A recent systematic review found limited and inconsistent evidence that treating micronutrient deficiencies with high-dose micronutrient supplements, including vitamins A, C, D, and E, and Fe, Zn, and Se, is effective in preventing and hastening recovery from diseases like COVID-19(Reference James, Ali and Armitage1). The researchers suggested that maintaining a balanced diet is more important for prevention of COVID-19. Furthermore, obesity and type 2 diabetes prevalence related to consumption of a Western diet high in refined foods increases a population’s risk for COVID-19 severity and mortality(Reference Butler and Barrientos2). Alternatively, plant-based diets that include fruits, vegetables, grains, legumes, nuts and seeds, while restricting foods from animal origins such as meat, dairy products and eggs, are proposed to prevent human disease, as well as reduce environmental damage and eliminate animal suffering associated with an omnivorous Western diet(Reference Alcorta, Porta and Tárrega3). Properly balanced plant-based diets provide adequate sources of protein, Ca, Fe, vitamin D and vitamin B12 (Reference Tuso, Ismail and Ha4).
Consumption of a Western diet leads to chronic inflammation by stimulating the innate immune system and impairing adaptive immunity, which reduces defences against viral infections(Reference Butler and Barrientos2). Neuroinflammatory mechanisms associated with peripheral inflammation in COVID-19 are also exacerbated by a poor diet, which can lead to neurodegenerative disease and dementia. Additionally, obese patients with chronic low-grade inflammation related to high adiposity are more susceptible to severe SARS-CoV-2 infection, as are malnourished patients, especially the elderly who lack immune protection provided by a balanced diet(Reference Morais, Aquino and da Silva-Maia5). During the outbreak of the COVID-19 pandemic in Wuhan, China, 52·7 % of infected patients aged 65 years and older were malnourished and an additional 27·5 % were at risk for malnutrition(Reference Li, Zhang and Gong6).
‘In both undernutrition and obesity, the ingestion of monotonous diets rich in ultra processed foods may lead to vitamin and mineral deficiencies, impairing the immune system and increasing susceptibility to SARS-CoV-2’(Reference Morais, Aquino and da Silva-Maia5).
An analysis of COVID-19 patients’ nutritional status in an Iranian population found that low fruit and vegetable intake was significantly associated with disease severity – 63 % of patients consumed between zero to one serving of fruit a day and 77 % reported no daily intake of vegetables(Reference Karimi, Tondro and Hematpour7). On the other hand, the Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) promote dietary patterns rich in unprocessed fruits and vegetables, and these dietary patterns are associated with anti-inflammatory outcomes(Reference Morais, Aquino and da Silva-Maia5). A systematic review and meta-analysis of seventeen randomised controlled trials found that adherence to the Mediterranean diet decreased inflammatory markers of endothelial dysfunction and CVD risk, such as C-reactive protein, IL-6 and intracellular adhesion molecule-1(Reference Schwingshackl and Hoffmann8). The Mediterranean diet is also associated with a protective effect against risk of COVID-19(Reference Perez-Araluce, Martínez-González and Gea9). Although research on the DASH diet and COVID-19 is lacking, the DASH diet is noted for reduced inflammation and lower cardiac injury and strain when combined with low Na consumption(Reference Juraschek, Kovell and Appel10).
Compared with plant-based diets, the Western diet contributes additional sources of Na from meat and poultry. Na is added to processed meats, and sodium chloride is injected into poultry during processing to improve texture and water-holding capacity(Reference Petracci, Bianchi and Mudalal11), which can increase the Na content of a four-ounce serving of chicken from 50–75 mg to 400 mg(Reference Conis12). A Canadian study found that Na was an added ingredient in 72 % of poultry products(Reference Parpia, L’Abbé and Goldstein13). Next to pizza consumed by young people between 6 and 19 years of age, and yeast breads consumed by people 51 years and older, chicken and chicken mixed dishes provided the most Na of all food categories among all age groups in an analysis of data from the US National Health and Nutrition Examination Survey (NHANES) 2003–2008(Reference Drewnowski and Rehm14).
A recent systematic review of global nations found that ultraprocessed food was most commonly consumed in the USA and Great Britain, with the least consumption in Italy, which the researchers attributed to the Italian population’s greater adherence to a traditional Mediterranean diet(Reference Marino, Puppo and Del Bo’15). In spite of this, Italy has experienced a high rate of COVID-19 infections(Reference Cook, Marshall and Fowler16). However, Italy is also known to have high dietary salt intake(Reference Donfrancesco, Lo Noce and Russo17). Consumers may add salt to whole-food recipes prepared with few or no foods processed with Na, and people often employ salt as a condiment at meals, emphasising an important point that not all whole-food diets are low in Na. Additionally, an Action on Salt survey of plant-based and vegan foods served in UK restaurants and fast-food outlets found a high level of salt in most items(18). Dietary Na intake in various cultures and nations needs to be considered in research investigating the association of COVID-19 prevention with whole-food plant-based diets (WFPB).
The present article proposes that COVID-19 prevention associated with a WFPB diet is potentially mediated by high intake of unprocessed fruits, vegetables, whole grains, legumes, nuts and seeds, with low intake of ultraprocessed foods, Na and foods of animal origin. A grounded theory method was used when writing this paper to search and select relevant research findings from the peer-reviewed literature on dietary Na, WFPB diets and COVID-19(Reference Wolfswinkel, Furtmueller and Wilderom19). A comparative analysis of the selected findings was used to conceptualise themes and synthesise the present grounded theory narrative.
Sodium toxicity and COVID-19
Sodium toxicity and COVID-19 symptoms
Na toxicity is a condition within the body caused by poisonous effects of excessive Na intake, as in overdose death from acute salt poisoning(Reference Mehlenbacher, Garbach and Eggleston20). Na toxicity can also occur from large amounts of Na ingested over long periods(Reference Soloway21). A daily Na dietary intake greater than 2300 mg is associated with increased risks of CVD and other chronic diseases(22). Furthermore, Na toxicity has been associated with the nutritional epidemiology and nutritional immunology of COVID-19(Reference Brown23). The effects of Na toxicity on mechanisms of COVID-19 symptoms are summarised in this section.
Acute respiratory distress syndrome is a fatal condition in COVID-19 that blocks the air sacs of the lungs with a gummy yellow fluid causing severe shortness of breath and reduced arterial oxygen saturation(Reference Begley24). Of relevance, lung fluid in acute respiratory distress syndrome appears identical to lung fluid in pulmonary oedema(Reference Carlson, Schaeffer and Michaels25). Recent research confirms that pulmonary oedema is a pathological feature in severe cases of COVID-19(Reference Cui, Chen and Zhou26). Furthermore, infusions of excess sodium chloride into the lungs have been found to cause pulmonary oedema(Reference Hutchin, Terzi and Hollandsworth27) – potentially relating acute respiratory distress syndrome and pulmonary oedema in COVID-19 to effects of Na toxicity from excessive sodium chloride and retained fluid that may accumulate in the lungs.
Other symptoms of COVID-19 include nasal sinus congestion, headache and fever which are also associated with Na toxicity. According to the WHO, sinuses in acute sinusitis are blocked with fluid which can cause headaches(28). Fluid blockage in sinuses may be due to hypervolemia and nasal mucosal oedema from Na toxicity. Migraine headache pain is also associated with COVID-19(Reference Sampaio Rocha-Filho and Magalhães29), and Na permeability through the blood–cerebral spinal fluid barrier as well as through the blood−brain barrier are increased in migraine(Reference Ghaffari, Grant and Petzold30). Fever is listed among adverse effects of pharmaceutical sodium chloride tablets(31). Furthermore, fever occurs from the pyrogen action of sodium chloride injected into laboratory animals, which may affect control of hyperthermia due to an imbalance between Ca and Na ions in the anterior hypothalamus(Reference Feldberg and Saxena32).
Virion aggregates are normally shed through the upper nasal passages of the mucosal immune system, but aggregates of SARS-CoV-2 may accumulate in the upper nasal passages due to impaired mucociliary clearance from the ciliostasis effect of sodium chloride(Reference Fu, Tong and Meng33). Prolonged mucociliary clearance was found in COVID-19 patients compared with other patients with non-nasal symptoms(Reference Koparal, Kurt and Altuntas34). Moreover, viral sepsis occurs as the accumulation of viruses and other particles in the upper nasal passages enter the bloodstream(Reference Li, Liu and Zhang35), and sepsis was increased in elderly patients with increased concentrations of plasma Na in hypernatremia(Reference De Freitas, Gudur and Vela-Ortiz36). A link between sepsis and excess Na could explain the occurrence of sepsis in COVID-19 patients potentially related to Na toxicity(Reference Li, Liu and Zhang35).
Sodium toxicity and COVID-19 immnue response
Na toxicity also affects immune response mechanisms in COVID-19, summarised as follows. Changed immune responses that promote inflammation and organ damage are associated with sodium chloride intake, which increase the release of inflammatory cytokines: TNF-α, IL-6 and macrophage inflammatory protein-2(Reference Afsar, Kuwabara and Ortiz37). Of relevance, responses to RNA viruses like SARS-CoV-2 are similarly associated with increased secretion of cytokines, IL-6 and TNF-α, with fewer antiviral responses and more pro-inflammatory responses(Reference Vabret, Britton and Gruber38).
Increased levels of sodium chloride stimulate T-cell proliferation and lower anti-inflammatory responses – pro-inflammatory M1 macrophages are increased and anti-inflammatory M2 macrophages are suppressed by increased levels of sodium chloride. Moreover, sodium chloride enhances IL-4 and IL-13 production and suppresses interferon-γ (IFN-γ) produced in memory T cells(Reference Matthias, Maul and Noster39). Furthermore, clearance of extracellular pathogens is assisted by IL-17-producing helper T cells (Th17), and increased levels of sodium chloride activate a kinase signalling pathway that induces development of Th17 cells(Reference Wu, Yosef and Thalhamer40).
Of significance, human receptor angiotensin-converting enzyme 2, a binding site for SARS-CoV-2, is found in alveolar macrophage cell membranes in the respiratory tract and in other immune system cells(Reference Rubins41), implying that angiotensin-converting enzyme 2 provides a protective mechanism in the endocytosis and lysis of pathogens. But this protection could be reduced as angiotensin-converting enzyme 2 expression is lowered by high sodium chloride dietary intake, as demonstrated in laboratory animal experiments(Reference Berger, Vassallo and de Oliveira Crajoinas42).
Plant-based diets and COVID-19
Plant-based diets that are high in unprocessed fruits, vegetables, grains, legumes, nuts and seeds and low in animal-based food products were associated with reduced severity of COVID-19 in a case–control study of frontline healthcare workers from six countries(Reference Kim, Rebholz and Hegde43). Compared with workers who reported following a plant-based diet, higher amounts of meat and poultry consumed by other workers was associated with several fold greater odds of moderate to severe COVID-19. Healthcare workers who did not follow a plant-based diet consumed 24 % more fish and seafood, 91·6 % more poultry, and 192·3 % more red and processed meats than other workers. Researchers of the study concluded that future studies are needed with more detailed data of macro- and micronutrient dietary intake associated with COVID-19 severity(Reference Kim, Rebholz and Hegde43), which includes dietary intake of Na and K.
A randomised controlled trial found that participants assigned to dietary patterns categorised as vegan (no animal-based foods), vegetarian (permits eggs and dairy products) and pescovegetarian (permits seafood) had lower Dietary Inflammatory Index (DII) scores compared with participants assigned to semivegetarian and omnivorous dietary patterns(Reference Turner-McGrievy, Wirth and Shivappa44). Importantly, although all groups followed diets high in Na, intake of dietary Na reported at the end of the 6-month trial was lowest in the vegan group that consumed no meat, poultry or seafood.
More recently, a healthy diet was assessed using a Plant-Based Diet Score, and the diet was associated with lower risk and severity of COVID-19 in participants from the COVID-19 Symptom Study(Reference Merino, Joshi and Nguyen45). The healthful Plant-Based Diet Index (hPDI) used in the study places emphasis on fruits, vegetables and whole grains. The association of a poor diet with COVID-19 risk in the study was stronger among people of lower socio-economic status (SES). Relatedly, a systematic review and meta-analysis of socio-economic determinants of dietary Na intake in high-income countries found that ‘people of low SES consume more Na than do people of high SES’(Reference de Mestral, Mayén and Petrovic46). This implies that the increased risk and severity of COVID-19 in people with lower SES is associated with a poor diet that may also be high in Na.
However, in addition to diet, many social determinants are also associated with risk of COVID-19, such as reduced access to healthcare services, crowded environments with greater exposure to the coronavirus, and stress and co-morbid conditions associated with poverty(Reference Patel, Nielsen and Badiani47). Additional social determinants include food insecurity, unavailability of healthy and affordable food, unemployment, discrimination, crime and violence, lack of quality education, and poor health literacy(48). More research is needed to investigate how social determinants interact with high-Na dietary patterns associated with COVID-19 risk in people with lower SES.
Sodium:potassium ratio
High intake of dietary K, which is abundant in fresh fruits and vegetables, was found to counter effects of high salt intake associated with hypertension and inflammation(Reference Crouch, Botha-Le Roux and Delles49). K induces natriuresis, or Na excretion by the kidneys, and a low Na:K urinary excretion ratio is more strongly associated with low blood pressure than Na or K levels alone(Reference Wei, Gritter and Vogt50). Compared with modern diets, preagricultural diets that emphasised whole plant-based foods were estimated to have much lower dietary Na:K ratios, providing preagricultural humans with approximately 600 mg of Na and 7000 mg of K a day(Reference Eaton, Eaton and Konner51). WFPB diets are not the only source of adequate K – health authorities encourage the general public to consume five to six servings of fruits and vegetables a day to meet K needs(Reference Steptoe, Perkins-Porras and McKay52). Nevertheless, considering modern global food consumption patterns that favour high salt intake and low K, implementing dietary guidelines for Na and K from the WHO (under 2000 mg Na and at least 3510 mg K for adults per d) ‘will be an enormous challenge for global public health’(Reference Drewnowski, Rehm and Maillot53).
Modern Na dietary intake is higher than K intake in China(Reference Li, Zhang and Wu54), and metabolic syndrome in Chinese adults is associated with a higher dietary Na:K ratio(Reference Li, Guo and Jin55). Moreover, hypokalemia (serum K < 3·5 mEq/l) was highly prevalent in patients hospitalised with COVID-19 in Italy(Reference Alfano, Ferrari and Fontana56), China(Reference Chen, Li and Song57) and Spain(Reference Moreno-Pérez, Leon-Ramirez and Fuertes-Kenneally58). Likewise, hyponatremia is also common in COVID-19 patients (serum Na < 135 mEq/l), but more research is needed to determine whether the type of hyponatremia associated with COVID-19 is hypervolemic hyponatremia caused by water retention related to excess Na(Reference Brown23,Reference Fortune and Garcia-Tsao59) . Interactions between Na and K in WFPB diets should be investigated in the prevention of COVID-19.
Plant-based diets, sodium and COVID-19 co-morbidities
Severe cases of COVID-19 are often co-morbid with chronic kidney disease(Reference Cheng, Luo and Wang60), hypertension(Reference Muhamad, Ugusman and Kumar61), and stroke(Reference Nannoni, de Groot and Bell62), and plant-based diets and dietary Na restriction have been found to be effective in the prevention of these diseases and conditions. Plant-based diets are recommended for prevention and management of chronic kidney disease(Reference Campbell and Liebman63–Reference Kim, Caulfield and Garcia-Larsen68), and dietary Na restriction has also been found beneficial in chronic kidney disease(Reference Bovée, Cuevas and Zietse69–Reference Valtuille72).
Hypertension is effectively managed by low Na diets(Reference Graudal, Hubeck-Graudal and Jurgens73–Reference Juraschek, Miller and Weaver75) as well as by plant-based diets(Reference Aljuraiban, Chan and Gibson76–Reference Joshi, Ettinger and Liebman78). Na restricted diets have also been associated with reduced risk of stroke(Reference Jayedi, Ghomashi and Zargar79,Reference Willey, Gardener and Cespedes80) , as have plant-based diets(Reference Campbell81). However, an exception to decreased stroke risk occurs in association with plant-based diets of low quality(Reference Baden, Shan and Wang82), possibly related to salt additives in processed foods like refined grain products and snack foods.
Other co-morbidities of severe COVID-19 include diabetes(Reference Landstra and de Koning83) and obesity(Reference Sjögren, Stenberg and Thuccani84), and plant-based diets are associated with reduced risk of diabetes(Reference Chen, Drouin-Chartier and Li85–Reference McMacken and Shah87) and obesity(Reference Najjar and Feresin88,Reference Tran, Dale and Jensen89) . High dietary Na is also associated with diabetes(Reference Hao, Liu and Halbert90,Reference Lin, Chattopadhyay and Yang91) and obesity(Reference Fang, He and Fang92,Reference Grimes, Bolton and Booth93) . Collectively, the above-cited studies suggest an association between Na, plant-based diets, and diseases and conditions co-morbid with severe COVID-19.
Conclusions
Based on the evidence presented in this paper, Fig. 1 proposes a causative pathway in which the association of WFPB diets with COVID-19 prevention (dashed arrow) is potentially mediated by the combination of low Na intake, increased Na excretion and reduced Na toxicity. Future studies should examine the Na content of WFPB diets and the impact of reduced dietary Na on prevention of COVID-19 and co-morbid diseases. Additionally, the interaction of Na and K and the dietary Na:K ratio in WFPB diets should be further investigated for the prevention of these diseases. Finally, other components of WFPB diets may also contribute causative pathways to COVID-19 prevention, such as high fibre and low fat content, as well as vitamins, minerals and phytonutrients. These additional WFPB diet components should be investigated separately and in combination with Na and K.
Fig. 1. The association of WFPB diets with COVID-19 prevention (dashed arrow) is potentially mediated by low sodium intake, increased sodium excretion and reduced sodium toxicity. WFPB, whole-food plant-based.
Acknowledgements
This research received no external funding.
The author declares no conflict of interest.
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