Lactate and the brain

The lactate shuttle theory has been around for a couple of decades. Essentially, it is associated with the idea that the brain prefers lactate as an energy substrate, but lactate shuttle theory is actually describing a (proposed) mechanism, not the implications. I had been aware of the idea, but was not sure of the context of functionality. From some prior research I had found that the brain stores glycogen.

Peter has a brief post on this.

You always find a high concentration of GLUTx transporters in high energy organs. Having a high concentration of GLUTx transporters points to earlier times and to some interesting ideas.

The fact that ROS (reactive oxygen species) from glucose causes problems in the brain has always seemed strange to me given the common idea that the brain prefers glucose. Bypassing glucose metabolism with either fructose 1,6-bisphosphate or ketones has anticonvulsant activity. Given the composition of the fatty acids in the brain ROS seems like a really really bad idea, and it is probably the reason that if ROS is reduced things start working better.

When I started researching neonatal ketosis, I saw that besides the elevated ketones in neonates, lactate was also elevated. Ketones and lactate seem to be essential for a developing brain. Here are some papers on lactate below that can be tied in with the neonatal ketosis post.

So given this, the question is why? Why in neonates are ketones and lactate elevated? Does the status of a neonate represent an optimal status that we as adults should mimic, or is the status of the neonate a contextual adaptation? I have my own ideas as to why. What are some of your thoughts?

Gladden, L. B. (2008). A lactatic perspective on metabolism. Medicine and science in sports and exercise, 40(3), 477–85. doi:10.1249/MSS.0b013e31815fa580

Hashimoto, T., & Brooks, G. A. (2008). Mitochondrial lactate oxidation complex and an adaptive role for lactate production. Medicine and science in sports and exercise, 40(3), 486–94. doi:10.1249/MSS.0b013e31815fcb04

Holmgren, C. D., Mukhtarov, M., Malkov, A. E., Popova, I. Y., Bregestovski, P., & Zilberter, Y. (2010). Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro. Journal of neurochemistry, 112(4), 900–12. doi:10.1111/j.1471-4159.2009.06506.x

Kasischke, K. (2011). Lactate fuels the neonatal brain. Frontiers in neuroenergetics, 3(June), 4. doi:10.3389/fnene.2011.00004

Philp, A., Macdonald, A. L., & Watt, P. W. (2005). Lactate–a signal coordinating cell and systemic function. The Journal of experimental biology, 208(Pt 24), 4561–75. doi:10.1242/jeb.01961

Tyzio, R., Allene, C., Nardou, R., Picardo, M. A., Yamamoto, S., Sivakumaran, S., … Ben-Ari, Y. (2011). Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(1), 34–45. doi:10.1523/JNEUROSCI.3314-10.2011

Wyss, M. T., Jolivet, R., Buck, A., Magistretti, P. J., & Weber, B. (2011). In vivo evidence for lactate as a neuronal energy source. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(20), 7477–85. doi:10.1523/JNEUROSCI.0415-11.2011

Zilberter, Y., Zilberter, T., & Bregestovski, P. (2010). Neuronal activity in vitro and the in vivo reality: the role of energy homeostasis. Trends in pharmacological sciences, 31(9), 394–401. doi:10.1016/

1 Comment Lactate and the brain

  1. Marco

    Wouldn’t this suggest fructose is good fuel for the brain? I can feel it is. On a high fat diet, I crave it.

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