A Randomized, Double-Blind, Placebo-Controlled Investigation of Selenium Supplementation in Women at Elevated Risk for Breast Cancer: Lessons for Re-Emergent Interest in Selenium and Cancer.

Damage to cellular macromolecules such as DNA and lipid, induced via reactive oxygen species, and indicators of cell proliferation potential such as insulin-like growth factor (IGF) metabolic status are intermediate biomarkers of breast cancer risk. Based on reports that selenium status can affect these markers, a randomized, placebo-controlled, double-blind experiment was conducted to investigate the potential of selenium supplementation to modulate breast cancer risk. Using a placebo tablet or a tablet containing 200 µg selenium provided as high-selenium yeast daily for one year, concentrations of the biomarkers in blood or urine were assessed at baseline and after 6 and 12 months of intervention. The selenium intervention used in this study is presumed to mediate its effect via the induction of glutathione peroxidase activity and the consequential impact of the active form of this protein on oxidative damage. We found no evidence to support this hypothesis or to indicate that systemic IGF metabolic status was affected. Critical knowledge gaps must be addressed for the resurgence of interest in selenium and cancer to garner clinical relevance. Those knowledge gaps include the identification of a specific, high-affinity selenium metabolite and the cellular target(s) to which it binds, and the demonstration that the cellular determinant that the selenium metabolite binds plays a critical role in the initiation, promotion, or progression of a specific type of cancer.

Calcium Supplementation Attenuates Disruptions in Calcium Homeostasis during Exercise.

An exercise-induced decrease in serum ionized calcium (iCa) is thought to trigger an increase in parathyroid hormone (PTH), which can stimulate bone resorption. PURPOSE: The purpose of this study was to determine whether taking a chewable calcium (Ca) supplement 30 min before exercise mitigates disruptions in Ca homeostasis and bone resorption in competitive male cyclists. METHODS: Fifty-one men (18 to 45 yr old) were randomized to take either 1000 mg Ca (CA) or placebo (PL) 30 min before a simulated 35-km cycling time trial. Serum iCa and PTH were measured before and immediately after exercise and a marker of bone resorption (C-terminal telopeptide of type I collagen) was measured before and 30 min after exercise. RESULTS: Serum iCa decreased in both groups from before to after exercise (mean ± SD, CA = 4.89 ± 0.16 to 4.76 ± 0.11 mg·dL, PL = 4.92 ± 0.15 to 4.66 ± 0.22 mg·dL, both P ≤ 0.01); the decrease was greater (P = 0.03) in the PL group. There was a nonsignificant (P = 0.07) attenuation of the increase in PTH by Ca supplementation (CA = 30.9 ± 13.0 to 79.7 ± 42.6 pg·mL, PL = 37.1 ± 14.8 to 111.5 ± 49.4 pg·mL, both P ≤ 0.01), but no effect of Ca on the change in C-terminal telopeptide of type I collagen, which increased in both groups (CA = 0.35 ± 0.17 to 0.50 ± 0.21 ng·mL, PL = 0.36 ± 0.13 to 0.54 ± 0.22 ng·mL, both P ≤ 0.01). CONCLUSION: It is possible that ingesting Ca only 30 min before exercise was not a sufficient time interval to optimize gut Ca availability during exercise. Further studies will be needed to determine whether adequate Ca supplementation before and/or during exercise can fully mitigate the exercise-induced decrease in serum iCa and increases in PTH and bone resorption.

Calcium supplementation and parathyroid hormone response to vigorous walking in postmenopausal women.

INTRODUCTION: Disruptions in calcium (Ca) homeostasis during exercise may influence skeletal adaptations to exercise training. In young men, vigorous cycling causes increases in parathyroid hormone (PTH) and bone resorption (C-terminal telopeptides of type I collagen [CTX]); responses are attenuated by Ca supplementation. The study aimed to determine whether vigorous walking causes similar increases in PTH and CTX in older women and how the timing of Ca supplementation before and during exercise influences these responses. METHODS: In experiment 1, 10 women (61 ± 4 yr) consumed 125 mL of either a Ca-fortified (1 g·L) or control beverage every 15 min during exercise starting 60 min before and continuing during 60 min of exercise. In experiment 2, 23 women (61 ± 4 yr) consumed 200 mL of a Ca-fortified (1 g·L) or control beverage every 15 min starting 15 min before and continuing during 60 min of exercise. The exercise was treadmill walking at 75%-80% V˙O2peak. RESULTS: In experiment 1, serum ionized Ca decreased in the control condition (P < 0.001), but not with Ca supplementation. PTH increased after exercise on both days (Ca, P = 0.05; control, P = 0.009) but was attenuated by Ca supplementation (8.3 vs 26.1 pg·mL; P = 0.03). CTX increased only on the control day (P = 0.02). In experiment 2, serum ionized Ca decreased on Ca and control days (Ca and control, P < 0.001), but less so on the Ca day (P = 0.04). PTH (Ca and control, P < 0.001) and CTX (Ca, P = 0.02; control P = 0.007) increased on the Ca and control day, and there were no differences in the changes. CONCLUSION: The timing of Ca supplementation may be a key mediator of Ca homeostasis during acute exercise. Further research is necessary to determine how this influences skeletal adaptations to training.

Relationship between intensity of quadriceps muscle neuromuscular electrical stimulation and strength recovery after total knee arthroplasty.

BACKGROUND: Neuromuscular electrical stimulation (NMES) can facilitate the recovery of quadriceps muscle strength after total knee arthroplasty (TKA), yet the optimal intensity (dosage) of NMES and its effect on strength after TKA have yet to be determined. OBJECTIVE: The primary objective of this study was to determine whether the intensity of NMES application was related to the recovery of quadriceps muscle strength early after TKA. A secondary objective was to quantify quadriceps muscle fatigue and activation immediately after NMES to guide decisions about the timing of NMES during rehabilitation sessions. DESIGN: This study was an observational experimental investigation. METHODS: Data were collected from 30 people who were 50 to 85 years of age and who received NMES after TKA. These people participated in a randomized controlled trial in which they received either standard rehabilitation or standard rehabilitation plus NMES to the quadriceps muscle to mitigate strength loss. For the NMES intervention group, NMES was applied 2 times per day at the maximal tolerable intensity for 15 contractions beginning 48 hours after surgery over the first 6 weeks after TKA. Neuromuscular electrical stimulation training intensity and quadriceps muscle strength and activation were assessed before surgery and 3.5 and 6.5 weeks after TKA. RESULTS: At 3.5 weeks, there was a significant association between NMES training intensity and a change in quadriceps muscle strength (R(2)=.68) and activation (R(2)=.22). At 6.5 weeks, NMES training intensity was related to a change in strength (R(2)=.25) but not to a change in activation (R(2)=.00). Furthermore, quadriceps muscle fatigue occurred during NMES sessions at 3.5 and 6.5 weeks, whereas quadriceps muscle activation did not change. LIMITATIONS: Some participants reached the maximal stimulator output during at least 1 treatment session and might have tolerated more stimulation. CONCLUSIONS: Higher NMES training intensities were associated with greater quadriceps muscle strength and activation after TKA.

Early neuromuscular electrical stimulation to improve quadriceps muscle strength after total knee arthroplasty: a randomized controlled trial.

BACKGROUND: The recovery of quadriceps muscle force and function after total knee arthroplasty (TKA) is suboptimal, which predisposes patients to disability with increasing age. OBJECTIVE: The purpose of this investigation was to evaluate the efficacy of quadriceps muscle neuromuscular electrical stimulation (NMES), initiated 48 hours after TKA, as an adjunct to standard rehabilitation. DESIGN: This was a prospective, longitudinal randomized controlled trial. METHODS: Sixty-six patients, aged 50 to 85 years and planning a primary unilateral TKA, were randomly assigned to receive either standard rehabilitation (control) or standard rehabilitation plus NMES applied to the quadriceps muscle (initiated 48 hours after surgery). The NMES was applied twice per day at the maximum tolerable intensity for 15 contractions. Data for muscle strength, functional performance, and self-report measures were obtained before surgery and 3.5, 6.5, 13, 26, and 52 weeks after TKA. RESULTS: At 3.5 weeks after TKA, significant improvements with NMES were found for quadriceps and hamstring muscle strength, functional performance, and knee extension active range of motion. At 52 weeks, the differences between groups were attenuated, but improvements with NMES were still significant for quadriceps and hamstring muscle strength, functional performance, and some self-report measures. LIMITATIONS: Treatment volume was not matched for both study arms; NMES was added to the standard of care treatment. Furthermore, testers were not blinded during testing, but used standardized scripts to avoid bias. Finally, some patients reached the maximum stimulator output during at least one treatment session and may have tolerated more stimulation. CONCLUSIONS: The early addition of NMES effectively attenuated loss of quadriceps muscle strength and improved functional performance following TKA. The effects were most pronounced and clinically meaningful within the first month after surgery, but persisted through 1 year after surgery.

Acute calcium ingestion attenuates exercise-induced disruption of calcium homeostasis.

PURPOSE: Exercise is associated with a decrease in bone mineral density under certain conditions. One potential mechanism is increased bone resorption due to an exercise-induced increase in parathyroid hormone (PTH), possibly triggered by dermal calcium loss. The purpose of this investigation was to determine whether calcium supplementation either before or during exercise attenuates exercise-induced increases in PTH and C-terminal telopeptide of Type I collagen (CTX; a marker of bone resorption). METHODS: Male endurance athletes (n = 20) completed three 35-km cycling time trials under differing calcium supplementation conditions: 1) 1000 mg of calcium 20 min before exercise and placebo during, 2) placebo before and 250 mg of calcium every 15 min during exercise (1000 mg total), or 3) placebo before and during exercise. Calcium was delivered in a 1000-mg·L(-1) solution. Supplementation was double-blinded, and trials were performed in random order. PTH, CTX, bone-specific alkaline phosphatase (BAP; a marker of bone formation), and ionized calcium (iCa) were measured before and immediately after exercise. RESULTS: CTX increased and iCa decreased similarly in response to exercise under all test conditions. When compared with placebo, calcium supplementation before exercise attenuated the increase in PTH (mean ± SE: 55.8 ± 15.0 vs 74.0 ± 14.2 pg·mL(-1), P = 0.04); there was a similar trend (58.0 ± 17.4, P = 0.07) for calcium supplementation during exercise. There were no effects of calcium on changes in CTX, BAP, and iCa. CONCLUSIONS: Calcium supplementation before exercise attenuated the disruption of PTH. Further research is needed to determine the effects of repeated increases in PTH and CTX on bone (i.e., exercise training) and whether calcium supplementation can diminish any exercise-induced demineralization.

A transfer-less, multi-well liquid culture feeding system for screening small molecules that affect the longevity of Caenorhabditis elegans.

Agricultural sciences rely almost entirely on chemical assays to screen the thousands of crop cultivars generated in a crop improvement program for potential human health benefits. This situation exists in part because most animal models are expensive to implement, utilize large amounts of plant material, and require specialized facilities and technical training. A cost-effective, high-throughput animal model to screen crop extracts for small molecules with biological activity related to human health benefits would provide a much-needed resource. Here we introduce a new, relatively high-throughput method incorporating the microscopic Caenorhabditis elegans nematode, which is suitable for screening chemical extracts for bioactivity without the need for robotics. This system was chosen because longevity extension in C. elegans has been previously associated with human health benefits. Through the use of cell culture inserts, C. elegans can be exposed to fresh crop extracts daily throughout their lifespan without mechanical manipulation of the worm, thus minimizing stress and creating an environment suitable for experiments measuring longevity. Additionally, the duration of longevity experiments can be reduced by using type II right censoring in experimental design and survival analyses.

A pilot study evaluating mindfulness-based stress reduction and massage for the management of chronic pain.

BACKGROUND: Mindfulness-based stress reduction (MBSR) and massage may be useful adjunctive therapies for chronic musculoskeletal pain. OBJECTIVE: To evaluate the feasibility of studying MBSR and massage for the management of chronic pain and estimate their effects on pain and mood. DESIGN: Randomized trial comparing MBSR or massage with standard care. PARTICIPANTS: Thirty patients with chronic musculoskeletal pain. MEASUREMENTS: Pain was assessed with 0 to 10 numeric rating scales. Physical and mental health status was measured with the SF-12. RESULTS: The study completion rate was 76.7%. At week 8, the massage group had average difference scores for pain unpleasantness of 2.9 and mental health status of 13.6 compared with 0.13 (P<.05) and 3.9 (P<.04), respectively, for the standard care group. These differences were no longer significant at week 12. There were no significant differences in the pain outcomes for the MBSR group. At week 12, the mean change in mental health status for the MBSR group was 10.2 compared with -1.7 in the standard care group (P<.04). CONCLUSIONS: It is feasible to study MBSR and massage in patients with chronic musculoskeletal pain. Mindfulness-based stress reduction may be more effective and longer-lasting for mood improvement while massage may be more effective for reducing pain.