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Clinical Trial
. 2021 Dec;12(6):1690-1703.
doi: 10.1002/jcsm.12766. Epub 2021 Oct 20.

Is muscle and protein loss relevant in long-term fasting in healthy men? A prospective trial on physiological adaptations

Claire Laurens  1   2 , Franziska Grundler  3   4 , Anthony Damiot  1 , Isabelle Chery  1 , Anne-Laure Le Maho  5 , Alexandre Zahariev  1 , Yvon Le Maho  1   6 , Audrey Bergouignan  1   7 , Guillemette Gauquelin-Koch  2 , Chantal Simon  8   9 , Stéphane Blanc  1 , Françoise Wilhelmi de Toledo  3
Affiliations
Clinical Trial

Is muscle and protein loss relevant in long-term fasting in healthy men? A prospective trial on physiological adaptations

Claire Laurens et al. J Cachexia Sarcopenia Muscle. 2021 Dec.

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.

Keywords: Apelin; Body composition; Energy metabolism; Lipids; Long-term fasting; Muscle function.

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Conflict of interest statement

Claire Laurens, Anthony Damiot, Isabelle Chery, Anne‐Laure Le Maho, Alexandre Zahariev, Yvon Le Maho, Audrey Bergouignan, Guillemette Gauquelin‐Koch, Chantal Simon, and Stephane Blanc declare that they have no conflict of interest. Françoise Wilhelmi de Toledo is managing director of Amplius GmbH, a company that coordinates the scientific documentation for the Buchinger Wilhelmi Clinics and is co‐worker of the Buchinger Wilhelmi Clinic. Franziska Grundler is co‐worker at the Buchinger Wilhelmi Clinic.

Figures

Figure 1
Figure 1
Changes in body weight (A), waist circumference (B), systolic (C), and diastolic (D) blood pressures before and during the 10 day fasting (n = 16) and after 3 months of Fup (n = 15). Data are lsmeans ± SE. F, fasting days; Fup, follow‐up; RF, food reintroduction days. *P < 0.05, **P < 0.01, ***P < 0.001 as indicated by the lines for the whole effect of fasting, the whole effect of RF or the effect of Fup vs. the end of fasting. #P < 0.05 vs. baseline during Fup.
Figure 2
Figure 2
Changes in body weight (BW), fat mass (FM), and lean soft tissues (LST) at F09 vs. baseline. LST change is estimated as the loss of metabolically active tissues (MAT), glycogen (Gly), and extracellular water (ECW) (A). Measurement of protein oxidation (B), urea excretion (C), creatinine excretion (D), plasma ASAT (E), plasma ALAT (F), plasma 3 methyl histidine (G), myostatin (H), 13CO2 of expired air (I) and plasma apelin (J) before and during the 10 day fasting (n = 16) and after 3 months of Fup (n = 15). Data are lsmeans ± SE. ALAT, alanine amino transferase; ASAT, aspartate amino transferase; F, fasting days; Fup, follow‐up; RF, food reintroduction days. *P < 0.05, **P < 0.01, ***P < 0.001 as indicated by the lines for the whole effect of fasting, the whole effect of RF or the effect of Fup vs. the end of fasting. ###P < 0.01 vs. baseline during Fup.
Figure 3
Figure 3
Changes in raw BMR (A) and BMR adjusted on LST calculated from changes in urinary nitrogen excretion (B) on 16 subjects during the whole fasting and 15 subjects at Fup. The figure also reports the changes in body composition assessed by impedancemetry at baseline and Fup (n = 12 subjects, C) used to adjust BMR at Fup (D). TSH concentrations are presented on panel (E). Data are lsmeans ± SE. BMR, basal metabolic rate; F, fasting days; Fup, follow‐up; LST, lean soft tissues; RF, food reintroduction days, TSH, thyroid stimulated hormone. *P < 0.05, **P < 0.01 as indicated by the lines for the whole effect of fasting, the whole effect of RF or the effect of Fup vs. the end of fasting. #P < 0.05, ##P < 0.01 vs. baseline.
Figure 4
Figure 4
Changes in maximal grip strength (A) and fatigability expressed in kg after 10 repeats (B) or as a percent of strength reduction after 10 repeats (C), leg strength (D), leg power during a submaximal exercise on an ergometer (E), skeletal muscle flexor carpi radialis tonus (F), stiffness (G) and decrement (H), rectus femoris tonus (I), stiffness (J) and decrement (K), and time to climb 40 steps (L) before and during the 10 day fasting (n = 16) and after 3 months of Fup (n = 15). Data are lsmeans ± SE. F, fasting days; Fup, follow‐up; RF, food reintroduction days. ***P < 0.001 as indicated by the lines for the whole effect of fasting, the whole effect of RF or the effect of Fup vs. the end of fasting. #P < 0.05, ##P < 0.01, ###P < 0.001 vs. baseline.
Figure 5
Figure 5
Changes in HDL (A), LDL (B), LDL/HDL ratio (C), total cholesterol (D), triglycerides (E), plasma NEFA (F), urine hydroxybutyrate (G), plasma glucose (H), plasma insulin (I), GGT (J), and plasma prealbumin (K) before and during the 10 day fasting (n = 16) and after 3 months of Fup (n = 15). Data are lsmeans ± SE. F, fasting days, Fup, follow‐up; GGT, gamma‐glutamyl transferase; HDL, high density lipoprotein; LDL, low density lipoprotein; NEFA, non‐esterified fatty acids; RF, food reintroduction days. *P < 0.05, **P < 0.01, ***P < 0.001 as indicated by the lines for the whole effect of fasting, the whole effect of RF or the effect of Fup vs. the end of fasting.
Figure 6
Figure 6
Changes in CRP (A), IFNg (B), TNFa (C), IL6 (D), IL10 (E), and MCP1 (F) before and during the 10 day fasting (n = 16) and after 3 months of Fup (n = 15). Data are lsmeans ± SE. CRP, C‐reactive protein; F, fasting days; Fup, follow‐up; IL, interleukin; INFg, interferon gamma; MCP, monocyte chemoattractant protein; RF, food reintroduction days. **P < 0.01, ***P < 0.001 as indicated by the lines for the whole effect of fasting, the whole effect of RF or the effect of Fup vs. the end of fasting.
Figure 7
Figure 7
Changes in plasma ghrelin (A), plasma PP (B), PYY (C), GLP‐1 (D), leptin (E), IGF1 (F), IGFBP1 (G), and two question on satiety derived from visual scale: ‘how hungry do you feel’ (H) and ‘how much do you think you can eat’ (I) before and during the 10 day fasting (n = 16) and after 3 months of Fup (n = 15). Data are lsmeans ± SE. F, fasting days; Fup, follow‐up; GLP‐1, glucagon like peptide 1; IGF1, insulin growth factor 1; IGFBP1, insulin growth factor binding protein; PYY, polypeptide YY; RF, food reintroduction days. *P < 0.05, **P < 0.01, ***P < 0.001 as indicated by the lines for the whole effect of fasting, the whole effect of RF or the effect of Fup vs. the end of fasting. #P < 0.05 vs. baseline during Fup.
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