Low Carbohydrate Diet for Post-COVID Syndrome

Overseen By Nuria Pastor-Soler, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Southern California

Must not be taking: KetoCitra, SGLT2 inhibitors, Antacids, others

Disqualifiers: Diabetes, Heart failure, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a low-carbohydrate diet can aid recovery from long COVID, which causes lingering symptoms such as fatigue, brain fog, and muscle pain. The researchers are testing if this diet, combined with a special supplement called KetoCitra, can enhance recovery by lowering blood sugar and increasing a compound called BHB in the blood. Participants will either follow this diet plan or maintain their usual eating habits. Individuals who had COVID-19 at least two months ago and still experience at least two common long COVID symptoms might be suitable for this study. As an unphased trial, this study offers a chance to contribute to groundbreaking research that could improve long COVID recovery strategies.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are using certain medications like KetoCitra, urine alkalizing agents, citrate treatments, calcium supplements, antacids or phosphate binders containing aluminum, SGLT2 inhibitors, or immunosuppressive treatments. It's best to discuss your current medications with the study personnel to see if they affect your eligibility.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that low-carbohydrate diets are generally easy to follow. Some studies have found that people can safely maintain these diets for a long time without major side effects. This diet reduces sugars and starches while increasing healthy fats and proteins.

Regarding COVID-19 recovery, early research suggests that low-carb diets might help manage symptoms by lowering blood sugar and increasing energy molecules called ketones. These changes could help the body use energy more efficiently, potentially easing long COVID symptoms like tiredness and difficulty concentrating.

The medical food used in this trial, called KetoCitra, includes ingredients like BHB and minerals, which are usually safe. It helps the body use fat for energy without requiring a strict ketogenic diet. While specific safety data for this treatment isn't available yet, the ingredients have been used in other diets without major problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike typical treatments for post-COVID syndrome that may focus on managing symptoms through medication or rehabilitation, a low carbohydrate diet intervention is unique because it uses dietary changes to potentially address the condition's root metabolic issues. This approach incorporates KetoCitra®, a medical food containing BHB (beta-hydroxybutyrate) and citrate, which supports a metabolic switch aimed at enhancing energy metabolism. Researchers are excited about this treatment because it offers a non-pharmacological option that targets metabolic processes, which could lead to significant improvements in energy levels and overall recovery for patients.

What evidence suggests that this trial's dietary interventions could be effective for post-COVID syndrome?

This trial will compare a low-carbohydrate diet intervention with a control group following their usual diet. Studies have shown that dietary changes can help alleviate long COVID symptoms. Research suggests that ketogenic diets, high in fats and low in carbohydrates, might enhance brain energy use and aid overall recovery. Some studies indicate that these diets could reduce severe symptoms by decreasing inflammation. In another study, participants with long COVID who received personalized dietary advice reported physical improvement. Early reports also show that a ketogenic diet may significantly improve several long COVID symptoms. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

Adults who had COVID-19 at least 2 months ago and are experiencing ongoing neurological or physical symptoms typical of long COVID, such as fatigue, loss of smell, or shortness of breath. Participants must not be hospitalized or have conditions like chronic kidney disease stage III+, heart failure, liver cirrhosis, autoimmune diseases, active infections, certain eating disorders or be on specific medications that could interfere with the study.

Inclusion Criteria

You tested positive for COVID-19 at least 2 months before the study starts.

I have at least two long COVID symptoms like fatigue or headache.

Exclusion Criteria

You have certain health conditions, such as chronic high potassium levels, HIV, drug or alcohol abuse, malabsorption syndrome, certain types of cancer, autoimmune disease, specific digestive and urinary tract issues, certain types of diabetes, heart and kidney problems, or other conditions that make you unsuitable for the study. You are pregnant, planning to become pregnant, or nursing. You are not willing to make dietary changes, undergo blood tests, or keep track of your health information for the study. You have certain dietary restrictions or allergies, or you rely on oxygen or dialysis treatment.

I am currently in the hospital.

Any significant systemic illness or medical condition or use of medication that could affect the safety of the research subject or could affect compliance with the study, as determined by the study personnel and a physician

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a low-carbohydrate dietary intervention with KetoCitra or follow a usual diet for 30 days

4 weeks

Weekly online journal entries

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low carbohydrate diet intervention

Trial Overview

The trial is testing a low-carbohydrate diet intervention aimed at reducing blood glucose and increasing blood BHB levels to improve long COVID symptoms. This includes avoiding sugars and starches while consuming healthy fats and proteins along with a medical food supplement. The control group will receive standard therapy without dietary changes.

How Is the Trial Designed?

Group I: Low Carbohydrate Experimental Treatment 1 Intervention

-Low-Carbohydrate Diet Intervention:Patients will receive a study kit. The kit will contain the following: * Instruction sheet containing medical food instructions and food journal and a web link to the weekly online journal * A 30-day supply of the medical food, KetoCitra, developed by Santa Barbara Nutrients, Inc. KetoCitra® is a ready-to-mix powder to be dissolved in water and taken twice per day with meals. KetoCitra® contains BHB, citrate, and a blend of minerals (potassium, calcium, magnesium) and is flavored with natural lemon flavor and stevia natural sweetener. KetoCitra® is sugar- and sodium-free and is intended to support the metabolic switch aimed for with the low-carbohydrate diet by providing exogenous BHB. (Package insert)

Group II: Control Active Control 1 Intervention

-Usual diet.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Published Research Related to This Trial

The ketogenic diet (KD) and ketone bodies, particularly β-hydroxybutyrate (BHB), have shown potential in supporting the immune response against COVID-19 by improving mitochondrial function and reducing glycolysis in immune cells, which may help during the virus's entry into host cells.

In animal studies, KD provided benefits such as protection against weight loss, faster recovery, and improved survival rates, while in humans, it was associated with increased survival and reduced hospitalization needs for COVID-19, suggesting it could be a valuable nutritional intervention, though further validation is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic Diet and Ketone Bodies as Clinical Support for the Treatment of SARS-CoV-2-Review of the Evidence. Bolesławska, I., Kowalówka, M., Bolesławska-Król, N., et al.[2023]

In a study on mice, a ketogenic diet (KD) improved survival rates and reduced weight loss after SARS-CoV-2 infection, indicating potential protective effects against the virus.

The KD was associated with decreased systemic inflammation, as shown by lower levels of pro-inflammatory cytokines and altered metabolic responses, suggesting it may help modulate the immune response during viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation. Palermo, A., Li, S., Ten Hoeve, J., et al.[2023]

Post-COVID disorders syndrome (PCDS) includes persistent symptoms like respiratory issues, fatigue, neuropsychiatric disorders, and gastrointestinal problems, highlighting the complexity of recovery after COVID-19.

Adequate intake of vitamins D, C, E, zinc, and omega-3 fatty acids may support immune function and aid in the rehabilitation of patients with PCDS, suggesting that dietary supplements could be beneficial, though more research is needed to establish effective dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of micronutrients in the comprehensive rehabilitation of patients with the novel coronavirus infection COVID-19]. Marchenkova, LA., Makarova, EV., Yurova, OV.[2021]

In a randomized, double-blind, placebo-controlled trial involving 463 patients with post-acute COVID-19 syndrome (PACS), the synbiotic preparation SIM01 significantly alleviated symptoms such as fatigue, memory loss, and difficulty in concentration after 6 months of treatment.

The safety profile of SIM01 was comparable to placebo, with similar rates of adverse events, suggesting it is a safe option for managing PACS symptoms through modulation of the gut microbiome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial. Lau, RI., Su, Q., Lau, ISF., et al.[2023]

A 2-month nutritional intervention using a high-fiber formula significantly alleviated gastrointestinal symptoms in a patient with post-acute COVID-19 syndrome, leading to improvements in appetite, anxiety, and medication dosage for nausea.

The intervention resulted in beneficial changes in the patient's gut microbiota, including the increase of short-chain fatty acid-producing bacteria, which may be linked to symptom relief, highlighting the potential of gut microbiota modulation as a therapeutic strategy for post-COVID-19 gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional Modulation of Gut Microbiota Alleviates Severe Gastrointestinal Symptoms in a Patient with Post-Acute COVID-19 Syndrome. Wang, Y., Wu, G., Zhao, L., et al.[2022]

Post-COVID-19 syndrome can lead to malnutrition, loss of muscle mass, and low-grade inflammation, highlighting the need for comprehensive health evaluations for COVID-19 survivors.

Personalized dietary recommendations are crucial for recovery, as they can help address persistent symptoms like fatigue, appetite loss, and psychological distress in patients recovering from COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Recommendations for Post-COVID-19 Syndrome. Barrea, L., Grant, WB., Frias-Toral, E., et al.[2022]

A telemedicine-delivered very-low-carbohydrate intervention targeting nutritional ketosis resulted in significant weight loss for both pandemic and pre-pandemic cohorts, with an average weight loss of 7.5% and 7.9% respectively over one year.

The weight loss trajectory was similar for both groups, indicating that the intervention was effective regardless of the pandemic's impact on lifestyle and stress, demonstrating its robustness as a weight management strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the COVID-19 Pandemic on the Effectiveness of a Metabolic Health Telemedicine Intervention for Weight Loss: A Propensity Score Matching Analysis. Athinarayanan, SJ., Adams, RN., VanTieghem, M., et al.[2022]

Ketogenic diets (KDs) can effectively reduce fat mass and improve metabolic health, which is crucial for individuals with obesity and related conditions that worsen COVID-19 outcomes.

The increase in ketone bodies from KDs has anti-inflammatory and immunomodulating effects, potentially helping to prevent severe COVID-19 complications by addressing critical risk factors like obesity, type 2 diabetes, and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dark side of the spoon - glucose, ketones and COVID-19: a possible role for ketogenic diet? Paoli, A., Gorini, S., Caprio, M.[2020]

In a study of 11 adults with refractory epilepsy, the ketogenic diet led to significant reductions in seizure frequency for some patients, with three experiencing a 90% decrease and three a 50-89% decrease after 8 months.

While the diet was generally tolerable, common side effects included constipation and menstrual irregularities, and some patients struggled to maintain ketosis at home, indicating the need for further research on its long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet for intractable epilepsy in adults: preliminary results. Sirven, J., Whedon, B., Caplan, D., et al.[2019]

In a study of ambulatory individuals with type 2 diabetes and obesity, those who followed a medically supervised ketogenic diet (MSKD) had higher ketone levels and greater weight loss, which were associated with a lower likelihood of hospitalization due to COVID-19.

Specifically, patients who experienced greater weight loss (6.8% compared to 4.2%) had a significantly reduced risk of hospitalization, suggesting that rapid weight loss through MSKD may help mitigate the severity of COVID-19 in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced COVID-19 severity elicited by weight loss from a medically supervised ketogenic diet in a geographically diverse ambulatory population with type 2 diabetes and obesity. Volk, BM., Roberts, CGP., VanTieghem, M., et al.[2023]

Nearly half of the 92 participants recovering from COVID-19 were at risk for malnutrition, which was linked to more severe symptoms and lower calorie intake, indicating that persistent malnutrition can hinder recovery.

Most participants failed to meet dietary recommendations for fruits, vegetables, and optimal protein intake, suggesting a critical need for nutritional education and support to improve recovery outcomes after COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of COVID-19 Infection and Persistent Lingering Symptoms on Patient Reported Indicators of Nutritional Risk and Malnutrition. Deer, RR., Hosein, E., Harvey, M., et al.[2022]

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