Molecular Aspects of Mind–Body Interaction: Do Mind–Body Therapies Influence Low-Grade Chronic Inflammation and Cardiovascular Disease Risk?
Year: 2024
Type: article
Abstract: Dear Editor, Mind–body interaction (MBI) has always been at the center of human interest. In most ancient cultures of the world, body and mind were considered unicum. In the West, however, with Descartes in philosophy,[1] Galileo with the scientific method, and Morgagni with the establishment of pathological anatomy, this unicum was no longer considered such. Furthermore, the rise of Mendelian genetics left no room for the influence of the environment/MBI on gene expression.[2] Western medicine, by breaking down complex phenomena into their constituent parts and treating each separately, has led to an exponential increase in life expectancy.[3] However, this approach now faces enormous challenges in the fight against stress-related noncommunicable diseases (NCDs), partly because of the divided view of the body/mind connection. In the East, on the other hand, the mind–body relationship has remained more closely connected to the present day, as can be seen in Traditional Chinese Medicine, Ayurveda, and in Mind–body Therapies (MBTs). As for MBTs, until 50 years ago in the West, the idea that MBTs had a role in medical treatment was considered fringe. However, since the late 20th century, due to the rise of studies on biofeedback, psychoneuroendocrineimmunology (PNEI) and epigenetics MBI have received renewed attention.[4] The researcher who brought the paradigm shift in the field of MBTs in the West was Herbert Benson, who studied how Tibetan monks control their autonomic nervous system (ANS) through meditation. Later, Robert Ader, coined the term PNEI,[4] according to which the mind influences the immune system through the ANS. Due to these advances, over the past three decades, MBTs have received increasing attention from the scientific community, which seeks to understand the effectiveness of these practices. Today, MBTs are no longer viewed with suspicion in the West: In the US, it is a top research priority, integrated in 80% of medical schools,[5] and 19% of US citizens use or have used them. Mind–body medicine, which hypothesizes the interconnectedness of the physical and mental, seeks to improve physical and mental health through MBTs: meditation, mindfulness, Tai Chi, breathing techniques, or yoga.[6] MBTs, which originated in ancient Eastern cultures, include approaches that combine balance training, low-intensity aerobic activity, and flexibility with or without relaxation, mindfulness, and meditation.[6,7] In recent decades, mental health professionals have declared their support for MBTs as they can reduce stress, depression, and anxiety and help cope with chronic diseases. Soon after, research showed that MBTs increase gray matter in brain regions related to emotion regulation, learning, memory, self-referential processes, and perspective taking.[6,8] In addition, the processes by which MBTs influence physical diseases are recently beginning to be unraveled. One line of research in this area is evaluating how MBTs may modulate, in addition to stress, also inflammation. Stress and low-grade chronic inflammation (LGCI) are considered key contributors to NCDs, including cancer and cardiovascular disease (CVD).[9] Today, LGCI-NCDs are the leading cause of mortality worldwide,[9] and by 2030, depression, stress-related disorders, and LGCI-NCDs will be the most prevalent health problems.[5] In addition to altered lifestyles, in fact, stress and psychological problems are driving factors[10] in contributing to the development of LGCI-NCDs. With regard to CVD, LGCI is predictive of CVD development even when a patient has reduced levels of low-density lipoprotein cholesterol (LDL-C).[11] Thus, LGCI is now considered a treatable outcome of CVD, and some experts advocate achieving the “dual goal” of LDL-C <70 mg/dL and high-sensitivity C-reactive protein (CRP) <2 mg/dL to reduce the risk of CVD.[11,12] LGCI plays a critical role in the development of atherosclerotic CVD (ASCVD) and aortic valve calcification, through activation of nuclear factor kappa B (NF-κB), inflammasome formation, increased immune cell release of interleukin-6 (IL-6), CRP, and tumor necrosis factor-α (TNF-α) that amplify the inflammatory cascade within the vascular wall and lead to macrocalcification.[11] Most of the drugs currently used in the treatment of CVD (statins, proprotein convertase subtilisin/kexin type 9 inhibitors, and ezetimibe) not only have lipid-lowering effects but also inflammation-reducing effects, further highlighting how crucial LGCI is in inducing CVD.[11,12] Since ASCVD risk attributed to inflammation remains high despite guideline therapies, and there are no drugs capable of reducing LGCI without simultaneously inducing immunosuppression, further interventions to reduce LGCI and cardiovascular risk are required but are currently an unmet need.[11] Therefore, we evaluated the most recent systematic-reviews (SRs) and meta-analyses (MAs) on MBTs and inflammation to determine whether MBTs may play a role in reducing LGCI and CVD risk. Buric et al. conducted an SR on the change in gene expression in immune cells underlying the psychological benefits of MBTs.[8] Studies with any type of research design were included. Eighteen articles were evaluated. The most studied transcription factor was NF-κB. The authors conclude that MBTs counteract the effects of stress on the immune system by resulting in significant downregulation of inflammation-related genes and/or NF-κB. Strehli et al. conducted an SR with MA on MBTs and stress-related physiological markers (heart rate, glycemia, cortisol, and blood pressure) in experimental or quasi-experimental studies in students.[7] Twenty-six articles were included. Regarding cortisol, a large and statistically significant pooled effect was found (Hedges’ G = −1.32, P = 0.026), characterized by a large heterogeneity among studies (χ2 [9] = 261.18, P < 0.001, I2 = 96.6%). Using Egger regression, no evidence of publication bias was found (bias = −7.01, P = 0.243). Therefore, MBTs were found to have large-scale, statistically significant aggregate effect in reducing cortisol. Regarding glycemia, no statistically significant aggregate effects were observed. The authors conclude that MBTs may have a positive impact on specific stress-related physiological markers. Dunn and Dimolareva conducted an SR with MA to evaluate the effects of mindfulness in sick and healthy subjects in randomized controlled trials (RCTs) on CRP, IL-6, NF-κB, CD4+ cells, telomere length (TL), and telomerase activity (TA).[13] The authors included 48 studies. They found that MBTs had a small postintervention effect on CD4+ (standardized mean change difference [SMCD] = 0.09, 95% confidential interval [CI] = −0.05–0.22), CRP (SMCD = −0.14, 95% CI = −0.26–0.01), and TL (SMCD = 0.12, 95% CI = 0.00–0.24), a moderate effect on IL-6 (SMCD = −0.35, 95% CI = −0.67–0.03), and a large effect on TA (SMCD = 0.81, 95% CI = 0.17–1.46). Follow-up data showed a small effect on IL-6 (SMCD = −0.13, 95% CI = −0.29–0.03) and a moderate effect on CD4+ (SMCD = 0.22, 95% CI = −0.08–0.52) and CRP (SMCD = −0.39, 95% CI = −0.68–0.10). The authors concluded that mindfulness provides some benefits to immune function by regulating CRP, IL-6, and protecting against cellular aging. Muñoz-Vergara et al. conducted an SR with MA focused on MBTs in RCTs conducted on healthy adults.[6] The authors evaluated: Systemic inflammatory proteins, lipids-steroid mediators, immune-cell counts, humoral response, and complement fractions. Twenty-three studies were included. MA was conducted on the effects of MBTs on CRP, TNF-α, and IL-6. Pooled effect size results in post-MBTs practice showed a decrease in systemic CRP levels (Hedges’ G = −0.351, 95% CI = −0.580–0.123, 95% prediction interval = −0.77–0.07, I2 = 11%), TNF-α (Hedges’ G = −0.366, 95% CI = −0.669–0.064, 95% prediction interval = −1.05–0.32, I2 = 0%), and IL-6 (Hedges’ G = −0.394, 95% CI = −0.819–0.030, 95% prediction interval = −1.81–1.02, I2 = 81%). MA showed a decrease in CRP, TNF-α, and IL-6 with long-term MBTs. Data regarding other inflammatory mediators were not sufficient to apply the MA. These SRs and MAs provide initial evidence that MBTs can reduce LGCI through the downregulation of NF-κB-related genes and the reduction of IL-6, CRP, and TNF-α levels. These findings are significant for the treatment and prevention of CVD. Indeed NF-κB plays a prominent role in the development of atherosclerosis by regulating the inflammasome and the expression of genes encoding cytokines.[11] Increased expression of IL-6 and CRP is related to atherosclerosis and increases the risk of CVD development, recurrence, and mortality.[11] TNF-α levels are positively associated with atherothrombotic disease; elevated TNF-α levels postmyocardial infarction are a strong predictor of recurrent events and heart failure mortality.[11] SRs and MAs demonstrate that MBTs impact LGCI through: A top-down pathway mediated by the cognitive-meditative component of MBTs, which acts by reducing chronic stress, hyperactivation of the sympathetic nervous system, and leukocyte NF-κB activity mediated by beta-adrenergic receptors.[14] A bottom-up mechanism mediated by the physical component of MBTs, which through the release of the muscle-derived anti-inflammatory IL-6, inhibits TNF-α and CRP production.[6] In conclusion, early evidence shows that MBTs can reduce LGCI. Furthermore, since chronic stress is recognized as the main cause of depression and common psychiatric disorders,[14] the stress reduction induced by MBTs could decrease the risk of developing these diseases, which are strongly associated with the development of overweight/obesity, Type 2 diabetes, and CVD.[10] Thus, MBTs could be effective in terms of primary and secondary prevention of CVD. To facilitate comparison in future SRs and MAs of the results obtained from MBTs RCTs, we also suggest that it would be useful to develop a core outcome set and standardized outcome measurement tools, which currently do not exist for MBTs. Author contributions Claro AE designed the study and wrote the first draft of the manuscript; Pitocco D and Muti P supervised and added important contributions to the paper. All authors have read and agreed to the published version of the manuscript. Conflicts of interest Dr. Angelo Emilio Claro is a Youth Editorial Board Member of Heart and Mind. The article was subject to the journal’s standard procedures, with peer review handled independently of Dr. Angelo Emilio Claro and the research groups. There are no conflicts of interest.
Source: Heart and Mind
Authors: Angelo Emilio Claro, Dario Pitocco, Paola Muti
Institutions: Università Cattolica del Sacro Cuore, University of Milan
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: diamond
OpenAlex ID: W4403967504