A Review on the Antiviral Activity of Functional Foods Against COVID-19 and Viral Respiratory Tract Infections

Figures & data

Table 1 The “FOSHU” Standards for Functional Foods are Used in Japan^10,213

1. Foods with applicable constituents are likely to have a specific health impact or foods that already have allergens removed. 2. Foods for which the impact of such a modification (addition or removal) has been clinically tested and permitted to make claims about the potential health benefits anticipated from their intake have been given. 3. Based on naturally occurring foods, products should be in the form of ordinary foods (ie, not powder, pills, or capsules). 4. Foods should have been part of a regular daily diet. 5. Foods serve a specific function in the human body, including;  ● improve immune system function,  ● prevent specific diseases,  ● aid in the treatment of specific diseases,  ● control physical and mental complaints,  ● delay the ageing process.

Table 2 Functional Foods Definitions by Different Nations and Organizations

Organization	Nations	Definitions	References
FOSHU	Japan	Processed foods containing ingredients that aid specific bodily functions in addition to being nutritious	^Citation10,Citation16
FUFOSE	Europe	Functional food has specific beneficial effects on one or more target functions in the body beyond the basic nutritional effects resulting from improved health state and well-being or reduced risk of diseases. It is consumed as a part of a regular diet and is not used in the form of pill or capsule, or any other form of dietary supplement	^Citation214
BNS	Canada	Similar in appearance to conventional food, consumed as part of the usual diet, with demonstrated physiological benefits, and/or to reduce the risk of chronic disease beyond basic nutritional functions	^Citation215
IFIC	USA	“Foods or dietary components that may provide a health benefit beyond basic nutrition”	^Citation216
ILSI	USA	Foods that, by virtue of physiologically active food components, provide health benefits beyond basic nutrition	^Citation216
EC	Europe	Satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, in a way that is relevant to either an improved state of health and well-being and/or reduction of risk of disease	^Citation217
IOM	USA	Foods in which the concentrations of one or more ingredients have been manipulated or modified to enhance their contribution to a healthful diet	^Citation215
ADA	USA	Whole foods and fortified, enriched, or enhanced foods, have a potentially beneficial effect on health when consumed as part of a varied diet and regularly, at adequate levels	^Citation215
FFC	USA	Natural or processed foods that contain known or unknown biologically active compounds; which, in defined, effective, non-toxic amounts, provide a clinically proven and documented health benefit for the prevention, management, or treatment of chronic disease	^Citation218

Abbreviations: FOSHU, foods of specified health use; FUFOSE, Functional Food Science in Europe; BNS, Bureau of Nutritional Sciences; IFIC, International Food Information Council; ILSI, International Life Sciences Institute of North America; EC, European Commission; IOM, Institute of Medicine of the National Academy of Sciences; ADA, American Dietetic Association; FFC, Functional Food Center; USA, United States of America.

Figure 1 Classification of functional foods based on their sources of origin.

Table 3 Functional Foods and Their Antiviral Properties with the Primary Dietary Sources

Functional Foods	Main Dietary Sources	Functional Description	References
Vitamin A	Milk, eggs, liver, oily fish, fortified cereals, dark orange or green vegetables, orange fruits, and tomato juice.	Decreased pneumonia morbidity and helps relieve clinical symptoms and signs of pneumonia and shorten the length of hospital stay in children.	^Citation219,Citation220
Vitamin C	Oranges and orange juice, red and green peppers, strawberries, blackcurrants, kiwi, broccoli, potatoes	Vitamin C reduced the duration of common colds, reduced the intensity of colds, and reduced the incidence and duration of pneumonia.	^Citation221,Citation222
Vitamin D	Oily fish, liver, eggs, fortified foods (spreads and some breakfast cereals)	Vitamin D has been shown to reduce the incidence of respiratory infections. Conversely, vitamin D insufficiency has been linked to an increased risk of community-acquired pneumonia.	^Citation223,Citation224
Vitamin E	Wheat germ, nuts and seeds, vegetable oils	Increases the activity of natural killer cells and has anti-inflammatory effects against colds and pneumonia.	^Citation225
Zinc, Copper, and Iron	Shellfish, meat, cheese, some grains and seeds, cereals, nuts, liver, and some vegetables	Chinese children with recurrent respiratory infections showed reduced zinc, copper, and iron levels in their hair.	^Citation226
Zinc	Shellfish, meat, cheese, and cereals	Oral zinc formulations may help to decrease the duration of common cold symptoms; they also reduce the prevalence of pneumonia	^Citation227,Citation228
Quercetin	Capers, onions, apple, berries, and Cilantro (coriander)	Interaction with the HA2 viral subunit to inhibit the H5N1 virus inhibitory activity in the early stage of influenza infection inhibits binding station ACE.	^Citation229,Citation230
Curcumin	Rhizome of turmeric (Curcuma longa)	Binding to three protein receptors: RBD-S (PDB ID:6LXT), PD-ACE2 (PDB ID:6VW1), and SARS-CoV-2 protease (PDB ID:6LU7)	^Citation231,Citation232
Polyphenols	Pomegranate, apricots, peaches, mango, spinach, broccoli, orange, tomato, apple and berries	Reduce the inflammatory response in adipocytes, macrophages, and other immune cells to prevent and combat inflammation.	^Citation171,Citation233

López-Varela S, González-Gross M, Marcos A. Functional foods and the immune system: a review. Eur J Clin Nutr. 2002;56(3):S29–S33. doi:10.1038/sj.ejcn.1601481

 PubMed Web of Science ®Google Scholar

Iwatani S, Yamamoto N. Functional food products in Japan: a review. Food Sci Hum Wellness. 2019;8(2):96–101. doi:10.1016/j.fshw.2019.03.011

 Google Scholar

Roberfroid MB. 1 - Defining functional foods. In: Gibson GR, Williams CMBT-F-F editors. Woodhead Publishing Series in Food Science, Technology and Nutrition. Woodhead Publishing; 2000:9–27. doi:10.1533/9781855736436.1.9.

 Google Scholar

Regulation EC. No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods. Off J Eur Union. 2007;50:3–18.

 Google Scholar

Hasler CM, Bloch AS, Thomson CA, Enrione E, Manning C. Position of the American Dietetic Association: functional foods. J Am Diet Assoc. 2004;104(5):814–826.

 PubMedGoogle Scholar

Bagchi D. Nutraceuticals and functional foods regulations in the United States and around the world. Toxicology. 2006;221(1):1–3. doi:10.1016/j.tox.2006.01.001

 PubMed Web of Science ®Google Scholar

Henry CJ. Functional foods. Eur J Clin Nutr. 2010;64(7):657–659. doi:10.1038/ejcn.2010.101

 PubMed Web of Science ®Google Scholar

Martirosyan DM, Singh J. A new definition of functional food by FFC: what makes a new definition unique? Funct Foods Heal Dis. 2015;5(6):209–223.

 Web of Science ®Google Scholar

Hu N, Li Q-B, Zou S-Y. Effect of vitamin A as an adjuvant therapy for pneumonia in children: a Meta analysis. Zhongguo Dang Dai Er Ke Za Zhi. 2018;20(2):146–153. doi:10.7499/j.issn.1008-8830.2018.02.013

 PubMedGoogle Scholar

Imdad A, Mayo-Wilson E, Herzer K, Bhutta ZA. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database Syst Rev. 2017;3(3):CD008524–CD008524. doi:10.1002/14651858.CD008524.pub3

 PubMed Web of Science ®Google Scholar

Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2013;1:45.

 Google Scholar

Hemilä H, Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst Rev. 2013;8:53.

 Google Scholar

Bergman P, Åu L, Björkhem-Bergman L, Lindh JD. Vitamin D and respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2013;8(6):e65835.

 PubMed Web of Science ®Google Scholar

Zhou Y-F, Luo B-A, Qin -L-L. The association between vitamin D deficiency and community-acquired pneumonia: a meta-analysis of observational studies. Medicine (Baltimore). 2019;98:38.

 Web of Science ®Google Scholar

Lee GY, Han SN. The role of vitamin E in immunity. Nutrients. 2018;10(11):1614.

 PubMed Web of Science ®Google Scholar

Mao S, Zhang A, Huang S. Meta-analysis of Zn, Cu and Fe in the hair of Chinese children with recurrent respiratory tract infection. Scand J Clin Lab Invest. 2014;74(7):561–567. doi:10.3109/00365513.2014.921323

 PubMed Web of Science ®Google Scholar

Johnstone J, Roth DE, Guyatt G, Loeb M. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. Cmaj. 2012;184(10):E551–E561.

 PubMed Web of Science ®Google Scholar

Hemilä H. Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage. JRSM Open. 2017;8(5):2054270417694291.

 Google Scholar

Wu W, Li R, Li X, et al. Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry. Viruses. 2016;8(1):6.

 Web of Science ®Google Scholar

Li Y, Yao J, Han C, et al. Quercetin, inflammation and immunity. Nutrients. 2016;8(3):167.

 PubMed Web of Science ®Google Scholar

Ali A, Banerjea AC. Curcumin inhibits HIV-1 by promoting Tat protein degradation. Sci Rep. 2016;6(1):1–9.

 PubMed Web of Science ®Google Scholar

Colpitts CC, Schang LM, Rachmawati H, et al. Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells. Gut. 2014;63(7):1137–1149.

 PubMed Web of Science ®Google Scholar

Lin SC, Ho CT, Chuo WH, Li S, Wang TT, Lin CC. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect Dis. 2017;17(1):1–10. doi:10.1186/s12879-017-2253-8

 PubMed Web of Science ®Google Scholar

Kaihatsu K, Yamabe M, Ebara Y. Antiviral mechanism of action of epigallocatechin-3-O-gallate and its fatty acid esters. Molecules. 2018;23(10):2475.

 PubMed Web of Science ®Google Scholar