A Prospective Pilot Study to Evaluate the Feasibility of Prolonged Fasting for the Treatment of Long COVID Patients
Phase: NA
Conditions: Long COVID Syndrome
Sponsor: Université de Sherbrooke

 
 
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Titre de l’étude: A prospective pilot study to evaluate the feasibility of 
prolonged fasting for the treatment of Long COVID patients  
 
Nom du chercheur principal:  Alain Piché, MD, MSc, FRCPC 
Microbiologiste-infectiologue, Service d’infectiologie, Département de Médecine, 
CIUSSSE-CHUS, professeur titulaire Université de Sherbrooke, professeur associé 
CRCHUS Cancer : biologie, pronostic et diagnostic  
Co-chercheurs:  
Simon Décary PhD:  
Professeur-chercheur, école de rédaptation, Université de Sherbrooke, professeur 
associé CRCHUS Santé : populations, organisation et pratiques 
Maxime Sasseville PhD:  
Professeur adjoint, faculté des sciences infirmières, Université Laval 
Coordonnatrice de l’étude : 
Christine Rioux-Perreault : CRCHUS 
Nutrionniste : 
Vanessa martinez : CIUSSSE-CHUS 
Promoteur de l’étude : initié par le chercheur principal. Support fnancier : PAFI - 
CRCHUS 
 
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1. INTRODUCTION 
1.1. Rationale 
There are more than 400 M of individuals worldwide have not fully recover to their 
previous level of health following an infection by severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2).1 These individuals developed persistent  symptoms that are 
now referred to as Long COVID (LC). LC is a complex and multisystemic condition 
potentially affecting any organ in the body. LC is characterized by persistent disabling 
fatigue, nonrestorative sleep, post-exertional malaise, and neurocognitive impairment, 
although many other symptoms have been reported.2 Diagnosis is clinical and based on 
symptom reports owing to the absence of diagnostic biomarkers. LC has emerged as a 
major public concern in this post-pandemic era. A recent survey by Statistics Canada 
showed that 3.5 M Canadians have LC and almost 50% still have symptoms after a year, 
and most are unable to work.3 Another study from Quebec showed that health care 
workers that reported at least one COVID-19 episode have an overall risk of 12% of 
developing LC.4 LC-associated symptoms can have a debilitating functional impact, 
significantly impairing health-related quality of life leading to anxiety and depression.5 LC 
is associated with a huge societal burden as symptoms may last for years. Most 
importantly, there is no validated treatment for this condition. 
The complexicity of the pathogenicity have hampered the rapid development of efficient 
pharmalogical treatments. As an alternative, non-pharmalogical approaches like fasting, 
which acts on multiple metabolic pathways, are being explored. Prolonged fasting (PF) is 
defined as voluntary renouncement of food intake for 7 days. Although robust data are 
lacking, based on case reports, small case series and personal clinical experience, PF have 
been associated in some LC patients with significant symptoms improvement, ability to 
return to work and even apparent clinical cure.6,7  
There is an urgent need for treatment in LC patients. Many have been suffering for years 
now with little clinical improvement. PF may represent a novel, cheap and efficient 
approach to improve the health-related quality of life (HRQoL) for these patients. 
 
1.2. Literature review 
 
The SARS-CoV-2 virus primarily enters the cells through interaction between the viral 
spike protein and the angiotensin-converting enzyme-2 (ACE2) receptor, which is 
expressed by various cell types in the body, leading to an inflammatory response that 
impairs organ function.8 The underlying mechanisms leading to LC is not fully understood 
but may involve chronic inflammation, oxidative stress, microclotting, production of auto-
antibodies, dysfunction of complement response, brian blood barrier permeability or viral 
persistence.8 Oxidative stress can lead to mitochondrial dysfunction.9 
 

 
 
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There is no consensus on therapeutic approaches to address LC. Fasting has been used by 
various cultures as a therapeutic modality. Prolonged fasting (PF) is defined as voluntary 
abstention of food intake lasting > 5 days. PF has shown multiple effects on pathological 
mechanisms involved in LC, such as decreasing inflammation or reducing oxidative 
stress.10,11 Furthermore, PF has been shown to reduce risk factors associated with severe 
COVID-19 courses.12 This includes weight loss, reduction in waist circumference,13 
normalization of blood pressure,16 as well as glucose and lipid levels.14,15 which are linked 
to COVID-19 comorbidities like obesity, hypertension, diabetes or dyslipidemia. 
 
Data on the effect of fasting in LC are lacking. The is currently no undergoing clinical trial 
on fasting  in LC. Further rational for evaluating the effect of fasting comes from clinical 
observation of patients which self decided to perfom PF and reported improvement of 
their condtion, and from case report or small case series.6,7.  
 
 
2. HYPOTHESIS, GOAL AND OBJECTIVES  
   
We hypothesize that in home supervised PF is feasible and may improve symptoms and 
health-related quality of life (HRQoL) in patients with LC. 
 
Primary objective:  
 
• To assess the fesability and acceptability of in home supervised PF (7 days) in 25 
patients with severe LC 
 
The secondary objectives are:  
 
• To assess mean changes from baseline to one month post-PF on the SF 36 physical 
component score questionnaire (PCS) 
 
• To assess mean changes from baseline to one month post-PF in functional status 
as measured by the Post-COVID functional status scale  
 
To assess mean changes from baseline to one month post-PF in LC-associated 
fatigues as measured by the Fatigue Severity Score questionnaire 
  
• To assess mean changes from baseline to one month post-PF in neurocognitive 
status as measured by the Cognitive failure questionnaire version 2.0  
 
 
3. METHODOLOGY 
 
3.1 Study design 
 

 
 
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To address our primary goal, we propose a prospective, open label, single-center, 
interventional pilot study in patients with LC. Participants with severe LC, as defined here 
by  a post-COVID functional status scale score (PCFS) of > 2, will undergo in home PF for 
7 days under medical surveillance. Patients with severe LC are prioritized because they 
are the ones that will most likely benefit from a new intervention as there are the less 
likely to improve overtime. Indeed, data have shown a < 10% improvement after a year 
post-infection in these patients.17 Patient-reported outcome measures (PROMs) will be 
assessed at baseline, at day 7, and at one month post-PF. 
 
3.2 Sample size 
 
It is hoped that the data collected by this study will contribute to the design for a larger 
clinical trial. Based on Lewis et al.'s recommendations for sample size calculation in 
feasibility studies,23 we defined two calculations: one for retention and one for 
acceptability. For participantetention, an unacceptable threshold was set at £ 50%, with 
an expected value of 80%. For acceptability, an unacceptable threshold was set at 70%, 
with an expected value of 90%, resulting in sample sizes of 18 and 25, respectively. Results 
were obtained using G*Power 3.1.9.4. Based on the number of LC patients in active care 
at our clinic (> 700), recruiting 18-25 participants with severe LC at our clinic is feasible.  
 
3.3 Study population 
 
This study focuses on patients with severe LC who have no exclusion criteria for PF. All 
participants (> 18 year-old) will be recruited at the CIUSSSE-CHUS post-COVID clinic. Our 
clinic sees 10-15 new patients per week and we have over 700 patients in active care. 
Most of these patients have severe LC. Recruting up to 25 patients for this study within 6 
months poses no problem. 
  
3.4 Eligibility and screening 
 
Because of reference bias (to be seen at the clinic, patients must be referred by a health 
care professional), most (> 80%) patients seen at the clinic have severe LC based on PCFS 
scores of 3 or 4. All new patients seen at our clinic are evaluated for their functional status 
with the PCFS tool as part of standard care. Potential participants will be screened by the 
principal investigator prior to entry into this study. If interested, an explanation of the 
study and discussion of the expected side effects, and full disclosure of the “informed 
consent” documents will take place by the study nurse. Participants will be recruited 
sequentially. Participants will continue to take their regular medication during PF. 
 
Inclusion criteria: 
 
• 
Age 18-64 years 
• 
Diagnosis Long Covid based on WHO criteria (post-acute COVID-19 symptoms 
persisting ≥12 weeks) and validiated by an experienced cinician 

 
 
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• 
Body Mass Index between 18.5 to 39 kg/m2) 
• 
Able to communicate in and comprehend English and/or French language 
• 
Present written / signed declaration of consent 
• 
Ability to understand the patient information and willingness to sign the consent 
form 
• 
Willing to limit physical activity during PF 
 
Exclusion criteria: 
• Current underweight condition (body mass index less than 18.5 kg/m2) or weight 
loss exceeding 3 kg within the last month or 5 kg within the last three months. 
• Current or history of eating disorder  (e.g., anorexia, bulimia). 
• Psychiatric condition that limits understanding of the examination protocol 
(unable to consent) 
• Participation in another intervention study. 
• Fasting during the last six months 
• Pregnancy or breastfeeding status. 
• Diagnosis of chronic inflammatory bowel diseases, celiac disease or colorectal 
cancer according to the guidelines of the Canadian Society of Gastroenterology 
• Use of anti-psychotic drugs 
• Start of novel drug therapy for long COVID 
• Contraindication for additional blood draws (e.g. hemoglobin <100) 
• Clinically significant kidney, heart, and hepatic impairment as determined by 
clinical judgement 
• Taking opioid analgesics or undergoing treatment for opioid addiction 
• Opioid dependence or withdrawal syndrome 
• Type 1 or 2 Diabetes, or history of hypoglycemia 
• Active cancer 
• Baseline E+ (Na, K, Mg, phosphate) within normal range 
• Baseline ALT < 60 
• Baseline Hb > 100 
• Baseline INR within normal range 
• Baseline DFG < 50   
   
3.5 Primary and secondary outcome measurement 
 
3.5.1 Diagnosis of LC 
There are no diagnostic tests for LC. It is a clinical condition, and the CHUS post-COVID 
clinic uses the WHO definition for LC (): “Long COVID occurs in individuals with a history 
of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-
19 with symptoms and that last for at least 2 months and cannot be explained by an 
alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive 
dysfunction but also others and generally have an impact on everyday functioning. 

 
 
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Symptoms may be new onset following initial recovery from an acute COVID-19 episode 
or persist from the initial illness. All LC diagnosis at the clinic are made by an experienced 
clinician after ruling out other conditions. 
 
3.5.2 Patient reported outcome measurements (PROMs) 
There is no consensus definition for LC severity. For the purpose of this study, LC severity 
is based on the Post-COVID functional status scale (PCFS) (scale 0-4; 4 being the worse) > 
2. The PCFS is part of the initial evaluation at the clinic and administered during follow up 
visits. There is no validated measurement instrument to assess neurocognitive 
impairment, but a recent Delphi consensus recommended that the Cognitive failures 
questionnaire (CFQ) could be used to assess cognitive impairment in patients with LC 
(Gorst). Performance to this test may be influence by fatigue (for example if participants 
have post-exertional malaise when the filled the surveys) or by depression. The CFQ is 
part of the initial evaluation at the clinic and administered during follow up visits.  
 
The following patient-reported outcome measures will be used to determine pre- and 
post-PF health status, i.e. baseline, day 7 and 30 days: 
• Post-COVID-19 functional status scale (0-4) scores: The Post-COVID Functional 
Status Scale (PCFS) is designed to assess the functional status and limitations of 
individuals experiencing LC. This PROM instrument captures the impact of LC on 
various aspects of daily functioning and overall well-being.18 This instrument has 
been validated for patients with LC.19 
• Fatigue: The Fatigue severity scale (FSS) (0-7 score) is one of the tool to assess 
the severity of fatigue. It is validated for LC patients.20 
• SF 36: Validated scale for assessment and monitoring of patients with LC.21 The 
36-item scale's subscales (scores) are physical symptom severity (0-100), 
functional disability (0-50), additional symptoms (0-60), and overall health (0-10).  
• Cognitive Failures Questionaire 2.0: to assess cognitive impairment (15 questions, 
0-100 score). High score indicates increased propensity to cognitive impairment. 
The MoCa and Folstein questionnaires are not sensitive enough to capture the 
cognitive impairments associated with LC.22 
 
3.5.3 Feasibility and acceptability 
The primary objective of a pilot study, is to determine the feasibility and acceptability. To 
assess acceptability, participants and research staff will be asked to complete at day 30 a 
short questionnaire (annexe 1 and 2) about their study appreciation. The rentation rate 
(feasibility) will be determined at day 7 (percentage of participants that completed PF) 
and day 30 (percentage of participants that completed PROMs).  
 
3.6. Study schedule 
 
3.6.1 Study intervention 
After informed consent signature, an initial nutritional evaluation will be done between 4 
to 7 days prior to PF start. At baseline, participants will undergo a superved in home PF 

 
 
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for 7 days. Adequat hydratation, prescribed drugs already taken by the patient, and 
vitamins and supplements will be permitted during PF (see attach list of vitamins and 
supplements recommended).The vitamins (Centrum forte) will be provided to each 
participants. Supplements such as NaPO4, Kdur and magnesium gluconate will be 
prescribed to participants (all covered by RAMQ). Participants will be meet in person, at 
baseline, by the research nurse for detailed instructions on how to do PF (see annexe 5). 
The PF will done at home under medical supervision. However, the baseline visit will be 
done at the CRCHUS were the participant will undergo a complete medical exam by the 
investigator and will complete PROMs. PF will start the next day. Vitamins and 
supplements will be taken during PF and stop at day 7, except for thiamine which will be 
given until day 10. 
  
3.6.2 Study medical supervision 
The nutrionist will determine the nutritional status of participants before the baseline 
visit. A trained nurse will meet the participant on day 0 (baseline) and day 9. During in 
person visit, the nurse will take vital signs and assess the participant’s well being. During 
PF study period, both the principal investigator and the study nutritionist will be available. 
At day 7, the nutritionist will contact participants to instruct them how to start refeeding. 
 
Visit schedule: 
1) The screening visit will occur between 4 to 7 days prior to the baseline visit to 
determine eligibility, obtain informed consent and assess nutritional status.  
2) The baseline visit wiil be in person at CRCHUS, to blood draw/Sociodemographic 
data (Annexe 4) and PROMs/review of PF instructions (Annexe 5) (day 0). 
3) PF starts the day after the baseline visit (day 1). Participants start recommended 
vitamins and supplements on day 1 (Annexe 3). 
4) Phone follow up at day 4 and 7 for clinical assessment. End of PF at day 7. PROMs 
at day 7. Participants stop vitamins and supplements. 
5) In person visit at CRCHUS on day 9. Blood draw during visits (E+). Refeeding 
syndrome surveillance 
6) Phone visit visit on day 30 post-PF. PROMs and acceptability questionnaire to be 
completed. 
 
At baseline, day 7 and day 30 (post-PF), participants will be asked to complete the 
different PROMS and sociodemographic data (baseline only) (Annexe 4). Data will be 
subsequently entered into a REDCap database. Patients who have a re-infection with 
COVID-19 during the study will follow all public health precautions and isolate as directed. 
In such cases, participants will be recommended to stop PF and undergo usual care for 
their infection. 
 
Aside from transient minor side effects related to PF such as malaise, transient weight 
loss, dehydration, and fatigue, there is a small (< 1%) risk of a refeeding syndrome.  
Refeeding syndrome is defined as medical complications that result from fluid and 

 
 
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electrolyte shifts as a result of aggressive nutritional rehabilitation.  ASPEN proposed 
unifying diagnostic criteria to stratify patients based on 3 levels of severity (mild, 
moderate, severe) are the following: 
• 
Mild - a decrease in any 1, 2, or 3 of serum phosphorus, potassium, or magnesium 
levels by 10% to 20% 
• 
Moderate - a decrease in any 1, 2, or 3 of serum phosphorus, potassium, or 
magnesium levels by 20% to 30% 
• 
Severe - a decrease in any 1, 2, or 3 of serum phosphorus, potassium, or 
magnesium levels by >30% or organ dysfunction resulting from a decrease in any 
of these or due to thiamine deficiency (severe), occurring within 5 days of a 
reintroduction of calorie 
 
This complication is mostly limited to high risk hospitalized patients. In this study, patients 
at high risk will be excluded (see exclusion criteria) which should considerably reduced 
the risk of refeeding syndrome. Although no data is available on the risk of refeeding 
syndrome in non-hospitalized patients, in the context of this study, the risk of refeeding 
syndrome is estimated to be < 0.5%. In an unlikely event of a patient presenting with a 
refeeding syndrome, he will be manage according to the refeeding syndrome treatment 
guidelines 
(https://myconnect.swbh.nhs.uk/wp-content/uploads/2024/02/Refeeding-
guidelines.pdf). To avoid this complication, the nutritionist will instruct participants on 
how to start refeeding after PF.  
 
Apart from the baseline visit which will take between 2 hours, each visit will take 
approximately 60 minutes or less to complete. 
 
3.6 Study duration 
 
We plan to complete patient accrual in about 3-6 months and expect patient participation 
in the last follow-up visit to be completed within 8 months. Given study interventions 
required, no more than two participants per week will be recruited. 
 
 
4. DATA ANALYSIS 
 
Continuous socio-demographic and clinical variables will be presented as means 
(standard deviation) if they follow a normal distribution, or as medians [interquartile 
range] otherwise. Categorical variables will be expressed as frequencies (percentages). 
The proportion of missing data will be reported for each variable if necessary. Variables 
with more than 10% missing data will be excluded from analyses. No multiple imputation 
is planned. A significance level of 5% will be applied, and analyses will be performed using 
R software (version 4.4.2). 
 
4.1 Primary outcome 
 

 
 
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Retention rate and acceptability will be assessed using predefined calculations, with a 
95% confidence interval provided to compare against unacceptable threshold. The 
acceptability questionnaire for participants contains two questions. Acceptability is 
defined as follow: « (Confiance OU Très confiance) ET (Plutôt acceptable OU Acceptable) 
aux deux questions ». The research staff acceptability questionnaires contains 4 questions 
(annexe 2). Accetability is defined as follow: « Score de 4 ou 5 sur au moins 2 des 
questions ». 
 
4.2 Secondary outcomes 
 
The within-group effect for each PROMs will be analyzed using linear mixed regression 
models, incorporating time as a fixed effect and patient-level variability as a random 
effect. Results will be reported as mean differences compared to baseline and 95% 
confidence intervals. Residuals normality and homoscedasticity assumptions will be 
validated. If violated, corrections will be made accordingly.  
 
 
5. STUDY LIMITATIONS 
 
In the absence of randomization, we cannot rule out the possibility of bias with patient  
selection and because of the small sample size results may not be generalizable. However, 
these are limitations associated with pilot studies. Sociodemographic data, including age, 
sex, comorbidities, initial disease severity (WHO classification), COVID vaccination status, 
number of infection, will be collected at baseline. No control group is included in this 
study. 
 
The primary and secondary outcomes are based on PROMs which are subjective. 
Although the PROMs used in this study to evaluate overall health status have been 
validated in LC patients, their sensitivity to detect changes in the condition overtime have 
not been well established. Nonetheless, the use of PROMs is a common research practice 
for post-COVID conditions.  
 
This pilot study in not intented to prove our hypothesis or assess the safety of the 
proposed intervention, but its goal is rather to enhance the rational for a larger scale 
study.  
 
6. ETHICAL CONSIDERATIONS 
 
The study will be conducted according to the current GCP, as well as the principles of the 
Declaration of Helsinki and its amendments. IRB committee will review and approve this 
protocol and informed consent. All subjects must provide a written informed consent 
before screening for participation in the study. This study will be performed by a qualified 
clinical investigator (Dr Piché) and in accordance with GCP.  
 

 
 
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The research team member will explain to the patient in lay terms the evidence that 
supports the study as well as the procedures, the risks and benefits, voluntary 
participation and the confidentiality of the study. Consenting participants will be 
informed that care will not be affected in any way should they decide to refuse 
participation or withdraw from the trial. All questions will be answered.  
 
Given the limited funding for this study, there will be no compensation to the participants 
for the study visits.  
 
 
6. ANTICIPATED RESULTS 
 
If PF is found to be feasible, well-accpeted by 95% of participants and safe, , the data will 
form the basis for a larger prospective, multicenter, randomized clinical trial in which 
patients with severe LC will undergo PF to determine its clinical efficacy to improve overall 
health. The study will be submitted to CIHR for funding. 
 
7. KNOWLEGE TRANSFERT 
 
Although this is a pilot study to determine whether there is a clinical rationale to pursue 
further assess PF, we attempt to publish our study in a peer-reviewed journal. Although 
our study focus on LC patient, it could also be relevant for patients suffering from other 
post-infectious conditions.  
 
8. REFERENCES 
1. Al-Aly, Z., Davis, H., McCorkell, L. et al. Long COVID science, research and policy. Nat 
Med 30, 2148–2164 (2024). https://doi.org/10.1038/s41591-024-03173-6  
2. Greenhalgh T, Sivan M, Perlowski A, Nikolich JŽ. Long COVID: a clinical update. Lancet. 
2024;404(10453):707-724. doi:10.1016/S0140-6736(24)01136-X. 
3. Statistics Canada. https://www150.statcan.gc.ca/n1/pub/75-006-
x/2023001/article/00015-fra.htm 
4. INSPQ.Affecion post-COVID-19 chez le personnel de la santé du Québec : 
fréquence,évolution et facteurs de risque. https://www.inspq.qc.ca/publications/3510 
5. Mercier K, Piché J, Rioux-Perreault C, Lemaire-Paquette S, Piché A. A longitudinal 
prospective cohort study of health-related quality of life assessment in outpatient adults 
with post-COVID-19 conditions. JAMMI, 2024 Jan 16;8(4):309-31. 

 
 
Piché, Alain 
Version 1.2 2025-03-12 
11 
6. Grundler F, Mesnage R, Cerrada A, Wilhelmi de Toledo F. Improvements during long-
term fasting in patients with long COVID - a case series and literature review. Front Nutr. 
2023 Nov 2;10:1195270. doi: 10.3389/fnut.2023.1195270. 
7. Christopher A. Rhule, Sahmla Gabriel, Toshia R. Myers, and Alan C. Goldhamer. 
Integrative and Complementary Therapies 2024 30:1, 11-13. 
8. Davis, H.E., McCorkell, L., Vogel, J.M. et al. Long COVID: major findings, mechanisms 
and recommendations. Nat Rev Microbiol 21, 133–146 (2023). 
https://doi.org/10.1038/s41579-022-00846-2 
9. Al-Hakeim, H.K., Al-Rubaye, H.T., Al-Hadrawi, D.S. et al. Long-COVID post-viral chronic 
fatigue and affective symptoms are associated with oxidative damage, lowered 
antioxidant defenses and inflammation: a proof of concept and mechanism study. Mol 
Psychiatry 28, 564–578 (2023). https://doi.org/10.1038/s41380-022-01836-9. 
10. Tavakoli, A., Akhgarjand, C., Ansar, H. et al. The effects of intermittent fasting on 
antioxidant and inflammatory markers and liver enzymes in postmenopausal, 
overweight and obese women with rheumatoid arthritis: a randomized controlled 
trial. Sci Rep 15, 2357 (2025). https://doi.org/10.1038/s41598-025-86734-0 
11. Roco-Videla, Á.; Villota-Arcos, C.; Pino-Astorga, C.; Mendoza-Puga, D.; Bittner-
Ortega, M.; Corbeaux-Ascui, T. Intermittent Fasting and Reduction of Inflammatory 
Response in a Patient with Ulcerative Colitis. Medicina 2023, 59, 1453. 
https://doi.org/10.3390/medicina59081453 
12. Horne BD, May HT, Muhlestein JB, Le VT, Bair TL, Knowlton KU, Anderson JL 
Association of periodic fasting with lower severity of COVID-19 outcomes in the SARS-
CoV-2 prevaccine era: an observational cohort from the INSPIRE Registry. BMJ Nutr Prev 
Health, 5 (2022), pp. 145-153, 10.1136/bmjnph-2022-000462 
13. Mark Ezpeleta, Sofia Cienfuegos, Shuhao Lin, Vasiliki Pavlou, Kelsey Gabel, Krista A 
Varady, Efficacy and safety of prolonged water fasting: a narrative review of human 
trials, Nutrition Reviews, Volume 82, Issue 5, May 2024, Pages 664–675,  
14. Jamshed H, Beyl RA, Della DL, Manna DL, Yang ES, Ravussin E, Peterson CM. Early 
time-restricted feeding improves 24-hour glucose levels and affects markers of the 
circadian clock, aging, and autophagy in humans 
Nutrients, 11 (2019), p. 1234.  
 
15. Antoni R., Johnston K.L., Collins A.L., Robertson M.D. Effects of intermittent fasting 
on glucose and lipid metabolism. Proc. Nutr. Soc. 2017;76:361–368. doi: 
10.1017/S0029665116002986. 
 

 
 
Piché, Alain 
Version 1.2 2025-03-12 
12 
16. Wilhelmi de Toledo F., Grundler F., Sirtori C.R., Ruscica M. Unravelling the health 
effects of fasting: A long road from obesity treatment to healthy life span increase and 
improved cognition. Ann. Med. 2020;52:147–161. doi: 
10.1080/07853890.2020.1770849. 
 
17. Sugiyama, A., Takafuta, T., Sato, T. et al. Natural course of post-COVID symptoms in 
adults and children. Sci Rep14, 3884 (2024). https://doi.org/10.1038/s41598-024-54397-
y. 
18. Klok FA, Barco S, Endres M et al. The Post-COVID-19 Functional Status scale: a tool to 
measure functional status over time after COVID-19. Eur Respir J. 2002 
https://erj.ersjournals.com/content/56/1/2001494. 
19. Ejalonibu, H., Amah, A., Aburub, A. et al. A review of Patient Reported Outcome 
Measures (PROMs) for characterizing Long COVID (LC)—merits, gaps, and 
recommendations. J Patient Rep Outcomes 8, 101 (2024). 
https://doi.org/10.1186/s41687-024-00773-1. 
20. Naik, H., Shao, S., Tran, K.C. et al. Evaluating fatigue in patients recovering from 
COVID-19: validation of the fatigue severity scale and single item screening 
questions. Health Qual Life Outcomes 20, 170 (2022). https://doi.org/10.1186/s12955-
022-02082-x 
21. Malesevic, S., Sievi, N.A., Baumgartner, P. et al. Impaired health-related quality of 
life in long-COVID syndrome after mild to moderate COVID-19. Sci Rep 13, 7717 (2023). 
https://doi.org/10.1038/s41598-023-34678-8 
22. Bland, A.R., Barraclough, M., Trender, W.R. et al. Profiles of objective and subjective 
cognitive function in Post-COVID Syndrome, COVID-19 recovered, and COVID-19 naïve 
individuals. Sci Rep 14, 13368 (2024). https://doi.org/10.1038/s41598-024-62050-x 
 
23. Lewis, M., Bromley, K., Sutton, C.J. et al. Determining sample size for progression 
criteria for pragmatic pilot RCTs: the hypothesis test strikes back!. Pilot Feasibility 
Stud 7, 40 (2021). https://doi.org/10.1186/s40814 -021-00770-x