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Evaluating adherence, tolerability and safety of oral calcium citrate in elderly osteopenic subjects: a real-life non-interventional, prospective, multicenter study.
Rondanelli, M, Minisola, S, Barale, M, Barbaro, D, Mansueto, F, Battaglia, S, Bonaccorsi, G, Caliri, S, Cavioni, A, Colangelo, L, et al
Aging clinical and experimental research. 2024;36(1):38
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The occurrence of fractures and osteoporosis are significant concerns in elderly adults, as ageing remains one of the primary risk factors for these conditions. While the incidence of fracture and risk may vary, the incidence of fragility fractures significantly increases with advancing age, particularly after the age of 50 years. This study's aim was to evaluate the adherence, tolerability, and safety of calcium citrate administration in an "outpatient" population in routine clinical practice. This study was a non-interventional, prospective, multicentre study. Two-hundred and sixty-eight individuals (comprised 245 females (91.4%) and 23 males (8.6%)) were enrolled. Results showed a high rate of adherence to calcium citrate supplementation over a one-year period in osteopenic elderly subjects. Additionally, the incidence of adverse reactions was low (3.9%), further emphasizing the tolerability of calcium citrate. Authors concluded that future studies designed to assess the long-term impact of calcium citrate supplementation on hard endpoints, such as bone density, fractures/falls, quality of life measures and adherence are needed.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The occurrence of fractures and osteoporosis are significant concerns in older adults, as ageing remains one of the primary risk factors for this condition.
- Calcium supplementation, usually with vitamin D, is a recommended complement to other specific pharmacological treatments of osteoporosis.
- This non-interventional, prospective multicentre study suggests a 91% adherence to calcium citrate supplementation over one year in elderly osteopenic patients with generally good (80%) tolerability and 4% reporting gastrointestinal adverse effects.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A non-interventional, prospective multicentre study was conducted to evaluate the adherence, safety, and tolerability of calcium citrate supplementation in elderly osteopenic subjects.
Method:
A total of 231 Caucasian female (91%) and male (8%) participants with a median age of 70 received 500mg of calcium citrate supplementation daily for one year. Adherence was assessed based on tolerability, compliance, and persistence. Safety evaluations included monitoring of adverse reactions (ARs), physical examinations, and clinical laboratory evaluations.
Results
A total of 222 out of 231 participants (96%) completed the study. Nine subjects did not return for assessments or complete their diaries.
The primary and secondary findings of this study were as follows:
- An average adherence of 91% of oral calcium citrate supplementation was observed which was higher than the reported reference rate of 57% (p = 0.0179).
- Subjects with adherence <80% experienced a higher frequency of adverse events compared to those with adherence >80% (32/77; 42% vs 16/145%, (p = 0.0001).
- Gastrointestinal ARs were the most commonly reported, with constipation comprising 50% of all reported ARs.
- Reductions in systolic (130.7 ± 16.9 mmHg to 127.9 ± 14.5 mmHg) (p = 0.0102) and diastolic blood pressure 79.5 ± 8.7 mmHg to 77.4 ± 8.6 mmHg (baseline to V2) (p = 0.0116) were observed from baseline to the second visit.
- Positive changes were also noted in nutritional status (p = 0.0116), circulatory system disorders (p = 0.0001), and muscles/skeleton disorders (p = 0.0067) from baseline to post-baseline visit.
Conclusion:
This study revealed a 91% adherence to calcium citrate supplementation over one year in older adults with osteopenia, Additionally, the 4% incidents of ARs reported were related to gastrointestinal disorders.
Clinical practice applications:
- The prevalence of osteoporosis rises as individuals age, with approximately 10% of women at 60 years, 20% at 70 years, and 40% at 80 years.
- Calcium supplementation, usually with vitamin D, is a recommended complement to other specific pharmacological treatments of osteoporosis.
- The safety of calcium supplements remains controversial regarding an increased risk of cardiovascular events. Therefore, it is essential to investigate the safety profile of calcium in these populations.
- This study reported adherence, tolerability, and safety of calcium citrate supplementation in osteopenic elderly patients with 4% of patients reporting gastrointestinal adverse effects.
Considerations for future research:
- This study was conducted on 91% Caucasian females and 8% males with a mean age of 70 years therefore, there is a need to include more male and Asian participants from various age groups in further research.
- Future studies are needed to assess the long-term impact of calcium citrate supplementation on bone density, fractures, and quality of life.
Abstract
BACKGROUND Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays a crucial role in improving bone health, reducing fracture risk, and supporting overall skeletal strength in this vulnerable population. However, there is conflicting evidence on the safety of calcium supplements in elderly individuals. AIM: The aim of this study was to evaluate the adherence, safety and tolerability of calcium citrate supplementation in elderly osteopenic subjects. METHODS In this non-interventional, prospective, multicenter study, subjects received daily 500 mg calcium citrate supplementation for up to one year. Adherence was calculated based on compliance and persistence. Safety was assessed through adverse reactions (ARs), deaths, and clinical laboratory evaluations. RESULTS A total of 268 Caucasian subjects (91.4% female, mean age 70 ± 4.5 years) participated in the study. Mean adherence to treatment was 76.6 ± 29.5% and half of subjects had an adherence of 91% and ~ 33% of participants achieved complete (100%) adherence. ARs were reported by nine (3.9%) subjects, primarily gastrointestinal disorders, with no serious ARs. The frequency of all adverse events (including ARs) was significantly higher in subjects with adherence of < 80% (41.6%; 32/77) vs. those with adherence ≥ 80% (11%; 16/145, p < 0.0001). Both systolic and diastolic blood pressure decreased from baseline to follow-up visit (change of -2.8 ± 13.9 mmHg, p = 0.0102 and -2.1 ± 10.4 mmHg, p = 0.0116, respectively). CONCLUSION This study demonstrated favorable adherence to calcium citrate supplementation in elderly osteopenic subjects. The occurrence of ARs, though generally mild, were associated with lower adherence to calcium supplementation.
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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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The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial.
Moore, AE, Dulnoan, D, Voong, K, Ayis, S, Mangelis, A, Gorska, R, Harrington, DJ, Tang, JCY, Fraser, WD, Hampson, G
Archives of osteoporosis. 2023;18(1):83
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Osteoporosis is the most common bone disease leading to weakening of the bones and is particularly prevalent in postmenopausal women. Osteoporosis-related fractures cause severe pain and disability, and strains on the healthcare systems. The typical treatment in postmenopausal osteoporosis involves the prescription of oral bisphosphonate medications. An important regulator in bone health is Vitamin K. Low vitamin K levels and intake are linked to reduced bone mineral density (BMD) and increased fractures. Some findings suggest that a combination treatment of bisphosphonate and vitamin K2 (MK-4) may enhance treatment efficacy and hence this randomised placebo-controlled trial sought further evidence. The study enrolled 105 women, between 55–85 years old, with osteoporosis and low vitamin K status. The women received either vitamin K1 (1 mg/day), vitamin K2 arm (MK-4; 45 mg/day) or a placebo for 18 months, alongside oral bisphosphonate and calcium and/or vitamin D treatment. Outcomes were measured in bone mineral density (BMD), structural characteristics of the hips (hip geometry) and bone turnover markers (BTMs). 91 candidates completed the trial. The results showed that the combination of vitamin K1 or MK-4 and oral bisphosphonate did not lead to significant improvement in bone mineral density or bone turnover. However it showed significant changes in hip geometry in the vitamin K1 group, suggesting a potential synergy here. Whereby there were positive trends in BMD too with vitamin K1 supplementation, the results did not reach significance. In the discussion the authors review the outcomes in the context of existing research, suggesting that perhaps a longer duration of treatment with vitamin K may be required to boost mineralisation and BMD outcomes. The effect of MK-4 on bone cells may also have been hindered by its poor bioavailability and the suppression of bone remodelling caused by long-term bisphosphonate therapy. Larger and longer-term studies are needed to confirm the effects of Vitamin K on hip remodelling and prevention of bone fractures and help clarify the mixed results in existing research.
Abstract
UNLABELLED This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. PURPOSE Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment. METHODS We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed. RESULTS Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03). CONCLUSION The addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed. TRIAL REGISTRATION The study was registered at Clinicaltrial.gov:NCT01232647.
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Effects of iron supplementation on neural indices of habituation in Bangladeshi children.
Larson, LM, Feuerriegel, D, Hasan, MI, Braat, S, Jin, J, Tipu, SMU, Shiraji, S, Tofail, F, Biggs, BA, Hamadani, JD, et al
The American journal of clinical nutrition. 2023;117(1):73-82
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Adversity during early life, including malnutrition, may influence the long-term cognitive development of children. Micronutrients, especially iron, may play a critical role in the developing infant brain The aim of this study was to determine the effects of supplementation with iron syrup and iron containing multiple micronutrient powders (MNPs) on neural indices of habituation in Bangladeshi children. This neurocognitive substudy was nested within the Benefits and Risks of Iron Supplementation in Children (BRISC) trial. BRISC was a 3-arm, double-blind, double-dummy, individual randomised, superiority trial. Children were randomly assigned to 1 of the 3 arms using a 1:1:1 allocation. Results showed that iron supplementation (provided through 2 different modes) did not affect neural indices of habituation. There wasn’t any identification of treatment effects for any of the outcomes measured, despite finding improvements in haemoglobin and ferritin concentrations for children given iron syrup or MNPs. Authors conclude that despite established links between iron availability and neurophysiological development, increased iron availability in children under one year of age does not lead to measurable changes in neural indices of habituation.
Abstract
BACKGROUND Iron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear. OBJECTIVE We aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs). METHODS This substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.5 mg iron), multiple micronutrient powders (MNPs) (including 12.5 mg iron), or placebo. Children were assessed after 3 mo of intervention (mo 3) and 9 mo thereafter (mo 12). The neurocognitive substudy comprised a randomly selected subset of children from the main trial. Brain activity elicited during an auditory roving oddball task was recorded using electroencephalography to provide an index of habituation. The differential response to a novel (deviant) compared with a repeated (standard) sound was examined. The primary outcome was the amplitude of the mismatch response (deviant minusstandard tone waveforms) at mo 3. Secondary outcomes included the deviant and standard tone-evoked amplitudes, N2 amplitude differences, and differences in mean amplitudes evoked by deviant tones presented in the second compared with first half of the oddball sequence at mo 3 and 12. RESULTS Data were analyzed from 329 children at month 3 and 363 at mo 12. Analyses indicated no treatment effects of iron interventions compared with placebo on the amplitude of the mismatch response (iron syrup compared with placebo: mean difference (MD) = 0.07μV [95% CI: -1.22, 1.37]; MNPs compared with placebo: MD = 0.58μV [95% CI: -0.74, 1.90]) nor any secondary ERP outcomes at mo 3 or 12, despite improvements in hemoglobin and ferritin concentrations from iron syrup and MNPs in this nested substudy. CONCLUSION In Bangladeshi children with >40% anemia prevalence, iron or MNP interventions alone are insufficient to improve neural indices of habituation. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.
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Macronutrient composition and its effect on body composition changes during weight loss therapy in patients with non-alcoholic fatty liver disease: Secondary analysis of a randomized controlled trial.
Lindqvist, C, Holmer, M, Hagström, H, Petersson, S, Tillander, V, Brismar, TB, Stål, P
Nutrition (Burbank, Los Angeles County, Calif.). 2023;110:111982
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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and it is closely linked to overweight and obesity. Weight loss leads to an amelioration of NAFLD, which preferably should lead to loss of fat mass while maintaining lean body mass. The aim of this study was to examine if different diet compositions during weight loss therapy were associated with different reductions in abdominal fat mass compared with standard weight loss advice given by a physician. This study was a secondary analysis of data collected in an open-label, randomised controlled trial. The trial examined the effect of two popular weight loss diets, calorie-restricted intermittent fasting (5:2) and a calorie-restricted low-carbohydrate high-fat (LCHF) diet, compared with standard of care (SOC) on reduction in liver fat in 74 persons with NAFLD. Results show that a dietitian-led nutrition counselling treatment with an LCHF or 5:2 diet reduced weight to a higher extent than physician-supported SOC during a 12-wk treatment. Improvements in most of the variables related to body composition parameters and metabolic function were found, independent of dietary composition. Furthermore, during weight loss, visceral fat was mobilized to a greater extent than subcutaneous fat. Authors conclude that further studies are needed with a focus on the effect of diet composition on body composition changes during weight loss.
Abstract
OBJECTIVES Dietary composition may affect body composition during weight loss therapy. We tested the hypothesis of whether dietary macronutrient composition influences the reduction of total abdominal adipose tissue, subcutaneous adipose tissue (SAT), or visceral adipose tissue (VAT) during weight loss. METHODS Dietary macronutrient composition and body composition were analyzed as a secondary outcome of a randomized controlled trial of 62 participants with non-alcoholic fatty liver disease. Patients were randomly assigned to a calorie-restricted intermittent fasting (5:2), calorie-restricted low-carbohydrate high-fat (LCHF), or healthy lifestyle advice (standard-of-care) diet in a 12-wk intervention phase. Dietary intake was assessed by self-reported 3-d food diaries and by characterization of total plasma fatty acid profile. Percentage of energy intake (E%) from different macronutrients was calculated. Body composition was assessed by magnetic resonance imaging and anthropometric measurements. RESULTS The macronutrient composition differed significantly between the 5:2 (fat 36 E% and carbohydrates 43 E%) and the LCHF (fat 69 E% and carbohydrates 9 E%) groups (P < 0.001). Weight loss was similar in the 5:2 and LCHF groups (-7.2 [SD = 3.4] kg versus 8.0 [SD = 4.8] kg; P = 0.44) and significantly larger than for standard of care (-2.5 kg [SD = 2.3]; P < 0.001). The volume of total abdominal fat, adjusted for height, decreased on average by 4.7% (standard of care), 14.3% (5:2), and 17.7% (LCHF), with no significant differences between the 5:2 and LHCF groups (P = 0.32). VAT and SAT, adjusted for height, decreased on average by 17.1% and 12.7% for 5:2, respectively, and by 21.2% and 17.9% for LCHF, with no significant group differences (VAT [P = 0.16] and SAT [P = 0.10]). VAT was mobilized to a greater extent than SAT in all diets. CONCLUSIONS The 5:2 and LCHF diets had similar effects on changes in intraabdominal fat mass and anthropometrics during weight loss. This might indicate that overall weight loss is more important than diet composition to achieve changes in total abdominal adipose tissue, VAT, or SAT. The results of the present study suggest that there is a need for further studies on the effect of diet composition on body composition changes during weight loss therapy.
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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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Muscle Mass Changes After Daily Consumption of Protein Mix Supplemented With Vitamin D in Adults Over 50 Years of Age: Subgroup Analysis According to the Serum 25(OH)D Levels of a Randomized Controlled Trial.
Kang, Y, Kim, N, Lee, Y, An, X, Chung, YS, Park, YK
Clinical nutrition research. 2023;12(3):184-198
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Sarcopenia is an age-related decrease in muscle mass and strength and increases the risk of falls and death. Protein intake and vitamin D are important for the maintenance of muscle mass, and the amino acid leucine plays a role in the regulation of muscle protein turnover. The aim of this 12-week double-blind, randomised, placebo-controlled trial was to evaluate the efficacy of a supplement containing protein, vitamin D, leucine and calcium for maintaining muscle mass, strength and physical functioning in healthy Koreans aged 50-80 years. Increases in muscle mass were seen in those with low vitamin D levels (< 30 ng/ml) but not in those with higher vitamin D levels. No differences were observed in muscle strength and physical functioning. The authors concluded that a supplement containing protein, including high levels of leucine, vitamin D and calcium may be of benefit for muscle mass to middle-aged and older adults with low vitamin D levels.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Consider supplementing protein in combination with leucine, vitamin D and calcium in middle-aged or older adults with insufficient vitamin D levels for prevention of sarcopenia.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
- Sarcopenia increases the risk of falls and death
- Protein and vitamin D are important for maintaining muscle mass whilst leucine is involved in regulating muscle protein turnover
- The aim of this study was to evaluate the effects of a supplement containing protein, vitamin D, leucine and calcium on muscle mass, physical functioning, muscle strength, and physical ability in middle-aged and older adults.
Methods
- Double-blind, randomised, placebo-controlled trial, with a duration of 12 weeks. Included 120 healthy Koreans aged 50-80 years
- Participants were assigned to “insufficient” subgroup if vitamin D levels were <30ng/ml and to the “sufficient” subgroup if vitamin D was 30ng/ml or higher
- Intervention: 2.5g powder (containing 20g protein (90% milk/10% soya, incl. 3g leucine), 800 IU vitamin D, 300 mg calcium) mixed into beverage of choice twice a day. Control: isocaloric placebo powder
- Primary outcome: Muscle mass determined by dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA)
- Secondary outcomes: Muscle strength (femoral muscle and grip strength); physical functioning (short physical performance battery (SPPB), International Physical Activity Questionnaire (IPAQ)).
Results
- At baseline, age of participants in the “sufficient” intervention subgroup was higher than that of the “sufficient” control subgroup (p=0.02)
- Increase in vitamin D levels in intervention group relative to control group, in both sufficient and insufficient subgroups (difference in changes between groups 11.5 ng/ml and 13.9 ng/ml, respectively, both p=0.00)
- No difference in change in muscle index as measured by DXA between groups
- In the “insufficient” subgroup, BIA increases in muscle mass were seen when normalised by height (p=0.037) and weight (p=0.05)
- No differences in changes in physical functioning or muscle strength between groups.
Conclusion
- The authors conclude that a supplement containing protein, with high levels of leucine, vitamin D and calcium may be of benefit for muscle mass to middle-aged and older adults with insufficient vitamin D levels.
Clinical practice applications:
- Middle-aged and older adults with insufficient vitamin D levels may gain muscle mass through supplementation of protein, leucine, vitamin D and calcium
- Middle-age and older adults with sufficient vitamin D levels do not appear to benefit from the same intervention.
Considerations for future research:
- Longer-term studies may help identify whether increases in muscle mass lead to improved physical functioning over time
- A study combining supplementation and exercise may help identify additive or synergistic effects.
Abstract
UNLABELLED Early prevention of sarcopenia can be an important strategy for muscle maintenance, but most studies target subjects at slightly pre-sarcopenic state. Our previous paper describes the effect of protein supplements rich in leucine and vitamin D on muscle condition, and in this paper, we performed a sub-analysis to evaluate who benefitted the most in terms of improvement in muscle health. A 12-week randomized clinical trial of 120 healthy adults (aged 50 to 80) assigned to an intervention group (n = 60) or control group (n = 60) were analyzed. Subjects in the intervention group received, twice per day, a protein supplement containing (per serving) 800 IU of vitamin D, 20 g of protein (3 g of total leucine), 300 mg of calcium, 1.1 g of fat, and 2.5 g of carbohydrate. The subjects were classified into 'insufficient' and 'sufficient' groups at 25-hydroxyvitamin D (25[OH]D) value of 30 ng/mL. The skeletal muscle mass index normalized to the square of the skeletal muscle mass (SMM) height (kg/m2) increased significantly in the 'insufficient group' difference value of change between weeks 0 and 12 (Δ1.07 ± 2.20; p = 0.037). The SMM normalized by body weight (kg/kg, %) was higher, but not significantly, in the insufficient group (Δ0.38 ± 0.69; p = 0.050). For people with insufficient (serum 25[OH]D), supplemental intake of protein and vitamin D, calcium, and leucine and adequate energy intake increases muscle mass in middle-aged and older adults and would be likely to exert a beneficial effect on muscle health. TRIAL REGISTRATION Clinical Research Information Service Identifier: KCT0005111.
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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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Acute Effects of Dietary Nitrate on Central Pressure and Endothelial Function in Hypertensive Patients: A Randomized, Placebo-Controlled Crossover Study.
Mattos, S, Cunha, MR, Marques, BC, D El-Rei, J, Baião, DDS, Paschoalin, VMF, Oigman, W, Neves, MF, Medeiros, F
Arquivos brasileiros de cardiologia. 2023;120(1):e20220209
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Eating habits influence several mechanisms involved with cardiovascular risk factors. The inorganic nitrate (NO3‾) content in root vegetables can provide a physiological substrate for the reduction to nitrite (NO2‾), nitric oxide and other metabolic products. The aim of this study was to evaluate the acute effects of dietary NO3‾ intake on blood pressure (BP) and endothelial function in treated hypertensive patients. This study was a randomised, crossover, placebo-controlled study which enrolled thirty-seven hypertensive patients aged between 40 and 70 years, of both genders, in regular use of antihypertensive drugs. Each participant was randomised to the crossover interventions; beetroot juice (BRJ) [rich in inorganic NO3‾] or water. Results show that after a single intake of inorganic NO3‾ there was an attenuation in the peripheral and central BP levels, reduction of ejection duration [the period in the cardiac cycle when the semilunar valves are open and blood is being ejected from the ventricles into the arterial system], increase in subendocardial viability ratio [an arterial stiffness parameter correlated with coronary flow reserve] and improvement of vascular function associated with elevated serum NO3‾ and NO2‾. Authors conclude that the intake of BRJ resulted in acute benefits on vascular parameters in hypertensive individuals, leading to greater subendocardial viability, higher performance in myocardial contraction and improvement in endothelial function.
Abstract
BACKGROUND The diet's inorganic nitrate (NO3-) may provide a physiological substrate for reducing nitrate (NO2-) to NO independent of the endothelium. Studies suggest that inorganic NO3- has beneficial effects on cardiovascular health. OBJECTIVE This study evaluated the acute effects of 500 mL nitrate-rich beetroot juice (BRJ; containing 11.5mmol NO3-) on blood pressure and endothelial function in treated hypertensive patients. METHODS A randomized, placebo-controlled, crossover study was conducted in treated hypertensive patients (n=37; women=62%) who underwent clinical and nutritional evaluation and assessment of central hemodynamic parameters and microvascular reactivity. The significance level was p<0.05. RESULTS The mean age was 59±7 years, and mean systolic and diastolic blood pressures were 142±10/83±9mmHg. There was a significant increase in the subendocardial viability ratio (SEVR; 149±25 vs. 165±30%, p<0.001) and reduction in ejection duration (ED; 37±4 vs. 34±4%, p<0.001) in the beetroot phase but no significant SEVR difference in the control phase. The % increase in perfusion (155 vs. 159 %, p=0.042) was significantly increased in the beetroot phase, which was not observed in the control phase. In the beetroot phase, the change in SEVR showed a significant correlation with the change in the area under the curve of post-occlusive reactive hyperemia (AUC-PORH) (r=0.45, p=0.012). The change in ED showed a significant correlation with the post-intervention perfusion peak (r=-0.37, p=0.031) and AUC-PORH (r=-0.36, p=0.046). CONCLUSIONS The acute ingestion of BRJ by hypertensive patients resulted in an improvement of endothelial function, which was associated with higher subendocardial viability and performance in myocardial contraction. FUNDAMENTO O nitrato inorgânico (NO3–) da dieta pode fornecer substrato fisiológico para reduzir o nitrito (NO2–) a óxido nítrico (NO) independente do endotélio. Estudos sugerem que o NO3– inorgânico tem efeitos benéficos na saúde cardiovascular. OBJETIVOS Este estudo avaliou os efeitos agudos de 500 mL de suco de beterraba rico em nitrato (SB; contendo 11,5mmol NO3–) na pressão arterial e na função endotelial em pacientes hipertensos tratados. MÉTODOS Estudo cruzado, randomizado, controlado por placebo foi realizado em pacientes hipertensos tratados (n=37; mulheres=62%) que foram submetidos à avaliação clínica e nutricional, avaliação dos parâmetros hemodinâmicos centrais e reatividade microvascular. O nível de significância foi p<0,05. RESULTADOS A média de idade foi 59±7 anos e das pressões sistólica e diastólica foi de 142±10/83±9 mmHg. Houve aumento significativo na taxa de viabilidade subendocárdica (RVSE; 149±25 vs. 165±30%, p<0,001) e redução na duração da ejeção (DE; 37±4 vs. 34±4%, p<0,001) na fase beterraba, mas nenhuma diferença significativa de RVSE na fase controle. O % de aumento na perfusão (155 vs. 159%, p=0,042) cresceu significativamente na fase beterraba, o que não foi observado na fase controle. Na fase beterraba, a alteração da RVSE apresentou correlação significativa com a alteração da área sob a curva de hiperemia reativa pós-oclusiva (ASC-HRPO) (r=0,45, p=0,012). A mudança na DE mostrou uma correlação significativa com pico de perfusão pós-intervenção (r=-0,37, p=0,031) e ASC-HRPO (r=-0,36, p=0,046). CONCLUSÃO: A ingestão aguda de SB por pacientes hipertensos resultou em melhora da função endotelial, que foi associada à maior viabilidade subendocárdica e desempenho na contração miocárdica. BACKGROUND The diet’s inorganic nitrate (NO3–) may provide a physiological substrate for reducing nitrate (NO2–) to NO independent of the endothelium. Studies suggest that inorganic NO3–has beneficial effects on cardiovascular health. OBJECTIVE This study evaluated the acute effects of 500 mL nitrate-rich beetroot juice (BRJ; containing 11.5mmol NO3–) on blood pressure and endothelial function in treated hypertensive patients. METHODS A randomized, placebo-controlled, crossover study was conducted in treated hypertensive patients (n=37; women=62%) who underwent clinical and nutritional evaluation and assessment of central hemodynamic parameters and microvascular reactivity. The significance level was p<0.05. RESULTS The mean age was 59±7 years, and mean systolic and diastolic blood pressures were 142±10/83±9mmHg. There was a significant increase in the subendocardial viability ratio (SEVR; 149±25 vs. 165±30%, p<0.001) and reduction in ejection duration (ED; 37±4 vs. 34±4%, p<0.001) in the beetroot phase but no significant SEVR difference in the control phase. The % increase in perfusion (155 vs. 159 %, p=0.042) was significantly increased in the beetroot phase, which was not observed in the control phase. In the beetroot phase, the change in SEVR showed a significant correlation with the change in the area under the curve of post-occlusive reactive hyperemia (AUC-PORH) (r=0.45, p=0.012). The change in ED showed a significant correlation with the post-intervention perfusion peak (r=-0.37, p=0.031) and AUC-PORH (r=-0.36, p=0.046). CONCLUSIONS The acute ingestion of BRJ by hypertensive patients resulted in an improvement of endothelial function, which was associated with higher subendocardial viability and performance in myocardial contraction.
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Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial.
Wood, E, Hein, S, Mesnage, R, Fernandes, F, Abhayaratne, N, Xu, Y, Zhang, Z, Bell, L, Williams, C, Rodriguez-Mateos, A
The American journal of clinical nutrition. 2023;117(6):1306-1319
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The risk of developing both cardiovascular and neurodegenerative diseases increases with aging. Growing evidence from epidemiological and human intervention trials indicates that (poly)phenols may have cardioprotective properties as well as the ability to improve cognitive function. The aim of this study was to investigate the effects of daily wild blueberry (WBB) (poly)phenol consumption on vascular function and cognitive performance in healthy older individuals. This study was a randomised, double-blinded, placebo-controlled parallel design study. A total of 61 healthy older individuals were recruited and randomly assigned to one of the two arms; placebo intervention or blueberry intervention group. Results showed that long-term consumption of a dietary achievable amount of WBB enhanced vascular and cognitive function in older adults. Authors conclude that gut microbiota and vascular blood flow may play important roles in mediating the cognitive benefits shown by the consumption of (poly)phenol-rich foods.
Abstract
BACKGROUND Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown. METHODS A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry. RESULTS A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found. CONCLUSIONS Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.