The Effects of Vitamin E Intake on Alzheimer’s Disease Risk
Abstract
Vitamin E has long been believed to affect cognitive function. Because of their anti-inflammatory properties and ability to reduce oxidative stress, antioxidants have the potential to protect brain health in the elderly and prevent neurodegenerative disorders such as Alzheimer’s disease (AD). However, scientific findings have been varied and inconsistent. The purpose of this literature review is to assess the most current research studies and reviews available to see whether or not current research is finding that vitamin E intake reduces the risk of developing AD. This paper analyzes five original research studies and three literature reviews published within the last five years, and also the set of nutritional guidelines established by the International Conference on Nutrition and the Brain. While half of the studies found that vitamin E supplementation did indeed reduce AD risk, the other half found no significant correlation, producing inconsistent results that cannot definitively establish a correlation. Consumption of vitamin E from food sources rather than supplements may increase its impact on AD risk, and long-term healthy dietary patterns may be more useful for preventing the disease than specific nutritional supplements.
Introduction
Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia, affecting 46 million people worldwide (Grimm, Mett, & Hartmann, 2016). It is associated with aging and produces symptoms of memory loss and cognitive deterioration (Boccardi, Baroni, Mangialasche, & Mecocci, 2016). Due to its antioxidant and anti-inflammatory properties, vitamin E has long been suggested to be neuroprotective and beneficial for preventing and treating AD. Although vitamin E is an essential nutrient, about 90% of the population still does not consume the RDA of 15 mg per day, averaging only about 7 mg (Cervantes & Ulatowski, 2017). Due to increasing life expectancy, the number of people diagnosed with AD is expected to double every twenty years (Grimm et al., 2016). This represents a major public health concern.
Although vitamin E intake has long been suspected to influence brain health and aging, scientific findings over the years have been varied and contradictory. The effectiveness of vitamin E as a neuroprotective agent may also be influenced by whether it is consumed as a supplement or from food sources. The purpose of this literature review is to compare the most current research studies to determine whether or not vitamin E intake reduces the risk of developing AD.
Methods
For this literature review, the researcher used the search parameters “vitamin E” AND “Alzheimer’s disease” AND prevention in ProQuest Central, PubMed, and Google Scholar. The search was limited to free full text and peer reviewed original research studies and literature reviews published within the last five years that sought to determine whether or not vitamin E supplementation could help to prevent AD. This review includes five original research studies, three literature reviews, and a set of guidelines produced by the International Conference on Nutrition and the Brain. The purpose of this review is to compare the most recent articles available in scientific literature to determine whether or not vitamin E supplementation reduces the risk of developing AD.
Results
A literature review by Grimm et al. (2016) summarized information on how vitamins E, A, D, and K influence AD risk and the treatment of AD patients. Due to its antioxidant properties, vitamin E has been suggested to be beneficial for preventing and treating AD. Vitamin E also has neuroprotective, anti-inflammatory, and hypocholesterolemic properties. Some studies have shown that lower levels of vitamin E have been found in patients with AD, and that high dietary intake of vitamin E can be associated with a reduced risk. However, results have been inconsistent, and other studies have found no association, or even that high dosages of vitamin E can increase all-cause mortality. Two beneficial properties of vitamin E—the anti-inflammatory and hypocholesterolemic effects—can actually negatively affect AD pathogenesis, suggesting that not all patients with AD may benefit from vitamin E supplementation. The researchers concluded that further studies are necessary to determine the effectiveness of these vitamins in AD patients and their ability to prevent the disease.
In a review by Gugliandolo, Bramanti, and Mazzon (2017), the researchers focused on vitamin E supplementation in animal models and AD patients. The experimental models found that vitamin E supplementation could reduce oxidative stress, which is involved in the development of AD. Combining vitamin E supplementation with other antioxidant compounds may increase the protective effect. In particular, combining vitamins E and C may lower the risk of cognitive decline. In addition to supplementation, a higher intake of foods rich in vitamin E may improve cognitive function. The review also addressed whether or not vitamin E supplementation increases all-cause mortality. While the researchers sited one study that did find an increase in mortality risk, they referenced four other studies that found either no association or a reduced risk.
In a literature review of the role of vitamin E in the pathogenesis and treatment of AD, Boccardi et al. (2016) found that high concentrations of vitamin E correlated with better cognitive performance. However, more evidence is needed to prove the ability to prevent AD or delay cognitive decline. They also found that tocotrienols seem to be superior to tocopherols in their anti-inflammatory and antioxidant functions. The vitamin E family is made up of four tocotrienols and four tocopherols, ⍺-tocopherol being the most abundant in nature and the most widely studied. Oxidative stress, the imbalance between reactive species and antioxidant defenses, is believed to be involved in the pathogenesis of AD. Although vitamin E is widely accepted as an extremely potent antioxidant, actual evidence of its ability to prevent AD is rare. The researchers sited several studies that found a protective role of vitamin E for the prevention of AD, and several other studies with conflicting and contradictory evidence. There is also a possible difference between vitamin E intake from food sources or supplements; several studies have found that there is a greater preventative effect from AD when the vitamin comes from foods, likely because food sources contain all different forms of tocotrienols and tocopherols. The researchers concluded that the roles of the different forms of vitamin E in preventing AD remained unclear and required additional research.
In a cross-sectional study, Berti et al. (2015) followed 52 cognitively normal individuals to determine whether or not there was an association between dietary nutrients and AD biomarkers. Using a food frequency questionnaire, the researchers assessed the intake of 35 nutrients thought to affect cognitive function. Most studies comparing nutrition and AD risk investigate single nutrients in their isolated forms; this study looked at the diet as a whole because “the human diet is strongly influenced by synergy or antagonism among components.” They found a protective effect associated with vitamins B12, D, E, A, and C, as well as zinc, dietary fiber, and mono- and polyunsaturated fats. The most AD protective diets were associated with higher intakes of fruits, vegetables, whole grains, fish, low-fat dairy products, and nuts, and lower intakes of sweets, processed meat, fried foods, and high-fat dairies. They concluded that dietary intervention may helpful in preventing AD. A possible limitation of the study is that the researchers did not ask participants to change their diet in any way, and 40% reported taking a multivitamin or other vitamin supplementation regularly in the year before the study. Future studies would benefit from having a supplement-free control group to replicate these findings.
In 2002, the Prevention of Alzheimer’s Disease with Vitamin E and Selenium (PREADViSE) recruited 7,540 men for a randomized controlled trial, 3,786 of whom continued on to participate in this cohort study by Kryscio et al. (2017). The study attempted to determine whether or not antioxidant supplementation of vitamin E or selenium, or a combination of the two, could help to prevent dementia in asymptomatic men over 60 years old. Participants were given vitamin E, selenium, vitamin E and selenium, or a placebo and were evaluated for dementia. The researchers found no significant protective effect of the supplements, however they recognized that the low incidence of AD observed during follow-up could have been a possible limitation to the study.
In a case-control study, Mullan et al. (2017) compared serum levels of dietary antioxidants in both 251 participants diagnosed with AD and 308 cognitively normal control participants. The researchers found that patients with AD had significantly lower levels of retinol, vitamin E (⍺-tocopherol) and six carotenoids. However, there were limitations to the study. The researchers did not account for energy or supplement intake between participants. Also, due to the cross-sectional nature of the study, whether there was a causal relationship between vitamin deficiency and AD remained unknown. They concluded that there was still insignificant evidence of a causal relationship between low antioxidant levels and the development of AD. Future large-scale studies that compare antioxidant status with declining cognitive function are necessary.
A study by Bhatia, Baron, Hagl, Eckert, and Fiebich (2016) aimed to evaluate the anti-inflammatory effects of rice bran extract (RBE) in rats to see whether or not it could help prevent neurodegenerative disorders. Neuroinflammation is an important factor in the occurrence of AD. Plant extracts containing polyphenols and vitamin E (such as RBE) are believed to have neuroprotective and anti-inflammatory properties. The researchers found beneficial effects of RBE due to the antioxidant and anti-inflammatory properties. They concluded that RBE had value as a nutraceutical for the prevention of microglial dysfunction related to AD.
Similarly, Hagl et al. (2016) conducted a study to determine whether or not RBE could help to prevent neurodegenerative diseases. The researchers studied the effects of long-term (6-month) RBE administration on the survival, behavior, and brain function of aged NMRI mice. They found that RBE significantly increased the chances of survival and the performance of the mice, and improved brain function and memory. Their findings suggested that long-term consumption of RBE could delay brain aging and prevent AD.
Finally, Barnard et al. (2014) summarized the results of the International Conference on Nutrition and the Brain held in Washington D.C. in July 2013. Asked to comment on AD prevention, the committee came up with seven preliminary guidelines related to diet and exercise that could be recommended to the public to help prevent AD. The guidelines that emerged are summarized as follows: minimize intake of saturated and trans fats; replace most meat and dairy products with vegetables, legumes, nuts, fruits, and whole grains; consume vitamin E from food sources rather than supplements; consume a reliable source of vitamin B12 daily; choose multivitamins without iron and only consume iron when directed by a physician; those who wish to minimize exposure to aluminum can avoid aluminum cookware and products; and exercise aerobically at least three times per week. In terms of vitamin E, the researchers summarized that the RDA is 15 mg per day, and food sources include nuts, seeds, leafy green vegetables, and whole grains. They stated that vitamin E from supplements has not been proven to reduce AD risk because many supplements contain only ⍺-tocopherol and do not replicate the wide range of vitamin E in whole foods. Even when scientific consensus concerning disease risk factors cannot be reached, it is important for the public, especially those at higher risk of AD, to act on the best information currently available that will not harm their health and could potentially reduce their risk.
Discussion
Although antioxidants such as vitamin E have long been believed to help protect cognitive function and prevent neurodegenerative diseases, the evidence in scientific literature is still lacking. Of the five research studies analyzed here, three found that vitamin E likely did have a neuroprotective effect. Bhatia et al. (2016) and Hagl et al. (2016) studied the effects of RBE on rats and mice, and concluded that RBE could help prevent AD. Studying foods and dietary patterns rather than nutrient specific supplements, Berti et al. (2015) found that diets high in fruits, vegetables, whole grains, fish, low-fat dairy products, and nuts could help protect cognitive function and reduce the risk of AD. Two studies did not find a significant correlation between vitamin E and AD risk. Attempting to determine whether or not vitamin E deficiency could cause AD, Mullan et al. (2017) found that AD patients had lower levels of various antioxidants (including ⍺-tocopherol), yet could not prove a causal relationship between the two. Studying specifically vitamin E and selenium supplementation, Kryscio et al. (2017) found no significant evidence that either antioxidant or a combination of the two would lower AD risk.
Of the three literature reviews analyzed in this paper, only one found significant evidence that vitamin E could lower AD risk, and two found varied and inconclusive evidence. The findings of Grimm et al. (2016) varied from vitamin E supplementation protects against AD, to vitamin E increases all-cause mortality and can worsen pathogenesis in patients. Boccardi et al. (2016) found that although vitamin E has been shown to improve cognitive performance, more evidence is needed to prove that it actually reduces AD risk. Gugliandolo et al. (2017) found that vitamin E could improve cognitive function and reduce oxidative stress associated with the development of AD, and that positive effects of the antioxidant may be enhanced when combined with vitamin C. They also addressed the above mentioned increase in all-cause mortality with four other studies that demonstrated no association or a reduced risk.
Several of these studies mentioned the possibility that vitamin E intake from foods rather than supplements could alter the results produced. The eight different forms of vitamin E found in foods may affect the body differently than the supplementation of one form (usually ⍺-tocopherol). This is congruent with the summary by Barnard et al. (2014) of the nutritional guidelines to prevent AD established by the International Conference on Nutrition and the Brain in 2013. One of the seven guidelines stated that vitamin E should be consumed from foods rather than supplements to gain the most benefit from the antioxidant. Consuming a diet of whole and unprocessed foods, with low intake of high-fat dairy products, sugar, processed meats, and fried foods, may help to promote healthy brain aging (Berti et al., 2015). However, more research is necessary.
Conclusions and Recommendations
With millions of elderly people affected worldwide by AD, finding a means to prevent the disease is a major public health concern for future generations. Although vitamin E has long been known to affect brain health and improve cognitive function, whether or not supplementation prevents AD remains unclear. It appears that vitamin E intake from foods rather than supplements may increase the benefits to the brain. Following a healthy and wholesome dietary pattern may be more important than consuming specific nutritional supplements. Additional studies are needed to definitely determine whether or not vitamin E supplementation lowers AD risk, and how that compares to high vitamin E intake from foods.
Future research could potentially follow participants with diets high in vitamin E who do not consume vitamin supplements. These groups could be compared to those that consume supplemental ⍺-tocopherol to see what differences occur between immediate brain function and cognitive health over time. Another possible study could compare two elderly samples, one with many years of high vitamin and mineral intake from whole foods, and one with low intakes of fruits, vegetables, seeds, whole grains, etc., to see whether or not differences existed between current brain health and AD risk. However, such a study would also have to account for supplement use over many years, and would rely on the accuracy and integrity of food frequency questionnaires. There is certainly potential for future studies to conclusively identify the relationship between vitamin E and AD. At this time, it remains unclear whether or not vitamin E supplementation reduces the risk of developing AD, although consuming the vitamin from food sources may increase its preventative effect.
References
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