Fish Oil Supplementation with Resistance Exercise Training Enhances Physical Function and Cardiometabolic Health in Postmenopausal Women.

Menopause is a condition associated with an increased risk of dysregulation in cardiovascular and metabolic health among older women. While fish oil (FO) has garnered great attention for its health-enhancing properties, its potential for enhancing cardiometabolic health in this demographic remains to be established. The purpose of this study was to determine the clinical efficacy of an 8 wk administration of FO combined with programmed resistance exercise training (RET) on physical function and risk factors associated with cardiometabolic health in healthy older women. Twenty, healthy, older women were randomly assigned to one of the two experimental groups: resistance training with placebo (RET-PL) or RET with fish oil (RET-FO). Physical function, blood pressure (BP), triglyceride (TG), and systemic inflammation and oxidative stress biomarkers were assessed before and after the intervention. Statistical significance was set at p ≤ 0.05. Physical function was greatly enhanced in both RET and RET-FO. Handgrip strength substantially increased only in RET-FO. RET-FO exhibited significant decreases in BP, TG, inflammatory cytokines (TNF-α and IL-6), and oxidative stress (MDA and 8-OHdG) levels, while no detectable changes were found in RET-PL. Our findings indicate that FO administration during 8 wks of RET appears to enhance muscle function and lower risk factors linked to cardiometabolic disorders in postmenopausal women.

Efficacy and Safety of SID142 in Patients With Peripheral Arterial Disease: A Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group, Phase III Clinical Trial.

PURPOSE: Renexin® is a combination pill of cilostazol and Ginkgo biloba leaf extract that is used for the improvement of ischemic symptoms associated with peripheral arterial disease (PAD). SID142 is a controlled-release tablet of cilostazol (200 mg) and G biloba leaf extract (160 mg) that was developed to address the limitation of BID administration with Renexin. This study aimed to verify that SID142 was not inferior to Renexin in the treatment of patients with PAD. METHODS: This was a multicenter, randomized, double-blind, active-controlled, parallel-group, Phase III clinical trial. Study subjects were randomized to receive SID142 once daily or Renexin twice a day for 12 weeks. The primary end point was a change in the patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. If the lower limit of the two-sided 95% CI was greater than -10, the study drug was declared noninferior to the reference drug. Secondary efficacy end points included cold sensation, ankle-brachial index, ankle systolic pressure, maximum walking distance, pain-free walking distance, and investigator's global assessment. Study group results were compared 4, 8, and 12 weeks after treatment. Adverse events were assessed as a safety end point. FINDINGS: In total, 344 subjects from 19 medical centers were screened, and a total of 170 subjects were randomly assigned to either the SID142 (n = 86) or the Renexin (n = 84) group. Analysis of the change in lower extremity pain at 12 weeks compared with baseline revealed that SID142 was not inferior to Renexin (21.44 [19.23] vs 22.30 [17.75]; 95% CI, -7.70 to 5.97; P = 0.5942). No significant differences were found between groups in any secondary efficacy end point. However, the incidence of adverse reactions was significantly lower in the SID142 group (22.35% vs 39.29%; P = 0.0171). IMPLICATIONS: SID142 once daily was not inferior to Renexin twice a day for efficacy in patients with PAD. SID142 had a favorable safety profile. CLINICALTRIALS: gov identifier: NCT03318276.

Inhibitory Effects of Aucklandia lappa Decne. Extract on Inflammatory and Oxidative Responses in LPS-Treated Macrophages.

Aucklandia lappa Decne., known as "Mok-hyang" in Korea, has been used for the alleviation of abdominal pain, vomiting, diarrhea, and stress gastric ulcers in traditional oriental medicine. We investigated the anti-inflammatory and antioxidative effects of the ethanol extract of Aucklandia lappa Decne. (ALDE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. ALDE significantly inhibited the LPS-induced nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. The production of other proinflammatory mediators, including COX-2, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α, was reduced by ALDE in LPS-stimulated RAW 264.7 cells. The mechanism underlying the anti-inflammatory effects of ALDE was elucidated to be the suppression of LPS-induced nuclear translocation of p65, followed by the degradation of IκB and the inhibition of the phosphorylation of mitogen-activated protein kinases (MAPK). In addition, ALDE showed enhanced radical scavenging activity. The antioxidant effect of ALDE was caused by the enhanced expression of heme oxygenase (HO-1) via stabilization of the expression of the nuclear transcription factor E2-related factor 2 (Nrf2) pathway. Collectively, these results indicated that ALDE not only exerts anti-inflammatory effects via the suppression of the NF-κB and MAPK pathways but also has an antioxidative effect through the activation of the Nrf2/HO-1 pathway.

Effects of conjugated linoleic acid/n-3 and resistance training on muscle quality and expression of atrophy-related ubiquitin ligases in middle-aged mice with high-fat diet-induced obesity.

PURPOSE: To investigate the effects of conjugated linoleic acid (CLA)/n-3 supplements and resistance exercise training (RT) for 20 weeks on muscle quality and genes related to protein synthesis/degradation in middle-aged mice with high-fat diet (HFD)-induced obesity. METHODS: Nine-month-old C57BL/6 male mice were randomly assigned to five groups: 1) normal diet (C), 2) high-fat diet (H), 3) H+RT (HRT), 4) H+CLA/n-3 (H-CN), and 5) H+RT+CLA/n-3 (H-RTCN). HFD groups were given a diet containing 60% fat for 20 weeks, and exercised groups underwent progressive RT using weighted ladder climbing. The CLA/n-3 mixed diet contained 1% CLA and 1% n-3. Grip strength was assessed, and triceps were removed. RT-PCR was used to analyze transcript levels. RESULTS: Grip strength of the H group was significantly lower than that of the C group; however, those in the H-CN, H-RT, and H-RTN groups were significantly greater than that in the H group. However, the muscle quality was significantly greater only in the H-RT group compared with the H and H-CN groups. Akt expression decreased in the H-CN, H-RT, and H-RTCN groups compared with those in the C and H groups, whereas mammalian target of rapamycin expression increased in the H, H-CN, H-RT, and H-RTCN groups compared with that in the C group. However, atrogin1 was significantly downregulated in the H-RTCN group compared with that in the H and H-CN groups, and MuRF1 expression was also decreased in the H-RT and H-RTCN groups. Interestingly, atrogin1 and MuRF1 were downregulated in the H-RTCN group compared with that in the H-CN group. CONCLUSION: HFD-mediated gene expression involved in protein degradation was attenuated following 20-week RT with CLA/n-3. Furthermore, RT with or without CLA/n-3 improved grip strength and muscle quality in middle-aged mice during HFD. Therefore, RT with CLA/n-3 during HFD may improve muscle strength and quality by suppressing protein degradation.

Effect of conjugated linoleic acids and omega-3 fatty acids with or without resistance training on muscle mass in high-fat diet-fed middle-aged mice.

NEW FINDINGS: What is the central question of this study? This study examined the effects of 20 weeks of administration of conjugated linoleic acids/omega-3 fatty acids with or without programed resistance exercise training on body composition, skeletal muscle properties and functional capacity in middle-aged mice fed a high-fat diet. What is the main finding and its importance? Chronic daily administration of conjugated linoleic acids/omega-3 fatty acids with resistance exercise training can help to blunt fat gain, alleviate loss of myogenic capacity and sensorimotor function and lower tissue inflammation in middle-aged mice during chronic high-fat diet-induced catabolism. This study investigated the effects of 20 weeks of combined conjugated linoleic acid (CLA)/omega-3 fatty acid (n-3) administration independently or combined with resistance exercise training (RET) on skeletal muscle in middle-aged mice consuming a high-fat diet (HFD). Nine-month-old C57BL/6 mice were randomly assigned into four experimental groups (H, high-fat diet; HE, H + RET; HCN, H + CLA/n-3; and HECN, H + CLA/n3 + RET). Body composition and functional capacity were assessed pre- and post-intervention. Muscle tissues were collected at 14 months of age. ANOVA was used, with significance set at P ≤ 0.05. Fat mass significantly increased in H (+74%), HE (+142%) and HECN (+43%) but not in HCN. Muscle wet weights were significantly lower in H and HCN than in HE and HECN. Grip strength substantially declined in H (-15%) and HCN (-17%), whereas sensorimotor function significantly declined only in H (-11%). HECN exhibited improvement in strength (+22%) and sensorimotor coordination (+17%). In comparison to H, muscle tumour necrosis factor-α mRNA expression was significantly lower in HE (-39%), HCN (-24%) and HECN (-21%), respectively. Mean myofibre cross-sectional areas were markedly lower in H and HCN than in HE and HECN. H showed significantly lower satellite cell abundance and numbers of myonuclei than all other groups. Our findings suggest that long-term daily CLA/n-3 intake with resistance training improved sensorimotor function, ameliorated fat gain and prevented loss of myogenic capacity while lowering tumour necrosis factor-α expression during chronic HFD.

Nitrate ingestion: a review of the health and physical performance effects.

This paper provides an overview of the current literature and scientific evidence surrounding inorganic nitrate (NO3-) supplementation and its potential for improving human health and physical performance. As indicative of the ever-expanding organic and natural food consumer market, athletes and health enthusiasts alike are constantly searching for ingredient-specific "super foods" and dietary supplements capable of eliciting health and performance benefits. Evidence suggests that NO3- is the viable active component within beetroot juice (BRJ) and other vegetables, responsible for health-promoting and ergogenic effects. Indeed, multiple studies support NO3- supplementation as an effective method to improve exercise performance. NO3- supplementation (either as BRJ or sodium nitrate [NaNO3-]) has also demonstrated modest benefits pertaining to cardiovascular health, such as reducing blood pressure (BP), enhancing blood flow, and elevating the driving pressure of O2 in the microcirculation to areas of hypoxia or exercising tissue. These findings are important to cardiovascular medicine/exercise physiology and suggest a possible role for NO3- supplementation: (1) as a low-cost prevention and treatment intervention for patients suffering from blood flow disorders; and (2) an effective, natural ergogenic aid for athletes. Benefits have been noted following a single bolus, as well as daily supplementation of NO3-. While results are promising, additional research is needed to determine the impact of NO3- supplementation on anaerobic exercise performance, to identify principle relationships between isolated nitrate and other ingredients found in nitrate-rich vegetables (e.g., vitamin C, polyphenols, fatty acids, thiocyanate), to explore the specific dose-response relationships needed to elicit health and ergogenic benefits, to prolong the supplementation period beyond a relatively short period (i.e., >15 days), to determine if more robust effects can be observed with longer-term treatment, and to fully examine the safety of chronic NO3- supplementation, as this continues to be a concern of some.

Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects.

BACKGROUND: Higenamine, also known as norcoclaurine, is an herbal constituent thought to act as a beta-2 adrenergic receptor agonist-possibly stimulating lipolysis. It was the purpose of this study to determine the impact of a higenamine-based dietary supplement on plasma free fatty acids and energy expenditure following acute oral ingestion. METHODS: Sixteen healthy subjects (8 men; 26.1 ± 2.5 yrs; 8 women 22.4 ± 3.1 yrs) ingested a dietary supplement containing a combination of higenamine, caffeine (270 mg), and yohimbe bark extract or a placebo, on two separate occasions in a double-blind, randomized, cross-over design, separated by 6-8 days. Blood samples were collected immediately before ingestion, and at 30, 60, 120, and 180 minutes post ingestion, and analyzed for plasma free fatty acids (FFA) and glycerol. Breath samples were collected at the same times for a measure of kilocalorie expenditure and respiratory exchange ratio (RER) using indirect calorimetry. Heart rate and blood pressure were recorded at all times. Data collection occurred in the morning following a 10 hour overnight fast. RESULTS: A condition effect was noted for both FFA (p < 0.0001) and kilocalorie expenditure (p = 0.001), with values higher for supplement compared to placebo at 60, 120, and 180 minutes post ingestion. No statistically significant effects were noted for glycerol or RER (p > 0.05). A condition effect was noted for heart rate (p = 0.03) and systolic blood pressure (p < 0.0001), with values higher for supplement compared to placebo. CONCLUSION: Ingestion of a higenamine-based dietary supplement stimulates lipolysis and energy expenditure, as evidenced by a significant increase in circulating FFA and kilocalorie expenditure. The same supplement results in a moderate increase in heart rate (~3 bpm) and systolic blood pressure (~12 mmHg), which is consistent with previous studies evaluating moderate doses of caffeine and yohimbine, suggesting that higenamine contributes little to the increase in these hemodynamic variables. These findings are in reference to young, healthy and active men and women.

Cissus quadrangularis reduces joint pain in exercise-trained men: a pilot study.

BACKGROUND: Strenuous, high-volume exercise is often associated with inflammation and joint pain. Cissus quadrangularis (CQ) has been reported to have anti-inflammatory activity. The purpose of our study was to determine the therapeutic effects of CQ supplementation in healthy, exercise-trained men with joint-specific pain. METHODS: Twenty-nine men between the ages of 20 and 46 years, who reportedly experienced chronic joint pain as a result of strenuous exercise, participated in our pilot study. All men received CQ 3200 mg daily for 8 weeks. Before and after the 8-week intervention period, subjects completed a questionnaire to determine their degree of joint pain (Western Ontario and McMaster Universities Index of Osteoarthritis [WOMAC]). Clinical measures (eg, heart rate, blood pressure, blood biomarkers) were also collected for each subject pre- (baseline) and post-intervention. RESULTS: Subject ratings for multiple variables within the WOMAC Index improved (decreased) significantly (P < 0.05), with the subject mean total WOMAC score decreasing from 25.4 ± 2.4 to 17.4 ± 2.1 (~31%), pre- to post-intervention. No clinical measure was significantly impacted by use of CQ supplementation. CONCLUSION: An 8-week course of supplementation with CQ reduced joint pain in a sample of 29 young, otherwise healthy, exercise-trained men. Additional study is needed to extend these findings, including comparison with a placebo-controlled cohort, and possibly, examining effects of CQ use in women and older adult subjects.