The Covid-19 pandemic has sparked both an increased clinical and public interest in the role of nutrition and health, particularly in supporting immunity. During this time, when people may be highly vulnerable to misinformation, there has been a plethora of media stories against authoritative scientific opinion, suggesting that certain food components and supplements are capable of ‘boosting’ the immune system. It is important to provide evidence-based advice and to ensure that the use of non-evidence-based approaches to ‘boost’ immunity is not considered as an effective alternative to vaccination or other recognised measures.
The role of nutrition in the immune system: Vitamin D and more
The immune system, the network of cells, tissues, and organs that work together to defend the body against attacks from pathogens, is complex. Adequate energy and nutrition are required to support normal immune function. Vitamin D has been a nutrient of particular interest; low vitamin D status has been associated with an increased risk of Covid-19 infection and hospitalisation, although this is based on observational research, and therefore cannot determine cause and effect.1
In December 2020, the National Institute for Health and Care Excellence (NICE), Public Health England (PHE) and Scientific Advisory Committee on Nutrition (SACN), jointly published a rapid guidance on vitamin D for Covid-19.2 This incorporated consideration of the evidence for vitamin D supplementation and prevention of acute respiratory tract infections, and noted a recent systematic review and meta-analysis that reported a modest protective effect.3 However, a number of important caveats were highlighted. Protection was only seen in children (aged 1 to 16 years), yet for Covid-19 poorer outcomes are more common in older adults. In addition, there were substantive limitations in the included studies with notable differences in study populations and methodologies [eg country, latitude, age ranges, comorbidities, dosing frequency, percentage of participants with low vitamin D status (<25 nmol/L) and definitions of outcomes (including type of respiratory infection)]. These limitations impact meaningful interpretation of the evidence to date.
In specific relation to Covid-19, the NICE guidance recognises that there is no robust evidence yet to recommend vitamin D supplementation solely to prevent or treat Covid-19 (unless as part of a clinical trial). NICE also recognise the pressing need for good quality, relevant data to ensure that guidance can be updated if necessary ie definitive large-scale randomised controlled trials, including BAME groups who have higher risk of vitamin D deficiency and are disproportionally affected by Covid-19. Pending results of these trials, it makes sense for the UK population to adhere to current government guidance to take a daily supplement containing 10 micrograms of vitamin D particularly between October and early March, and all year round for those at particular risk of low vitamin D status (eg frail, housebound or in a care home, or those who usually wear concealing clothes outdoors). These recommendations are to support good musculoskeletal health but may also provide some additional benefit in reducing the risk of acute respiratory tract infections. At the end of November 2020 the government announced free vitamin D supplements for those who are clinically extremely vulnerable and care home residents for the winter months.
Vitamin D is not the only nutrient associated with immunity. A number of nutrients including other vitamins, minerals, amino acids and fatty acids have been identified to have specific roles in immunity (see Table 1). The wide range of nutrients implicated suggests that a healthy, balanced and varied diet is important to support immune function.
Table 1: Nutrients involved in immunity and their food sources (adapted from Lockyer 2020)4
Effect of low status or deficiency on immunity
Deficiency is associated with impaired barrier function, altered immune responses, including impairment of the ability of macrophages to ingest and kill bacteria, and increased susceptibility to a range of infections.
Liver, eggs and cheese are dietary sources of retinol (‘pre-formed’ vitamin A). Dark green leafy vegetables and orange-coloured fruits and vegetables, (eg spinach, carrots, sweet potato, butternut squash, and cantaloupe melon), are dietary sources of carotenoids, which can be converted to vitamin A by the body.
Lymphocytes isolated from vitamin B6‐deficient individuals display reduced proliferation and reduced antibody production in response to immunisation.
Poultry, fish (eg tuna), pork, fortified breakfast cereals, fortified yeast extract, soya beans, sesame seeds and some fruit and vegetables, such as bananas, avocados and green peppers.
Vitamin B12‐deficient patients have been noted to have an abnormally high CD4+/CD8+ ratio and suppressed natural killer cell activity (which could be restored by administration of vitamin B12) and an impaired antibody response to pneumococcal polysaccharide vaccine.
Meat, fish, shellfish, milk, cheese, eggs, fortified yeast extract, fortified breakfast cereals and fortified dairy alternative products.
Vitamin C deficiency is associated with decreased T lymphocyte-mediated immune responses to recall antigens and susceptibility to severe respiratory infections such as pneumonia.
Citrus fruits, blackcurrants, strawberries, kiwi fruit, green vegetables (eg broccoli, kale, spinach), cauliflower, peppers and tomatoes.
Moderate and even marginal copper deficiency affects some activities of T-cells and phagocytic cells adversely. Severe copper deficiency changes the phenotypic profiles of immune cells in blood, bone marrow and lymphoid tissues and suppresses a number of activities of lymphocytes and phagocytic cells.
Wholegrain bread, wholegrain breakfast cereals, wholewheat pasta, quinoa, couscous, fish, shellfish, pulses, avocados, dried fruit, nuts and seeds.
Low vitamin D status is associated with reduced immune response and a higher risk of viral respiratory tract infections.Current UK data suggests that 19% of children aged 11-18 years, 16% of adults aged 19-64 years and 13% of adults aged 65 years and over, have low vitamin D status (<25 nmol/L).
Oily fish, eggs, some fortified breakfast cereals, fortified spreads, and fortified dairy products and some fortified dairy alternatives.
Folate deficiency reduces the proportion of circulating T-cells and their proliferation in response to mitogen activation.
Green vegetables (e.g. spinach, cabbage, broccoli, pak choi), peas, lettuce, pulses, oranges, berries, nuts and seeds (inc. nut butters and seed pastes), cheeses, wholemeal bread and fortified breakfast cereals.
Iron deficiency is associated with changes in the cell-mediated immune response including impaired neutrophil function, reduction of numbers of T-cells, B-cells and natural killer cells, defective T-lymphocyte-induced proliferative response, reduction of secretory IgA, reduction of levels of complement C3 and C4, and inhibition of the activity of IFN-γ.
Offal (eg kidney), red meat, beans, pulses, nuts and seeds, fish (such as canned sardines, cockles and mussels), quinoa, wholemeal bread and dried fruit.
Lower selenium status has been linked with diminished natural killer cell activity and increased mycobacterial disease. Selenium deficiency is associated with mutations of coxsackievirus, polio virus and murine influenza virus increasing virulence.
Nuts and seeds (for example Brazil nuts, cashews and sunflower seeds), eggs, poultry, fish and shellfish.
Zinc deficiency results in an abnormally low level of lymphocytes in the blood and thymic atrophy and is associated with a decline in most aspects of immune function including cell‐ and antibody‐mediated responses, the production of cytokines by mononuclear cells and the induction of apoptosis, resulting in a loss of B-cell and T-cell precursors within the bone marrow.
Meat, cheese, some shellfish (including crab, cockles and mussels), nuts and seeds (in particular pumpkin seeds and pine nuts), wholegrain breakfast cereals and wholegrain and seeded breads.
What about probiotics?
The gut microbiome plays a role in immunity locally within the gut where a robust population of beneficial bacteria can help improve intestinal barrier function and competitively inhibit potential pathogen-binding sites.1, 5 The gut microbiome also interacts with the immune system outside the gut. It seems reasonable, therefore, to consider whether dietary modification or modulation of gut microbes (eg adopting a healthy, dietary pattern with high fibre foods like fruit, vegetables, wholegrains, and pulses) may help support immune function.
Probiotics, by definition, are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host, and typically comprise bifidobacteria and lactobacilli.6 Evidence for the clinical efficacy of probiotics is inconsistent, and a lack of clarity for many strains and formulations can make it difficult for health professionals to make evidence-based decisions. Probiotics may be of benefit in some cases, including antibiotic-associated diarrhoea and for some symptoms of irritable bowel syndrome.7 It has also been suggested that probiotics may improve infectious diarrhoea, but whilst previous reviews from small studies indicated an effect, a 2020 systematic review based on large trials with low risk of bias concluded that probiotics probably make little or no difference to the number of people who have diarrhoea lasting 48 hours or longer, and it is unclear whether probiotics reduce the duration of diarrhoea.8
Importantly in the current pandemic no probiotics have been shown to prevent or treat Covid-19. A Cochrane review of human trials indicated that specific probiotics may reduce the incidence and duration of common upper respiratory tract infections (URTIs), especially in children.9 However, the quality of the evidence was low or very low and more trials are needed to confirm these findings, as well as determine the optimal strains, dosing regimens, time and duration of intervention. Further, we do not know how relevant these studies are for Covid-19, as the outcomes are for impact on URTIs, whereas Covid-19 is also a lower respiratory tract infection and inflammatory disease.
What about supplements?
Zinc and vitamin C supplements, with their popular associations with immunity and benefit to respiratory infections, have been of particular interest in the Covid-19 pandemic. However, there is a paucity of evidence supporting this. A recent systematic review concluded that due to the limited number of studies and very low quality of the existing evidence, there is uncertainty of the effect of vitamin C supplementation for the prevention and treatment of pneumonia.10 With colds, the failure of vitamin C supplementation in trials to reduce the incidence in the general population indicates that routine supplementation is not justified, although it may be useful for reduction of colds in extremely, physically active people.11 Some studies of zinc supplementation have shown to decrease risk of mortality with severe pneumonia in some settings, but not others.12, 13 Studies have been inconclusive, perhaps because of improper dosing, timing, or delivery route, and clinical data to date are insufficient to support a role for zinc supplementation in hospitalised patients.14 Whilst clinical supplementation trials in Covid-19 may be ongoing for both vitamin C and zinc, there are currently insufficient data to recommend their use for the prevention and/or treatment of Covid-19, and supplementation above the recommended dietary allowance should only be used in the context in clinical trials.15, 16
Clinical deficiencies of nutrients involved in immunity can leave individuals more vulnerable to infections. People with medically diagnosed micronutrient deficiencies can benefit from appropriate supplements prescribed by a registered health professional.
Maintaining a healthy weight
People living with obesity (PLWO) have an increased risk of poorer clinical outcomes with Covid-19 including hospitalisation, intensive care unit admission, intubation and mortality. There are a number of pathways linking obesity to these outcomes including lower cardiorespiratory fitness, susceptibility to inflammation, metabolic complications, poorer immune response and increased viral exposure.17 Whilst support to consume a healthy, balanced diet along with regular physical activity is important, it is crucial that this is done in recognition of the complex, intricacy of biological, societal, and psychological factors that underpin obesity, and without a culture of blame and guilt. Unusual life events, such as quarantine and lockdown, during the pandemic have had a negative impact on the diet and health behaviours of PLWO, further complicated with loss of access to support and treatment.18 Moreover, mental health issues have been exacerbated due to self-isolation, disruption of usual weight control strategies, stress and stigmatisation.19 Evidence-based tools for the treatment and long-term management of obesity during and beyond this pandemic are urgently needed.
The overall message?
No one food or supplement, or magic diet can support the immune system alone or prevent or treat Covid-19. Importantly physical distancing, masks, vaccines, and other preventive measures are key in preventing spread. However, eating a healthy diet (including the government recommendations to encourage adequate vitamin D intake), being physically active, managing stress, and getting enough sleep will help support immunity.