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., 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., Inherent to their function is the oxidative stress that the leukocytes encounter, triggered by their response to pathogens and other activating substances. 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., 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., Vitamin E deficiency also adversely affects neutrophil bacterial killing activity and phagocyte function (clearing of bacteria and debris) and impairs natural killer cell activity., 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.
Although severe vitamin E deficiency is uncommon and generally only occurs with severe malnutrition or fat malabsorption,,, 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., 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, 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, necessary for a normal, healthy immune response) and interferon (IFN)-γ (which decreases with age and is an important factor in our response against viruses), lymphocyte proliferation, and the responsiveness of lymphocytes and natural killer cells to stimuli.,,
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) and increased levels of IL-2. 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. 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.
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.
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. 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., 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. 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.
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%. 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.
Click here to see References
 Atkinson J, et al. Tocopherols and tocotrienols in membranes: a critical review. Free Radic Biol Med. 2008 Mar 1;44(5):739-64.
 Valenzuela A, et al. Cholesterol oxidation: health hazard and the role of antioxidants in prevention. Biol Res. 2003;36(3-4):291-302.
 Coquette A, et al. Role of vitamin E in the protection of the resident macrophage membrane against oxidative damage. Arch Int Physiol Biochim. 1986 Dec;94(5):S29-34.
 Sharmanov AT, et al. Effect of vitamin E deficiency on oxidative metabolism and antioxidant enzyme activity of macrophages. Ann Nutr Metab. 1990;34(3):143-6.
 Victor VM, De la Fuente M. Immune cells redox state from mice with endotoxin-induced oxidative stress. Involvement of NF-kappaB. Free Radic Res. 2003 Jan;37(1):19-27.
 Wu D, Meydani SN. Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention. J Leukoc Biol. 2008 Oct;84(4):900-14.
 Beharka AA, et al. Macrophage prostaglandin production contributes to the age-associated decrease in T cell function which is reversed by the dietary antioxidant vitamin E. Mech Ageing Dev. 1997 Feb;93(1-3):59-77.
 Hayek MG, et al. Age differences in eicosanoid production of mouse splenocytes: effects on mitogen‐induced T‐cell proliferation. J Gerontol 1994;49: B197–207.
 Adolfsson O, et al. Vitamin E‐enhanced IL‐2 production in old mice: naive but not memory T cells show increased cell division cycling and IL‐2‐producing capacity. J Immunol 2001;167: 3809–17.
 Miller ME. Phagocyte function in the neonate: selected aspects. Pediatrics. 1979 Nov 1;64(5):709-12.
 Adachi N, et al. Depressed natural killer cell activity due to decreased natural killer cell population in a vitamin E-deficient patient with Shwachman syndrome: reversible natural killer cell abnormality by alpha-tocopherol supplementation. Eur J Pediatr. 1997 Jun;156(6):444-8.
 Haynes L, Maue AC. Effects of aging on T cell function. Curr Opin Immunol. 2009 Aug;21(4):414-7.
 Sokol RJ, et al. Mechanism causing vitamin E deficiency during chronic childhood cholestasis. Gastroenterology. 1983 Nov;85(5):1172-82.
 Farrell PM, et al. The occurrence and effects of human vitamin E deficiency. A study in patients with cystic fibrosis. J Clin Invest. 1977 Jul;60(1):233-41.
 Kalra V, et al. Vitamin E deficiency and associated neurological deficits in children with protein-energy malnutrition. J Trop Pediatr 1998;44:291–5.
 Traber MG. Vitamin E inadequacy in humans: causes and consequences. Adv Nutr. 2014 Sep;5(5):503-14.
 Bailey RL, et al. Do dietary supplements improve micronutrient sufficiency in children and adolescents? J Pediatr. 2012 Nov;161(5):837-42.
 Fulgoni VL, et al. Foods, fortificants, and supplements: Where do Americans get their nutrients? J Nutr. 2011;141(10):1847-54.
 Liao W, et al. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr Opin Immunol. 2011 Oct;23(5):598-604.
 Bryan N, Sarwari AR. Immune response and infections in the elderly. Principles of Geriatric Critical Care. 2018 Aug 31:138-46.
 Han SN, et al. Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus. Immunology. 2000 Aug;100(4):487-93.
 Meydani SN, et al. Vitamin E supplementation suppresses prostaglandin E1(2) synthesis and enhances the immune response of aged mice. Mech Ageing Dev. 1986 Apr;34(2):191-201.
 Sakai S, Moriguchi S. Long-term feeding of high vitamin E diet improves the decreased mitogen response of rat splenic lymphocytes with aging. J Nutr Sci Vitaminol (Tokyo). 1997 Feb;43(1):113-22.
 Moriguchi S, et al. High dietary intakes of vitamin E and cellular immune functions in rats. J Nutr. 1990 Sep;120(9):1096-102.
 Disis ML, et al. Delayed-type hypersensitivity response is a predictor of peripheral blood T-cell immunity after HER-2/neu peptide immunization. Clin Cancer Res. 2000 Apr;6(4):1347-50.
 Meydani SN, et al. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr. 1990 Sep;52(3):557-63.
 Meydani SN, et al. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA. 1997 May 7;277(17):1380-6.
 De la Fuente M, et al. Vitamin E ingestion improves several immune functions in elderly men and women. Free Radic Res. 2008 Mar;42(3):272-80.
 Meydani SN, et al. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA. 2004 Aug 18;292(7):828-36.
 Graat JM, et al. Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA. 2002 Aug 14;288(6):715-21.
 Mezzetti A, et al. Vitamins E, C and lipid peroxidation in plasma and arterial tissue of smokers and non-smokers. Atherosclerosis. 1995 Jan 6;112(1):91-9.
 Pacht ER, et al. Deficiency of vitamin E in the alveolar fluid of cigarette smokers. Influence on alveolar macrophage cytotoxicity. J Clin Invest. 1986 Mar;77(3):789-96.
 Hemilä H, et al. Vitamin C, vitamin E, and beta-carotene in relation to common cold incidence in male smokers. Epidemiology. 2002 Jan;13(1):32-7.
 Hemilä H, et al. Vitamin E and beta-carotene supplementation and hospital-treated pneumonia incidence in male smokers. Chest. 2004 Feb;125(2):557-65.
 Hemilä H. Vitamin E administration may decrease the incidence of pneumonia in elderly males. Clin Interv Aging. 2016 Oct 3;11:1379-85.