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Effects of vitamin C stimulation on rehabilitation of dysphagia after stroke: a randomized trial.
Wang, J, Chang, E, Jiang, Y
European journal of physical and rehabilitation medicine. 2022;58(4):558-564
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Stroke refers to a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease. It has the characteristics of rapid onset, high morbidity, high mortality, and high disability. After a stroke, various dysfunction can be caused, and dysphagia is one of the most common symptoms. The acidity of vitamin C can promote the secretion of saliva by stimulating the tongue, which can accelerate the swallowing action, thereby improving the swallowing function. The aim of this study was to explore the effects of vitamin C stimulation on the rehabilitation process, Nourishment State Index and immune function indicator of stroke patients with dysphagia. This study is a randomised controlled trial which enrolled 120 participants with dysphagia. The participants were randomly assigned into control group and vitamin C stimulation group, with 60 cases in each group. Results show that vitamin C acid stimulation significantly improves rehabilitation, and the Nourishment State Index and Immune Function Index of stroke patients with dysphagia. Authors conclude that Vitamin C acid stimulation can further improve the nutritional status and immune function after stroke and promote post-operative recovery of patients. Thus, vitamin C stimulation therapy can be widely used in stroke rehabilitation management.
Abstract
BACKGROUND Stroke is a clinical syndrome of localized or global brain dysfunction caused by cerebrovascular disease. AIM: The aim of this study was to explore the effect of vitamin C acid stimulation on the rehabilitation process, Nourishment State Index and immune function indicators of stroke patients with dysphagia. DESIGN This is a prospective cohort study. SETTING This study was conducted at our hospital. POPULATION We analyzed stroke patients with dysphagia. METHODS A total of 120 stroke patients with dysphagia were randomly divided into a routine group and a test group, with 60 cases in each group. Routine swallowing training was performed in the routine group, and the test group was stimulated with vitamin C acid. The water swallow test (WST) and video fluoroscopic swallowing study (VFSS) were used to compare the rehabilitation of dysphagia in the two groups. Nourishment State Index was evaluated by BMI, serum albumin, total serum protein and hemoglobin. Immune Function Index was evaluated by IgA, IgM and IgG. RESULTS Compared with the control group, the WST level of patients treated with vitamin C acid stimulation intervention were significantly reduced, and the VFSS score were significantly increased. Serum levels of hemoglobin, albumin, total protein, IgA, IgM and IgG in the vitamin C acid stimulation group were remarkably increased than those in the control group. CONCLUSIONS Vitamin C acid stimulation exhibits a good application effect in patients with dysphagia after stroke. Moreover, vitamin C acid stimulation can further improve the nutritional status and immune function after stroke and promote postoperative recovery of patients. Therefore, we believe that vitamin C stimulation therapy can be widely used in stroke rehabilitation management. CLINICAL REHABILITATION IMPACT Vitamin C acid stimulation significantly improves rehabilitation of stroke patients with dysphagia and ameliorates the nutritional status and immune function of patients.
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Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly.
Despeghel, M, Reichel, T, Zander, J, Krüger, K, Weyh, C
Cells. 2021;10(4)
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As age advances, a gradual deterioration of immune function happens termed Immunosenescence, where different components of the immune system make a behavioural shift towards gradual decline. Immune ageing is characterized by changes in the ratio of naive memory T cells and CD4:CD8 and is associated with inflammatory cytokine production, which accelerates inflammatory ageing. This randomised controlled trial aimed to examine the effect of low-dose combined resistance and endurance training on the ageing immune system and inflammation in elderly subjects. Thirty participants (between the ages of 65 and 75) took part in a controlled low-threshold and care-oriented combined resistance and endurance training program for six weeks. This study showed an increase in CD4:CD8 ratio, decrease in low-grade inflammation and an improvement in strength capacity denoting improved immunosenescence and inflammaging among elderly participants. However, the study was conducted on a small sample for a short period. Therefore, robust long-term studies are required to elucidate further positive effects of different levels of physical activities in the elderly. Healthcare professionals can use these findings to understand how exercise influences immunosenescence and inflammation in the ageing body.
Abstract
With increasing age, the immune system undergoes a remodeling process, affecting the shift of T cell subpopulations and the development of chronic low-grade inflammation. Clinically, this is characterized by increased susceptibility to infections or development of several diseases. Since lifestyle factors can play a significant role in reducing the hallmarks of immune aging and inflammation, we investigated the effect of a 6 week low-dose combined resistance and endurance training program. Forty participants (70.3 ± 5.0 years) were randomly assigned to either a training (TG) or control group (CG) and performed a controlled low-threshold and care-oriented 6-week-long combined resistance and endurance training program. Changes in anthropometrics as well as strength capacity were measured. In subgroups of TG and CG, T cells and their subpopulations (CD4+, CD8+, naïve, central, effector memory, T-EMRA) were analyzed by flow cytometry. The changes of various plasma cytokines, chemokines, growth factors and adipokines were analyzed by luminex assays. The exercise program was followed by an increase in strength capacities. Participants of TG showed an increase of the CD4+/CD8+ T cell ratio over time (p < 0.05). Significant decreases in systemic levels of interleukin (IL-) 6, IL-8, IL-10 and vascular endothelial growth factor (VEGF) (p < 0.05) were observed for participants of TG over time. Even short-term and low-threshold training can reduce some of the hallmarks of immune aging in elderly and thus could be beneficial to stimulate immunity. The specific characteristics of the program make it easily accessible to older people, who may benefit in the longer term in terms of their immunocompetence.
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What is the effect of a Mediterranean compared with a Fast Food meal on the exercise induced adipokine changes? A randomized cross-over clinical trial.
Silva, D, Moreira, R, Beltrão, M, Sokhatska, O, Montanha, T, Pizarro, A, Garcia-Larsen, V, Villegas, R, Delgado, L, Moreira, P, et al
PloS one. 2019;14(4):e0215475
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Unhealthy dietary intake and sedentary behaviour in a genetically susceptible individual have been associated with adipokine dysregulation (adipokines are small proteins secreted by the fat tissue) resulting both in adverse metabolic and immune responses. The aim of this study was to evaluate the effect of a Mediterranean (MdM) compared with a Fast Food (FFM) iso-energy meal on the acute exercise-induced adipokine changes. The study is a double-blind randomised crossover clinical trial. Participants (n = 46) were randomly assigned to the intervention order in a double-blinded fashion, stratified by asthma diagnosis. Outcomes were measured blinded to the participant’s allocation order. Results indicate that MdM may blunt the adipsin (an adipokine) immediate response and potentiate its exercise induced increase in comparison with a FFM. MdM slightly attenuated the exercise induced cortisol increase. Authors conclude that their findings highlight the importance of the pre-exercise dietary intake on both the immune and metabolic response to acute exercise.
Abstract
BACKGROUND Adipose tissue-derived adipokines are pro-inflammatory cytokines involved in metabolic-related diseases and can be influenced by diet and exercise. We aimed to compare the effect of a Mediterranean (MdM) compared with Fast Food (FFM) meal on the exercise induced adipokines changes. METHODS In a double blinded cross over trial, 46 participants were randomly assigned to one of two standardized iso-energy pre-exercise meals: FFM or MdM-type. Three hours after each meal, participants completed a treadmill exercise test (EC). Serum adiponectin, resistin, PAI-1, lipocalin-2/NGAL and adipsin were determined by Luminex magnetic bead immunoassay. Wilcoxon signed rank test compared changes before/after meal and before/after EC and a linear mixed model evaluated the effect of meals on the adipokine response to exercise, adjusted for confounders. RESULTS Thirty-nine participants (mean age of 25, with a standard deviation of 5 years) completed the trial (56% females). For both interventions, a significant reduction of adipsin after each meal and a significant increase of lipocalin, PAI-1, adipsin and resistin, after exercise was observed. When exercise was preceded by a MdM meal a higher increase in adipsin levels was seen. CONCLUSION Acute exercise induced an increase of circulatory levels of adipsin, resistin, lipocalin and PAI-1, but not adiponectin. A pre-exercise Mediterranean meal potentiated the increase of adipsin after the exercise test, which possibly relates to the immune regulatory role of adipsin. These changes suggest a cross-talk between the immune and metabolic immediate response to exercise and its modulation by the pre-exercise diet composition.
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The effect of L-theanine supplementation on the immune system of athletes exposed to strenuous physical exercise.
Juszkiewicz, A, Glapa, A, Basta, P, Petriczko, E, Żołnowski, K, Machaliński, B, Trzeciak, J, Łuczkowska, K, Skarpańska-Stejnborn, A
Journal of the International Society of Sports Nutrition. 2019;16(1):7
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According to previous studies, strenuous exercise may contribute towards an imbalance in Th1/Th2 cytokines that are secreted by the immune system, resulting in an impairment of the immune system. The main aim of this study was to analyse the effect of L-theanine on cytokines of the immune system and establish the role of L-Theanine as immunomodulatory. This double blind randomised study recruited 20 men from the Polish rowing team. The subjects were randomised to the supplemented group and placebo group. The supplemented group received gelatine capsules with 150 mg L-theanine extract whilst the placebo group received visually identical capsules with corn starch. The participants in the study were asked to take two capsules per day for 6 weeks. Athletes from both the groups did not differ significantly in terms of their mean age, body height, body weight and years of training. After 24 hour recovery, the athletes in the supplemented group showed lower amount of cytotoxic cell. The authors concluded based on the study that supplementation with L- theanine in athletes exposed to strenuous exercise had beneficial effect.
Abstract
BACKGROUND The aim of this study was to analyze the response of selected components of the immune system in rowers to maximal physical exercise, and to verify if this response could be modulated by supplementation with L-theanine. METHOD The double-blind study included 20 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group (n = 10), receiving 150 mg of L-theanine extract for 6 weeks, or to the placebo group (n = 10). The participants performed a 2000-m test on a rowing ergometer at the beginning (1st examination) and at the end of the supplementation period (2nd examination). Blood samples were obtained from the antecubital vein before each exercise test, 1 min after completing the test, and after a 24-h recovery. Subpopulations of T regulatory lymphocytes (Tregs) (CD4+/CD25+/CD127-), cytotoxic lymphocytes (CTLs) (CD8+/TCRαβ+), natural killer (NK) cells (CD3-/CD16+/CD56+) and TCRδγ-positive (Tδγ) cells were determined by means of flow cytometry. The levels of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 10 (IL-10), interferon gamma (INF-ɤ) and total antioxidant capacity (TAC) were determined with commercially available diagnostic kits. RESULTS Supplementation with L-theanine contributed to a significant post-exercise decrease in IL-10 concentration, which was reflected by higher values of IL-2 to IL-10 and IFN-γ to IL-10 ratios. Moreover, a significant post-recovery decrease in CTL count, Treg to NK and Treg to CTL ratios was observed in the supplemented group. CONCLUSION Despite the decrease in the number of some cytotoxic cells (CTLs) and an increase in the proportion of Tregs to CTLs, supplementation with LTE seems to exert a beneficial effect on a disrupted Th1/Th2 balance in elite athletes, as shown by the decrease in IL-10 concentration.
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Evaluation of psoriasis severity and inflammatory responses under concomitant treatment with methotrexate plus micronutrients for psoriasis vulgaris: a randomized double blind trial.
Yousefzadeh, H, Jabbari Azad, F, Banihashemi, M, Rastin, M, Mahmoudi, M
Acta dermatovenerologica Alpina, Pannonica, et Adriatica. 2017;26(1):3-9
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Psoriasis Vulgaris is an immune-mediated chronic inflammatory disease that causes red, itchy, flaky, scaly skin. Methotrexate is an immune modulatory first-line conventional drug used to treat moderate psoriasis. Previous research suggests beneficial immune-modulatory and anti-inflammatory effects of micronutrient treatments. In this double-blinded trial, 30 Asian Psoriatic patients were randomly assigned either 7.5 to 15 mg of Methotrexate alone weekly or Methotrexate combined with daily micronutrient supplementation for 12 weeks. Patients in the micronutrient supplementation group received higher doses of micronutrients than the RDA and additional 5 mg folate supplementation on all days except the day of Methotrexate consumption. Inflammatory markers were significantly reduced by both treatments. Further, the combination of Methotrexate and micronutrient supplement resulted in greater immune modulation and decreased inflammation. For generalisation of the results, further robust research is needed. Using the results of this study, healthcare professionals can make effective therapeutic clinical decisions in the treatment of psoriasis by combining Methotrexate with micronutrient supplements.
Abstract
INTRODUCTION We evaluated the effectiveness of concomitant treatment with methotrexate (MTX) plus micronutrients in comparison with monotherapy with MTX only in psoriasis patients. Plasma levels of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were also measured and their association with clinical severity was evaluated. METHODS Thirty psoriasis patients 20 to 50 years old with a PASI score > 10 were divided randomly into two groups. Both groups were given oral methotrexate (0.2-0.3 mg/kg/week) for 12 weeks. In addition, Group B received one tablet of micronutrient supplement daily. Disease severity was calculated using the psoriasis area and severity index (PASI) score before and after 12 weeks. Levels of IL-1β and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS We found that 13 (86.6%) patients in Group B and 8 (53.3%) patients in Group A attained a mild PASI score (≤ 10% body involvement). IL-1β and TNF-α levels were significantly decreased in favor of Group B (p < 0.05). There was a significant correlation between changes in both IL-1β and TNF-α levels and PASI score after the study (p < 0.05). CONCLUSION The results obtained were positive, and therefore double-blind randomized trials with a larger sample size are highly suggested to confirm or reject these results.
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Superiority of a vitamin B12-containing emollient compared to a standard emollient in the maintenance treatment of mild-to-moderate plaque psoriasis.
Del Duca, E, Farnetani, F, De Carvalho, N, Bottoni, U, Pellacani, G, Nisticò, SP
International journal of immunopathology and pharmacology. 2017;30(4):439-444
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During inflammation, an enzyme named Nitric oxide synthase is produced, causing increased Nitric oxide production in psoriatic lesions. Vitamin B12 binds to Nitric oxide and serves as a scavenger. Earlier studies indicate that Vitamin B12 can reduce immunological factors, inflammation, and skin proliferation in people with psoriasis. This randomised, single-blinded, intra-patient, left-to-right comparison study aimed to evaluate the effectiveness of topical cream containing vitamin B12 as a therapeutic strategy in reducing psoriatic plaque lesions. 24 patients with mild-to-moderate psoriasis who were treated with emollient cream containing vitamin B12 for 16 weeks showed a reduction in the severity of psoriasis. Furthermore, vitamin B12 cream significantly reduced the severity of psoriasis compared to glycerol-petrolatum-based emollient creams. Vitamin B12 cream application also showed a great reduction in itching and psoriatic plaque formation. 16 weeks of treatment demonstrated the anti-inflammatory and immune modulatory effects of Vitamin B12 cream. To fully understand the effects of Vitamin B12 on different pathological pathways of psoriasis, further research is needed. The study can guide healthcare professionals in understanding the benefits of Vitamin B12 cream on mild-to-moderate psoriasis and its clinical applicability.
Abstract
Psoriasis is a chronic inflammatory skin disease affecting 2%-3% of the population. The wide range of drugs currently available for its treatment could be associated, in the long term, with organ toxicity and adverse events, thus, clinical monitoring throughout treatment is required. This investigator-initiated trial (IIT) evaluated the efficacy and the safety of a vitamin B12-containing ointment in comparison with glycerol-petrolatum-based emollient cream used twice a day to treat mild-to-moderate plaque psoriasis for a period over 12 weeks followed by a wash-out observation period of 4 weeks. This study was conducted as a randomized, controlled, single-blind, intra-patient left- to right-side trial comparing the efficacy and safety of vitamin B12-containing ointment (M-treatment) with a glycerol-petrolatum-based emollient cream (C-treatment). The Psoriasis Area Severity Index (PASI) was determined at baseline (T0), at time points T2 (14 days), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks) and 4 weeks after the end of the wash-out period (F1). In total, 24 patients with plaque psoriasis were randomized to receive left- or right-side treatment with B12 ointment. From time point T2 to time point F1, there was a statistically significant difference in PASI reduction between M-treatment side and C-treatment side. At time point T 12, the difference between the mean reductions from baseline PASI scores by 5.92 ± 2.49 (87, 6%) in the M-treatment side versus 1.08 ± 1.02 (23, 1%) C-treatment side was statistically highly significant ( PWex < 0.001). On the contemporary panorama in the treatment of psoriasis, we conclude that vitamin B12 ointment will represent a new concrete therapy option and should be considered in the update of therapeutic algorithm for the treatment of psoriasis.
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The Effect of Post-Resistance Exercise Amino Acids on Plasma MCP-1 and CCR2 Expression.
Wells, AJ, Hoffman, JR, Jajtner, AR, Varanoske, AN, Church, DD, Gonzalez, AM, Townsend, JR, Boone, CH, Baker, KM, Beyer, KS, et al
Nutrients. 2016;8(7)
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Background: Innate immune response is generally considered to have an important role in tissue remodeling of the damaged localised skeletal muscle as a result of intense resistance exercise. Monocytes are leukocytes that also influence our adaptive immune system. Aim & Objective: The purpose of this study was to examine the changes in the markers of monocytes recruitment after a bout of high resistance exercise and ingestion of amino acid supplement. Method: Ten resistant trained men between the ages of 18 and 35 were recruited in this randomised crossover design study. Blood sample were taken at various time to measure and assess the plasma concentrations of monocyte chemoattractant protein 1 (MCP-1), myoglobin, cortisol and insulin concentrations; and expressions of C-C chemokine receptor-2 (CCR2), and macrophage-1 antigen (CD11b) on classical monocytes. Result & conclusion: No significant differences were noted for the markers myoglobin, insulin or cortisol in the treatment group in this study. Ingestion of supplement increased the CCR2 expression on CD14+ monocytes at 1H, 2H and 5H(P’s ≤ 0.001) after the exercise, but did not appear to have any influence on CD11b expression on CD14++CD16- ́ monocytes. To conclude it seems that amino acids are important regulator of immune response but more research is needed.
Abstract
The recruitment and infiltration of classical monocytes into damaged muscle is critical for optimal tissue remodeling. This study examined the effects of an amino acid supplement on classical monocyte recruitment following an acute bout of lower body resistance exercise. Ten resistance-trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm) ingested supplement (SUPP) or placebo (PL) immediately post-exercise in a randomized, cross-over design. Blood samples were obtained at baseline (BL), immediately (IP), 30-min (30P), 1-h (1H), 2-h (2H), and 5-h (5H) post-exercise to assess plasma concentrations of monocyte chemoattractant protein 1 (MCP-1), myoglobin, cortisol and insulin concentrations; and expressions of C-C chemokine receptor-2 (CCR2), and macrophage-1 antigen (CD11b) on classical monocytes. Magnitude-based inferences were used to provide inferences on the true effects of SUPP compared to PL. Changes in myoglobin, cortisol, and insulin concentrations were similar between treatments. Compared to PL, plasma MCP-1 was "very likely greater" (98.1% likelihood effect) in SUPP at 2H. CCR2 expression was "likely greater" at IP (84.9% likelihood effect), "likely greater" at 1H (87.7% likelihood effect), "very likely greater" at 2H (97.0% likelihood effect), and "likely greater" at 5H (90.1% likelihood effect) in SUPP, compared to PL. Ingestion of SUPP did not influence CD11b expression. Ingestion of an amino acid supplement immediately post-exercise appears to help maintain plasma MCP-1 concentrations and augment CCR2 expression in resistance trained men.
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Physiological Effects of Nucleotide Supplementation on Resistance Exercise Stress in Men and Women.
Sterczala, AJ, DuPont, WH, Comstock, BA, Flanagan, SD, Szivak, TK, Hooper, DR, Kupchak, BR, Lee, EC, Volek, JS, Maresh, CM, et al
Journal of strength and conditioning research. 2016;30(2):569-78
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Nucleotides are essential building blocks to many biological processes including DNA and RNA synthesis, coenzyme synthesis, energy metabolism, cellular signalling, and balanced use of proteins. The main aim of this study was to determine whether nucleotide supplementation affects the acute hypothalamic-pituitary axis (HPA) and immune response to resistance exercise. A secondary aim was to determine whether nucleotide supplementation could improve physical performance capabilities during recovery from such strenuous exercise. The study is a double-blinded, placebo-controlled, mixed methods crossover design study. Twenty participants (women = 10; men = 10), who were resistance trained, completed the protocol. Results indicate that dietary nucleotide supplement reduced markers of HPA and inflammatory activity. Sex-specific differences in the response to nucleotide supplementation included the absence of improvement of physical recovery in women. Authors conclude that nucleotide supplementation may attenuate the stress response, reduce muscle damage, and preserve force production capabilities after intense resistance exercise. Thus, these effects could improve recovery from strenuous exercise.
Abstract
Nucleotide supplementation can reduce postexercise immunosuppression and hypothalamic-pituitary axis (HPA) axis activation in endurance exercise models. Nucleotide supplementation may aid recovery from other exercise modalities, such as heavy resistance exercise. Thus, the purpose of this investigation was to investigate the effects of nucleotide supplementation on the acute cortisol and immune responses to heavy resistance exercise and its effects on recovery. A double-blinded, crossover, mixed methods design with 10 men and 10 women was used. Each performed an acute heavy resistance exercise protocol (AHREP) after a loading period with a nucleotide or placebo supplement. Before and after the AHREP, and at 24, 48, and 72 hours post, blood samples were analyzed for cortisol, myeloperoxidase (MPO), and absolute neutrophil, lymphocyte, and monocyte counts. Creatine kinase (CK) was analyzed before and 24, 48, and 72 hours after the AHREP. Performance measures, including peak back squat isometric force and peak countermovement jump power were also analyzed. Nucleotide supplementation resulted in significant (p ≤ 0.05) decreases in cortisol and MPO immediately after the AHREP, and significantly lower CK values 24 hours later. The AHREP significantly affected leukocyte counts; however, no treatment effects were observed. Greater isometric force was observed immediately after AHREP and at 24 hours and 48 hours with nucleotide supplementation. Nucleotide supplementation seems to attenuate muscle damage, HPA axis and immune system activation, and performance decrements after heavy resistance exercise.
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Oral Curcumin (Meriva) Is Effective as an Adjuvant Treatment and Is Able to Reduce IL-22 Serum Levels in Patients with Psoriasis Vulgaris.
Antiga, E, Bonciolini, V, Volpi, W, Del Bianco, E, Caproni, M
BioMed research international. 2015;2015:283634
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Psoriasis is an immune-mediated inflammatory condition affecting the skin, nails, and joints. Turmeric contains curcumin, a yellow-pigmented polyphenol with anti-inflammatory properties. Several diseases, including psoriasis, have been treated with turmeric in Asian countries since ancient times as a topical application and dietary supplement. This phase 3, single-dose, randomised, double-blind, placebo-controlled clinical trial evaluated the efficacy of curcumin as a complementary therapy for the treatment of mild-to-moderate psoriasis. This study used Meriva, a curcumin supplement that contains lecithin to boost the bioavailability and absorption of curcumin. The study assessed the effect of curcumin supplementation on inflammatory cytokine secretion by the immune cells. For 12 weeks, sixty-three patients with mild-to-moderate psoriasis were randomly assigned to either receive 2 grams of oral curcumin supplement, Meriva, along with topical steroid cream (Methylprednisolone aceponate 0.1%), or topical steroid cream alone. Treatment with 2 grams of oral curcumin supplementation and topical steroid cream application for 12 weeks significantly reduced the secretion of inflammatory cytokine, IL-22, in the serum of psoriatic patients. Additionally, the treatment reduced the proliferation of outer skin cells. Further robust studies are required to analyse the beneficial effects of curcumin on other pathogenic pathways of psoriasis. The study can help healthcare professionals learn more about the benefits of curcumin supplements for treating psoriasis in conjunction with conventional medicine.
Abstract
Curcumin is a complementary therapy that may be helpful for the treatment of psoriasis due to its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects. In the present study we performed a randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a bioavailable oral curcumin in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris (PASI < 10) were randomly divided into two groups treated with topical steroids and Meriva, a commercially available lecithin based delivery system of curcumin, at 2 g per day (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning (T0) and at the end of the therapy (T12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At T12, both groups achieved a significant reduction of PASI values that, however, was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with oral curcumin. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22.
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A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function.
Vazquez-Roque, MI, Camilleri, M, Smyrk, T, Murray, JA, Marietta, E, O'Neill, J, Carlson, P, Lamsam, J, Janzow, D, Eckert, D, et al
Gastroenterology. 2013;144(5):903-911.e3
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The relationship between gluten exposure and diarrhoea-predominant irritable bowel syndrome (IBS-D) is not well understood. Non-celiac IBS-D patients who are positive for HLA-DQ2/8 genes associated with CD can show symptom improvement on a gluten-free diet (GFD). The aim of this 4-week parallel randomized controlled clinical trial in HLA-DQ2/8 positive and negative patients with IBS-D was to assess the effects of a gluten-containing diet (GCD) compared to a GFD on bowel function, gut transit, small bowel (SB) and colonic barrier functions as measured by two-sugar excretion permeability test and mRNA expression of TJ proteins in mucosa of the small bowel (SB) and rectosigmoid (RS) derived by biopsy. Immune response to diets was also measured as cytokine production from peripheral blood mononuclear cells (PBMCs). Patient were recruited from the Mayo clinic’s database of IBS suffers, and invited to participate. Patients with diagnosed CD were excluded. Genotype analysis was performed for HLA-DQ2 and HLA-DQ8. 22 patients were placed on the GCD (11 HLA-DQ2/8–negative and 11 HLA-DQ2/8–positive) and 23 on the GFD (12 HLA-DQ2/8−negative and 11 HLA-DQ2/8–positive. All meals and snacks were ingested or prepared in the Mayo Clinic. Patients were advised to eat only the foods provided by the study dieticians. Gluten-free and gluten-containing meals were prepared using the same macronutrient content (20% protein, 30% fat, 50% carb). Compliance to the diet was assessed by direct questioning by the dietitians and reported to be excellent. All patients were ingesting gluten in their diet prior to starting the study. At 4-weeks, a statistically significant decrease in stool frequency of subjects on GFD compared to subjects on GCD (p=0.04) was seen. This effect was more pronounced in subjects who were HLA-DQ2 or 8 positive (p=0.019) There was no significant diet effect (GFD vs. GCD) on, daily stool form, ease of passage or gastric emptying. The GCD was associated with higher small bowel (SB) permeability (based on 0–2 hr levels of mannitol (p=0.028) and lactulose:mannitol ratio (P=0.0012)). SB permeability was greater in HLA-DQ2/8–positive than −negative patients (P=.018). No significant differences in colonic permeability were observed. Significant diet-associated changes in occludin expression in SB mucosa in the HLA-DQ2 or 8 positive group were seen (p=0.017). Expressions of tight junction proteins (zonulin (ZO-1), occludin, and claudin-1 mRNA) in colonic mucosa were significantly lower in GCD relative to GFD in the overall groups, particularly in subjects with HLA-DQ2 or 8 positive status. Cytokine response was higher (interleukin-10) in response to GCD than GFD (unrelated to HLA genotype). A limitation in the quantification of TJ protein expression is that it was solely based on PCR (mRNA expression). In future, other methods should be included to directly identify these proteins and their distribution. The inability to document alterations in colonic permeability using the 2-sugar excretion profile from 8 to 24 hours is a limitation. This may be due to lack of sensitivity of the lactulose and mannitol excretion test, for example, due to the metabolism of both sugars by colonic bacteria. Another limitation is that the mechanism for improvement in stool frequency on a GFD in the absence of changes in colonic transit was not elucidated by our studies. This study does not specifically address the effects of gluten protein per se, and it is possible that other proteins in wheat flour may be responsible for the changes observed. The author concludes that this study provide mechanistic explanations for the observation that gluten withdrawal may improve patient symptoms in IBS. The data also partially explains that the biological effects of gluten were associated with HLA-DQ2 or 8 genotype. The relationship of dietary factors, innate and adaptive immune responses and mucosal interactions in IBS-D deserve further study. Further clinical studies evaluating the effects of gluten withdrawal in patients with IBS-D are needed.
Abstract
BACKGROUND & AIMS Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) could benefit from a gluten-free diet (GFD). METHODS We performed a randomized controlled 4-week trial of a gluten-containing diet (GCD) or GFD in 45 patients with IBS-D; genotype analysis was performed for HLA-DQ2 and HLA-DQ8. Twenty-two patients were placed on the GCD (11 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive) and 23 patients were placed on the GFD (12 HLA-DQ2/8 negative and 11 HLA-DQ2/8 positive). We measured bowel function daily, small-bowel (SB) and colonic transit, mucosal permeability (by lactulose and mannitol excretion), and cytokine production by peripheral blood mononuclear cells after exposure to gluten and rice. We collected rectosigmoid biopsy specimens from 28 patients, analyzed levels of messenger RNAs encoding tight junction proteins, and performed H&E staining and immunohistochemical analyses. Analysis of covariance models was used to compare data from the GCD and GFD groups. RESULTS Subjects on the GCD had more bowel movements per day (P = .04); the GCD had a greater effect on bowel movements per day of HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .019). The GCD was associated with higher SB permeability (based on 0-2 h levels of mannitol and the lactulose:mannitol ratio); SB permeability was greater in HLA-DQ2/8-positive than HLA-DQ2/8-negative patients (P = .018). No significant differences in colonic permeability were observed. Patients on the GCD had a small decrease in expression of zonula occludens 1 in SB mucosa and significant decreases in expression of zonula occludens 1, claudin-1, and occludin in rectosigmoid mucosa; the effects of the GCD on expression were significantly greater in HLA-DQ2/8-positive patients. The GCD vs the GFD had no significant effects on transit or histology. Peripheral blood mononuclear cells produced higher levels of interleukin-10, granulocyte colony-stimulating factor, and transforming growth factor-α in response to gluten than rice (unrelated to HLA genotype). CONCLUSIONS Gluten alters bowel barrier functions in patients with IBS-D, particularly in HLA-DQ2/8-positive patients. These findings reveal a reversible mechanism for the disorder. Clinical trials.govNCT01094041.