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Association of Folate and Vitamins Involved in the 1-Carbon Cycle with Polymorphisms in the Methylenetetrahydrofolate Reductase Gene (MTHFR) and Global DNA Methylation in Patients with Colorectal Cancer.
Ferrari, A, Torrezan, GT, Carraro, DM, Aguiar Junior, S
Nutrients. 2019;11(6)
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This 2012 cross-sectional observational study examines the role of epigenetic gene expression and methylation in 189 patients with colorectal adenocarcinoma, including 128 with MTHFR polymorphisms. The mean age was 61 years and there was a 50/50 gender split. The focus nutrients were folate, vitamins B2, B6, B12, choline, betaine, and methionine, all of which are known to be essential nutrients for DNA synthesis and more specifically have a key role in the 1-carbon cycle, and S-adenosylmethionine (SAM). The study is based on prospective data collection from food frequency and clinical evaluation questionnaires, and blood work. There does not appear to have been any control group or blinding of processes (at least not reported in the study). The results showed that serum folate levels were positively correlated with the equivalent total dietary folate intake and global DNA methylation. No significant differences were found between serum folate levels in relation to the different genotypes of MTHFR polymorphisms such as C677T. A weak association was found between the A1298C polymorphism and lower levels of methylation. No significant findings were reported for the vitamins used in the study. The study concludes that folate intake, serum folate levels, global DNA methylation and age were predictors of clinicopathological staging.
Abstract
Folate, vitamin B2, vitamin B6, vitamin B12, choline, and betaine are nutrients involved in the 1-carbon cycle that can alter the levels of DNA methylation and influence genesis and/or tumor progression. Thus, the objective of this study was to evaluate the association of folate and vitamins involved in the 1-carbon cycle and MTHFR polymorphisms in global DNA methylation in patients with colorectal cancer gene. The study included 189 patients with colorectal adenocarcinoma answering a clinical evaluation questionnaire and the Food Frequency Questionnaire (FFQ) validated for patients with colon and rectal cancer. Blood samples were collected for evaluation of MTHFR gene polymorphisms in global DNA methylation in blood and in tumor. The values for serum folate were positively correlated with the equivalent total dietary folate (total DFE) (rho = 0.51, p = 0.03) and global DNA methylation (rho = 0.20, p = 0.03). Individuals aged over 61 years (p = 0.01) in clinicopathological staging III and IV (p = 0.01) and with + heterozygous mutated homozygous genotypes for the MTHFR A1298C gene had higher levels of global DNA methylation (p = 0.04). The association between dietary intake of folate, serum folate, and tumor stage were predictive of global DNA methylation in patients' blood. The levels of serum folate, the dietary folate and the status of DNA methylation can influence clinicopathological staging.
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Micronutrient Gaps in Three Commercial Weight-Loss Diet Plans.
G Engel, M, J Kern, H, Brenna, JT, H Mitmesser, S
Nutrients. 2018;10(1)
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Globally, around 39% of adults are overweight and 13% obese, and more than one third of American adults are obese. Being overweight or obese is associated with many chronic conditions, such as heart disease, high blood pressure and type 2 diabetes. Weight loss, even at moderate level, can reduce the risk of these obesity-related chronic conditions. Commercial weight-loss diet plans can vary greatly, not only in energy content but also in macronutrient and micronutrient composition. Most plans restrict calories or certain macronutrients, particularly carbohydrate or fat, and in doing so, often overlook micronutrient, i.e. vitamin and mineral, content. Previous studies have shown that many weight-loss plans do not provide adequate amounts of all micronutrients, and in order to reach the reference daily intakes for various vitamins and minerals, dieters would need to increase their calorie intake significantly and often unrealistically. The authors of this paper analysed seven single-day menus of three select commercial diet plans to determine their micronutrient sufficiency. The diet plans included were Eat to Live-Vegan, Aggressive Weight Loss (ETL-VAWL), Fast Metabolism Diet (FMD), and Eat, Drink and Be Healthy (EDH). ETL-VAWL diet provided less than 90% of recommended amounts for B12, B3, D, E, calcium, selenium and zinc. The FMD diet was low in B1, D, E, calcium, magnesium and potassium, while EDH diet didn’t meet the recommended amounts for vitamin D, calcium and potassium. Even after adjusting all the plans to an intake of 2000 kcal/day, several micronutrients were found to remain inadequate (vitamin B12 in ETL-VAWL, calcium in FMD and EDH and vitamin D in all diets). The authors conclude that, in order to reduce the risk of micronutrient deficiencies, more attention needs to be paid to micronutrient rich foods when designing commercial diet plans. Alternatively, these nutrient gaps should be filled in other ways, e.g. using appropriate dietary supplements.
Abstract
Weight-loss diets restrict intakes of energy and macronutrients but overlook micronutrient profiles. Commercial diet plans may provide insufficient micronutrients. We analyzed nutrient profiles of three plans and compared their micronutrient sufficiency to Dietary Reference Intakes (DRIs) for male U.S. adults. Hypocaloric vegan (Eat to Live-Vegan, Aggressive Weight Loss; ETL-VAWL), high-animal-protein low-carbohydrate (Fast Metabolism Diet; FMD) and weight maintenance (Eat, Drink and Be Healthy; EDH) diets were evaluated. Seven single-day menus were sampled per diet (n = 21 menus, 7 menus/diet) and analyzed for 20 micronutrients with the online nutrient tracker CRON-O-Meter. Without adjustment for energy intake, the ETL-VAWL diet failed to provide 90% of recommended amounts for B12, B₃, D, E, calcium, selenium and zinc. The FMD diet was low (<90% DRI) in B₁, D, E, calcium, magnesium and potassium. The EDH diet met >90% DRIs for all but vitamin D, calcium and potassium. Several micronutrients remained inadequate after adjustment to 2000 kcal/day: vitamin B12 in ETL-VAWL, calcium in FMD and EDH and vitamin D in all diets. Consistent with previous work, micronutrient deficits are prevalent in weight-loss diet plans. Special attention to micronutrient rich foods is required to reduce risk of micronutrient deficiency in design of commercial diets.
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Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment.
Liu, SX, Li, YH, Dai, WK, Li, XS, Qiu, CZ, Ruan, ML, Zou, B, Dong, C, Liu, YH, He, JY, et al
World journal of gastroenterology. 2017;23(48):8570-8581
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This retrospective study investigated the safety and efficacy of faecal microbiota transplantation (FMT) in infants with allergic colitis (AC), which is characterised by severe diarrhoea and haemtochezia (the passing of fresh blood with stools). Out of 19 infants selected for FMT, 17 experienced a remission within 1-2 days and stayed in remission for at least 15 months, although 14 needed more than one FMT to maintain remission. The other two also went into remission but were lost to follow-up within less than one month. The donors included the infants’ mothers or their relatives, or healthy infants. For ten patients, faecal microbiota was analysed before FMT and during follow-ups. Microbiota diversity increased in six and decreased in three patients. Firmicutes (a phylum of bacteria which includes Lactobacilli) were increased in all ten patients, whilst in six of the ten patients Proteobacteria (which include many opportunistic pathogens) decreased after FMT. The authors conclude that there is a positive effect on FMT in the treatment of infantile AC and called for more research.
Abstract
AIM: To investigate the impact of fecal microbiota transplantation (FMT) treatment on allergic colitis (AC) and gut microbiota (GM). METHODS We selected a total of 19 AC infants, who suffered from severe diarrhea/hematochezia, did not relieve completely after routine therapy or cannot adhere to the therapy, and were free from organ congenital malformations and other contraindications for FMT. Qualified donor-derived stools were collected and injected to the AC infants via a rectal tube. Clinical outcomes and follow-up observations were noted. Stools were collected from ten AC infants before and after FMT, and GM composition was assessed for infants and donors using 16S rDNA sequencing analysis. RESULTS After FMT treatment, AC symptoms in 17 infants were relieved within 2 d, and no relapse was observed in the next 15 mo. Clinical improvement was also detected in the other two AC infants who were lost to follow-up. During follow-up, one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16S rDNA analysis in ten AC infants, most of them (n = 6) had greater GM diversity after FMT. As a result, Proteobacteria decreased (n = 6) and Firmicutes increased (n = 10) in post-FMT AC infants. Moreover, Firmicutes accounted for the greatest proportion of GM in the patients. At the genus level, Bacteroides (n = 6), Escherichia (n = 8), and Lactobacillus (n = 4) were enriched in some AC infants after FMT treatment, but the relative abundances of Clostridium (n = 5), Veillonella (n = 7), Streptococcus (n = 6), and Klebsiella (n = 8) decreased dramatically. CONCLUSION FMT is a safe and effective method for treating pediatric patients with AC and restoring GM balance.
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Anti-influenza viral effects of honey in vitro: potent high activity of manuka honey.
Watanabe, K, Rahmasari, R, Matsunaga, A, Haruyama, T, Kobayashi, N
Archives of medical research. 2014;45(5):359-65
Abstract
BACKGROUND AND AIMS Influenza viruses are a serious threat to human health and cause thousands of deaths annually. Thus, there is an urgent requirement for the development of novel anti-influenza virus drugs. Therefore, the aim of this study was to evaluate the anti-influenza viral activity of honey from various sources. METHODS Antiviral activities of honey samples were evaluated using MDCK cells. To elucidate the possible mechanism of action of honey, plaque inhibition assays were used. Synergistic effects of honey with known anti-influenza virus drugs such as zanamivir or oseltamivir were tested. RESULTS Manuka honey efficiently inhibited influenza virus replication (IC50 = 3.6 ± 1.2 mg/mL; CC50 = 82.3 ± 2.2 mg/mL; selective index = 22.9), which is related to its virucidal effects. In the presence of 3.13 mg/mL manuka honey, the IC50 of zanamivir or oseltamivir was reduced to nearly 1/1000th of their single use. CONCLUSIONS Our results showed that honey, in general, and particularly manuka honey, has potent inhibitory activity against the influenza virus, demonstrating a potential medicinal value.
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Celiac disease or non-celiac gluten sensitivity? An approach to clinical differential diagnosis.
Kabbani, TA, Vanga, RR, Leffler, DA, Villafuerte-Galvez, J, Pallav, K, Hansen, J, Mukherjee, R, Dennis, M, Kelly, CP
The American journal of gastroenterology. 2014;109(5):741-6; quiz 747
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Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is challenging, as both conditions respond to a gluten-free diet but present different clinically. At present, an effective diagnostic protocol specific to NCGS is not available. The aim of this review is to develop a diagnostic algorithm to differentiate CD from NCGS. Records of 238 subjects who presented with gluten-responsive symptoms were reviewed. This study resulted in a clinical model for efficient differential diagnosis of CD and NCGS. On the basis of this model, unnecessary endoscopies could have been avoided in over 60% of subjects. This model offers clinicians a stepwise algorithm for diagnosis and management of patients who present with symptoms responsive to gluten exclusion.
Abstract
OBJECTIVES Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is important for appropriate management but is often challenging. METHODS We retrospectively reviewed records from 238 patients who presented for the evaluation of symptoms responsive to gluten restriction without prior diagnosis or exclusion of CD. Demographics, presenting symptoms, serologic, genetic, and histologic data, nutrient deficiencies, personal history of autoimmune diseases, and family history of CD were recorded. NCGS was defined as symptoms responsive to a gluten-free diet (GFD) in the setting of negative celiac serology and duodenal biopsies while on a gluten-containing diet or negative human leukocyte antigen (HLA) DQ2/DQ8 testing. RESULTS Of the 238 study subjects, 101 had CD, 125 had NCGS, 9 had non-celiac enteropathy, and 3 had indeterminate diagnosis. CD subjects presented with symptoms of malabsorption 67.3% of the time compared with 24.8% of the NCGS subjects (P<0.0001). In addition, CD subjects were significantly more likely to have a family history of CD (P=0.004), personal history of autoimmune diseases (P=0.002), or nutrient deficiencies (P<0.0001). The positive likelihood ratio for diagnosis of CD of a >2× upper limit of normal IgA trans-glutaminase antibody (tTG) or IgA/IgG deaminated gliadan peptide antibody (DGP) with clinical response to GFD was 130 (confidence interval (CI): 18.5-918.3). The positive likelihood ratio of the combination of gluten-responsive symptoms and negative IgA tTG or IgA/IgG DGP on a regular diet for NCGS was 9.6 (CI: 5.5-16.9). When individuals with negative IgA tTG or IgA/IgG DGP also lacked symptoms of malabsorption (weight loss, diarrhea, and nutrient deficiencies) and CD risk factors (personal history of autoimmune diseases and family history of CD), the positive likelihood ratio for NCGS increased to 80.9. CONCLUSIONS On the basis of our findings, we have developed a diagnostic algorithm to differentiate CD from NCGS. Subjects with negative celiac serologies (IgA tTG or IgA/IgG DGP) on a regular diet are unlikely to have CD. Those with negative serology who also lack clinical evidence of malabsorption and CD risk factors are highly likely to have NCGS and may not require further testing. Those with equivocal serology should undergo HLA typing to determine the need for biopsy.
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Do existing psychologic scales measure the nonspecific benefit associated with CAM treatment?
Hyland, ME, Lewith, GT, Wheeler, P
Journal of alternative and complementary medicine (New York, N.Y.). 2008;14(2):185-9
Abstract
OBJECTIVE To determine whether existing psychologic well-being scales are sensitive to change after complementary and alternative medicine (CAM) treatment, and whether changes in those scales of well-being correlate with symptom change. This may limit the need for the development of new CAM-specific outcomes. DESIGN A study investigating change on several outcome measures over a 4-month period during CAM treatment. Patients attending the Centre for Complementary and Integrated Medicine (CCIM, Southampton, UK) for their first appointment were recruited and completed their baseline forms (T1) at the first consultation. Three (3) further sets of questionnaires (T2, T3 and T4) were mailed to them with a stamped addressed envelope at monthly intervals and were returned to CCIM. PATIENTS AND LOCATIONS People visiting the CCIM were treated by 1 of 3 practitioners with an individualized combination of homeopathy, dietary advice, and nutritional supplements for treatment of their chronic benign illness. OUTCOME The previously validated outcome measures were as follows: (1) symptoms (Measure Yourself Medical Outcome Profile: MYMOP); (2) mood (Positive and Negative Affect Scale; PANAS); and (3) Brief Assessment of Sense of Coherence (BASOC). RESULTS Forty-five (45) patients were recruited and 40 completed the study; MYMOP (p=0.001), PANAS negative (p=0.025), and BASOC (p=0.019) all showed similar patterns of significant improvement over time; PANAS positive showed a nonsignificant trend for improvement (p=0.074). Change on one scale was correlated with change on other scales. CONCLUSIONS Existing psychology scales of well-being are sensitive to change after CAM treatment and consistent with symptom improvement. Existing measures of positive affect provide an alternative to the negative, symptom-driven approach of conventional medicine.