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Remodelling of the intestinal ecosystem during caloric restriction and fasting.
Ducarmon, QR, Grundler, F, Le Maho, Y, Wilhelmi de Toledo, F, Zeller, G, Habold, C, Mesnage, R
Trends in microbiology. 2023;(8):832-844
Abstract
Benefits of fasting and caloric restriction on host metabolic health are well established, but less is known about the effects on the gut microbiome and how this impacts renewal of the intestinal mucosa. What has been repeatedly shown during fasting, however, is that bacteria utilising host-derived substrates proliferate at the expense of those relying on dietary substrates. Considering the increased recognition of the gut microbiome's role in maintaining host (metabolic) health, disentangling host-microbe interactions and establishing their physiological relevance in the context of fasting and caloric restriction is crucial. Such insights could aid in moving away from associations of gut bacterial signatures with metabolic diseases consistently reported in observational studies to potentially establishing causality. Therefore, this review aims to summarise what is currently known or still controversial about the interplay between fasting and caloric restriction, the gut microbiome and intestinal tissue physiology.
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Long-term fasting improves lipoprotein-associated atherogenic risk in humans.
Grundler, F, Plonné, D, Mesnage, R, Müller, D, Sirtori, CR, Ruscica, M, Wilhelmi de Toledo, F
European journal of nutrition. 2021;(7):4031-4044
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PURPOSE Dyslipidemia is a major health concern associated with an increased risk of cardiovascular mortality. Long-term fasting (LF) has been shown to improve plasma lipid profile. We performed an in-depth investigation of lipoprotein composition. METHODS This observational study included 40 volunteers (50% men, aged 32-65 years), who underwent a medically supervised fast of 14 days (250 kcal/day). Changes in lipid and lipoprotein levels, as well as in lipoprotein subclasses and particles, were measured by ultracentrifugation and nuclear magnetic resonance (NMR) at baseline, and after 7 and 14 fasting days. RESULTS The largest changes were found after 14 fasting days. There were significant reductions in triglycerides (TG, - 0.35 ± 0.1 mmol/L), very low-density lipoprotein (VLDL)-TG (- 0.46 ± 0.08 mmol/L), VLDL-cholesterol (VLDL-C, - 0.16 ± 0.03 mmol/L) and low-density lipoprotein (LDL)-C (- 0.72 ± 0.14 mmol/L). Analysis of LDL subclasses showed a significant decrease in LDL1-C (- 0.16 ± 0.05 mmol/L), LDL2-C (- 0.30 ± 0.06 mmol/L) and LDL3-C (- 0.27 ± 0.05 mmol/L). NMR spectroscopy showed a significant reduction in large VLDL particles (- 5.18 ± 1.26 nmol/L), as well as large (- 244.13 ± 39.45 nmol/L) and small LDL particles (- 38.45 ± 44.04 nmol/L). A significant decrease in high-density lipoprotein (HDL)-C (- 0.16 ± 0.04 mmol/L) was observed. By contrast, the concentration in large HDL particles was significantly raised. Apolipoprotein A1 decreased significantly whereas apolipoprotein B, lipoprotein(a), fibrinogen and high-sensitivity C-reactive protein were unchanged. CONCLUSION Our results suggest that LF improves lipoprotein levels and lipoprotein subclasses and ameliorates the lipoprotein-associated atherogenic risk profile, suggesting a reduction in the cardiovascular risk linked to dyslipidemia. TRIAL REGISTRATION Study registration number: DRKS-ID: DRKS00010111 Date of registration: 03/06/2016 "retrospectively registered".
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Is muscle and protein loss relevant in long-term fasting in healthy men? A prospective trial on physiological adaptations.
Laurens, C, Grundler, F, Damiot, A, Chery, I, Le Maho, AL, Zahariev, A, Le Maho, Y, Bergouignan, A, Gauquelin-Koch, G, Simon, C, et al
Journal of cachexia, sarcopenia and muscle. 2021;(6):1690-1703
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Abstract
BACKGROUND Fasting is attracting an increasing interest as a potential strategy for managing diseases, including metabolic disorders and complementary cancer therapy. Despite concerns of clinicians regarding protein catabolism and muscle loss, evidence-based clinical data in response to long-term fasting in healthy humans are scarce. The objective of this study was to measure clinical constants, metabolic, and muscular response in healthy men during and after a 10 day fast combined with a physical activity programme. METHODS Sixteen men (44 ± 14 years; 26.2 ± 0.9 kg/m2 ) fasted with a supplement of 200-250 kcal/day and up to 3 h daily low-intensity physical activity according to the peer-reviewed Buchinger Wilhelmi protocol. Changes in body weight (BW) and composition, basal metabolic rate (BMR), physical activity, muscle strength and function, protein utilization, inflammatory, and metabolic status were assessed during the 10 day fast, the 4 days of food reintroduction, and at 3 month follow-up. RESULTS The 10 day fast decreased BW by 7% (-5.9 ± 0.2 kg, P < 0.001) and BMR by 12% (P < 0.01). Fat mass and lean soft tissues (LST) accounted for about 40% and 60% of weight loss, respectively, -2.3 ± 0.18 kg and -3.53 ± 0.13 kg, P < 0.001. LST loss was explained by the reduction in extracellular water (44%), muscle and liver glycogen and associated water (14%), and metabolic active lean tissue (42%). Plasma 3-methyl-histidine increased until Day 5 of fasting and then decreased, suggesting that protein sparing might follow early proteolysis. Daily steps count increased by 60% (P < 0.001) during the fasting period. Strength was maintained in non-weight-bearing muscles and increased in weight-bearing muscles (+33%, P < 0.001). Glycaemia, insulinemia, blood lipids, and blood pressure dropped during the fast (P < 0.05 for all), while non-esterified fatty acids and urinary beta-hydroxybutyrate increased (P < 0.01 for both). After a transient reduction, inflammatory cytokines returned to baseline at Day 10 of fasting, and LST were still lower than baseline values (-2.3% and -3.2%, respectively; P < 0.05 for both). CONCLUSIONS A 10 day fast appears safe in healthy humans. Protein loss occurs in early fast but decreases as ketogenesis increases. Fasting combined with physical activity does not negatively impact muscle function. Future studies will need to confirm these first findings.
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Blood Pressure Changes in 1610 Subjects With and Without Antihypertensive Medication During Long-Term Fasting.
Grundler, F, Mesnage, R, Michalsen, A, Wilhelmi de Toledo, F
Journal of the American Heart Association. 2020;(23):e018649
Abstract
Background We investigated daily blood pressure (BP) changes during fasting periods ranging from 4 to 41 (10.0±3.8) days in a cohort of 1610 subjects, including 920 normotensive, 313 hypertensive nonmedicated, and 377 hypertensive medicated individuals. Methods and Results Subjects underwent a multidisciplinary fasting program with a daily intake of ≈250 kcal. Weight and stress scores decreased during fasting, and the well-being index increased, documenting a good tolerability. BP mean values decreased from 126.2±18.6/81.4±11.0 to 119.7±15.9/77.6±9.8 mm Hg (mean change, -6.5/3.8 mm Hg). BP changes were larger for hypertensive nonmedicated subjects (>140/90 mm Hg) and reduced by 16.7/8.8 mm Hg. This reduction reached 24.7/13.1 mm Hg for hypertensive nonmedicated subjects (n=76) with the highest BP (>160/100 mm Hg). In the normotensive group, BP decreased moderately by 3.0/1.9 mm Hg. Interestingly, we documented an increase of 6.3/2.2 mm Hg in a subgroup of 69 female subjects with BP <100/60 mm Hg. In the hypertensive medicated group, although BP decreased from 134.6/86.0 to 127.3/81.3 mm Hg, medication was stopped in 23.6% of the subjects, whereas dosage was reduced in 43.5% and remained unchanged in 19.4%. The decrease in BP was larger in subjects fasting longer. Baseline metabolic parameters, such as body mass index and glucose levels, as well as age, can be used to predict the amplitude of the BP decrease during fasting with a machine learning model. Conclusions Long-term fasting tends to decrease BP in subjects with elevated BP values. This effect persisted during the 4 days of stepwise food reintroduction, even when subjects stopped their antihypertensive medication. Registration URL: https://www.drks.de/drks_web/; Unique identifier: DRKS00010111.
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Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects.
Wilhelmi de Toledo, F, Grundler, F, Bergouignan, A, Drinda, S, Michalsen, A
PloS one. 2019;(1):e0209353
Abstract
Only few studies document longer periods of fasting in large cohorts including non-obese participants. The aim of this study was to document prospectively the safety and any changes in basic health and well-being indicators during Buchinger periodic fasting within a specialised clinic. In a one-year observational study 1422 subjects participated in a fasting program consisting of fasting periods of between 4 and 21 days. Subjects were grouped in fasting period lengths of 5, 10, 15 and 20±2 days. The participants fasted according to the Buchinger guidelines with a daily caloric intake of 200-250 kcal accompanied by a moderate-intensity lifestyle program. Clinical parameters as well as adverse effects and well-being were documented daily. Blood examinations before and at the end of the fasting period complemented the pre-post analysis using mixed-effects linear models. Significant reductions in weight, abdominal circumference and blood pressure were observed in the whole group (each p<0.001). A beneficial modulating effect of fasting on blood lipids, glucoregulation and further general health-related blood parameters was shown. In all groups, fasting led to a decrease in blood glucose levels to low norm range and to an increase in ketone bodies levels (each p<0.001), documenting the metabolic switch. An increase in physical and emotional well-being (each p<0.001) and an absence of hunger feeling in 93.2% of the subjects supported the feasibility of prolonged fasting. Among the 404 subjects with pre-existing health-complaints, 341 (84.4%) reported an improvement. Adverse effects were reported in less than 1% of the participants. The results from 1422 subjects showed for the first time that Buchinger periodic fasting lasting from 4 to 21 days is safe and well tolerated. It led to enhancement of emotional and physical well-being and improvements in relevant cardiovascular and general risk factors, as well as subjective health complaints.
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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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Plain language summary
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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Fasting therapy - an expert panel update of the 2002 consensus guidelines.
Wilhelmi de Toledo, F, Buchinger, A, Burggrabe, H, Hölz, G, Kuhn, C, Lischka, E, Lischka, N, Lützner, H, May, W, Ritzmann-Widderich, M, et al
Forschende Komplementarmedizin (2006). 2013;(6):434-43
Abstract
Fasting for medical purpose (fasting therapy) has a long tradition in Europe and is established as a defined therapeutic approach in specialized fasting hospitals or within clinical departments for integrative medicine. In 2002, the first guidelines for fasting therapy were published following an expert consensus conference; here we present a revised update elaborated by an expert panel. Historical aspects and definitions, indications, methods, forms, and accompanying procedures of fasting as well as safety and quality criteria of fasting interventions are described. Fasting has shown beneficial effects in various chronic diseases with highest level of evidence for rheumatic diseases. Preliminary clinical and observational data and recently revealed mechanisms of fasting and caloric restriction indicate beneficial effects of fasting also in other chronic conditions such as metabolic diseases, pain syndromes, hypertension, chronic inflammatory diseases, atopic diseases, and psychosomatic disorders. Fasting can also be applied for preventing diseases in healthy subjects. In order to guarantee successful use of fasting and to ensure adherence of all safety and quality standards it is mandatory that all interventions during fasting are guided/accompanied by physicians/therapists trained and certified in fasting therapy.