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The Relationship Between Blueberry Supplementation and Memory Function

By: Amy Nguyen, PharmD Candidate c/o 2020 and Alex Chu, PharmD Candidate c/o 2019

One of the most common problems with aging is the ability to maintain brain function. Dementia is a collective term describing conditions revolving the impairment of various brain functions.  Patients with dementia often experience progressive behavioral and neurological changes that include, but are not limited to, functional impairment, loss of independency, emotional problems, and behavioral disturbances.  Among the many cognitive conditions, Alzheimer’s disease is responsible for 60-80% of dementia and is the sixth leading cause of death in the United States, with estimates that 115 million people will develop the disease by 2050.1 This has become a public health concern, for our health systems are neither socially nor economically equipped to assist the affected population.  Currently, there is no cure and no effective therapy for dementia; however, there are possibilities of postponing or preventing cognitive decline with intake of various foods.

Stephen L. Defelice, the founder of the Foundation of Innovation Medicine, introduced the concept of nutraceutics, which utilizes “food, or parts of food, that provide medical or health benefits…beyond the tradition nutrients it contains” to prevent and treat diseases in 1989.2 This concept instigated studies of nutraceutical influences regarding antioxidants, vitamins, and phytochemicals on the cognitive abilities of human beings.  One of the most observed nutraceutical fruits is the Cyanococcus species in the Vaccinium genus, or more commonly known as the blueberry.

Principal ingredients of blueberries are water, carbohydrates, proteins, and fat; however, a serving of blueberries can provide approximately 192 kJ of energy and 10 mg of ascorbic acid, which equates to one-third of the daily-recommended intake.2 Moreover, blueberries possess a particular flavonoid subgroup of phytochemicals called anthocyanins, which “have been credited with [the] capacity to modulate cognitive and motor function, to enhance memory, and to have a role in preventing age-related declines in neural function”.3 These anthocyanins are able to cross and accumulate beyond the blood-brain barrier; thus, they have been identified in the hippocampus and neocortex of the human brain, both of which are crucial for cognitive functions.

In the first controlled human trial examining neurological response to dietary intervention held by the University of Cincinnati Medical Institution, blueberries were proven to have potential neurocognitive benefits in response to participants with Mild Cognitive Impairment (MCI), defined as an “increased risk for dementia and represents the first clinical appearance of neurodegeneration for a substantial subset of individuals who will progress” to Alzheimer’s disease.4,5

The study focused on sixteen older participants with age-related memory decline symptoms, such as prospective memory lapses.  Their levels of memory impairments were measured using the Clinical Dementia Rating (CDR), which classified each participant with no impairment, mild decline, or mild, moderate, or severe dementia.4 Nine of the participants were given a wild blueberry juice, prepared from ripe, frozen wild blueberries from Van Dyk’s Health Juice Products Ltd (Caledonia, Nova Scotia, Canada), while the other seven consumed a placebo comparison with no juice or natural polyphenol but matched in composition and caloric load.  Participants were dosed according to their body weight and were prescribed to drink the juice three times a day after meals for twelve weeks. Individuals between 54-64 kg consumed 444 mL/day, those between 65-76 kg consumed 532 mL/day, and those between 77-91 kg consumed 621 mL/day.4,6, To accurately assess each participants’ memory function, the Verbal Paired Associate Learning Test (V-PAL) and the California Verbal Learning Test (CVLT) were performed at the beginning of the treatment and in the final week of the treatment, with lower scores indicating a greater measure of memory decline.  The V-PAL assesses the participant’s ability to form novel associations, whereas the CVLT involves acquisition and retention of a list of words, both of which pertain to hippocampal processing and are pertinent to cognitive aging effects.

After twelve weeks, the V-PAL and CVLT cumulative learning scores of those given the blueberry juice improved significantly compared to those receiving the placebo juices (9.6 vs 7.2) [p=0.04].4 Although the preclinical research of this study mainly concerned the antioxidant and neuronal signaling properties of the blueberry, recent studies have “supported the notion that anthocyanins can also enhance glucose disposal through a number of mechanisms,” further enhancing neurocognitive functions.4 The studies did have a limitation of small sample size because it was the first human trial on assessing potential benefit of blueberry supplementation.4 Further research and larger clinical trials would have to be conducted in order to confirm a correlation between blueberry supplementation and decreased cognitive decline.

Based on preliminary findings, the outlook of blueberry supplementation to improve memory seems optimistic and sets a foundation to encourage and promote further human research on preventative supplemental measures on cognitive aging.


  1. Wortmann M. Dementia: a global health priority – highlights from an ADI and World Health Organization report. Alzheimers Res Ther. 2012;4(5):40. doi: 10.1186/alzrt143 Accessed February 28 2017.
  2. Keservani RK, Sharma AK, Kesharwani RK. Medicinal Effect of Nutraceutical Fruits for the Cognition and Brain Health. Scientifica (Cairo). 2;2016:3109254. doi: 10.1155/2016/3109254. Accessed February 28 2017.
  3. Lila MA. Anthocyanins and Human Health: An In Vitro Investigative Approach. J Biomed Biotechnol. 2;2004(5):306-313. doi: 10.1155/S111072430440401X Accessed February 28 2017.
  4. Krikorian R, Shidler MD, Nash TA, et al. Blueberry supplementation improves memory in older adults. J Agric Food Chem. 2010;58(7):3996-4000. doi: 10.1021/jf9029332. Accessed February 28 2017.
  5. Nooyens AC, Bueno-de-Mesquita HB, van Boxtel MP, et al. Fruit and vegetable intake and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study. Br J Nutr. 2011;106(5):752-61. doi: 10.1017/S0007114511001024 Accessed February 28 2017.
  6. Krikorian R, Nash TA, Shidler MD, Shukitt-Hale B, et al. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010;103(5):730-4. doi: 10.1017/S0007114509992364 Accessed February 28 2017.
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