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Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis.
Coggan, AR, Baranauskas, MN, Hinrichs, RJ, Liu, Z, Carter, SJ
Journal of the International Society of Sports Nutrition. 2021;18(1):66
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Previous reviews have concluded that dietary nitrate (NO3−) improves maximal neuromuscular power in humans, but these were based on a limited number of studies. This is the first systematic review and meta-analysis evaluating the effects of dietary NO3− supplementation on muscular power in humans. The study also aims to quantify the size of this beneficial effect. 19 studies with a total of 268 participants were included. Most of these used concentrated beetroot juice as the source of NO3− given as an acute dose (short term high level). A positive effect of dietary NO3− on muscle power was observed in all 19 studies. Analyses were done on sub groups - age, sex and the amount of muscle mass engaged in the activity. Dietary NO3− intake significantly increases maximal muscle power in humans. The magnitude of this effect has practical and clinical importance; not just for athletes but also for patient groups. This effect is independent of subject age, sex, or the amount of muscle mass engaged in the activity but may be greater with acute vs. repeated dosing. Further research is needed to determine factors such as the optimal supplementation regimen and target population.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This meta-analysis lends quantitative support to previous narrative reviews that nitrate supplementation can enhance maximal power output.
- These findings are highly relevant to team and strength sport athletes, who may not otherwise be supplementing with nitrates.
- These findings are also highly relevant for older populations, where risk of falls and fractures are high and can lead to significant adverse effects on health and quality of life.
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:
- In 2007, researchers uncovered the ingestion of dietary nitrates reduced the oxygen cost of submaximal exercise, and since, over 100 studies have examined the effects of nitrates on endurance performance.
- With regards to the impact of nitrates on maximal force output, only trivial results had been previously found.
- This review study found that while nitrates do not impact force development, they do demonstrate primary effect on the speed of muscle contraction (i.e. muscular power is the product of force x speed).
- The reviews primary finding was that nitrate intake can significantly enhance muscular power, regardless of subject age or sex.
Clinical practice applications:
- These new findings highlight the ability of dietary nitrates to improve neuromuscular power production is highly relevant for team sport athletes, due to the explosive nature of these sports with constant accelerations and decelerations during training and competition.
- In the general population, falls and fractures amongst older adults significantly reduces quality of life and costs the healthcare system hundreds of millions of pounds to treat.
- Improved contractile properties of muscle, most notably speed of contraction, may offer protection to older adults as well as the benefit of additional nitric oxide (NO) to support vascular health as well.
- The typical intake of dietary nitrates in the general population is about 31-185mg/day in Europe and 40-100mg/day in North America. Most studies use doses between 300-600mg of dietary nitrates. Increasing dietary or supplemental intake is key to achieving the neuromuscular effect.
Considerations for future research:
- The results of the present meta-analysis clearly demonstrate that dietary nitrates increases muscle power in humans, but the mechanism responsible for this effect is still unclear.
- There are notable differences between rodent and human metabolism of dietary nitrates, therefore the biochemical mechanism by which nitrate intake improves human muscle power requires additional study.
Abstract
BACKGROUND Previous narrative reviews have concluded that dietary nitrate (NO3-) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO3- on various aspects of exercise performance (i.e., endurance vs. strength vs. power) in better context. We therefore undertook a systematic review and individual participant data meta-analysis to quantify the effects of NO3- supplementation on human muscle power. METHODS The literature was searched using a strategy developed by a health sciences librarian. Data sources included Medline Ovid, Embase, SPORTDiscus, Scopus, Clinicaltrials.gov , and Google Scholar. Studies were included if they used a randomized, double-blind, placebo-controlled, crossover experimental design to measure the effects of dietary NO3- on maximal power during exercise in the non-fatigued state and the within-subject correlation could be determined from data in the published manuscript or obtained from the authors. RESULTS Nineteen studies of a total of 268 participants (218 men, 50 women) met the criteria for inclusion. The overall effect size (ES; Hedge's g) calculated using a fixed effects model was 0.42 (95% confidence interval (CI) 0.29, 0.56; p = 6.310 × 10- 11). There was limited heterogeneity between studies (i.e., I2 = 22.79%, H2 = 1.30, p = 0.3460). The ES estimated using a random effects model was therefore similar (i.e., 0.45, 95% CI 0.30, 0.61; p = 1.064 × 10- 9). Sub-group analyses revealed no significant differences due to subject age, sex, or test modality (i.e., small vs. large muscle mass exercise). However, the ES in studies using an acute dose (i.e., 0.54, 95% CI 0.37, 0.71; p = 6.774 × 10- 12) was greater (p = 0.0211) than in studies using a multiple dose regimen (i.e., 0.22, 95% CI 0.01, 0.43; p = 0.003630). CONCLUSIONS Acute or chronic dietary NO3- intake significantly increases maximal muscle power in humans. The magnitude of this effect-on average, ~ 5%-is likely to be of considerable practical and clinical importance.
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Effects of Nutrition/Diet on Brown Adipose Tissue in Humans: A Systematic Review and Meta-Analysis.
Heenan, KA, Carrillo, AE, Fulton, JL, Ryan, EJ, Edsall, JR, Rigopoulos, D, Markofski, MM, Flouris, AD, Dinas, PC
Nutrients. 2020;12(9)
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The body has many uses for the energy that is consumed in the diet, one of these is for the generation of heat. Brown adipose tissue (BAT), which is stored in the lower neck, collarbone, abdomen and along the spine, is a special type of fat that is activated when the body is cold and serves to generate heat. The activity of this fat is of benefit to humans, as it reduces weight gain, improves blood sugar balance, and helps reduce blood lipid levels, reducing the risk for heart disease and type 2 diabetes. This systematic review of 24 publications aimed to determine whether nutrition and/or diet affects the activity of BAT. The results showed that there was no change in BAT activity following a high calorie carbohydrate rich meal, a standard meal and during overfeeding. Supplementation of L-Arginine, which is a supplement that helps the body build muscle, also had no effect on BAT activity. It was concluded that BAT activity was not affected by nutrition or diet. This study could be used by healthcare professionals to understand that the effect of diet on risk for heart disease and type 2 diabetes may not involve the modification of BAT.
Abstract
BACKGROUND Brown adipose tissue (BAT) provides a minor contribution to diet-induced thermogenesis (DIT)-the metabolic response to food consumption. Increased BAT activity is generally considered beneficial for mammalian metabolism and has been associated with favorable health outcomes. The aim of the current systematic review was to explore whether nutritional factors and/or diet affect human BAT activity. METHODS We searched PubMed Central, Embase and Cochrane Library (trials) to conduct this systematic review (PROSPERO protocol: CRD42018082323). RESULTS We included 24 eligible papers that studied a total of 2785 participants. We found no mean differences in standardized uptake value of BAT following a single meal or after 6 weeks of L-Arginine supplementation. Resting energy expenditure (REE), however, was increased following a single meal and after supplementation of capsinoid and catechin when compared to a control condition (Z = 2.41, p = 0.02; mean difference = 102.47 (95% CI = 19.28-185.67)). CONCLUSIONS Human BAT activity was not significantly affected by nutrition/diet. Moreover, REE was only increased in response to a single meal, but it is unlikely that this was due to increased BAT activity. BAT activity assessments in response to the chronic effect of food should be considered along with other factors such as body composition and/or environmental temperature.
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The Effect of Nutrition Intervention with Oral Nutritional Supplements on Pancreatic and Bile Duct Cancer Patients Undergoing Chemotherapy.
Kim, SH, Lee, SM, Jeung, HC, Lee, IJ, Park, JS, Song, M, Lee, DK, Lee, SM
Nutrients. 2019;11(5)
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Despite the advantages of chemotherapy, it can cause cancer-related malnutrition leading to both reduced quality of life and reduced survival rate. Oral nutritional supplements (ONSs) provide balanced nutrients, calories, and protein to complement insufficient oral intake, and ONS provision during treatment may improve nutritional status. The aim of this study was to investigate the impact of ONS on nutritional status in patients undergoing chemotherapy for pancreatic and bile duct cancer. Patients were randomly allocated to the ONS group (15) and non-ONS group (19) and dietary intake and body weight were assessed at weeks 1, 2, 4 and 8. Body composition and quality of life was assessed at baseline and week 8. This study found the supply of ONS helped promote health by increasing body fat mass, improving quality of life and decreasing fatigue symptoms in pancreatic and bile duct cancer patients. These results were more pronounced in patients in the first cycle of chemotherapy. Based on these results, the authors conclude ONS may improve nutritional status by increasing fat mass and/or maintaining the body composition of patients undergoing chemotherapy.
Abstract
Chemotherapy may negatively affect nutritional status and quality of life (QOL) in pancreatic cancer patients. Our aim was to investigate the beneficial effects of oral nutrition supplements (ONS) on pancreatic and bile duct cancer patients undergoing chemotherapy. Among patients with progressive pancreatic and bile duct cancer receiving chemotherapy, the ONS group (n = 15) received two packs of ONS daily for 8 weeks while the non-ONS group (n = 19) did not. Anthropometric measures, dietary intake, nutritional status, and quality of life were assessed. ONS significantly increased daily intakes of energy, carbohydrates, proteins, and lipids at 8 weeks compared to the baseline. After 8 weeks, fat mass significantly increased in the ONS group. For patients in their first cycle of chemotherapy, body weight, fat-free mass, skeletal muscle mass, body cell mass, and fat mass increased in the ONS group but decreased in the non-ONS group. Fat mass increased in second or higher cycle only in the ONS group. Patient-generated subjective global assessments (PG-SGA) and fatigue scores in the Quality of Life Questionnaire Core 30 (QLQ-C30) improved in the ONS group. ONS might improve nutritional status by increasing fat mass and/or maintaining the body composition of pancreatic and bile duct cancer patients with chemotherapy, especially those in the first cycle, and alleviate fatigue symptoms.
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Association of Folate and Vitamins Involved in the 1-Carbon Cycle with Polymorphisms in the Methylenetetrahydrofolate Reductase Gene (MTHFR) and Global DNA Methylation in Patients with Colorectal Cancer.
Ferrari, A, Torrezan, GT, Carraro, DM, Aguiar Junior, S
Nutrients. 2019;11(6)
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This 2012 cross-sectional observational study examines the role of epigenetic gene expression and methylation in 189 patients with colorectal adenocarcinoma, including 128 with MTHFR polymorphisms. The mean age was 61 years and there was a 50/50 gender split. The focus nutrients were folate, vitamins B2, B6, B12, choline, betaine, and methionine, all of which are known to be essential nutrients for DNA synthesis and more specifically have a key role in the 1-carbon cycle, and S-adenosylmethionine (SAM). The study is based on prospective data collection from food frequency and clinical evaluation questionnaires, and blood work. There does not appear to have been any control group or blinding of processes (at least not reported in the study). The results showed that serum folate levels were positively correlated with the equivalent total dietary folate intake and global DNA methylation. No significant differences were found between serum folate levels in relation to the different genotypes of MTHFR polymorphisms such as C677T. A weak association was found between the A1298C polymorphism and lower levels of methylation. No significant findings were reported for the vitamins used in the study. The study concludes that folate intake, serum folate levels, global DNA methylation and age were predictors of clinicopathological staging.
Abstract
Folate, vitamin B2, vitamin B6, vitamin B12, choline, and betaine are nutrients involved in the 1-carbon cycle that can alter the levels of DNA methylation and influence genesis and/or tumor progression. Thus, the objective of this study was to evaluate the association of folate and vitamins involved in the 1-carbon cycle and MTHFR polymorphisms in global DNA methylation in patients with colorectal cancer gene. The study included 189 patients with colorectal adenocarcinoma answering a clinical evaluation questionnaire and the Food Frequency Questionnaire (FFQ) validated for patients with colon and rectal cancer. Blood samples were collected for evaluation of MTHFR gene polymorphisms in global DNA methylation in blood and in tumor. The values for serum folate were positively correlated with the equivalent total dietary folate (total DFE) (rho = 0.51, p = 0.03) and global DNA methylation (rho = 0.20, p = 0.03). Individuals aged over 61 years (p = 0.01) in clinicopathological staging III and IV (p = 0.01) and with + heterozygous mutated homozygous genotypes for the MTHFR A1298C gene had higher levels of global DNA methylation (p = 0.04). The association between dietary intake of folate, serum folate, and tumor stage were predictive of global DNA methylation in patients' blood. The levels of serum folate, the dietary folate and the status of DNA methylation can influence clinicopathological staging.
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Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder-A Randomized, Controlled 12-Month Trial.
Adams, JB, Audhya, T, Geis, E, Gehn, E, Fimbres, V, Pollard, EL, Mitchell, J, Ingram, J, Hellmers, R, Laake, D, et al
Nutrients. 2018;10(3)
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People with autism spectrum disorder (ASD) often have significant nutritional deficiencies, metabolic imbalances, and digestive problems. Many studies have previously looked at individual nutrients for ASD. This study was designed to look at the accumulative effect of using a wide range of dietary and nutritional interventions, including vitamin and mineral supplements, essential fatty acids, Epsom salt baths, carnitine, digestive enzymes, and a gluten-free, casein-free, soy-free (HGCSF) diet. The objective being to see if combining multiple interventions for a 12-month period, had greater benefits versus single nutrient interventions, and shorter trials. This US study recruited a wide age range of participants from 3-58yrs because it targeted, and was funded, by family groups of the Autism Society of Greater Phoenix. The study was deliberately single-blinded (meaning the participants knew what they were being given, but the clinical evaluators did not), as it was thought this would be more compelling and lead to less dropouts, especially considering the 12-month timing. In total 67 participants with ASD were recruited and 50 controls. Blood and urine samples were taking at the beginning and end of the study alongside autism severity assessments. Results showed an improvement in nutrient profiles for vitamins, minerals, fatty acids and carnitine alongside a significant decrease in homocysteine. There was an improvement in non-verbal IG test and cognitive function, and gastro-intestinal symptoms. There were no significant differences in complete blood count, blood chemistry panels or markers for inflammatory C-reactive protein (CRP). There was no change to BMI. Three exceptional cases of improvement were recorded in the control group and made into case studies highlighting improved physical strength and ability to walk, and resolution of urinary issues and pica eating disorder. Because it was single blinded there may be some ‘placebo effect’ but overall the researchers conclude that the study demonstrates how interventions can be safely and effectively implemented in families, with minimal adverse effect. And that combined nutrient and diet interventions should be considered for use in clinical practice.
Abstract
This study involved a randomized, controlled, single-blind 12-month treatment study of a comprehensive nutritional and dietary intervention. Participants were 67 children and adults with autism spectrum disorder (ASD) ages 3-58 years from Arizona and 50 non-sibling neurotypical controls of similar age and gender. Treatment began with a special vitamin/mineral supplement, and additional treatments were added sequentially, including essential fatty acids, Epsom salt baths, carnitine, digestive enzymes, and a healthy gluten-free, casein-free, soy-free (HGCSF) diet. There was a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group (+6.7 ± 11 IQ points vs. -0.6 ± 11 IQ points, p = 0.009) based on a blinded clinical assessment. Based on semi-blinded assessment, the treatment group, compared to the non-treatment group, had significantly greater improvement in autism symptoms and developmental age. The treatment group had significantly greater increases in EPA, DHA, carnitine, and vitamins A, B2, B5, B6, B12, folic acid, and Coenzyme Q10. The positive results of this study suggest that a comprehensive nutritional and dietary intervention is effective at improving nutritional status, non-verbal IQ, autism symptoms, and other symptoms in most individuals with ASD. Parents reported that the vitamin/mineral supplements, essential fatty acids, and HGCSF diet were the most beneficial.
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Dietary phytochemicals in breast cancer research: anticancer effects and potential utility for effective chemoprevention.
Kapinova, A, Kubatka, P, Golubnitschaja, O, Kello, M, Zubor, P, Solar, P, Pec, M
Environmental health and preventive medicine. 2018;23(1):36
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Bioactive phytochemicals are continually being studied for their role in cancer prevention with increasing evidence for flavonoids, carotenoids, phenolic acids, and organosulfur compounds (found in cruciferous vegetables). This 2018 review explores the protective effects of a broad spectrum of plant-derived substances. In total, more than 5000 individual phytochemicals have been identified in plant-derived foods, such as fruits, vegetables, and grains. These bioactive compounds have been shown to have antitumor activity, reduce inflammation, induce apoptosis (cell death), inhibit the proliferation of aggressive tumour cells, and impact on metastasis (migration of cancer cells). Specifically, in breast cancer, a few studies have examined phytochemicals on cancer stem cells (the originating tumour cells) and found that curcumin, genistein, indol-3-carbinol, c-phycocyanin, resveratrol, and quercetin downregulated their activity. Systematic reviews of dietary patterns and breast cancer show vegetables, and especially fibre, to be consistently protective against reduced risk of mammary carcinogenesis. Dietary polyphenols are considered a cost-effective approach to cancer care however there is still a lack of evidence due to the complex nature of combined phytochemicals versus isolated agents. Wholefood consumption is considered to improve bioavailability compared to supplementation however phytochemicals are a low-dose component of foods. There is also concern that some phytochemicals may act as carcinogens or tumour promoters (for example, beta-carotene). More clinical trials are required to fully understand phytochemicals and breast cancer care.
Abstract
Cancerous tissue transformation developing usually over years or even decades of life is a highly complex process involving strong stressors damaging DNA, chronic inflammation, comprehensive interaction between relevant molecular pathways, and cellular cross-talk within the neighboring tissues. Only the minor part of all cancer cases are caused by inborn predisposition; the absolute majority carry a sporadic character based on modifiable risk factors which play a central role in cancer prevention. Amongst most promising candidates for dietary supplements are bioactive phytochemicals demonstrating strong anticancer effects. Abundant evidence has been collected for beneficial effects of flavonoids, carotenoids, phenolic acids, and organosulfur compounds affecting a number of cancer-related pathways. Phytochemicals may positively affect processes of cell signaling, cell cycle regulation, oxidative stress response, and inflammation. They can modulate non-coding RNAs, upregulate tumor suppressive miRNAs, and downregulate oncogenic miRNAs that synergically inhibits cancer cell growth and cancer stem cell self-renewal. Potential clinical utility of the phytochemicals is discussed providing examples for chemoprevention against and therapy for human breast cancer. Expert recommendations are provided in the context of preventive medicine.
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Phytochemicals in Skin Cancer Prevention and Treatment: An Updated Review.
Ng, CY, Yen, H, Hsiao, HY, Su, SC
International journal of molecular sciences. 2018;19(4)
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This 2018 review discusses the anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenic effects of phytochemicals for the management of skin cancer. Melanoma and non-melanoma skin cancers are caused by cellular DNA damage, and as the skin is the body’s largest organ, it is most exposed to environmental stimulus. There are several promising phytochemicals in cancer chemoprevention including Epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin. Additionally, Gingerol has been applied topically to improve chemical stability in the skin. Caffeic Acid Phenethyl Ester (CAPE) is derived from bee propolis was shown to inhibit skin papilloma in animal studies. Capsaicin from red chillies induced apoptosis (cell death) in melanoma cells. Curcumin has been shown to modify numerous inflammatory markers including C-reactive protein and COX-2 whilst topically can promote remarkable symptomatic relief and reduce external cancer lesion size. Caffeic Acid exerts a protective effect towards skin cancer migration and invasion. EGCG has been shown to sensitize melanoma cells to inhibit growth, promote cell death and decrease cell proliferation. Genistein from soy has been shown to exert anti-angiogenesis properties, reduce tumour proliferation and metastasis. Resveratrol has a synergistic effect with other phytochemicals to suppress tumours. What all the studies reviewed show is the potential for phytochemicals in cancer treatment. They are widely available, cost effective and highly tolerated. They appear to have anti-carcinogenic effects through regulation of multiple different signalling pathways which help alter the typical progression of skin cancer.
Abstract
Skin is the largest human organ, our protection against various environmental assaults and noxious agents. Accumulation of these stress events may lead to the formation of skin cancers, including both melanoma and non-melanoma skin cancers. Although modern targeted therapies have ameliorated the management of cutaneous malignancies, a safer, more affordable, and more effective strategy for chemoprevention and treatment is clearly needed for the improvement of skin cancer care. Phytochemicals are biologically active compounds derived from plants and herbal products. These agents appear to be beneficial in the battle against cancer as they exert anti-carcinogenic effects and are widely available, highly tolerated, and cost-effective. Evidence has indicated that the anti-carcinogenic properties of phytochemicals are due to their anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenic effects. In this review, we discuss the preventive potential, therapeutic effects, bioavailability, and structure-activity relationship of these selected phytochemicals for the management of skin cancers. The knowledge compiled here will provide clues for future investigations on novel oncostatic phytochemicals and additional anti-skin cancer mechanisms.