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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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X
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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2.
The Association between Total Protein, Animal Protein, and Animal Protein Sources with Risk of Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Cohort Studies.
Talebi, S, Zeraattalab-Motlagh, S, Rahimlou, M, Naeini, F, Ranjbar, M, Talebi, A, Mohammadi, H
Advances in nutrition (Bethesda, Md.). 2023;14(4):752-761
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Expert Review
Conflicts of interest:
None
Take Home Message:
- According to the researchers, the effect of the high consumption of meat in increasing the risk of IBD is not related to the type of protein contained in it but could be due to cooking meat at high temperatures
- Other studies have reported that the consumption of animal proteins, especially processed and red meat, increases the risk of IBD
- Other studies related to dairy intake have been contradictory. There is also evidence reported of a positive effect from dairy exclusion in IBD patients.
- Further research is required to corroborate the findings of this systematic review.
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
The authors conducted a dose-dependent meta-analysis of prospective cohort studies which examined the relation between total protein, animal protein, and animal protein sources with inflammatory bowel disease (IBD) in adults because the prevalence and incidence of IBD have exceeded globally.
Methods
Cochrane methodology was undertaken for the systematic review. Data from 11 prospective cohort studies with 8067 cases and 4,302,554 participants was extracted by 2 independent investigators. Evaluation of the quality and possible biases of included studies was performed. Risk ratios (RR) with 95% confidence intervals were chosen as the effect estimate. Various subgroup analyses were undertaken as well as metaregression analyses.
Results
- Seven cohort studies (7232 cases, 1,097,040 participants) were included in the analysis of dairy intake. Higher intakes of dairy was associated with a lower risk of IBD (RR: 0.81; 95% CI: 0.72, 0.90; n = 7)
- Consumption of protein from dairy products was found to be protective against IBD risk (RR = 0.77; 95% CI: 0.68, 0.88)
- Three prospective cohort studies with 1214 cases of IBD among a total of 535,738 subjects were included in the total meat analyses. Higher dietary total meat intake was not associated with the risk of IBD (RR: 1.24; 95% CI: 0.90, 1.70; n = 4)
- A positive linear association was found between total meat intake and risk of IBD. 100 g/d increment in dietary total meat consumption was associated with a 38% greater risk of IBD (RR: 1.38, 95% CI: 1.13, 1.68)
- Three prospective cohorts, among 492,497 participants and 4025 cases were included in the analysis of egg consumption. No association was found between egg consumption and IBD risk (RR: 0.92; 95% CI: 0.81, 1.04; n = 4).
Conclusion
The findings indicated no notable correlation between the intake of the majority of dietary protein sources and the incidence of IBD. IBD risk only escalated with higher total meat consumption, while the intake of protein from dairy products emerged as a protective factor against the risk of IBD.
Clinical practice applications:
- Dairy product consumption may be protective against IBD. However the studies included with statistically significant results did not control for alcohol intake and other confounding factors. The type of dairy product consumed, as well as a personalised approach, should be considered
- This study did not find any association between red or processed meat consumption and risk of IBD. However the subgroup analysis did find a significant association between red meat intake and IBD risk. This difference in results may be caused by differences in cooking methods, genetic factors, amount of meat consumption, confounding factors, and other environmental factors
- Total meat intake, as well as type of meat intake, and how meat is cooked, should be reviewed in clients with IBD, Crohn's Disease and Ulcerative Colitis.
Considerations for future research:
- Intervention studies would need to be conducted to corroborate the findings of this systematic review
- Future research should fully consider cofounding factors, such as alcohol intake and body mass index (BMI)
- Future studies should further consider types of protein as well as dose and cooking implications.
Abstract
We aimed to conduct this dose-dependent meta-analysis to examine the relation between total protein, animal protein, and its sources with inflammatory bowel disease (IBD). We searched databases, comprising PubMed/Medline, Web of Science (ISI), Embase, and Google Scholar, for the published studies up to 28 March 2023. Prospective cohort study designs that investigated associations between dietary intake of various animal protein sources and with risk of IBD in the general population were identified. Eleven prospective cohort studies with 4,302,554 participants and 8067 cases were considered eligible. Findings indicated that higher intake of dairy was significantly associated with a lower risk of IBD (relative risk [RR]: 0.81; 95% confidence interval [CI]: 0.72, 0.90), Crohn disease (RR: 0.69; 95% CI: 0.56, 0.86), and ulcerative colitis (RR: 0.84; 95% CI: 0.75, 0.94). There was no association between different sources of animal protein and the risk of IBD. The dose-response analysis suggested that each 100 g/d increment in dietary total meat consumption was associated with a 38% greater risk of IBD. Moreover, a positive linear association was found between total meat intake and risk of IBD (Pnonlinearity = 0.522, Pdose-response = 0.005). Overall, among the dietary sources of protein, the risk of IBD increased only with increasing total meat intake, and the consumption of protein from dairy products was found to be a protective factor against the IBD risk. This trial was registered at PROSPERO as CRD42023397719.
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Effects of Probiotics in Adults with Gastroenteritis: A Systematic Review and Meta-Analysis of Clinical Trials.
Mitra, AK, Asala, AF, Malone, S, Mridha, MK
Diseases (Basel, Switzerland). 2023;11(4)
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Gastroenteritis is a major cause of morbidity and mortality globally and symptoms can range from mild to life-threatening. Some studies have suggested benefits of probiotics in the treatment of gastroenteritis in children whilst in adults, results are inconsistent. The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics on acute and chronic gastroenteritis in adults. 35 clinical trials were included in the systematic review and 22 in the meta-analysis. Of these, 23 dealt with inflammatory bowel disease, 5 with pouchitis, 3 with antibiotic-induced diarrhoea, 2 with Helicobacter pylori infection and one each with diverticulitis and acute watery diarrhoea. 27 (77%) of studies showed some benefits of probiotic administration. The meta-analysis of 22 studies did not show a statistically significant benefit of probiotics. Although statistical analysis showed the studies to be homogenous, the authors point out that studies differed widely in aetiologies and probiotics used. A subgroup analysis of 8 studies in patients with ulcerative colitis also showed no benefit. In all studies, probiotics were well tolerated and no adverse side effects were reported. The authors concluded that further research is needed to help identify the most appropriate use of probiotics for the different types of gastroenteritis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- For chronic inflammatory gastroenteritis conditions in adults, probiotics were effective in treating and preventing relapse
- In ulcerative colitis, probiotics were not effective and adverse events outweighed the benefits
- No safety concerns were found for probiotic use in any studies
- Aetiologies, disease severity and duration as well as the type of probiotics used were widely diverse.
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
To date, evidence has been mixed for probiotic effectiveness in gastrointestinal syndromes associated with gastroenteritis. The aim of this study was to review current evidence on the effect of probiotics on gastroenteritis in adults.
Methods
This was a systematic review (n=35; total sample size 4577, median 44) and meta-analysis (n=22) of randomised controlled trials. Quality was assessed using CADIMA as per a rating scale (0 to 4) and standards of critical appraisal.
Results
All 35 studies on gastroenteritis included participants with chronic diarrhoea of diverse aetiologies such as IBD, antibiotic-associated, except one which had acute watery diarrhoea.
51% (n=18) of studies assessed the effects of probiotics in the treatment of ulcerative colitis (UC) and Crohn's disease (CD). 60% (n=21) used multiple strains of probiotics while the rest used single strains. Lactobacilli, Bifidobacteria, Escherichia and Streptococcus were the most common and only a few studies administered probiotics with another conventional treatment.
19 studies (55%) rated highly in terms of quality while 15 (43%) scored moderately. The majority (63%) of the 27 studies where probiotics were shown to be effective were of high quality.
Systematic review results:
- 27/53 studies (77%) showed a favourable response after using probiotics (resolution, improvement, remission or no relapse), mostly in patients with IBDs
- 7 studies (20%) found probiotics to be ineffective
- 1 study was inconclusive
- Multiple strain probiotics (VSL #3) was found to be most effective in IBD
- All administered probiotics were well tolerated with no adverse side effects although caution in immunocompromised patients was mentioned in several studies.
The meta-analysis results:
- Overall effectiveness for 22 studies (p=0.37) highlighted there was not enough evidence that the intervention was more protective than controls.
- Probiotics were not effective in UC (p = 0.28), and adverse events caused by probiotics may outweigh the benefits in studies with UC patients.
Conclusion
While benefits of effectiveness were found for probiotic use in gastroenteritis in adults, results from the systematic review and meta-analysis showed a mixed effect.
Clinical practice applications:
- Based on the systematic review, probiotics may be an effective treatment or adjuvant treatment for gastroenteritis but ineffective for around 20% of patients
- It is worth noting that combined therapy with standard treatment showed effective results
- Beneficial effects of probiotics in other key clinical outcomes including disease prevention, relapse, quality of life, morbidity were found
- While the results are interesting it is difficult to apply them in practice as the type of probiotics used were widely different as were the causes, severity and duration of gastroenteritis.
Considerations for future research:
- Further and larger studies would be beneficial to understand the benefits of probiotics in terms of single therapy or in combination with standard treatment particularly for UC, CDs, gastroenteritis not due to viral infection
- Individual-level data instead of aggregated data could give a better idea of effectiveness of probiotics in the future
- In this study aetiologies and the type, dosage, duration of probiotics used were widely diverse therefore systematic reviews and meta-analysis on specific conditions, specific probiotic strains and combinations would be beneficial.
Abstract
Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions is inconclusive and conflicting. The aim of this study was to review the existing literature on the effects of probiotics on gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases, such as PubMed, Google Scholar, MEDLINE and Scopus databases, were searched for the data. The study followed standard procedures for data extraction using a PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was performed. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective, and 1 study's results were inconclusive. The meta-analysis did not demonstrate any significant protective effects of probiotics. Having a τ2 value of zero and I2 of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.
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Polyphenol supplementation and executive functioning in overweight and obese adults at risk of cognitive impairment: A systematic review and meta-analysis.
Farag, S, Tsang, C, Murphy, PN
PloS one. 2023;18(5):e0286143
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It is recognised that overweight and obesity pose an increased risk for the development of cardiometabolic disease, and increasing evidence indicates a link to cognitive impairment associated with early onset dementia in such populations. This study's aim was to elaborate on existing knowledge of the effectiveness or otherwise of polyphenols in general to improve executive function (EFs) in an obese/ overweight population at risk of cognitive impairment. This study was a systematic review and meta-analysis of twenty-three randomised controlled trials. Results showed a nonsignificant effect of polyphenols on EFs. Authors concluded that further research should consider investigating polyphenols supplementation in a younger population at risk of cognitive impairment.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Overweight and obesity have increasing evidence that indicates a link to compromised executive functions such as memory and decision-making processes and cognitive impairment
- This meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions among overweight and/or obese populations with a susceptibility to cognitive impairment.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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:
A systematic review and meta-analysis were undertaken to investigate the impact of polyphenol supplementation on executive functions (cognitive functions which constitute part of the working memory and decision-making processes) among overweight and/or obese populations.
Method:
A comprehensive literature search was conducted using four electronic databases: PubMed/Medline, PsycInfo, Scopus and the Cochrane Trials Library. Inclusion criteria encompassed primary research studies which investigated the impact of polyphenols versus placebo on executive function in overweight or obese adults.
The review comprised a total of 23 randomised controlled trials (RCTs), incorporating a participant pool of N = 1,976 individuals. The mean ages of participants in all 23 studies receiving polyphenol supplementation were 62.92 years (SD = 8.06 years) and the mean BMIs ranged from 25.5 kg/m2 to 33.7 kg/m2. Various dietary polyphenols were investigated in the studies, with the main groups being isoflavones, flavonoids, resveratrol, phenolic acid, curcumin, walnuts and blueberry powder.
- The JADAD scale was employed to assess the methodological quality of the incorporated studies
- Hedges g, accompanied by 95% confidence intervals (CI) for endpoints, was computed utilising a random effects model whenever applicable
- Various statistical methods were considered for potential application in evaluating publication bias
- Sensitivity analysis was conducted to assess the robustness of the obtained results.
Results
- Meta analysis of the 23 primary studies produced a non-significant effect of polyphenol supplementation on executive function (g = 0.076, CI = -0.018 to 0.170)
- A double-blind, randomised, placebo-controlled parallel study reported significant benefits in 60 participants (mean age 67 years) taking 80mg of curcumin over placebo for digital vigilance and serial subtraction tasks (p=0.041)
- A double-blind, randomised, placebo-controlled parallel intervention trial showed significant benefits in 79 patients (mean age of 61 years) taking 150mg of resveratrol for visuospatial working memory double span and trail making test (p= 0.012).
Conclusion:
This meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions among overweight and/or obese populations.
Clinical practice applications:
- Research has documented the association between compromised executive functions and obesity/overweight, emphasising neuroinflammation and oxidative stress as potential mechanisms
- A plausible intervention involves the utilisation of polyphenols, known for their antioxidant and anti-inflammatory properties
- This systematic review and meta-analysis revealed a non-significant effect of polyphenol supplementation on executive functions
- A potential beneficial impact for 80mg of curcumin and 150mg of resveratrol was revealed in younger populations (mean ages of 67 and 61 years).
Considerations for future research:
- A potential beneficial impact of 80mg of curcumin and 150mg of resveratrol supplementation was revealed in a younger population (mean ages of 67 and 61 years), highlighting the necessity for in-depth exploration in subsequent studies
- The diversity in tasks employed for assessing executive functions and the comprehensive reporting of the phenolic composition of supplements had limitations that warrant consideration in future research
- The exact constituent and dose of supplementation needs to be described as this is necessary for the identification of the potential beneficial compounds for cognitive health and to support clinical practice.
Abstract
BACKGROUND AND OBJECTIVES Increasing evidence indicates a link between obesity and cognitive impairment. Furthermore, there is limited literature regarding the effect of polyphenols, a plant derived compounds, on executive functioning in an overweight/obese population at-risk of cognitive impairment. The aim of the present systematic review and meta-analysis of randomized controlled trials is to examine the effect of polyphenol supplementation on executive functions in overweight and/or obese populations at risk of cognitive impairment. METHODS A comprehensive literature search was conducted from inception to March 2023 using four electronic databases: PubMed/Medline, PsycInfo, Scopus and Cochrane trials library. Published primary research studies in English that compared the effect of polyphenols with placebo on executive function in overweight/obese adults were considered eligible for the meta-analysis. Jadad scale was used for the methodological quality rating of the included studies. Hedges g with 95% confidence intervals (CI) for endpoints were calculated using random effect model where applicable. Rosenthal's Fail-safe N, funnel plots, the Begg and Mazumdar's rank correlation test (Kendall's S statistic P-Q), Egger's linear regression test, and Duval and Tweedie's trim-and-fill test were identified for potential use as appropriate, to examine publication bias. Sensitivity analysis was conducted to examine the robustness of the results. RESULTS AND CONCLUSION A total of 23 RCT studies involving N = 1,976 participants were included in the review. The results of the meta-analysis revealed a non-significant effect for polyphenol supplementation on executive function (g = 0.076, CI = -0.018 to 0.170). Observations from primary studies within the meta-analysis showed a potential positive effect of polyphenol supplementation in a younger population at-risk of cognitive impairment and it is recommended to investigate this further in future studies. Moreover, the variability of the tasks used to examine executive functions as well as the adequate reporting of supplement's phenolic composition is a limitation that future work should also consider.
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5.
Diet as an Optional Treatment in Adults With Inflammatory Bowel Disease: A Systematic Review of the Literature.
Jaramillo, AP, Abaza, A, Sid Idris, F, Anis, H, Vahora, I, Moparthi, KP, Al Rushaidi, MT, Muddam, M, Obajeun, OA
Cureus. 2023;15(7):e42057
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Plain language summary
Crohn's disease (CD) and ulcerative colitis (UC) are linked with significant morbidity and higher healthcare costs. The current model of CD pathogenesis implies that environmental variables and the gut microbiota interact in those who are genetically predisposed to the condition. The aim of this study was to investigate a treatment based on the diet of IBD patients. This study was a systematic review of nine studies. Results showed that following a diet that reduces inflammation may prevent its recurrence in UC patients in clinical remission. In fact, there were significant systemic changes in the intestinal microbiota of anti-inflammatory diet patients. Authors concluded that a four-week FODMAP diet combined with professional counseling and regular follow-up will be helpful in the therapy of persistent gastrointestinal symptoms in quiescent IBD, although care should be used in the long run.
Expert Review
Conflicts of interest:
None
Take Home Message:
Whilst concise, this limited review highlights the current lack of evidence supporting stand alone dietary strategies in preventing relapse for IBD patients. At the very least an anti-inflammatory diet should ideally be implemented alongside specific medical care and counselling to minimise risk of disease relapses.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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
This systematic review evaluated the efficacy of diet as a preventative therapeutic treatment for Inflammatory Bowel Disease (IBD).
Methods
A total of 9 studies (published in the last 5 years) were chosen. The articles included 6 randomised controlled trials (RCT), one systematic literature review (SLR) and two SLR and meta-analysis. The authors used the Assessment Systematic Reviews (AMSTAR) approach and an unspecified Cochrane Risk of Bias assessment tool.
Results
(The following refers to the original RCT articles as the review article data was sparse).
- A 6-month, open-label, randomised, placebo-controlled trial of 53 adult Ulcerative Colitis (UC) patients compared response to an Anti-inflammatory Diet (AID) with Canada’s Food Guide (CFG). The outcome showed that the faecal calprotectin value (<150 µg/g at the endpoint) was significantly higher in the AID group (69.2 vs. 37.0%, p = 0.02) (Keshteli et al., 2022).
- The Specific Carbohydrate Diet (SCD) was not superior to the Mediterranean Diet (MD) in terms of achieved symptomatic remission at 6 weeks (SCD 46.5%, MD 43.5%; p = .77) (Lewis et al., 2022).
- A single-blind, 4-week trial concluded significant relief from gut symptoms was achieved when comparing a low FODMAP diet (14/27, 52% of positive patient feedback) to a control diet (4/25, 16%, p=.007) (Cox et al., 2020).
- A 7-day trial of 28 volunteers compared individualised food-based diet (CD-TREAT), with similar composition to Exclusive Enteral Nutrition (EEN) and found a change in relative abundance in faecal microbiome genera of 58 (49.3%) and 38 (32.3%) following both feeding practices respectively (Svolos et al., 2019).
- Substantial reduction in red and processed meat was not significant in reducing time to symptomatic relapse in Crohn’s Disease (CD) patients when comparing 115 high red meat consumers with 87 low red meat CD patients (p = 0.61 any relapse and p = 0.50 for moderate to severe relapse) (Aldenberg et al., 2019).
Conclusion
An anti-inflammatory diet may prolong clinical remission for UC patients. CD patients, with mild to severe symptoms, may tolerate both the MD and SCD equally well. The authors advise a low FODMAP diet for a 4-week period combined with professional counselling and regular follow-up sessions to delay flare-up episodes. However the findings were based on a very limited number of scientific material that requires extensive further assessment prior to deriving any firm conclusions.
Clinical practice applications:
- In order to delay relapse in IBD it is imperative that foods that support anti-inflammatory mechanisms are incorporated and maintained
- Whilst limited, the papers reviewed highlight potential for an initial low FODMAP diet followed by a longer term MD or SCD combined with constant monitoring
- From one study, red meat consumption did not appear to exacerbate symptoms.
Considerations for future research:
- Future studies need to include larger cohorts to ascertain the efficacy of dietary interventions as a stand alone treatment option for IBD
- Longer periods of intervention are needed to confirm dietary intervention efficacy and safety in this population.
Abstract
While the exact cause of IBD is unknown, there are a number of factors that are thought to contribute to its development, including environmental and genetic factors. While exclusive enteral nutrition (EEN) is a promising therapy for Crohn's disease (CD), it is not yet considered a first-line treatment. Additionally, the efficacy of EEN compared to corticosteroid treatment is still being investigated. EEN is suggested as a first-line therapy by which guidelines and in which age groups, as it may differ in pediatric and adult recommendations. Another finding was that dietary changes involving an increase in anti-inflammatory foods and decreased intake of foods high in inflammatory compounds are linked to a beneficial outcome both metabolically and microbiologically in patients with ulcerative colitis (UC) in remission. For relevant medical literature, we examined PubMed/Medline, the Cochrane Library, and Google Scholar as examples of medical databases. The articles were identified, evaluated, and eligibility applied, and nine publications were found. The finished articles investigated the role of several diet alternatives for patients with IBD. Some others have shown that following a normal low-fat diet may be effective in reducing the occurrence of subclinical colitis. The EEN and partial enteral nutrition (PEN) indicated no significant differences between both regimens, but both had good outcomes during active IBD. Other strict diets, such as the specific carbohydrate diet (SCD) versus the Mediterranean diet (MD), demonstrate excellent outcomes in patients with IBD. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) dietary counseling improves gastrointestinal symptoms and quality of life in IBD patients. Based on the above, we concluded that more studies determining which component of the diet is not clear (proteins, carbs balanced) or diet types are required to establish a particular diet employed as a treatment intervention in these individuals.
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6.
The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review.
Zhang, T, Zhang, J, Duan, L
Nutrients. 2023;15(7)
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Inflammatory bowel disease (IBD), largely classified as Crohn’s disease (CD) or ulcerative colitis (UC), is a chronic intestinal inflammatory disorder mediated by genetic, immune, microbial, and environmental factors. The aim of this study was to summarise the efficacy of different genetically modified probiotics compared to wild-type probiotics in the treatment of IBD in animal models and patients and to investigate the specific effects and main mechanisms involved. This study was a systematic review of forty-five preclinical studies and one clinical study. Results showed a protective effect of genetically modified organisms (gm) probiotics in colitis. Several protective mechanisms have been identified: reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of the activity of oxidative stress in the colon, improvement of intestinal barrier integrity, modulation of the diversity and composition of gut microbiota, and production of favourable metabolites, including short-chain fatty acids, by beneficial bacteria. Authors concluded that gm probiotics are more effective and safer than wild-type probiotics, to facilitate clinical translation.
Expert Review
Conflicts of interest:
None
Take Home Message:
Conclusions of this review were largely based on mouse models and although treatment using probiotics is generally considered safe in humans, with only minor side-effects (flatulence), practitioners need to be aware that in an IBD population the use of GM formulations might not be completely without risk.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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
This paper summarises the efficacy of specific genetically modified (GM) probiotic formulations for Inflammatory Bowel Disease (IBD) when compared to wild type probiotics. The aim was to ascertain what specific effects and mechanisms such probiotics have on IBD symptomatology.
Methods
- A total of 46 published articles were included; 45 mouse experimental models (induced acute or chronic colitis) (n=15-130) and 1 human IBD population clinical trial (n=10)
- The effect of GM probiotics were compared to placebo and wild-type probiotics in trials including preclinical studies, randomised controlled trials and cohort studies
- Animals received probiotics via gastric gavage (105 - 4 x 1012 CFU) for 3-6 weeks
- The human placebo-uncontrolled trial lasted 7 days and patients received 10 GM capsules of L.lactis (1 x 1010 CFU) twice daily.
Results
- GM probiotics that secrete immunoregulatory cytokines such as IL-10 appear to reduce intestinal damage
- The human trial using GM L.lactis resulted in 5 patients who went into complete clinical remission (CDAI, <150) with 3 patients exhibiting a clinical response (decrease in CDAI, >70). with only minor adverse events (flatulence)
- However, human cytokines that promote intestinal barrier function and epithelial restitution were not enhanced with oral administration of probiotics
- Two studies concluded that GM L.lactis and S.boulardii, that secrete atrial natriuretic peptide, might be the most effective options in supporting colitis
- GM L.casei resulted in faster recovery from weight loss in acute colitis models
- Superoxide dismutase (SOD) producing GM L.fermentum increased SOD activity by almost eightfold compared to the wild type
- GM Lact. fermentum furthermore showed a higher survival rate and lower disease activity index (P <0·05) in colitis models
- GM L.lactis improved gut microbial composition and GM S.cerevisiae improved microbial diversity whilst reducing the Firmicutes to Bacteroides ratio
- GM E.coli significantly reduced weight loss, colon shortening plus lower disease activity and histological changes (P < 0.05).
Conclusion
Despite the heterogeneity of the trials, GM probiotics appear to play a notable part in ameliorating IBD symptomatology and disease severity when compared to wild-type probiotics. Human efficacy and potential adverse effects require more in-depth trials to ascertain safety and optimal dosages.
Clinical practice applications:
- Probiotics species used in the trials included S.thermophilus, E.coli, L.lactis, B.ovatus, S.boulardii, L.fermentum, B.longhum, L.casei, L.plantarum, and S.cerevisiae. Wild-types of some of these are already available to use in clinical practice
- Note that oral administration in the human trial showed no significant health outcome, therefore efficacy and safety need to be ascertained on an individual patient level
- Colonisation of beneficial bacteria in the gut of IBD patients might be difficult and any form of supplementation therefore needs to be closely monitored.
Considerations for future research:
- More evidence is needed to demonstrate that GM probiotic formulations result in significantly improved outcomes when compared to wild-types
- Future randomised placebo-controlled trials need to include larger cohorts to determine supplement efficacy
- Longer periods of intervention are needed to confirm efficacy, safety, and tolerance for both Crohn’s Disease and Colitis
- Optimal GM probiotic formulation, doses, and means of application need to be identified.
Abstract
BACKGROUND Many preclinical studies have demonstrated the effectiveness of genetically modified probiotics (gm probiotics) in animal models of inflammatory bowel disease (IBD). OBJECTIVE This systematic review was performed to investigate the role of gm probiotics in treating IBD and to clarify the involved mechanisms. METHODS PubMed, Web of Science, Cochrane Library, and Medline were searched from their inception to 18 September 2022 to identify preclinical and clinical studies exploring the efficacy of gm probiotics in IBD animal models or IBD patients. Two independent researchers extracted data from the included studies, and the data were pooled by the type of study; that is, preclinical or clinical. RESULTS Forty-five preclinical studies were included. In these studies, sodium dextran sulfate and trinitrobenzene sulfonic acid were used to induce colitis. Eleven probiotic species have been genetically modified to produce therapeutic substances, including IL-10, antimicrobial peptides, antioxidant enzymes, and short-chain fatty acids, with potential therapeutic properties against colitis. The results showed generally positive effects of gm probiotics in reducing disease activity and ameliorating intestinal damage in IBD models; however, the efficacy of gm probiotics compared to that of wild-type probiotics in many studies was unclear. The main mechanisms identified include modulation of the diversity and composition of the gut microbiota, production of regulatory metabolites by beneficial bacteria, reduction of the pro- to anti-inflammatory cytokine ratio in colonic tissue and plasma, modulation of oxidative stress activity in the colon, and improvement of intestinal barrier integrity. Moreover, only one clinical trial with 10 patients with Crohn's disease was included, which showed that L. lactis producing IL-10 was safe, and a decrease in disease activity was observed in these patients. CONCLUSIONS Gm probiotics have a certain efficacy in colitis models through several mechanisms. However, given the scarcity of clinical trials, it is important for researchers to pay more attention to gm probiotics that are more effective and safer than wild-type probiotics to facilitate further clinical translation.
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7.
Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study.
Das, JK, Banskota, N, Candia, J, Griswold, ME, Orenduff, M, de Cabo, R, Corcoran, DL, Das, SK, De, S, Huffman, KM, et al
Aging cell. 2023;22(12):e13963
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Plain language summary
Reducing calorie intake by 12% has been shown in one randomised control trial (RCT) called the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, to result in both fat and muscle loss but without any changes to muscle strength and function. The present study aimed to take 90 of the individuals from the original CALERIE study to understand the mechanisms behind this. The results showed that after 12 months individuals who were given a calorie reduced diet lost significant amounts of weight compared to control and this loss was maintained after 2 years. This included muscle loss, but despite this, there was no change in muscle strength of individuals on calorie reduced diet. Genetic analysis showed that genes are involved in muscle quality and anti-ageing. It was concluded that 2 years of calorie restriction resulted in both fat and muscle loss but did not compromise muscle function. The upregulation of genes involved in muscle quality and anti-ageing may be responsible for this.
Expert Review
Conflicts of interest:
None
Take Home Message:
- CR can aid weight loss and sustain losses long-term. Some lean muscle loss may also be seen, but this does not mean that muscle function has been compromised
- CR can trigger molecular and cellular mechanisms involved in skeletal muscle, sustaining functionality during a weight loss programme.
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
The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) randomised control trial (RCT) showed that 12% caloric restriction (CR) induced muscle loss, without compromising muscle strength. This analysis of 90 individuals from that study aimed to determine the mechanisms behind this.
Methods
- The CALERIE study was an RCT that assessed the effects of 25% CR over 2 years compared to an ad libitum control group
- This study ran alongside the CALERIE study and took skeletal muscle biopsies from a subset of 90 individuals at baseline, 12 months, and 24 months from the CR group and ad libitum control group
- This yielded 162 muscle biopsies over 2 years
- Skeletal muscle was taken from the vastus lateralis muscle and lean leg mass, and muscle strength were assessed
- In addition, RNA was extracted, and gene expression assessed.
Results
- Participants on CR lost significant amounts of weight (P=<0.001) at 12 months, with no further improvements at 2 years. Quantity or range of weight loss data was not provided
- Control participants maintained their weight over 2 years
- There were no changes in muscle strength in CR individuals despite a significant loss of muscle mass (no P value given)
- Although adjustments for change in lean leg mass resulted in less of a decline in the isokinetic muscle strength test compared to control (average power P=0.0058 and peak torque P=0.0144)
- RNA analysis showed 797 genes were overexpressed and 206 underexpressed in CR compared to control
- CR was associated with enhanced anti-ageing mechanisms with genes such as those involved in androgen receptor signalling, autophagy, circadian rhythms, DNA repair, FOXO mediated transcription, and mitochondrial biogenesis all upregulated and inflammatory genes downregulated
- These changes were responsible for the positive effect on muscle quality in individuals in the CR group.
Conclusion
- It was concluded that 2 years of CR preserved muscle function despite muscle mass loss, through upregulation of the genes involved in muscle quality and anti-ageing.
Clinical practice applications:
- Healthcare professionals may consider a 12% CR diet for individuals who would like to lose weight and maintain its loss long-term, without compromising muscle function
- Although lean muscle mass may be lost, muscle function should not be affected, but should be monitored to ensure functionality.
Considerations for future research:
- The possible effects of combining CR with muscle strength exercises should be considered for future research to determine if muscle mass loss is prevented and whether this impacts further fat loss.
Abstract
The lifespan extension induced by 40% caloric restriction (CR) in rodents is accompanied by postponement of disease, preservation of function, and increased stress resistance. Whether CR elicits the same physiological and molecular responses in humans remains mostly unexplored. In the CALERIE study, 12% CR for 2 years in healthy humans induced minor losses of muscle mass (leg lean mass) without changes of muscle strength, but mechanisms for muscle quality preservation remained unclear. We performed high-depth RNA-Seq (387-618 million paired reads) on human vastus lateralis muscle biopsies collected from the CALERIE participants at baseline, 12- and 24-month follow-up from the 90 CALERIE participants randomized to CR and "ad libitum" control. Using linear mixed effect model, we identified protein-coding genes and splicing variants whose expression was significantly changed in the CR group compared to controls, including genes related to proteostasis, circadian rhythm regulation, DNA repair, mitochondrial biogenesis, mRNA processing/splicing, FOXO3 metabolism, apoptosis, and inflammation. Changes in some of these biological pathways mediated part of the positive effect of CR on muscle quality. Differentially expressed splicing variants were associated with change in pathways shown to be affected by CR in model organisms. Two years of sustained CR in humans positively affected skeletal muscle quality, and impacted gene expression and splicing profiles of biological pathways affected by CR in model organisms, suggesting that attainable levels of CR in a lifestyle intervention can benefit muscle health in humans.
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8.
Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease.
Scheffers, LE, Vos, IK, Utens, EMWJ, Dieleman, GC, Walet, S, Escher, JC, van den Berg, LEM
Journal of pediatric gastroenterology and nutrition. 2023;77(2):214-221
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Plain language summary
Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory diseases of the gastrointestinal tract, characterised by periods of remission and relapse of symptoms. The aim of this study was to assess the effects of a tailored lifestyle intervention on physical fitness (maximal and submaximal exercise capacity, strength, and core stability), the patient-reported outcomes (quality of life, fatigue, and fear), clinical disease activity, and nutritional status. This study was a prospective single-centre randomised semi-crossover-controlled trial. Children were randomized into group A (start exercise) or group B (start control period). Results showed improved physical fitness, quality of life, and parent-reported fatigue. Additionally, a combination of lower clinical disease activity scores accompanied by fewer IBD symptoms suggests positive effects on intestinal inflammation. Authors concluded that based on the findings of their study, children and adolescents with IBD should be motivated and supported to acquire and maintain a healthy lifestyle.
Expert Review
Conflicts of interest:
None
Take Home Message:
- IBD is a chronic inflammatory disease of the gastrointestinal tract, characterised by periods of abdominal pain, severe diarrhoea, and fatigue
- This clinical trial suggests that a 12-week program of physical training plus personalised healthy dietary advice may improve physical fitness, quality of life, and fatigue in children with IBD.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
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 randomised semi-crossover controlled trial was conducted to investigate the impact of a 12-week lifestyle program (3 physical training sessions per week plus personalised healthy dietary advice) in children with Inflammatory Bowel Disease (IBD).
Method
- Sixteen children with a median age of 15 [IQR: 12–16]) that were diagnosed with IBD (CD, UC, or IBD-unclassified) were randomized to group A (start exercise) or group B (start control period). Group A started the intervention immediately after the first assessment and did not have a control period. Group B started after a control period (this was planned to last for 6 weeks but due to the COVID-19 lockdown extended to 6 months)
- The lifestyle intervention lasted 12 weeks and consisted of 3 physiotherapist-supervised training sessions per week, lasting 60 minutes each. In addition, all participants received a recommended caloric intake per day based on measured rest energy expenditure and a brochure regarding healthy diet in children
- Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (faecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition)
- A total of 15 out of 16 participants (93%) completed the program, one patient dropped out after one training session due to motivational problems.
Results
The primary findings of this study were as follows:
- While medical treatment remained unchanged, Paediatric Crohn's Disease Activity Index decreased versus the control period (15 [3–25] vs 2.5 [0–5], P = 0.012)
- The number of patients in clinical remission increased from 5 to 12 (P < 0.001), compared to the control period
- Quality of life (IMPACT-III) improved on 4 out of 6 domains and the total score (+13 points) versus the control period including a large improvement in bowel-related symptoms, P= 0.029)
- Fecal calprotectin decreased, but not compared to the control period, mainly due to relatively large intra-patient fluctuations (400 μg/g [57.1–1662.7] vs 128 μg/g [23.8–642.3], P = 0.016)
- Parents reported an improvement in the quality of life versus the control period on the child health questionnaire and total fatigue score (PedsQoL • Multidimensional Fatigue Scale) (+14 points, P = 0.048)
- Walking distance improved after the 12-week program, compared to the control period (P = 0.001).
Conclusion
This study revealed that a 12-week physical training program and personalised dietary advice improved bowel symptoms, quality of life, and fatigue in children with IBD.
Clinical practice applications:
- The mechanism behind the anti-inflammatory effects of exercise has not been clarified
- Multiple theories have been suggested in previously published studies such as a reduced release of adipokines due to less visceral fat, increased secretion of anti-inflammatory cytokines such as interleukin (IL)-6, and reduced transient stool time
- This clinical trial demonstrated that a 12-week program of physical training sessions plus personalised healthy dietary advice resulted in improved physical fitness, quality of life, and parent-reported fatigue.
Considerations for future research:
- A sample size calculation was not provided in the study report and it is therefore assumed that the sample size of 16 children in this trial was too small to draw a definite conclusion. A larger study over a longer period is therefore needed across diverse age and ethnic population groups to draw better conclusions
- This study did not measure mucosal inflammation before and after the intervention due to the invasive nature of the procedure. It would however be useful that future research investigate this to gain more insight into the effect of lifestyle interventions on IBD.
Abstract
OBJECTIVES Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD. METHODS This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD. Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (fecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition). Change in maximal exercise capacity (peak VO 2 ) was the primary endpoint; all others were secondary endpoints. RESULTS Fifteen patients (median age 15 [IQR: 12-16]) completed the program. At baseline, peak VO 2 was reduced (median 73.3% [58.8-100.9] of predicted). After the 12-week program, compared to the control period, peak VO 2 did not change significantly; exercise capacity measured by 6-minute walking test and core-stability did. While medical treatment remained unchanged, Pediatric Crohn's Disease Activity Index decreased significantly versus the control period (15 [3-25] vs 2.5 [0-5], P = 0.012), and fecal calprotectin also decreased significantly but not versus the control period. Quality of life (IMPACT-III) improved on 4 out of 6 domains and total score (+13 points) versus the control period. Parents-reported quality of life on the child health questionnaire and total fatigue score (PedsQoL Multidimensional Fatigue Scale) also improved significantly versus the control period. CONCLUSIONS A 12-week lifestyle intervention improved bowel symptoms, quality of life, and fatigue in pediatric IBD patients.
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9.
Additive Effects of Exercise and Vitamin D Supplementation (with and without Calcium) on Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis.
Fischer, C, Jakob, F, Kohl, M, Kast, S, Von Stengel, S, Kerschan-Schindl, K, Lange, U, Thomasius, F, Peters, S, Uder, M, et al
Journal of osteoporosis. 2023;2023:5570030
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Expert Review
Conflicts of interest:
None
Take Home Message:
- Whilst this study failed to show additive benefits of exercise and vitamin D, dual therapy may still have some validity especially in individuals with vitamin D deficiency.
- Given the high safety and low cost of vitamin D supplementation, it might be worth recommending dual therapy to patients, especially if they are vitamin D deficient, or at high risk of osteoporosis.
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
Exercise and vitamin D supplementation are thought to have positive effects on bone mineral density (BMD) and when in combination, benefits may be enhanced. This systematic review and meta-analysis aimed to determine the effects of vitamin D and exercise combination therapy on the BMD of the lumbar spine and proximal femur.
Methods
- The study looked at comparative ≥6 month vitamin D exercise trials in adults aged ≥50 years from 6 electronic databases.
- Outcome measures were BMD at lumbar spine, total hip, or femoral neck as determined by dual X-ray absorptiometry, dual photon absorptiometry, and quantitative computed tomography.
Results
- Five studies with 360 participants were found to fit the entry criteria. Three were randomised control trials and two were nonrandomised.
- One study was in Caucasian men, whilst the remaining four were in postmenopausal Caucasian women.
- Two studies were for 24 months, whilst three were 12-month durations.
- Exercise regimes varied amongst studies and focused on weight-bearing and non-weight-bearing exercises.
- Vitamin D supplementation ranged from 284-2000 IU/d.
- The addition of vitamin D to exercise did not affect the BMD of the lumbar spine, femoral neck, or hip compared to exercise alone (P=0.912, P=0.675, and P=0.976 respectively), even when a trial with low vitamin D doses was excluded.
Conclusion
The addition of vitamin D to exercise had no additive benefits on BMD at the lumbar spine or femoral neck. However, this may be due to the trials not employing bone specific exercises and the inclusion of studies which were not performed in individuals with vitamin D deficiency.
Clinical practice applications:
- Exercise in combination with vitamin D may have no further benefit than exercise alone on BMD of individuals who are not vitamin D deficient.
- However, this is based on only a small number of clinical trials in non-vitamin D deficient individuals.
- Combined vitamin D and exercise may still be of benefit to fracture risk in specific patients.
Considerations for future research:
- Studies should now extend to looking at exercise in combination with vitamin D supplementation on the BMD and fracture incidence of individuals with vitamin D deficiency.
Abstract
Exercise is a recognized component in the prevention and therapy of osteoporosis. The present systematic review and meta-analysis aimed to determine the effect of Vitamin D (Vit-D) added to exercise versus exercise alone on bone mineral density (BMD) at the lumbar spine (LS) or hip in older adults. A systematic review based on six literature databases according to PRISMA included (a) exercise trials, with an exercise (EX) and a combined exercise + Vit-D group (EX + Vit-D), (b) intervention ≥ 6 months, and (c) BMD assessments at LS or hip. Effects sizes (MD) and 95%-confidence intervals (95%-CI) were calculated using a random-effect model that includes the inverse heterogeneity model (IVhet). Five studies with 281 participants in the EX and 279 participants in the EX + Vit-D were included. No significant differences between EX versus EX + Vit-D were observed for BMD-LS (MD: 0.002, 95%-CI: -0.033 to 0.036) or BMD-hip (MD: 0.003, 95%-CI: -0.035 to 0.042). Heterogeneity between the trial results was moderate-substantial for LS (I2 = 0%) and moderate for hip-BMD (I2 = 35%). The funnel plot analysis suggests evidence for a publication/small study bias for BMD-LS and hip results. In summary, this present systematic review and meta-analysis were unable to determine significant positive interaction of exercise and Vit-D on LS- or hip-BMD. We predominately attribute this finding to (1) the less bone-specific exercise protocols of at least two of the five studies and (2) the inclusion criteria of the studies that did not consequently focus on Vit-D deficiency. This issue should be addressed in more detail by adequately powered exercise trials with promising exercise protocols and participants with Vit-D deficiency. This trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) ID: CRD42022309813.
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10.
The Effects of Polyphenols on Bone Metabolism in Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Control Trials.
Salvio, G, Ciarloni, A, Gianfelice, C, Lacchè, F, Sabatelli, S, Giacchetti, G, Balercia, G
Antioxidants (Basel, Switzerland). 2023;12(10)
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Plain language summary
Women who are post-menopause are at a higher risk of osteoporosis due to lower levels of the hormone oestrogen. Oestrogens promote bone building and limit breakdown. In addition, oestrogen protects the bones against oxidative stress, which can cause further bone breakdown. Polyphenols, which are naturally occurring chemicals found in fruits and vegetables, may prevent oxidative stress and subsequent bone breakdown. This systematic review and meta-analysis of 21 randomised control trials aimed to determine the effect of polyphenol supplementation on post-menopausal bone density. The results showed that polyphenol supplementation had no effect on bone density in the spine, leg, hip, or across the whole body. If polyphenol supplementation extended beyond 2 years, there was evidence of an improvement in spinal bone density. Supplementation also increased one biomarker associated with bone building and decrease one associated with its breakdown. It was concluded that polyphenol use is not recommended to improve bone health in postmenopausal women. This study could be used by healthcare professionals to understand polyphenol supplementation is ineffective for the prevention of osteoporosis and other lifestyle modifications should be considered.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Postmenopausal women are susceptible to decreased BMD due to lower oestrogen levels and oxidative stress.
- Although polyphenols have an antioxidant effect, supplementation does not seem to affect bone mineral density in postmenopausal women.
- Post-menopausal women should consider other lifestyle modifications to reduce the risk of osteoporosis.
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
- Postmenopausal, low oestrogen levels can decrease osteoclastic activity, increase osteoclastic apoptosis, and make bones more susceptible to oxidative stress, which in turn increases osteoclastogenesis and decreases osteoblastogenesis.
- Polyphenols from fruits and vegetables can have an antioxidant effect. They have been shown in vitro to enhance osteoblastic activity through effects on endothelial function and have been associated with a lower risk of fractures.
- This systematic review and meta-analysis aimed to evaluate the effect of polyphenol supplementation on postmenopausal bone mineral density (BMD).
Methods
- 21 randomised control trials were included.
- The primary outcome assessed the effect of polyphenols on BMD.
- The secondary outcome assessed the effect of polyphenols on bone turnover markers; deoxypyridinoline, osteocalcin, alkaline phosphatase, and pyridinoline.
- 18 studies reported on lumbar BMD, 12 on femoral neck BMD, and 7 on total body BMD.
- Study durations ranged from 3-36 months
Results
- Polyphenols did not affect BMD of the lumbar spine (sMD: 0.21, 95% CI [−0.08 to 0.51], p = 0.16), femoral neck (sMD: 0.16, 95% CI [−0.23 to 0.55], p = 0.42), total hip (sMD: 0.05, 95% CI [−0.14 to 0.24], p = 0.61), or whole body (sMD: −0.12, 95% CI [−0.42 to 0.17], p = 0.41). However, a sub-analysis based on studies longer than 24 months showed that lumbar BMD was improved (sMD: 1.00, 94% CI [0.19 to 1.81], p=0.02).
- Treatment duration did not affect femoral neck BMD, total hip BMD, or whole-body BMD.
- Polyphenols did not affect deoxypyridinoline or osteocalcin levels, however they did increase bone specific alkaline phosphatase (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and decrease pyridinoline (sMD: −0.58, 95% CI [−0.77 to −0.39], p < 0.0001).
- There was high heterogeneity amongst the studies and 14 showed high or unclear risk of bias.
Conclusion
- Polyphenol use is not recommended as the sole preventative therapy for postmenopausal osteoporosis.
Clinical practice applications:
- A polyphenol rich diet is not recommended to improve BMD and fracture risk in postmenopausal women.
- Other lifestyle modifications with more robust research should be recommended instead.
Considerations for future research:
- Future studies would be interesting in women in perimenopause to determine if life stage affects efficacy of polyphenols.
Abstract
Osteoporosis is a condition favored by the postmenopausal decline in estrogen levels and worsened by oxidative stress (OS). Polyphenols are natural compounds abundantly found in fruits and vegetables, and they exert antioxidant and hormonal effects that could be useful in osteoporosis prevention, as suggested by epidemiological studies showing a lower incidence of fractures in individuals consuming polyphenol-rich diets. The aim of our meta-analysis is to evaluate the effects of polyphenols on bone mineral density (BMD, primary endpoint) and bone turnover markers (BTMs, secondary endpoint) in postmenopausal women. Twenty-one randomized control trials (RCTs) were included in our analysis after in-depth search on PubMed, EMBASE, and Scopus databases. We found that supplementation with polyphenols for 3-36 months exerted no statically significant effects on BMD measured at lumbar spine (sMD: 0.21, 95% CI [-0.08 to 0.51], p = 0.16), femoral neck (sMD: 0.16, 95% CI [-0.23 to 0.55], p = 0.42), total hip (sMD: 0.05, 95% CI [-0.14 to 0.24], p = 0.61), and whole body (sMD: -0.12, 95% CI [-0.42 to 0.17], p = 0.41). Subgroup analysis based on treatment duration showed no statistical significance, but a significant effect on lumbar BMD emerged when studies with duration of 24 months or greater were analyzed separately. On the other hand, we found a significantly slight increase in bone-specific alkaline phosphatase (BALP) levels (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and a decrease in pyridinoline (PD) levels (sMD: -0.58, 95% CI [-0.77 to -0.39], p < 0.0001). High heterogeneity among studies and unclear risk of bias in one third of the included studies emerged. A subgroup analysis showed similar effects for different duration of treatment and models of dual-energy X-ray absorptiometry (DXA) scanner. More robust evidence is needed before recommending the prescription of polyphenols in clinical practice.