Dietary Vitamins C and E

Vitamins C and E are essential for proper health.  Some people with Alzheimer’s disease and dementia have low levels of these vitamins, although it has not been proven that the lack of vitamins caused their disease.  Observational studies suggest that increasing dietary intake of vitamins C and E might protect against dementia although vitamin C and E supplements may not offer the same protection.  Both vitamins are generally safe for supplementation in healthy people, although some studies have linked vitamin E supplementation with an increased risk of dying.  Maintaining healthy levels of vitamins C and E in the diet may be better for most people than supplementation.

EFFICACY
Possibly
with   Moderate  evidence
SAFETY WHEN
USED AS DIRECTED
Very likely
with   Strong  evidence

Because it dissolves easily in water and can scavenge many types of harmful reactive oxygen species, vitamin C (also called ascorbate or ascorbic acid) is commonly considered the most important antioxidant of the blood.  Vitamin C is also vital in the production of collagen and certain neurotransmitters.  Vitamin E refers to a family of 8 compounds, of which alpha-tocopherol has been considered the most important to human health and is the form that comprises most commercially-available vitamin E supplements.  Vitamin E is very fat-soluble and plays a critical role in preventing harmful fat oxidation.

Did You Know? Humans are one of the few mammals that don’t make vitamin C and must obtain it through food!

Vitamin C is common in citrus fruits, sweet peppers and Brussels sprouts.  Vitamin E is plentiful in green leafy vegetables, sunflower seeds and almonds.  Both vitamins are commercially available as dietary supplements from a variety of manufacturers, although their quality and content will vary by source.

As our brains and bodies use sugar (glucose) for energy, they create free radicals, potentially harmful molecules that can damage (“oxidize”) proteins and DNA.  Vitamins C and E are two of the body’s most important antioxidants and can bind to and stop free radicals and limit their damage.  Vitamin E is also required for our bodies to make collagen and certain neurotransmitters that are critical for proper brain functioning.  We absorb both vitamins in the gut from the food we eat.  Although we can absorb an unlimited amount of vitamin E, our bodies can only absorb about 400 milligrams (mg) per day of vitamin C.

Possibly prevents dementia, based on moderate evidence.  Preclinical animal studies suggest both vitamins C and E play neuroprotective roles.  However, it is difficult to prove similar benefits for people and there are differences between reported benefits of vitamin supplementation versus getting proper levels of vitamins C and E from foods.  One study found that people with low levels of dietary vitamin C were more likely to develop Alzheimer’s disease than people with normal levels, but this doesn’t prove that low vitamin C caused the disease [1].  Indeed, raising dietary intake of both vitamins might lower risk of Alzheimer’s disease by ~ 20-25%, although these studies looked at people with varying starting baseline levels of vitamins C and E [2].

Maintaining healthy levels of vitamins C and E in the diet may be more beneficial than supplementation.  An observational study reported supplementation with both vitamins C and E failed to slow cognitive decline over a one year period in women over 65 [3].  However, a clinical trial reported that vitamin C and E supplementation did slow cognitive decline in both men and women who also took a non-steroidal anti-inflammatory drug (NSAID) [4].  Very little is known about supplementation with individual vitamins.  It remains unclear whether vitamin C or E supplementation, alone or in combination, prevents cognitive decline or dementia.

Although alpha-tocopherol, one of the 8 vitamins that comprise the family of compounds known as “vitamin E”, has been traditionally thought to be the most important for human health (and, as such, is the most common form of vitamin E in commercially available supplements), recent research is revealing that other members of the vitamin E family may also be important, especially is cognitive health.  Indeed, the study found that older people with higher levels of gamma-tocopherol, beta-tocotrienol (two other members of the vitamin E family of molecules) were up to 70% less likely to develop mild cognitive impairment (MCI) or Alzheimer’s disease [5].  These findings are shedding light on the importance of the entire family of E vitamins, not just alpha-tocopherol.

Possibly, based on limited evidence.  The evidence that vitamin E supplementation can slow cognitive decline in people already suffering from MCI or dementia is conflicted.  Several trials have tested vitamin C and E supplementation either alone or in combination with another antioxidant, alpha-lipoic acid, and have reported very little or no cognitive improvement [6,7].  Very little is known about vitamin C supplementation alone.  However, several studies suggest vitamin E supplementation has very little to no protective effect [8].  A supplementation trial at 800IU/day found no improvement in cognitive function in Alzheimer’s disease patients [9] while another at 2000IU/day found only slight improvement [10].  A related study found that vitamin E supplementation at 2000IU/day did not slow the time to progression from mild cognitive impairment to Alzheimer’s disease [11].  Additionally, deficiencies in both vitamins that have been associated with Alzheimer’s disease and dementia could be due to malnutrition common in this population.  In contrast, however, a recent study of 152 mild-to-moderate Alzheimer’s patients given 2000IU/day of Vitamin E over reported almost 20% slower cognitive decline than a group of similar patients given a placebo [12].  These patients had different and more advanced disease pathology than the patients with MCI in the trials discussed above and were also treated for a shorter period of time, which may account for the different outcome.  These results warrant further investigation.

Some research supports roles for vitamins C and E in aging and mortality, but this data is limited to “test tube” experiments and observational studies in people.  Data from in vitro experiments suggest a role for vitamins C and E in the aging process [13,14].

Several meta-analyses have implicated vitamin E, but not vitamin C, supplementation in mortality.  A Cochrane group analysis in 2012 of 78 trials concluded that vitamin E supplementation above 225IU (150mg)/day increased mortality in 46 trials (relative risk: 1.03, i.e. 3% increased risk) [15].  This study expanded on a 2008 meta-analysis of 67 trials that found very similar results [16].  These studies contrast with a meta-analysis by Abner et al of 57 trials that found no association between vitamin E supplementation up to 5000IU/day and mortality [17].  These differences might be explained by the Cochrane group’s categorization of trials with low or high risk of bias (trials in disease populations).  Further work is needed to clarify the role of vitamin E supplementation in mortality.

Likely safe, based on strong evidence.  While these vitamins are essential for good health, it should be noted that excessive amounts of these vitamins may not be healthy.  Vitamin E supplementation about 225IU has been linked in some studies to a slightly increased risk of death [15,16] and a study of men with high selenium levels in their bodies recently reported that vitamin E supplementation at 400IU/day (as well as selenium supplementation) almost doubled their risk of prostate cancer [18].  It should also be noted that while vitamin E absorption is unlimited, vitamin C absorption is limited to about 400mg/day due to the vitamin C transport system.  Thus vitamin C doses higher than ~ 400mg/day are likely not delivering more than 400mg/day to the body.

• Ensure that your source is safe and reliable.  Several organizations offer independent testing of product quality to earn “seals-of-approval.”  More information about this quality testing and important facts about supplements are offered by the NIH Office of Dietary Supplements.

• Discuss your options and your supplement use with all your health care providers.  This will help ensure that your treatments are safe and will not interact dangerously with other drugs or treatments.

• If you are deficient in vitamins C or E, you might consider increasing your dietary intake by eating foods rich in these vitamins. Citrus fruits, sweet peppers and Brussels sprouts are rich in vitamin C and vitamin E is plentiful in green leafy vegetables, sunflower seeds and almonds.

Several clinical trials are planned or on-going to evaluate the role of vitamins C and E in cognitive decline and dementia.  More information about these and other clinical trials can be found at clinicaltrials.gov (U.S.) and at clinicaltrialsregister.eu (Europe).

• A long-term Alzheimer’s disease prevention trial called Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE), is currently on-going to determine the potential of vitamin E and selenium supplementation, together or individually, to prevent Alzheimer’s disease (NCT00040378).

• A small trial is currently enrolling 180 participants to study levels of various vitamins, including vitamins C and E, in healthy people and people with mild cognitive impairment (MCI) and Alzheimer’s disease (NCT01479855).

• An on-going study of 250 participants aims to study the potential of vitamin E supplementation to slow functional and cognitive decline in older adults with Down Syndrome, a disease with many similarities to Alzheimer’s disease (NCT00056329).

There are several on-line resources of information that can assist you when making decisions about whether to take vitamin C, vitamin E or other supplements.

• Quality Control of Sources: United States Pharmacopeial Convention (USP), ConsumerLab, and FDA Information on Dietary Supplements offer information on the quality of specific supplements and can assist in finding a trusted brand.

• The NIH Office of Dietary Supplements has created a freely-available “fact sheets” on both vitamin C (here) and vitamin E (here).

• WebMD offers information on vitamin C (here) and vitamin E (here), including dosing and safety as well as user reviews and ratings about specific brands.

1.  von Arnim CA, Herbolsheimer F, Nikolaus T, Peter R, Biesalski HK, Ludolph AC, Riepe M, Nagel G (2012) Dietary antioxidants and dementia in a population-based case-control study among older people in South Germany. J Alzheimers Dis 31:717-724.
2.  Li FJ, Shen L, Ji HF (2012) Dietary intakes of vitamin E, vitamin C, and beta-carotene and risk of Alzheimer's disease: a meta-analysis. J Alzheimers Dis 31:253-258.
3.  Kang JH, Cook NR, Manson JE, Buring JE, Albert CM, Grodstein F (2009) Vitamin E, vitamin C, beta carotene, and cognitive function among women with or at risk of cardiovascular disease: The Women's Antioxidant and Cardiovascular Study. Circulation 119:2772-2780.
4.  Fotuhi M, Zandi PP, Hayden KM et al (2008) Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study. Alzheimers Dement 4:223-227.
5.  Mangialasche F, Solomon A, Kareholt I et al (2013) Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults. Exp Gerontol 48:1428-1435.
6.  Arlt S, Muller-Thomsen T, Beisiegel U, Kontush A (2012) Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer's disease. Neurochem Res 37:2706-2714.
7.  Galasko DR, Peskind E, Clark CM et al (2012) Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 69:836-841.
8.  Farina N, Isaac MG, Clark AR, Rusted J, Tabet N (2012) Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database Syst Rev 11:CD002854.
9.  Lloret A, Badia MC, Mora NJ, Pallardo FV, Alonso MD, Vina J (2009) Vitamin E paradox in Alzheimer's disease: it does not prevent loss of cognition and may even be detrimental. J Alzheimers Dis 17:143-149.
10.  Sano M, Ernesto C, Klauber MR, Schafer K, Woodbury P, Thomas R, Grundman M, Growdon J, Thal LJ (1996) Rationale and design of a multicenter study of selegiline and alpha-tocopherol in the treatment of Alzheimer disease using novel clinical outcomes. Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 10:132-140.
11.  Petersen RC, Thomas RG, Grundman M et al (2005) Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 352:2379-2388.
12.  Dysken MW, Sano M, Asthana S et al (2014) Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA 311:33-44.
13.  Furumoto K, Inoue E, Nagao N, Hiyama E, Miwa N (1998) Age-dependent telomere shortening is slowed down by enrichment of intracellular vitamin C via suppression of oxidative stress. Life Sci 63:935-948.
14.  Xu Q, Parks CG, DeRoo LA, Cawthon RM, Sandler DP, Chen H (2009) Multivitamin use and telomere length in women. Am J Clin Nutr 89:1857-1863.
15.  Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2008) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst RevCD007176.
16.  Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2012) Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 3:CD007176.
17.  Abner EL, Schmitt FA, Mendiondo MS, Marcum JL, Kryscio RJ (2011) Vitamin E and all-cause mortality: a meta-analysis. Curr Aging Sci 4:158-170.
18.  Kristal AR, Darke AK, Morris JS et al (2014) Baseline Selenium Status and Effects of Selenium and Vitamin E Supplementation on Prostate Cancer Risk. J Natl Cancer Inst

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