Disclaimer: The aim of these rapid reviews is to retrieve, appraise, summarize and update the available evidence on COVID-related health technology. The reviews have not been externally peer- reviewed; they should not replace individual clinical judgement and the sources cited should be checked. The views expressed represent the views of the authors and not necessarily those of their host institutions. The views are not a substitute for professional medical advice.

Copyright Claims: This review is an intellectual property of the authors and of the Institute of Clinical Epidemiology, National Institutes of Health-UP Manila and Asia-Pacific Center for Evidence Based Healthcare Inc.

BACKGROUND

Virgin coconut oil is currently explored as an adjunctive treatment for patients with COVID-19 due to its antiviral and immunomodulatory properties. Virgin coconut oil is naturally extracted from fresh coconut kernel without using chemical or thermal treatment. It is rich in medium chain triglycerides. Lauric acid is the predominant fatty acid, comprising 45-52%, followed by myristic acid (15- 19%) and palmitic acid (10-11%). The hydrolysis of lauric acid in the body generates monolaurin, a pharmacologically active compound.1

Antiviral properties of lauric acid and monolaurin were demonstrated in previous studies. In vitro studies demonstrated the ability of monolaurin to disintegrate the viral cell envelope of both RNA and DNA viruses, possibly

through incorporation of fatty acids which destabilizes the lipid bilayer.2,3 Viral cell envelopes aid in viral entry into a host cell; its disintegration causes decreased or loss of infectivity. Lauric acid can inhibit viral maturation through reduction of viral glycoproteins and increased incorporation of triacylglycerols in the host plasma membrane. This inhibitory activity was demonstrated in vitro for the Junin virus and vesicular stomatitis virus, which are both enveloped single-stranded RNA (ssRNA) viruses.4,5,6 The salt form of lauric acid, sodium lauryl sulfate, also demonstrated inhibitory effects in vitro against human immunodeficiency virus (HIV) type 1 and Semliki Forest virus (both enveloped ssRNA viruses), herpes simplex virus type 1 and 2 (enveloped DNA viruses), and papillomavirus (non-enveloped DNA virus).6 Animal studies demonstrated that monolaurin has antiviral activity against avian influenza virus and Simean immunodeficiency virus, which are both enveloped ssRNA viruses.7,8 Clinical trials involving patients with HIV showed that virgin coconut oil reduces viral load and increases CD4+ T lymphocyte count.9,10

The immunomodulatory properties of virgin coconut oil were demonstrated in various studies. In vitro studies showed that virgin coconut oil suppresses inflammatory cytokines, including tumor necrosis factor-α, interferon-γ, interleukin-5, interleukin-6, and interleukin-8.11 Animal studies also demonstrated the anti-inflammatory effects of virgin coconut oil. Among rats with methotrexate- induced nephrotoxicity, virgin coconut oil supplementation resulted in decreased renal inflammatory markers and led to nephroprotective effects.12 Among rats with adjuvant- induced arthritis, virgin coconut oil supplementation resulted in decreased expression of inflammatory markers, including C-reactive protein, tumor necrosis factor-α, interleukin-6, nitric oxide and total white blood cell count. Histopathology of the paw tissue of the rats demonstrated decreased edema and cellular infiltration among those given virgin coconut oil.13

The current coronavirus disease (COVID-19) pandemic is caused by the novel human coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS- CoV-2 is an enveloped ssRNA virus.14 Data suggest that patients with severe COVID-19 symptoms may have cytokine release syndrome. Cytokine release syndrome is a systemic inflammatory response characterized by high levels of pro-inflammatory markers that is postulated to play a role in the morbidity and mortality of COVID-19.15

Due to these characteristics of COVID-19 infection, virgin coconut oil has been postulated as an effective adjuvant treatment. This review summarizes the available evidence on the efficacy and safety of virgin coconut oilin treating patients with COVID-19.

METHODS

See General Methods Section.

Articles were selected based on the following inclusion criteria:

•Population: COVID-19 patients of any age, with any co-morbidities, any severity

•Intervention: virgin coconut oil, any dose, any duration

•Comparator: placebo, any active control, no intervention

•Outcomes: clinical improvement, mortality

•Study designs: randomized controlled trials (RCTs), non-randomized studies, observational studies (e.g. cohort, case-control, cross-sectional, case report, case series)

RESULTS

There are no studies on the use of virgin coconut oil for the adjunctive treatment of COVID-19. There is an ongoing clinical trial that investigates the efficacy of virgin coconut oil for COVID-19 patients in the Philippines. It is a randomized controlled trial involving 80 study participants aged 18-59 years old admitted at the Philippine General Hospital with moderate to severe COVID-19. Forty participants will be given virgin coconut oil 15 mL three times daily for two weeks with standard care, while 40 participants will serve as the control group and will be given standard care. The primary outcome is recovery or resolution of symptoms, while the secondary outcomes include duration of hospital stay, time to first receiving ventilation or admitted to intensive care, white blood cell count, IL-6, ferritin, CRP, immunoglobulin, CD4+ counts at baseline, at one week and at two weeks, and negative test result for COVID-19 using reverse transcriptase-polymerase chain reaction.

To date, there are no guidelines that mention virgin coconut oil as an option for the adjunctive treatment of COVID-19.

DISCUSSION

There is currently no evidence to support the use of virgin coconut oil in the treatment of patients with COVID-19. Review of literature show the adverse events related to oral intake of virgin coconut oil.

No serious adverse events were reported with the use of virgin coconut oil. Among healthy volunteers aged 18 to 25 years old, daily intake of 30 mL of virgin coconut oil for eight weeks resulted in mild diarrhea in 71.9 percent, abdominal pain in 18.8 percent, and nausea/vomiting in 15.6 percent.16 Virgin coconut oil has also been associated with significant increase in high-density lipoprotein cholesterol but no significant change in low-density lipoprotein cholesterol, total cholesterol, and triglycerides.16,17 An open-label study on virgin coconut oil reported no significant adverse changes in lipid profiles, electrolytes, liver function tests and kidney function tests among obese volunteers with no other co- morbidities who were given 30 mL of virgin coconut oil daily for 4 weeks. Creatinine and alanine transferase levels

were significantly reduced.18 In contrast, a study among postmenopausal women given 30 mL of virgin coconut oil for four weeks reported significant increase in total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol.19 A study conducted among healthy volunteers in the Philippines given 15 mL of virgin coconut oil three times daily for six weeks reported significant increase in fasting blood sugar, creatinine, and platelet count, and a significant decrease in high-density lipoprotein cholesterol and white blood cell count.20

Data from the ongoing clinical trial on virgin coconut oil, and more trials on the use of virgin coconut oil in COVID-19 patients, are needed before definite conclusions and recommendations can be made on the use of virgin coconut oil for the adjunctive treatment of COVID-19.

CONCLUSION

At present, there are no studies that demonstrate the effectiveness of virgin coconut oil in the adjunctive treatment of COVID-19 infection.

In vitro and animal studies have proven the antiviral efficacy of virgin coconut oil against viruses with similar morphological characteristics to SARS-CoV-2. However, there are no studies that have established its antiviral properties in coronaviruses. In addition, the immunomodulatory effects of virgin coconut oil have been demonstrated through suppression of inflammatory cytokines and markers in both in vitro and animal studies.

Adverse events associated with virgin coconut oil intake include mild diarrhea, abdominal pain, and nausea/vomiting. No serious adverse effects have been reported. Studies have conflicting evidence regarding the effect of virgin coconut oil intake on serum lipid profiles and creatinine levels.

Declaration of Conflict of Interest

No conflict of interest.

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