The greatest Achilles’ heel to humanity is aging. As the individual ages, there is increased susceptibility to infections and even vaccines cease to be as effective. A fading immunity is behind all these consequences (Kovaiou et al., 2007; Webster, 2000). The decline in immunity with age is termed as immunosenescence (Globerson & Effros, 2000; Gruver et al., 2007; Miller, 1996). Clinical features of impaired immune response have been observed in animal and human models deficient in vitamin E (Han & Meydani, 2006). The discovery of Vitamin E can be traced back to 1922 by Herbert Evans and Katherine Bishop, who used it to impart protection to the fetus from being resorbed in pregnant rats.(Evans & ScottBishop, 1922).

Unlike most other micronutrients, the term Vitamin E refers to a family of compounds known as tocopherols and tocotrienols. Tocopherols and tocotrienols are further divided into subtypes (α, β, γ and δ) according to their ring structures. α-tocopherol transfer protein (α-TTP) is a specific transfer protein for α-tocopherol found in humans. This results in higher availability of this isoform (Traber, 2007). Therefore most of the daily recommended allowance guidelines deal with the α-tocopherol form of Vitamin E.

Vegetable oils and nuts are the primary while meat, fish and vegetables are other common sources consumed in the United States (Murphy et al., 1990). Nuts like almonds, sunflower seeds and spinach are the popular foods you can incorporate into your diet to increase your intake of α-tocopherol. Some cereals fortified with α- tocopherol are also available nowadays. The recommended daily allowance or RDA of α-tocopherol is 15mg per day for all individuals above 14 years of age. Requirement is not increased during pregnancy, but 19mg per day is advised for lactating mothers. Deficiency of α-tocopherol is usually a result of genetic defect in the α-TTP coding genetic sequence and is associated with a syndrome known as AVED or ataxia with vitamin E deficiency (Traber & Manor, 2012).

α-tocopherol plays a crucial role in keeping the immune system young and functioning via five main mechanisms of actions. These include its action on macrophages, dendritic cells, natural killer cells (NK), T cells and B cells (Lee & Han, 2018). The figure below throws some light on the key aspects of vitamin E and its effect on the immunoregulatory features of the body.

Natural killer cells (NK) are suppressed by myeloid-derived suppressor cells (MDSCs) via production of nitric oxide (Stiff et al., 2018). Vitamin E is believed to improve NK function by affecting the nitric oxide formation (Lee & Han, 2018). Increased plasma α-tocopherol levels in aged women correlated with enhanced NK cell activity in a study testing the effects of micronutrients on NK cell function (Ravaglia et al., 2000). The NK cell function of a boy with Shwachman syndrome who had low serum levels of α-tocopherol, improved after he was supplemented with α-tocopherol for a period of eight weeks (Adachi et al., 1997).

Macrophages are the enforcers of the body, presenting antigens to NK and T cells for the development of a stronger immune response and themselves possess the ability to activate into different cell populations with specific functions (Mosser & Edwards, 2008). With age, macrophage function declines due to their increased production of prostaglandin (PGE 2 ) via enhanced expression of cyclo-oxygenase (Cox-2) proteins. When supplemented with α-tocopherol, lower levels of PGE 2 and Cox-2 were detected in murine models (Wu et al., 1998). A study with asthmatic subjects has demonstrated that adding α-tocopherol to their diet ceased the inactivation of nuclear factor (erythroid-derived 2)-like 2 (NRF2) of macrophages present in the alveoli of these individuals (Dworski et al., 2011). Larger studies will be needed to consolidate these promising findings.

Allergies are often known to afflict people early in their lives and have a strong genetic predisposition. Certain classes of dendritic cells amongst others are involved in such allergic responses. Although its role in preventing the development of an allergy altogether is yet not established, α-tocopherol has shown promise in suppressing allergic response to allergens by reducing dendritic cell production. Administering alpha- tocopherol to allergic mothers of mice from the time of mating, resulted in decreased allergic response in its future offspring (Abdala-Valencia et al., 2014).

T cells play a significant role in almost any immune related process and as age progresses, defects in T cell functioning results in an inadequate immune system, vulnerable to infections. Incubating immature T cells derived from old mice with α-tocopherol increased levels of interleukin-2 (IL-2). Additionally, α-tocopherol was found to enable these cells to better progress through the cell division cycle (Adolfsson et al., 2001). Another study showed that incubating CD-4+ T cells from old mice with α-tocopherol resulted in increased proportion of T cells had effective immune synapses (Marko et al., 2007). LAT or linker for activation of T cells is an essential tool required to gather activating signals for T cells. A phosphoryl group needs to be attached to the LAT molecule so that effector and adaptor proteins can be collected. This process of phosphorylation of LAT begins to become deranged in the aged (Lee & Han, 2018). α-tocopherol was fed to old mice for eight weeks following which higher levels of LAT were found in the T cell receptor areas (Marko et al., 2009).

α-tocopherol works well individually as well as when administered with other micronutrients, like vitamin C. Autoimmune diseases result from naïve T cells and immature dendritic cells which are yet not immune-tolerant to the body’s own antigens. The nuclear factor kappa-B (NF-κB) pathway is essential in dendritic cell proliferation and maturation. When dendritic cells were treated with vitamin C and α-tocopherol results showed inhibition of activation of the NF-κB pathway and reduced levels of oxygen radical species. In fact, T cells grown with the same combination of vitamins were shown to attain anergy. These findings suggest that vitamin C and α-tocopherol could potentially be used to induce immune-tolerance to auto-antigens (Tan et al., 2005). Real life applications of the same were observed in reduced rates of post-transplant coronary arteriosclerosis (Fang et al., 2002) . Klotho is a protein found in membranes which regulates calcium entry into cells and is also responsible for suppressing NF-κB activation (Buendía et al., 2016). α-tocopherol enhances the expression of klotho which could further help explain α-tocopherol’s inhibitory effect on the NF-κB pathway (Xuan et al., 2016).

Vaccines are ingenious ways of conferring immune protection to those who need it the most without posing risk to their health. An immune response to vaccination is reduced in the elderly and α-tocopherol gives the body a boost to develop an appropriate immunity post vaccination. Daily intake of 200 mg of α-tocopherol resulted in a significantly increased antibody response to the hepatitis B and tetanus vaccine, although these were in-vivo measures of T cell mediated indexes (Meydani, 1997). Another benefit of α-tocopherol was seen in elderly mice suffering from streptococcus induced pneumonia. Neutrophils drive pulmonary inflammation and cause further deterioration of the infection. Elderly mice which were fed α-tocopherol had lower bacterial load and decreased number of neutrophils in the lungs, all of which contributed to controlling and halting the infection (Bou Ghanem et al., 2015).

Last but not the least, being a fat soluble vitamin, α-tocopherol binds to peroxyl radicals which would have bound to lipids present in cell membranes in the absence of α-tocopherol. This prevents oxidative damage to the cell membranes (Lee & Han, 2018). α-tocopherol or vitamin E is a useful compound for the human body and its use should be advocated, especially in the elderly. Most of its benefits to immunity are yet to be replicated in human models and thus it should be used as an adjunctive measure by the elderly population to give them the antioxidant boost they need.