The effects of omega-3 polyunsaturated fatty acids on muscle and whole-body protein synthesis: a systematic review and meta-analysis.

CONTEXT: Sarcopenia describes the age-related decline in skeletal muscle mass and strength that is driven, at least in part, by an imbalance between rates of muscle protein synthesis (MPS) and muscle protein breakdown. An expanding body of literature has examined the effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) ingestion on MPS rates in older adults, with mixed findings. OBJECTIVE: The aim of this systematic review and meta-analysis was to investigate the effectiveness of n-3 PUFA ingestion in stimulating rates of MPS and whole-body protein synthesis in healthy adults and clinical populations. DATA SOURCES: Searches were conducted of the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until December 2022 for articles on randomized controlled trials comparing the effect of n-3 PUFA ingestion vs a control or placebo on rates of MPS and whole-body protein synthesis. The search yielded 302 studies, of which 8 were eligible for inclusion. DATA EXTRACTION: The random effects inverse-variance model was used and standardized mean differences (SMDs) with 95%CIs were calculated to assess the pooled effect. Risk of bias was assessed by the Cochrane Risk-of-Bias 2 tool. DATA ANALYSIS: The main analysis indicated no effect of n-3 PUFA supplementation on MPS rates (k = 6; SMD: 0.03; 95%CI, -0.35 to 0.40; I2 = 30%; P = .89). Subgroup analysis based on age, n-3 PUFA dose, duration of supplementation, and method used to measure fractional synthetic rate also revealed no effect of n-3 PUFA ingestion on MPS. In contrast, the main analysis demonstrated an effect of n-3 PUFA ingestion on increasing whole-body protein synthesis rates (k = 3; SMD: 0.51; 95%CI, 0.12-0.90; I2 = 0%; P = .01). CONCLUSIONS: n-3 PUFA ingestion augments the stimulation of whole-body protein synthesis rates in healthy adults and clinical populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. 42022366986.

The Effect of Omega-3 Fatty Acids on Sarcopenia: Mechanism of Action and Potential Efficacy.

Sarcopenia, a progressive disease characterized by a decline in muscle strength, quality, and mass, affects aging population worldwide, leading to increased morbidity and mortality. Besides resistance exercise, various nutritional strategies, including omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation, have been sought to prevent this condition. This narrative review summarizes the current evidence on the effect and mechanism of n-3 PUFA on musculoskeletal health. Despite conflicting evidence, n-3 PUFA is suggested to benefit muscle mass and volume, with more evident effects with higher supplementation dose (>2 g/day). n-3 PUFA supplementation likely improves handgrip and quadriceps strength in the elderly. Improved muscle functions, measured by walking speed and time-up-to-go test, are also observed, especially with longer duration of supplementation (>6 months), although the changes are small and unlikely to be clinically meaningful. Lastly, n-3 PUFA supplementation may positively affect muscle protein synthesis response to anabolic stimuli, alleviating age-related anabolic resistance. Proposed mechanisms by which n-3 PUFA supplementation improves muscle health include 1. anti-inflammatory properties, 2. augmented expression of mechanistic target of rapamycin complex 1 (mTORC1) pathway, 3. decreased intracellular protein breakdown, 4. improved mitochondrial biogenesis and function, 5. enhanced amino acid transport, and 6. modulation of neuromuscular junction activity. In conclusion, n-3 PUFAs likely improve musculoskeletal health related to sarcopenia, with suggestive effect on muscle mass, strength, physical performance, and muscle protein synthesis. However, the interpretation of the findings is limited by the small number of participants, heterogeneity of supplementation regimens, and different measuring protocols.

Does omega-3 supplementation improve the inflammatory profile of patients with heart failure? a systematic review and meta-analysis.

Omega-3 fatty acids are potential anti-inflammatory agents that may exert beneficial outcomes in diseases characterised by increased inflammatory profile. The purpose of this study was to comprehensively evaluate the existing research on the effectiveness of n-3 fatty acid supplementation in lowering levels of circulating inflammatory cytokines in patients with heart failure (HF). From the beginning until October 2022, randomised controlled trials (RCTs) were the subject of PubMed, Scopus, Web of Science, and Cochrane Library literature search. Omega-3 fatty acid supplementation vs. placebo were compared in eligible RCTs to see how they affected patients with HF in terms of inflammation, primarily of tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and c-reactive protein (CRP). A meta-analysis employing the random effects inverse-variance model and standardised mean differences was performed to assess group differences. Ten studies were included in this systematic review and meta-analysis. Our main analysis (k = 5) revealed a beneficial response of n-3 fatty acid supplementation on serum TNF-a (SMD: - 1.13, 95% CI: - 1.75- - 0.50, I2 = 81%, P = 0.0004) and IL-6 levels (k = 4; SMD: - 1.27, 95% CI: - 1.88- - 0.66, I2 = 81%, P < 0.0001) compared to placebo; however, no changes were observed in relation to CRP (k = 6; SMD: - 0.14, 95% CI: - 0.35-0.07, I2 = 0%, P = 0.20). Omega-3 fatty acid supplementation may be a useful strategy for reducing inflammation in patients with HF, but given the paucity of current studies, future studies may increase the reliability of these findings.

Mortality and outcome in fragility hip fracture care during COVID-19 pandemic in Police General Hospital, Thailand.

Objectives: The objective of this study is to assess outcomes and patient's mortality of Police General Hospital's fracture liaison service (PGH's FLS) during Coronavirus disease 2019 (COVID-19) outbreak comparing to the former period. Methods: Retrospective cohort study was performed in patients aged 50 or older who were admitted with fragility hip fracture in Police General Hospital, Bangkok, between January 1, 2018 to December 31, 2019 (before pandemic) comparing to January 1, 2020 to December 31, 2021 (pandemic) using the electronic database. The outcomes were mortality and other outcomes in one-year follow up. Results: A total of 139 fragility hip fractures were recorded in 2018-2019 (before pandemic) compared with 125 in 2020-2021 (pandemic). The 30-day mortality in hip fracture numerically increased from 0% to 2.4% during the pandemic. One-year mortality was significantly escalated from 2 cases (1.4%) to 5 cases (4%) (P = 0.033). However, the cause of mortality was not related with COVID-19 infection. We also found a significantly shorter time to surgery but longer wait time for bone mineral density (BMD) testing and initiation of osteoporosis medication in pandemic period. Conclusions: The results of this study in COVID-19 pandemic period, 1-year mortality rate was significantly higher but they were not related with COVID-19 infection. We also found longer time to initial BMD testing and anti-osteoporotic medication and more loss of follow up, causing lower anti-osteoporotic medication taking. In contrast, the time to surgery became shorter during the pandemic.

Trabecular bone score as an additional therapeutic decision tool in osteoporosis and osteopenia.

Objectives: To evaluate the role of trabecular bone score (TBS), in addition to bone mineral density (BMD), and to aid decision making to initiate anti-osteoporotic treatment in postmenopausal women with osteopenia. Methods: TBS was assessed in a cohort of Thai postmenopausal women with BMD of femoral neck (FN), total hip (TH), and lumbar spine (LS) performed at the Police General Hospital, Bangkok, Thailand from July 2019 to October 2020. We retrospectively reviewed hospital database for underlying diseases, medication, and fractures, including relevant imaging and vertebral fracture assessment (VFA). Patients with previous osteoporosis treatment, skeletal malignancy, high-energy trauma, and uninterpretable BMD were excluded. Results: In total there were 407 postmenopausal women, including 115 with osteoporotic fractures. The mean TBS of the cohort was 1.264 ± 0.005. The proportion of osteoporotic subjects ranged from 9.1% by TH BMD to 27.0% by lowest BMD. In fractured patients, 21.7%-54.8% were found to have osteoporosis while osteopenia was found in 37.4%-43.5%. Among subjects with osteopenia and degraded TBS, fractures ranged from 21.7 to 50.9%. Addition of osteopenic subjects with degraded microarchitecture yielded a significantly higher number of subjects eligible for treatment with 3.25-fold increase in non-fractured participants, and 7 to 11 additional osteopenic patients should be treated to detect 1 fracture. Conclusions: Addition of TBS helped capturing osteopenic women with high risk of fracture. Decision to treat osteopenic women with degraded TBS increased the number of patients receiving treatment. We recommend evaluating TBS in osteopenic women without fractures to aid therapeutic decision on treatment initiation.

Efficacy of plain cholecalciferol versus ergocalciferol in raising serum vitamin D level in Thai female healthcare workers.

Objectives: To compare the efficacy of cholecalciferol and ergocalciferol in raising 25-hydroxyvitamin D (25(OH)D) level in Thai female healthcare workers. Methods: A randomized control trial was conducted in healthy female healthcare workers. Randomization allocated the participants into vitamin D2 group (N = 43), receiving ergocalciferol 20,000 IU weekly and vitamin D3 group (N = 40), receiving cholecalciferol 1000 IU daily for 12 months. Venous blood sample was collected at baseline, 6 and 12 months for serum 25(OH)D, parathyroid hormone and calcium. Compliance was also assessed. Results: The mean age of the participants was 50.6 ± 9.9 and 50.9 ± 8.4 years in vitamin D2 and D3 groups (P = 0.884). The mean 25(OH)D levels were 16.91 ± 6.07 ng/mL and 17.62 ± 4.39 ng/mL (P = 0.547), respectively. Both groups had significant improvement in 25(OH)D level at 6 months (from 16.91 ± 6.07 to 21.67 ± 5.11 ng/mL and 17.62 ± 4.39 to 26.03 ± 6.59 ng/mL in vitamin D2 and D3 group). Improvement was significantly greater with cholecalciferol (P = 0.018). The level plateaued afterwards in both groups. Only cholecalciferol could increase 25(OH)D in participants without vitamin D deficiency (6.88 ± 4.20 ng/mL increment). Compliance was significantly better in vitamin D2 group (P = 0.025). Conclusions: Daily cholecalciferol supplementation resulted in a larger increase in serum 25(OH)D level during the first 6 months comparing to weekly ergocalciferol. While vitamin D3 could increase serum 25(OH)D level in all participants, vitamin D2 could not do so in participants without vitamin D deficiency.

Trabecular Bone Score as a Risk Factor of Major Osteoporotic Fracture in Postmenopausal Women: The First Study in Thailand.

OBJECTIVES: To compare the trabecular bone score (TBS) between Thai postmenopausal women with and without major osteoporotic fracture, and to determine whether TBS is associated with fracture risk. METHODS: All postmenopausal women sent for dual-energy X-ray absorptiometry (DXA) at the Police General Hospital were retrospectively recruited. The hospital's online database and radiographs were reviewed to collect information on underlying disease, medication, previous fractures, bone mineral density, and trabecular bone score. Patients with anti-osteoporotic medication use, skeletal malignancy, fracture from high-energy trauma, and uninterpretable DXA images were excluded. RESULTS: A total of 407 Thai postmenopausal women were enrolled. They were divided into 292 women without fractures and 115 women with major osteoporotic fractures. The fracture group was older (73.36 ± 9.95 vs. 66.00 ± 8.58, P < 0.001) and had lower serum 25-hydroxyvitamin D levels (23.28 ± 9.09 vs. 26.44 ± 9.20, P = 0.023). The mean TBS was lower in the fracture group, compared to the non-fracture group (1.244 ± 0.101 vs. 1.272 ± 0.099, P = 0.011). The subgroup analysis resulted in noticeably lower TBS in spine fracture, but not other fracture sites. The odds ratio of fracture was 1.355 (P = 0.013) for a decrease in one standard deviation of TBS. CONCLUSIONS: TBS was significantly lower in postmenopausal women having fractures with an odd ratio of 1.355 (P = 0.013) per SD decrease in TBS. Categorizing by fracture sites, TBS was only found to be noticeably lower in the lumbar spine despite similar lumbar spine bone mineral density.

Comparison of bone mineral density and vertebral fracture assessment in postmenopausal women with and without distal radius fractures.

OBJECTIVES: To compare bone mineral density (BMD) in Thai postmenopausal women with and without distal radius fracture, and to investigate the role of vertebral fracture assessment (VFA) in diagnosing osteoporosis after distal radius fracture. METHODS: A cross-sectional study was conducted in Thai postmenopausal women with and without distal radius fracture. BMDs of the femoral neck (FN), total hip (TH), lumbar spine (LS), and VFA were obtained within 2 weeks of injury. BMD were compared between groups. Participants were classified into osteoporosis, osteopenia or normal using BMD alone, and BMD plus VFA, where a mere presence of vertebral compression fracture indicated osteoporosis. RESULTS: Fifty postmenopausal women with distal radius fractures and 111 non-fracture postmenopausal women participated. The mean BMD was significantly lower at all sites in the fracture group (FN BMD 0.590 ± 0.075 vs 0.671 ± 0.090, p = 0.007; TH BMD 0.742 ± 0.103 vs 0.828 ± 0.116, P = 0.009; LS BMD 0.799 ± 0.107 vs 0.890 ± 0.111, P = 0.009 in the fracture vs non-fracture group respectively). VFA increased the prevalence of osteoporosis from 16 (32%) to 23 (46%) in the fracture group, and 7 (6.31%) to 17 (16.22%) in the non-fracture group, with a number needed to treat 9. CONCLUSIONS: Postmenopausal women with distal radius fractures had lower BMD. Incorporating VFA into diagnosis of osteoporosis increased the prevalence of osteoporosis in both fracture and non-fracture groups. Postmenopausal women aged 50 years or older with distal radius fracture are a good target for the investigation of osteoporosis.

Is ankle fracture related to low bone mineral density and subsequent fracture? A systematic review.

OBJECTIVES: Ankle fractures are common in the elderly. However, their association with osteoporosis remains controversial. This systematic review aims to determine the relationship between ankle fracture and bone mineral density (BMD), and to investigate the risk of subsequent fractures after ankle fracture. METHODS: MEDLINE and Scopus publications were searched from inception to March and April 2019, respectively. Articles were selected by 2 independent reviewers for cross-sectional, cohort, or case-control studies comparing BMD or subsequent fracture risk in low-energy ankle fractures patients with that of the normal population. Data extraction was performed by 2 investigators. Discrepancies were resolved with the third reviewer. Quality assessment was conducted using the modified Newcastle-Ottawa Scale. RESULTS: Overall, 19 articles were included. The quality assessment showed a generally low-to-moderate risk of bias among studies, mainly due to potential confounders and inadequate follow-up. Of 13 studies exploring BMD in ankle fractured-patients, lower central and peripheral BMD was found in 3 and 2 studies, respectively. The risk of subsequent fracture was examined in 11 studies with relative risks ranging from 0.7 to 4.59. An increased risk of any subsequent fractures in women, both genders, and men was found in 5, 2, and 1 articles, respectively. CONCLUSIONS: Despite the lack of clear association with BMD, the contribution of ankle fracture to increased subsequent fracture risk and its associated microarchitectural changes cannot be overlooked. Moreover, its potential role as an early predictor of future fracture may promote secondary prevention. Further studies with longer follow-up and stricter confounder control are recommended.