The basics of ketogenic diet: works of Shaffer and Wilder & Winter

Glucose,Ketogenic diet,Ketone bodies,Ketosis, ketogenesis,Methodology — Tags: , — 6:16 am

It is interesting that while the ketogenic diet becomes well researched as a method for improving energy metabolism during quite a few medical conditions and the number of original research articles as well as reviews grow currently approaching 15,000, only 19 out of all of them cite the original work, which in fact is the basis of the diet. >>> Read more

The ketogenic diet is no longer considered a strictly anti-epileptic diet: its suggested and tested applications includes a broad spectrum of disorders of energy metabolism. The ketogenic ratio formula used in clinics for calculating the ketogenic diet composition was offered by Wilder and Winter in 1922 (1). They argued that the levels of ketogenic substances depend on the ratio between fatty acids and glucose of the metabolizing foods. The ratio when ketogenesis is initiated they called the threshold of ketogenesis: “When the proportion of acetoacetic acid to glucose in such mixtures was that of 1 (or possibly 2) molecules of acetoacetic acid to 1 of glucose, the former substance was completely oxidized. When the proportion of glucose was less, a considerable fraction of acetoacetic acid escaped oxidation.”

Shaffer (2, 3) calculated the number of molecules of ketogenic substrates corresponding to the number of molecules of glucose and concluded that the maximal ratio compatible with the oxidation of the ketogeniec compounds was reached when a ratio of of ketogenic molecules to the number of glucose molecules was 1: 1. He subsequently considered that each glucose molecule is ketolytic for 2 molecules of acetoacetic acid, a 2:l ratio.

Wilder and Winter, 1922 included in their formula the following measurements obtained in clinical settings:

1) basal metabolism for 24 hour periods plus 10 per cent for the specific dynamic action of food and 10 per cent for movements;

2) the calories from the protein metabolism assessed by nitrogen excretion;

3) the calories from fat metabolism taken as the sum of the calories of protein and carbohydrate combined subtracted from the total calories of the day.

The values for carbohydrate and fat are used in the calculation of the ratio between the ketogenic molecules and the glucose molecules (2, 3).

“Under the conditions of these experiments, provided these assumptions are tenable, the ratio between the ketogenic and the glucose molecules at which a clinically significant ketosis appears has a value of at least 2: 1. A ratio of this value implies that every molecule of glucose is ketolytic for 2 molecules of acetoacetic acid.”

References

  1. Wilder R., Winter M. Thew threshold of ketogenesis. J. Biol. Chem. 1922 52: 393-401.
  2. Shaffer, P. A., Antiketogenesis. I. An in vitro analogy, J. Biol.Chem., 1921, xlvii, 433.
  3. Shaffer, P. A., Antiketogenesis. II. The ketogenic antiketogenic balance in man, J. Biol. Chem., 1921, xlvii, 449.

 

 

 

Alzheimer’s disease and a long-standing exposure to glucose in the Western diet

Alzheimer's,Glucose,Ketone bodies,Lactate — 6:35 am

 

Chronic exposure to glucose due to the traditional Western diet impairs neuronal function and causes apoptosis (programmed neuronal death), concluded Drs Seneff & Wainwright (UK) and Mascitelli (Italy). Their reasoning was roughly the following:

The amyloid-beta peptide (AB) in Alzheimer’s disease (AD) plaques so far seen as a hallmark of this disease, in fact may be an early attempt of protection from its development.  AB switches neuronal metabolism from glycolysis-based to the use of other substrates, e.g., lactate and ketone bodies. This is a very important adjustment in the AD case since there’s an insulin resistance in the AD brain indicating an inadequate ability to utilize glucose. Moreover, the levels of advanced glycation end-products (harmful in any case) are increased in AD. The damage they induce interferes with delivery of fats and cholesterol to astrocytes, and consequently to neurons. This is important because for smooth communication between neurons, sufficient levels of fat and cholesterol is required and the AD CSF is deficient in both. Synthesis of AB is increased when lipid supply is deficient. In the condition of this deficiency, there’s an increase in synthesis of excitatory neurotransmitter glutamate leading to oxidative damage and toxic overexcitability.

The good news is, wrote the authors, a simple dietary change towards lower carbohydrate intake and higher fats intake, may be efficiently protective against AD.

Source:

European Journal of Internal Medicine 22 (2011) 134–140

Toxic glycolysis and brain aging

Glucose,Hormesis,Theories — Tags: , , , , , , — 8:29 am

Related article: Prescription-strength stress as a medicine

The intermittent glycolysis during fasting, physical exercise, and stress may delay senescence by lowering intracellular concentration of methylglyoxal, a common intermediate in the Maillard reaction (glycation).

A simple logic allows to imagine that a situation when food is available to an animal at all times and in any quantities should be very seldom. In real life, there are seasons when food is abundant and seasons when it’s scarce. To smoothen the energy delivery to vital organs, there all kind of depots, most famous (or rather infamous for us human beings in Western societies) is the fat depot, having practically unlimited capacity. There is clinical evidence that a human body can save in this depot enough energy to feed itself for a year. Vitamins and electrolyte fluids should be adequately supplied of course, but no calories enter the body – and it survives!

The opposite situation, when animals are allowed to eat as much as they can, as often as they can, is called ad libitum (AL). In experiments on beneficial effects of calorie restriction (CR), the food intake in the AL situation is taken for 100% and then different percentages of restrictions are applied to see CR effectiveness to slow down the process of aging, especially brain aging.

In an early study of the energy metabolism McCarter and Palmer (1) interesting differences were revealed, between rats fed CR diets and those fed the same food but AL. Although in both groups energy metabolism was mostly glycolytic, taping in carbohydrate metabolic way, CR very soon after feeding switched to using their bodies’ fat reserves with their glycolysis suppressed, while the AL group maintained practically non-stop glycolysis.

So it’s been suggested that that the beneficial effects of CR could be due to suppression of glycolysis and in experiments of Walker et al. (2) and Partridge and Brand (3) the question of whether the shortened life-span of AL animals results from some metabolic toxicity, specifically whether glycolysis is deleterious but possibly hormetic (4)

The hormesis hypotheses by Masoro (5) and Sinclair (6) suggests that intermittent stress may induce synthesis of long-term protective functions. Glycolytic intermediates dihydroxyacetone- and glyceraldehyde-3-phosphates are form methylglyoxal (MG), which is potentially toxic.

Hipkiss (7) suggested that non-stop glycolysis is deleterious due to the generation of MG, but periods of glycolysis interruption could be hormetic. MG damages mitochondria and induces a pro-oxidant state characteristics to cellular aging. The decreased glycolysis during CR may delay senescence by lowering intracellular MG concentration compared to AL animals.

Sources

1. Am. J. Physiol. 1992 263, E448-E452

2. Mech. Ageing Dev. 2005 126, 929-937

3. Mech. Ageing Dev. 2005 126, 911-912

4. Hormesis – An effect in which a toxic substance acts like a stimulant in small doses, but it is an inhibitor in large doses.

5. Mech. Ageing Dev. 2005 126, 913-922

6. Mech. Ageing Dev. 2005 126, 987-1002.

7. Mech. Ageing Dev. 2006 127 8-15

“Brain metabolism in vitro” and those sour energy substrates

Brain metabolism,Energy Substrates,Excitatory GABA,Glucose,Ketone bodies,Lactate,Pyruvate — Tags: , — 10:31 am

Part 2. Energy substrates: too sour?
Part 3. Let the neurons breathe!
This paper suggests that the developmental switch in the reversal potential for gamma-aminobutyric acid (GABA) is regulated by different energy sources

This paper suggests that the developmental switch in the reversal potential for gamma-aminobutyric acid (GABA) is regulated by different energy sources

An evaluation of our article (1) appeared in the “Faculty of 1000 postpublication peer reviews” the conclusion being:

The findings of Rheims et al. have a potentially major impact on our understanding of GABAergic function during development, bringing back an element of inhibition in developing neuronal networks that appeared to rely entirely on excitatory connections (2).

This article (1) along with the article (3) later became an indirect subject of another evaluation (4) although formally, the evaluation concerned a different paper (5), which has been commended because (the author’s words):

“It settles an important issue related to brain metabolism in vitro and the role of acidification in brain patterns.”

The acidification issue doesn’t seem to be resolved either in 5 nor in 4, so a comment to the evaluation appeared in May 2011,  stating among other things the following:

We showed that inhibition of spontaneous network activity in neonatal hippocampal slices by energy substrates is not correlated with intracellular acidification (7) and that they work altering intrinsic features of energy metabolism namely NAD(P)H and oxygen utilization (8).

Another data challenged in 5 is whether lactate as efficient as an energy substrate: “Lactate is not an efficient replacement for glucose” wrote Dr Ben-Ari and Y. Zilberter in his comment referred to the paper 8 titled “Lactate effectively covers energy demands during neuronal network activity in neonatal hippocampal slices” and the work of Wyss et al. (9) titled “In Vivo Evidence for Lactate as a Neuronal Energy Source”.

References

1. Rheims S, Holmgren CD, Chazal G, Mulder J, Harkany T, Zilberter T, Zilberter Y. (2009) J Neurochem.  Aug;110(4):1330-8. Epub 2009 Jun 22. (on Brain Fuels)

2. Scimemi A, Diamond J: 2009. F1000.com/1166168

3. Holmgren CD, Mukhtarov M, Malkov AE, Popova IY, Bregestovski P, Zilberter Y. (2010) J Neurochem. Feb;112(4):900-12. Epub 2009 Nov 24. (on Brain Fuels)

4. Ben-Ari Y: 2011. F1000.com/6913961

5. Ruusuvuori E, Kirilkin I, Pandya N, Kaila K (2010) J Neurosci.  Nov 17; 30(46):15638-42

6. Zilberter Y, Zilberter T, Bregestovski P. (2010) Trends Pharmacol Sci., 31(9):394-401 (on Brain Fuels)

7. Mukhtarov, M., Ivanov, A., Zilberter, Y., and Bregestovski, P. (2011) J Neurochem 116, 316-321

8. Ivanov A, Mukhtarov M, Bregestovski P and Zilberter Y (2011) Front. Neuroenerg. 3:2.

9. Wyss M, Jolivet R, Buck A, Magistretti P, and Weber B. (2011)  J Neuroscience, 31(20):7477-7485

Sweet and sour recipes for the brain. 1. “Sweet slices are fine”?

Applications,Energy Substrates,Glucose,Ketone bodies,Lactate,Pyruvate — 10:32 am

Part 2. Energy substrates: too sour?
Part 3. Let the neurons breathe!

Is glucose the absolutely exclusive fuel for the brain? In popular articles, you might always read that yes, it is.

Meanwhile, in special scientific literature the role of quite a few energy carriers including ketone bodies (mostly beta-hydroxybutirate, BHB), lactate, and pyruvate was unquestioned for decades. Recently, a series of three research reports published in the Journal of Neuroscience (Tyzio et al., 2011, Ruusuvuori et al., 2010 and Kirmse et al., 2010) arrived at the conclusion contradicting to the well known fact about brain energy metabolism in neonates. It seemed indisputable that in the neonatal brain, the use of glucose as an energy substrate is limited due to immaturity of the mechanisms of glucose utilization but the articles in question shed doubts on it. Why is it important to sort out these conflicting research results?

I already wrote about the importance of energy substrates other than glucose for the immature brain and the consequence of ignoring this role in experiments on neonatal brain slices discussing the results of Rheims et al., 2009 and Holmgren et al., 2010.

In 2010, at the meeting of the Society for Neuroscience in San Diego, CA, a poster has been presented announcing in its title: “BHB does not alter GABA signals in neonatal slices: sweet slices are fine, no need to alter conventional ACSF“. Neither poster nor its abstract (Picardo et al., 2010) contained methodical details and they remained unknown until 2011 when an article in the Journal of Neuroscience was published (Tyzio et al., 2011). It became possible to compare the differences in methods, which has been done in due time and published in the Frontiers in Neuroenergetics (Ivanov et al., 2011) — see parts 2-4.

Important is, that Ivanov et al. showed that in immature brain slices, glucose rendered less efficient energy carrier than lactate, BHB, and pyruvate.  Judged by the hallmarks of energy metabolism – oxygen utilization and nicotinamide adenine dinucleotide phosphate or NAD(P)H, neuronal activity robustness was higher in the presence of lactate alone or combined with glucose than with glucose alone. The authors concluded: “We show that in the presence of glucose, lactate is effectively utilized as an energy substrate, causing an  augmentation of oxidative metabolism. Moreover, in the absence of glucose lactate is fully capable of maintaining synaptic function. Therefore, during network activity in neonatal slices, lactate can be  an efficient energy substrate capable of sustaining and enhancing aerobic energy metabolism.”

References

  1. Garcia, A.J., 3rd, Putnam, R.W., and Dean, J.B. (2010). Hyperbaric hyperoxia and normobaric reoxygenation increase excitability and activate oxygen-induced potentiation in CA1 hippocampal neurons. J Appl Physiol 109, 804-819.
  2. Hajos, N., Ellender, T.J., Zemankovics, R., Mann, E.O., Exley, R., Cragg, S.J., Freund, T.F., and Paulsen, O. (2009). Maintaining network activity in submerged hippocampal slices: importance of oxygen supply. Eur J Neurosci 29, 319-327.
  3. Holmgren CD, Mukhtarov M, Malkov AE, Popova IY, Bregestovski P, Zilberter Y (2010) Energy substrate availability as a determinant of neuronal resting potential,GABAsignaling and spontaneous network activity in the neonatal cortex in vitro. J Neurochem 112:900 –912.
  4. Ivanov A, Mukhtarov M, Bregestovski P and Zilberter Y (2011). Lactate effectively covers energy demands during neuronal network activity in neonatal hippocampal slices. Front. Neuroenerg. 3:2.
  5. Kirmse K, Witte OW, Holthoff K. (2010). GABA Depolarizes Immature Neocortical Neurons in the Presence of the Ketone Body β-Hydroxybutyrate. J Neuroscience, 24; 30(47): 16002-16007
  6. Lehninger, A.L. (2005). “Oxydative phosphorylation and photophosphorylation,” in Principles of biochemistry, eds. D.L. Nelson & M.M. Cox. Forth ed: W. H. Freeman), 690-740.
  7. Rheims S, Holmgren CD, Chazal G, Mulder J, Harkany T, Zilberter T, Zilberter Y (2009) GABA action in immature neocortical neurons directly depends on the availability of ketone bodies. J Neurochem 110: 1330–1338.
  8. Schurr, A., and Payne, R.S. (2007). Lactate, not pyruvate, is neuronal aerobic glycolysis end product: an in vitro electrophysiological study. Neuroscience 147, 613-619.
  9. Tyzio, R., Allene, C., Nardou, R., Picardo, M.A., Yamamoto, S., Sivakumaran, S., Caiati, M.D., Rheims, S., Minlebaev, M., Milh, M., Ferre, P., Khazipov, R., Romette, J.L., Lorquin, J., Cossart, R., Khalilov, I., Nehlig, A., Cherubini, E., and Ben-Ari, Y. (2011). Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate. J Neurosci 31, 34-45.

MCT and beta-hydroxybutirate protect cognitive and synaptic functions

Energy Homeostasis,Energy Substrates,Glucose,Ketone bodies,Neuroprotectors — 7:57 am


Medium-Chain Fatty Acids Improve Cognitive Function and Support In Vitro Synaptic Transmission During Acute Hypoglycemia (1)

The brain can use alternative fuels such as monocarboxylic acids, lactate, and ketones to maintain energy homeostasis (2-8). Fasting or hypoglycemia causes adaptive changes in the brain, including an enhanced ability to utilize alternative fuels. The work conducted by joined teams from Yale School of Medicine, State University of New York, Winthrop University Hospital, Long Island, Department of Psychology, State University of New York, and University at Albany studied how alternative energy substrates influenced cognitive and synaptic functions disturbed by hypoglycemia.

Impaired verbal memory, digit symbol coding, digit span backwards, and map searching was observed during insulin-induced hypoglycemia. Medium-chain triglycerides given in a drink produced higher free fatty acids and beta-hydroxybutyrate levels and returned cognitive performance to normal levels without adversely affecting adrenergic or symptomatic responses to hypoglycemia.

1. Diabetes 58:1237–1244, 2009
2. Hasselbalch SG, Knudsen GM, Jakobsen J, Hageman LP, Holm S, Paulson
OB. Brain metabolism during short-term starvation in humans. J Cereb
Blood Flow Metab 1994;14:125–131
3. Maran A, Cranston I, Lomas J, Macdonald I, Amiel SA. Protection by
lactate of cerebral function during hypoglycaemia. Lancet 1994;343:16–20
4. Veneman T, Mitrakou A, Mokan M, Cryer P, Gerich J. Effect of hyperketonemia
and hyperlacticacidemia on symptoms, cognitive dysfunction,
and counterregulatory hormone responses during hypoglycemia in normal
humans. Diabetes 1994;43:1311–1317
5. Amiel SA, Archibald HR, Chusney G, Williams AJ, Gale EA. Ketone infusion
lowers hormonal responses to hypoglycaemia: evidence for acute cerebral
utilization of a non-glucose fuel. Clin Sci (Lond) 1991;81:189–194
6. Hawkins RA, Williamson DH, Krebs HA. Ketone-body utilization by adult
and suckling rat brain in vivo. Biochem J 1971;122:13–18
7. Pan JW, Rothman TL, Behar KL, Stein DT, Hetherington HP. Human brain
beta-hydroxybutyrate and lactate increase in fasting-induced ketosis.
J Cereb Blood Flow Metab 2000;20:1502–1507
8. Mason GF, Petersen KF, Lebon V, Rothman DL, Shulman GI. Increased
brain monocarboxylic acid transport and utilization in type 1 diabetes.
Diabetes 2006;55:929–934


Great Controversies in Neurobiogy

Excitatory GABA,Glucose,Ketone bodies,Methodology,Pyruvate — 9:47 am

“They teach us in our institutes that GABA is excitatory in the neonates, should we still believe it?” (Excitatory GABA scandal?)

There was an interesting development in the Department of Neuroscience of the Brown University who published a provocative recommendation to the Neuro 193E Course under the general title “Great Controversies in Neurobiogy.”

Since 80′s it was becoming a firmly established fact that in immature brain, the reversal potential for GABA receptors was more depolarized, making GABA excitatory and producing a special form of electrical activity named the giant depolarizing potentials, GDP, described by Ben-Ari in hippocampal slices of the immature brain.

“This is something which has been widely described in multiple brain regions by many different labs and is pretty much accepted as fact,” wrote the course’s authors. “However,” continues the chapter, “about a year ago, a couple of papers from the Zilberter’s lab (1, 2) have seriously brought this fact into question.”

The matter is, as multiple prior studies showed [as reviewed in 3, BF], the immature brain “is not very good at metabolizing glucose” due to the immaturity of glycolytic mechanisms and instead it relies on brain fuels alternative to glucose, such as ketones, lactate, and/or pyruvate.

“They noted that almost all papers published using brain slices use artificial cerebro-spinal fluid (ACSF) made with pleny of glucose, but no ketones. Which means that any immature slices cut and maintained in this media will likely be metabolically compromised.”

“They show quite convincingly that adding ketone bodies to ACSF used for immature slices actually makes GABA reversal potential more negative, similar to an adult neuron. Thus they suggest that the depolarizing actin of GABA during early development is an experimental artifact of metabolically-compromised brain slices,” concluded the author.

Source: Dept. of Neuroscience, Brown University. Course Neuro 193E. Last edited by Carlos Aizenman-Stern on Aug 24, 2010 15:34

References

  1. GABA Action in Immature Neocortical Neurons Directly Depends on the Availability of Ketone Bodies. Rheims S, Holmgren CD, Chazal G,Mulder J, Harkany T, Zilberter T, Zilberter Y. J Neurochem 2009;110(4):1330–13382.
  2. Energy Substrate Availability as a Determinant of Neuronal Resting Potential, GABA Signaling and Spontaneous Network Activity in the Neonatal Cortex In Vitro. Holmgren CD,MukhtarovM,Malkov AE, Popova IY, Bregestovski P, Zilberter Y. J Neurochem 2010;112(4):900–912
  3. Neuronal activity in vitro and the in vivo reality: the role of energy homeostasis. Trends Pharmacol Sci. 2010 Sep;31(9):394-401. Epub 2010 Jul 14. Zilberter Y, Zilberter T, Bregestovski P.

Energy substrates and neuroprotection: what does what

Epilepsy,Glucose,Ketone bodies,Lactate,Neuroprotectors,Pyruvate — Tags: — 6:05 am

A few interesting articles about glucose, lactate, and pyruvate
and their neuroprotective functions.

J Neurochem. 2010 Feb 15
Chronic in vitro ketosis is neuroprotective but not anticonvulsant.
Marina Samoilova, Michael Weisspapir, Peter Abdelmalik, Alexander A
Velumian, Peter L Carlen

Chronic in vitro treatment with a ketone body, D-beta-hydroxybutyrate
(DbetaHB), protected the cultures against chronic hypoglycemia,
oxygen-glucose deprivation and NMDA-induced excitotoxicity, but failed
to suppress intrinsic and induced seizure-like activity, indicating
improved neuroprotection is not directly translated into seizure
control. However, chronic in vitro ketosis abolished hippocampal
network hyperexcitability following a metabolic insult, hypoxia,
demonstrating for the first time a direct link between metabolic
resistance and better control of excessive, synchronous, abnormal
electrical activity.

Neuroscience. 2007 Jun 7
Lactate, not pyruvate, is neuronal aerobic glycolysis end product: An
in vitro electrophysiological study. A Schurr, R S Payne

We hypothesized that, in the brain, both aerobic and anaerobic
glycolysis terminate with the formation of lactate from pyruvate by the
enzyme lactate dehydrogenase (LDH). If this hypothesis is correct,
lactate must be the mitochondrial substrate for oxidative energy
metabolism via its oxidation to pyruvate, plausibly by a mitochondrial
LDH

Neurosci Res. 2004 Dec;50 (4):467-74
Glycolysis regulates the induction of lactate utilization for synaptic
potentials after hypoxia in the granule cell of guinea pig hippocampus.
Toshihiro Takata, Bo Yang, Takashi Sakurai, Yasuhiro Okada, Koichi
Yokono

Population spikes are not maintained with lactate following hypoxia in
10 mM glucose medium, but are maintained at their original levels with
lactate after exposure to hypoxia in lower concentration (5 mM) of
glucose.

Neurosci Res. 2003 Jul ;46 (3):333-7
Effects of lactate/pyruvate on synaptic plasticity in the hippocampal
dentate gyrus.
Bo Yang, Takashi Sakurai, Toshihiro Takata, Koichi Yokono

Replacement of glucose with lactate and pyruvate maintained population
spikes after transient depression, and supported a similar degree of
paired-pulse facilitation. These results indicate that monocarboxylates
could serve as sufficient substrates LTP but with less efficiency than
glucose.

Neuroscience. 2007 Jun 7
Lactate, not pyruvate, is neuronal aerobic glycolysis end product: An
in vitro electrophysiological study.A Schurr, R S Payne

 

We hypothesized that, in the brain, both aerobic and anaerobic
glycolysis terminate with the formation of lactate from pyruvate by the
enzyme lactate dehydrogenase (LDH). If this hypothesis is correct,
lactate must be the mitochondrial substrate for oxidative energy
metabolism via its oxidation to pyruvate, plausibly by a mitochondrial
LDH


Neurosci Res. 2004 Dec 50 (4):467-74
Glycolysis regulates the induction of lactate utilization for synaptic
potentials after hypoxia in the granule cell of guinea pig
hippocampus.Toshihiro Takata, Bo Yang, Takashi Sakurai, Yasuhiro Okada,
Koichi Yokono

 

Population spikes are not maintained with lactate following hypoxia in
10 mM glucose medium, but are maintained at their original levels with
lactate after exposure to hypoxia in lower concentration (5 mM) of
glucose.

 

Glucose or lactate as fuels in mature brain: whose primacy?

Astrocyte–neuron lactate shuttle,Glucose,Lactate — Tags: , — 5:32 am

Updates:
Glucose versus lactate in immature brain slices
Brain metabolism updates: Sweet and sour recipes for the brain
Astrocyte-neuron lactate transport is required for long-term memory formation – F1000.com evaluation

The primacy of glucose as a mature brain fuel has been questioned and lactate was suggested to be a substrate that active neurons prefer over glucose (1). Lactate has long been considered to be a potentially damaging end-metabolite of anaerobic glycolysis (conversion of glucose to pyruvate when little  or no oxygen is available). Since the original report by Pellerin & Magistretti, it has been widely assumed that lactate production takes place in astrocytes. Pellerin & Magistretti (2) proposed that lactate may not be a metabolic dead-end product but rather the dominant oxidative substrate for neurons.

“Over the past decade scientists have passionately debated whether the activated brain burns glucose completely to water or incompletely to lactate,” said Karl Kasischke, a researcher in the Cornell University, Ithaca, NY (3). “Our results unify existing contradictory opinions and should be a win-win situation for both factions,” said Kasischke.

On the other hand there are opponents of the hypothesis discussing the theoretical background and critically reviewing the experimental evidence  (e.g., 4)

Sources

1. Magistretti PJ. 1999. Brain energy metabolism. (In) Fundamental neuroscience New York, Academic Press New York, Academic Press (pp) 389−413.

2. Pellerin, L. and Magistretti, P. J. (1994). Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. USA 91, 10625-10629

3. Karl A. Kasischke, Harshad D. Vishwasrao, Patricia J. Fisher, Warren R. Zipfel, Watt W. Webb. Neural Activity Triggers Neuronal Oxidative Metabolism Followed by Astrocytic Glycolysis. Science 2 July 2004: Vol. 305. no. 5680, pp. 99 – 103

4. Ching-Ping Chih, Eugene L Roberts Jr.. Energy Substrates for Neurons During Neural Activity: A Critical Review of the Astrocyte-Neuron Lactate Shuttle Hypothesis. J Cerebral Blood Flow & Metabolism (2003) 23, 1263–1281;

The brain believes the sweet taste rather than metabolic facts

Adaptive regulation,Glucose — Tags: , , , , , — 11:15 am
It’s a well known fact that drinking carbohydrate-rich beverages during high-intensity exercise improves performance even if it’s relatively short, which made researchers suspect that direct metabolic effect could hardly be the reason since there’s simply not enough time to digest the carbs and deliver the energy to the muscles. The only alternative seemed to be “all in the brain”. To check this hypothesis, the metabolic input excluded completely: the athletes didn’t swallow the drink but only rinsed the mouth with it – and performance also improved!
Now, the discussion is going on, which brain structures are responsible and how they overrule the chemical senses inside the body that tells the truth: no energy has been ingested, The brain for some reason believe the sense of sweetness rather than the qualitative report from the blood.
Why any sweet taste, coming with any sweetener, raises glucose concentration in the blood *before* the food has a chance to be digested? Because your body knows that eventually, it will have all the carbs you’ve swallowed and it doesn’t wait until it that happens and borrows real carbohydrates from carbohydrate depots. In the case of physical performance, the brain recruits muscles in anticipation of real energy coming into the blood soon, and this always happened in the past, before artificial sweeteners and wicked experimental protocols were invented.
Sources:
Current Opinion in Clinical Nutrition and Metabolic Care 2010, 13
BMJ 2004; 329: 755-756
Response: http://www.bmj.com/cgi/eletters/329/7469/755#78439

It’s a well known fact that drinking carbohydrate-rich beverages during high-intensity exercise improves performance even if it’s relatively short, which made researchers suspect that direct metabolic effect could hardly be the reason since there’s simply not enough time to digest the carbs and deliver the energy to the muscles. The only alternative seemed to be “all in the brain”. To check this hypothesis, the metabolic input excluded completely: the athletes didn’t swallow the drink but only rinsed the mouth with it  - and performance also improved!

Now, the discussion is going on, which brain structures are responsible and how they overrule the chemical senses inside the body that tells the truth: no energy has been ingested, The brain for some reason believe the sense of sweetness rather than the qualitative report from the blood.

Why any sweet taste, coming with any sweetener, raises glucose concentration in the blood *before* the food has a chance to be digested? Because your body knows that eventually, it will have all the carbs you’ve swallowed and it doesn’t wait until it that happens and borrows real carbohydrates from carbohydrate depots. In the case of physical performance, the brain recruits muscles in anticipation of real energy coming into the blood soon, and this always happened in the past, before artificial sweeteners and wicked experimental protocols were invented.

Source: Jeukendrup, Chambers. Oral carbohydrate sensing and exercise performance. Current Opinion in Clinical Nutrition and Metabolic Care 2010, 13:447-451

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