Chronic cannabis use is associated with altered monocyte phenotype, immune response, and depression in physically active individuals.

Introduction: This study evaluated depression, monocyte phenotype, and immune function in physically active cannabis users. Methods: Participants (N = 23) were classified as either cannabis users (CU, n = 11) or non-users (NU, n = 12). White blood cells isolated from blood were analyzed for co-expression of cluster of differentiation 14 and 16 using flow cytometry. Lipopolysaccharide (LPS) was cultured with whole blood and assessed for interleukin-6 and tumor necrosis factor-α (TNF-α) release. Results: The percentage of white blood cells classified as monocytes was not different between groups; however, CU had a significantly greater percentage of monocytes classified as intermediate (p = 0.02). When standardized per milliliter of blood, CU had significantly greater numbers of total monocytes (p = 0.01), classical monocytes (p = 0.02), and intermediate monocytes (p = 0.01). Intermediate monocytes per milliliter of blood were positively correlated to the number of times CU used cannabis per day (r = 0.864, p < 0.01) and Beck Depression Inventory-II (BDI-II) score (r = 0.475, p = 0.03), which was significantly greater in CU (5.1 ± 4.8) compared with NU (0.8 ± 1.0; p < 0.01). CU released significantly less TNF-α per monocyte in response to LPS. Conclusions: CU had altered monocyte phenotypes and functions compared with NU. Elevations in intermediate monocytes were positively correlated with measures of cannabis use and BDI-II score.

Artemisia dracunculus L. Ethanolic Extract and an Isolated Component, DMC2, Ameliorate Inflammatory Signaling in Pancreatic ß-Cells via Inhibition of p38 MAPK.

Non-resolving pancreatic islet inflammation is widely viewed as a contributor to decreases in ß-cell mass and function that occur in both Type 1 and Type 2 diabetes. Therefore, strategies aimed at reducing or eliminating pathological inflammation would be useful to protect islet ß-cells. Herein, we described the use of 2',4'-dihydroxy-4-methoxydihydrochalcone (DMC2), a bioactive molecule isolated from an ethanolic extract of Artemisia dracunculus L., as a novel anti-inflammatory agent. The ethanolic extract, termed PMI 5011, reduced IL-1ß-mediated NF-κB activity. DMC2 retained this ability, indicating this compound as the likely source of anti-inflammatory activity within the overall PMI 5011 extract. We further examined NF-κB activity using promoter-luciferase reporter constructs, Western blots, mRNA abundance, and protein secretion. Specifically, we found that PMI 5011 and DMC2 each reduced the ability of IL-1ß to promote increases in the expression of the Ccl2 and Ccl20 genes. These genes encode proteins that promote immune cell recruitment and are secreted by ß-cells in response to IL-1ß. Phosphorylation of IκBα and the p65 subunit of NF-κB were not reduced by either PMI 5011 or DMC2; however, phosphorylation of p38 MAPK was blunted in the presence of DMC2. Finally, we observed that while PMI 5011 impaired glucose-stimulated insulin secretion, insulin output was preserved in the presence of DMC2. In conclusion, PMI 5011 and DMC2 reduced inflammation, but only DMC2 did so with the preservation of glucose-stimulated insulin secretion.

Kefir Is a Viable Exercise Recovery Beverage for Cancer Survivors Enrolled in a Structured Exercise Program.

PURPOSE: This study investigated the effects of 12 wk of postexercise kefir consumption in cancer survivors who have undergone chemotherapy and/or radiation therapy. METHODS: All participants were enrolled in a structured exercise training program and separated into kefir (KEF) or control (CON) treatment groups. KEF consumed 8 oz. of kefir after exercise sessions (3 d·wk-1) for 12 wk. Outcome measures included assessments for body size and composition, aerobic fitness and muscular strength, medical history, and psychological state at pre- and postintervention time points. Blood was collected and analyzed for C-reactive protein (CRP), interleukin 6 (IL-6), and lipopolysaccharide (LPS) concentrations, and LPS-stimulated whole blood IL-6 and tumor necrosis factor α production were obtained using enzyme-linked immunosorbent assays at both time points. Monocyte numbers and phenotype were obtained using flow cytometry. RESULTS: Participants (N = 24; 9 males and 15 females) were an average of 61 ± 9.9 yr old. Kefir consumption was associated with 6.3% (P = 0.034) improvements in lean body mass, as well as 51.4% (P = 0.046), 39.3% (P = 0.017), and 64.7% (P = 0.021) improvements in measures of depression, fatigue, and gastric distress, respectively. KEF also experienced a significant 35.4% (P = 0.01) reduction in circulating LPS along with an 18.0% increase (P < 0.001) in classical monocytes % and a 22.3% decrease (P = 0.04) in nonclassical monocytes %. There were no significant changes in any other variables. CONCLUSION: Twelve weeks of kefir consumption improved lean body mass, depression, fatigue, gastric distress, and a biomarker of gut dysbiosis. Kefir improved overall and classical monocyte numbers. Kefir should be considered as a component of a postexercise dietary regimen for cancer survivors.

Structured Exercise in Cancer Survivors: Is it Enough for Neural, Mental Health and Well-being?

The purpose of this cross-sectional study was to explore physical activity, depression, fatigue, and quality of life (QOL), and their relationship to brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in cancer survivors enrolled in a structured exercise program. Participants were recruited into two groups: in-treatment (IT), currently receiving chemotherapy and/or radiotherapy, and out of treatment (OT), not undergoing therapy. Participants wore accelerometers for 7 days and completed cardiorespiratory fitness, muscular strength, and depression, fatigue, and QOL assessments. Circulating BDNF and NGF concentrations were obtained using enzyme-linked immunosorbent assays. Thirty-two participants (IT: n = 13, OT: n = 19) with an average age of 63 years and BMI of 27.5, spent 78% of their waking hours engaged in sedentary behavior outside of exercise training. Significant correlations were observed between light physical activity (LPA) outside of exercise training and QOL in IT (r = 0.626, p = 0.030), and fatigue in OT (r = 0.553, p = 0.021). Moderate to vigorous physical activity (MVPA) outside of exercise training significantly correlated with leg press strength (r = 0.700, p = 0.008) in IT, and cardiorespiratory fitness (r = 0.440, p = 0.013) when groups were combined. Concentrations of NGF did not differ between groups, and in IT, BDNF was positively related to LPA outside of training and was significantly lower (87 ± 28.5 pg/mL) than in OT (137 ± 54 pg/mL; p=0.010). While structured exercise programs should focus on improving cardiorespiratory fitness and muscular strength during exercise training, these programs should consider physical activity outside of training, if well-tolerated, to potentially further lower fatigue and improve QOL in cancer survivors.

Botanical Interventions to Improve Glucose Control and Options for Diabetes Therapy.

Diabetes mellitus is a major public health problem worldwide. This endocrine disease is clustered into distinct subtypes based on the route of development, with the most common forms associated with either autoimmunity (T1DM) or obesity (T2DM). A shared hallmark of both major forms of diabetes is a reduction in function (insulin secretion) or mass (cell number) of the pancreatic islet beta-cell. Diminutions in both mass and function are often present. A wide assortment of plants have been used historically to reduce the pathological features associated with diabetes. In this review, we provide an organized viewpoint focused around the phytochemicals and herbal extracts investigated using various preclinical and clinical study designs. In some cases, crude extracts were examined directly, and in others, purified compounds were explored for their possible therapeutic efficacy. A subset of these studies compared the botanical product with standard of care prescribed drugs. Finally, we note that botanical formulations are likely suspects for future drug discovery and refinement into class(es) of compounds that have either direct or adjuvant therapeutic benefit.

Chronic cannabis use and circulating biomarkers of neural health, stress, and inflammation in physically active individuals.

Previous research has associated cannabis use with altered circulating neurotrophins and biomarkers of immune health, but these relationships have yet to be fully explored in physically active individuals. The specific aim of this study was to explore the relationships between biomarkers of neural health: nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), immune health: interleukin 6 (IL-6), C-reactive protein (CRP), and cortisol, as well as the presence of depression, in physically active cannabis users (CU) and nonusers (NU). Male and female participants (N = 30; CU, n = 15, NU, n = 15) provided intravenous blood samples and underwent assessment of body composition, maximal oxygen consumption, and depression (Beck Depression Inventory-II (BDI-II)). Samples were analyzed for concentrations of NGF, BDNF, IL-6, CRP, and cortisol using ELISAs. CU and NU were compared using an unpaired t test. Pearson's correlation and multiple linear regression were used to evaluate relationships among variables. There were no significant differences in body size or composition, maximal oxygen consumption, total BDI-II Score, concentrations of NGF, IL-6, CRP, or cortisol between groups. BDNF was significantly lower in CU compared with NU (p = 0.02), with a significant negative relationship between BDNF and CRP (p = 0.02). Mean concentrations of CRP placed CU at higher risk for cardiovascular disease compared with NU. Total BDI-II score negatively correlated with BDNF (p = 0.02) and positively correlated with CRP (p = 0.02). Novelty Plasma BDNF was significantly lower in physically active cannabis users compared with NU. CU were classified at moderate risk for cardiovascular disease based on average circulating CRP compared with low risk for NU.

Cardiorespiratory fitness, visceral fat, and body fat, but not dietary inflammatory index, are related to C-reactive protein in cancer survivors.

BACKGROUND: The control of chronic inflammation has emerged as a target for improving the health of cancer survivors (CS). AIM: To examine differences in fitness and dietary characteristics of CS when grouped by low vs. moderate to high serum C-reactive protein (CRP). METHODS: CS (N = 26, mean age = 68 ± 12 years) were evaluated for body mass index (BMI), body composition, cardiorespiratory fitness, dietary intake, dietary inflammatory index (DII), and serum CRP. Participants were assigned to one of two groups based on serum CRP concentrations: low CRP (≤1 mg/L) (LWC; n = 13) or moderate to high (CRP > 1 mg/L) (MHC; n = 13) and t-tests compared them. Data are presented as mean ± SD. RESULTS: LWC had higher VO2peak values (mL/kg/min) (p = 0.0003), and lower visceral fat area (cm2) (p = 0.02) and body fat mass (kg) (p = 0.04). Secondary analysis using Pearson's correlation coefficients, including all current study participant data, found significant negative relationships between CRP and total dietary fat intake (p = 0.02), saturated fat (p = 0.03), and polyunsaturated fat (p = 0.03). CONCLUSION: CS with moderate to high serum CRP concentrations had higher fat mass, visceral fat mass, and lower cardiorespiratory fitness. There was a significant negative relationship between dietary, fat, polyunsaturated and saturated fat, and CRP. However, these dietary fat related findings warrant further investigation. To summarize, improving cardiorespiratory fitness, maintaining lower body fat, may be helpful in altering chronic inflammation in CS.

Performance and Health-Related Characteristics of Physically Active Males Using Marijuana.

Lisano, JK, Smith, JD, Mathias, AB, Christensen, M, Smoak, P, Phillips, KT, Quinn, CJ, and Stewart, LK. Performance and health-related characteristics of physically active men using marijuana. J Strength Cond Res 33(6): 1659-1669, 2019-The influence of chronic marijuana use on the performance and health of physically active individuals has yet to be fully elucidated. The purpose of this study was to explore pulmonary function, aerobic and anaerobic fitness, strength, serum testosterone, cortisol, C-reactive protein (CRP), Δ-9-tetrahydrocannabinol (THC), 11-nor-9-carboxy-Δ-9-tetrahydrocannabinol (THC-COOH), and 11-hydroxy-Δ-9-tetrahydrocannabinol (THC-OH) concentrations in a physically active population either using or not using marijuana. Healthy, physically active males (N = 24) were compared based on their marijuana-use status: marijuana users (MU; n = 12) and nonusers (NU; n = 12). Statistical analysis (p = 0.05) revealed no difference between groups for age, body mass, body mass index, body fat, forced expiratory volume in 1 second percentage, VO2max, anaerobic power output, strength measures, testosterone, or cortisol concentrations. Although not statistically significant, MU showed a trend to fatigue to a greater percentage of absolute power output than NU from the beginning to the end of the Wingate Anaerobic Power Assessment (p = 0.08, effect size = 0.75). C-reactive protein in MU (1.76 ± 2.81 mg·L) and NU (0.86 ± 1.49 mg·L) was not significantly different (p = 0.60) but placed MU at moderate risk and NU at low risk for cardiovascular disease. Anaerobic fatigue was the only performance variable to show a trend for difference between groups. These results suggest that marijuana use in physically active males may not have significant effects on performance; however, it may be linked to elevated concentrations of CRP which place users at a higher risk for cardiovascular disease.

Cognitive Function and Salivary DHEA Levels in Physically Active Elderly African American Women.

Serum and plasma dehydroepiandrosterone sulfate (DHEAS) concentration has been associated with several health parameters associated with aging including cognitive function, bone mineral density, and muscular strength. However, the effectiveness of salivary DHEA for the prediction of cognitive function, bone mineral density, and muscular strength in older adults is currently unknown. Thirty elderly African American females provided early morning salivary samples and DHEA levels were determined using a commercially available immunoassay. Participants completed testing for psychomotor and executive function via Trail Making Tests (TMT) A and B, respectively. Bone ultrasound attenuation (BUA) was used to bone density and an isometric mid-thigh pull (IMTP) was used to determine isometric strength. Age significantly correlated with time on TMT A (r=0.328) and B (r=0.615) but was not related to DHEA, BUA, or IMTP outcomes. Elevated DHEA was associated with longer time to completion for TMT A (χ (2) = 5.14) but not to TMT B. DHEA levels were not associated with BUA or IMTP outcomes. While elevated levels of DHEA were correlated with impaired psychomotor function, salivary DHEA is not associated with executive function, bone mineral density, or isometric strength in elderly African American women.