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Acute beetroot juice reduces blood pressure in young Black and White males but not females.
Grosicki, GJ, Flatt, AA, Cross, BL, Vondrasek, JD, Blumenburg, WT, Lincoln, ZR, Chall, A, Bryan, A, Patel, RP, Ricart, K, et al
Redox biology. 2023;63:102718
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Cardiovascular (CV) disease is the leading cause of death in the United States. Out of all ethnic groups, CV disease is particularly common in black Americans. High blood pressure (BP) is one of the main contributors to CV disease, and black Americans exhibit a disproportionally higher incident rate of high BP when compared to other ethnic groups. Partly this is due to genetic and physiological differences, yet is also influenced by social, socioeconomic, and environmental factors. One physiological difference that may contribute to higher BP in black adults appears to be a reduced availability of nitric oxide (NO). NO is a gas that is abundant in the human body. It regulates vascular tone and elasticity of the arteries, and therefore helps to manage blood pressure. Nitrates that occur in foods can be converted to NO and thus contribute to NO levels in the body. Beetroot juice (BRJ) is rich in nitrates. This study examined whether BRJ supplementation can reduce resting BP and cardiovascular reactivity in adults. The randomized, placebo-controlled, crossover-design study was completed by 18 black and 20 white young adults, male and female, with an average age of 21. The study monitored heart rate, BP and arterial stiffness in a variety of settings. The study also assessed socioeconomic status, perceived discrimination, sleep and dietary intake. The main findings from this investigation were that despite young black adults having higher resting BP, acute BRJ supplementation reduced the pressure to a similar extent in young black and white adults, but primarily in males. This reduction correlated with increased levels of circulating nitrites. However, acute BRJ supplementation did not influence resting arterial stiffness. The result also highlighted previously seen racial differences relating to social determinants of health and lifestyle, which may contribute to the elevated BP values seen in black participants. The study demonstrated that dietary nitrate from beetroot juice has the potential to be a cost-effective blood pressure-lowering strategy for young black and white males. Yet the findings also highlighted the complex interplay of social, lifestyle, and underlying physiological factors that influence racial differences when it comes to CV health
Abstract
A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.
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Exploring choices of early nutritional support for patients with sepsis based on changes in intestinal microecology.
Yang, XJ, Wang, XH, Yang, MY, Ren, HY, Chen, H, Zhang, XY, Liu, QF, Yang, G, Yang, Y, Yang, XJ
World journal of gastroenterology. 2023;29(13):2034-2049
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Sepsis is a condition brought about by infection and results in organ dysfunction and gut microbiota imbalance. Nutrition plays a large part in recovery from sepsis, however it is unclear as to the optimal diet for gut microbial balance in individuals with sepsis. This randomised control trial of 30 individuals with sepsis aimed to determine the optimal delivery of nutrition for gut microbial health either through a gastric tube (TEN), through the jugular vein (TPN), or a mixture of the two modes (SPN). The results showed differences in gut microbiota composition between the different modes of nutrition. Enterococcus increased in TEN, Campylobacter decreased in TPN, and Dialister decreased in SPN groups. Fermentation products produced by gut microbiota also changed depending on the mode of nutrition, with the TEN group showing improvements amongst the most fermentation products. Individuals in the TEN group also showed improved immune system function alongside those in the SPN group. It was concluded that based upon improvements to the immune system and gut microbiota, TEN is the most suitable mode for nutrition in individuals with sepsis. This study could be used by healthcare professionals to understand that nutrition methods for individuals with sepsis aren’t equally effective and recovery may be faster if individuals receive nutrition through a gastric tube.
Abstract
BACKGROUND Sepsis exacerbates intestinal microecological disorders leading to poor prognosis. Proper modalities of nutritional support can improve nutrition, immunity, and intestinal microecology. AIM: To identify the optimal modality of early nutritional support for patients with sepsis from the perspective of intestinal microecology. METHODS Thirty patients with sepsis admitted to the intensive care unit of the General Hospital of Ningxia Medical University, China, between 2019 and 2021 with indications for nutritional support, were randomly assigned to one of three different modalities of nutritional support for a total of 5 d: Total enteral nutrition (TEN group), total parenteral nutrition (TPN group), and supplemental parenteral nutrition (SPN group). Blood and stool specimens were collected before and after nutritional support, and changes in gut microbiota, short-chain fatty acids (SCFAs), and immune and nutritional indicators were detected and compared among the three groups. RESULTS In comparison with before nutritional support, the three groups after nutritional support presented: (1) Differences in the gut bacteria (Enterococcus increased in the TEN group, Campylobacter decreased in the TPN group, and Dialister decreased in the SPN group; all P < 0.05); (2) different trends in SCFAs (the TEN group showed improvement except for Caproic acid, the TPN group showed improvement only for acetic and propionic acid, and the SPN group showed a decreasing trend); (3) significant improvement of the nutritional and immunological indicators in the TEN and SPN groups, while only immunoglobulin G improved in the TPN group (all P < 0.05); and (4) a significant correlation was found between the gut bacteria, SCFAs, and nutritional and immunological indicators (all P < 0.05). CONCLUSION TEN is recommended as the preferred mode of early nutritional support in sepsis based on clinical nutritional and immunological indicators, as well as changes in intestinal microecology.
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Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3-5: a randomized controlled trial.
Yang, WC, Hsieh, HM, Chen, JP, Liu, LC, Chen, CH
BMC nephrology. 2023;24(1):372
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Chronic kidney disease (CKD) is a prevalent clinical issue often observed in older adults. Nutritional management has become essential for older adults with CKD. Recent nutritional guidelines have suggested that a low-protein diet (LPD) can be prescribed. The aim of this study was to compare the effects of a regular LPD alone or a 6% LPF combined with a regular LPD prescription on nutrition status, physical performance, and clinical parameter changes in older adults with CKD stages 3–5. This study was a single-centre, two-armed, open-label, parallel, randomised controlled clinical trial. Participants were allocated at a 1:1 ratio - (1) the control group, patients received a regular LPD prescription; (2) the intervention group, patients received a regular LPD prescription with 6% LPF. Results showed that an LPD plus a 6% LPF provided no changes in energy and protein intake while increasing fatty acid and specific micronutrient intake during the 3-month follow-up period. Furthermore, blood urea nitrogen (clinical parameter) was significantly reduced in the intervention group over three months. Authors concluded that an LPD prescription with a 6% LPF can delay physical performance deterioration and increase micronutrient intake in three months compared to LPD education alone in older adults with CKD stages 3–5.
Abstract
BACKGROUND Although combining a low-protein diet (LPD) with oral nutritional supplements increases treatment adherence and nutritional status in patients with chronic kidney disease (CKD), the effect of this combination approach in older adults remains unclear. This study examined the impact of a 6% low-protein formula (6% LPF) with diet counseling in older adults with stage 3-5 CKD. METHODS In this three-month randomized controlled study, 66 patients (eGFR < 60 mL/min/1.73 m2, non-dialysis, over 65 years of age) were randomly assigned to an intervention group (LPD plus a 6% LPF) or control group (LPD alone). The 6% LPF comprised 400 kcal, 6 g of protein, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and various micronutrients. All data were collected at baseline and after three months, including physical performance based on hand grip strength (HGS) and gait speed, nutritional status using Mini Nutritional Assessment-Short Form (MNA-SF) scores, body composition through bioelectrical impedance analysis, and dietary intake from 24-h dietary records. RESULTS This study incorporated 47 participants (median age, 73; median eGFR, 36 ml/min/1.73 m2; intervention group: 24; control group: 23). The intervention group exhibited significant differences in HGS and gait speed, and micronutrient analysis revealed significantly higher monounsaturated fatty acids (MUFA), EPA, DHA, calcium, iron, zinc, copper, thiamine, riboflavin, niacin, B6, B12, and folic acid intake than the control group. MNA-SF scores, macronutrient intake, and body composition did not differ significantly between the two groups. CONCLUSIONS Compared to LPD counseling alone, an LPD prescription with 6% LPF in older adults with CKD stages 3-5 helped relieve physical deterioration and increased micronutrient intake after three months. TRIAL REGISTRATION ClinicalTrials.gov NCT05318014 (retrospectively registered on 08/04/2022).
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Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial.
Johnstone, JM, Hatsu, I, Tost, G, Srikanth, P, Eiterman, LP, Bruton, AM, Ast, HK, Robinette, LM, Stern, MM, Millington, EG, et al
Journal of the American Academy of Child and Adolescent Psychiatry. 2022;61(5):647-661
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Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that affects about 5-7% of children. Characteristics of ADHD are age-inappropriate hyperactivity, impulsivity, and difficulties in focusing attention which arise from an impaired ability to regulate executive and emotional functions. The condition often persists into adulthood, where it presents an increased risk for poor educational achievements, substance abuse, incarceration, and mental health problems. In many cases, drug treatment can improve ADHD symptoms, yet concern remains about the side effects of these treatments. Some research has investigated the impact of nutrient supplementation on ADHD management, as many nutrients are essential for healthy brain function and are also involved in the production of neurotransmitters. In previous studies, supplementation with nutrients has shown some benefits but likewise also inconsistent results. This eight-week randomised placebo-controlled clinical trial evaluated the effects of a multi-nutrient supplement in 135 children with ADHD, aged 6-12 years. The study specifically focused on irritable mood symptoms. The multi-nutrient formula contained vitamins, minerals, amino acids, and antioxidants. Outcomes were measured by scores rated by clinicians (Clinical Global Impression-Improvement aka CGI-I) and scores rated by parents (Child and Adolescent Symptom Inventory-5 aka CASI-5). The multi-nutrient formula showed overall benefit in the blinded clinician rating but not by parental reports. According to the parents, overall improvement was reported, both in the placebo and intervention groups. The authors discussed how this absence of difference can be explained. Yet, on a subscale, the multi-nutrient group parents were more likely to report improvements. In addition, children with the additional micronutrients demonstrated greater height growth during the intervention. The supplement was well tolerated with good adherence and the monitored blood markers demonstrated safety of use.
Expert Review
Conflicts of interest:
None
Take Home Message:
This fully-blinded RCT of micronutrients addresses several concerns related to existing ADHD treatment, including the possibility of counteracting height suppression and treating associated irritable mood, emotional dysregulation, and aggression.
Although further research is needed, multinutrient supplementation should be considered for children with ADHD.
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
Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric condition that can result in low educational performance and achievement. Around 5-7% of children are believed to be affected. Alongside inattention and hyperactivity, emotional dysregulation is a common feature of ADHD. Psychiatric problems can continue into adulthood and an increased risk of incarceration and substance abuse have been reported.
Treatment with prescription medications may improve symptoms of ADHD, however, potential side effects include mild growth suppression, and mood and emotional dysregulation. Non-pharmacological treatments are therefore being investigated.
Previous research on single nutrients have shown mixed results for emotional dysregulation and mood issues in ADHD. The aim of this study was to test whether supplementation with a multi-nutrient could be beneficial to children aged 6-12 years with ADHD and irritability.
Methods
126 unmedicated children from North America with ADHD (mean age 9.8 years) completed this 8-week study. All participants had at least 1 symptom of anger, irritability, peer conflict or Disruptive Mood Dysregulation Disorder (DMDD).
Randomisation was into an intervention (n=71) or placebo (N=55) group with a 3:2 ratio to promote enrolment. Participants were required to take 6-12 capsules daily, depending on age and tolerance, of micronutrients or a placebo. Micronutrient dosages were above the recommended dietary allowance (RDA). Outcomes were measured using clinician and parent rated assessments and by a further adult who knew the child well.
The trial was blinded to all participants, parents and study staff.
Results
The clinician-rated results found 54% of the micronutrient group and 18% of the placebo group had improvements in irritability symptoms (Risk ratio =2.97, 97.5% CI: 1.5, 5.90, p<0.001). This was not replicated in the parent/adult rated results. Children in the micronutrient group grew on average 6mm more than the placebo group (p=0.002). No serious adverse treatment effects were reported. Adherence to protocol was met by >74% of participants (n=93).
Conclusions
In this study, clinicians reported that micronutrients showed greater benefits than placebo for treating irritability and supporting growth in children with ADHD.
The study and authors received funding from several research and association bodies. However, no funder was involved in the study design or reporting. No conflicts of interest were declared.
Clinical practice applications:
- Multinutrient supplementation including vitamins, minerals, amino acids, and antioxidants may support height growth in children who take pharmacologic treatment
- Multi nutrient supplementation may also help with irritable mood, emotional dysregulation, and aggression in ADHD children
- Micronutrients given at doses between the Recommended Dietary Allowance and Upper Tolerable Intake Level appear safe and may be developed into an alternative or complementary treatment for ADHD.
Considerations for future research:
- Further large scale research is needed into the potential benefits of micronutrients for children with ADHD and irritability
Abstract
OBJECTIVE To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample. METHOD A 3-site, 8-week, placebo-controlled, randomized clinical trial of micronutrients was conducted in nonmedicated children aged 6 to 12 years with ADHD and at least 1 impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory-5 (CASI-5). A priori-defined primary outcomes were Clinical Global Impression-Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores. RESULTS Of 135 randomized (mean age 9.8 years), 126 youths (93%) comprised the modified intention-to-treat population. Blinding was maintained. For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (risk ratio = 2.97, 97.5% CI = 1.50, 5.90, p < .001). CASI-5 composite scores improved significantly for both groups (p < .01), with a mean change of -0.31 (95% CI = -0.39, -0.23) in the micronutrient group and a mean change of -0.28 (95% CI = -0.38, -0.19) in the placebo group. However, the between-group difference was not significant (mean change = -0.02; 97.5% CI = -0.16, 0.12, effect size = 0.07, p = .70). The micronutrient group grew 6 mm more than the placebo group (p = .002). No serious adverse events or clinically significant changes from baseline in blood and urine tests occurred. CONCLUSION Micronutrients showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Micronutrients showed greater height growth. Micronutrients were well tolerated, and the majority of participants adhered to the number of capsules prescribed. This randomized controlled trial replicates safety and efficacy reported for ADHD in 2 smaller trials of a similar formula containing all vitamins and known essential minerals in amounts between the Recommended Dietary Allowance and Upper Tolerable Intake Level. CLINICAL TRIAL REGISTRATION INFORMATION Micronutrients for ADHD in Youth (MADDY) Study; https://clinicaltrials.gov; NCT03252522.
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Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial.
Liu, S, D'Amico, D, Shankland, E, Bhayana, S, Garcia, JM, Aebischer, P, Rinsch, C, Singh, A, Marcinek, DJ
JAMA network open. 2022;5(1):e2144279
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Older adults are the fastest growing age group in the world. As we age, we tend to lose muscle mass and strength which has consequences. Studies have shown that mitochondrial dysfunction plays an important part in age-related diseases. A reduction in the cells ability to dispose of its dysfunctional mitochondria (mitophagy) contributes to poor mitochondrial quality. Urolithin A is a natural food metabolite of the gut microbiome and has been shown to boost mitochondrial health by triggering mitophagy in both preclinical models of aging and in older adults. In this double-blind, placebo-controlled randomized clinical trial, 66 older adults were given either 1000mg of urolithin A or a placebo for 4 months. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 months, and 4 months. Six-minute walk distance and maximal ATP production were assessed using magnetic resonance spectroscopy at baseline and at the end of study at 4 months. This study found that the improvements in the 6-minute walk distance and maximal ATP production in hand muscles were not significant for urolithin A. However, long-term supplementation with urolithin A significantly enhanced skeletal muscle endurance and improved the metabolic markers of mitochondrial function in older adults. This trial suggests that urolithin A may be a promising approach to counteract age-associated muscle decline. Future study is needed to confirm the role of urolithin A supplementation in healthy aging.
Abstract
Importance: Aging is associated with a decline in mitochondrial function and reduced exercise capacity. Urolithin A is a natural gut microbiome-derived food metabolite that has been shown to stimulate mitophagy and improve muscle function in older animals and to induce mitochondrial gene expression in older humans. Objective: To investigate whether oral administration of urolithin A improved the 6-minute walk distance, muscle endurance in hand and leg muscles, and biomarkers associated with mitochondrial and cellular health. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial in adults aged 65 to 90 years was conducted at a medical center and a cancer research center in Seattle, Washington, from March 1, 2018, to July 30, 2020. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 months, and 4 months. Six-minute walk distance and maximal ATP production were assessed using magnetic resonance spectroscopy at baseline and at the end of study at 4 months. The analysis used an intention-to-treat approach. Interventions: Participants were randomized to receive daily oral supplementation with either 1000 mg urolithin A or placebo for 4 months. Main Outcomes and Measures: The primary end point was change from baseline in the 6-minute walk distance and change from baseline to 4 months in maximal ATP production in the hand skeletal muscle. The secondary end points were change in muscle endurance of 2 skeletal muscles (tibialis anterior [TA] in the leg and first dorsal interosseus [FDI] in the hand). Cellular health biomarkers were investigated via plasma metabolomics. Adverse events were recorded and compared between the 2 groups during the intervention period. Results: A total of 66 participants were randomized to either the urolithin A (n = 33) or the placebo (n = 33) intervention group. These participants had a mean (SD) age of 71.7 (4.94) years, were predominantly women (50 [75.8%]), and were all White individuals. Urolithin A, compared with placebo, significantly improved muscle endurance (ie, increase in the number of muscle contractions until fatigue from baseline) in the FDI and TA at 2 months (urolithin A: FDI, 95.3 [115.5] and TA, 41.4 [65.5]; placebo: FDI, 11.6 [147.4] and TA, 5.7 [127.1]). Plasma levels of several acylcarnitines, ceramides, and C-reactive protein were decreased by urolithin A, compared with placebo, at 4 months (baseline vs 4 mo: urolithin A, 2.14 [2.15] vs 2.07 [1.46]; placebo, 2.17 [2.52] vs 2.65 [1.86]). The mean (SD) increase from baseline in the 6-minute walk distance was 60.8 (67.2) m in the urolithin A group and 42.5 (73.3) m in the placebo group. The mean (SD) change from baseline to 4 months in maximal ATP production in the FDI was 0.07 (0.23) mM/s in the urolithin A group and 0.06 (0.20) mM/s in the placebo group; for the TA, it was -0.03 (0.10) mM/s in the urolithin A group and 0.03 (0.10) mM/s in the placebo group. These results showed no significant improvement with urolithin A supplementation compared with placebo. No statistical differences in adverse events were observed between the 2 groups. Conclusions and Relevance: This randomized clinical trial found that urolithin A supplementation was safe and well tolerated in the assessed population. Although the improvements in the 6-minute walk distance and maximal ATP production in the hand muscle were not significant in the urolithin A group vs the placebo group, long-term urolithin A supplementation was beneficial for muscle endurance and plasma biomarkers, suggesting that urolithin A may counteract age-associated muscle decline; however, future work is needed to confirm this finding. Trial Registration: ClinicalTrials.gov Identifier: NCT03283462.
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Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans.
Nascimento, EBM, Moonen, MPB, Remie, CME, Gariani, K, Jörgensen, JA, Schaart, G, Hoeks, J, Auwerx, J, van Marken Lichtenbelt, WD, Schrauwen, P
The Journal of clinical endocrinology and metabolism. 2021;106(5):1437-1447
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Brown fat is a type of fat that burns energy to regulate the body’s temperature in cold conditions. A high level of activity in the brown fat has been associated with healthy whole-body metabolism. Several supplements have been investigated for their potential to activate brown fat, however many of these have limiting side effects. Nicotinamide riboside (NR), also known as vitamin B3, is a supplement which can boost energy burning pathways within the body. This randomised control trial was part of a larger trial including a study on human brown fat cells and aimed to determine whether NR supplementation in overweight and obese individuals may act on the activity of brown tissue. The results showed that 6 weeks of NR supplementation had no effect on brown tissue activity or energy expenditure. It was concluded that NR supplementation for 6 weeks in individuals with obesity had no effect on brown fat tissue for reasons unknown, as the cellular study showed an increase in activity. This study could be used by healthcare professionals to better understand the role of brown fat in metabolism.
Abstract
CONTEXT Elevating nicotinamide adenine dinucleotide (NAD+) levels systemically improves metabolic health, which can be accomplished via nicotinamide riboside (NR). Previously, it was demonstrated that NR supplementation in high-fat-diet (HFD)-fed mice decreased weight gain, normalized glucose metabolism, and enhanced cold tolerance. OBJECTIVE Because brown adipose tissue (BAT) is a major source of thermogenesis, we hypothesize that NR stimulates BAT in mice and humans. DESIGN AND INTERVENTION HFD-fed C56BL/6J mice were supplemented with 400 mg/kg/day NR for 4 weeks and subsequently exposed to cold. In vitro primary adipocytes derived from human BAT biopsies were pretreated with 50 µM or 500 µM NR before measuring mitochondrial uncoupling. Human volunteers (45-65 years; body mass index, 27-35 kg/m2) were supplemented with 1000 mg/day NR for 6 weeks to determine whether BAT activity increased, as measured by [18F]FDG uptake via positron emission tomography-computed tomography (randomized, double blinded, placebo-controlled, crossover study with NR supplementation). RESULTS NR supplementation in HFD-fed mice decreased adipocyte cell size in BAT. Cold exposure further decreased adipocyte cell size on top of that achieved by NR alone independent of ex vivo lipolysis. In adipocytes derived from human BAT, NR enhanced in vitro norepinephrine-stimulated mitochondrial uncoupling. However, NR supplementation in human volunteers did not alter BAT activity or cold-induced thermogenesis. CONCLUSIONS NR stimulates in vitro human BAT but not in vivo BAT in humans. Our research demonstrates the need for further translational research to better understand the differences in NAD+ metabolism in mouse and human.
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NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults.
Connell, NJ, Grevendonk, L, Fealy, CE, Moonen-Kornips, E, Bruls, YMH, Schrauwen-Hinderling, VB, de Vogel, J, Hageman, R, Geurts, J, Zapata-Perez, R, et al
The Journal of nutrition. 2021;151(10):2917-2931
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Ageing is associated with the progressive loss of muscle, which can result in impaired movement, an increased risk for falls and disrupted energy production. During ageing there is a decrease in one of the substrates involved in producing energy known as NAD+. Studies in animals have shown that supplementing with a precursor of NAD+ promotes longevity and energy production. In humans supplementation with a precursor of NAD+ has been shown to improve heart health and be of benefit to individuals with obesity. This randomised control trial aimed to determine the effect of supplementing the NAD+ precursors, tryptophan, nicotinic acid, and nicotinamide on muscle function in 14 older adults with impaired physical function. The results showed that supplementation had no effect on NAD+ and had no effect on muscular energy production nor exercise performance following a cycling test. It was concluded that supplementation with an NAD+ precursor does not improve muscle function. This study could be used by healthcare professionals to understand that a combination supplement of tryptophan, nicotinic acid, and nicotinamide may not benefit the physical function of older adults.
Abstract
BACKGROUND Boosting NAD+ via supplementation with niacin equivalents has been proposed as a potential modality capable of promoting healthy aging and negating age-dependent declines of skeletal muscle mass and function. OBJECTIVES We investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skeletal muscle mitochondrial function in physically compromised older adults. METHODS A randomized, double-blind, controlled trial was conducted in 14 (female/male: 4/10) community-dwelling, older adults with impaired physical function [age, 72.9 ± 4.0 years; BMI, 25.2 ± 2.3 kg/m2]. Participants were supplemented with 207.5 mg niacin equivalents/day [intervention (INT)] and a control product (CON) that did not contain niacin equivalents, each for 32 days. The primary outcomes tested were mitochondrial oxidative capacity and exercise efficiency, analyzed by means of paired Student's t-tests. Secondary outcomes, such as NAD+ concentrations, were analyzed accordingly. RESULTS Following supplementation, skeletal muscle NAD+ concentrations [7.5 ± 1.9 compared with 7.9 ± 1.6 AU, respectively] in INT compared with CON conditions were not significantly different compared to the control condition, whereas skeletal muscle methyl-nicotinamide levels were significantly higher under NAD+-precursor supplementation [INT, 0.098 ± 0.063 compared with CON, 0.025 ± 0.014; P = 0.001], suggesting an increased NAD+ metabolism. Conversely, neither ADP-stimulated [INT, 82.1 ± 19.0 compared with CON, 84.0 ± 19.2; P = 0.716] nor maximally uncoupled mitochondrial respiration [INT, 103.4 ± 30.7 compared with CON, 108.7 ± 33.4; P = 0.495] improved under NAD+-precursor supplementation, nor did net exercise efficiency during the submaximal cycling test [INT, 20.2 ± 2.77 compared with CON, 20.8 ± 2.88; P = 0.342]. CONCLUSIONS Our findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function. This study was registered at clinicaltrials.gov as NCT03310034.
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Effect of a Parent-Focused eHealth Intervention on Children's Fruit, Vegetable, and Discretionary Food Intake (Food4toddlers): Randomized Controlled Trial.
Røed, M, Medin, AC, Vik, FN, Hillesund, ER, Van Lippevelde, W, Campbell, K, Øverby, NC
Journal of medical Internet research. 2021;23(2):e18311
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Diet in childhood tends to reflect that in adolescence and adulthood and so healthy eating habits established during this time may prevent increased weight, non-communicable diseases and even cancer. Healthy diet promotion to parents may be able to ensure that a healthy food environment is established, which will then continue throughout life. This randomised controlled trial of 404 parents aimed to determine the effect of parent-focused healthy food promotion via the internet for 12 months. The results showed that after 6 months that frequency of vegetable intake increased but this was not seen at 12 months. No differences were seen in the frequency of intake of sweet foods at either time point. It was concluded that intervention through a web-based healthy diet programme increased vegetable intake in the short-term, however in the long-term a personalised intervention or reminders may be needed. This study could be used by healthcare professionals to understand the importance of establishing a healthy diet from a young age and that parental support may be required to do this.
Abstract
BACKGROUND In Western countries, children's diets are often low in fruits and vegetables and high in discretionary foods. Diet in early life tends to track through childhood and youth and even into adulthood. Interventions should, therefore, be delivered in periods when habitual traits are established, as in toddlerhood when children adapt to their family's diet. OBJECTIVE In this study, we assessed the effect of the Food4toddlers eHealth intervention, which aimed to enhance toddlers' diets by shaping their food and eating environment. METHODS The Food4toddlers randomized controlled trial was conducted in Norway in 2017-2018. Parent-child dyads were recruited through social media. In total, 298 parents completed an online questionnaire at baseline (mean child age 10.9 months, SD 1.2). Postintervention questionnaires were completed immediately after the intervention (ie, follow-up 1; mean child age 17.8 months, SD 1.3) and 6 months after the intervention (ie, follow-up 2; mean child age 24.2 months, SD 1.9). The intervention was guided by social cognitive theory, which targets the linked relationship between the person, the behavior, and the environment. The intervention group (148/298, 49.7%) got access to the Food4toddlers website for 6 months from baseline. The website included information on diet and on how to create a healthy food and eating environment as well as activities, recipes, and collaboration opportunities. To assess intervention effects on child diet from baseline to follow-up 1 and from baseline to follow-up 2, we used generalized estimating equations and a time × group interaction term. Between-group differences in changes over time for frequency and variety of fruits and vegetables and frequency of discretionary foods were assessed. RESULTS At follow-up 1, a significant time × group interaction was observed for the frequency of vegetable intake (P=.02). The difference between groups in the change from baseline to follow-up 1 was 0.46 vegetable items per day (95% CI 0.06-0.86) in favor of the intervention group. No other significant between-group differences in dietary changes from baseline to follow-up 1 or follow-up 2 were observed. However, there is a clear time trend showing that the intake of discretionary foods increases by time from less than 1 item per week at baseline to more than 4 items per week at 2 years of age (P<.001), regardless of group. CONCLUSIONS A positive intervention effect was observed for the frequency of vegetable intake at follow-up 1 but not at follow-up 2. No other between-group effects on diet were observed. eHealth interventions of longer duration, including reminders after the main content of the intervention has been delivered, may be needed to obtain long-terms effects, along with tailoring in a digital or a personal form. TRIAL REGISTRATION International Standard Randomized Controlled Trial Number (ISRCTN) 92980420; https://doi.org/10.1186/ISRCTN92980420.
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The Effect of Moderate Weight Loss on a Non-Invasive Biomarker of Liver Fibrosis: A Randomised Controlled Trial.
Koutoukidis, DA, Jebb, SA, Aveyard, P, Astbury, NM
Obesity facts. 2020;13(2):144-151
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Non-alcoholic fatty liver disease covers a range of conditions from excess fat in the liver through inflammation and fibrosis, to advanced fibrosis, and cirrhosis. The Enhanced Liver Fibrosis (ELF) score is emerging as a promising blood biomarker for fibrosis. The aim of this study was to examine whether a community weight loss programme reduces ELF score over 12 months compared with a weight-loss intervention which is less effective. This study is a secondary analysis of a published randomised controlled trial. Participants (n=73) were equally randomised to a community weight loss programme (WeightWatchers) or usual care. Results indicate that there was no evidence of an effect of a community weight loss programme on changes in the ELF score and no association between weight loss and the ELF score in people who had, on average, an ELF score compatible with moderate fibrosis. Authors conclude that using the ELF test to assess weight loss treatment efficacy in improving liver fibrosis may be of limited value, thus biopsy remains the gold-standard assessment for liver fibrosis.
Abstract
BACKGROUND Referral to weight loss programmes is the only effective treatment for non-alcoholic fatty liver disease (NAFLD). Clinicians should advise weight loss and screen for liver fibrosis using the Enhanced Liver Fibrosis (ELF) score. AIM: To examine if the ELF score changes with weight loss. DESIGN AND SETTING Randomised controlled trial (ISRCTN85485463) in UK primary care during 2007-2008. METHOD Adults with a BMI of 27-35 kg/m2 and ≥1 risk factor for obesity-related disease were randomised to attend a community weight loss programme (n = 45) or receive usual weight loss advice from a practice nurse (n = 28). Weight and the ELF score were measured at baseline and 1 year. Analysis of covariance examined mean changes in the ELF score between groups and its relationship with weight loss. RESULTS Mean (SD) BMI was 31.10 kg/m2 (2.55) with evidence of moderate levels of liver fibrosis at baseline (mean ELF score: 8.93 [0.99]). There was no evidence that the community weight loss programme reduced the ELF score compared with usual care (difference +0.13 points, 95% CI: -0.25 to 0.52) despite greater weight loss (difference: -2.66 kg, 95% CI: -5.02 to -0.30). Mean weight loss in the whole cohort was 7.8% (5.9). There was no evidence of an association between weight change and change in ELF; the coefficient for a 5% weight loss was -0.15 (95% CI: -0.30 to 0.0002). CONCLUSION We found no evidence that the ELF score changed meaningfully following moderate weight loss. Clinicians should not use the ELF score to measure improvements in NAFLD fibrosis following weight loss programmes.
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Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese.
Edinburgh, RM, Bradley, HE, Abdullah, NF, Robinson, SL, Chrzanowski-Smith, OJ, Walhin, JP, Joanisse, S, Manolopoulos, KN, Philp, A, Hengist, A, et al
The Journal of clinical endocrinology and metabolism. 2020;105(3)
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Following exercise, various metabolic changes occur which may be of benefit in fighting diseases such as type 2 diabetes and obesity. However, the degree of change may vary depending on whether the exercise has been performed pre or post meal consumption. This 6-week randomised crossover trial of 30 overweight or obese men aimed to determine the effect of exercising before or after breakfast on the use of fats and sugars by the body. The results showed that exercise before breakfast increased fat and sugar use in the body and also resulted in the alteration of eight genes associated with metabolism. Exercise before carbohydrate consumption also increased lipid use and improved insulin sensitivity, however body composition was similar regardless of when exercise was performed. It was concluded that exercising in the fasted state can optimise the body’s response without having to change intensity or effort. This study could be used by health care professionals to advise patients with obesity or overweight that exercising whilst in the fasted state could optimise their outcomes without having to increase exercise intensity or frequency.
Abstract
CONTEXT Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. OBJECTIVE To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism. DESIGN (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study). SETTING General community. PARTICIPANTS Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study). INTERVENTIONS Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion. RESULTS Acute Study-exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: -3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P < 0.01) and type II fibers (-1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P < 0.05). Training Study-postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P > 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs -21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P < 0.05). CONCLUSIONS Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.