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Widespread Nutrient Shortfalls May Increase the Risk of Infections

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Ideally, a well-balanced, nutrient-dense diet, including a variety of fruits and vegetables, whole grains, legumes, and healthy fats can meet all of one’s daily requirements for vitamins and minerals, as well as essential fatty acids and other nutrients.

In practice, however, it is difficult for many individuals to obtain a sufficient variety and/or quantity of wholesome foods to fulfill their nutritional needs on a regular basis. There is often a gap between what we consume versus what we require.[1]

In addition to compromising overall health, inadequacies in key nutrients can impair immune function. A recent article (which we’ll refer to as “the 2020 study”), published in the peer-reviewed journal Nutrients, highlights the magnitude of the problem.[2] The authors carried out an analysis of usual micronutrient intakes based on data from the National Health and Nutrition Examination Surveys (NHANES), a nationwide survey conducted by Centers for Disease Prevention and Control (CDC). 

Using data obtained between 2005 and 2016, the authors compared the usual dietary intakes from food and supplements to the estimated average requirement (EAR) for a particular nutrient, with a focus on nutrients of importance for immune function. The results revealed substantial inadequacies in vitamins A, C, D, and E, as well as zinc, across the population, especially among individuals who relied on food alone to meet their nutrient needs. Insufficient intakes of these nutrients may increase the risk of infection, which we will look at further here.

Vitamin D

Vitamin D deficiency is a major public health problem worldwide in all age groups. The 2020 study showed that 95% percent of non-supplemented adults had vitamin D intakes below the EAR.[2]

The high prevalence of vitamin D deficiency among individuals of all ages is of great concern from a public health perspective.[2],[3] Vitamin D is mainly thought of in terms of bone health, but this fat-soluble vitamin has emerged as a central regulator of the body’s defense against infections.[4],[5],[6] Among its many immune-supportive functions, vitamin D induces the expression of peptides known as defensins and cathelicidins,[7],[8] which are capable of inhibiting many different viruses and bacteria.[9],[10],[11],[12]

In addition to dietary sources, vitamin D is generated within the skin upon exposure to ultraviolet B rays from the sun.[13],[14] Vitamin D status tends to be at its lowest in winter,[15],[16] coinciding with the seasonal prevalence of respiratory infections. Insufficient production and /or intake of vitamin D can have a significant impact on immune health. During the 1918–1919 “Spanish flu” pandemic, for example, greater fatality rates occurred in those with less sunlight exposure.[17]

Low levels of vitamin D are associated with an increased risk of upper respiratory tract infections, as well as otitis media, urinary tract infections, infectious hepatitis, and other infectious diseases.[5],[18],[19] Research suggests that vitamin D supplementation may cut the risk of acute respiratory tract infections by an average of one-third or more,5,[20] and that individuals with low starting levels of 25(OH)D (<40 nmol/l) are likely to see the most benefit.[21],[22] A recent systematic review further concluded that vitamin D supplementation was safe and that it protected against acute respiratory tract infections overall.[23]

To reach a 25(OH)D blood level of at least 75 nmol/L (30 ng/mL), which is the level advised by many experts, requires 1,000 to 2,000 IU per day of supplemental vitamin D3 (cholecalciferol), or even more, particularly in those with a low level of sun exposure.3,[24],[25],[26],[27] There is good rationale to combine vitamin D with vitamin C and zinc (discussed below), in light of their synergistic effects on respiratory tract infections.[28]

Vitamin C

Vitamin C (ascorbic acid) is a water-soluble antioxidant that is indispensable for a healthy immune response against viral and bacterial infections.[29],[30],[31],[32],[33],[34] This vitamin has a pivotal impact on the innate and adaptive immune response.[30] The 2020 study, however, showed that 46% of non-supplemented adults had vitamin C intakes below the EAR.[2]

Vitamin C is quickly depleted during the common cold, influenza, or pneumonia, meaning that vitamin C requirements go up dramatically when one is ill.[31],[35]Ascorbate levels in white blood cells were shown to decline by 50% when subjects contracted a cold, and only returned to the original levels one week after recovery.[36]

Among its many functions, vitamin C stimulates the production of interferon (IFN) at the initial stage of viral infection, thereby heightening the body’s defenses.[33],[34] Clinical trials have shown that vitamin C supplementation may shorten the duration and severity of common cold symptoms, and also reduce the incidence of colds in individuals with suboptimal vitamin C levels.[37]

In healthy individuals, a daily vitamin C intake of 100 to 200 mg provides an adequate amount of vitamin C to saturate the plasma.[38],[39] However, more vitamin C is consumed by the cells of the body in the course of fighting infections, so doses that are 10 times higher may be needed once an infection has taken hold.[32],[40],[41] Consuming 1 gram per day of vitamin C was shown to shorten the duration of colds in adults by 6% on average, and consuming ≥2 grams per day shortened the duration of colds by 21%.[42] A meta-analysis showed that extra doses of vitamin C could benefit patients who contract the common cold, even if they were already supplementing vitamin C regularly.40

Vitamin A

Adequate vitamin A has long been associated with resistance to infections.[43],[44] This vitamin plays a critical role in the differentiation, maturation, and function of immune cells, both for innate and adaptive immunity,[45],[46],[47],[48] and it can even favorably modulate the gut microbiota.[49]

The 2020 study showed that 45% of non-supplemented adults had vitamin A intakes below the EAR.[2] Vitamin A deficiency has been observed to increase the risk for viral infections in both children and adults.[50],[51],[52] Acute illnesses and infections may further deplete serum retinol concentrations and increase the requirements for this vitamin.[53],[54],[55]

A study conducted in China showed that the serum levels of vitamins A, along with vitamins D and E, were significantly lower in children with active respiratory infections than in the control groups.[50] Also, researchers in Italy found that a high percentage of adults with hepatitis C infection had serum vitamin A deficiency, which was associated with the lack of a response to antiviral therapy.[51]

The importance of vitamin A for the immune system has been studied extensively with respect to measles, one of the most contagious infectious diseases known to humans. In 1932, Dr. Joseph Ellison and colleagues were the first to associate vitamin A status with the severity of pulmonary disease during measles infection.[56] Subsequent studies found that vitamin A supplementation reduced mortality from measles in vitamin A-deficient children.[44],[57] Both the American Academy of Pediatrics and the World Health Organization recommend supplemental vitamin A for the management of measles.[58]

Vitamin E

Vitamin E , the main lipid-soluble antioxidant in the body, prevents oxidative damage to polyunsaturated fatty acids of cellular membranes, and thereby preserves the function of immune cells.[59] The 2020 study showed that 84% percent of non-supplemented adults had vitamin E intakes below the EAR.[2]

Vitamin E deficiency impairs both humoral and cell-mediated immune functions.[60],[61],[62] A deficiency of this vitamin can increase the risk of infections,[63] and exacerbate the damage that occurs once an infection takes hold.[64],[65] Vitamin E supplementation has been shown to improve measures of immune function and to reduce the incidence and severity of respiratory infections in the elderly, whose immune systems may be compromised due to age.[66],[67],[68],[69]


Zinc supports innate and acquired immunity through direct, indirect, and antioxidant mechanisms.[70],[71],[72],[73] The 2020 study showed that 15% of non-supplemented adults had zinc intakes below the EAR.2 Additional studies have shown that the prevalence of marginal zinc intakes depends on age, ranging from 12% of younger adults to 30% or more of individuals over the age of 60.[74],[75],[76]

Even mild zinc deficiencies can increase the risk and severity of viral infections, including respiratory infections such as influenza and pneumonia.[77],[78],[79],[80] Zinc deficiency not only compromises immunity, but also shifts the immune system toward an inflammatory state that can predispose the body for damage to the lungs and other organs.[81],[82] Conversely, supplemental zinc may help reduce the risk of infections.[83],[84],[85] A combination of zinc (10 to 30 mg daily) with vitamin C (1 gram daily) has also been suggested to shorten the duration of respiratory tract infections, including the common cold.[86]

Summing up

The immune system needs multiple micronutrients, including vitamins and minerals, which play vital, often synergistic roles at every stage of the immune response. The 2020 study shows that a significant number of Americans typically do not take in the estimated average requirements for vitamins A, C, D, and E, and zinc – each key players in a normal, healthy, balanced immune response.[2] Selenium was not identified as having a high prevalence of inadequacy in the 2020 study, but a separate study of infectious disease patients found that 47% were deficient in selenium.[87] Health care providers should be aware that their patients may need to adjust their diets, and/or consider supplementation, to obtain adequate intakes of immune health nutrients. 

Marina MacDonald, MS, PhD completed her graduate work in nutrition at the University of Wisconsin (Madison) and the University of California (Davis).  She conducted postdoctoral research in Metabolism and Endocrinology at the Howard Hughes Medical Institute (University of Washington, Seattle). Her experience in the biopharmaceutical industry includes product development, research, and discovery. Dr. MacDonald enjoys doing freelance writing and research in the fields of nutrition and physiology.


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