The association between driving time and unhealthy lifestyles: a cross-sectional, general population study of 386 493 UK Biobank participants.

BACKGROUND: Driving is a common type of sedentary behaviour; an independent risk factor for poor health. The study explores whether driving is also associated with other unhealthy lifestyle factors. METHODS: In a cross-sectional study of UK Biobank participants, driving time was treated as an ordinal variable and other lifestyle factors dichotomized into low/high risk based on guidelines. The associations were explored using chi-square tests for trend and binary logistic regression. RESULTS: Of the 386 493 participants who drove, 153 717 (39.8%) drove <1 h/day; 140 140 (36.3%) 1 h/day; 60 973 (15.8%) 2 h/day; and 31 663 (8.2%) ≥3 h/day. Following adjustment for potential confounders, driving ≥3 h/day was associated with being overweight/obese (OR = 1.74, 95% CI: 1.64-1.85), smoking (OR = 1.48, 95% CI: 1.37-1.63), insufficient sleep (1.70, 95% CI: 1.61-1.80), low fruit/vegetable intake (OR = 1.26, 95% CI: 1.18-1.35) and low physical activity (OR = 1.05, 95% CI: 1.00-1.11), with dose relationships for the first three, but was not associated with higher alcohol consumption (OR = 0.94, 95% CI: 0.87-1.02). CONCLUSIONS: Sedentary behaviour, such as driving, is known to have an independent association with adverse health outcomes. It may have additional impact mediated through its effect on other aspects of lifestyle. People with long driving times are at higher risk and might benefit from targeted interventions.

Comparing the effects of low and high load resistance exercise to failure on adaptive responses to resistance exercise in young women.

The aim of this study was to compare the effect of 6 weeks of resistance training to volitional failure at low (30% 1 repetition maximum (RM)) or high (80%1RM) loads on gains in muscle size and strength in young women. Thirteen women (age: 29.7 ± 4.7years; height 166.7 ± 6.4cm; weight 64.2 ± 12.2kg) completed 2 training sessions per week for 6 weeks and muscle strength (1RM), muscle thickness (ultrasound) were measured before and after training. Training comprised 1 set to volitional failure of unilateral leg extensions and bicep curls with each limb randomly assigned to train at either 80% 1RM or 30% 1RM. Increases in muscle thickness [arms: 6.81 ± 3.15% (30% 1RM), 5.90 ± 3.13% (80% 1RM) and legs: 9.37 ± 5.61% (30% 1RM), 9.13 ± 7.9% (80% 1RM)] and strength [arms: 15.4 ± 12.2% (30% 1RM), 18.26 ± 12.2% (80% 1RM) and legs: 25.30 ± 18.4 (30% 1RM), 27.20 ± 14.5 (80% 1RM)] were not different between loads. When resistance exercise is performed to volitional failure gains in muscle size and strength are independent of load in young women.

Wastewater recycling in Antarctica: Performance assessment of an advanced water treatment plant in removing trace organic chemicals.

The Australian Antarctic Division (AAD) operates Australia's Davis Station in the Antarctic. In 2005, Davis Station's wastewater treatment plant failed and since then untreated, macerated effluent has been discharged to the ocean. The objectives of this study were to determine whether an advanced water treatment plant (AWTP) commissioned by the AAD and featuring a multi-barrier process involving ozonation, ceramic microfiltration, biologically activated carbon filtration, reverse osmosis, ultraviolet disinfection and chlorination was capable of producing potable water and a non-toxic brine concentrate that can be discharged with minimal environmental impact. The AWTP was tested using water from a municipal wastewater treatment plant in Tasmania, Australia. We used spot water and passive sampling combined with two multi-residue chromatographic-mass spectrometric methods and a range of recombinant receptor-reporter gene bioassays to screen trace organic chemicals (TrOCs), toxicity and receptor activity in the Feed water, in the environmental discharge (reject water), and product water from the AWTP for six months during 2014-15, and then again for three months in 2016. Across the two surveys we unambiguously detected 109 different TrOCs in the feed water, 39 chemicals in the reject water, and 34 chemicals in the product water. Sample toxicity and receptor activity in the feed water samples was almost totally removed in both testing periods, confirming that the vast majority of the receptor active TrOCs were removed by the treatment process. All the NDMA entering the AWTP in the feed and/or produced in the plant (typically < 50 ng/L), was retained into the reject water with no NDMA observed in the product water. In conclusion, the AWTP was working to design, and releases of TrOCs at the concentrations observed in this study would be unlikely cause adverse effects on populations of aquatic organisms in the receiving environment or users of the potable product water.

Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants.

BACKGROUND: Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study. METHODS: This study included cross-sectional data from 48 170 white European adults, aged 37-73 years, participating in the UK Biobank. Interactions between GPRS-obesity and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated. RESULTS: The 93-single-nucleotide polymorphism (SNP) GPRS was associated with a higher BMI (ß: 0.57 kg m-2 per s.d. increase in GPRS (95% confidence interval: 0.53-0.60); P=1.9 × 10-183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P(interaction)=0.007). Among high-fat-intake individuals, BMI was higher by 0.60 (0.52, 0.67) kg m-2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low-fat-intake individuals (ß: 0.50 (0.44, 0.57) kg m-2). Significant interactions with similar patterns were observed for saturated fat intake (high ß: 0.66 (0.59, 0.73) versus low ß: 0.49 (0.42, 0.55) kg m-2, P(interaction)=2 × 10-4) and for total energy intake (high ß: 0.58 (0.51, 0.64) versus low ß: 0.49 (0.42, 0.56) kg m-2, P(interaction)=0.019), but not for protein intake, carbohydrate intake and fibre intake (P(interaction) >0.05). The findings were broadly similar using WC as the outcome. CONCLUSIONS: These data suggest that the benefits of reducing the intake of fats and total energy intake may be more important in individuals with high genetic risk for obesity.

The relationship between vitamin D status and muscle strength in young healthy adults from sunny climate countries currently living in the northeast of Scotland.

The current study examined the relationship between vitamin D status and muscle strength in young healthy adults: residents (>6 months) and newcomers (0-3 months), originally from sunny climate countries but currently living in the northeast of Scotland. Our longitudinal data found a positive, albeit small, relationship between vitamin D status and knee extensor isometric strength. INTRODUCTION: Vitamin D has been suggested to play a role in muscle health and function, but studies so far have been primarily in older populations for falls prevention and subsequent risk of fractures. METHODS: Vitamin D status was assessed in a healthy young adults from sunny climate countries (n = 71, aged 19-42 years) with 56% seen within 3 months of arriving in Aberdeen [newcomers; median (range) time living in the UK = 2 months (9-105 days)] and the remainder resident for >6 months [residents; 23 months (6-121 months)]. Participants attended visits every 3 months for 15 months. At each visit, fasted blood samples were collected for analysis of serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type I collagen (P1NP). Maximal voluntary contractions (MVC) were performed for grip strength (both arms) and for maximal isometric strength of the knee extensors (right knee). RESULTS: There were small seasonal variations in 25(OH)D concentrations within the newcomers and residents, but no seasonal variation in bone turnover markers. There was a positive, albeit small, association between 25(OH)D and knee extensor maximal isometric strength. Mixed modelling predicted that for each 1 nmol/L increase in 25(OH)D, peak torque would increase by 1 Nm (p = 0.04). CONCLUSIONS: This study suggests that vitamin D may be important for muscle health in young adults migrating from sunnier climates to high latitudes, yet the potential effect is small.

The Effect of Fish Oil, Vitamin D and Protein on URTI Incidence in Young Active People.

Upper respiratory tract infections (URTI) are a frequent illness among athletes. We investigated the effect of a multi-nutrient supplement (vitamin D, fish oil and protein) on the occurrence of URTI in young active people. 42 young recreational athletes were randomly assigned to receive either supplementation (550 mg DHA, 550 mg EPA, 10 µg vitamin D3 and 8 g whey protein) or placebo for 16 weeks. Unstimulated saliva samples were collected by passive drool. Samples were analysed for IgA (sIgA) concentration and the secretion rate extrapolated by multiplying concentration by saliva flow rate. Physical activity levels and URTI incidence were monitored by questionnaire. Training status was not different between the 2 groups. There were no differences in the incidence, severity and duration of URTI. However the number of symptom days was lower in the supplemented compared to the control group (1.72±1.67 vs. 2.79±1.76; P<0.05). sIgA concentration and secretion rate did not differ between groups. This study demonstrates that 16 weeks of supplementation with fish oil, vitamin D and protein did not modify the incidence, severity and duration of URTI, although the total number of symptom days was reduced, in a healthy active population.

The effect of krill oil supplementation on skeletal muscle function and size in older adults: A randomised controlled trial.

BACKGROUND & AIMS: The aim of this study was to determine the effect of krill oil supplementation, on muscle function and size in healthy older adults. METHODS: Men and women, aged above 65 years, with a BMI less than 35kg/m2, who participated in less than 1h per week of structured self-reported exercise, were enrolled in the study (NCT04048096) between March 2018 and March 2020. Participants were randomised to either control or krill oil supplements (4g/day) for 6 months in this double blind randomised controlled trial. At baseline, 6 weeks and 6 months, knee extensor maximal torque was measured as the primary outcome of the study. Secondary outcomes measured were grip strength, vastus lateralis muscle thickness, short performance physical battery test, body fat, muscle mass, blood lipids, glucose, insulin, and C-Reactive Protein, neuromuscular (M-Wave, RMS and voluntary activation), and erythrocyte fatty acid composition. RESULTS: A total of 102 men and women were enrolled in the study. Ninety-four participants (krill group (26 women and 23 men) and placebo group (27 women and 18 men)) completed the study (mean (SD): age 71.2 (5.1) years and weight 71.8 (12.3) kg). Six months supplementation with krill oil resulted in, an increase in knee extensor maximal torque, grip strength and vastus lateralis muscle thickness, relative to control (p<0.05). The 6-month treatment effects were 9.3% (95%CI: 2.8, 15.8%), 10.9% (95%CI: 8.3, 13.6%) and 3.5% (95%CI: 2.1, 4.9%) respectively. Increases in erythrocyte fatty acid profile were seen with krill oil for EPA 214% (95%CI: 166, 262%), DHA 36% (95%CI: 24, 48%) and the omega-3 index 61% (95%CI: 49, 73%), relative to control (p < 0.05). Krill oil resulted in an increased, relative to control (p < 0.05), M-Wave of 17% (95%CI: 12.7, 38.1%) but there was no effect of krill oil on RMS, voluntary activation, or on any other secondary outcomes such as performance of the short performance physical battery test or quality of life. CONCLUSION: Krill oil supplementation for 6 months results in statistically and clinically significant increases in muscle function and size in healthy older adults. GOV IDENTIFIER: NCT04048096.

Detection and enumeration of Dekkera anomala in beer, cola, and cider using real-time PCR.

AIMS: In this article, a quantitative real-time PCR assay for detection and enumeration of the spoilage yeast Dekkera anomala in beer, cola, apple cider, and brewing wort is presented as an improvement upon existing detection methods, which are very time-consuming and not always accurate. METHODS AND RESULTS: Primers were designed to exclude other organisms common in these beverages, and the assay was linear over 6 log units of cell concentrations. The addition of large amounts of non-target yeast DNA did not affect the efficiency of this assay. A standard curve of known DNA was established by plotting the C(t) values obtained from the QPCR against the log of plate counts on yeast peptone dextrose medium and unknowns showed exceptional correlation when tested against this standard curve. The assay was found to detect D. anomala at levels of 10-14 CFU ml⁻¹ in either cola or beer and at levels of 9·4-25·0 CFU ml⁻¹ in apple cider. The assay was also used to follow the growth of D. anomala in brewing wort. CONCLUSIONS: The results indicate that real-time PCR is an effective tool for rapid, accurate detection and quantitation of D. anomala in beer, cola and apple cider. SIGNIFICANCE AND IMPACT OF THE STUDY: This method gives a faster and more efficient technique to screen beer, cola, and cider samples and reduce spoilage by D. anomala. Faster screening may allow for significant reduction in economic loss because of reduced spoilage.

The significance of interactions between organic compounds on low pressure membrane fouling.

Fouling of hollow fibre microfiltration and ultrafiltration membranes by solutions of pure organic compounds and mixtures of these compounds was studied with a backwashable membrane filtration apparatus. Small molecular weight compounds resulted in little fouling, while their polymeric analogues resulted in more severe fouling. Neutrally charged dextran resulted in minor, irreversible fouling, that was considered to be associated with blocking of small pores. Cationically charged chitosan produced gross fouling for which the extent of reversibility increased with salt addition. Anionically charged alginic acid resulted in gross irreversible fouling, except when being filtered by a hydrophilic membrane in the absence of calcium where a high degree of flux recovery was observed. Calcium addition to the alginic acid solutions resulted in gross fouling of all membranes and calcium bridging was considered to be responsible for this behaviour. Greater fouling occurred on the hydrophilic membrane compared to the hydrophobic membranes for bovine serum albumin (BSA) solutions, and this was considered to be due to physical blocking of pores, because addition of calcium resulted in lower flux declines. Addition of BSA and calcium to alginic acid solutions resulted in lower flux recoveries for the alginic acid system, consistent with the proposition that interactions between polysaccharide and other compounds are required for irreversible fouling on hydrophilic membranes.

Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome.

The aim of the current study was to investigate the levels of interleukin-6 (IL-6), its soluble receptors (sIL-6R and sgp130) and F(2)-isoprostanes, at rest and during exercise, in patients with chronic fatigue syndrome (CFS). Six male CFS patients and six healthy controls performed an incremental exercise test to exhaustion and a submaximal exercise bout to exhaustion. Blood samples taken in the submaximal test at rest, immediately post-exercise and 24 h post-exercise were analyzed for IL-6, sIL-6R, sgp130 and F(2)-isoprostanes. A further 33 CFS and 33 healthy control participants gave a resting blood sample for IL-6 and sIL-6R measurement. During the incremental exercise test only power output at the lactate threshold was lower (P<0.05) in the CFS group. F(2)-isoprostanes were higher (P<0.05) in CFS patients at rest and this difference persisted immediately and 24 h post-exercise. The exercise study found no differences in IL-6, sIL-6R or sgp130 at any time point between groups. In the larger resting group, there were no differences in IL-6 and sIL-6R between CFS and control groups. This investigation has demonstrated that patients with CFS do not have altered plasma levels of IL-6, sIL-6R or sgp130 either at rest or following exercise. F(2)-isoprostanes, however, were consistently higher in CFS patients.

Associations between diet and handgrip strength: a cross-sectional study from UK Biobank.

The aim of the current study was to investigate the association between diet and handgrip strength. The current study included 68,002 participants (age 63.8 ± 2.7 years, 50.3% women, 49.7% men) from UK Biobank. Diet and nutritional data (carotene, retinol, potassium, vitamin C, foliate, vitamin B12, vitamin B6, iron, vitamin E, calcium, magnesium, carbohydrates, protein, polyunsaturated fat, fat, starch and saturated fat) were collected and handgrip strength measured. Associations were compared, stratified by sex, using regression analyses, after adjustment for age, sex, month of assessment, ethnicity, deprivation index, height, comorbidities and total energy intake. The current data revealed negative associations between carbohydrate intake and handgrip strength as well as positive associations between oily fish, retinol and magnesium intake and grip strength in both sexes. In women, positive associations were observed between intake of red meat, fruit and vegetables, vitamin E, iron, vitamin B12, folate and vitamin C and hand grip strength. In men only negative associations were seen between bread and processed meat with grip strength. We have shown associations of several nutrients and food items with muscle strength and appropriately designed trials are needed to investigate whether these nutrients/food items may be beneficial in the maintenance of muscle during ageing.

The response of circulating levels of the interleukin-6/interleukin-6 receptor complex to exercise in young men.

The formation of an interleukin-6/IL-6 receptor (IL-6/IL-6R) complex increases the biological activity and half-life of IL-6, with its response to exercise currently unknown. The aim of the present study was to determine the response of circulating levels of the IL-6/IL-6R complex to exercise. Nine healthy male participants performed 1h of cycling exercise at a workload required to elicit 90% lactate threshold. Venous blood samples were taken at rest, immediately post-exercise and after 1.5 h rest. Hemoglobin concentration and hematocrit were measured to estimate changes in plasma volume during exercise. The concentrations of IL-6, sIL-6R and the IL-6/IL-6R complex were measured via ELISA and corrected for changes in plasma volume. A single bout of acute exercise resulted in a 5-fold increase (P<0.05) in IL-6 and a 1.2-fold increase (P<0.05) in sIL-6R immediately after exercise. These returned to baseline at 1.5 h after the cessation of exercise. There was a 2.1-fold increase (P<0.05) in the levels of the IL-6/IL-6R complex post-exercise with levels remaining 1.8 times elevated (P<0.05) after 1.5 h rest. The present study has demonstrated, for the first time, that circulating levels of the IL-6/IL-6R complex are increased in response to acute exercise in young males.

Lysosomes can fuse with a late endosomal compartment in a cell-free system from rat liver.

The passage of pulse doses of asialoglycoproteins through the endosomal compartments of rat liver hepatocytes was studied by subcellular fractionation and EM. The kinetics of disappearance of radiolabeled asialofetuin from light endosomes prepared on Ficoll gradients were the same as the kinetics of disappearance of asialoorosomucoid-horse radish peroxidase reaction products from intracellular membrane-bound structures in the blood sinusoidal regions of hepatocytes. The light endosomes were therefore identifiable as being derived from the peripheral early endosome compartment. In contrast, the labeling of dense endosomes from the middle of the Ficoll gradient correlated with EM showing large numbers of reaction product-containing structures in the nonsinusoidal parts of the hepatocyte. In cell-free, postmitochondrial supernatants, we have previously observed that dense endosomes, but not light endosomes, interact with lysosomes. Cell-free interaction between isolated dense endosomes and lysosomes has now been reconstituted and analyzed in three ways: by transfer of radiolabeled ligand from endosomal to lysosomal densities, by a fluorescence dequenching assay which can indicate membrane fusion, and by measurement of content mixing. Maximum transfer of radiolabel to lysosomal densities required ATP and GTP plus cytosolic components, including N-ethylmaleimide-sensitive factor(s). Dense endosomes incubated in the absence of added lysosomes did not mature into vesicles of lysosomal density. Content mixing, and hence fusion, between endosomes and lysosomes was maximal in the presence of cytosol and ATP and also showed inhibition by N-ethyl-maleimide. Thus, we have demonstrated that a fusion step is involved in the transfer of radiolabeled ligand from an isolated endosome fraction derived from the nonsinusoidal regions of the hepatocyte to preexisting lysosomes in a cell-free system.

Fusion of lysosomes with late endosomes produces a hybrid organelle of intermediate density and is NSF dependent.

Using a cell-free content mixing assay containing rat liver endosomes and lysosomes in the presence of pig brain cytosol, we demonstrated that after incubation at 37 degrees C, late endosome-lysosome hybrid organelles were formed, which could be isolated by density gradient centrifugation. ImmunoEM showed that the hybrids contained both an endocytosed marker and a lysosomal enzyme. Formation of the hybrid organelles appeared not to require vesicular transport between late endosomes and lysosomes but occurred as a result of direct fusion. Hybrid organelles with similar properties were isolated directly from rat liver homogenates and thus were not an artifact of cell-free incubations. Direct fusion between late endosomes and lysosomes was an N-ethylmaleimide-sensitive factor-dependent event and was inhibited by GDP-dissociation inhibitor, indicating a requirement for a rab protein. We suggest that in cells, delivery of endocytosed ligands to an organelle where proteolytic digestion occurs is mediated by direct fusion of late endosomes with lysosomes. The consequences of this fusion to the maintenance and function of lysosomes are discussed.

The role of intraorganellar Ca(2+) in late endosome-lysosome heterotypic fusion and in the reformation of lysosomes from hybrid organelles.

We have investigated the requirement for Ca(2+) in the fusion and content mixing of rat hepatocyte late endosomes and lysosomes in a cell-free system. Fusion to form hybrid organelles was inhibited by 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA), but not by EGTA, and this inhibition was reversed by adding additional Ca(2+). Fusion was also inhibited by methyl ester of EGTA (EGTA-AM), a membrane permeable, hydrolyzable ester of EGTA, and pretreatment of organelles with EGTA-AM showed that the chelation of lumenal Ca(2+) reduced the amount of fusion. The requirement for Ca(2+) for fusion was a later event than the requirement for a rab protein since the system became resistant to inhibition by GDP dissociation inhibitor at earlier times than it became resistant to BAPTA. We have developed a cell-free assay to study the reformation of lysosomes from late endosome-lysosome hybrid organelles that were isolated from the rat liver. The recovery of electron dense lysosomes was shown to require ATP and was inhibited by bafilomycin and EGTA-AM. The data support a model in which endocytosed Ca(2+) plays a role in the fusion of late endosomes and lysosomes, the reformation of lysosomes, and the dynamic equilibrium of organelles in the late endocytic pathway.

Associations of dietary protein intake with bone mineral density: An observational study in 70,215 UK Biobank participants.

PURPOSE: Adequate dietary protein intake is important for the maintenance of bone health; however, data in this area is ambiguous with some suggestion that high protein intake can have deleterious effects on bone health. The aim of the current study was to explore the associations of protein intake with bone mineral density (BMD). METHODS: We used baseline data from the UK Biobank (participants aged 40-69 years) to examine the association of protein intake with BMD (measured by ultrasound). These associations were examined, in women (n = 39,066) and men (n = 31,149), after adjustment for socio-demographic and lifestyle confounders and co-morbidities. RESULTS: Protein intake was positively and linearly associated with BMD in women (ß-coefficient 0.010 [95% CI 0.005; 0.015, p < 0.0001]) and men (ß-coefficient 0.008 [95% CI 0.000; 0.015, p = 0.044]); per 1.0 g/kg/day increment in protein intake, independently of socio-demographics, dietary factors and physical activity. CONCLUSIONS: The current data have demonstrated that higher protein intakes are positively associated with BMD in both men and women. This indicates that higher protein intakes may be beneficial for both men and women.

Effect of membrane character and solution chemistry on microfiltration performance.

To help understand and predict the role of natural organic matter (NOM) in the fouling of low-pressure membranes, experiments were carried out with an apparatus that incorporates automatic backwashing and long filtration runs. Three hollow fibre membranes of varying character were included in the study, and the filtration of two different surface waters was compared. The hydrophilic membrane had greater flux recovery after backwashing than the hydrophobic membranes, but the efficiency of backwashing decreased at extended filtration times. NOM concentration of these waters (7.9 and 9.1mg/L) had little effect on the flux of the membranes at extended filtration times, as backwashing of the membrane restored the flux to similar values regardless of the NOM concentration. The solution pH also had little effect at extended filtration times. The backwashing efficiency of the hydrophilic membrane was dramatically different for the two waters, and the presence of colloid NOM alone could not explain these differences. It is proposed that colloidal NOM forms a filter cake on the surface of the membranes and that small molecular weight organics that have an adsorption peak at 220nm but not 254nm were responsible for "gluing" the colloids to the membrane surface. Alum coagulation improved membrane performance in all instances, and this was suggested to be because coagulation reduced the concentration of "glue" that holds the organic colloids to the membrane surface.

Homoarginine and inhibition of human arginase activity: kinetic characterization and biological relevance.

The inhibition of arginase, resulting in higher arginine (ARG) availability for nitric oxide synthesis, may account for the putative protective effect of homoarginine (HOMOARG) against atherosclerosis and cardiovascular disease. However, uncertainty exists regarding the significance of HOMOARG-induced arginase inhibition in vivo. A novel UPLC-MS method, measuring the conversion of ARG to ornithine (ORN), was developed to determine arginase 1 and arginase 2 inhibition by HOMOARG, lysine (LYS), proline (PRO), agmatine (AG), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and NG-Monomethyl-L-arginine (L-NMMA). Plasma HOMOARG, ARG and ORN concentrations were further measured in 50 healthy older adults >65 years (27 males and 23 females). HOMOARG inhibited arginase 1 with IC50 and Ki values of 8.14 ± 0.52 mM and 6.1 ± 0.50 mM, and arginase 2 with IC50 and Ki values of 2.52 ± 0.01 mM and 1.73 ± 0.10 mM, respectively. Both arginase isoforms retained 90% activity vs. control when physiological HOMOARG concentrations (1-10 µM) were used. In partial correlation analysis, plasma HOMOARG was not associated with ARG (P = 0.38) or ARG/ORN ratio (P = 0.73) in older adults. Our results suggest that arginase inhibition is unlikely to play a significant role in the reported cardio-protective effects of HOMOARG.

Sex Differences in the Associations between L-Arginine Pathway Metabolites, Skeletal Muscle Mass and Function, and their Responses to Resistance Exercise, in Old Age.

OBJECTIVES: The current study was designed to explore the associations between L-arginine metabolites and muscle mass and function in old age, which are largely unknown. DESIGN: The study used a randomised, double-blind, placebo-controlled design. SETTING: The study was carried out in a laboratory setting. PARTICIPANTS: 50 healthy older adults [median age 70 years (IQR 67-73); 27 males]. INTERVENTION: Participants undertook an 18-week resistance exercise program, and a nutritional intervention (fish oil vs. placebo). MEASUREMENTS: Serum homoarginine, ornithine, citrulline, asymmetric dimethylarginine (ADMA), NG-monomethyl-L-arginine (L-NMMA), and symmetric dimethylarginine (SDMA), maximal voluntary contraction (MVC) and isokinetic torque of the knee extensors at 30° s-1 (MIT), muscle cross sectional area (MCSA) and quality (MQ) were measured at baseline and after the intervention. RESULTS: No significant exercise-induced changes were observed in metabolite concentrations. There were significant sex differences in the associations between metabolites and muscle parameters. After adjusting for age, glomerular filtration rate and fish oil intervention, citrulline (P=0.002) and ornithine (P=0.022) were negatively associated with MCSA at baseline in males but not females. However, baseline citrulline was negatively correlated with exercise-induced changes in MVC (P=0.043) and MQ (P=0.026) amongst females. Furthermore, amongst males, baseline homoarginine was positively associated with exercise-induced changes in MVC (P=0.026), ADMA was negatively associated with changes in MIT (P=0.026), L-NMMA (p=0.048) and ornithine (P<0.001) were both positively associated with changes in MCSA, and ornithine was negatively associated with changes in MQ (P=0.039). CONCLUSION: Therefore, barring citrulline, there are significant sex differences in the associations between L-arginine metabolites and muscle mass and function in healthy older adults. These metabolites might enhance sarcopenia risk stratification, and the success of exercise programs, in old age.