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Three new trials suggest a novel antidepressant hides inside the blue-skinned fruit.
Food is an ideal drug delivery system, and an intriguing trio of studies suggest antidepressant potential for 1 food in particular: the blueberry.
All 3 studies hail from a single group lead by Claire Williams at the University of Reading, England.1,2 They tested the effect of a powdered blueberry drink—equivalent to 1 cup of fresh blueberries—on mood in 144 children, adolescents, and young adults through 3 randomized, placebo-controlled trials. The placebo drink had the same sugar and vitamin C content as the blueberry juice, and both drinks were made to look the same by mixing them with concentrated orange juice. The Table outlines the key points from these studies.
The first 2 studies (which were published in a single paper) examined mood 2 hours after a single drink, and the third looked at longer term effects of a daily drink over 4 weeks.1,2 All 3 studies were positive, with effect sizes that ranged from small (0.27) to medium (0.65).
Impressive, But What Is the Catch?
The main limitation is the fact that the studies were small and came from a single research group. Also, they all enrolled healthy participants, so we don’t know if blueberries actually treat clinical depression. No risks were identified, though one might wonder if blueberries can trigger mania. Reassuringly, 3 animal studies found anti-manic effects with blueberries, 1 of which compared them with lithium.3
These findings are supported in part by a Canadian study where blueberry juice prevented postpartum blues (ie, the brief lability seen after delivery known as the “baby blues”) in healthy pregnant women, but the juice in that small controlled trial also contained tryptophan (2 g) and tyrosine (10 g).4 In contrast, 2 other independent groups that tested blueberries in healthy older patients did not find any mood benefits.5,6
This does not mean blueberries are only helpful in the young. Although the berries did not improve mood in the geriatric studies, they did improve cognition, which was the primary outcome. There are 13 controlled trials of the cognitive effects of blueberries and their extracts all age groups, and 85% of those trials are positive.7-10
A Closer Look
What is the medication inside this efficient drug delivery system? Blueberries have several positive effects on the brain. They are neuroprotective, increasing brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1); anti-inflammatory; and raise production of serotonin precursors.7 Most of these effects are because of anthocyanins, a group of antioxidants that give the fruit its purplish-blue hue.
Anthocyanins are found in other purple-tinted foods, like blackberries, blackcurrants, acai, black “forbidden” rice, eggplant, and the exotic purple varieties of cauliflower, asparagus, and sweet potatoes. Anthocyanins are also featured in red produce like cranberries, cherries, pomegranate, and red cabbage.
The Bottom Line
Blueberries sound like a brain super-food, but super-foods are not what nutritional psychiatry is all about. When working with medications, we shy away from polypharmacy, and aim instead to bring about the miracle of remission with a single pill. In nutritional psychiatry, polypharmacy is the ideal. The brain and body do best with a healthy mix of nutrients, and while 1 cup a day of blueberries is unlikely to cause harm, too much of a good thing is not the intent of this research.
What do you think? Share comments with your colleagues by emailing PTEditor@mmhgroup.com. Comments may be shared online pending review and editing for style.
Dr Aiken is the Mood Disorders Section Editor for Psychiatric TimesTM, the Editor in Chief of The Carlat Psychiatry Report, and the Director of the Mood Treatment Center. He has written several books on mood disorders, most recently The Depression and Bipolar Workbook. He can be heard in the weekly Carlat Psychiatry Podcast with his co-host Kellie Newsome, PMH-NP. The author does not accept honoraria from pharmaceutical companies but receives royalties from PESI for The Depression and Bipolar Workbook and from W.W. Norton & Co. for Bipolar, Not So Much.
1. Khalid S, Barfoot KL, May G, et al. Effects of acute blueberry flavonoids on mood in children and young adults.Nutrients. 2017;9(2):158.
2. Fisk J, Khalid S, Reynolds SA, Williams CM. Effect of 4 weeks daily wild blueberry supplementation on symptoms of depression in adolescents.Br J Nutr. 2020;10:1-8.
3. Spohr L, Soares MSP, Oliveira PS, et al. Combined actions of blueberry extract and lithium on neurochemical changes observed in an experimental model of mania: exploiting possible synergistic effects.Metab Brain Dis. 2019;34(2):605-619.
4. Dowlati Y, Ravindran AV, Segal ZV, et al. Selective dietary supplementation in early postpartum is associated with high resilience against depressed mood.Proc Natl Acad Sci U S A. 2017;114(13):3509-3514.
5. Boespflug EL, Eliassen JC, Dudley JA, et al. Enhanced neural activation with blueberry supplementation in mild cognitive impairment.Nutr Neurosci. 2018;21(4):297-305.
6. Miller MG, Hamilton DA, Joseph JA, Shukitt-Hale B. Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Eur J Nutr. 2018;57(3):1169-1180.
7. Travica N, D'Cunha NM, Naumovski N, et al. The effect of blueberry interventions on cognitive performance and mood: A systematic review of randomized controlled trials.Brain Behav Immun. 2020;85:96-105.
8. Rutledge GA, Sandhu AK, Miller MG, et al. Blueberry phenolics are associated with cognitive enhancement in supplemented healthy older adults.Food Funct. 2021;12(1):107-118.
9. Whyte AR, Rahman S, Bell L, et al. Improved metabolic function and cognitive performance in middle-aged adults following a single dose of wild blueberry. Eur J Nutr. 2020;10.1007.
10. Bensalem J, Dudonné S, Etchamendy N, et al. Polyphenols from grape and blueberry improve episodic memory in healthy elderly with lower level of memory performance: a bicentric double-blind, randomized, placebo-controlled clinical study. J Gerontol A Biol Sci Med Sci. 2019;74(7):996-1007.