Stress and inflammations contribution to chronic disease

 

The Impact of Stress

Large bodies of research indicate that chronic stress, whether experienced in early life or as an adult, is linked to increased coronary heart disease risk.1,6 In particular, childhood adversity, including physical and sexual abuse in childhood, has been shown to relate to higher morbidity of cardiovascular events.7,8 Work-related stressors, poor sleep, and emotional disturbances have been correlated with adult-related cardiovascular disease.1 Racism and discrimination create additional daily stressors for Black, Indigenous, and People of Color (BIPOC) communities, impacting their increased cardiovascular disease risks.9-12

A 2018 finding using data from the Jackson Heart Study suggested that in African American adults, global stress (overall stress level) and major life events were associated with increased risk of metabolic syndrome (MetS) severity.13 Additionally, men and women’s MetS and stress responses varied in severity. For example, men significantly increased their MetS severity at medium levels of stress, whereas women significantly increased their MetS severity at high levels of stress.13

LEARN MORE ABOUT FUNCTIONAL MEDICINE

Chronic psychological stress and inflammation are also associated with a greater risk of depression, autoimmune diseases, upper respiratory infections, and poor wound healing.3 In a large study published in 2019 in the journal Molecular Psychiatry, a team of researchers from Cambridge examined the link between depression and coronary heart disease.14 Their findings suggest that the connection between these two conditions cannot be explained by a common genetic predisposition; rather, it is environmentally related. They used Mendelian randomization to investigate 15 biomarkers associated with the risk of coronary heart disease; of these biomarkers, they found that triglycerides and the inflammation-related proteins IL-6 and CRP were also risk factors for depression. What’s more, the authors note that with regard to shared environmental factors, the depression–coronary heart disease comorbidity could be linked with early-life factors influencing inflammatory regulation, such as impaired fetal development or childhood maltreatment/trauma. Low birth weight and childhood maltreatment were associated with increased levels of circulating inflammatory markers, depression, and coronary heart disease in adulthood.14

Similarly, researchers have for years speculated that disorders of the gastrointestinal tract, such as Crohn’s disease and ulcerative colitis, are related to stress and inflammation,15 but the underlying mechanism remained largely unresolved. An elegant 2018 study in mice suggests a clue, showing that chronic stress disturbs gut microbiota, triggering an immune system response and facilitating dextran sulfate sodium-induced colitis.16 Recently, a 2020 systematic review of 19 clinical prospective cohort studies also concluded that while evidence suggests that psychological factors have a weak to moderate causal involvement in inflammatory bowel disease symptom exacerbation, overall results remain inconclusive and additional studies are warranted.17

Managing Stress

With a wide range of stress-related chronic diseases on the rise, how can functional medicine clinicians target stress-related factors with interventions that improve the health of their patients? Accumulating evidence points to the beneficial effects of regular exercise in preventing or improving the metabolic and psychological comorbidities brought about by chronic stress.18 Recent meta-analyses indicate that physical exercise improves the inflammatory state in children with obesity19 and improves inflammatory biomarkers in middle-aged and older adults.20

In 2017, a first-of-its-kind study on yoga and meditation showed improvement in biomarkers of cellular aging, which are associated with oxidative stress and complex lifestyle diseases like depression, diabetes, and cardiovascular disease.21 The researchers suggested that the improvement in stress and inflammatory response was mediated by changes in cortisol, ?-endorphin, IL-6, and other factors, with regulation by changes in the brain through the hypothalamic-pituitary-adrenal (HPA) axis.21

Many diseases stemming from chronic stress and inflammation have early warning signs, meaning some cases may be prevented or improved with lifestyle changes that help manage stress. The functional medicine model focuses in on identifying stress as a cause of dysfunction and utilizing specific interventions like exercise, meditation, and yoga that work for the individual patient. Tools such as the functional medicine timeline can also help clinicians identify areas of life where stress may be problematic and design treatments that focus on improving stress management.Learn more about tools and strategies to help patients achieve sustainable lifestyle change and improve their well-being through IFM’s new course Lifestyle: The Foundations of Functional Medicine.

References

1. Liu YZ, Wang YX, Jiang CL. Inflammation: the common pathway of stress-related diseases. Front Hum Neurosci. 2017;11:316. doi:10.3389/fnhum.2017.00316
2. Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822-1832. doi:10.1038/s41591-019-0675-0
3. Cohen S, Janicki-Deverts D, Doyle WJ, et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci U S A. 2012;109(16):5995-5999. doi:10.1073/pnas.1118355109
4. Miller GE, Cohen S, Ritchey AK. Chronic psychological stress and the regulation of pro-inflammatory cytokines: a glucocorticoid-resistance model. Health Psychol. 2002;21(6):531-541. doi:10.1037//0278-6133.21.6.531
5. Walsh CP, Bovbjerg DH, Marsland AL. Glucocorticoid resistance and ?2-adrenergic receptor signaling pathways promote peripheral pro-inflammatory conditions associated with chronic psychological stress: a systematic review across species. Neurosci Biobehav Rev. 2021;128:117-135. doi:10.1016/j.neubiorev.2021.06.013
6. Su S, Jimenez MP, Roberts CTF, Loucks EB. The role of adverse childhood experiences in cardiovascular disease risk: a review with emphasis on plausible mechanisms. Curr Cardiol Rep. 2015;17(10):88. doi:10.1007/s11886-015-0645-1
7. Rich-Edwards JW, Mason S, Rexrode K, et al. Physical and sexual abuse in childhood as predictors of early-onset cardiovascular events in women. Circulation. 2012;126(8):920-927. doi:10.1161/CIRCULATIONAHA.111.076877
8. Kreatsoulas C, Fleegler EW, Kubzansky LD, McGorrian CM, Subramanian SV. Young adults and adverse childhood events: a potent measure of cardiovascular risk. Am J Med. 2019;132(5):605-613. doi:10.1016/j.amjmed.2018.12.022
9. Acosta JN, Leasure AC, Both CP, et al. Cardiovascular health disparities in racial and other underrepresented groups: initial results from the All of Us research program. J Am Heart Assoc. 2021;10(17):e021724. doi:10.1161/JAHA.121.021724
10. Javed Z, Maqsood MH, Amin Z, Nasir K. Race and ethnicity and cardiometabolic risk profile: disparities across income and health insurance in a national sample of US adults. J Public Health Manag Pract. 2022;28(Suppl 1):S91-S100. doi:10.1097/PHH.0000000000001441
11.  Javed Z, Haisum Maqsood M, Yahya T, et al. Race, racism, and cardiovascular health: applying a social determinants of health framework to racial/ethnic disparities in cardiovascular disease. Circ Cardiovasc Qual Outcomes. 2022;15(1):e007917. doi:10.1161/CIRCOUTCOMES.121.007917
12.  Panza GA, Puhl RM, Taylor BA, Zaleski AL, Livingston J, Pescatello LS. Links between discrimination and cardiovascular health among socially stigmatized groups: a systematic review. PLoS One. 2019;14(6):e0217623. doi:10.1371/journal.pone.0217623
13.  Cardel MI, Min YI, Sims M, et al. Association of psychosocial stressors with metabolic syndrome severity among African Americans in the Jackson Heart Study. Psychoneuroendocrinology. 2018;90:141-147. doi:10.1016/j.psyneuen.2018.02.014
14.  Khandaker GM, Zuber V, Rees JMB, et al. Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort. Mol Psychiatry. 2020;25(7):1477-1486. doi:10.1038/s41380-019-0395-3
15.  Pereira C, Grácio D, Teixeira JP, Magro F. Oxidative stress and DNA damage: implications in inflammatory bowel disease. Inflamm Bowel Dis. 2015;21(10):2403-2417. doi:10.1097/MIB.0000000000000506
16.  Gao X, Cao Q, Cheng Y, et al. Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response. Proc Natl Acad Sci U S A. 2018;115(13):E2960-E2969. doi:10.1073/pnas.1720696115
17.  Schoultz M, Beattie M, Gorely T, Leung J. Assessment of causal link between psychological factors and symptom exacerbation in inflammatory bowel disease: a systematic review utilising Bradford Hill criteria and meta-analysis of prospective cohort studies. Syst Rev. 2020;9(1):169. doi:10.1186/s13643-020-01426-2
18.  Tsatsoulis A, Fountoulakis S. The protective role of exercise on stress system dysregulation and comorbidities. Ann N Y Acad Sci. 2006;1083:196-213. doi:10.1196/annals.1367.020
19.  Sirico F, Bianco A, D’Alicandro G, et al. Effects of physical exercise on adiponectin, leptin, and inflammatory markers in childhood obesity: systematic review and meta-analysis. Child Obes. 2018;14(4):207-217. doi:10.1089/chi.2017.0269
20.  Zheng G, Qiu P, Xia R, et al. Effect of aerobic exercise on inflammatory markers in healthy middle-aged and older adults: a systematic review and meta-analysis of randomized controlled trials. Front Aging Neurosci. 2019;11:98. doi:10.3389/fnagi.2019.00098
21.  Tolahunase M, Sagar R, Dada R. Impact of yoga and meditation on cellular aging in apparently healthy individuals: a prospective, open-label single-arm exploratory study. Oxid Med Cell Longev. 2017;2017:7928981. doi:10.1155/2017/7928981

Highly processed foods as Addictive as Tobacco

 Highly Processed Foods 'as Addictive' as Tobacco: <https://www.medscape.com/viewarticle/984600>

LONDON — Highly processed foods meet the same criteria as tobacco for addiction, and labeling them as such might benefit public health, according to a new US study that proposes a set of criteria to assess the addictive potential of some foods.

The research suggests that healthcare professionals are taking steps towards framing food addiction as a clinical entity in its own right; it currently lacks validated treatment protocols and recognition as a clinical diagnosis.

Meanwhile, other data, reported by researchers last week at the Diabetes Professional Care (DPC) 2022 conference in London, UK, also add support to the clinical recognition of food addiction.

Clinical psychologist Jen Unwin, PhD, from Southport, UK, showed that a 3-month online program of low carbohydrate diet together with psychoeducational support significantly reduced food addiction symptoms among a varied group of individuals, not all of whom were overweight or had obesity.

Unwin said her new data represent the first widescale clinical audit of its kind, other than a prior report of three patients with food addiction who were successfully treated with a ketogenic diet. 

"Food addiction explains so much of what we see in clinical practice, where intelligent people understand what we tell them about the physiology associated with a low-carb diet, and they follow it for a while, but then they relapse," said Unwin, explaining the difficulties faced by around 20% of her patients who are considered to have food addiction.

Meanwhile, the authors of the US study, led by Ashley N. Gearhardt, PhD, a psychologist from the University of Michigan, Ann Arbor, write that the ability of highly processed foods (HPFs) "to rapidly deliver high doses of refined carbohydrates and/or fat appear key to their addictive potential. Thus, we conclude that HPFs can be considered addictive substances based on scientifically established criteria."

They assert that the contribution to preventable deaths by a diet dominated by highly processed foods is comparable to that of tobacco products, and as such, like Unwin, the authors seek clinical recognition and a more formalized protocol to manage food addiction.

"Understanding whether addiction contributes to HPF intake may lead to new treatments, as preliminary research finds that behavioral and pharmacological interventions that target addictive mechanisms may reduce compulsive HPF intake," they state

The study led by Gearhardt was published this month in the journal Addiction, and the study led by Unwin was also recently published in Frontiers in Psychiatry.

Addiction Criteria Similar to Tobacco

HPFs can be associated with an eating phenotype "that reflects the hallmarks of addiction," say Gearhardt and co-authors; typically, loss of control over intake, intense cravings, inability to cut down, and continued use despite negative consequences.

Acknowledging the lack of a single addictive agent, they explain that food addiction reflects mechanisms implicated in other addictive disorders such as smoking.

As such, in their study, Gearhardt and colleagues propose a set of scientifically based criteria for the evaluation of whether certain foods are addictive. "Specifically, we propose the primary criteria used to resolve one of the last major controversies over whether a substance, tobacco products, was addictive."

They consider certain foods according to the primary criteria that have stood the test of time after being proposed in 1988 by the US Surgeon General to establish the addictive potential of tobacco: (1) they trigger compulsive use, (2) they have psychoactive effects, and (3) they are reinforcing.

They have updated these criteria to include the ability to trigger urges and cravings, and add that "both these products [tobacco and HPFs] are legal, easily accessible, inexpensive, lack an intoxication syndrome, and are major causes of preventable death."

For example, with compulsive use, tobacco meets this criterion because evidence suggests that most smokers would like to quit but are unable to do so.

Likewise, write Gearhardt and colleagues, even "in the face of significant diet-related health consequences (eg, diabetes and cardiovascular disease), the majority of patients are unable to adhere to medically recommended dietary plans that require a reduction in HPF intake.”

Reinforcement, through tobacco use, is demonstrated by its 'being sufficiently rewarding to maintain self-administration" due to its ability to deliver nicotine, they say, quoting the Surgeon General's report, and likewise, with food addiction, "both adults and children will self-administer HPFs (eg, potato chips, candy, and cookies) even when satiated."

Online Group Food Addiction Intervention Study

Unwin and co-authors want people with food addiction to be able to access a validated treatment protocol. Their study aimed to evaluate an online group intervention across multiple sites in the United States, Canada, and the UK, involving an abstinent, low-carbohydrate diet and biopsychosocial education focused on addiction and recovery in people self-identifying as having food addiction.

"Lots of people with food addiction go to GPs who don't clinically recognize this, or if they attend addiction services and psychiatry, then they tend to only specialize in drugs, alcohol, and gambling. Eating disorder services are linked but their programs mostly don't work for a food addict," Unwin remarked in an interview with Medscape Medical News.

"We feel running groups, as well as training professionals to run groups, is the best way to manage food addiction," she said, reflecting on the scale of the problem, with around 10% of adults in the UK general population considered to have food addiction. In Unwin's study, some people had type 2 diabetes and some overweight/obesity, but she added that some participants were underweight or of normal weight.

Initially, the 103 participants received weekly group (8-24 people) sessions for 10-14 weeks, and then monthly maintenance comprising follow-up that involved coaching participants on how to cope with relapse and get back on track.

Food addiction symptoms were assessed pre- and post-program using the modified Yale Food Addiction Scale (mYFAS) 2.0; ICD-10 symptoms of food-related substance use disorder (CRAVED); and mental health well-being measured using the short version of the Warwick Edinburgh Mental Wellbeing scale and body weight.

"The program eliminates processed foods with a personalized, abstinence food plan that involves education around mechanisms involved," said Unwin, who explained that processed foods deliver a dopamine high, and in response to this, the brain lowers the number of dopamine receptors to effectively counteract the increase in dopamine. This drop in dopamine receptors explains the depression often associated with food addiction.

Unwin reported that food addiction symptoms were significantly reduced, with the mYFAS dropping by 1.52, the CRAVED score by 1.53, and body weight by 2.34 kg (5.2 lb). Mental health, as measured by the Warwick Edinburgh Mental Wellbeing scale, improved by 2.37 points.

"We were very interested in mental health and well-being because it impacts so much across our lives, and we saw significant improvements here, but we were less interested in weight because food addicts come in all shapes and sizes with some people underweight," remarked Unwin. "Food addiction symptoms were significantly improved in the group, but we now need to look at the longer-term outcomes."

Unwin runs a low-carbohydrate program for type 2 diabetes with her husband David Unwin, MD, who is a GP in Southport, UK. She said that they ask patients if they think they have food addiction, and most say they do.

"I always try to explain to patients about the dopamine high, and how this starts the craving which makes people wonder when and where they can find the next sugar hit. Just thinking about the next chocolate bar gets the dopamine running for many people, and the more they tread this path then the worse it gets because the dopamine receptors keep reducing."

Lorraine Avery, RN, a diabetes nurse specialist for Solent NHS Trust, UK, who attended the DPC conference, welcomed Unwin's presentation.

"My concern as a diabetes nurse specialist is that I'm unsure all our patients recognize their food addiction, and there are often more drivers to eating than just the food in front of them," she told Medscape Medical News. "I think there's an emotional element, too. These people are often 'yo-yo' dieters, and they join lots of expert companies to help them lose weight, but these companies want them to regain and re-join their programs," she said.

"I think there is something about helping patients recognize they have a food addiction and they need to consider that other approaches might be helpful."

Addiction. Published online November 9, 2022. Full text

Front Psychiatry. Published online September 28, 2022. Full text

Unwin has reported no relevant financial relationships; some other authors have fee-paying clients with food addiction. Gearhardt and Avery have reported no relevant financial relationships.

Tucker Carlson interviews Dr Aseem Malhotra on the corruption of medicin...

Breath

 I breathe in and all dissolves. I breathe out and create anew.  Every breath is an opportunity to create.   I get to choose that creation as I am recreated with every breath.