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Melatonin: Roles in influenza, Covid-19, and other viral infections.
Anderson, G, Reiter, RJ
Reviews in medical virology. 2020;30(3):e2109
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Viruses like influenza and coronaviruses change quickly, making it challenging to develop effective treatments and vaccines in a short time frame. Consequently, the use of generic substances that limit viral effects are of high interest. In this paper, the authors summarize a range of mechanisms in which melatonin can alter the impact of virus infections and infection-associated inflammatory overdrive aka cytokine storm. Melatonin, the sleep hormone, is well known for its potent antioxidant and anti-inflammatory action. It seems highly likely that melatonin can modulate the cellular function of all cells, mostly via mitochondrial function. This is particularly relevant in immune cells. For example, the daytime variance in immune function seems to be closely linked with mitochondrial activity and energy production. Other relevant mechanisms described are the antiviral role of melatonin-induced sirtuins - proteins that regulate cellular health-, the impact of viruses on cell coordinating microRNA, the role of the gut microbiome and gut permeability, as well as sympathetic nervous system activation and the protective effects of parasympathetic activation. Also considered are pre-existing health conditions and conditions that are linked with a decline in melatonin along with ageing, all being groups in which severity of viral infections is felt. This paper may be of interest to those who like to explore in more depth the mechanisms behind melatonin and its ability to influence viral disease progression.
Abstract
There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid-19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial "cytokine storm", as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian "resetting" of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl-CoA is a necessary cosubstrate for arylalkylamine N-acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus- and cytokine-storm-driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus-and cytokine storm-driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid-19 and other viral infections.
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How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS.
Nacul, L, O'Boyle, S, Palla, L, Nacul, FE, Mudie, K, Kingdon, CC, Cliff, JM, Clark, TG, Dockrell, HM, Lacerda, EM
Frontiers in neurology. 2020;11:826
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A good understanding of the disease course is vital not only for the design of preventative and intervention studies, but also to assess the timing and type of intervention that minimizes disease risk or optimizes prognosis. The aim of this review was to explore the long-term course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and how presentation and pathophysiological abnormalities may vary with time. Literature shows that it is unknown how the initial host response to a stressor or insult compares in individuals who do or do not develop typical symptoms of ME/CFS. However, the return to good health, following exposure to mild or moderate levels of insult, seems to be impeded in ME/CFS when symptoms persist for longer than 3–6 months. Authors sought to provide a simple framework, similar to those of other chronic diseases, in an effort to extend the temporal perception of ME/CFS and better incorporate the less defined pre-illness stages of the disease. In fact, they conclude that by applying this framework to ME/CFS research efforts could better elucidate the pathophysiological mechanisms of the disease and identify potential therapeutic targets at distinct stages.
Abstract
We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to singular or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states. Thus, the predominantly neuro-immune manifestations, underlined by a hyper-metabolic state, that characterize early disease, may be followed by various processes leading to multi-systemic abnormalities and related symptoms. This abnormal state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production. These processes do not seem to happen uniformly; although a spiraling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. With time variation in disease presentation, no single ME/CFS case description, set of diagnostic criteria, or molecular feature is currently representative of all patients at different disease stages. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may support future research design and health care interventions for people with ME/CFS.
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The Functional Medicine Approach to COVID-19: Nutrition and Lifestyle Practices for Strengthening Host Defense.
Minich, DM, Hanaway, PJ
Integrative medicine (Encinitas, Calif.). 2020;19(Suppl 1):54-62
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Lifestyle interventions can be an effective means to help patients regain their locus of control during times of uncertainty like those experienced in a pandemic. The study is a review about emerging research focusing on nutrition and lifestyle practices for strengthening host defense. Research indicates that there are three mechanisms that may be involved in the ability of food-derived compounds to reduce viral infection and severity: a. balancing inflammatory pathways, b. reducing oxidative stress and increasing antioxidant levels, and c. harmonizing the gut microbiome. Clinical recommendations focus mainly on nutrition, stress reduction/management, sleep quality and quantity, physical activity programme and social factors/connections. Authors conclude by emphasising that the findings of this study are only intended to identify lifestyle practices that may boost the immune system as they have not been proven effective against COVID-19.
Abstract
The developing symptoms of COVID-19, as well as the progression of illness and fatality, are a clearly a function of the overall health status of the individual. Complex, chronic diseases such as obesity, hypertension, and diabetes are directly correlated with risk of disease severity and mortality. We explore lifestyle interventions that have specifically been demonstrated to strengthen host defense, reduce the probability and mitigate the severity of viral infection. Lifestyle interventions, from a Functional Medicine perspective, include nutrition, sleep, exercise, stress reduction, and connection. These factors, when in balance, provide a foundation for optimal health and immune function.
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Usefulness of a Lifestyle Intervention in Patients With Cardiovascular Disease.
Broers, ER, Gavidia, G, Wetzels, M, Ribas, V, Ayoola, I, Piera-Jimenez, J, Widdershoven, JWMG, Habibović, M
The American journal of cardiology. 2020;125(3):370-375
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Modifiable (behavioural) risk factors such as sedentary lifestyle and low sleep efficiency, are associated with increased mortality risk and disease progression in individuals with cardiovascular disease. The main aim of this study was to evaluate changes in objectively measured lifestyle and health data derived from wearable devices. This study was part of an international, multicenter randomized controlled trial, the Do Cardiac Health Advanced New Generation Ecosystem 2 study. Only the participants (n=70) randomised to the intervention group were analysed. The participants received the devices to monitor their lifestyle and health parameters. Results indicate significant changes over time in the number of steps and activity level. No significant improvement over time was observed in other outcome measures (i.e., blood pressure, weight, and sleep efficiency). Secondary analysis showed demographic (gender, nationality, marital status), clinical (co-morbidities, heart failure), and psychological (anxiety, depression) profiles that were associated with lifestyle measures. Authors conclude that a personalised approach might be the way forward in order to improve health outcomes in the future.
Abstract
The importance of modifying lifestyle factors in order to improve prognosis in cardiac patients is well-known. Current study aims to evaluate the effects of a lifestyle intervention on changes in lifestyle- and health data derived from wearable devices. Cardiac patients from Spain (n = 34) and The Netherlands (n = 36) were included in the current analysis. Data were collected for 210 days, using the Fitbit activity tracker, Beddit sleep tracker, Moves app (GPS tracker), and the Careportal home monitoring system. Locally Weighted Error Sum of Squares regression assessed trajectories of outcome variables. Linear Mixed Effects regression analysis was used to find relevant predictors of improvement deterioration of outcome measures. Analysis showed that Number of Steps and Activity Level significantly changed over time (F = 58.21, p < 0.001; F = 6.33, p = 0.01). No significant changes were observed on blood pressure, weight, and sleep efficiency. Secondary analysis revealed that being male was associated with higher activity levels (F = 12.53, p < 0.001) and higher number of steps (F = 8.44, p < 0.01). Secondary analysis revealed demographic (gender, nationality, marital status), clinical (co-morbidities, heart failure), and psychological (anxiety, depression) profiles that were associated with lifestyle measures. In conclusion results showed that physical activity increased over time and that certain subgroups of patients were more likely to have a better lifestyle behaviors based on their demographic, clinical, and psychological profile. This advocates a personalized approach in future studies in order to change lifestyle in cardiac patients.
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Intramyocellular Lipids, Insulin Resistance, and Functional Performance in Patients with Severe Obstructive Sleep Apnea.
Chien, MY, Lee, PL, Yu, CW, Wei, SY, Shih, TT
Nature and science of sleep. 2020;12:69-78
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Obstructive sleep apnoea syndrome (OSA) is characterized by repeated occlusion of the upper airway during sleep, resulting in periods of intermittent hypoxemia [low level of oxygen in blood]. The aim of this study was to (a) investigate the intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL), biochemical data, and functional performance in patients with severe OSA versus controls, and (b) examine the correlations between intra-muscular lipid contents and biochemical and performance variables. This study is a clinical trial that recruited 20 patients with OSA and body mass index(BMI)-matched controls. Results demonstrate that patients with OSA had significantly lower IMCL and EMCL values when compared with their age-, and BMI-matched controls without OSA. Furthermore, compared with controls, patients with OSA had significantly reduced functional performance and exhibited abnormal biochemical data, including glucose and insulin levels and lipid profiles. Authors conclude that additional large-scale clinical trials are required to further explore the complex mechanism between OSA, muscle metabolism, and insulin action.
Abstract
PURPOSE An increasing number of studies have linked the severity of obstructive sleep apnea (OSA) with metabolic dysfunction. However, little is known about the lipid compartments (intramyocellular [IMCL] and extramyocellular [EMCL] lipids) inside the musculature in these patients. The present study was designed to investigate the IMCL and EMCL, biochemical data, and functional performance in patients with severe OSA, and to examine the correlations between intramuscular lipid contents and test variables. PARTICIPANTS AND METHODS Twenty patients with severe OSA (apnea-hypopnea index [AHI]: ≥30/h; body mass index [BMI]: 26.05±2.92) and 20 age- and BMI-matched controls (AHI <5/h) were enrolled. Proton magnetic resonance spectroscopy was used to measure the IMCL and EMCL of the right vastus lateralis muscle. Biochemical data, including levels of fasting plasma glucose, insulin, lipid profiles, and high-sensitivity C-reactive protein (hsCRP), were measured. Insulin resistance index (IR) was calculated using the homeostasis model assessment method. Performance tests included a cardiopulmonary exercise test and knee extension strength and endurance measurements. RESULTS Patients with severe OSA had significantly (P<0.05) lower values of IMCL (14.1±5.4 AU) and EMCL (10.3±5.8 AU) compared to the control group (25.2±17.6 AU and 14.3±11.1 AU, respectively). Patients with severe OSA had significantly higher hsCRP, IR, and dyslipidemia compared with controls (all P<0.05). Furthermore, IMCL was negatively correlated with AHI, cumulative time with nocturnal pulse oximetric saturation lower than 90% (TSpO2<90%) (ρ=-0.35, P<0.05), IR (ρ=-0.40, P<0.05), glucose (ρ=-0.33, P<0.05), and insulin (ρ=-0.36, P<0.05), and positively correlated with lowest oximetric saturation (ρ=0.33, P<0.01). CONCLUSION Skeletal muscle dysfunction and metabolic abnormalities were observed in patients with OSA that did not have obesity. IMCL was positively correlated with aerobic capacity and muscular performance, but negatively correlated with AHI and IR. Large-scale clinical trials are required to explore the complicated mechanism among OSA, intramuscular metabolism, and insulin action. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00813852.
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Development and Effects of College-Based Lifestyle Modification Program for Menstrual Health of Young Adult Women with Irregular Menses: A Randomized Controlled Trial.
Park, YJ, Shin, H, Jeon, S, Cho, I, Park, HJ
International journal of environmental research and public health. 2020;18(1)
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Irregular menstruation is characterized by abnormal uterine bleeding, unpredictable menstrual volume, and irregularity of menstruation. A regular menstrual cycle demonstrates a normal sex hormone profile and functioning of reproductive organs, whereas irregularity may suggest a dysfunctional sex hormone profile or disorder of reproductive organs. This study is a randomised controlled trial intended to develop a College-based Lifestyle Modification Programme (LMP) to improve the menstrual health of young adult women who experienced irregular menstruation less than ten times a year, and its effects on their health. The study has two arms: intervention and control group. Female participants (n=46) were randomly assigned 1:1 to one of the two groups. Results show that the College-based LMP had positive effects on the alleviation of depression and anxiety, and improvement of sleep duration. Whereas there were no significant differences for certain variables (menstrual cycle index, sex hormone binding globulin, testosterone, free androgen index), overall premenstrual syndrome, menstrual volume, body composition parameters, and nutrient intake. Authors conclude that their findings demonstrated the importance of lifestyle modifications, which could provide ordinary young adult women with healthy menstruation. However, further studies with the use of supplements are required to address the limitations of the current study.
Abstract
Purpose: This study was conducted to develop the 'College-based Lifestyle Modification Program' (College-based LMP) for young adult women with irregular menstruation and examine its effects after intervention. Methods: The College-based LMP consisted of small group education, individual physical exercise counseling/training, individual diet counseling, and feedback and support. Participants were comprised of 38 females who reported less than 10 irregular menstruations in a year and were randomly assigned to the experimental and control groups. The primary outcome variables consisted of menstrual cycle index (MCI), sex hormone binding globulin (SHBG), and androgenic profile (testosterone-T, free androgen index-FAI), while the outcome variables included premenstrual symptoms (PMS), menstrual volume, body composition parameters, glycemic parameters (fasting blood sugar-FBS, insulin, HOMA-IR), sleep duration, perceived stress, and nutrient intake.. Results: There were no significant differences in primary outcome variables (MCI, SHBG, T, and FAI). In the variables, there were no significant differences except for the partial domain of PMS (symptoms of depression and anxiety) and sleep duration. Conclusions: The study was significant in that it demonstrated the importance of lifestyle, which could provide ordinary young adult women with healthy menstruation. The College-based LMP needs to be elaborated with further studies.
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Effect of menstrual cycle on resting metabolism: A systematic review and meta-analysis.
Benton, MJ, Hutchins, AM, Dawes, JJ
PloS one. 2020;15(7):e0236025
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Resting metabolic rate (RMR) plays a key role in energy balance and weight management. For more than 20 years, researchers have controlled for menstrual cycle fluctuations when designing studies that require measurement of RMR in young women. In fact, data regarding the influence of menstrual cycle on metabolism are inconsistent. The aim of this study was to systematically review and analyse existing research to determine whether the menstrual cycle influences RMR in women. This study is a systematic review and meta-analysis of thirty studies. Results show that when all studies were considered, the menstrual cycle exerted a small, but statistically significant effect on RMR in women. Specifically, RMR was found to be greater during the luteal phase compared to the follicular phase. However, when only larger studies (of more than 10 women) were considered, the effect of the menstrual cycle was slightly reduced, and when only studies published since 2000 were considered, the effect was even smaller and no longer significant. Authors conclude that researchers should be aware of the potential confounding influence of the menstrual cycle and control for it by testing consistently in one phase of the cycle when measuring RMR in premenopausal women.
Abstract
BACKGROUND The need to control for the potential influence of menstrual cycle phase on resting metabolism (RMR) places a burden on research participants who must self-report onset of menstruation and researchers who must schedule metabolic testing accordingly. PURPOSE To systematically review and analyze existing research to determine the effect of menstrual cycle on RMR. METHODS We searched PubMed, CINAHL, MEDLINE, SPORTDiscus, and Scopus databases using the search terms "menstrual cycle and metabolic rate" and "menstrual cycle and energy expenditure." Eligibility criteria were English language, single-group repeated measures design, and RMR as either a primary or secondary outcome. Risk of bias was assessed based on study sample, measurement, and control of confounders. Differences between the follicular and luteal phases of the menstrual cycle were analyzed using the standardized mean difference in effect size. RESULTS Thirty English-language studies published between 1930 and December 2019 were included in the systematic review, and 26 studies involving 318 women were included in the meta-analysis. Overall, there was a small but significant effect favoring increased RMR in the luteal phase (ES = 0.33; 95% CI = 0.17, 0.49, p < 0.001). DISCUSSION Limitations include risk of bias regarding measurement of both menstrual cycle and RMR. Sample sizes were small and studies did not report control of potential confounders. Sub-group analysis demonstrated that in more recent studies published since 2000, the effect of menstrual phase was reduced and not statistically significant (ES = 0.23; 95% CI = -0.00, 0.47; p = 0.055). Until larger and better designed studies are available, based on our current findings, researchers should be aware of the potential confounding influence of the menstrual cycle and control for it by testing consistently in one phase of the cycle when measuring RMR in pre-menopausal women.
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Pharmaceutical Interventions in Chronic Fatigue Syndrome: A Literature-based Commentary.
Richman, S, Morris, MC, Broderick, G, Craddock, TJA, Klimas, NG, Fletcher, MA
Clinical therapeutics. 2019;41(5):798-805
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Myalgic encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/ CFS), is a disease characterized by an inability to exert oneself physically, often coupled with a combination of other symptoms, including sleep disorders, severe unpredictable pain, and compromised cognitive abilities. The aim of this review was to delineate a number of the more prominent treatments for ME/CFS into different categories and evaluate the methods and results of corresponding drug trials. Results indicate that: • antiviral drugs appear to show limited efficacy in treating ME/CFS over a broad demographic. • there is a lack of clinical research focusing on the use of specific cyclooxygenase-2 inhibitors [analgesic] to treat ME/CFS. • antidepressants may be of use in delivering improvements in the quality of life of patients with ME/CFS. • recalibration of endocrine-immune regulation may be involved in supporting the persistence of ME/CFS and may be responsible at least in part for its resistance to single agent interventions. Authors conclude that there is a great need for larger, longitudinal studies focused on a more clearly defined subset of ME/CFS as well as a greater consideration of potential synergies between interventions and the suitability of combination therapies.
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by prolonged periods of fatigue, chronic pain, depression, and a complex constellation of other symptoms. Currently, ME/CFS has no known cause, nor are the mechanisms of illness well understood. Therefore, with few exceptions, attempts to treat ME/CFS have been directed mainly toward symptom management. These treatments include antivirals, pain relievers, antidepressants, and oncologic agents as well as other single-intervention treatments. Results of these trials have been largely inconclusive and, in some cases, contradictory. Contributing factors include a lack of well-designed and -executed studies and the highly heterogeneous nature of ME/CFS, which has made a single etiology difficult to define. Because the majority of single-intervention treatments have shown little efficacy, it may instead be beneficial to explore broader-acting combination therapies in which a more focused precision-medicine approach is supported by a systems-level analysis of endocrine and immune co-regulation.
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Change in physical activity and quality of life in endometrial cancer survivors receiving a physical activity intervention.
Robertson, MC, Lyons, EJ, Song, J, Cox-Martin, M, Li, Y, Green, CE, Pinto, BM, Carmack, CL, Harrison, C, Baum, G, et al
Health and quality of life outcomes. 2019;17(1):91
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Endometrial cancer survivors suffer from high rates of obesity and physical activity-related co-morbidities that are related to cancer-specific and overall mortality. The aim of this study was to investigate how change in physical activity over time related to change in multiple, specific measures of quality of life for endometrial cancer survivors receiving a physical activity intervention. This study was a one-group, pre-post design which recruited 100 women diagnosed with stage I, II, or IIIa endometrial cancer. Each participant received a customized exercise prescription that was based on the results of baseline fitness tests. Results indicate change in physical activity was positively associated with change in SF-36 (Short Form Health Survey) subscale scores for role limitations due to physical health and general health. Furthermore, change in physical activity was negatively associated with change in pain and somatic distress. Authors conclude that increasing physical activity was positively associated with improvements in role limitation due to physical health, general health, pain, and somatic distress.
Abstract
BACKGROUND Endometrial cancer survivors are at an increased risk of poor quality of life outcomes. Physical activity is positively associated with general quality of life in this population, however, little is known about how changes in physical activity may be associated with changes in specific aspects of quality of life. The aim of this secondary data analysis was to explore the relationships between change in physical activity and change in physical, mental, social, and other aspects of quality of life in endometrial cancer survivors receiving a physical activity intervention. METHODS Endometrial cancer survivors (N = 100) participated in a telephone-based physical activity intervention for six months. At baseline and post-intervention we measured physical activity via accelerometry and ecological momentary assessment, and quality of life via the Short Form Health Survey (SF-36), the Quality of Life of Adult Cancer Survivors instrument, the Brief Symptom Inventory, the Pittsburgh Sleep Quality Index, and the Perceived Stress Scale. We conducted structural equation modeling path analyses to investigate how physical activity post-intervention was associated with the quality of life measures' subscales post-intervention, adjusting for baseline levels and potentially confounding covariates. RESULTS Increasing physical activity was positively associated with improvements in general health (p = .044), role limitation due to physical health (p = .005), pain (p = .041), and somatic distress (p = .023). There was no evidence to indicate that change in physical activity was associated with change in other aspects of quality of life. CONCLUSIONS Endometrial cancer survivors are at higher risk for suffering from challenges to physical quality of life, and findings from this study suggest that increasing physical activity may alleviate some of these problems. Further research is needed to determine whether other aspects of quality of life are linked to change in physical activity. TRIAL REGISTRATION Trial registration number: NCT00501761 Name of registry: clinicaltrials.gov Date of registration: July 16, 2007. Date of enrollment: June 16, 2005.
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A Large Randomized Trial: Effects of Mindfulness-Based Stress Reduction (MBSR) for Breast Cancer (BC) Survivors on Salivary Cortisol and IL-6.
Lengacher, CA, Reich, RR, Paterson, CL, Shelton, M, Shivers, S, Ramesar, S, Pleasant, ML, Budhrani-Shani, P, Groer, M, Post-White, J, et al
Biological research for nursing. 2019;21(1):39-49
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Breast cancer survivors (BCS) often experience physiological and psychological stressors related to their diagnosis and treatment, and a disruption of cortisol function can affect cancer risk and progression. Increased levels of the stress hormone cortisol and interleukin-6 (IL-6), a pro-inflammatory immune mediator, have been associated with acute and chronic stress levels. Mindfulness-Based Stress Reduction (MBSR) is a clinical stress-reducing program, which has been found to decrease psychological and physical symptoms associated with stress. The purpose of this randomised study, involving 299 BCS, was to evaluate the efficacy of MBSR in reducing cortisol and IL-6 levels, compared to a usual-care control treatment. Statistically significant reductions in cortisol levels were seen after the delivery of the MBSR program at both time points (week 1 and 6), and at week 6 only for IL-6. There was no significant difference in change in cortisol or IL6 levels over time between the MBSR and the usual-care groups. An association was observed between levels of IL-6 and psychological and physical symptoms and quality of life, but not for cortisol. The authors conclude that MBSR can alleviate the stress response in the short term for breast cancer survivors.
Abstract
Breast cancer survivors (BCS) often experience psychological and physiological symptoms after cancer treatment. Mindfulness-based stress reduction (MBSR), a complementary and alternative therapy, has reduced subjective measures of stress, anxiety, and fatigue among BCS. Little is known, however, about how MBSR affects objective markers of stress, specifically the stress hormone cortisol and the pro-inflammatory cytokine interleukin-6 (IL-6). In the present study, BCS ( N = 322) were randomly assigned to a 6-week MBSR program for BC or usual-care control. Measurements of cortisol, IL-6, symptoms, and quality of life were obtained at orientation and 6 weeks. Cortisol and IL-6 were also measured prior to and after the MBSR(BC) class Weeks 1 and 6. The mean age of participants was 56.6 years and 69.4% were White non-Hispanic. Most had Stage I (33.8%) or II (35.7%) BC, and 35.7% had received chemotherapy and radiation. Cortisol levels were reduced immediately following MBSR(BC) class compared to before the class Weeks 1 and 6 (Wilcoxon-signed rank test; p < .01, d = .52-.56). IL-6 was significantly reduced from pre- to postclass at Week 6 (Wilcoxon-signed rank test; p < .01, d = .21). No differences were observed between the MBSR(BC) and control groups from baseline to Week 6 using linear mixed models. Significant relationships with small effect sizes were observed between IL-6 and both symptoms and quality of life in both groups. Results support the use of MBSR(BC) to reduce salivary cortisol and IL-6 levels in the short term in BCS.