Introduction
Scientists are keenly interested in the potential age and disease-preventive benefits of blueberries. Additionally, the desire for “natural” medications to diminish risk factors of disease is popular among older adults, especially those with hypertension, diabetes and fear of mental decline. Furthermore, the marketing hype promotes blueberry consumption as a reasonable answer to these concerns and a way to retard aging.
Interestingly, blueberries are a plausible “anti-aging” candidate. The thought is that perhaps blueberries can retard aging. That is because these berries contain many compounds with antioxidative capability. A prominent, although contested, theory of aging states that unabated oxidative activity drives the aging process (1). Oxidative activity avidly damages proteins and DNA, eventually diminishing essential functions. Hence, increasing antioxidative activity in the body with consumption of food loaded with this potential should block oxidation and retard aging.
But can blueberry consumption provide sufficient amounts of the right kind of antioxidants to retard aging? Over 40 clinical trials have to date tested this hypothesis. The results as to whether blueberries can retard aging are plentiful, cautiously positive but definitely preliminary. All of this is discussed in this blog.
Inside the Blueberry
The ripe blueberry contains a selection of compounds, termed polyphenols. The polyphenols fall into two classes: the flavonoids and the non flavonoids. The chief contributors to antioxidant activity are the anthocyanin flavonoids. They make up approximately 60% of the polyphenols (2). In fact, they are the red and purple pigments in these berries. They are the ones of most interest to researchers.
Compared to select fruits e.g. apples, raspberries, nectarines, red and black plums, grapes, strawberries, the amount of anthocyanins in blueberries (mg/3.5 oz flesh) is approximately 4-40 times higher. Some fruits such as bananas, melons, yellow plums, oranges, kiwi contain no anthocyanins (3).
In addition to polyphenols, blueberries contain fiber, sugars, vitamin C and protein, none of which compare in concentration to the anthocyanins (4).
Exactly how much of the anthocyanins get absorbed is complex and poorly understood. Generally, anthocyanins that are absorbed are rapidly broken down and excreted. However, many breakdown products (metabolites) persist in tissues. These metabolites are abundant in the large intestine due to activity of the resident bacteria (5)
Observational Study Results
There are a number of observational studies, some fairly large, that have shown a statistical correlation between increased consumption of anthocyanins and reduced risk of cardiovascular disease, diabetes and neurological issues specifically related to Parkinson’s disease (reviewed in 3). Although observational studies provide inspiring information for continuing investigations, they lack the scientific rigor of randomized clinical trials.
Clinical Trial Results
Thus far, the goal of randomized clinical trials is the determination of the effect of blueberry consumption on human health in three areas: a) reduction of risk factors for cardiovascular disease, b) increased insulin sensitivity in diabetes and c) prevention of cognitive decline.
a) Blueberries and Cardiovascular Disease
Trial results show that blueberry consumption (8 wks, freeze-dried powder or berries) lowers blood pressure (about 5%) both systolic and diastolic pressure, in post menopausal women with low grade hypertension (6) and in obese males with metabolic syndrome, a condition of abnormal lipid levels and uncontrolled blood sugar (7). Additionally, twelve weeks of daily blueberry powder consumption lowered systolic pressure in healthy older adults (4). In contrast, a 6 week consumption of blueberry powder in obese diabetic participants did not change blood pressure (8). Several trials reported improvement in vascular function (increased blood flow, reduced arterial stiffness) with either freeze-dried powder or berries (4,8-11). Consumption of blueberry equivalents of ~1.6-3 cups of berries acutely improved blood flow (dose-related manner),1-6 hours post consumption (12).
b) Blueberries and Insulin Sensitivity
As reviewed by Stull (2016) (13), four clinical trials reported consumption of blueberries improved insulin sensitivity in patients with Type 2 Diabetes. However, three other studies found no effect. Apparently, differing methodologies contributed to these opposite results (13). A 6 month trial of blueberry powder (equivalent to 1 cup blueberries) did not improve insulin sensitivity in patients with metabolic syndrome (14). However, the addition of blueberries (one cup equivalent) after a high fat/high sugar meal, reduced the 3 hour spike in glucose and insulin and moderated the level of harmful lipids (15). This blueberry-dependent effect is considered beneficial since a spike in sugar/lipids after a meal is the most harmful aspect of the metabolic syndrome.
c) Blueberries and Prevention of Cognitive Decline
In middle-aged overweight adults with memory complaints, 12 week of powdered blueberry (0.5 cup equivalent) improved scores on some memory and executive tests (word retrieval, memory interference, memory encoding) (16). In a similar study with healthy older adults (65-80), blueberry powder equivalent to 70 wild blueberries/day for 12 weeks improved word recall (4). Twelve older adults consuming concentrated blueberry juice for 12 weeks exhibited increased brain perfusion while completing cognitive tasks compared to controls (17).
Results of a 6 month study of daily consumption of wild blueberry powder improved information reaction time assessed both with a test on the computer and electrophysiologically in those with memory complaints, 75-80 yrs of age (18). In opposition, no effect was observed in those 60-75 years of age. Curiously, the study explanation for the difference is that memory loss in these individuals was disease-dependent and not a consequence of aging as in the older group (18). A similarly puzzling finding occurred with 6 months supplementation with 3 different doses of blueberries (500 mg powder, 1000 mg powder and 100 mg purified extract). In this study, several cognitive test results increased at 3 months in older adults taking the 100 mg purified extract dose. However, cognitive response at 6 months in those consuming blueberries was no better than placebo, regardless of the dose (19).
Assessment of Clinical Trial Results – Considerations
It is important to review several caveats regarding the above clinical trial results with blueberries.
First, most of these trials were funded fully or in part by blueberry associations e.g. Wild Blueberry Association of North America; US Highbush Blueberry Council. In some cases, blueberry associations acted in collaboration. Such relations create a clear bias.
Second, the trials are small enrolling 25-100 participants divided into those consuming blueberries and the controls. On average, small trials show positive effects. Therefore, small studies always require larger ones for confirmation.
Third, the duration of these trials is short, 6 weeks to 6 months. A longer trial is always preferable in cases where the treatment is intended to be a life-long remedy. Additionally, age changes are dynamic. Evaluation of a small window gives little indication of a long term effect in a changing body. Hence, determination of long term efficacy is essential.
Fourth, the participants in these trials consumed freeze-dried powders (17.5 -180 g/day) prepared from blueberries, with poorly defined equivalent to whole berries. One study reported 50 g freeze-dried powder as equivalent to 2.3 cups blueberries (7) but another study stated 150 g freeze dried berries as equivalent to 1 cup of blueberries (11). This is a relevant issue because the older adult needs to know how many berries to consume to experience the purported benefit. Unless a blueberry powder is available as a supplement (and there are issues with supplements, see (Vitamin-mineral supplements: Are they beneficial?) and related blogs (e.g. Blog 30), whole blueberry consumption may contribute important nutrients but add nothing to retard aging.
Key Issue with Blueberries
Issue – Inter-individual Variability. While the above caveats are correctable, the issue of inter-individual variability remains a large black box. One of the most important clinical trials on blueberry and blueberry powder consumption revealed a huge inter-individual variability on response to vascular and cognitive changes (20). Specifically, the results were between “31–71% of participants showing improved responses (up to +11 to +525%) and 29–66% of participants showing worsened responses (up to −12 to −141%) for the vascular and cognitive endpoints”(20). This is related to the unique metabolic capabilities of each person and the diversity of the intestinal bacteria (20). Absent an understanding here, application of clinical trial results to the general population of older adults is currently impossible.
Summary Points – can blueberries retard aging
1. The data supporting an anti-aging effect of blueberry consumption are preliminary and inconclusive.
2. Future studies need to focus on the metabolism of blueberry components before generating large long term trials testing effects in the older adult.
3. Blueberries provide vitamin C and fiber and are a good addition to a varied healthy diet; the data at present does not support an anti-aging effect with blueberry consumption.
Select References (https://pubmed.ncbi.nlm.nih.gov/)
Full list on request
1. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol . 1956 Jul;11(3):298-300. doi: 10.1093/geronj/11.3.298.
3. Kalt W., Cassidy A., Howard L.R., Krikorian R., Stull A.J., Tremblay F., Zamora-Ros R. Recent Research on the Health Benefits of Blueberries and Their Anthocyanins. Adv. Nutr. 2020;11:224–236. doi: 10.1093/advances/nmz065
13. Stull AJ. Blueberries’ Impact on Insulin Resistance and Glucose Intolerance..Antioxidants (Basel). 2016 Nov 29;5(4):44. doi: 10.3390/antiox504004419.
20. Wang Y, Haskell-Ramsay C, Gallegos JL, Lodge JK Inter-Individual Responses to a Blueberry Intervention across Multiple Endpoints. .Nutrients. 2024 Mar 20;16(6):895. doi: 10.3390/nu16060895