7 replies to this topic

[Dan1976]

As you know glucose is very important for the brain. While dieting cognitive performance is impaired because of the hypoglycemia.

The brain-blood barrier responds by upregulating glucose transport.

From the Wikipedia GLUT3 article:

Although GLUT3 was found to be expressed in various tissues, it is most specifically expressed in neurons, found predominantly in axons and dendrites and also, but less prominently, in the cell body. GLUT3 has both a higher affinity for glucose and at least a fivefold greater transport capacity than GLUT1, GLUT2 and GLUT4, which is particularly significant for its role in neuronal glucose transport, where ambient glucose levels are fivefold lower than in serum.

Glucose delivery and utilization in the mammalian brain is mediated primarily by a high molecular weight form of GLUT1 in the blood–brain barrier, GLUT3 in neuronal populations and a less glycosylated form of GLUT1 in the remainder of the parenchyma. GLUT3 is considered the main but not the exclusive neuronal glucose tansporter, whereas other glucose transporters have also been observed in neurons.

... and also:

The central role of GLUT3 in cerebral metabolism has been challenged by the astrocyte-neuron lactate shuttle (ANLS) hypothesis, which proposes thatastrocytes play the key role in the coupling of neuronal activity and cerebral glucose utilization. In this hypothesis, the astrocyte, which relies on GLUT1 for glucose transport, is the primary consumer of glucose in the brain, providing lactate as the primary energetic fuel for neurons.

So, GLUT3 and GLUT1 seem to be the most important for transporting glucose into the neurons.


How can we upregulate glucose transport into the brain in order to protect it when being hypoglycemic for weeks on a VLCD diet?


Racetams come to mind. I have tried Pramiracetam for this, and it appears to work. However, I wonder which racetam is the best for this purpose, and if there are other drugs or supplements to synergise with it.

Is there any other drug or supplement, preferably supported by studies?

[rwac]

You are on a VLCD. Most of your other cells have already become insulin resistant to spare glucose for the brain. Liver glycogen stores are probably low. So you're making glucose for your brain by gluconeogenesis (making glucose from protein), which involves increasing glucocorticoids like cortisol.

So the short answer is no, you can't provide lots of glucose to your brain while VLCDing.

[blood]

Metformin?

[maximum411]

Your body goes to extreme measures to spare glucose for the brain, as this is the only tissue that cannot utilize fatty acids as fuel (it can, however, sometimes use ketone bodies). It is extremely difficult to make your brain "hypoglycemic" unless you are truly starving. Hypoglycemia is only possible under extreme conditions (like not eating for a day and then running a marathon) for a healthy individual.


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[Dan1976]

Then why does my cognitive ability (including memory, attention, logical thinking, etc) plummet when I'm following a very low calorie diet?

Regarding agents which could upregulate brain glucose uptake, I have found the following interesting studies:


The abstract bellow mentions GLUT3 exactly once. It does not seem to be upregulated by green tea extract. Green tea extract probably doesn't work.

J Agric Food Chem. 2007 Jul 25;55(15):6372-8. Epub 2007 Jul 6.

Green tea polyphenol extract regulates the expression of genes involved in glucose uptake and insulin signaling in rats fed a high fructose diet.

Cao H1, Hininger-Favier I, Kelly MA, Benaraba R, Dawson HD, Coves S, Roussel AM, Anderson RA.

Green tea has antidiabetic, antiobesity, and anti-inflammatory activities in animal models, but the molecular mechanisms of these effects have not been fully understood. Quantitative real-time polymerase chain reaction (PCR) was used to investigate the relative expression levels and the effects of green tea (1 and 2 g solid extract/kg diet) on the expression of glucose transporter family genes (Glut1/Slc2a1, Glut2/Slc2a2, Glut3/Slc2a3, and Glut4/Slc2a4) and insulin signaling pathway genes (Ins1, Ins2, Insr, Irs1, Irs2, Akt1, Grb2, Igf1, Igf2, Igf1r, Igf2r, Gsk3b, Gys1, Pik3cb, Pik3r1, Shc1, and Sos1) in liver and muscle of rats fed a high-fructose diet known to induce insulin resistance and oxidative stress. Glut2 and Glut4 were the major Glut mRNAs in rat liver and muscle, respectively. Green tea extract (1 g) increased Glut1, Glut4, Gsk3b, and Irs2 mRNA levels by 110, 160, 30, and 60% in the liver, respectively, and increased Irs1 by 80% in the muscle. Green tea extract (2 g) increased Glut4, Gsk3b, and Pik3cb mRNA levels by 90, 30, and 30% but decreased Shc1 by 60% in the liver and increased Glut2, Glut4, Shc1, and Sos1 by 80, 40, 60, and 50% in the muscle. This study shows that green tea extract at 1 or 2 g/kg diet regulates gene expression in the glucose uptake and insulin signaling pathway in rats fed a fructose-rich diet.

PMID: 17616136

[socialpiranha]

http://www.ncbi.nlm....pubmed/10816070

[maximum411]

It could be lower levels of neurotransmitters. I know, for example, that serotonin is increased by carbohydrate consumption, and that dopamine production is supported by consumption of the amino acid tyrosine.

[Major Legend]

Well its possible that most of us are so used to high sugar that optimal performance is only achieved when we have higher than normal glucose levels in our blood stream or... -

... there are studies that increased glucose uptake does increase cognitive performance, but perhaps this could be because of a "spike" in glucose uptake when the body isn't used to elevated glucose levels, spiking cognitive performance to beyond status quo performane temporarily.

I like to think there should be a "baseline" and a "peak", with peak reserved for scenarios where optimal performance isn't sufficient, but an overdrive is required, with the peak being unachievable over long periods of time due to homeostasis and general wear and tear.

If anyone has ideas on how to achieve peak glucose uptake constantly that would be very interesting. For most parts I don't think diet improves cognitive performance above normal levels due to the reasons stated above, though the life extension and health reasons are more than enough to go on diet for most people.

Edited by Major Legend, 26 March 2014 - 02:16 PM.