1.
Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: An observational cohort study.
Lionetto, L, Ulivieri, M, Capi, M, De Bernardini, D, Fazio, F, Petrucca, A, Pomes, LM, De Luca, O, Gentile, G, Casolla, B, et al
Biochimica et biophysica acta. Molecular basis of disease. 2021;1867(3):166042
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Covid-19 infection may alter the immune system, but exactly how is still unclear. A key pathway in the regulation of the immune system is the kynurenine pathway of tryptopham. This observational cohort study aimed to determine how this pathway was affected following infection with Covid-19. The results showed that compared to healthy patients, individuals who tested positive to Covid-19 had an increased ratio of kynurenine:tryptopham and the increase was more pronounced in those who had severe infection and if they were male. It was concluded that the kynurenin:tryptopham ratio could be used as a marker for disease severity and useful for treatments. This study could be used by healthcare professionals to use the kynurenine:tryptopham ratio as a marker for disease severity and stratify patients accordingly for treatments.
Abstract
Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention.
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Effects of Periodic Fasting on Fatty Liver Index-A Prospective Observational Study.
Drinda, S, Grundler, F, Neumann, T, Lehmann, T, Steckhan, N, Michalsen, A, Wilhelmi de Toledo, F
Nutrients. 2019;11(11)
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Non-alcoholic fatty liver disease (NAFLD) comprises a number of liver disorders and is thought to have a prevalence of 20% in industrialised countries. NAFLD has been associated with dietary excess of saturated fatty acids, refined carbohydrates, and fructose. This prospective observational study evaluated the effects of periodic fasting on the fatty liver index (FLI), a combination of waist circumference, body mass index (BMI) and biochemical characteristics, which has been shown to closely correlate to magnetic resonance imaging (MRI) results, the gold standard for NAFLD diagnosis. 697 subjects fasted for 6-38 days (mean 8.5 days) in a clinical setting, whilst also engaging in an exercise programme, mindfulness and relaxation. Study subjects included both non-diabetics and type 2 diabetics. There were significant decreases in FLI, weight, BMI and waist circumference, as well as improvements in a number of metabolic blood parameters, in both diabetics and non-diabetics. There were no serious side effects and the intervention was well tolerated. The authors conclude that periodic fasting is an easily realisable, well-tolerated, non-pharmaceutical intervention, which effectively reduces the FLI.
Abstract
This prospective observational trial investigated effects and safety of periodic fasting in subjects with and without type 2 diabetes mellitus (T2DM). The primary end point was set as the change of fatty liver index (FLI) as a surrogate parameter of non-alcoholic fatty liver disease (NAFLD). Six-hundred and ninety-seven subjects (38 with T2DM) were enrolled. A baseline FLI ≥ 60 (the threshold for fatty liver) was found in 264 subjects (37.9%). The mean duration of fasting was 8.5 ± 4.0 days (range 6-38). FLI decreased significantly (-14.02 ± 11.67; p < 0.0001), with a larger effect in individuals with T2DM (-19.15 ± 11.0; p < 0.0001; p = 0.002 compared to non-diabetic subjects). Body mass index (BMI) decreased by -1.51 ± 0.82 kg/m2, and 49.9% of the subjects lost ≥5% body weight. After fasting, nearly half of the 264 subjects with FLI ≥ 60 (highest risk category) shifted to a lower category. The improvement of FLI correlated with the number of fasting days (r = -0.20, p < 0.0001) and with the magnitude of BMI reduction (r = 0.14, p = 0.0001). Periodic fasting with concomitant weight reduction leads to significant rapid improvement of FLI in subjects with and without T2DM.
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Effect of Weight Loss after Bariatric Surgery on Thyroid-Stimulating Hormone Levels in Euthyroid Patients with Morbid Obesity.
Juiz-Valiña, P, Outeiriño-Blanco, E, Pértega, S, Varela-Rodriguez, BM, García-Brao, MJ, Mena, E, Pena-Bello, L, Cordido, M, Sangiao-Alvarellos, S, Cordido, F
Nutrients. 2019;11(5)
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Obesity is associated with many health issues, including thyroid problems. The aim of this observational study was to investigate the effect of weight loss surgery on thyroid hormones. 129 morbidly obese people with normal thyroid function were included in the study. 12 months after weight loss surgery, the levels of thyroid stimulating hormone (TSH) had significantly decreased from 3.3 to 2.1 µU/mL. Levels of the thyroid hormone free thyroxine (T4) also significantly decreased from 1.47 to 1.12 ng/dL. Those that lost more weight following surgery tended to have a greater reduction in TSH. Fasting blood glucose also significantly improved after surgery. The authors concluded that obesity is associated with raised TSH levels, and this makes diagnosing thyroid problems in people with morbid obesity more complicated.
Abstract
Obesity is associated with several endocrine abnormalities, including thyroid dysfunction. The objective of this study was to investigate the effect of weight loss after bariatric surgery on thyroid-stimulating hormone (TSH) levels in euthyroid patients with morbid obesity. We performed an observational study, evaluating patients with morbid obesity submitted to bariatric surgery. We included 129 patients (92 women) and 31 controls (21 women). Clinical, anthropometric, biochemical, and hormonal parameters were evaluated. The primary endpoint was circulating TSH (µU/mL). Fasting TSH levels were higher in the obese group (3.3 ± 0.2) than in the control group (2.1 ± 0.2). The mean excessive body mass index (BMI) loss (EBMIL) 12 months after bariatric surgery was 72.7 ± 2.1%. TSH levels significantly decreased in the obese patients after surgery; 3.3 ± 0.2 vs. 2.1 ± 0.2 before and 12 months after surgery, respectively. Free thyroxine (T4) (ng/dL) levels significantly decreased in the obese patients after surgery; 1.47 ± 0.02 vs. 1.12 ± 0.02 before and 12 months after surgery, respectively. TSH decreased significantly over time, and the decrement was associated with the EBMIL. In euthyroid patients with morbid obesity, weight loss induced by bariatric surgery promotes a significant decline of the increased TSH levels. This decrement of TSH is progressive over time after surgery and significantly associated with excess BMI loss.
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Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis.
Rao, SSC, Rehman, A, Yu, S, Andino, NM
Clinical and translational gastroenterology. 2018;9(6):162
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D-lactic acid is produced by intestinal bacteria and a rise in levels can lead to D-lactic acidosis, causing neurological changes such as slurred speech and gait disturbances. This is frequently observed in short bowel syndrome. This small, observational study aimed to determine if brain fogginess (mental confusion, impaired judgement, poor short-term memory and difficulty concentrating) and intestinal gas and bloating is associated with D-lactic acidosis and small intestinal bacterial overgrowth (SIBO). 38 patients presenting with gas and bloating in the absence of short bowel syndrome, and with or without brain fog were assessed. All patients with brain fog were consuming probiotics, with a higher proportion of them diagnosed with SIBO and D-lactic acidosis, when compared to the non-brain fog group. The researchers stopped probiotics in all patients and administered antibiotics, observing a significant reduction in brain fog and gastrointestinal symptoms. Whilst this is a small, observational study, nutrition practitioners may wish to assess the likelihood of SIBO and D-lactic acidosis before recommending probiotics, especially in the presence of brain fog.
Abstract
BACKGROUND D-lactic acidosis is characterized by brain fogginess (BF) and elevated D-lactate and occurs in short bowel syndrome. Whether it occurs in patients with an intact gut and unexplained gas and bloating is unknown. We aimed to determine if BF, gas and bloating is associated with D-lactic acidosis and small intestinal bacterial overgrowth (SIBO). METHODS Patients with gas, bloating, BF, intact gut, and negative endoscopic and radiological tests, and those without BF were evaluated. SIBO was assessed with glucose breath test (GBT) and duodenal aspiration/culture. Metabolic assessments included urinary D-lactic acid and blood L-lactic acid, and ammonia levels. Bowel symptoms, and gastrointestinal transit were assessed. RESULTS Thirty patients with BF and 8 without BF were evaluated. Abdominal bloating, pain, distension and gas were the most severe symptoms and their prevalence was similar between groups. In BF group, all consumed probiotics. SIBO was more prevalent in BF than non-BF group (68 vs. 28%, p = 0.05). D-lactic acidosis was more prevalent in BF compared to non-BF group (77 vs. 25%, p = 0.006). BF was reproduced in 20/30 (66%) patients. Gastrointestinal transit was slow in 10/30 (33%) patients with BF and 2/8 (25%) without. Other metabolic tests were unremarkable. After discontinuation of probiotics and a course of antibiotics, BF resolved and gastrointestinal symptoms improved significantly (p = 0.005) in 23/30 (77%). CONCLUSIONS We describe a syndrome of BF, gas and bloating, possibly related to probiotic use, SIBO, and D-lactic acidosis in a cohort without short bowel. Patients with BF exhibited higher prevalence of SIBO and D-lactic acidosis. Symptoms improved with antibiotics and stopping probiotics. Clinicians should recognize and treat this condition.