Nursing & Health
Permanent URI for this collectionhttps://research.avondale.edu.au/handle/123456789/457
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Item Saturated Fatty Acid Intake Is Associated With Increased Inflammation, Conversion of Kynurenine to Tryptophan, and Delta-9 Desaturase Activity in Healthy Humans(2020-12-17) Grant, Ross; Seyedsadjadi, Neda; Berg, JadeSaturated fat ingestion has previously been linked to increases in inflammation. However the relationship between saturated fatty acid (SFA) intake and the kynureine:tryptophan ratio ([Kyn]:[Trp]), a marker of inflammation, has not been previously investigated. This study evaluated in healthy, middle aged, individuals (men = 48, women = 52), potential relationships between SFA intake, red blood cell (RBC) membrane SFAs and monounsaturated fatty acids (MUFA), the [Kyn]:[Trp] ratio, C-reactive protein (CRP), TNF-α and Δ9 desaturase activity. [Kyn]:[Trp] was positively associated with increases in Total fat (P = .034) intake, including Total SFA (P = .029) and Total MUFA (P = .042) intakes. Unexpectedly the [Kyn]:[Trp] ratio was inversely associated with the percentage of Total SFA (P = .004) and positively associated with percentage of Total MUFA (P = .012) present in the RBC membrane. We found a positive association between Δ9 desaturase activity, responsible for the desaturation of a various SFAs to MUFAs, and [Kyn]:[Trp] (P = .008). [Kyn]:[Trp] was also positively associated with CRP (P = .044), however no significant relationship between [Kyn]:[Trp] and TNF-α was found. This study shows for the first time that SFA consumption increases inflammatory pathways linked to increased tryptophan to kynurenine conversion, even in healthy humans. Our data also suggests that SFA linked increases in inflammation occur concomitantly with an upregulation of Δ9 desaturase activity resulting in increased desaturation of SFA substrates to their MUFA derivatives.
Item The Status of Folate, Vitamin B-12 and Homocysteine among Australian Vegetarian and Non-Vegetarian Teenagers(2021-01-08) Morris, Margaret; Pearce, Robyn; Berg, Jade; Bilgin, Ayse A.; Vos, Paul; Grant, Ross; Pawlak, RomanBackground/Aims: Vegetarians have a high risk of abnormal vitamin B-12 (B-12), and homocysteine (Hcy), status. The objectives included assessment of: 1) folate, B-12, and Hcy status; 2) incidence rate of abnormal folate, B-12, and Hcy; and 3) associations between folate and B-12 with Hcy status among vegetarian and non-vegetarian adolescents.
Methods: A cross-sectional plasma folate, B-12, and Hcyassessment in 49 vegetarian and 639 non-vegetarian, 14-17 year-old, participants from New South Wales, Australia.
Results: Mean (range) folate (nmol/L), B-12 (pmol/L), and Hcy (μmol/L), were: 33.4 (9.57-101) vs. 27.7 (2.7-86), p=0.033; 287.81 (134-702) vs. 392.22 (119-1300), p
Conclusions: B-12 is a nutrient of a concern for vegetarian teenagers. To improve B-12 status, vegetarian adolescents should consume foods fortified with B-12, and/or take B-12 supplements.
Item Acute Caffeine Intake in Humans Reduces Post Exercise Performance in Learning and Memory(2021-05-03) Grant, Ross; Seyed Sadjadi, Neda; Salonikas, Chris; Cooper, Jesse; Berg, JadeObjective
To clarify the acute effect of caffeine on postexercise memory and learning performance.
Methods
Eight male slow‐to‐normal caffeine metabolizers, unhabituated to caffeine, were recruited into this randomized, double blind, placebo controlled, cross over study. Caffeine (150 mg) or the placebo was consumed one hour prior to two 30 min submaximal cycling sessions. Blood was collected at the beginning, after 20 and 35 min of exercise and 30 min postexercise. Mature brain‐derived neurotrophic factor (BDNF) and proBDNF concentrations were determined. Auditory memory was assessed immediately, 30 min and 24 h postexercise.
Results
Participants averaged lower scores in every measure of learning and memory after ingesting caffeine compared to the placebo. Although the mean did not differ significantly for all measures, significant differences were found between the caffeine and placebo groups for the three indices; learning over time, short‐term index and retroactive interference. The ratio of serum mBDNF:proBDNF increased with exercise across all time points. No significant difference in the mBDNF:proBDNF ratio was observed between treatment groups.
Conclusion
The consumption of caffeine prior to exercise may impair an unhabituated individual's capacity to learn and recall auditory information postexercise. However it is yet to be elucidated whether this is through caffeine's modulating effects on brain BDNF.
Item Visceral Fat Mass: Is it the Link Between Uric Acid and Diabetes Risk?(2017-07-24) Grant, Ross; Bilgin, Ayse A.; Berg, Jade; Seyed-Sadjadi, NedaBackground
Uric acid (UA) has been suggested as a novel risk factor for diabetes. However, its definite role in this prevalent disease is still the subject of much discussion because it is always accompanied with other major risk factors such as obesity and high visceral adiposity. In order to clarify the role of UA in diabetes, this study aimed to investigate the associations between plasma UA and fasting plasma glucose, HbA1c, lipid profile and inflammatory markers after accounting for the contribution of other diabetes risk factors such as BMI and VAT fat mass.
Methods
In the present cross-sectional study, 100 non-diabetic middle-aged males (n = 48) and females (n = 52) were recruited. Central fat distribution measures including android to gynoid fat ratio, VAT and subcutaneous adipose tissue (SAT) fat mass were determined using dual-energy X-ray absorptiometry (DXA). Biochemical analysis was done using methods well established for clinical and research laboratories. Multiple linear regression analysis was performed to analyse the association between plasma UA and the biochemical and central fat distribution measures.
Results
UA was positivly associated with body mass index (BMI) (r (98) = 0.42, P ≤ 0.001), android to gynoid fat ratio (r (98) = 0.62, P ≤ 0.001) and VAT fat mass (r (96) = 0.55, P ≤ 0.001). UA was also positively associated with plasma glucose (r (98) = 0.33, P ≤ 0.001), hemoglobin A1c (r (93) = 0.25, P = 0.014), plasma triglyceride (r s (95) = 0.40, P ≤ 0.001), HDL cholesterol (r (98) = − 0.61, P ≤ 0.001) and CRP (r s (98) = 0.23, P = 0.026). However, these associations were no longer significant after accounting for BMI or/and VAT fat mass. No significant association was observed between UA and SAT fat mass (r (97) = 0.02, P ≥ 0.05), Total cholesterol (r (98) = 0.03, P ≥ 0.05), LDL cholesterol (r (98) = 0.13, P ≥ 0.05), TNF-α (r (97) = 0.12, P ≥ 0.05) and IL-6 (r (96) = −0.02, P ≥ 0.05).
Conclusion
Results from this study suggest, for the first time, that the association between plasma UA and glucose in a non-diabetic population is not direct but rather dependent on VAT fat mass.
Item Significant Relationships Between a Simple Marker of Redox Balance and Lifestyle Behaviours; Relevance to the Framingham Risk Score(2017-11-06) Grant, Ross; Tung, Chin; Bilgin, Ayse A.; Berg, Jade; Seyed-Sadjadi, NedaOxidative stress has been closely linked to the progressive cell damage associated with emerging non-communicable disease (NCDs). Early detection of these biochemical abnormalities before irreversible cell damage occurs may therefore be useful in identifying disease risk at an individual level. In order to test this hypothesis, this study assessed the relationship between a simple measure of redox status and lifestyle risk factors for NCDs, and the population-based risk score of Framingham. In a cross-sectional study design, 100 apparently healthy middle-aged males (n = 48) and females (n = 52) were asked to complete a comprehensive lifestyle assessment questionnaire, followed by body fat percentage and blood pressure measurements, and blood collection. The ratio of plasma total antioxidant capacity to hydroperoxide (TAC/HPX) was used as an index of redox balance. One-way ANOVA and multiple linear regression analysis were performed to analyse the association between TAC/HPX, lifestyle components and other plasma biomarkers. The TAC/HPX ratio was higher in males compared to females (t96 = 2.34, P = 0.021). TAC/HPX was also lower in participants with poor sleep quality (t93 = 2.39, P = 0.019), with high sleep apnoea risk (t62.2 = 3.32, P = 0.002), with high caffeine (F(2, 93) = 3.97, P = 0.022) and red meat intake (F(2, 93) = 5.55, P = 0.005). These associations were independent of gender. Furthermore, the TAC/HPX ratio decreased with increasing body fat percentage (F(2, 95) = 4.74, P = 0.011) and depression score (t94 = 2.38, P = 0.019), though these associations were dependent on gender. Importantly, a negative association was observed between TAC/HPX levels and the Framingham risk score in both males (r(45) = -0.39, P = 0.008) and females (r(50) = -0.33, P = 0.019) that was independent of other Framingham risk score components. Findings from this study suggests that a relatively simple measure of redox balance such as the TAC/HPX ratio may be a sensitive indicator of redox stress, and may therefore serve as a useful biomarker for assessing an individual’s specific NCD risk linked to unhealthy lifestyle practices.
Item A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+(2019-09-12) Watson, James; Broom, Susan; Bennett, James; Braidy, Nady; Mestayer, Richard; Berg, Jade; Grant, RossAccumulating evidence suggests that active maintenance of optimal levels of the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+) is beneficial in conditions of either increased NAD+ turnover or inadequate synthesis, including Alzheimer’s disease and other neurodegenerative disorders and the aging process. While studies have documented the efficacy of some NAD+ precursors such as nicotinamide riboside (NR) in raising plasma NAD+, no data are currently available on the fate of directly infused NAD+ in a human cohort. This study, therefore, documented changes in plasma and urine levels of NAD+ and its metabolites during and after a 6 h 3 μmol/min NAD+ intravenous (IV) infusion. Surprisingly, no change in plasma (NAD+) or metabolites [nicotinamide, methylnicotinamide, adenosine phosphoribose ribose (ADPR) and nicotinamide mononucleotide (NMN)] were observed until after 2 h. Increased urinary excretion of methylnicotinamide and NAD+ were detected at 6 h, however, no significant rise in urinary nicotinamide was observed. This study revealed for the first time that: (i) at an infusion rate of 3 μmol/min NAD+ is rapidly and completely removed from the plasma for at least the first 2 h; (ii) the profile of metabolites is consistent with NAD+ glycohydrolase and NAD+ pyrophosphatase activity; and (iii) urinary excretion products arising from an NAD+ infusion include NAD+ itself and methyl nicotinamide (meNAM) but not NAM.
Item Increased Consumption of Plant Foods is Associated with Increased Bone Mineral Density(2020-04-01) Grant, Ross; Seyed Sadjadi, Neda; Berg, JadeObjectives
To determine the relationship between plant food consumption and bone mineral density (BMD) in a healthy population when age, gender, BMI and physical activity are accounted for.
Design
Cross-sectional study.
Setting
Participants were recruited from the Sydney Adventist hospital and the University of New South Wales, Sydney, Australia.
Participants
33 males and 40 females (total n=73) participated in this study. The mean age was 56.1 ± 8.5 years. All participants were non-diabetic and in general good health.
Measurements
A principle component analysis (PCA) was performed on 12 month self-report food intake data, gathered using the Cancer Council Victoria Dietary Questionnaire for Epidemiological Studies Version 2. Dual-energy X-ray absorptiometry was used to measure total BMD. Fasting plasma total protein, calcium and 25-Hydroxy Vitamin D levels were analysed by the Sydney Adventist Hospital pathology laboratory. Anthropometric measures were obtained using a standardized protocol. Self-reported physical activity levels were assessed using the International Physical Activity Questionnaire.
Results
The PCA revealed three principle components. These were termed ‘Meat Based’, ‘Junk Food’ and ‘Plant Based.’ After controlling for age, gender, physical activity and BMI, the Plant Based component correlated positively with BMD (p=0.054, R2=0.439) and T-score (p=0.053, R2=0.221). Using a similar model no association between the Meat Based component and BMD or T-score was found. However, when the Plant Based component was included the Meat Based component correlated positively with BMD (p=0.046, R2=0.474) and T-score (p=0.046, R2=0.279). There was no significant association between the Junk Food component and BMD or T-score. People in the third Plant (927 ± 339 vs 751 ± 255 g/day, p=0.025) and Meat Based (921 ± 270 vs 676 ± 241 g/day, p=0.002) tertile had higher calcium intakes than those in the first. People in the second Plant Based tertile had higher plasma Vitamin D levels than those in the first (63.5 ± 16.8 vs. 52.3 ± 22.1 nmol/L, p=0.053) while those in the third Junk Food tertile had lower levels than those in the first (52.4 ± 18.5 vs. 65.4 ± 19.8 nmol/L, p=0.027). No association between Plant Based tertiles and protein intake was observed, however those in the third Meat Based (99.7 ± 25.1 vs. 50.9 ± 13.8 g/day, p=0.000) and Junk Food (87.4 ± 30.7 vs. 56.6 ± 22.2 g/day, p=0.000) tertile had higher protein intake compared to those in the first tertile.
Conclusion
In a healthy middle aged population with normal BMD, an increase in plant food consumption, either alone or in combination with a diet containing meat, is associated with improved bone mineralisation markers. This positive relationship is most likely due to the extensive range of micronutrients and phytochemicals packaged within plants.
Item Promoting NAD+ Metabolism: A new Target for Treating Degenerative Disease(2016-12-01) Braidy, Nady; Berg, Jade; Grant, RossNAD+ is found in every cell of the body and is essential for life. It serves as a cofactor for dehydrogenase, reductase and hydroxylase enzymes where it facilitates electron transfer in major metabolic pathways such as glycolysis, the triacarboxylic acid (TCA) cycle, fatty acid synthesis and steroid hormone synthesis, enabling the conversion of the food we eat into the energy and chemical products the body needs. More recently it has been found that NAD+ is also required as a substrate by enzymes that regulate the expression of genes involved in cell viability and aging and in repair of damaged DNA. Through these reactions, NAD+ influences a variety of cell processes involved in cell health, including improving mitochondrial efficiency, enhancing cell viability, down-regulating inflammation, increasing the antioxidant capacity of cells and tissues, and activating the ‘longevity’ enzyme SIRT1. An increasing body of evidence indicates that enhancing NAD+ availability in the brain has the potential to moderate elements of the neurodegenerative disease processes associated with oxidative stress and aging, including Alzheimer’s disease. However there are difficulties associated with raising NAD+ levels using the classical pathway and vitamin B3 precursors nicotinic acid and nicotinamide. The recent discovery of two alternative naturally occurring B3 vitamins; nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) may resolve these problems. NR in particular has shown good efficacy in its ability to raise NAD+ levels under a variety of conditions. Directly boosting [NAD+] may present a new and exciting approach to preventing the natural decline in cellular energy and function as we age, particularly in the brain.
Item Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes(2019-01-10) Sachdev, Perminder; Grant, Ross; Jayasena, Tharusha; Poljak, Anne; Khorshidi, Fatemeh; Clement, James; Berg, Jade; Braidy, NadySignificance: Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that serves as an essential cofactor and substrate for a number of critical cellular processes involved in oxidative phosphorylation and ATP production, DNA repair, epigenetically modulated gene expression, intracellular calcium signaling, and immunological functions. NAD+ depletion may occur in response to either excessive DNA damage due to free radical or ultraviolet attack, resulting in significant poly(ADP-ribose) polymerase (PARP) activation and a high turnover and subsequent depletion of NAD+, and/or chronic immune activation and inflammatory cytokine production resulting in accelerated CD38 activity and decline in NAD+ levels. Recent studies have shown that enhancing NAD+ levels can profoundly reduce oxidative cell damage in catabolic tissue, including the brain. Therefore, promotion of intracellular NAD+ anabolism represents a promising therapeutic strategy for age-associated degenerative diseases in general, and is essential to the effective realization of multiple benefits of healthy sirtuin activity. The kynurenine pathway represents the de novo NAD+ synthesis pathway in mammalian cells. NAD+ can also be produced by the NAD+ salvage pathway.
Recent Advances: In this review, we describe and discuss recent insights regarding the efficacy and benefits of the NAD+ precursors, nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), in attenuating NAD+ decline in degenerative disease states and physiological aging.
Critical Issues: Results obtained in recent years have shown that NAD+ precursors can play important protective roles in several diseases. However, in some cases, these precursors may vary in their ability to enhance NAD+ synthesis via their location in the NAD+ anabolic pathway. Increased synthesis of NAD+ promotes protective cell responses, further demonstrating that NAD+ is a regulatory molecule associated with several biochemical pathways.
Future Directions: In the next few years, the refinement of personalized therapy for the use of NAD+ precursors and improved detection methodologies allowing the administration of specific NAD+ precursors in the context of patients' NAD+ levels will lead to a better understanding of the therapeutic role of NAD+ precursors in human diseases.
Item High Protein Intake is Associated with Low Plasma NAD+ Levels in a Healthy Human Cohort(2018-08-16) Grant, Ross; Salonikas, Chris; Braidy, Nady; Bilgin, Ayse; Berg, Jade; Seyed Sadjadi, NedaHigh protein intake and reduced levels of the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+) have both been independently associated with promotion of the ageing phenotype. However, it has not yet been shown whether these two independent observations are biochemically linked. To investigate this possibility, we used a cross-sectional study design of 100 apparently healthy middle-aged males (n = 48) and females, in which we assessed average dietary intakes of multiple components using a validated questionnaire. We also analysed fasting blood levels of urea, NAD+ and its metabolites, and inflammation-linked biomarkers, including interleukin-6 (IL-6), Kynurenine (Kyn), and Tryptophan (Trp). One-way ANOVA and ANCOVA were then performed for statistical analysis. Our results have shown for the first time that plasma levels of NAD+ and Total NAD(H) were lower with increasing protein intake (F (2, 92) = 4.61, P = 0.012; F (2, 92) = 4.55, P = 0.013, respectively). The associated decrease in NAD+ and NAD(H) levels was even stronger with increasing plasma levels of the protein breakdown product urea (F (2, 93) = 25.11, P≤0.001; F (2, 93) = 21.10, P≤0.001). These associations were all independent of age, gender and energy intake. However, no significant association was observed between protein intake or plasma urea, and plasma levels of NAD+ metabolites. We also observed that plasma levels of the inflammatory cytokine IL-6, and both Kyn, and Trp, but not the Kyn/Trp ratio were higher with increasing plasma urea levels (F (2, 94) = 3.30, P = 0.041; F (2, 95) = 7.41, P≤0.001; F (2, 96) = 4.23, P = 0.017, respectively). These associations were dependent on eGFR and energy intake, except for the urea and Trp association that was independent of all. In conclusion, we report for the first time, a novel association between protein intake, its metabolism, and plasma NAD+ levels with a possible link to inflammation. These findings provide further insight into how protein restriction may contribute to the anti-ageing process observed in several studies.