The Effect of a 10-Day Western Diet on Plasma Brain-Derived Neurotrophic Factor

Preclinical research suggests that consuming a western diet (WD) may contribute to the development of cognitive impairment by reducing the production of brain-derived neurotrophic factor (BDNF), a neuroprotective protein associated with learning and memory. However, the effect of a WD on plasma BDNF in humans has yet to be characterized. Objective: To determine whether consuming a WD reduces plasma BDNF in men and women. We hypothesized that a 10-day WD would reduce plasma BDNF compared to baseline (BL). Additionally, we hypothesized that changes in cardiometabolic risk factors, such as blood pressure, blood lipids, and blood glucose, would be associated with the change in plasma BDNF following the WD. Methods: Middle-aged men and women (50-64 years) were recruited to participate in a controlled feeding study. Participants consumed a 10-day WD that was high in added sugar content (25% of total energy). Blood was collected at BL (a brief visit prior to the WD) and at day 10 of the WD for analysis of blood glucose, blood lipids, and BDNF. Resting systolic and diastolic blood pressure (SBP and DBP) were also assessed at BL and following the consumption of the WD. BDNF was measured on a Quanterix SR-X using a Simoa BDNF Discovery Kit. Normality was assessed via Shapiro-Wilk tests. A Wilcoxon test was used to assess the effect of the WD on plasma BDNF. When appropriate, either Pearson’s or Spearman’s correlations were used to determine whether changes in cardiometabolic risk factors were associated with the change in plasma BDNF following the WD. Results: 24 adults completed the WD (7 males, 17 females, aged 57 ± 4 years). Plasma BDNF was significantly reduced compared to BL following the WD (BL: 2355 ± 1383 vs. WD: 1366 ± 804 pg/mL, p = 0.001). However, there were no significant associations between the changes in any of the cardiometabolic risk factors assessed and the change in plasma BDNF following the WD (ΔSBP: r = -0.280, p = 0.183; ΔDBP: r = -0.097, p = 0.653; Δblood glucose: r = -0.230, p = 0.286; Δtotal cholesterol: r = 0.120, p = 0.587; ΔLDL cholesterol: r = -0.017, p = 0.936; ΔHDL cholesterol: r = 0.042, p = 0.844; Δtriglycerides: r = 0.040, p = 0.854). Conclusion: Our main finding is that plasma BDNF is reduced following a 10-day WD, indicating a potential means by which a WD may contribute to the development of cognitive impairment. However, since the change in plasma BDNF was not associated with a change in any of the cardiometabolic risk factors assessed, the exact mechanism by which a WD reduces plasma BDNF remains unclear. Supported by NIH Grant P20 GM113125 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.