found that a median loss of 13% had the greatest benefit on cardiovascular risk factors, type 2 diabetes, hypertension, and dyslipidemia.¹⁰

While an energy-deficit (i.e., negative energy balance) is critical for weight loss, the challenge of executing such a deficit with diet alone without suppressing immune function is a genuine art. This is where exercise recommendations come into play. In a systematic review, physical activity alone led to only modest reductions in weight.¹¹  However, routine exercise has been found to be a keystone habit of those losing and maintaining significant weight loss in the largest prospective investigation of long-term successful weight loss maintenance known as the National Weight Control Registry. Yet, exercise has its own complication when it comes to immune function. While a sedentary lifestyle increases respiratory tract infection risk, so does prolonged or intense exercise.¹²

As practitioners it is our job to thread the needle between hyponutrition and hypernutrition and simultaneously balance hypoactivity and excess activity to achieve the goal of weight loss for the purposes of immune health.

Some thoughts from the trenches on this include:

• Not relying exclusively on a dietary calorie deficit for weight loss as this can lead to insufficient nutrition and immune dysfunction.
• Exercise should be used as a tool, but duration and intensity should be recorded and methodically reported to the primary practitioner supporting the patient.
• Adequate protein intake is necessary during weight loss since protein is essential to build tissues including skeletal, and muscle, and makes up the components of the immune system.
• Maintain micronutrient levels through supplementation as necessary. This may include a high potency multivitamin, macrominerals such as calcium and/ or magnesium, omega-3 fatty acids, and personalized needs based on clinical, biochemical, and dietary assessment.
• Consider tracking leptin levels at baseline and throughout the weight loss journey.
• Weight loss goals can be broken up into four discrete goals rather than a single programmatic goal:
• Short-term 5% weight loss
• Moderate-term 13% weight loss
• Moderate-long-term reaching healthy BMI
• Long-term, maintaining healthy BMI for more than 12 months

The bottom line is that weight loss should take center stage in a patient-centric model of care and urgency to do so has never been greater. Weight loss often requires a team approach with the patient leading the charge, supported primarily by a practitioner with expert knowledge, and other ancillary specialists and support staff such as coaches, trainers, and nutrition professionals.

References

1. Center for Disease Control and Prevention. Adult Obesity Prevalence Maps. Accessed at https://www.cdc.gov/obesity/data/prevalence-maps.html
2. Center for Disease Control and Prevention. Obesity, Race/Ethnicity, and COVID-19Accessed at https://www.cdc.gov/media/releases/2020/s0917-adult-obesity-increasing.html
3. Tartof SY, Qian L, Hong V, et al. Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization [published online ahead of print, 2020 Aug 12]. Ann Intern Med. 2020;M20-3742. doi:10.7326/M20-3742
4. Center for Disease Control and Prevention. People with Certain Medical Conditions. Accessed at https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-underlying-medical-conditions.html
5. Simonnet A, Chetboun M, Poissy J, et al. High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation. Obesity (Silver Spring). 2020;28(7):1195-1199. doi:10.1002/oby.22831
6. Tanaka S, Isoda F, Ishihara Y, Kimura M, Yamakawa T. T lymphopaenia in relation to body mass index and TNF-alpha in human obesity: adequate weight reduction can be corrective. Clin Endocrinol (Oxf). 2001;54(3):347-354.
7. Nieto-Vazquez I, Fernández-Veledo S, Krämer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo M. Insulin resistance associated to obesity: the link TNF-alpha. Arch Physiol Biochem. 2008;114(3):183-194. doi:10.1080/13813450802181047
8. Alwarawrah Y, Kiernan K, MacIver NJ. Changes in Nutritional Status Impact Immune Cell Metabolism and Function. Front Immunol. 2018;9:1055. Published 2018 May 16. doi:10.3389/fimmu.2018.01055
9. Magkos F, Fraterrigo G, Yoshino J, et al. Effects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with Obesity. Cell Metab. 2016;23(4):591-601. doi:10.1016/j.cmet.2016.02.005
10. Searing, L. Losing 13 percent of your weight could lead to big improvements in your health. Washington Post. Accessed at https://www.washingtonpost.com/health/weight-loss-better-health/2020/09/11/d55ca5fa-f37f-11ea-bc45-e5d48ab44b9f_story.html
11. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017;30(3):157-160. doi:10.2337/ds17-0013
12. Martin SA, Pence BD, Woods JA. Exercise and respiratory tract viral infections. Exerc Sport Sci Rev. 2009;37(4):157-164. doi:10.1097/JES.0b013e3181b7b57b

By: Corey Schuler, RN, MS, LN, CNS, CNSC, DC

Corey Schuler, RN, MS, LN, CNS, CNSC, DC serves as the Director of Clinical Affairs for Integrative Therapeutics and is adjunct professor at New York Chiropractic College and Southwest College of Naturopathic Medicine. He practices integrative and functional medicine in the Greater Minneapolis-St. Paul, Minnesota area, and is a member of Institute for Functional Medicine and American Nutrition Association. Dr. Schuler is a Certified Nutrition Specialist, registered nurse, licensed nutritionist, and earned a Master of Science degree in human nutrition and a degree in chiropractic medicine.