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Vitamin D supplementation and exercise for improving physical function, body composition and metabolic health in overweight or obese older adults with vitamin D deficiency: a pilot randomized, double-blind, placebo-controlled trial.
Mesinovic, J, Rodriguez, AJ, Cervo, MM, Gandham, A, Xu, CLH, Glavas, C, de Courten, B, Zengin, A, Ebeling, PR, Scott, D
European journal of nutrition. 2023;62(2):951-964
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Overweight and obese older adults are at increased risk for vitamin D deficiency, which is associated with poor metabolic and musculoskeletal health, unfavourable body composition, and attenuated responses to exercise. The aim of this study was to determine whether, compared with placebo, vitamin D3 supplementation (4000 IU/day) taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight or obese older adults with vitamin D deficiency. This study is a 24-week parallel-group, double-blind, placebo-controlled pilot randomised controlled trial. Fifty overweight or obese participants were enrolled for the study, and randomised to either 4000 IU/day of oral vitamin D3 or identical placebo. Results demonstrated that 4000 IU/day vitamin D3 supplementation: - did not affect gait speed when taken with or without exercise, - helped achieve optimal serum 25-hydroxyvitamin D levels and decreased waist circumference (compared with placebo) following multi-modal exercise. - taken alone without exercise reduced stair climb times. However, vitamin D3 supplementation did not have any beneficial effects on other biochemical, body composition or physical function parameters when taken alone or during exercise. Authors conclude that future studies should focus on populations with moderate or severe vitamin D deficiency as they are more likely to experience therapeutic benefits from vitamin D supplementation.
Abstract
PURPOSE Vitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency. METHODS Fifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups. RESULTS Vitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes. CONCLUSION Vitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency.
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Effect of a Hop Extract Standardized in 8-Prenylnaringenin on Bone Health and Gut Microbiome in Postmenopausal Women with Osteopenia: A One-Year Randomized, Double-Blind, Placebo-Controlled Trial.
Lecomte, M, Tomassi, D, Rizzoli, R, Tenon, M, Berton, T, Harney, S, Fança-Berthon, P
Nutrients. 2023;15(12)
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Osteoporosis is a bone condition characterized by weakened and brittle bones, leading to an increased risk of fractures. Oestrogens play a vital role in maintaining bone health, whereby oestrogen deficiency elevates the risk of osteoporosis and fractures, particularly in menopausal women due to the decline in oestrogen levels. Phytoestrogens, plant-derived compounds capable of interacting with human oestrogen receptors, have presented an intriguing non-pharmaceutical avenue for preventing bone loss. Other phytoestrogens have received some attention in the field, however, limited human research exists on prenylflavonoids, a phytoestrogens found in hops (Humulus lupulus). This randomized, double-blinded, placebo-controlled trial aimed to investigate the effects of a year-long supplementation of standardised hop extract (8-PN) Lifenol® on bone mineral density in postmenopausal women. Additionally, the study explored potential mechanisms, particularly focusing on changes in gut bacteria. Notably, gut bacteria play a role in bone metabolism and the pathogenesis of osteoporosis. They are also, along with the liver, responsible for converting hops phenols into active phytoestrogenic compounds. The trial was completed by 95 postmenopausal, women with Osteopenia aged 50 to 85. They all received calcium and vitamin D3 tablets in addition either a hop extract (100mcg) or a placebo for 48 weeks. Changes were monitored using DXA scans for bone mineral density (BMD) and bone metabolism, blood samples for markers for bone health, a quality of life questionnaire, gut microbiome testing, and tests for short-chain fatty acid (SCFA) levels. In conclusion, the intake of hop extract confirmed a previously observed trend of a slight increase in total bone mineral density (BMD), in addition to the benefits linked to calcium and vitamin D supplementation. Although there were no significant changes in the composition of gut bacteria and SCFA levels, the hop extract candidates had a higher abundance of specific genera associated with total body BMD, suggesting a potential positive impact. Larger studies are required to validate these findings.
Abstract
Estrogen deficiency increases the risk of osteoporosis and fracture. The aim of this study was to investigate whether a hop extract standardized in 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve bone status of osteopenic women and to explore the gut microbiome roles in this effect. In this double-blind, placebo-controlled, randomized trial, 100 postmenopausal, osteopenic women were supplemented with calcium and vitamin D3 (CaD) tablets and either a hop extract (HE) standardized in 8-PN (n = 50) or a placebo (n = 50) for 48 weeks. Bone mineral density (BMD) and bone metabolism were assessed by DXA measurements and plasma bone biomarkers, respectively. Participant's quality of life (SF-36), gut microbiome composition, and short-chain fatty acid (SCFA) levels were also investigated. In addition to the CaD supplements, 48 weeks of HE supplementation increased total body BMD (1.8 ± 0.4% vs. baseline, p < 0.0001; 1.0 ± 0.6% vs. placebo, p = 0.08), with a higher proportion of women experiencing an increase ≥1% compared to placebo (odds ratio: 2.41 ± 1.07, p < 0.05). An increase in the SF-36 physical functioning score was observed with HE versus placebo (p = 0.05). Gut microbiome α-diversity and SCFA levels did not differ between groups. However, a higher abundance of genera Turicibacter and Shigella was observed in the HE group; both genera have been previously identified as associated with total body BMD. These results suggest that an 8-PN standardized hop extract could beneficially impact bone health of postmenopausal women with osteopenia.
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A 2-yr Randomized Controlled Trial on Creatine Supplementation during Exercise for Postmenopausal Bone Health.
Chilibeck, PD, Candow, DG, Gordon, JJ, Duff, WRD, Mason, R, Shaw, K, Taylor-Gjevre, R, Nair, B, Zello, GA
Medicine and science in sports and exercise. 2023;55(10):1750-1760
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Osteoporosis is a bone disease that gradually develops when bone mineral density (BMD) or bone mass decreases and the quality of bone is impaired. This randomised controlled trial conducted over 2 years wanted to test the effects of creatine monohydrate supplementation on BMD at several bone sites during a supervised resistance training and walking program in post menopausal women. 120 were randomly allocated to creatine and 117 to placebo. All participants received a daily supplement of 500 mg of calcium and 10 μg -400 IU of vitamin D. The researchers were particularly interested in finding out whether the creatine group showed improved (BMD) at the femoral neck, lower spine and upper thigh bone also known as the proximal femur which connects the hip joint. Bone density scans, dual-energy X-ray’s and ultrasounds were used to measure BMD and assess areas of bone. Falls and fractures were recorded for a total of 3 years. Dietary intake and physical activity outside of study requirements was assessed using food frequency and exercise questionnaires. Fasting blood and urine analyses along with 24-h urine analysis were taken. The authors conclude that creatine supplementation during a resistance training and walking program had no effect on BMD at the femoral neck, total hip, or lower spine. They further acknowledge relatively low compliance with the creatine supplements, and exercise protocols, along with a high drop out rate. Further studies of larger sample sizes are needed.
Abstract
PURPOSE Our purpose was to examine the effects of 2 yr of creatine monohydrate supplementation and exercise on bone health in postmenopausal women. METHODS Two hundred and thirty-seven postmenopausal women (mean age, 59 yr) were randomized to receive creatine (0.14 g·kg -1 ·d -1 ) or placebo during a resistance training (3 d·wk -1 ) and walking (6 d·wk -1 ) program for 2 yr. Our primary outcome was the femoral neck bone mineral density (BMD), with lumbar spine BMD and proximal femur geometric properties as the secondary outcomes. RESULTS Compared with placebo, creatine supplementation had no effect on BMD of the femoral neck (creatine: 0.725 ± 0.110 to 0.712 ± 0.100 g·cm -2 ; placebo: 0.721 ± 0.102 to 0.706 ± 0.097 g·cm -2 ), total hip (creatine: 0.879 ± 0.118 to 0.872 ± 0.114 g·cm -2 ; placebo: 0.881 ± 0.111 to 0.873 ± 0.109 g·cm -2 ), or lumbar spine (creatine: 0.932 ± 0.133 to 0.925 ± 0.131 g·cm -2 ; placebo: 0.923 ± 0.145 to 0.915 ± 0.143 g·cm -2 ). Creatine significantly maintained section modulus (1.35 ± 0.29 to 1.34 ± 0.26 vs 1.34 ± 0.25 to 1.28 ± 0.23 cm 3 (placebo), P = 0.0011), predictive of bone bending strength, and buckling ratio (10.8 ± 2.6 to 11.1 ± 2.2 vs 11.0 ± 2.6 to 11.6 ± 2.7 (placebo), P = 0.011), predictive of reduced cortical bending under compressive loads, at the narrow part of the femoral neck. Creatine reduced walking time over 80 m (48.6 ± 5.6 to 47.1 ± 5.4 vs 48.3 ± 4.5 to 48.2 ± 4.9 s (placebo), P = 0.0008) but had no effect on muscular strength (i.e., one-repetition maximum) during bench press (32.1 ± 12.7 to 42.6 ± 14.1 vs 30.6 ± 10.9 to 41.4 ± 14 kg (placebo)) and hack squat (57.6 ± 21.6 to 84.4 ± 28.1 vs 56.6 ± 24.0 to 82.7 ± 25.0 kg (placebo)). In the subanalysis of valid completers, creatine increased lean tissue mass compared with placebo (40.8 ± 5.7 to 43.1 ± 5.9 vs 40.4 ± 5.3 to 42.0 ± 5.2 kg (placebo), P = 0.046). CONCLUSIONS Two years of creatine supplementation and exercise in postmenopausal women had no effect on BMD; yet, it improved some bone geometric properties at the proximal femur.
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Effects of an 18-month community-based, multifaceted, exercise program on patient-reported outcomes in older adults at risk of fracture: secondary analysis of a randomised controlled trial.
Talevski, J, Gianoudis, J, Bailey, CA, Ebeling, PR, Nowson, CA, Hill, KD, Sanders, KM, Daly, RM
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2023;34(5):891-900
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Fragility fractures are associated with both personal and healthcare system burdens. It is well established that bone loss leading to osteopenia or osteoporosis results in increased risk of fractures. Prescription of pharmacological agents is commonly used as first-line treatment. The aim of this study was to evaluate the effect of the Osteo-cise: Strong Bones for Life program on the patient-reported outcomes including health related quality of life (HRQoL), osteoporosis knowledge and osteoporosis attitudes and beliefs. This study is a secondary analysis of an 18-month randomised controlled trial in which participants were randomly allocated to either the community-based Osteo-cise: Strong Bones for Life program (‘Osteo-cise’) or a standard care control group. Results showed that there were no significant effects on HRQoL, osteoporosis knowledge or osteoporosis attitudes and beliefs compared with usual care. However, per protocol analyses revealed that those most adherent to exercise training did experience significant improvements in both HRQoL and osteoporosis knowledge compared with usual care. Authors concluded that their findings highlight the need to identify strategies that promote long-term adherence to multifaceted exercise programs in community-dwelling older adults.
Abstract
UNLABELLED This study identified that an 18-month community-based, multifaceted, exercise program consisting of resistance, weight-bearing impact, and balance/mobility training combined with osteoporosis education and behavioural support can improve health-related quality of life (HRQoL) and osteoporosis knowledge in older adults at risk of fracture, but only for those adherent to the exercise regime. PURPOSE To evaluate the effects of an 18-month community-based exercise, osteoporosis education and behaviour change program (Osteo-cise: Strong Bones for Life) on HRQoL, osteoporosis knowledge and osteoporosis health beliefs. METHODS This was a secondary analysis of an 18-month randomised controlled trial in which 162 older adults aged ≥ 60 years with osteopenia or increased falls/fracture risk were randomized to the Osteo-cise program (n = 81) or control group (n = 81). The program consisted of progressive resistance, weight-bearing impact and balance training (3 days/week); osteoporosis education to facilitate self-management of musculoskeletal health and behavioural support to enhance adherence to exercise. HRQoL, osteoporosis knowledge and osteoporosis health beliefs were assessed using the EuroQoL questionnaire (EQ-5D-3L), Osteoporosis Knowledge Assessment Tool and Osteoporosis Health Belief Scale, respectively. RESULTS Overall, 148 participants (91%) completed the trial. Mean exercise adherence was 55% and mean attendance for the three osteoporosis educational sessions ranged from 63-82%. After 12 and 18 months, there were no significant effects of the Osteo-cise program on HRQoL, osteoporosis knowledge or health beliefs relative to controls. Per protocol analyses (≥ 66% exercise adherence; n = 41) revealed a significant net benefit in EQ-5D-3L utility for the Osteo-cise group relative to controls after 12 months (P = 0.024) and 18 months (P = 0.029) and a significant net improvement in osteoporosis knowledge scores at 18 months (P = 0.014). CONCLUSION This study supports the importance of adherence to exercise regimes, as adherence to the Osteo-cise: Strong Bones for Life program was associated with improvements in HRQoL and osteoporosis knowledge in older adults at increased risk for falls and fractures. TRIAL REGISTRATION NUMBER ACTRN12609000100291.
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Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial.
Wong, RH, Thaung Zaw, JJ, Xian, CJ, Howe, PR
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2020;35(11):2121-2131
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Osteoporosis is a silent disease characterized by progressive deterioration of bone tissue, gradually compromising bone strength. Phytoestrogens such as soy isoflavones and resveratrol have structural similarity to oestrogen and can bind to oestrogen receptors to exert a multitude of benefits for which oestrogen is responsible, and they have attracted interest as potential bone health therapies in oestrogen-deficient postmenopausal women. The aim of this study was to investigate whether (a) resveratrol has beneficial effects on bone mineral density (BMD) in postmenopausal women, and (b) there is any potential interaction between resveratrol and vitamin D and/or calcium supplements. The Resveratrol for Healthy Aging in Women trial is a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention. This study focuses on outcomes for bone health and biomarkers of bone metabolism. Results show that low-dose resveratrol supplementation significantly improved BMD of the lumbar spine and femoral neck. It also reduced the bone resorption marker, CTX, in postmenopausal women. The magnitude of benefit was greater for women with suboptimal bone metabolism. Authors conclude that improvement of the microcirculation may be an additional area to target in preventing postmenopausal osteoporosis.
Abstract
Resveratrol, a naturally occurring polyphenol in red grapes and berries, can act as a phytoestrogen. It has been shown to improve both systemic and cerebral circulatory functions, possibly through activation of endothelial estrogen receptors. in vitro and in vivo studies in rodent models also indicate a bone-protective role for resveratrol, particularly in ovariectomized rat models that mimic postmenopausal osteoporosis caused by estrogen deficiency. Hypothesizing a circulatory benefit of resveratrol in bone tissue, we investigated whether resveratrol supplementation could improve bone health in postmenopausal women. The Resveratrol for Healthy Aging in Women (RESHAW) trial was a 24-month randomized, double-blind, placebo-controlled, two-period crossover intervention conducted to evaluate the effects of resveratrol (75 mg twice daily) on cognition, cerebrovascular function, bone health, cardiometabolic markers, and well-being in postmenopausal women. After 12 months of supplementation with resveratrol versus placebo, there were positive effects on bone density in the lumbar spine (+0.016 ± 0.003 g/cm2 ) and neck of femur (+0.005 ± 0.002 g/cm2 ), which were accompanied by a 7.24% reduction in C-terminal telopeptide type-1 collagen levels, a bone resorption marker, compared with placebo. The increase in bone mineral density in the femoral neck resulted in an improvement in T-score (+0.070 ± 0.018) and a reduction in the 10-year probability of major and hip fracture risk. The magnitude of improvement was higher in women with poor bone health biomarker status. Importantly, the improvement in femoral neck T-score with resveratrol correlated with improvement in perfusion. Our subanalysis also revealed that the bone-protective benefit of resveratrol was greater in participants who supplemented with vitamin D plus calcium. Regular supplementation with 75 mg of resveratrol twice daily has the potential to slow bone loss in the lumbar spine and femoral neck, common fracture sites in postmenopausal women without overt osteoporosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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Role of Calcium and Low-Fat Dairy Foods in Weight-Loss Outcomes Revisited: Results from the Randomized Trial of Effects on Bone and Body Composition in Overweight/Obese Postmenopausal Women.
Ilich, JZ, Kelly, OJ, Liu, PY, Shin, H, Kim, Y, Chi, Y, Wickrama, KKAS, Colic-Baric, I
Nutrients. 2019;11(5)
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A woman’s menopausal years are believed to bring about weight gain due to various biological mechanisms, such as depletion of oestrogen. Many women undertake weight loss diets, in an attempt to control the weight gain, and although weight loss can reduce the risk factors for metabolic and cardiovascular disease etc, it can also lead to accelerated loss bone density and muscle mass. The objective of this study was to investigate whether by complementing a low-calorie diet with 4 to 5 servings of low-fat dairy foods per day and/or supplementing with calcium and vitamin D supplements would aid weight loss and preserve either/both bone and muscle mass. The study was conducted on 189 early postmenopausal, obese women. It was a randomized, placebo-controlled clinical trial conducted over 6 months. Researchers found that results were better for the participants on the low-fat dairy foods and those supplementing with calcium and vitamin D when compared to the placebo group (who only had placebo pills). They suggest that when embarking on a weight loss program it is beneficial to include 4 to 5 servings of low-fat dairy foods each day and take calcium and vitamin D supplements will have a positive impact on weight loss, bone density and muscle mass in post-menopausal women.
Abstract
Several studies have investigated the possibility of dairy foods and calcium (Ca) mediating weight and body composition, but a consensus has not been reached. We aimed to investigate weight-loss-related outcomes during intervention with low-fat dairy foods or Ca + vitamin D supplements, both as complements to hypocaloric diets. Overweight/obese Caucasian, early-postmenopausal women (n = 135) were recruited for a 6 month energy-restricted weight loss study complemented with either low-fat dairy foods (D; 4-5 servings/day), or Ca + vitamin D supplements (S); both to amount a total of ~1500 mg/day and 600 IU/day of Ca and vitamin D, respectively, or placebo pills (C). Bone mineral density (BMD) and lean and fat tissue were measured by Lunar iDXA. Serum and urinary markers of bone turnover were analyzed. Diet and physical activity were assessed with 3-day records. Participants on average lost ~4%, ~3%, and ~2% of body weight, fat, and lean tissue, respectively. The significantly better outcomes were noticed in participants in the D group regarding body composition (fat loss/lean tissue preservation) and in participants in the S group regarding the BMD outcomes, compared to those in the C group. Therefore, increasing low-fat dairy foods to 4-5 servings/day and/or increasing Ca & vitamin D intake by supplements (in those who are at the borderline dietary intake) may be beneficial for weight loss/maintenance and may lead to more favorable bone and body composition outcomes in postmenopausal women during moderate weight loss.
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Temporal Change in Biomarkers of Bone Turnover Following Late Evening Ingestion of a Calcium-Fortified, Milk-Based Protein Matrix in Postmenopausal Women with Osteopenia.
Hettiarachchi, M, Cooke, R, Norton, C, Jakeman, P
Nutrients. 2019;11(6)
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Low bone mineral density (bone mineral content) and a diminution in bone quality (bone microarchitecture) are attributes of risk of fracture in people with osteopenia. The aim of this study was to investigate the effect of feeding a milk protein-based matrix (MBPM) fortified with calcium and vitamin D prior to bedtime on the biomarkers of bone remodelling in postmenopausal women with osteopenia. The study is a block-randomised cross-over design which recruited a sample of 41 postmenopausal women aged 50 to 70 years. Out of the 24 participants classified as osteopenic, 16 volunteers progressed to the RCT and randomly assigned to receive either a milk-based protein supplement (MBPM) or an isoenergetic, control. Results indicate that a dairy-based protein supplement fortified with calcium (MBPM) fed at bedtime has a potent effect on nocturnal rates of bone resorption in healthy osteopenic postmenopausal women. Furthermore, the synergistic, pluripotent quality of a milk-based protein matrix and timing of ingestion to the nocturnal, peak rate of bone remodelling transiently depressed bone turnover. Authors conclude that a late-evening supplement of calcium-fortified milk protein affects a beneficial decrease in the homeostatic rate of bone remodelling in persons at risk of degenerative bone disease.
Abstract
The diurnal rhythm of bone remodeling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of bedtime ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or maltodextrin (CON) on acute (0-4 h) blood and 24-h urinary change in biomarkers of bone remodeling in postmenopausal women with osteopenia. In CON, participants received 804 ± 52 mg calcium, 8.2 ± 3.2 µg vitamin D and 1.3 ± 0.2 g/kg BM protein per day. MBPM increased calcium intake to 1679 ± 196 mg, vitamin D to 9.2 ± 3.1 µg and protein to 1.6 ± 0.2 g/kg BM. Serum C-terminal cross-linked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), and urinary N-telopeptide cross-links of type I collagen (NTX), pyridinoline (PYD) and deoxypyridinoline (DPD) was measured. Analyzed by AUC and compared to CON, a -32% lower CTX (p = 0.011, d = 0.83) and 24% (p = 0.52, d = 0.2) increase in P1NP was observed for MBPM. Mean total 24 h NTX excreted in MBPM was -10% (p = 0.035) lower than CON. Urinary PYD and DPD were unaffected by treatment. This study demonstrates the acute effects of bedtime ingestion of a calcium-fortified, milk-based protein matrix on bone remodeling.