Lactate as Brain Fuel – Experiments and Implications

Lactate as Brain Fuel - Experiments and Implications

Introduction

I follow the work of Dr. Rhonda Patrick. She’s a very knowledgeable researcher. She’s been the mentee of Prof. Bruce Ames, who’s been doing science experiments for more than 60 years.

During one of her interviews, Dr. Patrick invited Dr. George Brooks, who researches Exercise Physiology and Metabolism at U.C. Berkeley, to talk about lactate as brain fuel. To better understand this write-up, I’d recommend listening to the interview.

Few people are aware that lactate can serve as efficient fuel for the brain, especially in the situations of fasting, strenuous exercise or traumatic brain injury, to name a few. While listening to the talk between Dr. Patrick and Dr. Brooks I made the connection. I remembered the mental clarity that I always get after a hard weight lifting workout in a fasted state.

Brain Metabolic Flexibility

I would like to introduce the concept of brain metabolic flexibility which refers to the ability of the brain to run on various different fuels rather than 100% on glucose, which happens in people who do not go on a very-low-carb diet or fast for more than 30 hours (i.e. under normal conditions).

Lactate as Brain Fuel - Experiments and Implications - 1

As seen in this graph (Cahill, 2006), it is known for more than 60 years, that in the normal fed state, the brain derives its energy solely from glucose. However, when metabolically challenged, during long periods of fasting, fuel dynamics of the body and the brain change.

Please do not confuse fasting with starvation. Many people may make this mistake and use them interchangeably. They talk about the starving body if no food has been consumed for a couple of hours. To put it mildly, this is naive.

Fasting is when your body derives its energy from its own reserves (fat stores) as no food or calorically significant nutritional components are consumed.

Starvation, the real one, happens when body fat is so low (<3%) that it cannot be used efficiently for fuel, and to survive your body starts catabolizing lean tissue, which has been protected so far.

To make a case in point, lean individuals, like me for example, could go several weeks without food while mostly preserving all lean mass, given that they’re healthy and that they consume decent amounts of water.

Overweight and obese people (other factors considered normal) could run several months on their own fat, allowing their bodies to take a breath of fresh air from digesting food stuff. Hunger is the last problem one could think of in prolonged fasting; it mostly does not exist.

Rather, there is a psychological attachment to food that may sometimes become problematic for the faster.

In fact, during the 60s one of the medical approaches to treating obesity involved prolonged fasting. Some of these fasts would last for dozens, if not hundreds of days. The longest medically recorded fast was of 382 days. It was a success.

However, some of these fasts lead to death. I would suspect that subject’s bodies were not prepared to handle such a stress and I would also suspect that some of them suffered from additional diseases of the metabolic syndrome. That is a totally different story; and it highlights the complexity, dual nature, and implications of fasting.

But what about lactate as brain fuel?

As it can be seen above, during fasting two thirds of the brain fuel is derived from ketones, while the remaining is provided by lactate, pyruvate, amino-acids, glycerol and other gluconeogenic precursors. Gluconeogensis (endogenous glucose production) may also come from:

BOHB -> AcAc -> Acetone -> Propanediol -> Pyruvate -> Glucose.

You can view some absolute values for these substrates in an older article [14].

In the medical community it was known that fatty acids cannot be used as brain fuel because they cannot cross the blood brain barrier. However, that may not seem very accurate. In fact, fatty acids do cross the blood brain barrier, but they do it so slowly that they are not efficiently metabolized —- see study.

When it comes to lactate, community’s opinions are all over the spectrum. There are some proponents who claim for its potentially positive effects, while others only discuss its downsides. Lets seem some facts.

I searched for lactate brain fuel on Google Scholar and I randomly picked some results from the first page. Then I limited my research for studies that have been conducted since 2013. I’m not sure if this can be called cherry picking since we’ll see opinions from both sides. But if you want to discuss this further, please do it in either of the comment sections below…

One of the studies that I found fails to account for alternative brain fuels, describing the aspects of hypoglycemia, brain failure and brain death [1].

“Recent interest in alternative brain fuels (including lactate derived from glucose largely within the brain; refs. 4-6) notwithstanding, glucose is an obligate metabolic fuel for the brain under physiologic conditions (7). Because brain cannot synthesize glucose or store substantial amounts of glycogen in astrocytes, the brain requires a virtually continuous supply of glucose from the circulation.”

Is this lying by omission or lack of knowledge due to poor background research?

The purpose of the study is not to discuss alternative brain fuels though, but a suggestion to avoid procedures that lead to hyperglycemia in the context of profound hypoglycemia. An inexperienced reader may fail to grasp a bigger picture due to the nature and the perspective in which this study was written.

Glucose is indeed required by the brain at all times. But the brain can thrive and even function better with only 20-30% of its fuel coming from glucose, compared to when it’s using 100% glucose.

In fact, several in vitro and in vivo studies show a necessity for lactate as brain fuel after episodes of brain injury (i.e. strokes). Dr. Brooks also talks about this in his interview. Another study states [2]:

“Lactate has been considered for many years to be a useless, and frequently, harmful end-product of anaerobic glycolysis. In the present in vitro study, lactate-supplied rat hippocampal slices showed a significantly higher degree of recovery of synaptic function after a short hypoxic period than slices supplied with an equicaloric amount of glucose.”

From another study [3]:

“Elevation of lactate (within a physiological range) substantially diminished catecholamines, growth hormone, cortisol, and symptomatic responses to hypoglycaemia and lowered the glucose level at which these responses began. Glucagon responses were unaffected. Lactate was also associated with a significant lowering of the glucose level at which brain function deteriorated, suggesting that brain function was protected during the hypoglycaemia.

The defect in counter-regulation is similar to that seen in hypoglycaemia-prone diabetic patients. Initiation of the protective responses to hypoglycaemia (except glucagon) can be delayed by supporting metabolism with an alternative metabolic fuel. Cerebral cortical dysfunction of severe hypoglycaemia is also delayed. Our demonstration that higher brain function can be protected during hypoglycaemia may have therapeutic potential.”

Several other studies are worth mentioning:

On the possible beneficial role of lactate after traumatic brain injury [4].
Lactate administration attenuates cognitive deficits following traumatic brain injury [5].
Brain lactate uptake increases at the site of impact after traumatic brain injury [6].
Another review article draws its references from dozens of human and rat studies and describes cerebral metabolic adaptations and ketone metabolism after brain injury [7].

But what about healthy people? Or lactate during/after workouts?

In healthy humans, in vivo experiments show that circulating lactate is used by the brain at euglycemia (normal blood glucose levels), with sparing of glucose [8].

In another study of healthy adults, researchers observed rising beta-hydroxybutyrate and lactate in the brain during fasted induced ketosis (2-3 days of fasting). They propose that lactate increase may result from ketones displacing lactate oxidation without interfering with glycolysis and glucose phosphorylation [9].

We know that lactate is produced at rest by many cells in the periphery and in the brain. However, higher plasma lactate (induced by exercise) increases the uptake of lactate in the brain in a proportional fashion [10]:

“Lactate uptake in the brain is less established, but during exhaustive physical exercise with intense activation of large muscle groups, during which anaerobic metabolism prevails and arterial lactate is elevated, the brain takes up lactate in amounts that may supersede the uptake of glucose (9). Thus, lactate uptake may be on the order of 1 mmol/min and glucose uptake on the order of 0.5 mmol/min.”

Lactate as Brain Fuel - Experiments and Implications - 2

Lactate as Brain Fuel - Experiments and Implications - 3

Similar studies for brain lactate usage at rest and under different exercising protocols.

How can I benefit from this?

While these may not serve as solid evidence for the short-lived boost in mental clarity and overall increased wellbeing post exercise (compound heavy lifting in my case), it does not prevent me from sticking to my protocol (ketosis, IF, CT, etc).

Even though, this may only be surface level research that was triggered by my spark interest in alternative peripheral and brain fuels, I believe the research on this subject is extensive. Following Dr. George Brooks’ work and reviewing similar studies on the topic could be a good exploratory path. I may do it in the future.

Other interesting venues would include studying lactate as a signaling molecule as well as its implications in muscle hypertrophy.

I get many ideas for future researches and experiments from the books I’m reading. I have a fair amount of knowledge about alternative fuels from the study I did while writing my books Ketone Power and Periodic Fasting. Here’s something interesting from Periodic Fasting:

“To explain the euphoria, Bloom [12] postulated that accumulation of aceto-acetic acid produces a mild intoxication similar to ethanol. Phillips [13] from studies in animals speculated that the accumulation of isopropyl alcohol in neural tissue might be responsible for fasting-induced religious, mystical or hallucinatory experiences.”

You read that right. Prolonged fasting can lead to mood enhancement similarly to alcohol consumption. Count me in! The benefit is there, but there’s no alcohol involved. I also reported my experience in the book:

I often experience the euphoric states that some researchers link to ketosis. And during my 5 day total fasting experiment these states have increased significantly. However, they did not reach the point of religious revelations. Who knows? Maybe if I had kept on with my fast, I may have reached that point.

Reading Cunnane and Stewart’s textbook [11] on the evolution of the human brain was another myth dispeller for the superficial and outdated information that is currently circulating in the public.

And this is a paradox. All of us have, roughly, the same access to information but we refuse to do our homework. Instead we repeat, propagate and apply knowledge in a broken-record-like fashion (without conscious thought and rigorous reasoning). No wonder why so few are living optimally and are consistent with their goals/results.

To make a long story short, I’d rather have my brain be able to run on multiple fuels than relying solely on glucose, which may be detrimental in some cases. People adapted to a ketogenic diet (a couple of months of constant and strict ketosis) or people who engage in long term fasting are the living testimony for this.

I’ve also experienced tremendous cognitive improvements since embarking on this journey.

But then again, there may be numerous confounding factors to my observations, such as the implementation of a certain supplement regime, the increased intake of DHA, the fact that I quit smoking and stopped competitive drinking). Anyways, even though I may not know for sure, I am aware that ketosis is a contributing factor.

My brain running on lactic acid made me keener to visiting the gym more often and train harder. My quick recovery allows for that. I suspect I recover faster because of: my testosterone protocol, cold thermogenesis, the strategic use of phytochemicals, fasting and because of other possible interventions.

References

  1. Cryer, P. E. (2007). Hypoglycemia, functional brain failure, and brain death. Journal of Clinical Investigation, 117(4), 868.
  1. Schurr, A., Payne, R. S., Miller, J. J., & Rigor, B. M. (1997). Brain lactate, not glucose, fuels the recovery of synaptic function from hypoxia upon reoxygenation: an in vitro study. Brain research, 744(1), 105-111.
  1. Maran, A., Cranston, I., Lomas, J., Amiel, S. A., & Macdonald, I. (1994). Protection by lactate of cerebral function during hypoglycaemia. The Lancet, 343(8888), 16-20.
  1. CHEN, T., QIAN, Y. Z., DI, X., RICE, A., ZHU, J. P., & BULLOCK, R. (2000). Lactate/glucose dynamics after rat fluid percussion brain injury. Journal of neurotrauma, 17(2), 135-142.
  1. Rice, A. C., Zsoldos, R., Chen, T., Wilson, M. S., Alessandri, B., Hamm, R. J., & Bullock, M. R. (2002). Lactate administration attenuates cognitive deficits following traumatic brain injury. Brain research, 928(1), 156-159.
  1. Chen, T., Qian, Y. Z., Rice, A., Zhu, J. P., Di, X., & Bullock, R. (2000). Brain lactate uptake increases at the site of impact after traumatic brain injury. Brain research, 861(2), 281-287.
  1. Prins, M. L. (2008). Cerebral metabolic adaptation and ketone metabolism after brain injury. Journal of Cerebral Blood Flow & Metabolism, 28(1), 1-16.
  1. Smith, D., Pernet, A., Hallett, W. A., Bingham, E., Marsden, P. K., & Amiel, S. A. (2003). Lactate; A Preferred Fuel for Human Brain Metabolism In Vivo. Journal of Cerebral Blood Flow & Metabolism, 23(6), 658-664.
  1. Pan, J. W., Rothman, D. L., Behar, K. L., Stein, D. T., & Hetherington, H. P. (2000). Human Brain Beta-Hydroxybutyrate and Lactate Increase in Fasting-Induced Ketosis. Journal of Cerebral Blood Flow & Metabolism, 20(10), 1502-1507.
  1. Quistorff, B., Secher, N. H., & Van Lieshout, J. J. (2008). Lactate fuels the human brain during exercise. The FASEB Journal, 22(10), 3443-3449.
  1. Cunnane, S., & Stewart, K. (Eds.). (2010). Human brain evolution: the influence of freshwater and marine food resources. John Wiley & Sons.
  1. Bloom, W. L. (1959). Fasting as an introduction to the treatment of obesity. Metabolism: clinical and experimental, 8(3), 214-220.
  1. Phillips, R. W. (1978). Religious revelations and bovine ketosis (a nonsacred cow). Perspectives in biology and medicine, 21(3), 398-405.
  1. Hasselbalch, S. G., Knudsen, G. M., Jakobsen, J., Hageman, L. P., Holm, S., & Paulson, O. B. (1994). Brain metabolism during short-term starvation in humans. Journal of Cerebral Blood Flow & Metabolism, 14(1), 125-131.

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5 Responses to Lactate as Brain Fuel – Experiments and Implications

  1. Rebecca Sinha says:

    Hi Cristi,

    Very interesting article. I wonder if this explains something with my diabetes. When I used to go to the gym and just did normal workouts or classes, my blood sugar always shot up too high, there was a time I even had to take a pill to be able to go to the gym. That no longer happens. I think it is partly due to doing a ketogenic diet for a long time, losing a lot of weight, and now my gym routine is only lifting heavy. I have been amazed my blood sugar no longer goes up with exercise and have wondered why it has changed, the use of lactate as brain fuel could be a parital answer. My insulin resistance has also improved, but I think that is due to my experimentation with a little bit of fasting.

    Rebe

    • Chris Chris says:

      hmm, that’s interesting. it could be that you adapted well to using alternative fuels. Im sure that in the near future we will be able to monitor in real time what happens inside the body from a biomarker perspective. then we’ll know for sure.

    • Jack Kruse says:

      When you go to the “gym” you are under blue light which is known to stimulate blood glucose while ruining the respirtory proteins on the inner mitochondrial membrane. That is why going to the gym with diabetes and walking outside in the sun are not equivalent behaviors when your mitochondria have a low redox state.

  2. Dr. Laura Margaritis ND says:

    Hi Chris,

    Peter over at Hyperlipid has talked several times about the role of lactate in the brain…check out:

    http://high-fat-nutrition.blogspot.ca/2012/08/protons-lactate.html

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