Framingham Offspring Cohort study suggests older adults reap neuroprotective benefits from flavonoid-rich food

Diets that are higher in flavonoids — including red wine, tea, or berries, for example — may reduce the risks of developing Alzheimer’s disease related dementias (ADRD), according to a recent analysis of data from the Framingham Offspring Cohort Study published in The American Journal of Clinical Nutrition. Researchers also found that diets high in flavonols and anthocyanins, two specific classes of flavonoids, also reduced the risks for Alzheimer’s disease (AD).

Flavonoids are plant-based substances and are found in fruits and vegetables such as apples, berries, pears, and onions, as well as plant-based beverages such as tea and wine. Dark chocolate is also a rich source of flavonoids.

“Although earlier evidence from in vitro studies suggested that the beneficial neuroprotective effect of flavonoids is due to their antioxidant potential, either by means of their ability to scavenge reactive species or through influence on intracellular redox status, more recent evidence has emerged that flavonoids are more likely to exert favorable cognitive effects by protecting neurons from neurotoxins and combating neuroinflammation,” according to these researchers, led by Esra Shishtar, of the Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts. “Human intervention studies assessing the acute effects of flavonoid-rich foods, such as cocoa, blueberries, and orange juice, have revealed promising findings in the areas of memory, attention, and executive function. However, given the short duration of these trials, it is not possible to extrapolate their findings to ADRD risk.”

Thus, these researchers evaluated the effects of flavonoid intake on risk of ADRD in 2,801 participants from the Framingham Heart Study Offspring Cohort Study, and on the risk of AD in 2,800.

Participants were highly educated, with 60.4% having at least a college degree, engaged in light physical activity; overweight (mean BMI: 27.8); had a low prevalence of smoking, diabetes, and stroke; and a high prevalence of hypertension and hypercholesterolemia, and moderate DGAI scores.

Shishtar et al included data from participants (mean age at baseline: 59.1 years; 52.0% female) who were free of ADRD and AD, assessed flavonoid intake at each exam, and categorized participants according to percentile categories of their flavonoid intakes.

Key dietary sources of flavonoids in the study included red wine, orange juice, tea, oranges, apples/pears, and strawberries, and researchers used the USDA flavonoid content of foods to determine participants’ flavonoid intake.

Those in the highest category of flavonoid intake were older, more likely to be female, more educated, more physically active, consumed more calories, and had a better overall diet quality compared with those in the lowest category. They also had a higher intake of omega-3 fatty acids (EPA and DHA), lutein, zeaxanthin, and multivitamin/mineral supplements; smoked less; had lower BMI; and less hypercholesterolemia.

Researchers determined participant risk of developing dementia through the following:

  • A decline in routine Mini-Mental State Exam score.
  • A decline in any neuropsychological testing during Framingham NP Ancillary exams.
  • A referral by Framingham Heart Study researchers.
  • Suspected cognitive decline as reported by self or family.

  • Suspected cognitive decline as evidenced in primary care physician or nursing home records.

After a mean follow-up of 19.7 years, they identified 193 cases of ADRD, of which 158 were AD.

Upon multivariate and dietary adjustments, Shishtar and fellow researchers found a lower risk of ADRD in those with the highest intakes of flavonols (>60th percentile; HR: 0.54; 95% CI: 0.32-0.90; Ptrend=0.003), anthocyanins (HR: 0.24; 95% CI: 0.15-0.39; Ptrend less than 0.001), and flavonoid polymers (HR: 0.58; 95% CI: 0.35-0.94; P-trend=0.03) compared with those with the lowest intakes (≤15th percentile). They saw the same results upon analysis for AD for flavonols and anthocyanins, but not for flavonoid polymers.

Upon further analysis, they found that higher total flavonoid intakes had a significant protective association on declining cognitive function. Those with the highest intakes of total flavonoids were approximately 40% less likely to develop ADRD (HR: 0.58; 95% CI: 0.32-1.08; P-trend=0.05) compared with those with the lowest intakes.

After conducting a further sensitivity analysis to determine the effects of age at ADRD diagnosis on associations with flavonoid intake, Shishtar and colleagues found a stronger inverse association between total flavonoid intake and the flavonoid classes (flavonols, anthocyanins, and flavonoid polymers) with the risk of ADRD in those who were diagnosed at 80 years or older compared with those diagnosed before 80 years of age.

“In conclusion, our findings are an important addition to the limited evidence that higher long-term flavonoid intake could reduce the risk of ADRD and AD. These findings also add to the evidence that diet could be an important contributor to ADRD and AD risk. Future studies in larger and more racially and ethnically diverse subjects are warranted to confirm our findings,” concluded Shishtar and fellow researchers.

Limitations of their study include their inability to assess independent contributions of the individual flavonoid classes to the incidence of ADRD, the lack of simple continuous or categorical modeling due to the nonlinear nature of flavonoid intake associations with ADRD and AD, the data-driven nature of the flavonoid category cutoff values, and the limited accountability for certain ADRD risk factors such as cognitive status at a young age. In addition, the interactions between flavonoids and other dietary nutrients were assessed. Finally, because the majority of participants were white and of European descent, these results may not be generalizable.

Nevertheless, their results bolster the growing evidence that dietary factors play a key role in protecting cognitive health.

“The present study is an important addition to the growing literature on flavonoids and dementia. While we wait for the results of the MIND trial, we should recall the robust evidence base supporting beneficial health effects of maintaining a healthy diet in combination with other healthy lifestyle choices across all stages of life,” wrote Majken K. Jensen, MSc, PhD, of the University of Copenhagen, Copenhagen, Denmark, and Professor Aedin Cassidy, of Queen’s University Belfast, Belfast, UK, in an accompanying editorial.

  1. In older adults, a higher intake of flavonoids may protect against Alzheimer’s disease and Alzheimer-related dementias.

  2. Foods rich in flavonoids, like dark chocolate, red wine, tea, and berries, may confer neuroprotective effects in older adults.

E.C. Meszaros, Contributing Writer, BreakingMED™

Shishtar reported no conflicts of interest.

This study was supported by the USDA Agricultural Research Service, the National Heart, Lung, and Blood Institute, the National Institute on Aging, The National Institute of Neurological Disorders and Stroke, and the Embassy of the State of Kuwait.

Jensen reported no conflicts of interest. Cassidy has received funding from the U.S. Highbush Blueberry council.

Cat ID: 33

Topic ID: 82,33,404,485,730,33,361,192,362