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Berberine reduces circulating inflammatory mediators in patients with severe COVID-19.
Zhang, BY, Chen, M, Chen, XC, Cao, K, You, Y, Qian, YJ, Yu, WK
The British journal of surgery. 2021;108(1):e9-e11
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Berberine has a long history in traditional Chinese medicine for the treatment of diarrhoea and gastroenteritis owing to its antimicrobial, antimotility and antisecretory properties. The aim of this study was to examine the effect of berberine on laboratory parameters in patients who have been hospitalised due to COVID-19. This study enrolled prospectively 39 patients with severe COVID-19 who were hospitalized, of which 18 patients were allocated to the berberine group and 17 to the control group. Patients in the berberine group were given berberine plus routine therapy within 14 days of admission, and those in the control group received only routine therapy. Results indicate that there wasn’t any significant difference between the two groups in relation to the laboratory parameters namely interleukin-6, tumour necrosis factor-alpha, C-reactive protein, procalcitonin and white blood cells levels within 14 days. In subgroup analyses of patients with diarrhoea, berberine significantly improved the changes in interleukin-6, tumour necrosis factor-alpha and C-reactive protein. Authors conclude that it is unclear whether berberine has any antiviral effect on SARS-CoV-2, and further experiments are needed to clarify this.
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Vegan diet in young children remodels metabolism and challenges the statuses of essential nutrients.
Hovinen, T, Korkalo, L, Freese, R, Skaffari, E, Isohanni, P, Niemi, M, Nevalainen, J, Gylling, H, Zamboni, N, Erkkola, M, et al
EMBO molecular medicine. 2021;13(2):e13492
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As vegan diets gain popularity amongst families, there is little known about the impact of strict plant-based diets on metabolism and micronutrient status in children, apart from reduced average growth within the norm. This small study looked at 40 Finnish children from one day centre, and compared children following an omnivore or vegetarian diet to those raised on a vegan diet. The diets were analysed, and biomarkers and metabolites were measured. The metabolic profile and nutrient status of children who followed a vegan diet from birth were distinctively different to other diet patterns, including vegetarians. The authors suggest that little animal source foods are enough to shift the metabolism of children. Dietary analysis showed that vegan children had higher folate consumption and lower protein and saturated fats intake. Despite intake appearing adequate, serum markers for fat-soluble vitamins A and D were low. While the fatty acid ALA was higher compared to omnivores, DHA and overall cholesterol were decreased. The authors concluded that the bodies own cholesterol production does not seem to compensate for a lack of dietary cholesterol in this case and it remains to be established whether lower cholesterol in vegan children are negative to health. Furthermore, the circulating amino acids pool was decreased in vegan children, particularly branch chained amino acids. The most distinct difference, however, was seen in the variance of bile acid patterns. The physiological functions of bile acids go beyond digestion, yet the consequences of diverging bile acid profiles in children’s health are unknown. In conclusion, the data shows that a strict vegan diet affects the metabolism of healthy children, but much of the long-term impact on health is currently still unclear. This article highlights some of the differences, risks and uncertainties that come with raising young children on a strictly vegan diet.
Abstract
Vegan diets are gaining popularity, also in families with young children. However, the effects of strict plant-based diets on metabolism and micronutrient status of children are unknown. We recruited 40 Finnish children with a median age 3.5 years-vegans, vegetarians, or omnivores from same daycare centers-for a cross-sectional study. They enjoyed nutritionist-planned vegan or omnivore meals in daycare, and the full diets were analyzed with questionnaires and food records. Detailed analysis of serum metabolomics and biomarkers indicated vitamin A insufficiency and border-line sufficient vitamin D in all vegan participants. Their serum total, HDL and LDL cholesterol, essential amino acid, and docosahexaenoic n-3 fatty acid (DHA) levels were markedly low and primary bile acid biosynthesis, and phospholipid balance was distinct from omnivores. Possible combination of low vitamin A and DHA status raise concern for their visual health. Our evidence indicates that (i) vitamin A and D status of vegan children requires special attention; (ii) dietary recommendations for children cannot be extrapolated from adult vegan studies; and (iii) longitudinal studies on infant-onset vegan diets are warranted.
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The Effects of Time-Restricted Eating versus Standard Dietary Advice on Weight, Metabolic Health and the Consumption of Processed Food: A Pragmatic Randomised Controlled Trial in Community-Based Adults.
Phillips, NE, Mareschal, J, Schwab, N, Manoogian, ENC, Borloz, S, Ostinelli, G, Gauthier-Jaques, A, Umwali, S, Gonzalez Rodriguez, E, Aeberli, D, et al
Nutrients. 2021;13(3)
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Metabolic syndrome (MS) is a collection of conditions such as obesity, high blood pressure and impaired ability to balance blood sugars, that increase the sufferers risk of diabetes, stroke, and heart disease. Weight loss and lifestyle modifications are the main recommendations to improve MS. Intermittent fasting is a dietary regime that involves restricting the intake of food to certain times of the day, without restricting calories and has been shown in animal and human studies to result in fat loss and an increased ability to balance blood sugars. This randomised control trial of 218 adults over 6 months aimed to firstly determine relationships between eating duration, unprocessed and processed foods, and lifestyle factors on health and secondly to determine if a 12-hour time restricted eating pattern leads to an improvement in MS. The results showed that higher consumption of processed foods was associated with poorer metabolic health. A 12-hour restricted eating pattern resulted in weight loss, whereas individuals on a standard daily eating pattern did not, however differences between the two groups were not significant. Other measures of metabolic health failed to show any differences between the two groups. It was concluded that a 12-hour restricted eating pattern was feasible over 6 months, however further research is needed to assess if a more restricted time would result in greater weight loss. This study could be used by healthcare professionals to understand that a restricted eating pattern may be of benefit to those with MS, however further research would be needed to determine the optimal timeframe.
Abstract
Weight loss is key to controlling the increasing prevalence of metabolic syndrome (MS) and its components, i.e., central obesity, hypertension, prediabetes and dyslipidaemia. The goals of our study were two-fold. First, we characterised the relationships between eating duration, unprocessed and processed food consumption and metabolic health. During 4 weeks of observation, 213 adults used a smartphone application to record food and drink consumption, which was annotated for food processing levels following the NOVA classification. Low consumption of unprocessed food and low physical activity showed significant associations with multiple MS components. Second, in a pragmatic randomised controlled trial, we compared the metabolic benefits of 12 h time-restricted eating (TRE) to standard dietary advice (SDA) in 54 adults with an eating duration > 14 h and at least one MS component. After 6 months, those randomised to TRE lost 1.6% of initial body weight (SD 2.9, p = 0.01), compared to the absence of weight loss with SDA (-1.1%, SD 3.5, p = 0.19). There was no significant difference in weight loss between TRE and SDA (between-group difference -0.88%, 95% confidence interval -3.1 to 1.3, p = 0.43). Our results show the potential of smartphone records to predict metabolic health and highlight that further research is needed to improve individual responses to TRE such as a shorter eating window or its actual clock time.
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Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.
Kim, CS, Cha, L, Sim, M, Jung, S, Chun, WY, Baik, HW, Shin, DM
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;76(1):32-40
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Aging is characterized by progressive decline in biological functions of the organism. Diet is one of the critical lifestyle factors for physical and mental well-being throughout the life span, including later life. The aim of this study was to investigate the effects of probiotics consumption on intestinal and brain health in elders over the age of 65. This study is a randomised, double-blind, placebo-controlled, multicentre trial. All participants, study coordinators, and researchers were blinded throughout the entire study. Sixty-three participants were randomized, with 31 and 32 subjects in the placebo and probiotics group, respectively. Results demonstrate that probiotics have system-wide effects on the gut–brain axis in healthy community-dwelling older adults by promoting cognitive and mental health and changing the gut microbial composition. Authors conclude that their findings provide evidence that probiotics have health-promoting properties as part of a healthy diet in the general population of independently living older adults.
Abstract
Probiotics have been proposed to ameliorate cognitive impairment and depressive disorder via the gut-brain axis in patients and experimental animal models. However, the beneficial role of probiotics in brain functions of healthy older adults remains unclear. Therefore, a randomized, double-blind, and placebo-controlled multicenter trial was conducted to determine the effects of probiotics on cognition and mood in community-dwelling older adults. Sixty-three healthy elders (≥65 years) consumed either placebo or probiotics containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 12 weeks. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Brain functions were measured using the Consortium to Establish a Registry for Alzheimer's disease, Satisfaction with life scale, stress questionnaire, Geriatric depression scale, and Positive affect and negative affect schedule. Blood brain-derived neurotrophic factor (BDNF) was determined using enzyme-linked immunosorbent assay. Relative abundance of inflammation-causing gut bacteria was significantly reduced at Week 12 in the probiotics group (p < .05). The probiotics group showed greater improvement in mental flexibility test and stress score than the placebo group (p < .05). Contrary to placebo, probiotics significantly increased serum BDNF level (p < .05). Notably, the gut microbes significantly shifted by probiotics (Eubacterium and Clostridiales) showed significant negative correlation with serum BDNF level only in the probiotics group (RS = -0.37, RS = -0.39, p < .05). In conclusion, probiotics promote mental flexibility and alleviate stress in healthy older adults, along with causing changes in gut microbiota. These results provide evidence supporting health-promoting properties of probiotics as a part of healthy diet in the older adults.
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The Effects of Dairy Product and Dairy Protein Intake on Inflammation: A Systematic Review of the Literature.
Nieman, KM, Anderson, BD, Cifelli, CJ
Journal of the American College of Nutrition. 2021;40(6):571-582
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Systemic inflammation contributes to the risk and progression of chronic disease, which is in turn influenced by several factors including diet. The aim of this study was to conduct a systematic review to evaluate the effect of dairy products and dairy protein on markers of inflammation in adults that do not have inflammatory-related disorders. The authors analysed 27 previous randomised controlled trial, of which 19 looked at dairy products, and eight looked at dairy protein (casein or whey). In the trials which evaluated dairy products, 10 reported no effect of the intervention, while eight reported a reduction in at least one biomarker of inflammation. All eight trials that investigated dairy protein intake on markers of inflammation reported no effect. The researchers concluded that the available literature suggests that dairy products and dairy proteins have neutral to beneficial effects on biomarkers of inflammation. Additional clinical studies designed using inflammatory biomarkers as the primary outcome are needed to fully understand the effects of dairy intake on inflammation.
Abstract
Systemic inflammation is associated with obesity and chronic disease risk. Intake of dairy foods is associated with reduced risk of type 2 diabetes and cardiovascular disease; however, the impact of dairy foods on inflammation is not well-established. The objective of this study was to conduct a systematic review to evaluate the effect of dairy product (milk, cheese, and yogurt) and dairy protein consumption on low-grade systemic inflammation in adults without severe inflammatory disorders. A literature search was completed in September 2019 using PubMed and CENTRAL as well as inspection of reference lists from relevant review articles. The search resulted in the identification of 27 randomized controlled trials which were included in this analysis. In the 19 trials which evaluated dairy products, 10 reported no effect of the intervention, while 8 reported a reduction in at least one biomarker of inflammation. All 8 trials that investigated dairy protein intake on markers of inflammation reported no effect of the intervention. The available literature suggests that dairy products and dairy proteins have neutral to beneficial effects on biomarkers of inflammation. Additional clinical studies designed using inflammatory biomarkers as the primary outcome are needed to fully elucidate the effects of dairy intake on inflammation.
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Safety and efficacy of alpha-lipoic acid oral supplementation in the reduction of pain with unknown etiology: A monocentric, randomized, double-blind, placebo-controlled clinical trial.
Esposito, C, Ugo Garzarella, E, Santarcangelo, C, Di Minno, A, Dacrema, M, Sacchi, R, Piccinocchi, G, Piccinocchi, R, Daglia, M
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;144:112308
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The management of pain with no apparent cause, or idiopathic pain, is a real challenge. In the absence of any underlying disease that is treatable, idiopathic pain is usually addressed by relieving symptomatic pain with medication. Whereby these medications can be fast and effective, they can have limited benefits and, in some cases, considerable side effects. Alpha-lipoic acid (ALA) is a food supplement and naturally occurring compound in humans, animals and plants. Previous research suggested that it is effective in managing diabetic nerve pain. As reactive oxygen species and antioxidants appear to play a role in pain regulation, the antioxidant and anti-inflammatory activities of ALA are of interest here. In addition, ALA has a strong safety record. This study sought to investigate the safety and effectiveness of ALA in non-diabetic individuals who were diagnosed with idiopathic pain. 210 male and female subjects, from age 18-75, who were non-diabetic and on no pain medication were randomly assigned to receive either a placebo or 400 mg/day or 800 mg/day of ALA over a course of two months. The pain was tracked with two pain scoring questionnaires, whilst blood samples were monitored for adverse effects, including blood sugar, kidney and liver markers. The ALA intervention group showed a significant reduction in both pain scores compared to placebo. Treated subjects showed a marginal decrease in blood sugars of no clinical significance and no other adverse effects were reported. The authors concluded that ALA as a food supplement has suitable potential for the management of idiopathic pain. And given its safety and efficacy compared to commonly used pain medication it could be of interest in clinical application.
Abstract
INTRODUCTION Extensive evidence suggests that alpha-lipoic acid (ALA) is effective in diabetic neuropathy pain management. However, little is known on its safety and efficacy in reducing idiopathic pain in normoglycemic subjects. The aim of this study was to evaluate ALA food supplement safety and efficacy in the reduction of different forms of idiopathic pain. METHODS Two-hundred and ten normoglycemic adults suffering from idiopathic pain (i.e. 57 subjects with primitive neuropathic pain, 141 subjects with arthralgia with unknown etiology, and 12 subjects with idiopathic myalgia) were randomized to receive placebo, 400 mg/day, or 800 mg/day of ALA. Participants underwent two visits (at baseline = t0, and after 2 months = t1) in which two validated questionaries for pain (numerical rating scale [NRS] and visual analogue scale [VAS]) were collected; fasting blood glucose assessment, adverse effects, and renal and hepatic toxicity were also monitored. RESULTS At t1, none of subjects treated with ALA reported a decreased glycemia or adverse effects. The treated subjects showed a significant reduction in NRS (p < 0.001) while the placebo group did not show any NRS reduction (p = 0.86). Similar results were also obtained for VAS. Statistical analysis aimed at detecting possible differences in NRS and VAS scores among treatment groups based on the source of pain did not reveal any significant effect. CONCLUSIONS Since the management of idiopathic pain is challenging for physicians, the use of ALA food supplements could be a feasible option, based on its safety and efficacy compared to commonly-used analgesic drugs.
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Igg Food Antibody Guided Elimination-Rotation Diet Was More Effective than FODMAP Diet and Control Diet in the Treatment of Women with Mixed IBS-Results from an Open Label Study.
Ostrowska, L, Wasiluk, D, Lieners, CFJ, Gałęcka, M, Bartnicka, A, Tveiten, D
Journal of clinical medicine. 2021;10(19)
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IBS, also known as irritable bowel syndrome, is a debilitating condition characterised by abdominal pain, irregular bowel movements, and changes in the consistency of stool. Symptoms of IBS may appear shortly after eating a meal. Excluding foods high in FODMAP carbohydrates, such as fermentable oligo- and di-saccharides, mono- and disaccharides, and polyols, or following an elimination rotation diet to reduce IgG-dependent food hypersensitivity, which has been shown to improve IBS symptoms previously. The purpose of this open-label study is to investigate the effectiveness of a low-FODMAPS diet and an elimination rotation diet based on IgG as well as a control diet in reducing symptoms of IBS. During the eight-week study, 73 female subjects with a mix of IBS were assigned to either of the three dietary treatments. Compared to the other diet groups, the IgG based elimination rotation diet group showed a significant improvement in the IBS symptoms and comorbid symptoms after the intervention period. In order to determine whether IgG-mediated food hypersensitivity plays a role in IBS and the efficacy of an IgG-dependent elimination rotation diet in the general population, further robust research is required. Healthcare professionals, however, can make use of these results to gain a better understanding of how an IgG based elimination diet tailored to each individual can improve IBS symptoms.
Expert Review
Conflicts of interest:
None
Take Home Message:
- After implementing the three diets, among patients with IBS-M, a statistically significant reduction of the frequency of the idiopathic abdominal pain, abdominal pain after a meal, abdominal pain during defecation, and sensation of incomplete defecation before and after the diet plans, were only found in Group 2.
- Significantly, only in the Group 2 IgG based elimination-rotation-diet was there a high decrease or complete disappearance of dyspeptic IBS symptoms and co-morbidities together with IBS symptoms.
- This study shows that a personalised dietary approach is more effective in treating IBS than generalised diet recommendations, with elimination diets focused on IgG antibodies providing the best results.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Science supports the use of a low-FODMAP diet for symptom relief of IBS. However, more recently evidence suggests that IBS is a low-grade inflammatory disease that may result from or lead to IgG-dependent food hyper-sensitivities.
This study compared the effectiveness of three dietary treatment plans in 73 female patients diagnosed with mixed-form IBS based on Rome III criteria and no other gastrointestinal condition over 8 weeks.
The 3 dietary groups were:
- Group 1-low FODMAP diet
- Group 2- IgG based elimination-rotation-diet
- Group 3-control diet (control group)
Diets of G1 and G2 were determined individually by a dietitian, based on low-FODMAP dietary information and results from IgG food sensitivity testing respectively. Group 3 received nutrition advice from a gastroenterologist.
In G1, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). Gurgling sensation and gastric fullness also reach statistical significance in G1.
IBS symptoms as well as co-morbid symptoms significantly improved or disappeared completely in G2 (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008; sensation of incomplete defecation p = 0.001; difficulty to defecate (constipation) p = 0.002; bloating p = < 0.001; gurgling sensation < 0.001; gastric fullness p = < 0.001. However, blood and mucus in the stool were impossible to test because the symptoms were not reported by any patient during the 2nd examination). (p-values less than 0.05 were considered statistically significant).
In group G3 no statistically significant improvements were seen in any measure.
Based on the results of this open-label study, it was concluded that personalised dietary interventions were more effective in the treatment of IBS-M patients than generalised diet recommendations. Dietary elimination based on IgG food sensitivity test results had the greatest impact on IBS and related symptoms.This study supports results from other studies showing an IgG-guided diet as an effective strategy in co-morbid conditions such as fatigue, headache/migraine, and skin conditions.
Conflicts of Interest
C.F.J.L., M.G. and A.B. are employees of the Institute of Microecology in Poznan ,where the ImuPro tests were determined. D.T. is the Head of Laboratory and shareholder of Lab1, offering ImuPro tests in Norway.
Clinical practice applications:
- Low FODMAP diets studies (NICE) showed GI improvements for abdominal pain, abdominal cramps, diarrhoea, gas, and bloating, largely because FODMAPs mainly cause an excessive production of gas, leading to discomfort and pain and an increased osmotic effect leading to increased bowel movement and diarrhoea. However 30% of patients still suffered from bloating on the FODMAP diet. Gurgling sensation decreased from 65% to 15%, and gastric fullness decreased from 58% to 11% in the patients on the low FODMAP diet.
- A potential new approach to resolve functional symptoms of gastrointestinal conditions could be to start with an IgG-guided elimination diet, as it was proven to be the more effective diet in this open study, and in cases of persistent symptoms, it could be combined with a low-FODMAP diet.
- Calprotectin is currently one of the best-known diagnostic markers indicating mucosa inflammation and changes in the inflammation intensity. In this study serious intestinal inflammation was diagnosed at the faecal calprotectin concentration of >50 mg/kg of stool. During the first examination, no statistically significant differences were found in calprotectin concentrations between the compared groups of patients, and the values were low, suggesting that the included patients suffered from low-grade inflammation and were suitable for diet alteration as the best choice of treatment.
Limitations:
- The main limitations of this study are the open-labeled nature, the low number of participants and the bias of only including female participants with only the patients in the G2 group tested for IgG food antibodies.
- Foods consumed by the patients before they entered the study were not ascertained.
Considerations for future research:
- Claims that IgG food antibodies only reveal exposure to food and not intolerance should be reinvestigated in larger double-blinded studies.
Abstract
Irritable bowel syndrome (IBS) is a chronic disease with recurrent abdominal pain, disturbed bowel emptying, and changes in stool consistency. We compared the effectiveness of three different dietary treatment plans (G1-FM-low FODMAP diet, G2-IP IgG based elimination-rotation-diet, and as control group, the G3-K control diet recommended by an attending gastroenterologist) in treating patients diagnosed with mixed irritable bowel syndrome. A total of seventy-three female patients diagnosed with a mixed form of irritable bowel syndrome (IBS-M) were enrolled in the study. The diet of each patient in Group 1 (G1-FM) and 2 (G2-IP) was determined individually during a meeting with a dietitian. Patients from Group 3 (G3-K) received nutrition advice from a gastroenterologist. Significant differences in the reduction of IBS symptoms were found between the groups. IBS symptoms as well as comorbid symptoms significantly improved or disappeared completely in the G2-IP group (idiopathic abdominal pain, p < 0.001; abdominal pain after a meal, p < 0.001; abdominal pain during defecation, p = 0.008), while in the G1-FM group, some of the IBS symptoms significantly improved (mucus in stool, p = 0.031; bloating, p < 0.001). In group G3-K no significant improvement was seen. Based on the results of this open-label study, it was concluded that various dietary interventions in the treatment of IBS-M patients do not uniformly affect the course and outcomes of disease management. Rotation diets based on IgG show significantly better results compared to other diets.
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Oral birch pollen immunotherapy with apples: Results of a phase II clinical pilot study.
Nothegger, B, Reider, N, Covaciu, CE, Cova, V, Ahammer, L, Eidelpes, R, Unterhauser, J, Platzgummer, S, Raffeiner, E, Tollinger, M, et al
Immunity, inflammation and disease. 2021;9(2):503-511
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The prevalence of birch pollen allergy (BPA) has increased in recent years and has led to a rise in birch pollen-related food allergy (prFA). The current immunotherapy approach for BPA is to use birch pollen extract to attenuate the allergic response. While it has been successful for BPA, it has shown little to no effect on prFA, illuminating a current gap in the research. The aim of this pilot study was to assess the clinical efficacy of immunotherapy by daily apple consumption in developing permanent oral tolerance to apples and simultaneously to birch‐pollen. Sixteen participants consumed apples daily over an eight month period. Various allergy responses were measured during the peak birch pollen season. The results demonstrated continuous consumption of apples by BPA patients with prFA to apples could both improve prFA and birch-pollen induced allergic reactions. Based on these results, the authors conclude that oral immunotherapy with fresh apples is feasible and safe for the treatment of both BPA and birch prFA. As this was a small pilot study, a larger controlled trial is needed to confirm the potential of this treatment option in the clinical setting.
Abstract
BACKGROUND Seventy percent of patients suffering from birch pollen allergy (BPA) develop a pollen-related food allergy (prFA), especially to apples, due to a clinically relevant cross-reactivity between the major allergen in birch Bet v 1 and Mal d 1 in apples. Therefore allergen-specific immunotherapy with fresh apples (AITA) could be a promising natural treatment of both BPA and prFA. OBJECTIVE To assess the clinical efficacy of immunotherapy by daily apple consumption for patients with BPA and prFA. METHODS A daily defined increasing amount of selected cultivars (Red Moon®, Pink Lady®, Topaz, Golden Delicious) was continuously consumed by 16 patients (12 female; median age; 50; range, 23-68 years), leading to increased intake of allergen over a period of at least 8 months. Specific IgE and IgG4 to Bet v 1 and Mal d 1, conjunctival and oral provocation tests, skin reactivity, and the average daily rhinoconjunctivitis combined symptom and medication score (CSMS) were measured during the peak birch pollen season. RESULTS After 8 months of therapy, patients showed increased tolerance to apples (p < .001) and a decreased skin reactivity to apples. Oral allergy syndrome to other birch prFA than apple also decreased (p < .05). Moreover, daily rhinoconjunctivitis CSMS declined by 34% (p < .001), as did conjunctival reactivity to birch pollen extract by 27% (p < .01), while specific IgG4 to Mal d 1 and Bet v 1 increased (p < .01).
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Persistent Anti-Borrelia IgM Antibodies without Lyme Borreliosis in the Clinical and Immunological Context.
Markowicz, M, Reiter, M, Gamper, J, Stanek, G, Stockinger, H
Microbiology spectrum. 2021;9(3):e0102021
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Borrelia burgdorferi (BD) specific Immunoglobulin (Ig) antibodies are a diagnostic key for infection and Lyme’s disease. Generally, IgM is reflective of recent infection and converts to IgG after several weeks during disease progression or inadequate treatment. Yet, in the early phase of infection, not all cases present with antibodies and at the same time, both IgM and IgG can persist in healthy people after tick exposure or treatment. This study sought to investigate further the common phenomenon of persistence of IgM, regardless of symptomatic BD infection. The study examined the serum of 59 predominantly female patients, that showed persistent IgM antibodies in the absence of IgG. The majority of subjects experienced non-specific symptoms, and half of them had a history of antibiotic treatment, yet IgM persisted. The observation went on for >6 months, thus excluding the likelihood of any acute infection. The results showed that in people with lower IgM count a greater improvement of non-specific symptoms was observed as opposed to those with higher IgM count. Furthermore, the assay identified multiple cross-reactivity patterns from other plants, bacteria and human tissue to the antigen-binding receptor OspC typically used for BD testing. The authors postulate that the phenomena of IgM persistence potentially originates from a previous infection with BD, but may be maintained in some individuals by continuous stimulation with cross-reactive antigens from other sources. This is important knowledge for the interpretation and improvement of testing for BD. Of clinical interest here is that IgM persistence, beyond the acute phase, maybe no longer be reflective of the original BD infection. And in such cases, non-specific symptoms may be sustained by other triggers such as foods, other microorganisms and autoimmunity.
Abstract
The aim of the study was to investigate the etiology of persistent IgM antibodies against Borrelia burgdorferi sensu lato (sl) and to analyze their association with nonspecific symptoms. The study group comprised individuals with persistent IgM antibodies in the absence of IgG. The relation between ELISA values and time elapsed since past erythema migrans (EM) was analyzed. Previous antibiotic treatments were assessed. The association between persistent IgM and nonspecific symptoms was evaluated statistically. Specificity of IgM antibodies for outer surface protein C (OspC) of B. burgdorferi sl was examined by immunoblotting. Further, we investigated the cross-reactivity with Borrelia-unrelated proteins. Fifty-nine patients (46 women; 78%) were included in the study group. The mean IgM-ELISA values did not change significantly during follow-up (median 6.2 months). The mean ELISA value in the study group was dependent on time elapsed since past EM. Nonspecific symptoms improved significantly more often in patients with lower IgM ELISA results. Persistent IgM antibodies were specific for the C-terminal PKKP motif of OspC. Cross-reacting C-terminal PKKP antigens from both human and prokaryotic origins were identified. We demonstrate that the C-terminal PKKP motif plays a main role for the reactivity of persistent Borrelia IgM toward OspC. However, cross-reactivity to other eukaryotic and/or prokaryotic antigens may hamper the specificity of OspC in the serological diagnosis of Lyme borreliosis. Lack of improvement of nonspecific symptoms was associated with higher IgM ELISA values. IMPORTANCE The reactivity of human IgM with the outer surface protein C (OspC) of Borrelia burgdorferi sensu lato is frequently used to detect Borrelia specific IgM in commercial immunoassays, and such antibodies usually occur in the early phase of the infection. We identified a group of individuals with persistent Borrelia IgM without symptoms of Lyme borreliosis. We used their sera to demonstrate that the C-terminal epitope of OspC binds the IgM. Strikingly, we found that the same epitope occurs also in certain proteins of human and environmental origin; the latter include other bacteria and food plants. Our experimental data show that these Borrelia-unrelated proteins cross-react with the OpsC-specific IgM. This knowledge is important for the development of serologic assays for Lyme borreliosis and provides a cross-reactive explanation for the persistence of Borrelia-IgM.
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Association of Migraine with Its Comorbidities and Food Specific Immunoglobulin G Antibodies and Inflammatory Cytokines: Cross-Sectional Clinical Research.
Zhao, Z, Jin, H, Yin, Y, Hou, Y, Wang, J, Tang, C, Fu, J
Journal of pain research. 2021;14:2359-2368
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Migraine is a chronic, multifactorial headache with multiple comorbid conditions. Previous studies have shown a correlation between food-specific IgG antibodies and chronic inflammation in migraineurs. IgG antibody detection may therefore be a biomarker for migraine since it plays a crucial role in the pathogenesis of the disease. This cross-sectional clinical trial investigated the relationship between IgG antibodies against food antigens and headaches, gastrointestinal symptoms, anxiety, depression, sleep disorders, dermatosis and inflammatory cytokines such as IL-6, TNFα, and IL-10. In this study, migraine patients who had positive food-specific IgG antibodies had severe migraine, anxiety, gastrointestinal symptoms, and elevated levels of proinflammatory cytokines such as IL-6 and TNFα, indicating a causal relationship. However, further studies are required to determine the immune reaction to food antigens and the effect of eliminating IgG positive foods on migraine and its associated comorbidities. Nevertheless, this study can help healthcare professionals understand how food-specific antibodies play a role in diagnosing and treating migraine.
Abstract
PURPOSE The relationship between food allergy caused by food specific IgG antibodies and migraine has received increased attention in recent years. Here, we aimed to evaluate the effects of food specific IgG antibodies on headache, gastrointestinal symptoms, anxiety, depression, sleep disorders, dermatosis, and serum inflammatory cytokines in migraine patients, and to quantitatively assess the effect of IgG levels on the severity of headache and its comorbidities. METHODS Of 89 migraine patients, those who had one or more food specific IgG antibodies ≥50 U/mL were classified into the IgG positive group, which was then further divided into subgroups based on differing numbers of food allergens. All other subjects were classified into the IgG negative group. We compared the frequency and severity of migraine, anxiety, depression, sleep disorders, dermatosis, and inflammatory cytokines between groups. A regression model was performed to further assess the effect of overall positive IgG concentration and the mediation effect of inflammatory cytokines. RESULTS Participants in the positive IgG group (n = 67) were more likely to have longer time elapsed since diagnosis, more frequent and severe migraine, a higher risk of developing anxiety and gastrointestinal symptoms, along with higher IL-6 and TNF-α. Subgroups with more food allergens generally had worse conditions as well. After adjusting for the inflammatory cytokines, the effect of IgG was reduced. CONCLUSION Migraine patients with positive food specific IgG antibodies had worse migraine, anxiety, and gastrointestinal symptoms. Inflammatory cytokines partially mediate the causal pathway between food specific IgG antibodies, migraine, and migraine comorbidities.