Transcendental Meditation practitioners show reduced expression of the Conserved Transcriptional Response to Adversity.

Background and objectives: A recent exploratory study of transcriptional effects of long-term practice of Transcendental Meditation (TM) technologies found evidence for altered expression of genes associated with health and disease. In the present secondary analysis of those data, we test the more specific hypothesis that this sample of long-term practitioners shows a significant reduction in markers of the "Conserved Transcriptional Response to Adversity" (CTRA), an RNA profile characterized by up-regulated inflammation and down-regulated Type I interferon (IFN) activity. Materials and methods: Data come from a previously published study providing genome-wide transcriptional profiles of peripheral blood mononuclear cells (PBMC) from healthy, 38-year practitioners of TM technologies and matched controls (n = 12, mean age 65). The current analysis specifically tests for differential expression of a previously established CTRA indicator gene score, with cross-validation by promoter-based bioinformatic analysis of CTRA-typical differences in transcription factor activity and monocyte subset cellular origins. Results: Compared to controls, the TM group showed lower expression of a pre-specified set of CTRA indicator genes. These effects were accompanied by genome-wide indications of down-regulated pro-inflammatory transcription factor activity (NF-κB, AP-1), up-regulated activity of Interferon Response Factors (IRF) and reduced transcriptional activity of classical monocytes. Conclusions: A sample of long-term practitioners of TM showed reduced CTRA gene expression in PBMC compared to matched controls, supporting the likely value of further research to evaluate causality and specificity of this potential mechanism of health benefits in meditators.

Transcriptomics of Long-Term Meditation Practice: Evidence for Prevention or Reversal of Stress Effects Harmful to Health.

Background and Objectives: Stress can overload adaptive mechanisms, leading to epigenetic effects harmful to health. Research on the reversal of these effects is in its infancy. Early results suggest some meditation techniques have health benefits that grow with repeated practice. This study focused on possible transcriptomic effects of 38 years of twice-daily Transcendental Meditation® (TM®) practice. Materials and Methods: First, using Illumina® BeadChip microarray technology, differences in global gene expression in peripheral blood mononuclear cells (PBMCs) were sought between healthy practitioners and tightly matched controls (n = 12, age 65). Second, these microarray results were verified on a subset of genes using quantitative polymerase chain reaction (qPCR) and were validated using qPCR in larger TM and control groups (n = 45, age 63). Bioinformatics investigation employed Ingenuity® Pathway Analysis (IPA®), DAVID, Genomatix, and R packages. Results: The 200 genes and loci found to meet strict criteria for differential expression in the microarray experiment showed contrasting patterns of expression that distinguished the two groups. Differential expression relating to immune function and energy efficiency were most apparent. In the TM group, relative to the control, all 49 genes associated with inflammation were downregulated, while genes associated with antiviral and antibody components of the defense response were upregulated. The largest expression differences were shown by six genes related to erythrocyte function that appeared to reflect a condition of lower energy efficiency in the control group. Results supporting these gene expression differences were obtained with qPCR-measured expression both in the well-matched microarray groups and in the larger, less well-matched groups. Conclusions: These findings are consistent with predictions based on results from earlier randomized trials of meditation and may provide evidence for stress-related molecular mechanisms underlying reductions in anxiety, post-traumatic stress disorder (PTSD), cardiovascular disease (CVD), and other chronic disorders and diseases.

Trials of Maharishi Ayurveda for cardiovascular disease: A pooled analysis of outcome studies with carotid intima-media thickness.

Objective: To investigate a multimodality, natural medicine systems approach-Maharishi Ayurveda (MAV)-for prevention or reversal of atherosclerotic cardiovascular disease (ASCVD). Design: Pooled analysis of data from existing trials that used MAV to reduce carotid artery intima-media thickness (CIMT). Settings: Two large medical centers in the U.S. Midwest. Subjects: Thirty-four elderly patients with or at high risk for ASCVD. Interventions: Four components of MAV: Transcendental Meditation™, Ayurvedic diet, Ayurvedic exercise, and Ayurvedic herbal food supplements. Primary outcome measure: CIMT, a surrogate measure of ASCVD, was determined by B-mode ultrasonography. Results: After 9-12 months of intervention, CIMT declined in the MAV group (change in CIMT = -0.15 ± 0.22 mm; 95% CI = -0.22 to 0.01 mm) and increased in the usual care group (change in CIMT = + 0.02 ± 0.06 mm; 95% CI = -0.02 to 0.04). This difference between groups of -0.17 mm was significant [F(1,29) = 14.1, p << .01]. In the MAV group, those individuals showing the largest reductions in CIMT with treatment also had the highest risk factor levels at the start. Baseline data from this subgroup indicated the presence of hypertension, (systolic blood pressure (SBP) = 141 ± 11 mmHg, diastolic blood pressure (DBP) = 80 ± 12 mmHg, means ± SD). They also had elevated waist circumference (91 ± 8 cm), and dyslipidemia (triglyceride-to-HDL-cholesterol ratio = 4.8 ± 2.9). Each individual in this "high-CIMT-change" group, 80% of whom were women, improved notably in one or more risk factors with the MAV intervention. Conclusions: The pooled results of these two trials suggest that MAV multimodality intervention programs, including the Transcendental Meditation technique and heart-healthy Ayurvedic diet, exercise, and herbal food supplements, may be effective in the regression of ASCVD, especially in patients at high risk for cardiovascular disease.

Cardiovascular disease prevention and health promotion with the transcendental meditation program and Maharishi consciousness-based health care.

This article summarizes the background, rationale, and clinical research on a traditional system of natural health care that may be useful in the prevention of cardiovascular disease (CVD) and promotion of health. Results recently reported include reductions in blood pressure, psychosocial stress, surrogate markers for atherosclerotic CVD, and mortality. The randomized clinical trials conducted so far have involved applications to both primary and secondary prevention as well as to health promotion more generally. The results support the applicability of this approach for reducing ethnic health disparities associated with environmental and psychosocial stress. Proposed mechanisms for the effects of this traditional system include enhanced resistance to physiological and psychological stress and improvements in homeostatic and self-repair processes. This system may offer clinical and cost effectiveness advantages for health care, particularly in preventive cardiology.

Psychosocial stress and cardiovascular disease. Part 3: Clinical and policy implications of research on the transcendental meditation program.

Cardiovascular disease (CVD) remains the leading cause of death in the United States today and a major contributor to total health care costs. Psychosocial stress has been implicated in CVD, and psychosocial approaches to primary and secondary prevention are gaining research support. This third article in the series on psychosocial stress and CVD continues the evaluation of one such approach, the Maharishi Transcendental Meditation program, a psychophysiological approach from the Vedic tradition that is systematically taught by qualified teachers throughout the world. Evidence suggests not only that this program can provide benefits in prevention but also that it may reduce CVD-related and other health care expenses. On the basis of data from the studies available to date, the Transcendental Meditation program may be responsible for reductions of 80% or greater in medical insurance claims and payments to physicians. This article evaluates the implications of research on the Transcendental Meditation program for health care policy and for large-scale clinical implementation of the program. The Transcendental Meditation program can be used by individuals of any ethnic or cultural background, and compliance with the practice regimen is generally high. The main steps necessary for wider adoption appear to be: (1) educating health care providers and patients about the nature and expected benefits of the program, and (2) adjustments in public policies at the state and national levels to allow this program to be included in private and public health insurance plans.

Review of controlled research on the transcendental meditation program and cardiovascular disease. Risk factors, morbidity, and mortality.

Because of growing evidence for stress as a major factor contributing to cardiovascular disease (CVD), techniques of meditation are being increasingly used. The Transcendental Meditation (TM) technique is distinct from other techniques of meditation not only in its origin and procedure, but also in the amount and breadth of research testing it. Evidence for its ability to reduce traditional and novel risk factors for CVD includes: 1) decreases in blood pressure, 2) reduced use of tobacco and alcohol, 3) lowering of high cholesterol and lipid oxidation, and 4) decreased psychosocial stress. Changes expected to result from reducing these risk factors, namely, reversal of atherosclerosis, reduction of myocardial ischemia and left ventricular hypertrophy, reduced health insurance claims for CVD, and reduced mortality, also have been found with TM practice. Research on mechanisms suggests that some of the CVD-related benefits as a result of this technique could arise from normalization of neuroendocrine systems whose function has been distorted by chronic stress. Further randomized clinical trials are in progress with a focus on underserved minority populations.

Lowering cortisol and CVD risk in postmenopausal women: a pilot study using the Transcendental Meditation program.

Unlike younger women, the risk of cardiovascular disease in older women matches or exceeds that of men. Excessive cortisol may play a role in this increased risk. Here we explore the possibility that the Transcendental Meditation (TM) program may reduce the cortisol response to a metabolic stressor as a way of reducing disease risk in older women. Data from 16 women who were long-term practitioners of transcendental meditation (mean = 23 y) were compared with data from 14 control women matched for age (mean = 75 y, range = 65-92 y). Data on demographics, disease symptoms, and psychological variables were collected, and cortisol response to a metabolic stressor (75 g of glucose, orally) was examined in saliva and urine. Pre-glucose levels of salivary cortisol were identical for the two groups. Post-glucose cortisol rose faster in the controls and was significantly higher than that in the TM women (P < 1 3 10(-4)). Urinary excretion of cortisol during this period was 3 times higher in controls than in the TM women (2.4 +/- 0.17 and 0.83 +/- 0.10 microg/h, respectively; P = 2 x 10(-4)). In addition, the number of months practicing transcendental meditation was inversely correlated with CVD risk factors. Lower cortisol response to metabolic challenge may reflect improved endocrine regulation relevant to the disease-preventing effects of transcendental meditation in older women.

Psychosocial stress and cardiovascular disease: pathophysiological links.

The remarkable decline in cardiovascular disease (CVD) experienced in developed countries over the last 40 years appears to have abated. Currently, many CVD patients continue to show cardiac events despite optimal treatment of traditional risk factors. This evidence suggests that additional interventions, particularly those aimed at nontraditional factors, might be useful for continuing the decline. Psychosocial stress is a newly recognized (nontraditional) risk factor that appears to contribute to all recognized mechanisms underlying cardiac events, specifically, (a) clustering of traditional cardiovascular risk factors, (b) endothelial dysfunction, (c) myocardial ischemia, (d) plaque rupture, (e) thrombosis, and (f) malignant arrhythmias. A better understanding of the behavioral and physiologic associations between psychosocial stress and CVD will assist researchers in identifying effective approaches for reducing or reversing the damaging effects of stress and may lead to further reductions of CVD morbidity and mortality.

Effect of a multimodality natural medicine program on carotid atherosclerosis in older subjects: a pilot trial of Maharishi Vedic Medicine.

Although the onset and progression of coronary heart disease (CHD) involve multiple risk factors, few intervention studies have attempted to modify these factors simultaneously. This pilot study tested the effect of a multimodality intervention involving dietary, exercise, herbal food supplement, and stress reduction approaches from a traditional system of natural medicine, Maharishi Vedic Medicine (MVM). The primary outcome measure was carotid intima-media thickness (IMT), a noninvasive measure of peripheral atherosclerosis and surrogate measure of coronary atherosclerosis. Comparison groups included modern medicine (conventional dietary, exercise, and multivitamin approaches) and usual care (no added intervention). Of 57 healthy seniors (mean age 74 years) randomized to the 3 treatment groups, 46 completed IMT post-testing. Carotid IMT was determined by B-mode ultrasound before and after 1 year of treatment. IMT decreased in a larger fraction of MVM subjects (16 of 20) than in the modern (5 of 9) and usual care (7 of 14) groups combined (i.e., 12 of 23; odds ratio 3.7, p = 0.05). For subjects with multiple CHD risk factors ("high-risk" subjects, n = 15), IMT decreased more in the MVM (-0.32 +/- 0.23 mm, mean +/- SD) than in the usual care (+0.022 +/- 0.085; p = 0.009) or modern (-0.082 +/- 0.095, p = 0.10) groups. Within-group reductions in IMT were significant for all MVM subjects (-0.15 +/- 0.21, n = 20, p = 0.004) and for high-risk MVM subjects (n = 6, p = 0.01). These results show that this multimodality traditional approach can attenuate atherosclerosis in older subjects, particularly those with marked CHD risk.

Psychosocial stress and cardiovascular disease Part 2: effectiveness of the Transcendental Meditation program in treatment and prevention.

Psychosocial stress is a nontraditional risk factor for cardiovascular morbidity and mortality that may respond to behavioral or psychosocial interventions. To date, studies applying such interventions have reported a wide range of success rates in treatment or prevention of cardiovascular disease (CVD). The authors focus on a natural medicine approach that research indicates reduces both psychosocial and traditional risk factors for cardiovascular disease-the Transcendental Meditation (TM) program. Randomized controlled trials, meta-analyses, and other controlled studies indicate this meditation technique reduces risk factors and can slow or reverse the progression of pathophysiological changes underlying cardiovascular disease. Studies with this technique have revealed reductions in blood pressure, carotid artery intima-media thickness, myocardial ischemia, left ventricular hypertrophy, mortality, and other relevant outcomes. The magnitudes of these effects compare favorably with those of conventional interventions for secondary prevention.