In January 2020 researchers from the USA and Switzerland published their review on nutrients and the immune system. It has been established that multiple nutrients, including vitamins A, D, C, E, B6 and B12, folate, zinc, iron, copper and selenium, have roles to play at every stage of an immune response. Adequate amounts of these nutrients are therefore essential to ensure the proper functioning of the immune system. However, it has been suggested that the daily intake of nutrients necessary to support the immune system may be higher than current recommended dietary allowances. Certain populations have an inadequate dietary nutrient intake, and there are situations which can further reduce stores of these nutrients within the body. A stressful lifestyle, often accompanied by lack of sleep and reduced physical activity, can increase oxidative stress thereby increasing the need for antioxidants such as vitamins C and E, as well as magnesium to help repair DNA. Certain health conditions, such as diabetes and obesity, can also reduce nutrient levels. Seasonal changes are also known to decrease nutrient levels, for example lower levels of vitamin D are common in the dark months of winter or in northern climates. Multiple nutrients, for example magnesium, zinc, and iron, may also be lost during sweating in hot countries or during exercise. In fact, increased energy expenditure uses the body’s store of nutrients to produce more energy, resulting in low levels of B vitamins, vitamin C, calcium, iron, zinc, and magnesium in active individuals. Air pollution has also been seen to reduce the level of certain nutrients, such as vitamin D if the pollution reduces exposure to the sun, or antioxidants such as vitamins C and E, which may be necessary to fight oxidative stress which is caused by the pollution itself.
Several nutrients therefore may be deficient, and even a slight deficiency can reduce immunity and increase an individual’s risk to infection. For example, deficiencies in vitamin A, iron, and iodine are common, and are amongst the leading contributors to disease. Vitamin D and calcium deficiencies are also common, whilst potassium intake is also recognized to be inadequate in most countries. It is thought that potassium deficiency may increase the risk of hypertension and cardiovascular disease. The severity of many medical conditions largely depends on the extent and duration of the nutrient deficiency.
Multiple nutrient deficiencies frequently occur simultaneously in children and adults worldwide. The most recent data indicates that between 25–75% of people have a dietary intake that is less than the RDA, depending on the nutrient. In Europe, reported intakes have been shown to be inadequate for vitamins D and E, folate, and selenium throughout all age groups. Intakes were also inadequate for vitamin A, zinc, and magnesium in children over 10 years and adults; vitamin C in boys over 10 years and adults; iron in children and adults, but not older adults; vitamin B12 in adults; and vitamin B6 in older adults. In the USA, dietary intake for all nutrients appears to be less than the estimated average requirements or the adequate intake, but particularly for vitamins A, D and E, calcium, magnesium, zinc, and potassium in all adults; vitamin C especially in adult smokers; vitamin B6 in older people; folate in females; and copper in females. It is also important to consider the dietary source of nutrients. For example, it is well known that the availability of nutrients such as iron, zinc or magnesium in a plant-based diet is low because of the presence of substances that prevent its absorption into the body, eg iron found in plant-based foods such as vegetables, cereals, beans and lentils, is non-haem iron which is not absorbed as well by the body.
The body may also lose nutrients when exposed to bacteria, a virus or other microorganism that can cause disease, which causes the immune system to become increasingly active. The nutrient loss is increased during an active infection (including vitamins A, C, and E, calcium, zinc, and iron), and levels only return to normal once symptoms improve. An adequate nutrient intake is therefore essential to help recovery from infection, which is made more difficult by the fact that food intake may decrease during illness, and that antibiotic use can also reduce the level of certain nutrients. For example, levels of vitamin C can rapidly fall to half their original level during an infection, levels which may indicate an insufficient level with a risk of deficiency. However, the high intake of vitamin C required to counteract the fall in levels after infection, or even simply to help reduce the risk of infection may be difficult to achieve when data shows that people already often fail to reach the current RDA for vitamin C especially when inadequate vitamin C intake is already more widespread than many individuals realize. The question therefore remains whether there are any benefits of supplementation with vitamins and/or minerals, either singly or in the form of an multivitamin/multimineral supplement, ie does a nutrient supplementation have any effect on reducing the risk of infections or in the management of acute infections?
Vitamin A
There is low-to-moderate evidence that vitamin A supplementation (50,000–200,000 IU every 4–6 months) in children can reduce the incidence of diarrhoea and measles. However, other studies in children have not found that vitamin A significantly reduces the incidence of pneumonia or lower respiratory tract infections. There is also low-to-moderate quality evidence that vitamin A supplementation in children after a non-measles pneumonia can reduce the recurrence of bronchopneumonia and time to remission. Low-to-moderate evidence has also suggested that vitamin A supplementation in children produces a significant reduction in deaths from diarrhoea and respiratory diseases associated with measles. However, vitamin A supplementation after pneumonia in children did not appear to significantly reduce mortality, the duration of illness or the duration of hospital stay.
Vitamin C
The effects of vitamin C in reducing the risk of the common cold have long been debated. An analysis of mainly high-quality studies reported that vitamin C supplementation produced no reduction in incidence in the general population, whereas vitamin C supplementation (≥0.2 g/day) in those who regularly underwent physical exercise reduced the incidence of the common cold by more than half. There is also low-quality evidence which further supports a reduced risk of upper respiratory tract infection in athletes following vitamin C supplementation (0.3–2.0 g/day), but no additional benefits were seen when either vitamin E or zinc were taken at the same time as the vitamin C supplementation. In addition, there is low-to-moderate quality evidence that there is a significant reduction in the risk of pneumonia following vitamin C supplementation in adults and children, particularly when the dietary intake was low. Further low-to-moderate quality evidence suggests that vitamin C (100 mg/day) supplementation during pregnancy may reduce the risk of urinary tract infections.
Mainly high-quality evidence has demonstrated that vitamin C supplementation (≥0.2 g/day, or therapeutic doses of 4–8 g/day) in adults and children with a common cold significantly reduces its duration and severity, shorten the time of confinement indoors, and relieve cold symptoms including chest pain, fever, and chills. The greatest benefits are often seen in children, although no studies have specifically looked at the effect of treating the common cold in children with vitamin C. In older people with pneumonia, there is low-to-moderate quality evidence that vitamin C can significantly reduce the severity of disease and the risk of premature death, especially if blood levels were initially low. The duration of the pneumonia may also be reduced following vitamin C supplementation in adults, in a dose-dependent manner. No benefits following vitamin C supplementation have however been seen in hospital-acquired pneumonia.
Vitamin D
Five reviews of mainly high-quality studies have reported that vitamin D (300–3653 IU/day) in adults and children can reduce the risk of respiratory tract infections. However, better results were achieved in those individuals who had a low vitamin D level at the beginning of the study. Low-to-moderate quality evidence has revealed that vitamin D supplementation may reduce the risk of upper respiratory tract infections, tuberculosis, and influenza in adults and children, although there are other analyses which have found no such effect. Low-to-moderate evidence has also suggested that giving vitamin D supplementation to adults and children with tuberculosis, influenza, or upper respiratory tract infection may be beneficial. However, the results were noted to be inconclusive when vitamin D supplementation was given at the same time as antibiotics in children with pneumonia.
Iron
Moderate and high quality evidence has indicated that iron supplementation in children may reduce the risk of respiratory tract infection, but not the overall risk of infection or other illnesses such as diarrhoea or malaria.
Zinc
Mainly high-quality evidence has indicated that zinc supplementation (5–50 mg/day) may reduce the incidence of otitis media in younger or undernourished children. In addition low-to-moderate evidence has shown that zinc supplementation (20–140 mg/week) in children may reduce the incidence of lower respiratory tract infections, although this outcome appears to depend on the definition for lower respiratory tract infection. An analysis of mainly high-quality studies has found that zinc supplementation in children may reduce the risk of respiratory tract infection or pneumonia as well as diarrhoea or dysentery. However, other studies which are of low-to-moderate quality found that zinc (5 to ≥20 mg/day) had no protective effect against the risk of respiratory tract infection or malaria in children, although it should be noted that these studies did identify a reduction in mortality associated with respiratory disease, diarrhoea, and malaria. No additional benefits were seen when iron was added to the zinc supplementation.
Mainly high-quality evidence has indicated that the duration of the common cold may be reduced in adults and children following zinc supplementation of over 75 mg/day, but not at lower doses. It was also seen that the type of zinc used in the supplementation could also have an effect, with greater benefits being seen with zinc acetate than other zinc salts. However, low-to-moderate quality evidence has shown that zinc supplementation (10–20 mg/day) appears to have no significant effect on pneumonia in children, failing to reduce the time to recovery or duration of hospital stay.
Multivitamin/multimineral supplementation
In children, low-to-moderate quality studies have demonstrated that multivitamin/multimineral supplementation may result in significantly fewer episodes of infection in younger adults. In older adults, there was low-to-moderate quality evidence that multivitamin/multimineral supplementation reduced the average number of days the individual experienced the infection, but it did not appear to have any effect on the number of episodes experienced. It has also stated that supplementation may be more beneficial in older adults if they were undernourished or had taken the supplementation for more than six months.
Conclusion
Although contradictory information exists, eg through inconsistent study designs, different populations used and differences in the type, dosage and source of nutrients studied, evidence suggests that supplementing the diet with a combination of multiple, selected, immune-supporting nutrients may improve immune function and reduce the risk of infection. Overall the nutrients with the strongest evidence for immune support are vitamins C and D and zinc. However, further research is urgently required to further investigate the possible effects of supplementation on the risk of infection and its management in different types of populations, taking into consideration their nutrient status.
Gombart AF et al. A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients. 2020 Jan 16;12(1). pii: E236.