Predictive Factors for Critical Weight Loss in Saudi Head and Neck Cancer Patients Undergoing (Chemo)Radiotherapy.

Weight loss is a significant health problem among patients with head and neck cancer (HNC) that is attributable primarily to the tumor or tumor therapy. Critical weight loss (CWL) is defined as the unintentional loss of ≥5% of weight. Therefore, this study's goal was to investigate and determine the possible factors influencing CWL among patients with HNC who have received radiotherapy or concurrent chemoradiotherapy (CCRT). We conducted a retrospective analysis of 175 patients who received radiotherapy or CCRT as either their primary, adjuvant, or combined treatment at the Oncology Center in King Abdullah Medical City. All patients were ≥18 years of age and diagnosed with HNC with no metastasis. The study results showed that 107 patients (61%) had CWL, while 68 (39%) did not. The following factors were significantly predictive of CWL with a multivariate regression analysis: pretreatment BMI (AOR = 1.1, 95% CI = 1.02-1.17), oral cavity cancer (AOR = 10.36, 95% CI = 1.13-94.55), and male sex (AOR = 3.15, 95% CI = 1.39-7.11). In conclusion, weight loss is highly prevalent among HNC patients during treatment. Accordingly, pretreatment BMI, cancer in the oral cavity, and being male can be considered predictive factors for CWL.

The effect of bariatric surgery on dietary Behaviour, dietary recommendation Adherence, and micronutrient deficiencies one year after surgery.

Bariatric surgery (BS) is associated with vitamin and mineral deficiencies, which might be augmented by low adherence to dietary guidelines and inappropriate dietary behaviours. The aim of this study was to determine the influence of BS on eating behaviour, prevalence of nutrient deficiency, level of commitment to diet, and lifestyle recommendations one-year post-BS. A cross-sectional study was conducted among adult patients who underwent BS in 2019 and had follow-up for a year. Age, gender, and clinical data were collected from the hospital system and other information was obtained from questionnaires during phone interviews. A total of 160 patients participated in the study. At 12 months, a significant increase from the baseline values in plasma levels of vitamin B12, folate, vitamin D, iron, corrected calcium, albumin, CRP, and MCV, as well as a significant decrease in BMI was observed. Adherence to dietary and lifestyle recommendations was moderate to high. Emotional, and restrained eating behaviours were moderate with 64.4%, and 77.5%, respectively. External eating was low at 58.1%. The study concluded that pre-and post-bariatric surgery nutrients should be closely monitored.

Moderate doses of dietary nitrate elicit greater effects on blood pressure and endothelial function than a high dose: A 13-week pilot study.

BACKGROUND & AIMS: Few studies have explored the prolonged effects of dietary nitrate on vascular health. This pilot study tested the effects of prolonged consumption (13 weeks) of a range of doses of dietary nitrate (NO3-), provided as beetroot juice (BJ), on blood pressure (BP) and endothelial function in overweight and obese older participants. METHODS AND RESULTS: Sixty-two overweight or obese older participants (60-75 years) were randomized to the following interventions: (1) high NO3- (2) medium NO3-, (3) low NO3-, or (4) placebo. Resting clinic and home BP were measured pre- and post-intervention. Laser Doppler iontophoresis was used to quantify changes in endothelial-dependent and independent microvascular blood flow. RESULTS: This pilot study showed that medium and low doses of NO3- were more effective in lowering resting-clinic SBP (P = 0.04 and, P = 0.03, respectively) than was PL. The lower doses of NO3- also resulted in significant increases in microvascular perfusion (medium, P = 0.02; low, P = 0.002) relative to baseline values. CONCLUSION: These findings indicate that supplementation with medium and low, but not high, doses of NO3- for 13 weeks had positive effects on BP and endothelial function in older overweight and obese adults. These findings require confirmation in larger studies.

Incremental Doses of Nitrate-Rich Beetroot Juice Do Not Modify Cognitive Function and Cerebral Blood Flow in Overweight and Obese Older Adults: A 13-Week Pilot Randomised Clinical Trial.

Nitrate-rich food increases nitric oxide (NO) production and may have beneficial effects on vascular, metabolic, and brain function. This pilot study tested the effects of prolonged consumption of a range of doses of dietary nitrate (NO3-), provided as beetroot juice, on cognitive function and cerebral blood flow (CBF) in overweight and obese older participants. The study had a 13-week single-blind, randomised, parallel design, and 62 overweight and obese older participants (aged 60 to 75 years) received the following interventions: (1) high NO3- (2 × 70 mL beetroot juice/day) (2) medium NO3- (70 mL beetroot juice/day), (3) low NO3- (70 mL beetroot juice on alternate days), or (4) placebo (70 mL of NO3--depleted beetroot juice on alternate days). Cognitive functions were assessed using the Computerised Mental Performance Assessment System (COMPASS) assessment battery. CBF, monitored by concentration changes in oxygenated and deoxygenated haemoglobin, was assessed in the frontal cortex using near-infrared spectroscopy. The findings of this pilot study showed that cognitive function and CBF were not affected by supplementation with NO3--rich beetroot juice for 13 weeks, irrespective of the NO3- dose administered. These findings require confirmation in larger studies using more sophisticated imaging methods (i.e., MRI) to determine whether prolonged dietary NO3- supplementation influences brain function in older overweight people.

Dietary nitrate and brain health. Too much ado about nothing or a solution for dementia prevention?

Dementia is a significant public health priority with approximately 55 million cases worldwide, and this number is predicted to quadruple by 2050. Adherence to a healthy diet and achieving optimal nutritional status are vital strategies to improve brain health. The importance of this area of research has been consolidated into the new term 'nutritional psychiatry'. Dietary nitrate, closely associated with the intake of fruits and vegetables, is a compound that is increased in dietary patterns such as the Mediterranean and MIND diets and has protective effects on cognition and brain health. Nitrate is characterised by a complex metabolism and is the precursor of the nitrate­nitrite­nitric oxide (NO) pathway contributing to systemic NO generation. A higher intake of dietary nitrate has been linked to protective effects on vascular outcomes including blood pressure and endothelial function. However, the current evidence supporting the protective effects of dietary nitrate on brain health is less convincing. This article aims to provide a critical appraisal of the current evidence for dietary nitrate supplementation for improving brain health and provide suggestions for future research.

Acceptability and Feasibility of a 13-Week Pilot Randomised Controlled Trial Testing the Effects of Incremental Doses of Beetroot Juice in Overweight and Obese Older Adults.

Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO3-) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m2) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO3- (HN: 2 × 70 mL BJ/day) (2) medium-NO3- (MN: 70 mL BJ/day), (3) low-NO3- (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO3--depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO3- intake, and by measuring NO3- and NO2- concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO3- dose and the increase in plasma and urinary NO3- concentration (R2 = 0.71, P < 0.001 and R2 = 0.46 P < 0.001, respectively), but relationships between NO3- dose and changes in salivary NO3- and NO2- were non-linear (R2 = 0.35, P = 0.002 and R2 = 0.23, P = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults.

Relationship between urinary nitrate concentrations and cognitive function in older adults: findings from the NHANES survey.

This study evaluated the association of urinary nitrate concentrations with cognition in older subjects enrolled in the NHANES study. We also explored whether associations between urinary nitrate and cognition were modified by cardiovascular risk, vitamin D status and vitamin C intake. Two NHANES cycles were merged (2011-2012 and 2013-2014) and a total of 1,015 adults aged 60-80 (69.4 ± 0.3) years were included. Cognition was assessed using the Word List Learning, Word List Recall, Animal Fluency and the Digit Symbol Substitution tests. Urinary nitrate was analysed using electrospray tandem mass spectrometry. Urinary nitrate concentrations were not associated with cognitive performance on any of the cognitive tests. Associations were also not significant in subjects at greater risk for cognitive impairment (i.e. high cardiovascular risk and non-optimal vitamin D status). Longitudinal analyses are needed to explore the associations of urinary nitrate concentrations with dietary nitrate intake and cognitive function.

Protocol and recruitment results from a 13-week randomized controlled trial comparing the effects of different doses of nitrate-rich beetroot juice on cognition, cerebral blood flow and peripheral vascular function in overweight and obese older people.

BACKGROUND: Nitrate-rich food can increase NO production and may induce positive effects on brain function. This study examined the feasibility of a randomized clinical trial (RCT) testing the effects of prolonged consumption of incremental doses of dietary nitrate (NO3 -) in overweight and obese older participants. Secondary aims tested dose-dependent changes in cognitive, vascular and pulmonary functions and cerebral blood flow (CBF). METHODS: This was a single blind, four-arm parallel RCT conducted in 60 overweight and obese older participants. Eligible participants were randomized to:1) high NO3 - (140 ml of beetroot juice (BJ) per day, ~800 mg of NO3 -/day), 2) moderate NO3 - (70 ml of BJ per day, ~400 mg of NO3 -/day), 3) low NO3 - (70 ml on alternate days, ~400 mg of NO3 -) or 4) NO3 - depleted (70 ml on alternate days, ~0.001 mg of NO3). Measurements of cognitive, vascular and pulmonary functions and CBF were conducted at baseline and 13-weeks NO3 - intake was assessed by six 24-h recalls, and by measuring NO3 - intake biomarkers. Feasibility was assessed by obtaining qualitative feedback and evaluating trial recruitment, retention, compliance with study visits and measurement protocols. RESULTS: Participant recruitment started in July 2018 and ended in April 2019. Of all the recruitment strategies that were used, advertisement of the study via Facebook generated the highest response rate. Sixty-two participants consented and were enrolled. Overall, characteristics of included participants matched our recruitment criteria. CONCLUSION: The findings from this study provide evidence of the acceptability and feasibility of an intervention investigating the effects of incremental doses of high-nitrate BJ over a prolonged period. TRIAL REGISTRATION: The intervention study was registered with clinical trial ISRCTN registry (ISRCTN14746723) on 27 December 2018.

Knowledge and beliefs about dietary inorganic nitrate among UK-based nutrition professionals: Development and application of the KINDS online questionnaire

OBJECTIVES: To examine knowledge and beliefs about the biological roles of dietary inorganic nitrate in UK-based nutrition professionals, and to explore potential differences by participants' education level. SETTING: An online questionnaire was administered to UK-based nutrition professionals, exploring knowledge and/or beliefs across five areas: (1) health and performance effects of nitrate; (2) current and recommended intake values for nitrate; (3) dietary sources of nitrate; (4) methods of evaluating nitrate intake and (5) nitrate metabolism. PARTICIPANTS: One hundred and twenty-five nutrition professionals. PRIMARY OUTCOME: Knowledge and beliefs about inorganic nitrate. RESULTS: Most nutrition professionals taking part in the survey had previously heard of inorganic nitrate (71%) and perceived it to be primarily beneficial (51%). The majority believed that nitrate consumption can improve sports performance (59%) and reduce blood pressure (54%), but were unsure about effects on cognitive function (71%), kidney function (80%) and cancer risk (70%). Knowledge of dietary sources of nitrate and factors affecting its content in food were generally good (41%-79% of participants providing correct answers). However, most participants were unsure of the average population intake (65%) and the acceptable daily intake (64%) of nitrate. Most participants (65%) recognised at least one compound (ie, nitric oxide or nitrosamines) that is derived from dietary nitrate in the body. Knowledge of nitrate, quantified by a 23-point index created by summing correct responses, was greater in individuals with a PhD (p=0.01; median (IQR)=13 (9-17)) and tended to be better in respondents with a masters degree (p=0.054; 13 (8-15)) compared with undergraduate-level qualifications (10 (2-14)). CONCLUSIONS: UK-based nutrition professionals demonstrated mixed knowledge about the physiology of dietary nitrate, which was better in participants with higher education. More efficient dissemination of current knowledge about inorganic nitrate and its effects on health to nutrition professionals will support them to make more informed recommendations about consumption of this compound.

Validity and reliability of test strips for the measurement of salivary nitrite concentration with and without the use of mouthwash in healthy adults.

The nitrate (NO3-)-nitrite (NO2-)-nitric oxide (NO) pathway has received considerable interest in recent years as a potential target for nutritional interventions designed to increase NO production, and elicit therapeutic effects in humans. In particular, studies have evaluated the effects of supplemental dietary NO3-, which serves as a 'substrate' for this pathway, on numerous different health outcomes. One challenge has been to evaluate compliance with the NO3- interventions. A recent advance in this field has been the development of a non-invasive, simple and rapid method to measure nitrite concentrations in saliva using small test salivary strips. In the present study, ten healthy adults were recruited to a randomised, crossover study and received an acute dose of NO3--rich beetroot juice (BJ) after rinsing their mouth with either water or commercially available antibacterial mouthwash. Salivary NO3- and NO2- concentrations were measured at baseline and up to 5 h after BJ consumption using the gold-standard chemiluminescence and a colorimetric Griess assay. In addition, two salivary test strips (Berkeley Test strips, CA, USA) were used to measure NO2-concentrations at the same time points. Five observers read the strips and inter- and intra-observer reliability was measured. The Bland-Altman method was used to provide a visual representation of the agreement between the methods used to evaluate salivary NO3-/NO2-concentration. Sialin concentrations were measured at baseline and up to 5 h after BJ consumption. BJ elevated salivary NO3- and NO2- concentrations when the mouth was rinsed with water (both P < 0.01), as assessed via both chemiluminescence and Griess methods. Rinsing the mouth with antibacterial mouthwash attenuated markedly the increase in NO2- (P < 0.001), while NO3-concentrations were unaffected (P > 0.05). The Intra-Class Coefficients of Correlation (ICC) showed a high inter- and intra-observer reliability (r > 0.8). A significant positive correlation was found between absolute salivary NO2- concentrations measured by strips and Griess and chemiluminescence methods (rho = 0.83 and 0.77, respectively) and also when expressed as changes in salivary NO2- concentrations (rho = 0.80 and 0.79, respectively). Bland Altman analysis indicated a poor agreement for absolute NO2- concentrations between salivary strips and the chemiluminescence and Griess methods. A small significant negative correlation was found between changes in salivary sialin and salivary NO2- concentrations (r = -0.20, P = 0.04). A non-significant positive correlation was observed between the change in salivary sialin and salivary NO3- concentrations (r = 0.18, P = 0.06). This study suggests that commercially available salivary NO2- test strips provide a reasonable surrogate marker for monitoring changes in salivary NO2- concentrations in humans. However, the strips do not provide accurate estimates of absolute NO2- concentrations.

Effects of inorganic nitrate and nitrite consumption on cognitive function and cerebral blood flow: A systematic review and meta-analysis of randomized clinical trials.

We conducted a systematic review and meta-analysis of randomized clinical trials examining the effect of inorganic nitrate or nitrite supplementation on cognitive function (CF) and cerebral blood flow (CBF). Two databases (PubMed, Embase) were searched for articles from inception until May 2017. Inclusion criteria were: randomized clinical trials; participants >18 years old; trials comparing a nitrate/nitrite intervention with a control. Thirteen and nine trials were included in the meta-analysis to assess CF and CBF, respectively. Random-effects models were used and the effect size described as standardized mean differences (SMDs). A total of 297 participants (median of 23 per trial) were included for CF; 163 participants (median of 16 per trial) were included for CBF. Nitrate/nitrite supplementation did not influence CF (SMD +0.06, 95% CI: -0.06, 0.18, P = 0.32) or CBF under resting (SMD +0.14, 95% CI: -0.13, 0.41, P = 0.31), or stimulated conditions (SMD + 0.23, 95% CI: -0.11, 0.56, P = 0.19). The meta-regression showed an inverse association between duration of the intervention and CBF (P = 0.02) but no influence of age, BMI or dose (P < 0.05). Nitrate and nitrite supplementation did not modify CBF or CF. Further trials employing larger samples sizes and interventions with longer duration are warranted.

Assessment of dietary nitrate intake in humans: a systematic review.

Background: The nitrate content of foods and water is highly variable, which has implications for the compilation of food-composition databases and assessment of dietary nitrate intake. Objective: A systematic review was conducted to ascertain the dietary assessment methods used and to provide estimates of daily nitrate intake in humans. Design: Relevant articles were identified by a systematic search of 3 electronic databases (PubMed, Web of Science, and Embase) from inception until February 2018. Observational studies conducted in adult populations and reporting information on dietary assessment methods and daily nitrate intake were included. Ecological analyses were conducted to explore the association of nitrate intake with indexes of economic development [Gross Domestic Product (GDP) and KOF Index of Globalization]. Results: A total of 55 articles were included. Forty-two studies investigated associations between nitrate intake and disease risk; 36 (87%) of these studies examined the association between nitrate intake and cancer risk, whereas only 6 studies explored the association of nitrate intake with the risk of diabetes, glaucoma, kidney failure, hypertension, and atherosclerotic vascular disease. The majority of studies used food-frequency questionnaires to assess nitrate intake (n = 43). The median daily nitrate intakes in healthy and patient populations were 108 and 110 mg/d, respectively. We found a significant inverse correlation of nitrate intake with GDP (r = -0.46, P < 0.001) and KOF index (r = -0.31, P = 0.002). Conclusions: The median estimated daily nitrate intakes by healthy and patient populations were similar, and these values were below the safe upper intake of daily intake (3.7 mg nitrate ion/kg body weight). However, there is considerable heterogeneity in the application of food-composition tables, which may have implications for the accuracy of estimated daily nitrate intake. The association between nitrate intake and risk of cardiometabolic diseases needs further investigation. The protocol for this systematic review has been registered in the PROSPERO database (https://www.crd.york.ac.uk/prospero; CRD number: 42017060354).

Cardiovascular Disease, the Nitric Oxide Pathway and Risk of Cognitive Impairment and Dementia.

PURPOSE OF REVIEW: In this review, we summarise the evidence on the association between cardiovascular disease (CVD) and cognitive impairment and explore the role of the nitric oxide (NO) pathway as a causal mechanism. RECENT FINDINGS: Evidence from epidemiological studies suggests that the presence of CVD and its risk factors in midlife is associated with an increased risk of later life cognitive impairment and dementia. It is unclear what is driving this association but risk may be conveyed via an increase in neurodegeneration (e.g. amyloid deposition), vascular changes (e.g. small vessel disease) and mechanistically due to increased levels of oxidative stress and inflammation as well as changes in NO bioavailability. CVDs and dementia are major challenges to global health worldwide. The NO pathway may be a promising biological candidate for future studies focused on reducing not only CVD but also risk of cognitive decline and dementia.