Blood Flow Restriction and Veterans With Multiple Sclerosis and Advanced Disability: Protocol for a Randomized Controlled Trial.

OBJECTIVE: The purpose of this study will be to determine the efficacy of low intensity lower extremity resistance training with and without blood flow restriction (BFR) on quadriceps muscle strength and thickness in veterans with advanced multiple sclerosis (MS). METHODS: This will be an assessor-blinded, 2-group (1 to 1 allocation) randomized controlled trial targeting an enrollment of 58 participants with advanced MS as defined by Patient-Determined Disease Steps scale levels 4 to 7. Both groups will complete 10 weeks of twice weekly low-load resistance training (20%-30% of 1-repetition max) targeting knee and hip extension, knee flexion, and ankle plantarflexion. The intervention group will perform all training using BFR, with limb occlusion pressures between 60% and 80% of maximal limb occlusion pressure. Primary outcomes will be quadriceps muscle strength and thickness. Secondary outcomes will include knee flexion and ankle plantarflexion strength, functional mobility, physical activity, and patient-reported measures. All outcomes will be assessed at baseline before the intervention, immediately after the intervention, and at a 2-month follow-up assessment. The change between groups postintervention and after the 2-month follow-up will be reported for all outcomes. All analyses will assume a 2-sided test of hypothesis (α = .05). IMPACT: There is very little evidence for the efficacy of exercise interventions in people with MS who have advanced mobility disability. Resistance training with BFR may be an important approach for people with advanced MS who may not tolerate more conventional, moderate-to-high intensity resistance training. The results of this study will inform clinicians regarding exercise decisions for people with advanced MS and future investigations on the role of BFR in people with MS.

Amino acid and lipid associated plasma metabolomic patterns are related to healthspan indicators with ageing.

Advancing age is associated with impairments in numerous physiological systems, leading to an increased risk of chronic disease and disability, and reduced healthspan (the period of high functioning healthy life). The plasma metabolome is thought to reflect changes in the activity of physiological systems that influence healthspan. Accordingly, we utilized an LC-MS metabolomics analysis of plasma collected from healthy young and older individuals to characterize global changes in small molecule abundances with age. Using a weighted gene correlation network analysis (WGCNA), similarly expressed metabolites were grouped into modules that were related to indicators of healthspan, including clinically relevant markers of morphology (body mass index, body fat, and lean mass), cardiovascular health (systolic/diastolic blood pressure, endothelial function), renal function (glomerular filtration rate), and maximal aerobic exercise capacity in addition to conventional clinical blood markers (e.g. fasting glucose and lipids). Investigation of metabolic classes represented within each module revealed that amino acid and lipid metabolism as significantly associated with age and indicators of healthspan. Further LC-MS/MS targeted analyses of the same samples were used to identify specific metabolites related to age and indicators of healthspan, including methionine and nitric oxide pathways, fatty acids, and ceramides. Overall, these results demonstrate that plasma metabolomics profiles in general, and amino acid and lipid metabolism in particular, are associated with ageing and indicators of healthspan in healthy adults.

Curcumin supplementation and motor-cognitive function in healthy middle-aged and older adults.

BACKGROUND: Recent studies suggest curcumin is a promising nutraceutical for improving important clinical and physiological markers of healthy aging, including motor and cognitive function. OBJECTIVE: To determine if curcumin supplementation improves motor and cognitive function in healthy middle-aged and older adults. METHODS: 39 healthy men and postmenopausal women (45-74 yrs) were randomized to 12 weeks of placebo (n = 19) or curcumin supplementation (2000 mg/day Longvida®; n = 20) with motor and cognitive function assessed at week 0 and 12. RESULTS: Using measures of the NIH Toolbox and other standardized tests, there were no changes in muscle strength and rate of torque development, dexterity, fatigability, mobility, endurance, and balance between the placebo and curcumin groups after 12 weeks (all P > 0.05). Additionally, there were no changes after 12 weeks of placebo and curcumin supplementation in measures of fluid cognitive ability, a cognitive domain that declines with age, including processing speed, executive function, working memory, and episodic memory (all P > 0.3). There were marginal changes in language, a measure of crystallized cognitive ability that is stable with age, following the intervention, wherein reading decoding increased 3% in the curcumin group (post: 2428±35 vs. pre: 2357±34, P = 0.003), but was unchanged in the placebo group (post: 2334±39 vs. pre: 2364±40, P = 0.07). CONCLUSIONS: Overall, 12 weeks of curcumin supplementation does not improve motor and cognitive functions in healthy middle-aged and older adults. It is possible that curcumin may enhance these functions in groups with greater baseline impairments than those studied here, including adults greater than 75 years of age and/or patients with clinical disorders.

Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress.

We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults. Thirty-nine healthy men and postmenopausal women (45-74 yrs) were randomized to 12 weeks of curcumin (2000 mg/day Longvida®; n=20) or placebo (n=19) supplementation. Forearm blood flow response to acetylcholine infusions (FBFACh; resistance artery endothelial function) increased 37% following curcumin supplementation (107±13 vs. 84±11 AUC at baseline, P=0.03), but not placebo (P=0.2). Curcumin treatment augmented the acute reduction in FBFACh induced by the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA; P=0.03), and reduced the acute increase in FBFACh to the antioxidant vitamin C (P=0.02), whereas placebo had no effect (both P>0.6). Similarly, brachial artery flow-mediated dilation (conduit artery endothelial function) increased 36% in the curcumin group (5.7±0.4 vs. 4.4±0.4% at baseline, P=0.001), with no change in placebo (P=0.1). Neither curcumin nor placebo influenced large elastic artery stiffness (aortic pulse wave velocity or carotid artery compliance) or circulating biomarkers of oxidative stress and inflammation (all P>0.1). In healthy middle-aged and older adults, 12 weeks of curcumin supplementation improves resistance artery endothelial function by increasing vascular nitric oxide bioavailability and reducing oxidative stress, while also improving conduit artery endothelial function.

Habitual aerobic exercise does not protect against micro- or macrovascular endothelial dysfunction in healthy estrogen-deficient postmenopausal women.

Aging causes micro- and macrovascular endothelial dysfunction, as assessed by endothelium-dependent dilation (EDD), which can be prevented and reversed by habitual aerobic exercise (AE) in men. However, in estrogen-deficient postmenopausal women, whole forearm microvascular EDD has not been studied, and a beneficial effect of AE on macrovascular EDD has not been consistently shown. We assessed forearm blood flow in response to brachial artery infusions of acetylcholine (FBFACh), a measure of whole forearm microvascular EDD, and brachial artery flow-mediated dilation (FMD), a measure of macrovascular EDD, in 12 premenopausal sedentary women (Pre-S; 24 ± 1 yr; V̇o2max = 37.5 ± 1.6 ml·kg-1·min-1), 25 estrogen-deficient postmenopausal sedentary women (Post-S; 62 ± 1 yr; V̇o2max = 24.7 ± 0.9 ml·kg-1·min-1), and 16 estrogen-deficient postmenopausal AE-trained women (Post-AE; 59 ± 1 yr; V̇o2max = 40.4 ± 1.4 ml·kg-1·min-1). FBFACh was lower in Post-S and Post-AE compared with Pre-S women (135 ± 9 and 116 ± 17 vs. 193 ± 21 AUC, respectively, both P < 0.008), whereas Post-S and Post-AE women were not different (P = 0.3). Brachial artery FMD was 34% (5.73 ± 0.67%) and 45% (4.79 ± 0.57%) lower in Post-S and Post-AE, respectively, vs. Pre-S women (8.69 ± 0.95%, both P ≤ 0.01), but not different between Post-S and Post-AE women (P = 0.3). Post-AE women had lower circulating C-reactive protein and oxidized low-density lipoprotein compared with Post-S women (0.5 ± 0.1 vs. 1.1 ± 0.2 mg/l and 40 ± 4 vs. 55 ± 3 U/l, respectively, both P = 0.01), but these markers were not correlated to FBFACh (P = 0.3) or brachial artery FMD (P = 0.8). These findings are consistent with the idea that habitual AE does not protect against age/menopause-related whole forearm micro- and macrovascular endothelial dysfunction in healthy nonobese estrogen-deficient postmenopausal women, despite being associated with lower systemic markers of inflammation and oxidative stress. NEW & NOTEWORTHY: This is the first study to demonstrate that habitual aerobic exercise may not protect against age/menopause-related whole forearm microvascular endothelial dysfunction in healthy nonobese estrogen-deficient postmenopausal women, consistent with recent findings regarding macrovascular endothelial function. This is in contrast to what is observed in healthy middle-aged and older aerobic exercise-trained men.