Dr Emma Derbyshire and Dr Joanne Delange, from the UK nutritional and biomedical consultancy Nutritional Insight, have written an article outlining the importance of nutrition to optimal immune function, especially for those over the age of 65, concluding that the use of certain nutrients should be tested for their efficacy in the prevention, severity and recovery of infections such as COVID-19.
The article states: "One recent review identified that an array of micronutrients are required to meet the complex needs of the immune system, including vitamins A, D, C, E, B6, B12, folate, copper, iron, zinc and selenium, with many of these having potential synergistic relationships. Of the evidence, however, it was concluded that the largest body of evidence related to immune function existed for vitamin C, D and zinc."
The doctors say the evidence behind vitamin C as a support for immunity has been mounting for nearly a century.
A review in 2017 concluded that three controlled trials found that vitamin C prevented pneumonia and two controlled trials observed a treatment benefit of vitamin C for patients with pneumonia. An earlier Cochrane review, undertaken in 2013, collated evidence from three prophylactic trials, finding a statistically significant (80% or greater) reduction in pneumonia incidence in the vitamin C groups. It was subsequently concluded that therapeutic use of vitamin C supplementation could be reasonable for patients with pneumonia and low plasma vitamin C levels given its low cost and health risks.
"In terms of potential mechanisms, it is well recognised that infections increase oxidative stress," the article states. "Infections typically activate phagocytes which release reactive oxygen species, which are oxidising agents. Vitamin C is a renowned antioxidant which can counteract these effects. In one study a respiratory syncytial virus reduced the expression of antioxidant enzymes and subsequently increased oxidative damage."
The doctors note it is well appreciated that vitamin D is a powerful immunoregulator, with vitamin D receptors being expressed by the majority of immune cells (B and T lymphocytes, macrophages and monocytes). It has also been proposed that immune cells themselves can convert 25(OH)D3 into 1,25(OH)2D3, its active form.
Zdrenghea et al reported in their review that respiratory epithelial cells, macrophages and monocytes express vitamin D receptor, and concluded that vitamin D could act as a potential adjuvant in protecting and treating patients with respiratory viral infections who typically have lower vitamin D status. Greiller and Martineau also reported that vitamin D deficiency is associated with a higher risk of viral acute respiratory infection and found that vitamin D metabolites modulated the expression and secretion of type 1 interferon, chemokines CXCL8 and CXCL10, and proinflammatory cytokines, including tumour necrosis factor and interleukin-6.
A systematic review and meta-analysis has collated evidence from 25 separate randomised controlled trials (n=11 321 participants) studying the effects of vitamin D supplementation on acute respiratory infections among those aged 0–95 years. Protective effects were seen among all participants, but particularly among those with baseline 25-hydroxyvitamin D levels <25 nmol/L, indicative of deficiency. Overall, the authors concluded that vitamin D appeared to be a safe strategy to protect against acute respiratory tract infections.
Zinc is regarded as a ‘gatekeeper’ of immune function as zinc ions play a role in the regulation of intracellular signalling pathways in adaptive and innate immune cells, the doctors explain. Zinc is also involved in inflammation, elevating inflammatory responses and inducing cell-mediated immunity, and is a key component of pathogen-eliminating transduction pathways that contribute to neutrophil extracellular traps (networks which bind pathogens) formation.
No meta-analysis or Cochrane reviews currently appear to have been undertaken in this field. Among paediatric populations a review of several studies concluded that zinc supplementation for more than 3 months could be effective in preventing pneumonia in children younger than 5 years of age, although the evidence was not robust enough to advocate prophylactic properties if given for shorter periods of time. Among the elderly it is recognised that inadequate zinc status impairs immune function, reduces pathogenic resistance, and is linked to an increased incidence and duration of pneumonia, along with overall mortality.
Nutrition for 'prehabilitation'
The doctors conclude: "Public health strategies involving immunonutrition could be an alternative way to promote prehabilitation and reduce burdens on healthcare systems.
"The general public and indeed the ageing population should be encouraged to follow guidance from Public Health England and continue taking supplements containing 10 μg of vitamin D daily, given the fact that low vitamin D status appears to correlate with reduced immune function. Family and friends should help communicate this information to older generations given that they may have limited awareness of these guidelines.
"Foods that are naturally abundant in vitamin C such as broccoli (60 mg/100 g), blackcurrants (130 mg/100 g), fortified breakfast cereals (up to 134 mg/100 g) and oranges (37–52 mg/100 g) should be made accessible to older individuals who are most in need of their nutritional benefits.
"In the UK 5.5% of men and 4% of women 65 years and over (around 1 in 20) presently have zinc intakes lower than the lower reference nutrient intake (the level below which deficiency could occur). The consumption of foods naturally abundant in zinc such as canned crab (5.7 mg/100 g), canned shrimps (3.7 mg/100 g), canned adzuki beans (≈2.3 mg/100 g) and boiled eggs (1.3 mg/100 g) should be encouraged as a supplementation strategy to reinforce immunity.
"Among those with established respiratory conditions or pneumonia, specific nutrients such as vitamin C, D or zinc could be considered as potential adjuvants to conventional treatment pathways.
"Now that a pandemic has arisen with SARS-CoV-2, and given the easy access, low cost and limited side effects of the discussed nutrients, now could be an appropriate time to trial and test their efficacy in relation to prevention, severity and recovery of such infections.
"What remains to be confirmed are the dosages and durations that these would need to be taken to be most beneficial and whether different combinations of micronutrients would be most effective in helping to fight against infection.
"Ongoing research is urgently needed within the field of immunonutrition and, in particular, how this could benefit vulnerable, at risk groups."