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Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis.
Prokopidis, K, Mazidi, M, Sankaranarayanan, R, Tajik, B, McArdle, A, Isanejad, M
The British journal of nutrition. 2023;129(5):759-770
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Reduced muscle mass and reduction in physical activity may lead to sarcopenia in older people. Age-related sarcopenia is associated with increased systemic low-grade inflammation and obesity. Protein supplementation is found to be beneficial in reducing circulating pro-inflammatory cytokines in old people. Previous research has shown that supplementation with isolated whey and soy protein reduces the levels of inflammatory cytokines in older adults. However, there is limited research on intact whey and soy protein supplementation in reducing age-related inflammation. This systematic review and meta-analysis investigated the effect of intact whey and soy protein on serum inflammatory markers such as C-reactive protein (CRP), Interleukin-6 (IL6) and TNF-α in older adults. The results of this meta-analysis show a significant reduction in circulating IL-6 and TNF-α levels after the supplementation with whey and soy protein. The addition of soy isoflavones resulted in a further decline in serum CRP levels. Subgroup analysis showed that the whey protein supplementation significantly improved sarcopenia and pre-frailty. Healthcare professionals can use the result of this systematic review and meta-analysis to understand the anti-inflammatory properties of intact whey and soy protein and soy isoflavones. However, further robust studies are required to assess the anti-inflammatory properties of whey and soy protein due to the high heterogeneity of included studies in this review.
Abstract
BACKGROUND AND AIMS Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers. METHODS We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases from inception until September 2021. To determine the effectiveness of isolated proteins on circulating levels of C-reactive protein (CRP), IL-6 and TNF-α, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42021252603). RESULTS Thirty-one RCT met the inclusion criteria and were included in the systematic review and meta-analysis. A significant reduction of circulating IL-6 levels following whey protein [Mean Difference (MD): -0·79, 95 % CI: -1·15, -0·42, I2 = 96 %] and TNF-α levels following soy protein supplementation (MD: -0·16, 95 % CI: -0·26, -0·05, I2 = 68 %) was observed. The addition of soy isoflavones exerted a further decline in circulating TNF-α levels (MD: -0·20, 95 % CI: -0·31, -0·08, I2 = 34 %). According to subgroup analysis, whey protein led to a statistically significant decrease in circulating IL-6 levels in individuals with sarcopenia and pre-frailty (MD: -0·98, 95 % CI: -1·56, -0·39, I2 = 0 %). These findings may be dependent on participant characteristics and treatment duration. CONCLUSIONS These data support that whey and soy protein supplementation elicit anti-inflammatory effects by reducing circulating IL-6 and TNF-α levels, respectively. This effect may be enhanced by soy isoflavones and may be more prominent in individuals with sarcopenia.
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Are dietary intake and nutritional status of specific polyunsaturated fatty acids correlated with sarcopenia outcomes in community-dwelling older adults with sarcopenia? - Exploratory results from ENHANce.
Dupont, J, Wauters, E, Dedeyne, L, Vercauteren, L, Amini, N, Lapauw, L, Matthys, C, Verschueren, S, Tournoy, J, Koppo, K, et al
BMC geriatrics. 2023;23(1):272
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Diet plays an important role in the development and treatment of sarcopenia, the age-related loss of muscle mass and function. Besides protein intake, the intake of polyunsaturated fatty acids (PUFAs) is also suggested to influence muscle physiology and sarcopenia progression. The aim of this study was to assess the dietary intake of PUFAs and PUFAs status in a sample of well-defined sarcopenic older adults. This study was a secondary, exploratory, cross-sectional analysis of 29 older adults (aged 65 years or older) with sarcopenia. Results showed that omega-3 PUFAs intake was low in older adults with sarcopenia. Moreover, PUFAs intake and status did not correspond well in this population. Authors concluded that intake or status of omega-3 was positively associated with measures of sarcopenia, whereas intake of omega-6 was negatively associated.
Abstract
AIMS: To explore the relationship between dietary polyunsaturated fatty acids (PUFAs) intake, nutritional PUFAs status and sarcopenia outcomes in sarcopenic older adults. METHODS The Exercise and Nutrition for Healthy AgeiNg (ENHANce) is an ongoing 5-armed triple blinded randomized controlled trial, in sarcopenic older adults (> 65y) aiming to assess the effect of combined anabolic interventions (protein, omega-3 supplement and exercise) on physical performance in these adults, compared to single/placebo interventions. Baseline data were used for a secondary, exploratory, cross-sectional analysis. Dietary PUFAs intake was assessed with 4-day food records, status with RBC membrane fatty acids profiles. Spearman's rho(ρ) correlation coefficients were calculated to explore associations of PUFAs intake and status with sarcopenia-defining parameters (muscle strength, mass and physical performance), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS In total, 29 subjects (9♂/20♀, mean age 76.3 ± 5.4y) were included. Total omega-3 intake of participants (1.99 ± 0.99 g/d) was below the recommended intake (♂:2.8-5.6 g/d; ♀:2.2-4.4 g/d). Intake and status of PUFAs were not correlated. Regarding correlations with outcomes, α-linolenic acid status was inversely associated with appendicular lean mass (aLM) (ρ:-0.439; p = 0.017), whereas docosahexaenoic acid status was positively associated with aLM (ρ:0.388; p = 0.038). Some omega-3 PUFAs intake and status markers were positively associated with step count, SF-36 and SarQoL scores, whereas gamma-linolenic acid status was inversely associated with SF-36 physical component summary score (ρ = -0.426; p = 0.024). CONCLUSIONS Although intake of omega-3 and omega-6 was low, the present exploratory study generated new hypotheses for potential correlations of PUFAs intake and status with sarcopenia outcomes in older adults with sarcopenia.
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Are inflammatory markers associated with sarcopenia-related traits in older adults with sarcopenia? - A cross-sectional analysis of the ENHANce study.
Dupont, J, Vercauteren, L, Amini, N, Lapauw, L, De Schaepdryver, M, Poesen, K, Dedeyne, L, Verschueren, S, Tournoy, J, Koppo, K, et al
Experimental gerontology. 2023;178:112196
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Sarcopenia is a muscle disease, characterised by loss of muscle mass and function, leading to ‘muscle failure’. Primary sarcopenia is age-driven and one of the major mechanisms behind the onset and progression of sarcopenia is the chronic low grade inflammatory state related with ageing, the so-called ‘Inflammageing’. The aim of this study was to explore the levels of inflammatory markers (CRP, albumin, IL-1β, IL-6, IL-8 and TNF-α) in older adults with sarcopenia. This study was an exploratory, secondary, cross-sectional analysis. In total, 40 older adults (15 men and 25 women) with probable, confirmed, or severe sarcopenia were included. Results showed subclinical low levels of inflammatory markers in older adults suffering from sarcopenia, compatible with age-related Inflammageing. Positive associations were found between the examined inflammatory markers and sarcopenia-related traits. Furthermore, gender had a significant influence on the associations between these inflammatory markers and sarcopenia-related traits. Authors concluded that their findings stress the complexity of the inflammageing-sarcopenia interplay and the importance of not only looking at muscle mass or the sarcopenia construct when researching sarcopenia, but also considering other sarcopenia-related traits and gender in future research.
Abstract
AIMS: To explore the relationship between inflammatory markers and sarcopenia-related traits in sarcopenic older adults. METHODS Baseline data of the ongoing Exercise and Nutrition for Healthy AgeiNg (ENHANce) study were used for a secondary, exploratory, cross-sectional analysis. ENHANce is a 5-armed triple blinded randomized controlled trial, in older adults (>65y) with sarcopenia defined according to the revised criteria of the European Working Group of Sarcopenia in Older People (EWGSOP2) aiming to assess the effect of combined anabolic interventions (protein supplement, omega-3 supplement and physical exercise) on physical performance, compared to single/placebo interventions. Inflammatory markers C-reactive protein (hs-CRP), albumin, interleukin-1β (IL-1β), IL-6, IL-8, and tumour necrosis factor-α (TNF-α) were assessed at baseline. Spearman's rho (ρ) correlation coefficients were calculated to associate these inflammatory markers with baseline sarcopenia-defining parameters (handgrip strength, chair stand test, appendicular lean mass [aLM], gait speed, Short Physical Performance Battery), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS We included 40 sarcopenic subjects (15 men/25 women, age 77.1 ± 6.8 years). Contrary to expectations, the pro-inflammatory IL-1β correlated positively with handgrip strength (ρ: 0.376; p = 0.024) and IL-6 with aLM (ρ: 0.334; p = 0.0433). IL-6 inversely correlated with step count (ρ:-0.358; p = 0.048). Subgroup analysis revealed important gender differences. IL-8 inversely correlated with handgrip strength in women (ρ: -0.425; p = 0.034) but not in men. In contrast, pro-inflammatory cytokines CRP (ρ: -0.615; p = 0.019), IL-6 (ρ: -0.604; p = 0.029) and TNF-α (ρ: -0.615; p = 0.025) inversely correlated with the SF-36 physical component score in men but not in women. CONCLUSION Although Inflammageing might play a role in sarcopenia-related traits, this exploratory study highlights an important role of gender. Future research should take this into account when elucidating the Inflammageing-sarcopenia interplay.
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Effects of multi-domain intervention on intrinsic capacity in older adults: A systematic review of randomized controlled trials (RCTs).
Liao, X, Shen, J, Li, M
Experimental gerontology. 2023;174:112112
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With the increase of age, the physiological reserve of the elderly decreases, which leads to the increase of physical vulnerability and the decrease of anti-stress ability, showing a series of frailty manifestations. Intrinsic capacity (refers to the comprehensive capacity of all physical and mental capacities of an individual) is central to maintaining function in older adults, and maintaining optimal intrinsic capacity is important to promote healthy aging. The aim of this study was to assess randomised controlled trials of multidomain interventions to further validate their effectiveness in the maintenance and enhancement of function in older adults, and to formulate strategies for preventive care and clinical practice. This study was a systematic review and meta-analysis of twenty-five publications. Results showed that multi-domain interventions can improve indicators of vital domains in older adults and integrate to optimise intrinsic capacity (refers to the comprehensive capacity of all physical and mental capacities of an individual) through potential interaction mechanisms. Authors concluded that because older adults may not be able to receive overly complex interventions due to limitations in their integrative abilities, the involvement of older adults and the sustainability of interventions should be considered before implementing them.
Abstract
Intrinsic capacity is central to the maintenance of function in older adults, and maintaining optimal intrinsic capacity is of great importance to promote healthy aging. The purpose of this systematic review and meta-analysis was to analyze the impact of multi-domain interventions on intrinsic capacity in older adults, intervention components, and potential interactions between components. A total of 6740 published articles were screened until August 2022, and the review included 25 randomized controlled trials that analyzed populations, interventions, control groups, and outcomes. The meta-analysis showed improvements in the primary outcome indicators in the intervention group compared to the control group. These included increased scores on the Mini-Mental State Examination as an indicator of cognitive function, decreased scores on the Geriatric Depression Scale (GDS-15) as an indicator of psychological ability and increased scores on the Short Physical Performance Battery (SPPB) as an indicator of physical performance, with only the SPPB indicator analyzed showing greater heterogeneity. Significant improvements were also seen in the secondary indicators Time-to-Walk Test (TUG), gait speed, Chair Stand Test (CST), grip strength values and BMI. There was insufficient data for the Mini Nutritional Assessment (MNA) as an indicator of vitality to conduct a meta-analysis. Studies were of moderate to high quality. The results of this review indicate that multi-domain interventions can maintain the level of intrinsic capacity in older adults and are equally effective in older adults with declining self-care abilities.
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Reducing hip and non-vertebral fractures in institutionalised older adults by restoring inadequate intakes of protein and calcium is cost-saving.
Baek, Y, Iuliano, S, Robbins, J, Poon, S, Seeman, E, Ademi, Z
Age and ageing. 2023;52(6)
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Older adults in aged care account for 30% of the population burden of hip fractures. Inadequate intakes of protein and calcium are common in older adults living in aged care homes. The aims of this study were to determine cost-effectiveness of this dietary intervention, and the threshold at which nutritional intervention was cost-effective, from the Australian healthcare perspective. This study was a 2-year cluster-randomised controlled trial which was conducted in 60 residential aged care homes. Aged care homes prepared all foods on-site and were randomised in a 1:1 ratio to nutritional intervention (calcium and protein enriched menu) or control (regular menu). Results showed that reducing fracture risk in older adults in residential aged care homes by restoring calcium and protein intakes to recommended levels using high-calcium and high-protein foods is cost-saving. Authors concluded that averting hip and other non-vertebral fractures in older adults living in aged care homes by restoring nutritional inadequacy of protein and calcium is cost-saving and supports the wide-spread implementation of this type of nutritional intervention in similar settings.
Abstract
BACKGROUND older adults in aged care account for 30% of the population burden of hip fractures. Nutritional interventions to correct under nutrition reduce these debilitating fractures, perhaps partly by reducing falls and slowing deterioration in bone morphology. OBJECTIVE to determine whether a nutritional approach to fracture risk reduction in aged care homes is cost-effective. DESIGN cost-effectiveness was estimated based on results from a prospective 2-year cluster-randomised controlled trial and secondary data. Intervention residents consumed a total of 3.5 daily servings of milk, yoghurt and/or cheese, resulting in 1,142 mg of calcium and 69 g of protein compared with the daily intakes of 700 mg of calcium and 58 g of protein consumed by the control group. SETTING fifty-six aged care homes. PARTICIPANTS residents for 27 intervention (n = 3,313) and 29 control (n = 3,911) homes. METHODS ambulance, hospital, rehabilitation and residential care costs incurred by fracture were estimated. The incremental cost-effectiveness ratios per fracture averted within a 2-year time horizon were estimated from the Australian healthcare perspective applying a 5% discount rate on costs after the first year. RESULTS intervention providing high-protein and high-calcium foods reduced fractures at a daily cost of AU$0.66 per resident. The base-case results showed that the intervention was cost-saving per fracture averted, with robust results in a variety of sensitivity and scenario analyses. Scaling the benefits of intervention equates to a saving of AU$66,780,000 annually in Australia and remained cost-saving up to a daily food expenditure of AU$1.07 per resident. CONCLUSIONS averting hip and other non-vertebral fractures in aged care residents by restoring nutritional inadequacy of protein and calcium is cost-saving.
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Impact of a specialized oral nutritional supplement on quality of life in older adults following hospitalization: Post-hoc analysis of the NOURISH trial.
Baggs, GE, Middleton, C, Nelson, JL, Pereira, SL, Hegazi, RM, Matarese, L, Matheson, E, Ziegler, TR, Tappenden, KA, Deutz, N
Clinical nutrition (Edinburgh, Scotland). 2023;42(11):2116-2123
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Malnutrition in hospitalised adults is recognized as a challenging health concern that is associated with many adverse outcomes. Malnutrition screening and assessment are essential for all patients admitted to the hospital and are particularly important for adults who are vulnerable. The aim of this study was to determine whether specialised oral-nutritional supplements (S-ONS) benefits were further associated with measurable improvements in quality of life (QoL) domains during the post-hospitalisation period. This study was a post-hoc analysis of NOURISH trial data. The NOURISH trial was a multicentre, prospective, randomised, double-blind, placebo-controlled, parallel-group study. Six-hundred and twenty-two patients were included in the intent-to-treat analysis. Results showed that malnourished, older patients who received daily interventions with S-ONS (during hospital stay and for 90-day post-discharge) had significantly better QoL domain scores compared to those who received only placebo intervention. Specifically, there were significant differences in the QoL domains of mental health/ cognition, vitality, social functioning, and general health. Further, there were significant QoL differences for physical component, physical functioning, bodily pain, and emotional role. Authors concluded that among malnourished, hospitalised patients (aged 65 years and over), supplementation with S-ONS during the hospitalisation and 90-days post discharge resulted in improvements in QoL.
Abstract
BACKGROUND & AIMS Both during and after hospitalization, nutritional care with daily intake of oral nutritional supplements (ONS) improves health outcomes and decreases risk of mortality in malnourished older adults. In a post-hoc analysis of data from hospitalized older adults with malnutrition risk, we sought to determine whether consuming a specialized ONS (S-ONS) containing high protein and beta-hydroxy-beta-methylbutyrate (HMB) can also improve Quality of Life (QoL). METHODS We analyzed data from the NOURISH trial-a randomized, placebo-controlled, multi-center, double-blind study conducted in patients with congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. Patients received standard care + S-ONS or placebo beverage (target 2 servings/day) during hospitalization and for 90 days post-discharge. SF-36 and EQ-5D QoL outcomes were assessed at 0-, 30-, 60-, and 90-days post-discharge. To account for the missing QoL observations (27.7%) due to patient dropout, we used multiple imputation. Data represent differences between least squares mean (LSM) values with 95% Confidence Intervals for groups receiving S-ONS or placebo treatments. RESULTS The study population consisted of 622 patients of mean age ±standard deviation: 77.9 ± 8.4 years and of whom 52.1% were females. Patients consuming placebo had lower (worse) QoL domain scores than did those consuming S-ONS. Specifically for the SF-36 health domain scores, group differences (placebo vs S-ONS) in LSM were significant for the mental component summary at day 90 (-4.23 [-7.75, -0.71]; p = 0.019), the domains of mental health at days 60 (-3.76 [-7.40, -0.12]; p = 0.043) and 90 (-4.88 [-8.41, -1.34]; p = 0.007), vitality at day 90 (-3.33 [-6.65, -0.01]; p = 0.049) and social functioning at day 90 (-4.02 [-7.48,-0.55]; p = 0.023). Compared to placebo, differences in LSM values for the SF-36 general health domain were significant with improvement in the S-ONS group at hospital discharge and beyond: day 0 (-2.72 [-5.33, -0.11]; p = 0.041), day 30 (-3.08 [-6.09, -0.08]; p = 0.044), day 60 (-3.95 [-7.13, -0.76]; p = 0.015), and day 90 (-4.56 [-7.74, -1.38]; p = 0.005). CONCLUSIONS In hospitalized older adults with cardiopulmonary diseases and evidence of poor nutritional status, daily intake of S-ONS compared to placebo improved post-discharge QoL scores for mental health/cognition, vitality, social functioning, and general health. These QoL benefits complement survival benefits found in the original NOURISH trial analysis. CLINICAL TRIAL REGISTRATION NCT01626742.
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The Influence of Whey Protein on Muscle Strength, Glycemic Control and Functional Tasks in Older Adults with Type 2 Diabetes Mellitus in a Resistance Exercise Program: Randomized and Triple Blind Clinical Trial.
Soares, ALS, Machado-Lima, A, Brech, GC, Greve, JMD, Dos Santos, JR, Inojossa, TR, Rogero, MM, Salles, JEN, Santarem-Sobrinho, JM, Davis, CL, et al
International journal of environmental research and public health. 2023;20(10)
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Type 2 Diabetes Mellitus (T2DM) is a common metabolic disease and the prevalence of T2DM is increasing among older adults. Resistance training is known to be an effective therapeutic strategy as it can positively influence the mechanisms of T2DM pathophysiology. Previous research suggests that whey protein supplementation can positively influence the different mechanisms of T2DM pathophysiology and improve muscle mass and glycaemic control. This triple-blinded, randomised controlled parallel-arm trial included twenty-eight male older adults to assess the effect of whey protein supplementation combined with resistance training for twelve weeks on glycaemic control, functional tasks, muscle strength, and body composition. The control group was supplemented with maltodextrin. All participants followed resistance training and were given nutritional guidance. Twelve weeks of resistance training improved muscle strength significantly. However, 20g whey protein supplementation did not improve performance in functional tasks, glycaemic control, or body composition in the test group of older adults with T2DM. Whey protein supplementation showed no significant synergetic effects when combined with resistance training in the test group. Due to the heterogeneity of the present study, further robust studies are warranted to investigate the effects of whey protein supplementation and resistance training. However, healthcare professionals can use the results of this study to understand the effect of resistance training alone and the safety profile of whey protein supplementation in older adults with T2DM.
Abstract
OBJECTIVES To evaluate the effect of whey protein (WP) supplementation associated with resistance training (RT) on glycemic control, functional tasks, muscle strength, and body composition in older adults living with type 2 diabetes mellitus (T2DM). Secondly, to evaluate the safety of the protocol for renal function. METHODS The population comprised twenty-six older men living with T2DM (68.5 ± 11.5 years old). The participants were randomly assigned to the Protein Group (PG) and the Control Group (CG). The handgrip test and evolution of exercise loads, according to the Omni Resistance Exercise Scale, evaluated muscle strength. Functional tasks were assessed by force platform in three different protocols: Sit-to-Stand, Step/Quick Turn, and Step Up/Over. Body composition was evaluated by bioimpedance and glycemic control and renal function were assessed by biochemical analyses. Both groups performed RT for 12 weeks, twice a week, prioritizing large muscle groups. Protein supplementation was 20 g of whey protein isolate and the CG was supplemented with an isocaloric drink, containing 20 g of maltodextrin. RESULTS There was a significant difference in muscle strength, according to the evolution of the exercise loads, but it was not confirmed in the handgrip test. However, there was no significant difference between the groups, regarding performance in functional tasks, glycemic control, or body composition. Renal function showed no alteration. CONCLUSION The intake of 20 g of WP in older male adults living with T2DM did not increase the effect of RT on muscle strength, functional tasks, and glycemic control. The intervention was proven safe regarding renal function.
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Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial.
Katayoshi, T, Uehata, S, Nakashima, N, Nakajo, T, Kitajima, N, Kageyama, M, Tsuji-Naito, K
Scientific reports. 2023;13(1):2786
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Nicotinamide adenine dinucleotide (NAD+) is a coenzyme that plays a crucial role in energy metabolism and different biological processes. Sirtuins (SIRT1) are NAD+-dependent deacetylases, an enzyme that plays a key role in enhancing metabolic efficiency. Nicotinamide mononucleotide (NMN) is a precursor to NAD+. NMN supplementation may help to reduce the risk of developing metabolic diseases and cardiovascular diseases. This randomised, double-blinded, and placebo-controlled, parallel trial investigated the effects of 12 weeks of 125 mg NMN supplementation on metabolic health parameters, including CVD risk factors, blood NAD+ metabolites level, and SIRT1 expression in middle-aged men and women. Serum nicotinamide was significantly higher and arterial stiffness was lower in the NMN test group of middle-aged men and women after 12 weeks of NMN supplementation. The results of the study indicate that the administration of 250mg of nicotinamide mononucleotide (NMN) daily for an extended period is considered safe and well-tolerated. Healthcare professionals can use this finding to understand the significant implications of the use of NMN as a potential therapeutic agent in individuals seeking to improve their metabolic and cardiovascular health. Further robust studies are required to evaluate the effects of NMN supplementation due to the limitations and high baseline variability between the participants of this study.
Expert Review
Conflicts of interest:
None
Take Home Message:
- As we age, NAM levels decline, which could have a negative effect on cardiovascular health.
- Middle-aged adults may like to consider NMN supplementation to improve NAM metabolism and arterial stiffness.
- However, without data on CVD events, it is difficult to determine actual risk reductions.
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
- Nicotinamide adenine dinucleotide (NAD+) is a coenzyme involved in metabolism. When we age, NAD+ levels decline resulting in poorer metabolism and age-related disease such as cardiovascular disease (CVD). Nicotinamide mononucleotide (NMN) is a precursor in the biosynthesis of NAD+.
- This double-blind, randomised control trial aimed to determine the effect of supplementing NMN on NAD+ levels, CVD risk factors and sirtuin 1 (SIRT1) expression, which relies on NAD+ for adequate functioning.
Methods
- 36 healthy male and female individuals aged between 40-65 years of age were assigned to either NMN (125mg/day) or placebo for 12 weeks.
- One capsule was taken twice per day after meals.
- Serum nicotinamide (NAM), NAD+, NMN, advanced glycation end products (AGES), 8-hydroxydeoxyguanosine (8-OHdG) and SIRT1 mRNA expression were measured.
- The condition of blood vessels (arterial stiffness) was also assessed using the ankle brachial index (ABI).
- In a sub-analysis, individuals with hypertension, above average body mass index (BMI), or blood glucose level were also assessed for blood vessel condition using the ABI.
Results
- The results showed that from baseline serum NAM decreased in the placebo group (P=0.014), whereas it increased in the NMN group (P=0.006). This resulted in an increase in the NMN group compared to placebo (P=0.037).
- Interestingly serum NAM was lower in the NMN group compared to placebo at baseline (P=0.001).
- There was no statistically significant difference in ABI with NMN supplementation.
- Amongst those with hypertension there was also no change in ABI. However, those with high BMI or blood glucose, there was an improvement in vascular condition compared to placebo (P=<0.007 and P=0.019 respectively).
- 8-OHdG, SIRT1 mRNA and AGEs remained unchanged by NMN supplementation
Conclusion
- NMN supplementation enhanced NAD+ metabolism in middle-aged adults.
- It also relieved arterial stiffness and reduced CVD risk factors.
Clinical practice applications:
- Apparently healthy middle-aged adults who would like to activate NAD metabolism and decrease their risk for CVD, should consider 12-week supplementation with NMN (125mg/day).
- ABI should be monitored to ensure desired effects.
- It is unclear as to the effects of NMN supplementation after 12-weeks.
Considerations for future research:
- Future research should consider longer supplementation duration and/or adding in a follow-up period to determine duration of effect.
- Different supplemental doses should also be researched to determine an optimal dose.
Abstract
Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.
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The effects of time-restricted eating and weight loss on bone metabolism and health: a 6-month randomized controlled trial.
Papageorgiou, M, Biver, E, Mareschal, J, Phillips, NE, Hemmer, A, Biolley, E, Schwab, N, Manoogian, ENC, Gonzalez Rodriguez, E, Aeberli, D, et al
Obesity (Silver Spring, Md.). 2023;31 Suppl 1:85-95
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Intermittent fasting (IF) involves an alternation of abstinence and consumption of food and caloric beverages over a cycle of hours to days. Time-restricted feeding (in animals) or eating (TRE in humans) is a form of IF that entails restricting eating within a window of 4 to 12 hours per 24-hour cycle and prolonging the time spent in the fasted state to realign eating-fasting patterns with circadian rhythms. The aim of this study was to explore the impact of a 6-month randomised controlled trial of TRE versus standard dietary advice (SDA, active control arm) on bone metabolism and health in a population with at least one component of the metabolic syndrome. This study is a secondary analysis of an open-label 6-month randomised controlled trial in which participants who ate within a time interval > 14 hours per 24-hour cycle (n=54) were randomised to TRE or SDA (active control) with a 1:1 allocation ratio. A total of 42 participants (76% women) with available bone turnover markers and/or bone mass measurements were included in this study. Results show that there weren’t any detrimental effects on bone health outcomes i.e. bone metabolism or bone loss after 6 months of TRE. Additionally, weight loss following a period of TRE might be associated with small bone-sparing effects compared with SDA. Authors conclude that future studies of longer duration (>6 months) assessing multiple bone phenotypes are required in order to confirm the study’s findings and explore the effects of various TRE regimens particularly among individuals at risk for bone fragility such as postmenopausal women and the elderly.
Abstract
OBJECTIVE This study explored the impact of time-restricted eating (TRE) versus standard dietary advice (SDA) on bone health. METHODS Adults with ≥1 component of metabolic syndrome were randomized to TRE (ad libitum eating within 12 hours) or SDA (food pyramid brochure). Bone turnover markers and bone mineral content/density by dual energy x-ray absorptiometry were assessed at baseline and 6-month follow-up. Statistical analyses were performed in the total population and by weight loss response. RESULTS In the total population (n = 42, 76% women, median age 47 years [IQR: 31-52]), there were no between-group differences (TRE vs. SDA) in any bone parameter. Among weight loss responders (≥0.6 kg weight loss), the bone resorption marker β-carboxyterminal telopeptide of type I collagen tended to decrease after TRE but increase after SDA (between-group differences p = 0.041), whereas changes in the bone formation marker procollagen type I N-propeptide did not differ between groups. Total body bone mineral content decreased after SDA (p = 0.028) but remained unchanged after TRE (p = 0.31) in weight loss responders (between-group differences p = 0.028). Among nonresponders (<0.6 kg weight loss), there were no between-group differences in bone outcomes. CONCLUSIONS TRE had no detrimental impact on bone health, whereas, when weight loss occurred, it was associated with some bone-sparing effects compared with SDA.
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Insufficient sleep predicts poor weight loss maintenance after 1 year.
Bogh, AF, Jensen, SBK, Juhl, CR, Janus, C, Sandsdal, RM, Lundgren, JR, Noer, MH, Vu, NQ, Fiorenza, M, Stallknecht, BM, et al
Sleep. 2023;46(5)
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Plain language summary
Short sleep duration, defined as less than 6 hours/night, is associated with all-cause mortality, cardiovascular diseases, hypertension, diabetes, and obesity. Sleep restriction causes metabolic and behavioural changes suggesting that short sleep duration may contribute to the development of obesity. The aim of this study was to investigate associations between short sleep duration or poor sleep quality and weight regain after weight loss. This study is based on data from the S-LiTE randomised, controlled trial. Participants followed a low-calorie diet (800 kcal/day) for eight weeks prior to randomisation. Those who lost at least 5% of initial weight were randomised to the control or intervention group. Results showed that participants with objectively measured short sleep duration after a diet-induced weight loss had less success during weight loss maintenance than those with longer sleep duration. Worse sleep quality was associated with less weight loss during a low-calorie diet and subsequent weight maintenance. Authors conclude that insufficient sleep predicts weight regain during interventional efforts to maintain weight loss. Exercise maintained low-calorie diet-induced improvements in sleep quality during 1 year of weight loss maintenance, and liraglutide transiently increased sleep duration.
Abstract
STUDY OBJECTIVES Insufficient sleep may attenuate weight loss, but the role of sleep in weight loss maintenance is unknown. Since weight regain after weight loss remains a major obstacle in obesity treatment, we investigated whether insufficient sleep predicts weight regain during weight loss maintenance. METHODS In a randomized, controlled, two-by-two factorial study, 195 adults with obesity completed an 8-week low-calorie diet and were randomly assigned to 1-year weight loss maintenance with or without exercise and liraglutide 3.0 mg/day or placebo. Sleep duration and quality were measured before and after the low-calorie diet and during weight maintenance using wrist-worn accelerometers (GENEActiv) and Pittsburgh Sleep Quality Index (PSQI). To test associations between insufficient sleep and weight regain, participants were stratified at randomization into subgroups according to sleep duration (≥6 h/night) or sleep quality (PSQI score ≤/>5). RESULTS After a diet-induced 13.1 kg weight loss, participants with short sleep duration at randomization regained 5.3 kg body weight (p = .0008) and had less reduction in body fat percentage compared with participants with normal sleep duration (p = .007) during the 1-year weight maintenance phase. Participants with poor sleep quality before the weight loss regained 3.5 kg body weight compared with good quality sleepers (p = .010). During the weight maintenance phase, participants undergoing liraglutide treatment displayed increased sleep duration compared with placebo after 26 weeks (5 vs. -15 min/night) but not after 1 year. Participants undergoing exercise treatment preserved the sleep quality improvements attained from the initial weight loss. CONCLUSIONS Short sleep duration or poor sleep quality was associated with weight regain after weight loss in adults with obesity.