Philip M. Jakeman

Antioxidative peptides: enzymatic production, in vitro and in vivo antioxidant activity and potential applications of milk-derived antioxidative peptides.

The beneficial effects of food-derived antioxidants in health promotion and disease prevention are being increasingly recognized. Recently, there has been a particular focus on milk-derived peptides; as a source of antioxidants, these peptides are inactive within the sequence of the parent protein but can be released during enzyme hydrolysis. Once released, the peptides have been shown to possess radical scavenging, metal ion chelation properties and the ability to inhibit lipid peroxidation. A variety of methods have been used to evaluate in vitro antioxidant activity, however, there is no standardised methodology, which hinders comparison of data. This review provides an overview on the generation of antioxidative peptides from milk proteins, the proposed mechanisms of protein/peptide induced antioxidant activity, in vitro measurement of antioxidant activity, in vivo evaluation of plasma antioxidant capacity and the bioavailability of antioxidative peptides. The understanding gained from other food proteins is referred to where specific data on milk-derived peptides are limited. The potential applications and health benefits of antioxidant peptides are discussed with a particular focus on the aging population. The regulatory requirements for peptide-based antioxidant functional foods are also considered.

Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory peptides for the management of type 2 diabetes

The prevalence of type 2 diabetes mellitus (T2DM) is increasing and it is estimated that by 2030 approximately 366 million people will be diagnosed with this condition. The use of dipeptidyl peptidase IV (DPP-IV) inhibitors is an emerging strategy for the treatment of T2DM. DPP-IV is a ubiquitous aminodipeptidase that cleaves incretins such as glucagon like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), resulting in a loss in their insulinotropic activity. Synthetic DPP-IV drug inhibitors are being used to increase the half-life of the active GLP-1 and GIP. Dietary intervention is accepted as a key component in the prevention and management of T2DM. Therefore, identification of natural food protein-derived DPP-IV inhibitors is desirable. Peptides with DPP-IV inhibitory activity have been identified in a variety of food proteins. This review aims to provide an overview of food protein hydrolysates as a source of the DPP-IV inhibitory peptides with particular focus on milk proteins. In addition, the proposed modes of inhibition and structure-activity relationship of peptide inhibitors are discussed. Milk proteins and associated peptides also display insulinotropic activity and help regulate blood glucose in healthy and diabetic subjects. Therefore, milk protein derived peptide inhibitors may be a unique multifunctional peptide approach for the management of T2DM.

Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study

OBJECTIVE It is not established whether myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is associated with structural brain changes. The aim of this study was to investigate this by conducting the largest voxel-based morphometry study to date in CFS. METHODS High-resolution structural 3 T cerebral MRI scanning was carried out in 26 patients with CFS and 26 age- and gender-matched healthy volunteers. Voxel-wise generalised linear modelling was applied to the processed MR data using permutation-based non-parametric testing, forming clusters at t>2.3 and testing clusters for significance at p<0.05, corrected for multiple comparisons across space. RESULTS Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced grey matter volume in the CFS group were noted in the occipital lobes (right and left occipital poles; left lateral occipital cortex, superior division; and left supracalcrine cortex), the right angular gyrus and the posterior division of the left parahippocampal gyrus. Significant voxels (p<0.05, corrected for multiple comparisons) depicting reduced white matter volume in the CFS group were also noted in the left occipital lobe. CONCLUSION These data support the hypothesis that significant neuroanatomical changes occur in CFS, and are consistent with the complaint of impaired memory that is common in this illness; they also suggest that subtle abnormalities in visual processing, and discrepancies between intended actions and consequent movements, may occur in CFS.

Ultrasound measurement of subcutaneous adipose tissue thickness accurately predicts total and segmental body fat of young adults.

This study evaluated the ability of ultrasound measurement of subcutaneous adiposity to accurately determine whole body and segmental body fat in young adults aged 18-29 years. Subcutaneous adipose tissue (SAT) thickness was measured by ultrasound at five body sites in 135 subjects (83 men, 52 women) and compared with the corresponding segmental fat mass measured by dual energy X-ray absorptiometry (DXA). Ultrasound measures of SAT thickness were strongly correlated to segmental fat mass and total percentage (%) body fat (r = 0.697-0.907, p < 0.01). Prediction equations generated using quantile regression found SAT thickness at the abdomen and thigh to accurately predict % body fat in men (standard error of the estimate, SEE = 1.9%, 95% limits of agreement (LoA); -3.6% to +3.8%) and SAT thickness at the abdomen and medial calf to accurately predict % body fat in women (SEE = 3.0%, LoA; -6.5% to +5.4%). These data indicate that ultrasound measurement of SAT thickness proportionally reflects segmental fat mass and accurately predicts % body fat in young adults.

Exercise in the community for people with minimal gait impairment due to MS: an assessor-blind randomized controlled trial

Background: While there is an increasing body of evidence supporting the efficacy of exercise in people with multiple sclerosis (MS), additional information on the effectiveness of combining aerobic and resistance training, and yoga is required. Objectives: This study evaluated the effectiveness of community exercise interventions for people with MS having minimal gait impairment. Methods: A multi-centred, block-randomised, assessor-blinded, controlled trial was conducted. Participants were randomised in groups of eight to physiotherapist (PT)-led exercise (n = 80), yoga (n = 77), fitness instructor (FI)-led exercise (n = 86) and they took part in weekly community-based group exercise sessions. Those in the control group were asked not to change of their exercise habits (n = 71). The primary outcome was the Multiple Sclerosis Impact Scale (MSIS) 29v2 physical component, measured before and after the 10-week intervention. Secondary outcomes were the MSIS 29v2 psychological component, the Modified Fatigue Impact Scale (MFIS) and the 6-Minute Walk Test (6MWT). Results: The group x time interaction approached significance for the MSIS-29v2 physical component (f = 2.48, p = 0.061) and MFIS total (f = 2.50, p = 0.06), and it was significant for the MFIS physical subscale (f = 4.23, p = 0.006). All three exercise interventions led to a statistically significant improvement on the MSIS-29 psychological component and both the MFIS total and physical subscales, which were greater than the control (p < 0.05). Only the PT-led and FI-led interventions significantly improved the MSIS-29 physical and 6MWT to levels greater than the control (p < 0.05). Conclusions: This study provides evidence for the positive effect of exercise on the physical impact of MS and fatigue. The group nature of the classes may have contributed to the positive effects seen on the psychological impact of MS.

Protein Supplementation at Breakfast and Lunch for 24 Weeks beyond Habitual Intakes Increases Whole-Body Lean Tissue Mass in Healthy Older Adults

BACKGROUND Key areas of research on the preservation of lean tissue mass (LTM) during aging are determinations of the protein requirement and optimal protein intake at meals. OBJECTIVE The aim of this study was to determine the effect of protein supplementation at breakfast and lunch for 24 wk beyond habitual intakes on whole-body LTM in healthy adults aged 50-70 y. METHODS In a single-blinded, randomized, controlled design, 60 healthy older men and women (aged 61 ± 5 y) with a body mass index (in kg/m(2)) of 25.8 ± 3.6 consumed either 0.165 g/kg body mass of a milk-based protein matrix (PRO) or an isoenergetic, nonnitrogenous maltodextrin control (CON) at breakfast and midday meals, the lower protein-containing meals of the day, for 24 wk. Dual-energy X-ray absorptiometry was used to measure the change in LTM. RESULTS After the intervention, protein intake in the PRO group increased from 0.23 ± 0.1 to 0.40 ± 0.1 g/kg for breakfast and from 0.31 ± 0.2 to 0.47 ± 2 g/kg for the midday meal. In response, LTM increased by 0.45 (95% CI: 0.06, 0.83) kg in the PRO group compared with a decrease of 0.16 (95% CI: -0.49, 0.17) kg in the CON group (P = 0.006). Appendicular LTM accounted for the majority of the difference in LTM, increasing by 0.27 (95% CI: 0.05, 0.48) kg in the PRO group compared with no change in the CON group (P = 0.002). CONCLUSIONS Protein supplementation at breakfast and lunch for 24 wk in healthy older adults resulted in a positive (+0.6 kg) difference in LTM compared with an isoenergetic, nonnitrogenous maltodextrin control. These observations suggest that an optimized and balanced distribution of meal protein intakes could be beneficial in the preservation of lean tissue mass in the elderly. This trial was registered at clinicaltrials.gov as NCT02529124.

Exercise in the community for people with multiple sclerosis--a follow-up of people with minimal gait impairment.

Background: Although there are many studies evaluating exercise interventions, few studies have evaluated the effect at follow-up. Objectives: This paper presents follow-up data for participants who completed the exercise interventions in a large randomised controlled trial. Methods: One hundred twenty-one people with multiple sclerosis (MS) with minimal gait impairment who completed 10 weeks of community-based exercise interventions were evaluated by a blinded assessor 12 weeks after the intervention. The primary outcome measure was the Multiple Sclerosis Impact Scale-29 version 2 (MSIS-29,v2) physical component. Other outcomes were the MSIS-29 psychological component, the Modified Fatigue Impact Scale (MFIS) and the 6-minute walk test (6MWT) distance. Results: The positive effect on the physical impact of MS was not maintained from baseline to follow-up (−1.6, 95% CI −0.8, 4.0, p=0.189). The psychological impact and the impact of fatigue remained significantly improved (−3.5, 95% CI −6.1, −1.0, p = 0.006 and −4.68, 95% CI −6.9, −2.5, p < 0.001, respectively). There was no time effect for the 6MWT (f = 1.76, p = 0.179) although the trend suggests reversal of the benefits gained from the physiotherapist (PT)- and fitness instructor (FI)-led intervention. Conclusion: The maintained benefit on the psychological impact of MS and fatigue may have important personal and socioeconomic consequences; however, it is important to find ways to maintain the physical benefits of exercise over the long term.

Technical considerations for accurate measurement of subcutaneous adipose tissue thickness using B-mode ultrasound

The search for valid, reliable and inexpensive methods of measuring body composition is an ongoing issue for many researchers. In particular, the measurement of subcutaneous adipose tissue (SAT) is carried out by numerous methods, each with its own drawbacks. Skinfold thickness measurement is the most common in-field method, but it is limited by its tendency to deform the adipose layer, by the limited caliper opening which prevents measurement of larger skinfolds, and the lack of correction for elastic properties of tissue between individuals. Therefore non-invasive field measures which overcome these limitations would be desirable. Ultrasound scanning provides such a device due to its portability and availability, allowing reduced tissue compression and on-screen views of the adipose tissue. Despite a number of papers referring to the use of ultrasound for measuring adipose tissue, the method of measurement has not been fully described. This paper describes our work in determining an accurate method for the measurement of SAT at different body sites, including a comparison of scanning directions and sites. We also describe our investigations into the degree to which compression force through the transducer affects adipose tissue measurement, and the reliability and sensitivity of our methods. We conclude with a recommended reliable scanning protocol for the measurement of SAT.

Generalised equations for the prediction of percentage body fat by anthropometry in adult men and women aged 18-81 years

Anthropometric data indicate that the human phenotype is changing. Todays adult is greater in stature, body mass and fat mass. Accurate measurement of body composition is necessary to maintain surveillance of obesity within the population and to evaluate associated interventions. The aim of the present study was to construct and validate generalised equations for percentage body fat (%BF) prediction from anthropometry in 1136 adult men and women. Reference values for %BF were obtained using dual-energy X-ray absorptiometry. Skinfold thickness (SF) at ten sites and girth (G) at seven sites were measured on 736 men and women aged 18-81 years (%BF 5·1-56·8%). Quantile regression was employed to construct prediction equations from age and log-transformed SF and G measures. These equations were then cross-validated on a cohort of 400 subjects of similar age and fatness. The following generalised equations were found to most accurately predict %BF: Men: (age x 0·1) + (logtricepsSF x 7·6) + (logmidaxillaSF x 8·8) + (logsuprspinaleSF x 11·9) - 11·3 (standard error of the estimate: 2·5%, 95% limits of agreement: - 4·8, + 4·9) Women: (age x 0·1) + (logabdominalG x 39·4) + (logmidaxillaSF x 4·9) + (logbicepsSF x 11·0) + (logmedialcalfSF x 9·1) - 73·5 (standard error of the estimate: 3·0%, 95% limits of agreement: - 5·7, + 5·9) These generalised anthropometric equations accurately predict %BF and are suitable for the measurement of %BF in adult men and women of varying levels of fatness across the lifespan.

An in vivo microdialysis characterization of the transient changes in the interstitial dialysate concentration of metabolites and cytokines in human skeletal muscle in response to insertion of a microdialysis probe.

Skeletal muscle has recently been described as an endocrine organ, capable of releasing cytokines and regulators of metabolism. Microdialysis of the interstitial space of skeletal muscle enables analysis of the release of such cytokines. The purpose of this study was to determine the transient changes in concentration of metabolites and cytokines in human skeletal muscle in a 7h period following the insertion of a microdialysis probe. In total, sixteen microdialysis catheters were inserted into the vastus lateralis of male participants (age 26.2±1.35y, height 180.8±3.89cm, mass 83.9±3.86kg, BMI 25.7±0.87kgm(-2), body fat 26.1±3.0%). Serial samples were analyzed by micro-enzymatic and multiplexed immunoassay. Muscle interstitial glucose and lactate levels remained stable throughout, amino acid concentrations stabilized after 2.5h, however, insertion of a microdialysis catheter induced a 29-fold increase in peak IL-6 (p<0.001) and 35-fold increase in peak IL-8 concentrations (p<0.001) above basal levels 6h post insertion. In contrast to stable amino acid, glucose and lactate concentrations after 2h, commonly reported markers of tissue homeostasis in in vivo microdialysis, the multi-fold increase in IL-6 and IL-8 following insertion of a microdialysis catheter is indicative of a sustained disturbance of tissue homeostasis.