Enzymes and Probiotics for Post-Covid Fatigue!

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Anatomy, Bacteria, Bacterium, Bowels, Diarrhea

by Dr. Valerie Donaldson via Regenerative Medicine Center

One of the biggest complaints when infected with Covid is the exhaustive fatigue which can be unrelenting. Fatigue is the most persistent and debilitating symptom of Long Haul Covid”.1

Last week’s blog reviewed the use of Thymosin Alpha in Long Haul Covid.

This week is a review of a randomized, multicentric, double blind, placebo-controlled study conducted in India of 200 participants using enzymes and probiotics to treat post-Covid fatigue.

Prevalence of Post-Covid Fatigue

Post-viral fatigue, also called Chronic Fatigue Syndrome or CFS, has been identified following many viral infections including coronaviruses, leading to diminished quality of life and even disability. 48% of individuals infected with Middle East respiratory syndrome (MERS) had persistent fatigue after 12 months. Individuals infected with severe acute respiratory syndrome (SARS) experienced significant fatigue with 64% at 3 months, 54% at 6 months and 60% at 12 months.   Post-Covid-19 fatigue is seen in up to 52% of Covid patients.

Although there is no unifying mechanism, biomarker or blood test to identify the cause of CFS to date, at RMC there seems to be a correlation with chronically elevated SARS CoV2 IgM and Long Haul Covid symptoms.  Other hypotheses for the cause of CFS include global inflammation, increased stress, shift in neurotransmitter levels, mitochondrial or immune dysfunction. In addition, an emerging connection between gut dysbiosis and Chronic Fatigue Syndrome has been implicated.2,3

Gut Health and Covid

Gut health is crucial to immune function as it is estimated 80% of immune cells live in the gut.4 When functioning properly, trillions of gut microbes fight toxins, eliminate pathogens, boost metabolism and immunity, and even produce neurotransmitters such as serotonin.  Gut flora imbalance has been implicated in many other conditions such as depression, irritable bowel syndrome, inflammatory bowel disease, arthritis, neurodegenerative diseases, colorectal cancer and even autism.9,10,11,12

Several studies have implicated poor gut health as a predictor of severe Covid disease. Patients with at least one gastrointestinal symptom on presentation with Covid had more severe disease and worsened outcomes.5,6,7 Probiotics given to Covid patients with acute infection showed early promise in decreasing gastrointestinal symptoms, inflammatory markers, and time to a negative test.8

Studies show the use of probiotics in management of CFS has been successful in improving general well-being as well as decreasing anxiety symptoms.

Digestive enzymes have also been identified to be immunomodulatory and anti-inflammatory and have been used for decades in chronic disease states.

The Study: Efficacy of Systemic Enzymes and Probiotics in the Resolution of Post-COVID Fatigue

This study demonstrates a positive outcome when combining digestive and systemic enzymes and probiotics in the treatment of post-Covid fatigue.

200 patients were enrolled who were confirmed negative for active Covid infection and had a complaint of post-Covid fatigue.  The test arm and control arm each consisted of 100 patients, receiving either the probiotic and enzyme combination or placebo for 14 days. Both control and test arms had similar fatigue scores on day 0.

The placebo arm was given capsules containing maltodextrin.   The test arm was treated with ImmunoSEB, a systemic enzyme formulation,  2 capsules twice a day;  plus ProbioSEB, a blend of probiotics, 2 capsules once a day at noon.

Improvement scores were calculated using CFQ-11, a self-reported fatigue scale. Physical fatigue was measured via ranking the following: drowsiness, need to rest, ability to do things, energy level, feeling of weakness, muscle strength and tiredness. Mental fatigue was measured via the following: ability to focus or think clearly, memory difficulties, difficulty concentrating. Endpoints were determined by assessing improvement in mental fatigue and physical fatigue on days 4, 8 and 11.

Study Results

By day 14, the group treated with probiotics and systemic enzymes showed a complete resolution of fatigue in 91% of subjects versus 15% in the control group.  In addition, over half of the remaining 9% in the treatment group showed a lower fatigue score compared to baseline.  Compared to the control arm, the test arm showed a significantly greater reduction in both physical and mental fatigue at all time points as seen illustrated in the graph below.


In conclusion,  results of this study demonstrate a 14-day supplementation of probiotics and digestive and systemic enzymes can improve and even resolve post-Covid fatigue.

Optimizing gut flora may not just be beneficial in the management of acute and Long Haul Covid but also has much broader implications among many disease processes and those individuals suffering from fatigue of all causes.  Targeting gut health can bring new opportunities for prevention, treatment, and improvement of many diseases.

Have an awesome day!   Dr D

  1. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8472462/
  2. https://www.nature.com/articles/s41380-021-01032-1
  3. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8584653/
  4. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8001875/
  5. https://link.springer.com/article/10.1007/s12602-021-09875-4
  6. https://journals.asm.org/doi/10.1128/mbio.03022-20?permanently=true
  7. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7438210/
  8. https://apm.amegroups.com/article/view/86721/html
  9. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5900870/
  10. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8303183/
  11. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6673757/pdf/fpsyt-10-00473.pdf
  12. https://www.frontiersin.org/articles/10.3389/fcimb.2021.625913/full

Reprinted with permission from Regenerative Medicine Center.