The Effect of Exogenous Ketone Monoester Ingestion on Plasma BDNF During an Oral Glucose Tolerance Test

Abstract

Brain-derived neurotrophic factor (BDNF) is important for brain and metabolic function. Ingestion of a ketone monoester (KME) drink containing beta-hydroxybutyrate (β-OHB) attenuates hyperglycemia in humans and increases neuronal BDNF in rodents. Whether KME affects BDNF in humans is currently unknown. This study examined the effect of KME ingestion before an oral glucose tolerance test (OGTT) on plasma BDNF in normalweight adults (NW) and adults with obesity (OB). Methods: Exploratory, secondary analyses of two studies were performed. Study 1 included NW (n = 18; age = 25.3 ± 4.3 years; BMI = 22.2 ± 2.3 kg/m 2) and Study 2 included OB (n = 12; age = 48.8 ± 9.5 years; BMI = 33.7 ± 5.0 kg/m 2). Participants ingested 0.45 ml/kg −1 body weight KME or Placebo 30-min prior to completing a 75 g OGTT. β-OHB and BDNF were measured via blood samples at fasting baseline (pre-OGTT) and 120 min post-OGTT. Results: Study 1: KME significantly increased β-OHB by 800 ± 454% (p < 0.001). BDNF significantly decreased post-OGTT compared to pre-OGTT in Placebo (718.6 ± 830.8 pg/ml vs. 389.3 ± 595.8 pg/ml; p = 0.018), whereas BDNF was unchanged in KME (560.2 ± 689.6 pg/ ml vs. 469.2 ± 791.8 pg/ml; p = 0.28). Study 2: KME significantly increased β-OHB by 1,586 ± 602% (p < 0.001). BDNF was significantly higher post-OGTT in the KME condition in OB (time × condition interaction; p = 0.037). There was a moderate relationship between β-OHB and ∆ %BDNF (r = 0.616; p < 0.001). Fasting plasma BDNF was significantly lower in OB compared to NW (132.8 ± 142.8 pg/ml vs. 639.4 ± 756.8 pg/ml; g = 0.845; p = 0.002). Conclusions: Plasma BDNF appears differentially impacted by KME ingestion with OGTT in OB compared to NW. Raising β-OHB via KME may be a strategy for increasing/ protecting BDNF during hyperglycemia.

Short‐term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross‐over trial

“…Improvements in cognitive function with β-OHB may be facilitated by BDNF (Arentoft et al 2009;Erickson et al 2012;Sun et al 2018). Animal and in vitro models show that β-OHB upregulates BDNF in neurons (Sleiman et al 2016;Marosi et al 2016;Hu et al 2018) and we have shown that β-OHB ingestion (0.45 mL kg -1 body weight; 3.4 mm peak) prior to an oral-glucose tolerance test (OGTT) increases plasma BDNF in adults with obesity (Walsh et al 2020). Accordingly, exogenous β-OHB supplementation may be a viable strategy for increasing BDNF and potentially proffering some neuroprotective effects, especially in vulnerable individuals.…”

“…By contrast to our hypothesis, there was no effect on either plasma or serum BDNF. BDNF is lower in adults with obesity compared to normal weight adults (Krabbe et al 2007;Walsh et al 2020), which may have implications for cognitive dysfunction (Alosco & Gunstad, 2014;Prickett et al 2018;Sun et al 2018). Recently, we reported that acute β-OHB ingestion prior to an OGTT increases plasma BDNF 2 h following the consumption of a glucose load of 75 g in adults with obesity (Walsh et al 2020); however, the combination of β-OHB with OGTT precludes any inferences regarding the direct effect of β-OHB on BDNF.…”

“…BDNF is lower in adults with obesity compared to normal weight adults (Krabbe et al 2007;Walsh et al 2020), which may have implications for cognitive dysfunction (Alosco & Gunstad, 2014;Prickett et al 2018;Sun et al 2018). Recently, we reported that acute β-OHB ingestion prior to an OGTT increases plasma BDNF 2 h following the consumption of a glucose load of 75 g in adults with obesity (Walsh et al 2020); however, the combination of β-OHB with OGTT precludes any inferences regarding the direct effect of β-OHB on BDNF. In the present study, unchanged BDNF levels may be a result of the lack of β-OHB in the circulation in the fasting samples, and the 14 day supplementation period was probably too brief to meaningfully alter basal levels.…”

“…The present study reports secondary J Physiol 599.21 outcomes from a larger trial and may not have been powered to detect changes in BDNF. It is also possible that the BDNF response to β-OHB ingestion is transient (Walsh et al 2020) and went uncaptured in the fasting, non-supplemented state. Follow-up studies are warranted aiming to systematically investigate the impact of β-OHB supplementation on circulating BDNF.…”

Serum proBDNF Is Associated With Changes in the Ketone Body β-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF: Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults

“…BDNF is one of the most wellstudied neurotrophins and is essential for brain function (Lima Giacobbo et al, 2019). Previous exploratory studies in human adults have found some associations between BHB and serum BDNF within a ketogenic diet intervention (Mohorko et al, 2019), and between BHB and plasma BDNF in the context of exogenous ketone ingestion (Walsh et al, 2020). Whether intake of kMCT, and subsequent ketosis, is associated with altered BDNF levels has to our knowledge not been studied.…”