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Impact of a ketogenic diet intervention during radiotherapy on body composition: V. Final results of the KETOCOMP study for head and neck cancer patients.
Klement, RJ, Sweeney, RA
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]. 2022;198(11):981-993
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Head and neck cancer (HNC) describes cancers originating from the lip, oral and nasal cavity, paranasal sinuses, pharynx, larynx, and trachea. Patients with HNC frequently present with feeding difficulties and malnutrition, which are often further aggravated by tobacco and alcohol abuse and a general unhealthy lifestyle. This study aimed to investigate the impact of a ketogenic diet (KD) versus an unspecified standard diet (SD) on body composition and survival in HNC patients undergoing radio(chemo)therapy. This study is a controlled clinical trial. Results show that an individualized KD supplemented with essential amino acids consumed during curative radio(chemo)therapy of HNC patients was able to slow down the negative consequences of therapy on body composition to some extent. Authors conclude that further research of KDs in frail cancer patient populations is required which may help to motivate their implementation as complementary therapies for select patients.
Abstract
PURPOSE Patients with head and neck cancer (HNC) are at risk of malnutrition, especially during radiochemotherapy. We aimed to study the impact of a ketogenic diet (KD) versus an unspecified standard diet (SD) on body composition and survival in HNC patients undergoing radio(chemo)therapy. METHODS As part of a controlled clinical trial, non-metastasized HNC patients were enrolled into either a KD (N = 11) or an SD (N = 21) group between May 2015 and May 2021. Body composition was measured weekly by bioimpedance analysis and analyzed using linear mixed effects models. Overall and progression-free survival was assessed during regular follow-up. RESULTS A total of 7 KD and 21 SD patients completed the study and were eligible for comparative analysis. Chemotherapy was significantly associated with declines in all body composition parameters, while the KD had opposing, yet nonsignificant effects. In patients receiving chemotherapy, average weekly reductions of body mass (BM) and skeletal muscle mass (SMM) were 0.9 kg and 0.31 kg in the KD group versus 1.2 kg and 0.57 kg in the SD group, respectively. Patients in the KD group receiving no chemotherapy achieved an average increase of 0.04 kg BM and 0.12 kg SMM per week. After a median follow-up of 42 months (range 6.7-78 months) there were no significant differences in progression-free or overall survival between the groups. CONCLUSION The KD may partially counteract the detrimental effects of radiochemotherapy on body composition in HNC patients. This should encourage further research into KDs in frail cancer patient populations and motivate their implementation as complementary therapy for selected patients.
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Effects of Roux-en-Y Gastric Bypass on Osteoclast Activity and Bone Density in Morbidly Obese Patients with Type 2 Diabetes.
Tangalakis, LL, Tabone, L, Spagnoli, A, Muehlbauer, M, Omotosho, P, Torquati, A
Obesity surgery. 2020;30(1):290-295
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Gastric surgery and the resultant weight loss can improve an individual’s outcomes in a number of diseases, such as heart disease and type 2 diabetes, however an unfortunate side effect is bone loss. Roux-en-Y gastric bypass is a process whereby the size of your stomach is significantly reduced, and it is unclear as to the effect this type of surgery has on bone density. This cohort study of sixty-one individuals who underwent Roux-en-Y gastric bypass aimed to determine the effect on bone density one year post surgery. The results showed that following surgery, bone resorption was increased compared to control and although bone density was similar between the two groups, bone mineral content and bone surface area were decreased. Women who were post-menopausal demonstrated diminished bone health, although this was not significant. It was concluded that Roux-en-Y gastric bypass surgery results in a negative impact on bone health. This study could be used by healthcare professionals to understand the importance of considering bone health when recommending surgery, especially in those at high-risk of bone loss such as post-menopausal women.
Abstract
INTRODUCTION Roux-en-Y gastric bypass (RYGB) is a well-established treatment for morbid obesity and type 2 diabetes. The effects of RYGB on bone metabolism and bone health are largely unknown. OBJECTIVE Determine the changes in osteoclast function and bone density 1 year after RYGB as compared with a control group undergoing a diabetes support and education program (DSE). DESIGN A prospective cohort study with patients matched for weight and age assigned to RYGB or DSE. SETTING Large academic institution. PATIENTS OR OTHER PARTICIPANTS Patients with type 2 diabetes mellitus and morbid obesity (body mass index greater than 35 kg/m2). INTERVENTION Subjects either received laparoscopic RYBG or DSE, which consisted of nutritional, exercise, and dietary counseling performed by a certified diabetic educator and a nutritionist three times over a year. MAIN OUTCOME MEASURE Osteoclast activity, bone mineral density. RESULTS One year after, intervention subjects undergoing RYGB have a 280% increase in osteoclast activity as compared with a 7.6% increase in the DSE control group (P < 0.001). Furthermore, there was a statistically significant increase in sclerostin levels in subjects undergoing RYGB compared with an increase in the control group. The total bone mineral density was statistically unchanged within 1 year of intervention in both groups. A statistically significant decrease in bone mineral density in the left ribs (decrease of 6.8%, P < 0.05) and lumbar spine (decrease of 4.0%, P < 0.05) was seen 1 year after RYGB. CONCLUSIONS There is a significant increase in osteoclast activity observed 1 year after RYGB; the long-term clinical implications of this increased bone metabolism are unknown.
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Effect of preoperative immunonutrition on complications after salvage surgery in head and neck cancer.
Mueller, SA, Mayer, C, Bojaxhiu, B, Aeberhard, C, Schuetz, P, Stanga, Z, Giger, R
Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale. 2019;48(1):25
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Surgery, radiotherapy (RT) and chemo-radiotherapy (CRT) are the main treatments for head and neck cancer, but (C)RT has significant side effects on local tissues due to impaired wound healing. Malnutrition is also common in these patients and may add to poor wound healing and recovery. Immunonutrition (IN) are medical dietary formulas designed to provide the essential nutrients for an adequate immune reaction during medical treatment. The aim of this study was to evaluate the effect of preoperative IN on postoperative complications after salvage surgery in head and neck cancer. Patients in the intervention group received 3 IN units per day for 5 days before surgery. The IN units contained 300 kcal and were enriched with omega-3 fatty acids, arginine, RNA-nucleotides and soluble guar fibre. The control group, who did not receive IN, included consecutive patients treated prior to the intervention group. 96 patients were evaluated, of which 51 received IN. The total number of patients suffering any complications was significantly lower in the group receiving IN (35% vs. 58%). There was also a significant reduction in length of hospital stay in the IN group compared to the control group (6 days vs. 17 days). Limitations of this study include the use of a historical control group, and the limited number of patients.
Abstract
BACKGROUND Patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma are at high risk of postoperative complications due to the adverse effects of radiotherapy on wound healing. Malnutrition is an additional risk factor and we tested the hypothesis that preoperative administration of immunonutrition would decrease complications in this high risk population. METHODS This single armed study with historical control included consecutive patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma. We compared outcomes before and after implementation of preoperative immunonutrition and adjusted the regression analysis for gender, age, body mass index, Nutritional Risk Screening (NRS 2002), tobacco and alcohol consumption, tumor localization, tumor stage, and type of surgery. The primary endpoint was overall complications from surgery within a follow-up of 30 days. RESULTS Ninety-six patients were included (intervention group: 51, control group: 45). Use of preoperative immunonutrition was associated with a significant reduction in overall complications (35% vs. 58%, fully-adjusted odds ratio 0.30 (95%CI 0.10-0.91, p = 0.034). Length of hospital stay was also significantly reduced (17 days vs. 6 days, p = < 0.001). No differences in mortality and hospital readmission were found. These results remained robust in multivariate analysis. CONCLUSIONS In patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma, preoperative immunonutrition exhibited favorable effects on the complication rate and consequently reduced the length of hospital stay. By improving both tissue regeneration and immune response, immunonutrition may help to improve surgical outcomes in this high-risk population.
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Effect of A Very Low-Calorie Ketogenic Diet on Food and Alcohol Cravings, Physical and Sexual Activity, Sleep Disturbances, and Quality of Life in Obese Patients.
Castro, AI, Gomez-Arbelaez, D, Crujeiras, AB, Granero, R, Aguera, Z, Jimenez-Murcia, S, Sajoux, I, Lopez-Jaramillo, P, Fernandez-Aranda, F, Casanueva, FF
Nutrients. 2018;10(10)
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Obesity is a multi-factorial disorder involving genetic, environmental, metabolic and behavioural factors. Few studies have examined the effect of weight-loss therapy on various psychobiological parameters associated with obesity. Therefore the aim of this 4-month nutritional intervention was to evaluate food and alcohol cravings, physical activity levels, sleep quality, sexual function and quality of life in patients with obesity after following a very low-calorie ketogenic (VLCK) diet. Twenty obese patients were enrolled and participated in psychological questionnaires and anthropometric measurements at four points throughout the intervention: at baseline, maximum ketosis, reduced ketosis and endpoint. A specialist physician and expert dietician closely monitored participants to ensure safety and duration of the ketosis state. This study found that rapid and sustained weight loss induced by a VLCK-diet is associated with better food control and improvements in quality of life in obese subjects. Based on these results, the authors conclude a VLCK-diet is a suitable and valuable treatment option for obese patients.
Abstract
Psychological well-being and hunger and food control are two relevant factors involved in the success of weight-loss therapy in treating obesity. Thus, this study aims to evaluate food and alcohol cravings, physical and sexual activity, sleep, and life quality (QoL) in obese patients following a very low-calorie ketogenic (VLCK) diet, as well as the role of weight lost and ketosis on these parameters. A battery of psychological test was performed in twenty obese patients (12 females, 47.2 ± 10.2 year and BMI of 35.5 ± 4.4) through the course of a 4-month VLCK diet on four subsequent visits: baseline, maximum ketosis, reduced ketosis, and endpoint. Each subject acted as their own control. Relevantly, the dietary-induced changes in body composition (7.7 units of BMI lost, 18 kg of fat mass (1.2 kg of visceral fat mass)) were associated with a statistically significant improvement in food craving scores, physical activity, sleepiness, and female sexual function. Overall, these results also translated in a notable enhancement in QoL of the treated obese patients. Therefore, the rapid and sustained weight and fat mass (FM) loss induced by the VLCK diet is associated with good food control and improvements in the psychological well-being parameters in obese subjects, which could contribute to the long-term success of this therapy.
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Cardiovascular Biomarkers in Association with Dietary Intake in a Longitudinal Study of Youth with Type 1 Diabetes.
Sanjeevi, N, Lipsky, LM, Nansel, TR
Nutrients. 2018;10(10)
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Cardiovascular disease (CVD) is the major cause of mortality and morbidity in patients with type 1 diabetes, whose risk is several-fold higher than the general population. The objective of this study was to investigate relationships of CVD biomarkers with overall diet quality, and its dietary components in youth with type 1 diabetes. This study is a secondary analysis of a randomised controlled trial of a family-based behavioural nutrition intervention. The control group had an equal frequency of contact with the research staff but did not receive any nutrition advice besides that included as part of regular type 1 diabetes care. Results indicate that greater intake of whole grains and whole fruits, and lower added sugar and polyunsaturated fatty acids were associated with more favourable CVD biomarkers. Authors conclude that overall diet quality was not associated with CVD biomarkers in youth with type 1 diabetes. However, specific dietary components were associated with CVD biomarkers, independent of glycaemic control.
Abstract
Despite cardioprotective effects of a healthy diet in the general population, few studies have investigated this relationship in individuals with type 1 diabetes, who are at elevated risks of cardiovascular disease (CVD) due to hyperglycemia. The objective of this study was to examine the association of CVD biomarkers with overall diet quality, as measured by the Healthy Eating Index-2015 (HEI-2015), and its dietary components in youth with type 1 diabetes. Youth with type 1 diabetes (n = 136, 8⁻16.9 years) were enrolled in an 18-month behavioral nutrition intervention trial. Dietary intake from three-day diet records, CVD biomarkers (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C); triglycerides (TG), C-reactive protein (CRP), 8-iso-prostaglandin-F2alpha (8-iso-PGF2α), systolic and diastolic blood pressure (SBP and DBP, respectively), and glycated hemoglobin (HbA1c) were assessed at baseline, 6, 12 and 18 months. Linear mixed-effects models estimated associations of dietary intake with CVD biomarkers, adjusting for HbA1c and other covariates. Separate models estimated associations of time-varying change in dietary intake with time-varying change in CVD biomarkers. HEI-2015 was not associated with CVD biomarkers, but whole grain intake was inversely associated with TC, HDL-C and DBP, and a greater increase in whole fruit intake was associated with lower DBP. Added sugar, saturated fat and polyunsaturated fat were positively related to serum TG, HDL-C, and DBP, respectively. Findings suggest that the intake of specific dietary components, including whole grains, whole fruits, added sugar and PUFA, may influence cardiometabolic health in youth with type 1 diabetes, independent of glycemic control.
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Food-specific IgGs Are Highly Increased in the Sera of Patients with Inflammatory Bowel Disease and Are Clinically Relevant to the Pathogenesis.
Xiao, N, Liu, F, Zhou, G, Sun, M, Ai, F, Liu, Z
Internal medicine (Tokyo, Japan). 2018;57(19):2787-2798
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Inflammatory bowel disease (IBD) is an umbrella term incorporating ulcerative colitis (UC) and Crohn’s disease (CD). The exact reasons for the development of IBD are still being debated, however food allergy has been implicated. Diagnosis of food allergy is normally performed looking at the body’s immediate immune response, however the delayed immune response may be of importance in IBD. This study of 301 patients with IBD and 178 healthy controls aimed to look at the delayed immune response of individuals with IBD following the introduction of certain foods. It also looked at the efficacy of a drug treatment, infliximab (IFX) on this immune response. The results showed that the delayed immune response to egg, milk, wheat, corn, rice, tomato, codfish, and soya was increased in those with CD compared to those with UC and healthy control. Infliximab treatment was effective in suppressing this immune response in individuals with CD. It was concluded that in individuals with IBD, measuring the delayed immune response to foods may be an important diagnosis and management tool. This study could be used by healthcare professionals to understand that measuring the immediate immune response to certain foods in individuals with IBD, may not be sufficient. Measuring the delayed immune response in combination with the immediate immune response may give a better picture of foods which should be avoided in those with IBD. Infliximab treatment may be an effective treatment in patients with IBD and a delayed immune response to certain foods.
Abstract
Objective Dietary antigens are common luminal antigens in the gastrointestinal tract and have been considered to contribute to the pathogenesis of inflammatory bowel disease (IBD). We analyzed the levels of food-specific IgGs against a variety of dietary antigens, explored the clinical relevance of food allergy to the pathogenesis of IBD, and investigated whether or not infliximab (IFX) treatment could regulate the immune responses induced by dietary antigens. Methods A total of 301 IBD patients, including 201 patients with Crohn's disease (CD) and 100 patients with ulcerative colitis (UC), were recruited, and their serum food-specific IgGs against 14 food antigens were detected by a semi-quantitative enzyme linked immunosorbent assay (ELISA). Total serum IgG and IgE levels were measured by immunonephelometry and fluorescent enzyme immunoassay, respectively. Simultaneously, the relevant medical records and clinical data were collected for further analyses. Results Food-specific IgGs against egg, milk, wheat, corn, rice, tomato, codfish, and soybean antigens were found to be significantly increased in the sera of CD patients compared with UC patients and healthy controls (p<0.01). The levels of total serum IgG and IgE were also significantly higher in CD patients than in healthy controls (p<0.01). The titers of corn- and tomato-specific IgGs were found to be significantly correlated with total serum IgG in CD patients (p<0.05), while the titers of egg-, milk-, and wheat-specific IgGs were correlated with total serum IgE (p<0.05). Interestingly, IFX therapy was able to down-regulate the food-specific IgG-mediated immune response markedly in active CD patients. Conclusion Food-specific IgGs against egg, milk, wheat, corn, rice, tomato, codfish, and soybean are highly increased in the sera of CD patients. IFX treatment was able to down-regulate the levels of food-specific IgGs by suppressing intestinal inflammation and promoting mucosal healing. Therefore, food-specific IgGs may serve as an important approach in the diagnosis and management of food allergy in IBD.
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Could a change in diet revitalize children who suffer from unresolved fatigue?
Steenbruggen, TG, Hoekstra, SJ, van der Gaag, EJ
Nutrients. 2015;7(3):1965-77
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Up to 46% of children report suffering from fatigue, which can affect their ability to learn at school, mental health, immune system function and quality of sleep. Where there is no medical cause for the fatigue, a deficiency of micronutrients in the diet may be to blame. In this non-randomised controlled trial, a group of 98 children aged 2–18 years old with unexplained symptoms of fatigue was examined. Children in the intervention group were advised to follow a nutrient-rich diet for three months, consisting of green vegetables 5 times a week, beef 3 times a week, 200ml of whole milk daily and the use of full-fat butter. The control-group followed their normal diet. Children who followed the diet showed a significant decrease in the need to sleep. They slept better through the night and took fewer naps. General fatigue and cognitive fatigue also showed greater improvement in the intervention group, but the difference between the groups was not statistically significant. When analysing individual components of the diet, a significant improvement in cognitive fatigue symptoms was associated with eating green vegetables. A lower need to sleep was seen when whole milk was consumed almost daily. The authors suggest that nutritional advice is an elegant, and effective method for decreasing some symptoms of medically unresolved fatigue in children.
Abstract
Many children deal with fatigue for which no proper treatment can be given. A possible explanation for their fatigue is a micro deficiency of minerals and vitamins. In this non-randomized controlled trial, we clinically evaluated symptoms of fatigue in children for whom a nutrient-rich diet was advised. A group of 98 children (2-18 years old) with unexplained symptoms of fatigue was examined. The dietary modifications consisted of green vegetables, beef, whole milk and full-fat butter. Children in the intervention group were asked to follow the diet for three months, whereas the control-group followed their normal diet. The primary outcome was symptoms of fatigue, as determined by a PedsQL Multidimensional Fatigue Scale, and secondary outcomes were compliance with the diet and BMI. Children, who followed the diet showed a significant decrease in the need to sleep (CI 0.83; 14.86, p = 0.03). They slept better through the night and took fewer naps. When analyzing components of the advised diet separately, a significant larger decrease in cognitive fatigue symptoms was seen for eating green vegetables according to the diet guidelines (CI 2.27; 30.63, p = 0.024). Furthermore, a lower need to sleep was seen when whole milk was consumed almost daily (CI 0.02; 14.62, p = 0.049). Our study showed that nutritional advice is an elegant, and effective method for decreasing some symptoms of medically unresolved fatigue in children.
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Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity.
Hollon, J, Puppa, EL, Greenwald, B, Goldberg, E, Guerrerio, A, Fasano, A
Nutrients. 2015;7(3):1565-76
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Celiac disease (CD) and non-celiac gluten sensitivity (GS) are conditions caused by a reaction to gluten in the small intestines. When gluten is ingested, patients with CD produce an immune-mediated response in the intestinal mucosa whereas GS react symptomatically but do not produce an immune response. Due to this difference, it is thought that there may be a common defect in the intestinal barrier function in these two conditions. The aim of this study was to evaluate the response to gliadin exposure, both in terms of intestinal barrier function and immune cell secretion. Gliadin is a peptide in gluten that is responsible for the disassembly of intestinal tight junctions and therefore increased intestinal permeability. The study included intestinal explants from 23 patients. The findings of this study showed that gliadin exposure leads to a significant increase in intestinal permeability in all individuals. A deficiency in anti-inflammatory immune cells was also measured in patients with CD or GS, which is suggested to contribute to increased intestinal permeability.
Abstract
BACKGROUND Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). METHODS Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. RESULTS Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. CONCLUSIONS Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity.
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Effect of shiitake (Lentinus edodes) extract on antioxidant and inflammatory response to prolonged eccentric exercise.
Zembron-Lacny, A, Gajewski, M, Naczk, M, Siatkowski, I
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2013;64(2):249-54
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Shiitake (Lentinus edodes) is a popular culinary and medicinal mushroom. It contains numerous active compounds including ergothioneine which has anti-inflammatory and antioxidant properties. This study evaluated the antioxidant and anti-inflammatory effect of shiitake extract in healthy men exposed to exercise-induced muscle damage. Fourteen healthy males participated in this placebo-controlled crossover study. Subjects ingested shiitake extract or placebo for 10 days prior to exercise, with a 30 day period between the two phases of the crossover. Bloods were drawn at 20 minutes, 24 hours and 48 hours after exercise. There was no statistically significant difference between the shiitake and the placebo group in the inflammation related parameters measured. But there was a significant change in certain compounds suggesting an increased antioxidant activity in the shiitake group. The authors conclude that shiitake does not affect the inflammatory response following exercise but has antioxidant action, and that further studies are needed to make recommendations for use of shiitake by athletes.
Abstract
The shiitake (Lentinus edodes) extract is purported to have potent antioxidant, anti-inflammatory and regenerative properties due to presence of many bioactive compounds such as ergothioneine. This study was designed to assess the antioxidant and anti-inflammatory activity of shiitake extract in healthy men exposed to exercise-induced skeletal muscles damage. Subjects ingested shiitake mushroom extract (700 mg, two times per day) or placebo for 10 days prior to two separate exercise trials (crossover study). The exercise session involved 90 min run at 65% VO2max (0% gradient) and 15-min eccentric phase at 65% VO2max (-10% gradient). Subjects experienced creatine kinase (peak 461±206 IU/L) and leukocytes (peak 9.82 x 103/μL) elevations indicating muscle damage and inflammation. Exercise altered plasma IL-6 (peak 5.29±0.78 pg/mL), IL-10 (peak 24.75±6.22 pg/mL) and IL-1β (peak 0.54±0.09 pg/mL) levels but did not affect tumour necrosis factor α (TNF-α) level relative to baseline. Shiitake extract did not demonstrate any effect on immune cells number and inflammatory mediators level, with the exception of IL-10. Thiol redox status (GSHtotal-2GSSG/GSSG) and niric oxide (NO) concentration increased after shiitake extract whereas H2O2 and 8-isoprostanes did not change. In conclusion, shiitake mushroom extract had no effect on markers of inflammation following prolonged eccentric exercise but demonstrated an antioxidant activity through the regulation of nitric oxide concentration and thiol redox status.
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Methionine-adequate cysteine-free diet does not limit erythrocyte glutathione synthesis in young healthy adult men.
Courtney-Martin, G, Rafii, M, Wykes, LJ, Ball, RO, Pencharz, PB
The Journal of nutrition. 2008;138(11):2172-8
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The amino acid cysteine is believed to be a rate-limiting substrate for synthesis of the antioxidant glutathione. The aim of this study was to determine whether cysteine supplementation increased glutathione synthesis in healthy men. Four healthy men of average age 20 years were each given five levels of cysteine intake ranging from 0 to 40mg per kg body weight per day. Each level of intake was given for a period of 3 days, with glutathione levels in red blood cells measured on the 3rd day of each period. Subjects were also provided with a standardised diet, an amino acid mixture equivalent to that found in egg protein, a daily multivitamin supplement, a choline supplement and methionine throughout the study. In this study, increasing cysteine intake did not result in increased glutathione synthesis. The authors concluded that a diet with adequate protein intake is sufficient for glutathione synthesis in healthy adults.
Abstract
Most methods of determining amino acid (AA) requirements are based on endpoints that determine adequacy for protein synthesis. However, the sulfur AA (SAA) cysteine is believed to be the rate-limiting substrate for synthesis of the most abundant intracellular antioxidant, glutathione (GSH). Our objectives were to determine whether supplementation of cysteine in a diet containing adequate SAA for protein synthesis, as methionine, increased GSH synthesis by measuring the fractional and absolute synthesis rates, and if concentration of GSH changed in response to feeding 5 graded intakes of cysteine (0, 10, 20, 30, and 40 mg x kg(-1) x d(-1)) in a random order with a fixed methionine intake of 14 mg x kg(-1) x d(-1) and a protein intake of 1 g x kg(-1) x d(-1). Each subject received a multivitamin and choline supplement during the study. Four healthy adult men each underwent 5 isotope infusion studies of 7-h duration after a 2-d adaptation to the level of cysteine intake being studied on the isotope infusion day. The isotope used was [U-(13)C(2)-(15)N]glycine. Analyses included erythrocyte GSH synthesis rates and concentration and urinary sulfate excretion. The GSH synthesis rates and concentration, measured at a methionine intake of 14 mg x kg(-1) x d(-1), did not change with increasing intakes of cysteine. Urinary sulfate excretion showed a significant positive relationship with cysteine intake (r = 0.92; P < 0.01). In conclusion, this study provides preliminary evidence that consumption of SAA adequate to meet the requirement for protein synthesis does not limit GSH synthesis in healthy adult men receiving an otherwise adequate diet.