Glucose, also known as grape sugar, is a ubiquitous fuel in biology: it is used as an energy source in most organisms, from bacteria to humans. It has 2 geometrical variants: the d-isomer (d-glucose, also known as dextrose) occurs widely in nature, but the l-isomer (l-glucose) does not and is biologically inactive.
Dextrose, or d-glucose, is made during photo-synthesis by plants from water and carbon dioxide (CO2) using energy from sunlight. The reverse of the photo-synthesis reaction, the so-called glycolysis which releases this energy, is a very important source of power for cellular respiration. Glucose is stored as a polymer, in plants as starch and in animals as glycogen, for times when the organism will need it: dextrose is then made freely available for cells through the breakdown of glycogen called glycogeno-lysis. The body can also produce glucose in the liver and kidneys by a process known as gluco-neogenesis, which takes place during periods of fasting, starvation, low-carbohydrate diets, or intense exercise, however this pathway is less “economical” from a cellular point of view.
Brain is our most energy-consuming organ. Representing only 2% of the total body weight, it demands 20% of our resting metabolic rate just to keep things in order: the bulk of it is used to fuel electrical impulses that neurons employ to communicate with one another. However, even during sleep with very little brain activity there is still a high baseline power utilization in the central nervous system. Most organs do not require so much energy for basic house-keeping, but the brain must actively maintain appropriate concentrations of charged particles such as sodium (Na+) and potassium (K+) ions across the membranes of billions of neurons, called membrane potential, even when those cells are not firing. This is because the brain is the body’s all-powerful control center and it has to be able to cope with a flood of tasks at all times even when we are at rest.
Despite its massive energy needs, the brain is a picky eater: it only uses d-glucose (dextrose) which it cannot store, therefore neurons are reliant on a continuous sugar supply from the blood. In addition to the gluttonous baseline intake, when neurons in a particular brain region fire, local capillaries dilate to deliver even more blood than usual, along with extra glucose and oxygen1,2.
Carbohydrates, abundantly present in foods such as breads, cereals, fruits and vegetables, contain various sugar-units. Individual or single units of sugar including glucose and fructose are the simplest forms of carbohydrates called mono-saccharides, whereas the complex ones (poly-saccharides such as starch and fiber) are made up of long chains of multiple glucose units joined together by chemical bonds. During digestion, a series of enzymatic reactions break down the large carbohydrates into simple saccharides that are easily absorbed in the small intestine: this conversion, however, takes time. Being a small molecule, glucose is then rapidly shuttled around the body. It makes its way out of the blood vessels, and moves into the various tissues primed to deliver energy to hungry cells. But despite its ambition, it cannot cross the cell membrane to get to the inside of cells where it is converted to energy. Special proteins, called glucose transporters, line cell membranes and help pass sugar from the outside to the inside of cells. There are several different types of glucose transporters found throughout in the body, for instance GLUT-3 is expressed mostly in neurons. The majority of these transporters simply act as a conduit, allowing sugar to passively move through the cell membrane. But GLUT-4, the type found in fat and muscles, must be activated by the hormone insulin, which is produced by the pancreas. When near a cell, insulin binds to a membrane protein called an insulin-receptor, and sends a chemical message to GLUT-4 that it is time to start letting glucose in.
Diabetes, a disease affecting millions of people, occurs when something goes wrong with the insulin-glucose interaction in cells. In type-1 diabetes, there is simply not enough insulin circulating in the blood-stream. Tissues that have GLUT-4 transporters, which require insulin to get glucose into cells, starve. In type-2 diabetes cells have become insensitive or resistant to insulin: this means that there is plenty of insulin in the blood-stream to go around, but either the hormone cannot bind to the insulin receptor, or once bound there is no chemical message sent from the receptor to the glucose transporter to start allowing sugar to enter. The pancreas, sensing there is still a large amount of carbohydrates in the blood, releases more and more insulin, compounding the situation: excessive hormone concentrations not only render the body less receptive to insulin, but secreting high amounts on the long-run may ultimately also exhaust the pancreas.
Muscles are the biggest glucose competitors to the brain: their energy demand increases massively during physical training. Unlike the central nervous system, muscles store sugar in the form of glycogen, but only for their own use. Just as vigorous exercise tires our bodies, intellectual exertion should drain the brain. Complex thought, challenging assignment and intense concentration require more energy than routine mental processes because there are more neural activities and, likewise, eating foods rich in sugars should improve performance on such tasks. Dextrose, or d-glucose, is the best choice for a quick boost of power: it can travel directly to the brain right away.
Failure of appropriate fuel supply to the central nervous system contributes to a wide range of neurological disorders, including cognitive dysfunction. Indeed, impaired cerebral glucose metabolism is one of the many central features of Alzheimer’s dementia: it occurs early in the disease and correlates with symptoms and progression3. By leaving neurons less able to utilize glucose for fuel, it leads to an energy shortage in the brain. In such cases the liver naturally produces so-called “ketone bodies” primarily from fatty acids in the diet or body fat as an alternative power source for the cells4. While ketone bodies are the brain’s natural back-up energy, neurons prefer sugar and an ongoing supply of carbohydrates determines performance.
However, sometimes less is more. The constantly high level of glucose in both type-1 and type-2 diabetes can damage organs such as the blood vessels, the heart, the kidneys, or the eyes, just to name a few, and involvement of cerebral arteries ultimately leads to impaired blood flow to the brain, causing neurons to starve. Moreover, elevated insulin concentration, as seen in type-2 diabetes, promotes the formation of abnormal proteins called neuro-fibrillary tangles and senile plaques inside and between the nerve cells, respectively, which are the hallmark features of Alzheimer’s disease5. Nevertheless, diabetes may not only contribute to dementia. Even though the brain-specific GLUT-3 is independent of insulin, there are several areas of the central nervous system that have insulin receptors including the cerebral cortex and hippocampus which are heavily involved in memory formation and organization. Insulin resistance is linked to reduced blood sugar use specifically in these key areas often affected by dementia6. Because of the improper glucose and insulin handling that occurs directly in the brain of such patients, Alzheimer’s disease is now regarded as type-3 diabetes7,8.
For years, sugar has been the silent killer, slowly chipping away at our body’s sensitivity to insulin, and contributing to the obesity epidemic. We still do not have enough evidence to say for sure whether there is a direct link between Alzheimer’s disease and diabetes, and current reports are often incongruent and even contradictory9. But the fact that glucose- and insulin-signaling irregularities cause problems in the brain creates yet another reason to reconsider the role of carbohydrates.
Firing neurons summon extra blood, oxygen and glucose. Normally, mono-saccharides provide the additional energy needed, but cells may metabolically adapt to situations of excess sugar in diabetes; however, tissues flooded with glucose are ultimately rendered insensitive and can no longer regulate their own needs. In contrast to the constantly high levels of carbohydrates, pulsatile glucose stimulus, akin to natural rises of blood sugar levels following meals (called post-prandial), shows greater insulin responsiveness10. Studies have also confirmed that administration of mono-saccharides can facilitate memory in healthy humans and in patients with Alzheimer’s disease11. In addition, certain medications – including a number of anti-diabetics – increase the risk of hypoglycemia: once the brain stops receiving enough glucose, energy is needed as soon as possible. Low-grade pulsatile carbohydrate may help neuronal sugar intake through both the insulin-dependent and independent transporters in healthy and diabetic individuals alike.
This delicate glucose pulse – as delivered via MEMENTUM in its purest form, dextrose, in a gentle dose suitable for diabetics as well – gives you an optimal boost in the morning for a great start to the day with beneficial effects on many biological processes to spice up your brain.
