Impact of modified short-term fasting and its combination with a fasting supportive diet during chemotherapy on the incidence and severity of chemotherapy-induced toxicities in cancer patients - a controlled cross-over pilot study.

BACKGROUND: This pilot trial aimed to investigate whether modified short-term fasting (mSTF) reduces the incidence of chemotherapy-induced toxicities and whether an initial ketogenic diet (KD) as fasting supportive diet reduces fasting-related discomfort and improves the compliance. METHODS: In this controlled cross-over trial, gynaecologic cancer patients undergoing chemotherapy with a minimum of 4 cycles fasted for 96 h during half of their chemotherapy cycles and consumed a normocaloric diet during the other chemotherapy cycles. The caloric intake during mSTF was restricted to 25% of each patient's daily requirement. In addition, half of the patients should eat a 6-day normocaloric KD prior to each mSTF period to investigate a KD's hunger-suppression effect. Chemotherapy-induced toxicities, fasting-related discomfort, body composition, quality of life, laboratory values, and compliance were assessed at each chemotherapy. RESULTS: Thirty patients aged 30-74 years (median 54 years) completed the study. During mSTF the frequency and severity score of stomatitis [- 0.16 ± 0.06; 95% CI -0.28 - (- 0.03); P = 0.013], headaches [- 1.80 ± 0.55; 95% CI -2.89 - (- 0.71); P = 0.002], weakness [- 1.99 ± 0.87; 95% CI -3.72 - (- 0.26); P = 0.024] and the total toxicities' score were significantly reduced [- 10.36 ± 4.44; 95% CI -19.22 - (- 1.50); P = 0.023]. We also observed significantly fewer chemotherapy postponements post-mSTF, reflecting improved tolerance of chemotherapy [- 0.80 ± 0.37; 95% CI -1.53 - (- 0.06); P = 0.034]. A significant reduction in mean body weight by - 0.79 ± 1.47 kg during mSTF was not compensated and remained until study's conclusion (P < 0.005). On average, Insulin [- 169.4 ± 44.1; 95% CI -257.1 - (- 81.8); P < 0.001] and Insulin-like growth factor 1 levels [- 33.3 ± 5.4; 95% CI -44.1 - (- 22.5); P < 0.001] dropped significantly during fasting. The KD as a fasting supportive diet neither reduced fasting-related discomfort nor improved compliance of our fasting regimen. CONCLUSION: MSTF is safe and feasible in gynaecologic cancer patients. Our results indicate that mSTF during chemotherapy can reduce chemotherapy-induced toxicities and enhance the tolerance of chemotherapy. Larger clinical trials are required to recommend mSTF for cancer patients. TRIAL REGISTRATION: germanctr.de: DRKS00011610, registered 30 January, 2017.

Effect of Ultraviolet Light-Exposed Mushrooms on Vitamin D Status: Liquid Chromatography-Tandem Mass Spectrometry Reanalysis of Biobanked Sera from a Randomized Controlled Trial and a Systematic Review plus Meta-Analysis.

BACKGROUND: Randomized controlled trial (RCT) data on the response of serum total 25-hydroxyvitamin D [25(OH)D] in healthy participants consuming UV light-exposed edible mushrooms are limited and mixed. OBJECTIVE: The objective was to undertake a systematic review and meta-analysis of responses of serum 25(OH)D [and serum 25-hydroxyergocalciferol, 25(OH)D2, and serum 25-hydroxycholecalciferol, 25(OH)D3, if available] to consumption of UV-exposed mushrooms by healthy participants. Biobanked sera from one RCT (originally analyzed by immunoassay) were reanalyzed by LC-MS/MS to generate serum 25(OH)D2 and serum 25(OH)D3 data. METHODS: Ovid MEDLINE, EMBASE, and Cochrane CENTRAL were searched for RCTs of UV-exposed mushrooms and data on serum 25(OH)D. Studies were screened for eligibility, and relevant data were extracted. Serum 25(OH)D data were re-analyzed by ANOVA and paired t tests. RESULTS: Our structured search yielded 6 RCTs meeting our inclusion criteria. Meta-analysis of all 6 RCTs showed serum 25(OH)D was not significantly increased (P = 0.12) by UV-exposed mushrooms, but there was high heterogeneity (I(2) = 87%). Including only the 3 European-based RCTs [mean baseline 25(OH)D, 38.6 nmol/L], serum 25(OH)D was increased significantly by UV-exposed mushrooms [weighted mean difference (WMD): 15.2 nmol/L; 95% CI: 1.5, 28.8 nmol/L, P = 0.03, I(2) = 88%], whereas there was no significant effect in the 3 US-based RCTs [P = 0.83; mean baseline 25(OH)D: 81.5 nmol/L]. Analysis of serum 25(OH)D2 and serum 25(OH)D3 (n = 5 RCTs) revealed a statistically significant increase (WMD: 20.6 nmol/L; 95% CI: 8.0, 33.3 nmol/L, P = 0.001, I(2 =) 99%) and decrease (WMD: -13.3 nmol/L; 95% CI: -15.8, -10.7 nmol/L, P < 0.00001, I(2) = 0%) after supplementation with UV-exposed mushrooms. CONCLUSIONS: Consumption of UV-exposed mushrooms may increase serum 25(OH)D when baseline vitamin D status is low via an increase in 25(OH)D2 (24.2 nmol/L) and despite a concomitant but relatively smaller reduction in 25(OH)D3 (-12.6 nmol/L). When baseline vitamin D status is high, the mean increase in 25(OH)D2 (18.3 nmol/L) and a relatively similar reduction in 25(OH)D3 (-13.6 nmol/L) may explain the lack of effect on serum 25(OH)D.

Impact on Vitamin D2, Vitamin D4 and Agaritine in Agaricus bisporus Mushrooms after Artificial and Natural Solar UV Light Exposure.

Commercial mushroom production can expose mushrooms post-harvest to UV light for purposes of vitamin D2 enrichment by converting the naturally occurring provitamin D2 (ergosterol). The objectives of the present study were to artificially simulate solar UV-B doses occurring naturally in Central Europe and to investigate vitamin D2 and vitamin D4 production in sliced Agaricus bisporus (button mushrooms) and to analyse and compare the agaritine content of naturally and artificially UV-irradiated mushrooms. Agaritine was measured for safety aspects even though there is no rationale for a link between UV light exposure and agaritine content. The artificial UV-B dose of 0.53 J/cm(2) raised the vitamin D2 content to significantly (P < 0.001) higher levels of 67.1 ± 9.9 µg/g dry weight (DW) than sun exposure (3.9 ± 0.8 µg/g dry DW). We observed a positive correlation between vitamin D4 and vitamin D2 production (r(2) = 0.96, P < 0.001) after artificial UV irradiation, with vitamin D4 levels ranging from 0 to 20.9 µg/g DW. The agaritine content varied widely but remained within normal ranges in all samples. Irrespective of the irradiation source, agaritine dropped dramatically in conjunction with all UV-B doses both artificial and natural solar, probably due to its known instability. The biological action of vitamin D from UV-exposed mushrooms reflects the activity of these two major vitamin D analogues (D2, D4). Vitamin D4 should be analysed and agaritine disregarded in future studies of UV-exposed mushrooms.

Body mass index and bioelectrical impedance phase angle as potentially modifiable nutritional markers are independent risk factors for outcome in allogeneic hematopoietic cell transplantation.

Beside many risk factors in patients considered for alloHCT, only body mass index (BMI) as a broad marker of nutritional status has prognostic value in these patients. This is the first prospective study to investigate the validity of further nutritional markers: adjusted BMI, normalized for gender and age; Subjective Global Assessment questionnaire and standardized phase angle, normalized for gender, age and BMI in 105 patients as independent risk factors for outcomes [overall survival (OS), non-relapse mortality (NRM), relapse mortality (RM), progression-free survival (PFS)] until 2 years after alloHCT. In Cox proportional-hazards regression models, we included a variety of accepted risk factors. The two most influential pre-transplant risk factors identified and associated with similarly increased hazard ratios (HR) for OS, RM, and PFS were a low-standardized phase angle (HR = 1.97, P = 0.043; HR = 3.18, P = 0.017, and HR = 1.91, P = 0.039) and advanced disease. Under- and overweight according BMI percentiles (≤10th; ≥90th) revealed associations with increased risk of NRM (HR = 2.90, P = 0.018; HR = 3.02, P = 0.062), although only low BMI was weakly associated with OS (HR = 1.82, P = 0.09). In conclusion, our results demonstrate that pre-transplant phase angle is an independent predictor for 2-year outcomes in these patients. Further investigation is necessary to demonstrate whether the theoretically modifiable phase angle can be increased by physical training combined with nutritional support, and if this improves outcome after alloHCT.

High-fat diet impact on intestinal cholesterol conversion by the microbiota and serum cholesterol levels.

Cholesterol-to-coprostanol conversion by the intestinal microbiota has been suggested to reduce intestinal and serum cholesterol availability, but the relationship between intestinal cholesterol conversion and the gut microbiota, dietary habits, and serum lipids has not been characterized in detail. We measured conserved proportions of cholesterol high and low-converter types in individuals with and without obesity from two distinct, independent low-carbohydrate high-fat (LCHF) dietary intervention studies. Across both cohorts, cholesterol conversion increased in previous low-converters after LCHF diet and was positively correlated with the fecal relative abundance of Eubacterium coprostanoligenes. Lean cholesterol high-converters had increased serum triacylglycerides and decreased HDL-C levels before LCHF diet and responded to the intervention with increased LDL-C, independently of fat, cholesterol, and saturated fatty acid intake. Our findings identify the cholesterol high-converter type as a microbiome marker, which in metabolically healthy lean individuals is associated with increased LDL-C in response to LCHF.

Course of serum 25-hydroxyvitamin D(3) status and its influencing factors in adults undergoing allogeneic hematopoietic cell transplantation.

Hypovitaminosis D (<30 ng/ml) is highly prevalent in allogeneic hematopoietic cell transplantation (alloHCT), but the relevance of influencing factors for serum 25-hydroxyvitamin D(3) [25(OH)D(3)] status in adult patients remains unknown. We are the first to have prospectively assessed 25(OH)D(3) status and its influencing factors in 102 patients before and at days +30 and +100 after alloHCT. Among others, we evaluated age, gender, weight, fat mass, season, sun exposure habits, and dietary and supplemental vitamin D intake as factors potentially influencing baseline vitamin D status in uni- and multivariate linear regression analysis. Furthermore, we investigated the impact of changes in fat mass, duration of parenteral nutrition, and acute graft-versus-host disease (aGVHD) on the course of serum 25(OH)D(3). Baseline 25(OH)D(3) concentrations were 16.4 ± 8.9 ng/ml, revealing that the majority (89%) had concentrations beneath the normal range. In multivariate linear regression model, only higher body fat mass remained an independent risk factor for reduced baseline 25(OH)D(3) concentrations (P = 0.007). In the early post-transplant period, 25(OH)D(3) status remained low, revealing a tendency to further deterioration, especially in patients with corticosteroid-treated aGVHD (≥II). Reduced vitamin D status was very common in these patients before and after alloHCT, whereby the most important influencing factors, namely season and dietary factors seem to have little impact. Our findings suggest that monitoring and if necessary, correcting vitamin D status may be indicated at regular intervals before alloHCT and during long-term follow-up. Further investigations of these patients' vitamin D requirements are needed, especially if they are on long-term corticosteroids.

Role of antioxidants in buccal mucosa cells and plasma on the incidence and severity of oral mucositis after allogeneic haematopoietic cell transplantation.

PURPOSE: Oral mucositis (OM) is known to be a significant complication of chemotherapy preceding haematopoietic cell transplantation (HCT). Antioxidants (AOX) scavenge free radicals, which play a major role in the initiation of OM and may reduce the OM risk. STUDY DESIGN: The primary objective of this prospective study was to investigate the association between the incidence and severity of OM (WHO oral toxicity scale) and the AOX status in buccal mucosa cells (BMC) and plasma. The α-tocopherol, ascorbic acid and ß-carotene concentrations in BMC and plasma were assessed at admission in 70 patients with a median age of 58 years before undergoing allogeneic HCT. RESULTS: Severe OM (III-IV), ulcerative OM (II-IV) and no or mild OM (0-I) were documented in 14 (20.0%), 32 (45.7%) and 38 (54.3%) patients, respectively. We observed no significant differences in baseline AOX concentrations in plasma or BMC among the OM groups. However, between patients with at least one plasma AOX beneath the normal range (39/70) and those with all plasma AOX in the normal range (31/70), we noted a trend towards longer duration of parenteral nutrition (PN) during the study period (10 vs. 8 days; p = 0.066). CONCLUSIONS: No single AOX, either in plasma or BMC (α-tocopherol, ascorbic acid and ß-carotene), revealed predictive value for the incidence or severity of OM. However, patients with an overall good plasma AOX status tended to require less PN, a common clinical marker for OM, which may be more relevant than any one AOX at reducing the risk of OM.

Health Risk Assessment of Heavy Metals (Pb, Cd, Hg) in Hydroalcoholic Gels of Abidjan, Côte d'Ivoire.

Despite the high consumption of hydroalcoholic gels worldwide and particularly in Côte d'Ivoire since the outbreak of the COVID-19 pandemic, very few studies have measured the heavy metal content and human exposure in this product. Thus, 30 samples from supermarkets in Abidjan, Côte d'Ivoire, were collected for the study of risk assessment of exposure to heavy metals contained in hydroalcoholic gels. This study consists of the characterization of the danger by calculating the carcinogenic and non-carcinogenic risk by skin contact. Almost all samples analysed contain trace of lead, cadmium and mercury but at concentrations below the Canadian limit in cosmetic products applied to the skin and below the US FDA limit as an impurity in colour additives used in cosmetic products. The mean values of chronic daily intake via dermal absorption (CDIdermal) for adults were found in the order of mercury > lead > cadmium. The health risk estimation indicated that the mean total hazard quotient for dermal adsorption (HIdermal) obtained is 7.10 × 10-5 ± 5.52 × 10-5. This value was below 1, the acceptable limit, representing a non-carcinogenic risk for Abidjan residents through dermal adsorption. Moreover, the incremental lifetime cancer risk (ILCR) evaluation for lead and cadmium was insignificant, and the cancer risk can be neglected, but in case of their overusing, they can cause long-term health problems for consumers.

Effects of a Non-Energy-Restricted Ketogenic Diet on Clinical Oral Parameters. An Exploratory Pilot Trial.

Ketogenic diets (KDs) may be a helpful complement in the prevention of and therapy for several diseases. Apart from their non-cariogenic properties, it is still unclear how KDs affect oral parameters. The aim of this study was to investigate the influence of a KD on clinical periodontal parameters. Twenty generally healthy volunteers with an average age of 36.6 years underwent a KD for 6 weeks. Their compliance was monitored by measuring their urinary ketones daily and by keeping 7-day food records. Clinical oral parameters included plaque (PI), gingival inflammation (GI), a complete periodontal status (probing depths, bleeding on probing), and general physical and serologic parameters at baseline and after 6 weeks. The results showed a trend towards lower plaque values, but with no significant changes from baseline to the end of the study with regard to the clinical periodontal parameters. However, their body weight and BMI measurements showed a significant decrease. The regression analyses showed that the fat mass and the BMI were significantly positively correlated to periodontal inflammation, while HDL, fiber, and protein intake were negatively correlated to periodontal inflammation. The KD change did not lead to clinical changes in periodontal parameters in healthy participants under continued oral hygiene, but it did lead to a significant weight loss.

In Vivo Fat Quantification: Monitoring Effects of a 6-Week Non-Energy-Restricted Ketogenic Diet in Healthy Adults Using MRI, ADP and BIA.

The ketogenic diet (KD) is a very low-carbohydrate, high-fat, and adequate-protein diet that induces many metabolic adaptations when calorie intake is not limited. Its therapeutic use in a range of diseases including cancer is currently being investigated. Our objective was to firstly assess the impact of a 6-week non-energy-restricted KD on the abdominal fat distribution and the hepatic fat composition in healthy adults. Body fat distribution and composition were measured by comparing magnetic resonance imaging (MRI) and spectroscopy (MRS) results with air displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) measurements. A total of 12 subjects from the KetoPerformance study were recruited for this ancillary study. Body mass index (BMI), total mass, total fat mass, total subcutaneous mass, and subcutaneous fat mass decreased significantly. None of the MRS parameters showed a significant change during the study. Even though the average change in body weight was >2kg, no significant changes in intrahepatic lipid (IHL) content could be observed. Total fat mass and total fat-free mass derived from MRI has a strong correlation with the corresponding values derived from BIA and ADP data. BMI and the absolute fat parameter of all three modalities decreased, but there were no or only minor changes regarding the fat-free parameter. Magnetic resonance imaging provides body composition information on abdominal fat distribution changes during a ketogenic diet. This information is complementary to anthropomorphic and laboratory measures and is more detailed than the information provided by ADP and BIA measures. It was shown that there was no significant change in internal fat distribution, but there was a decrease in subcutaneous fat.

Impact of a 6-week non-energy-restricted ketogenic diet on physical fitness, body composition and biochemical parameters in healthy adults.

BACKGROUND: The ketogenic diet (KD) is a very low-carbohydrate, high-fat and adequate-protein diet that without limiting calories induces different metabolic adaptations, eg, increased levels of circulating ketone bodies and a shift to lipid metabolism. Our objective was to assess the impact of a 6-week non-energy-restricted KD in healthy adults beyond cohorts of athletes on physical performance, body composition, and blood parameters. METHODS: Our single arm, before-and-after comparison study consisted of a 6-week KD with a previous preparation period including detailed instructions during classes and individual counselling by a dietitian. Compliance with the dietary regimen was monitored by measuring urinary ketones daily, and 7-day food records. All tests were performed after an overnight fast: cardiopulmonary exercise testing via cycle sprioergometry, blood samples, body composition, indirect calorimetry, handgrip strength, and questionnaires addressing complaints and physical sensations. RESULTS: Forty-two subjects aged 37 ± 12 years with a BMI of 23.9 ± 3.1 kg/m2 completed the study. Urinary ketosis was detectable on 97% of the days, revealing very good compliance with the KD. Mean energy intake during the study did not change from the habitual diet and 71.6, 20.9, and 7.7% of total energy intake were from fat, protein, and carbohydrates, respectively. Weight loss was -2.0 ± 1.9 kg (P < 0.001) with equal losses of fat-free and fat mass. VO2peak and peak power decreased from 2.55 ± 0.68 l/min to 2.49 ± 0.69 l/min by 2.4% (P = 0.023) and from 241 ± 57 W to 231 ± 57 W by 4.1% (P < 0.001), respectively, whereas, handgrip strength rose slightly from 40.1 ± 8.8 to 41.0 ± 9.1 kg by 2.5% (P = 0.047). The blood lipids TG and HDL-C remained unchanged, whereas total cholesterol and LDL-C increased significantly by 4.7 and 10.7%, respectively. Glucose, insulin, and IGF-1 dropped significantly by 3.0, 22.2 and 20.2%, respectively. CONCLUSIONS: We detected a mildly negative impact from this 6-week non-energy-restricted KD on physical performance (endurance capacity, peak power and faster exhaustion). Our findings lead us to assume that a KD does not impact physical fitness in a clinically relevant manner that would impair activities of daily living and aerobic training. However, a KD may be a matter of concern in competitive athletes. TRIAL REGISTRATION: DRKS00009605, registered 08 January 2016.

Monitoring for compliance with a ketogenic diet: what is the best time of day to test for urinary ketosis?

BACKGROUND: The ketogenic diet (KD) is a very low-carbohydrate, high-fat and adequate-protein diet with no calorie limit that induces a metabolic condition called "physiological ketosis". It was first introduced to treat epilepsy in the 1920s and has become quite popular recently as weight-loss and performance-enhancing diet. Its therapeutic use in a range of diseases is under investigation. During KD interventions people are supposed to monitor compliance with the dietary regimen by daily urine testing for ketosis. However, there are no studies investigating the best time for testing. FINDINGS: Twelve healthy subjects (37 ± 11 years; BMI = 23.0 ± 2.5 kg/m2) were instructed to, during the sixth week of a KD and with stable ketosis, measure their urine (8×) and blood (18×) ketone concentration at regular intervals during a 24-h period. According to their 1-day food record, the subjects consumed on average a diet with 74.3 ± 4.0 %, 19.5 ± 3.5 %, and 6.2 ± 2.0 % of total energy intake from fat, protein and carbohydrate, respectively. The lowest blood ß-hydroxybutyrate (BHB) (0.33 ± 0.17 mmol/l) and urine acetoacetate (AA) (0.46 ± 0.54 mmol/l) concentrations were measured at 10:00, respectively. The highest BHB (0.70 ± 0.62 mmol/l) and AA concentrations were noted at 03:00, respectively. Via urine testing the highest levels of ketosis were found at 22:00 and 03:00 and the highest detection rates (>90 %) for ketosis were at 07:00, 22:00 and 03:00, respectively. CONCLUSIONS: These results indicate that ketonuria in subjects with stable ketosis is highest and can be most reliably detected in the early morning and post-dinner urine. Recommendations can be given regarding precise time of the day for measuring ketone bodies in urine in future studies with KDs.

Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms.

The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 µg/g up to 3.9 ± 0.8 µg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 µg/g DW (P < 0.0001), which is equivalent to 17.6 µg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon.