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1.
Glycomacropeptide: long-term use and impact on blood phenylalanine, growth and nutritional status in children with PKU.
Daly, A, Evans, S, Chahal, S, Santra, S, Pinto, A, Jackson, R, Gingell, C, Rocha, J, Van Spronsen, FJ, MacDonald, A
Orphanet journal of rare diseases. 2019;(1):44
Abstract
UNLABELLED In phenylketonuria, casein glycomacropeptide (CGMP) requires modification with the addition of some essential and semi essential amino acids to ensure suitability as a protein substitute. The optimal amount and ratio of additional amino acids is undefined. AIM: A longitudinal, parallel, controlled study over 12 months evaluating a CGMP (CGMP-AA2) formulation compared with phenylalanine-free L-amino acid supplements (L-AA) on blood Phe, Tyr, Phe:Tyr ratio, biochemical nutritional status and growth in children with PKU. The CGMP-AA2 contained 36 mg Phe per 20 g protein equivalent. METHODS Children with PKU, with a median age of 9.2 y (5-16y) were divided into 2 groups: 29 were given CGMP-AA2, 19 remained on Phe-free L-AA. The CGMP-AA2 formula gradually replaced L-AA, providing blood Phe concentrations were maintained within target range. Median blood Phe, Tyr, Phe:Tyr ratio and anthropometry, were compared within and between the two groups at baseline, 26 and 52 weeks. Nutritional biochemistry was studied at baseline and 26 weeks only. RESULTS At the end of 52 weeks only 48% of subjects were able to completely use CGMP-AA2 as their single source of protein substitute. At 52 weeks CGMP-AA2 provided a median of 75% (30-100) of the total protein substitute with the remainder being given as L-AA. Within the CGMP-AA2 group, blood Phe increased significantly between baseline and 52 weeks: [baseline to 26 weeks; baseline Phe 270 μmol/L (170-430); 26 weeks, Phe 300 μmol/L (125-485) p = 0.06; baseline to 52 weeks: baseline, Phe 270 μmol/L (170-430), 52 weeks Phe 300 μmol/L (200-490), p < 0.001)]. However, there were no differences between the CGMP-AA2 and L-AA group for Phe, Tyr, Phe:Tyr ratio or anthropometry at any of the three measured time points. Within the CGMP-AA2 group only weight (p = 0.0001) and BMI z scores (p = 0.0001) increased significantly between baseline to 52 weeks. Whole blood and plasma selenium were significantly higher (whole blood selenium [p = 0.0002]; plasma selenium [p = 0.0007]) at 26 weeks in the CGMP-AA2 group compared L-AA. No differences were observed within the L-AA group for any of the nutritional markers. CONCLUSIONS CGMP-AA increases blood Phe concentrations and so it can only be used partly to contribute to protein substitute in some children with PKU. CGMP-AA should be carefully introduced in children with PKU and close monitoring of blood Phe control is essential.
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Efficacy of fluorides and CPP-ACP vs fluorides monotherapy on early caries lesions: A systematic review and meta-analysis.
Tao, S, Zhu, Y, Yuan, H, Tao, S, Cheng, Y, Li, J, He, L
PloS one. 2018;(4):e0196660
Abstract
The study aimed to evaluate the efficacy of the combination of CPP-ACP and fluorides compared with fluorides monotherapy on patients with early caries lesions. The Medline, Embase and Cochrane databases up to August 2017 were scanned, with no restrictions. Studies satisfied the guideline of randomised controlled trials (RCTs), the patients with early caries lesions and data considering the efficacy of fluorides and CPP-ACP versus fluorides alone were selected. There was no language restriction during the literature search process, however, only papers in English or Chinese were included during the selection process. Outcome variables include laser fluorescence, quantitative light-induced fluorescence, lesion area and visual inspection scores. Mean differences were calculated during the data extraction process. Ten studies including 559 patients were selected in the meta-analysis. Fluorides combined with CPP-ACP achieved the same efficacy for early caries lesions on smooth surfaces compared with fluorides monotherapy (mean difference: -13.90, 95% confidence interval: [-39.25, 11.46], P = 0.28), and the combination treatment showed significantly better efficacy than fluorides monotherapy for occlusal early caries lesions (mean difference: -21.02, 95% confidence interval: [-27.94, -14.10], P<0.01). However, further well-designed studies are still needed.
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3.
Can milk proteins be a useful tool in the management of cardiometabolic health? An updated review of human intervention trials.
Fekete, ÁA, Givens, DI, Lovegrove, JA
The Proceedings of the Nutrition Society. 2016;(3):328-41
Abstract
The prevalence of cardiometabolic diseases is a significant public health burden worldwide. Emerging evidence supports the inverse association between greater dairy consumption and reduced risk of cardiometabolic diseases. Dairy proteins may have an important role in the favourable impact of dairy on human health such as blood pressure (BP), blood lipid and glucose control. The purpose of this review is to update and critically evaluate the evidence on the impacts of casein and whey protein in relation to metabolic function. Evidence from short-term clinical studies assessing postprandial responses to milk protein ingestion suggests benefits on vascular function independent of BP, as well as improvement in glycaemic homeostasis. Long-term interventions have been less conclusive, with some showing benefits and others indicating a lack of improvement in vascular function. During chronic consumption BP appears to be lowered and both dyslipidaemia and hyperglacaemia seem to be controlled. Limited number of trials investigated the effects of dairy proteins on oxidative stress and inflammation. Although the underlying mechanisms of milk proteins on cardiometabolic homeostasis remains to be elucidated, the most likely mechanism is to improve insulin resistance. The incorporation of meals enriched with dairy protein in the habitual diet may result in the beneficial effects on cardiometabolic health. Nevertheless, future well-designed, controlled studies are needed to investigate the relative effects of both casein and whey protein on BP, vascular function, glucose homeostasis and inflammation.
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4.
Casein-derived lactotripeptides reduce systolic and diastolic blood pressure in a meta-analysis of randomised clinical trials.
Fekete, ÁA, Givens, DI, Lovegrove, JA
Nutrients. 2015;(1):659-81
Abstract
There is an urgent need to treat individuals with high blood pressure (BP) with effective dietary strategies. Previous studies suggest a small, but significant decrease in BP after lactotripeptides (LTP) ingestion, although the data are inconsistent. The study aim was to perform a comprehensive meta-analysis of data from all relevant randomised controlled trials (RCT). Medline, Cochrane library, EMBASE and Web of Science were searched until May 2014. Eligibility criteria were RCT that examined the effects of LTP on BP in adults, with systolic BP (SBP) and diastolic BP (DBP) as outcome measures. Thirty RCT met the inclusion criteria, which resulted in 33 sets of data. The pooled treatment effect for SBP was -2.95 mmHg (95% CI: -4.17, -1.73; p < 0.001), and for DBP was -1.51 mmHg (95% CI: -2.21, -0.80; p < 0.001). Sub-group analyses revealed that reduction of BP in Japanese studies was significantly greater, compared with European studies (p = 0.002 for SBP and p < 0.001 for DBP). The 24-h ambulatory BP (AMBP) response to LTP supplementation was statistically non-significant (p = 0.101 for SBP and p = 0.166 for DBP). Both publication bias and "small-study effect" were identified, which shifted the treatment effect towards less significant SBP and non-significant DBP reduction after LTP consumption. LTP may be effective in BP reduction, especially in Japanese individuals; however sub-group, meta-regression analyses and statistically significant publication biases suggest inconsistencies.
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Gluten-free and casein-free diets in the therapy of autism.
Lange, KW, Hauser, J, Reissmann, A
Current opinion in clinical nutrition and metabolic care. 2015;(6):572-5
Abstract
PURPOSE OF REVIEW The purpose of this study is to discuss the role of gluten-free and casein-free diets in the treatment of autism. RECENT FINDINGS In a recent UK survey, more than 80% of parents of children with autism spectrum disorder reported some kind of dietary intervention for their child (gluten-free and casein-free diet in 29%). When asked about the effects of the gluten-free and casein-free diet, 20-29% of the parents reported significant improvements on the autism spectrum disorder core dimensions. The findings of this study suggest additional effects of a gluten-free and casein-free diet on comorbid problems of autism such as gastrointestinal symptoms, concentration, and attention. The findings of another recent investigation suggested that age and certain urine compounds may predict the response of autism symptoms to a gluten-free and casein-free diet. Although these results need to be replicated, they highlight the importance of patient subgroup analysis. Intervention trials evaluating the effects of a gluten-free and casein-free diet on autistic symptoms have so far been contradictory and inconclusive. SUMMARY Most investigations assessing the efficacy of a gluten-free and casein-free diet in the treatment of autism are seriously flawed. The evidence to support the therapeutic value of this diet is limited and weak. A gluten-free and casein-free diet should only be administered if an allergy or intolerance to nutritional gluten or casein is diagnosed.
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Dairy foods and dairy proteins in the management of type 2 diabetes: a systematic review of the clinical evidence.
Pasin, G, Comerford, KB
Advances in nutrition (Bethesda, Md.). 2015;(3):245-59
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Abstract
Type 2 diabetes mellitus (T2DM) is a growing public health concern affecting hundreds of millions of people worldwide and costing the global economy hundreds of billions of dollars annually. This chronic disease damages the blood vessels and increases the risk of other cardiometabolic ailments such as cardiovascular disease and stroke. If left unmanaged it can also lead to nerve damage, kidney damage, blindness, and amputation. For the most part, many of these symptoms can be prevented or reduced through simple dietary modifications and proper nutrition. Therefore, identifying relatively inexpensive and easily implementable dietary modifications for the prevention and management of T2DM is of considerable value to human health and healthcare modalities around the globe. Protein-rich dairy products have consistently been shown in epidemiologic studies to be beneficial for reducing the risk of developing T2DM. The clinical evidence regarding both dairy foods and dairy proteins (i.e., casein and whey protein) have shown promise for improving insulin secretion in individuals with T2DM. However, the clinical research on dairy protein supplementation in subjects with T2DM has been limited to acute studies. These studies have been mostly descriptive and have not been focused on important T2DM endpoints such as prevention, management, or treatment. Long-term studies are clearly needed to help researchers and medical professionals better understand the effects of consistent dairy protein intake on the metabolic health of humans with T2DM.
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Evidence of the gluten-free and casein-free diet in autism spectrum disorders: a systematic review.
Marí-Bauset, S, Zazpe, I, Mari-Sanchis, A, Llopis-González, A, Morales-Suárez-Varela, M
Journal of child neurology. 2014;(12):1718-27
Abstract
In autism spectrum disorders, many parents resort to alternative treatments and these are generally perceived as risk free. Among these, the most commonly used is the gluten-free, casein-free diet. The objective of this work was to conduct a systematic review of studies published from 1970 to date related to the gluten-free, casein-free diet in autism spectrum disorder patients. Few studies can be regarded as providing sound scientific evidence since they were blinded randomized controlled trials, and even these were based on small sample sizes, reducing their validity. We observed that the evidence on this topic is currently limited and weak. We recommend that it should be only used after the diagnosis of an intolerance or allergy to foods containing the allergens excluded in gluten-free, casein-free diets. Future research should be based on this type of design, but with larger sample sizes.
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Novel nutritional treatment for manic and psychotic disorders: a review of tryptophan and tyrosine depletion studies and the potential of protein-based formulations using glycomacropeptide.
Badawy, A
Psychopharmacology. 2013;(3):347-58
Abstract
RATIONALE Current amino acid (AA) mixtures used in acute tryptophan (Trp) and tyrosine (Tyr) plus phenylalanine (Phe) depletion and loading tests are unpalatable and lack specificity. Specificity is improved by reducing content of branched-chain amino acids (BCAA) and palatability to a certain extent by dose reduction. OBJECTIVES This study aims to identify a palatable naturally occurring alternative(s) to amino acids with the desired BCAA content for use in the above tests. METHODS A palatable alternative lacking in Trp, Tyr and Phe has been identified in the whey protein fraction caseino-glycomacropeptide (c-GMP). The absence of these three aromatic amino acids renders GMP suitable as a template for seven formulations for separate and combined depletion or loading and a placebo control. The absence of Phe and Tyr enables GMP to provide a unique nutritional therapy of manic and psychotic disorders by inhibition of cerebral dopamine synthesis and release and possibly also by enhancing glutamatergic function, in general, and in patients resistant to anti-psychotic medication, in particular. RESULTS Seven GMP-based formulations for the above tests are proposed, two of which can be used in the above nutritional therapy and a third formulation as a placebo control in clinical trials. CONCLUSIONS Development of these formulations should advance the above research and diagnostic tests, open new avenues for neuroscience research on monoamine function, and improve the therapy of bipolar and psychotic disorders and enhance the quality of life of sufferers.
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Original features of cell-envelope proteinases of Lactobacillus helveticus. A review.
Sadat-Mekmene, L, Genay, M, Atlan, D, Lortal, S, Gagnaire, V
International journal of food microbiology. 2011;(1):1-13
Abstract
Lactobacillus helveticus is a lactic acid bacterium very used in fermented milks and cheese. The rapid growth of L. helveticus in milk is supported by an efficient cell envelope proteinase (CEP) activity, due to subtilisin-like serine proteases. These enzymes play also crucial roles in texture and flavor formation in dairy products as well as in generating in situ bioactive peptides. In L. helveticus, several genes encoding putative CEPs were detected and characterized by a large intraspecific diversity; little is known about regulation of expression of CEP-encoding genes. Anchored at the bacterial surface, CEPs are large-sized enzymes (> 150 kDa) hydrolyzing β- and α(s1)-casein as well. Substrate cleavages occur after almost all types of amino acids residues, but mass spectrometry analysis revealed L. helveticus strains with specific profiles of substrate hydrolysis, which could explain identification of strains associated with interesting technological properties. In this review, the most recent data regarding CEP-encoding genes, CEP activities toward caseins and L. helveticus strain diversity are discussed.
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Innate and specific gut-associated immunity and microbial interference.
Singh, V, Singh, K, Amdekar, S, Singh, DD, Tripathi, P, Sharma, GL, Yadav, H
FEMS immunology and medical microbiology. 2009;(1):6-12
Abstract
Certain bacterial species isolated from the gastrointestinal microbial communities release low-molecular-weight peptides into milk products using bacteria-derived proteases that degrade milk casein, and thereby generate peptides, triggering immune responses. The intestinal microbial communities contributes to the processing of food antigens in the gut. The present study was designed to investigate the immunomodulatory effects of microbial interference to determine whether casein degraded by probiotic bacteria-derived enzymes could modulate the cytokine production and peripheral blood mononuclear cells in atopic infants with cow or other synthetic milk allergy. Without hydrolyzation, casein reduced the production of interleukin-4, which indicates that probiotics modify the structure of potentially harmful antigens and thereby alter the mode of their immunogenicity. Intraluminal bacterial antigens have been reported to elicit specific responses in the gut-associated lymphoid tissue (GALT) through the binding capacity of intraluminal bacterial antigens to epithelial cells, which allows antigen entry via enterocytes and aids in evading the tolerance function in Peyer's patches. Such tonic immune responses in the GALT may allow control of the metabolic activity and balance of the gut microbial communities.