Did you know that vitamin E is actually a group of eight fat-soluble molecules in different forms: α-, β-, γ-, and δ-tocopherol and α-, β-, γ-, and δ-tocotrienol? Pretty neat, eh? Of all the forms of vitamin E mentioned α-tocopherol shows the greatest biological activity. Natural α-tocopherol made by plants found in food has an RRR-configuration versus chemically synthesized all-rac-α-tocopherol (1). Vitamin E is unique in that it is one of the best protectors of fat.
You may be wondering why protecting fat is so important. There's two major reasons. First of all our brain has fat surrounding every neuron and this fat layering protects our neurons while also insulating them, allowing faster signals to be transmitted in the brain. Secondly, every cell in our body has 2 fat layers that surround it (lipid bilayer) providing protection, allowing proper communication with surrounding cells and ultimately allows beneficial things in and harmful things out. We have omega-3's in our cell membranes, and vitamin E's antioxidant activity keeps them from being oxidized and damaged. A damaged cell membrane is an unhealthy cell. Vitamin E also decreases the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) which are products our body produces during normal metabolism but also damage our cell membranes when they are not neutralized (2). Without vitamin E our cell membranes would be destroyed and our cells would function very poorly.
Vitamin E, as α-tocopherol, has cell, animal and human studies showing benefits ranging from cognition, cardiovascular, immune and as an anti-cancer nutrient. α-Tocopherol is also involved in strengthening certain aspects of cell-mediated immunity (no antibodies needed) and prevents LDL cholesterol from being oxidized in our blood stream, which is a primary mechanism in the development in atherosclerosis and coronary heart disease (3).
Unfortunately we don't stay forever young, and as we age our bodies need all the help they can get from vitamin E. Aging affects multiple organs, and its effects on the immune system have been studied extensively (4). It's a well established fact that immune function begins to decline with age making the elderly more susceptible to infectious agents, such as influenza, showing increasing morbidity and mortality with increased age. Many studies also show that vaccination is also less efficient in aged individuals as well and they have higher risks of developing cancers and autoimmune diseases (5).
The ability of vitamin E to boost immune function has been observed in animal and human models under normal and disease conditions. Vitamin E influences immune development, function, and regulation of dendritic cells (DCs), macrophages, natural killer (NK) cells, T cells, and B cells. Without vitamin E the ability of our body to recognize invaders is greatly weakened (6).
How Does Vitamin E Enhance Immune Responses As We Get Older?
As we age our immune system begins to decline as well. We'll explore a handful of ways vitamin E on it's own boosts immune function. Vitamin E does work synergystically with other nutrients, but it would take much more time to describe immune benefits even in combination with vitamin C (6,7).
Just as our memory may get worse as we age, our T cells give our immune system it's memory and also decline in function and overall function. Without the ability to remember the pathogens we encounter our immune system will take longer to kill off an invader each time they come back. Vitamin E influences T cell function from growth, development, maturation and it's ability to properly attack pathogens. T-helper cell responses (Th1 and Th2) are also affected, which prevents autoimmune attacks as we age as well.
B cells largely are responsible for antibody production and without vitamin E our ability to make these "pathogen target tags"are reduced as well. Vitamin E enhances what's called the humoral immune response, and shows that it can increase IgG production which is an antibody that can bind to bacteria directly and remove them after inactivating them.
Dendritic cells (DCs) detect pathogens with their arm-like branches and alert other immune cells to be on guard. DCs also show other natural killer cells and white blood cells the proteins that help them quickly identify the pathogen and kill it. Vitamin E helps DCs mature, taking on more complex roles involved in the immune system like cytokine production, PAMPs and DAMPs signaling, T cell instructions, and even preventing autoimmune responses by promoting immune tolerance via Tregs. Without vitamin E the immune system would become hypersensitive and set off very easily.
Macrophages are very large white blood cells that eat pathogens, debris and other dead cells that need to be cleaned up. They play a key role in not only defense but repair processes as well. They also display antigens (non-self toxin) for other immune cells to remember, can produce cytokines which signal or enhance an immune response and activate natural killer cells. Macrophages can also shift into different cell populations and change their function. Vitamin E reduces PGE2 and COX-2 enzyme activity, which decreases prostaglandin production the local and systemic inflammatory responses and overall immune responses.
Natural killer (NK) cells are white blood cells that reject viral infected cells by releasing toxic proteins that punch holes in damaged and infected cells allowing more toxic proteins to be injected, and ultimately inducing cell suicide (apoptosis). This stops them from continuing to grow and reproduce more viruses - as viruses need a host cell to replicate. With low NK cell counts our bodies allow infected cells to continue to replicate and infect neighboring cells. Vitamin E boosts NK cell counts and potency significantly. In 37 women aged 90–106 years old, NK cell cytotoxicity was positively associated with plasma vitamin E concentration (8). A two-week supplementation of 750 mg vitamin E in colorectal cancer patients resulted in increased NK activity in six out of seven patients (9).
Clinical Studies on Vitamin E in Older Adults and Infectious Disease
Does vitamin E actually work? We're going to take brief look at some studies that were done in older adults and some common cold and flu situations. Of course this isn't comprehensive and there are probably many studies I may have not added that should be.
A small study in older adults (mean age, 70 years) showed that supplementation with 200 mg/day of synthetic vitamin E (equivalent to 100 mg of natural vitmain E) for three months significantly improved natural killer's cell killing ability (cytotoxicity), neutrophil's ability to move quickly (chemotaxis), ability to engulf bacteria and viruses (phagocytic response), and enhanced ability to produce lymphocytes and signaling proteins (IL-2) production compared to starting measures, and in comparison to the group who received no vitamin E supplements. The authors states that the findings suggest that supplementation with vitamin E can produce an improvement of immune functions and health in elderly people (10).
In another trial daily supplementation of 200 mg of synthetic vitamin E for 235 days in healthy older adults (≥65 years of age) improved T lymphocyte-mediated immunity (via DTH skin test) and made vaccines more effective by increasing the production of antibodies in response to hepatitis B and tetanus vaccines (11).
A randomized, placebo-controlled trial in 617 nursing home residents (≥65 years of age) reported that daily supplementation with 200 IU of synthetic vitamin E (90 mg) for one year significantly lowered the risk of contracting upper respiratory tract infections, especially the common cold, but had no effect on lower respiratory tract (lung) infections (12).
A double-blind, placebo-controlled trial in 161 patients (65-80 year old) showed that 6 months of supplementing with 100 mg of vitamin E enhanced the DTH response and IL-2, however IFN-gamma production decreased and IL-4 increased. This study showed beneficial effects of 100-mg vitamin E supplementation, and may be more pronounced in particular subgroups of elderly subjects (13).
In a double-blind, placebo-controlled trial, healthy older adults (60 years or above) in a metabolic research unit received either a placebo or oral vitamin E supplements (800 mg ) for 30 days. The E supplementation improved some in vivo and in vitro parameters of immune function. This study further supports the evidence that vitamin E supplementation enhances the immune response in the elderly (14).
Another study on vitamin E found that it decreased the incidence of pneumonia in elderly males. Of 2,216 participants who smoked 5–19 cigarettes per day and exercised at leisure, it was found that vitamin E supplementation reduced the incidence of pneumonia by 69% (57 pneumonia cases). In this subgroup, vitamin E prevented pneumonia in 12.9% of participants with an age of 74 years. Among 5,253 participants who smoked ≥20 cigarettes per day or did not exercise, the incidence of pneumonia was 14% lower in the vitamin E participants (139 cases). One-third of the participants quit smoking for a period, of whom 27 got pneumonia. The incidence of pneumonia was 72% lower in the vitamin E group, and this benefit was also seen among those males who smoked ≥20 cigarettes per day at baseline or did not exercise (15).
In a 2004 review study published in the Lancet the authors concluded that those with higher vitamin E intake had fewer colds. They concluded that vitamin E supplementation may reduce the number of colds experienced by elderly people in the US. Consuming extra vitamin E may be an inexpensive way to reduce the appreciable mortality and morbidity associated with such infections in elderly people, improving their quality of life while reducing the costs associated with their care (16).
Vitamin E Food Sources and Recommendations
The best sources of vitamin E come from plant seeds such as sunflower seeds, almonds, and hazelnuts, and many vegetable oils (e.g., olive oil, sunflower oil and soybean oil). Other sources include tomato, avocado, spinach, asparagus, Swiss chard, and broccoli.
Vitamin E deficiency can result in anemia, skeletal myopathy, ataxia, peripheral neuropathy, retinopathy, impairment of the immune response and nerve damage. Deficiency can be caused by fat malabsorption disorders such as abetalipoproteinemia (a condition that prevents the body from completely absorbing certain dietary fats) or by genetic abnormalities that affect vitamin E transport.
Recommended Daily Allowance (RDA) and established Upper Limits (UL) according to the NIH:
Infants up to age 6 months, the RDA is 4 mg (6 IU), UL = NA
6 month to one year, 5 mg (7.5 IU), UL = NA
From ages 1 to 3 years old, 6 mg (9 IU), 200 mg UL
4 to 8 years old and 7 mg (10.4 IU), 300 mg UL
9 to 13 years old, 11 mg (16.4 IU), 600mg UL
14-18, 800 mg UL
19+ 1,000 mg UL