Does the Brain-Derived Neurotrophic Factor Val66Met Polymorphism Modulate the Effects of Physical Activity and Exercise on Cognition?

Abstract

The Val66Met is a polymorphism of the brain-derived neurotrophic factor (BDNF) gene that encodes a substitution of a valine (Val) to methionine (Met) amino acid. Carrying this polymorphism reduces the activity-dependent secretion of the BDNF protein, which can potentially affect brain plasticity and cognition. We reviewed the biology of Val66Met and surveyed 26 studies (11,417 participants) that examined the role of this polymorphism in moderating the cognitive response to physical activity (PA) and exercise. Nine observational studies confirmed a moderating effect of Val66Met on the cognitive response to PA but differences between Val and Met carriers were inconsistent and only significant in some cognitive domains. Only five interventional studies found a moderating effect of Val66Met on the cognitive response to exercise, which was also inconsistent in its direction. Two studies showed a superior cognitive response in Val carriers and three studies showed a better response in Met carriers. These results do not support a general and consistent effect of Val66Met in moderating the cognitive response to PA or exercise. Both Val and Met carriers can improve specific aspects of cognition by increasing PA and engaging in exercise. Causes for discrepancies among studies, effect moderators, and future directions are discussed.

Effects of different physical activities on brain-derived neurotrophic factor: A systematic review and bayesian network meta-analysis

“…Therefore, exercise-induced increase in CTSB levels is a crucial protective factor. Several studies have also found a correlation between a decrease in muscle mass or an increase in body fat percentage and memory loss and cognitive decline (Beeri et al, 2021;Anand et al, 2022;De Las Heras et al, 2022). RT prevents muscle atrophy and increases the expression of muscle secretory factors, exerting a better effect on brain health than other forms of physical activity.…”

Acute and Chronic Exercise Effects on Human Memory: What We Know and Where to Go from Here

“…However, it is important to remember that we are still relatively naïve as to the role of BDNF in this relationship. In humans, there is inconsistent evidence that this protein [ 41 , 62 ], or the gene that encodes this protein [ 63 ], influences the effects of acute exercise on memory. Furthermore, the specific role of BDNF in explaining the effects of exercise on memory are complicated by the fact that it can only be measured peripherally in humans, so that inferences about the central levels of BNDF are speculative.…”

Memory Modulation by Exercise in Young Adults Is Related to Lactate and Not Affected by Sex or BDNF Polymorphism

“…In our study, we could not find any association between the BDNF polymorphism with the cognitive response following exercise in young adults. Unfortunately, this observation does nothing but add up to the conflicting evidence on the role of BDNF polymorphism in the exercise–cognition relationship [ 11 ]. Along this line of thought, and in parallel with the findings by de Las Heras, Rodrigues, Cristini, Weiss, Prats-Puig, and Roig [ 11 ], this disparity in the reported results could indicate that, in fact, the cognitive gains associated with physical exercise are not dependent on the genetic profile, and all individuals could derive benefits from exercise on cognitive function.…”

“…Evidence suggests that the practice of physical exercise has positive effects on cognitive function, with benefits attributed to both acute [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ] and chronic exercise [ 2 , 5 , 6 , 7 , 8 , 9 ]. However, there is high variability in the observed effect sizes [ 10 ], which may be explained by the distinct characteristics of the physical exercise design, such as the type or dose, the cognitive domain assessed, or individual differences, such as the genotype [ 11 ]. Moreover, most studies on the relationship between exercise and cognitive function were conducted in children or older adults; meanwhile, adolescent and young adult populations remain underrepresented [ 7 ].…”