Vitamin E and Immunity, Part 1 of 2

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The aging immune system and vitamin E

Many are familiar with the antioxidant principles of the vitamin E family, and their importance for the protection of cellular membranes and prevention of cholesterol oxidation.^[1],[2] Vitamin E also is important for a healthy functioning immune system, and deficiency can play a role in declining immune function, particularly with age.

The protective effect that vitamin E has on cellular membranes also is critically important for the cells of the immune system.^[3],[4] Inherent to their function is the oxidative stress that the leukocytes encounter, triggered by their response to pathogens and other activating substances.^[5] Oxidative stress damages cellular membranes inside and surrounding the cells, and can lead to diminished function as well as cellular death.

Studies suggest that vitamin E deficiency is a factor that contributes to age-related decline in T cell function.

Studies suggest that vitamin E deficiency is a factor that contributes to age-related decline in T cell function.^[6],[7] T cells are the lymphocytes that participate in our more active, or adaptive, immune response, which includes our response to viral invaders. Interestingly, the impact of vitamin E on T cell activity is in part due to its anti-inflammatory properties, and related to its inhibitory effect on macrophage production of prostaglandin (PG) E2, which increases with age.^[8],[9] Vitamin E deficiency also adversely affects neutrophil bacterial killing activity and phagocyte function (clearing of bacteria and debris) and impairs natural killer cell activity.^[10],[11] The declining function of T cells with age is a factor that not only puts the elderly at an increased risk of infectious disease, it also impairs the effectivity of vaccinations.^[12]

Although severe vitamin E deficiency is uncommon and generally only occurs with severe malnutrition or fat malabsorption,^{[13],[14],[15]} it has been estimated that 90% of U.S. adults and more than 80% of U.S. children do not consume sufficient amounts of vitamin E.^[16],[17] A 2003 to 2006 survey of more than 18,000 adults found that the average dietary intake of α-tocopherol from food is 7.2 mg/day,^[18] far below the Recommended Daily Allowance (RDA) for adults of 15 mg/day (22.5 IU/day).

About 90% of U.S. adults and more than 80% of U.S. children do not consume sufficient amounts of vitamin E.

Although not everyone may benefit from supplemental vitamin E in excess of the RDA, ensuring nutritional adequacy is important. The very reason we have recommended guidelines like this is because numerous studies have shown that a certain level of nutrients such as vitamin E is necessary. Herein, we take a look at where supplementation in excess of the RDA for vitamin E (as α-tocopherol) has been shown to be of benefit.

The immune enhancing effects of vitamin E

Numerous human studies have also shown that vitamin E enhances immune function, protecting against infection and improving the vaccination response. Dietary supplementation of vitamin E to animals has been shown to increase levels of interleukin (IL)-2 (which promotes T cell growth and differentiation,^[19] necessary for a normal, healthy immune response) and interferon (IFN)-γ (which decreases with age^[20] and is an important factor in our response against viruses),^[21] lymphocyte proliferation, and the responsiveness of lymphocytes and natural killer cells to stimuli.^{[22],[23],[24]}

Alpha-tocopherol. Of the vitamin E family, α-tocopherol is the isoform with the most research backing its use. The tocopherol forms of vitamin E have been known for far longer than the tocotrienols, hence they predominate research. Multiple studies have assessed the effects of α-tocopherol supplementation on the immune response and susceptibility to respiratory infections in aging individuals and smokers, two populations at greater risk.

In older adults, supplementation of 800 mg of α-tocopherol for 30 days increased the response to the delayed-type hypersensitivity (DHT) test (a common parameter used to assess immune responsiveness in vivo^[25]) and increased levels of IL-2.^[26] A subsequent study looked at the effects of dose, comparing the impact of 60, 200, or 800 mg of α-tocopherol taken daily for 4.5 months on immune function of individuals over 65 years of age.^[27] Interestingly, it was shown that the immune response was enhanced the most by taking 200 mg daily rather than the higher dosage. At the 200-mg dose, there was a 65% increase in the DTH response and a 6-fold increase in antibody titer to hepatitis B vaccination.

In elderly nursing home residents, one year of α-tocopherol supplementation at a dose of 200 IU/day significantly reduced the number of residents having respiratory infections and the incidence of the common cold.

An additional study in which α-tocopherol was also taken at a dose of 200 mg/day by an elderly population (average age of 70) found that numerous immune parameters, including neutrophil chemotaxis (migration to the affected area) and phagocytosis activity, lymphocyte chemotaxis and proliferation, and natural killer cell activity, were nearly restored to the levels of healthy, younger (average age of 30) controls.^[28]

These markers of cellular function and response, of course, are only part of the picture, and the greater questions is what impact α-tocopherol has on the occurrence and severity of infectious disease. In these studies, findings are mixed, but generally positive or neutral. In a randomized, double-blind, placebo-controlled trial of elderly nursing home residents, one year of α-tocopherol supplementation at a dose of 200 IU/day was shown to have an effect of significantly reducing the number of residents having respiratory infections (all types and upper specifically) and incidence of the common cold.^[29]

However, in a population of otherwise healthy individuals over 60 years of age in which only 0.2% were had suboptimal α-tocopherol plasma levels, supplementation of 200 mg of α-tocopherol did not reduce the incidence of upper respiratory infections over a 15 month period.^[30] Collectively, these findings suggest that if α-tocopherol levels are adequate, additional supplementation may not be of benefit.

In long-term smokers, supplementation with 50 mg of α-tocopherol daily reduced the incidence of colds in individuals over 65 years of age over a four-year period.

The impact of α-tocopherol on respiratory infections also has been assessed in smokers. Because smoking creates a high level of oxidative stress, smokers have significantly lower levels of vitamin E and higher markers of lipid peroxidation (damage to cellular membranes and other lipids) than non-smokers.^[31],[32] In one study of long-term smokers, supplementation with 50 mg of α-tocopherol daily reduced the incidence of colds in individuals over 65 years of age over a four-year period, with the greatest reductions seen in older city-dwellers who smoked less than 15 cigarettes per day.^[33] In male smokers ranging in age from 50 to 69 years of age, supplementation with 50 mg of α-tocopherol daily was observed to have no effect on the incidence of pneumonia in the total population, but did decrease the risk in those who started smoking when they were 21 years of age or older.^[34]

In a more recent analysis of a large population of male smokers aged 50 to 69 years, it was shown that in otherwise healthy (exercising) smokers who started to smoke at ≥21 years and smoked 5 to 19 cigarettes per day, supplementation with 50 mg of α-tocopherol daily reduced the incidence of pneumonia by 69%.^[35] In individuals who quit smoking for a period of time during this study, the incidence of pneumonia was also significantly lower (six versus 21 cases) in those taking vitamin E. Overall, in exercising smokers supplementation with α-tocopherol significantly reduced the number of cases of pneumonia (ignoring the possible effects of number of cigarettes smoked daily), whereas in non-exercising individuals there was not a benefit.

As we scramble to figure out how to best protect individuals worldwide against respiratory infections, sufficient vitamin E may be one of many nutritional things we are missing. Read on in Part 2 of this two-part article on the immune benefits of vitamin E to learn about how tocotrienols also may positively impact immune system function.

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