REGULATION OF KETOGENESIS

(Sung to the tune of “Clementine”)

In starvation, diabetes, sugar levels under strain

You need fuel to keep going saving glucose for your brain

Ketone bodies, Ketone bodies, both acetoacetate

And its partner on reduction, 3-hydroxybutyrate.



Glucagon’s up, with low glucose, insulin is down in phase

Fatty acids mobilised by hormone-sensitive lipase

Ketone bodies, Ketone bodies, all start thus from white fat cell

Where through lack of glycerol-P, TG making’s down as well



…Don’t despise them, they’re good fuels for your muscles, brain and heart

When you’re bodies overloaded though, that’s when your troubles start

Ketone bodies, ketone bodies, make acetone, lose CO2

You can breath those out, but watch out - acidosis does for you!

Source: “The Biochemists’ Songbook, 2nd ed.” Harold Baum. London: Taylor and Francis Publishers, 1995.

Ketogenic diet is a high fat diet with a moderate protein intake and a very low carbohydrate allowance. ketogenic diet, aims at reducing the average calorie intake by minimizing carbohydrates and replacing them with healthy fats and moderate amounts of high-quality protein. This causes our internal biochemical pathways to switch to using our stored fat for fuel instead of utilizing glucose.

As blood-glucose, drops our liver starts to produce ketones — a process that shifts our body cells towards fat utilization as an alternative source of fuel. This new mode of metabolism, also known as ketosis, can come about in several different ways, including starvation, type 1 diabetes, and alcoholism.

Once the body is using ketones as a main source of fuel, all sorts of beneficial effects become apparent, a ketone producing diet is terrific for weight reduction, slows down the aging process and is potent in the management of diabetes. In fact, being in ketosis can offer hope against cancer, both for prevention and treatment. The antioxidant and anti-inflammatory effect of nutritional ketosis can be used to address many metabolic diseases.

Historical Perspective:

The ketogenic diet is not a new treatment in addressing chronic diseases. Throughout history, it has been recognized that if a person with epilepsy stops eating (fasts) their seizures generally stop. Physicians of ancient Greece treated diseases, including epilepsy, by altering their patients' diet. However, the classic therapeutic ketogenic diet was developed for treatment of paediatric epilepsy in the 1920s and was widely used into the 1930’s, but its popularity waned with the introduction of effective anticonvulsant drugs.

Fuel metabolism and the ketogenic diet

There are four substances, which the body can derive calories from: carbohydrate, protein, fats, and alcohol. The body tends to utilize a given fuel for energy in relation to its availability and concentration in the bloodstream. Carbohydrates are the most preferred source of calories because they can be broken down quickly to glucose, the main metabolic fuel of the body. However, the body can increase or decrease its use of glucose in direct proportion to the amount of dietary carbohydrate consumed. Fat utilization is dependent on carbohydrate and alcohol consumption.

ketogenic diet aims at reducing the average calorie intake by minimizing carbohydrates and replacing them with large amount of healthy fats and moderate amounts of protein. This mimics starvation or fasting state as our bodies enter into a condition known as ketosis. Ketosis means that the body is in a state where it doesn't have enough glucose available to use as energy, forcing it to metabolize free fatty acids as an alternative fuel. Some tissues in the body like the brain cannot utilize fats for their energy needs. However, when the body is running primarily on fats, large amounts of acetyl-CoA are produced which exceed the capacity of the Krebs cycle, leading to the production of Ketone bodies (acetoacetate, β-hydroxybutyrate and acetone) which are by-products of the incomplete breakdown of free fatty acids within liver mitochondria and are readily utilize by the brain and heart muscles.

It is noteworthy to mention that some people confuse ketoacidosis, an extremely abnormal form of ketosis, with the normal benign dietary ketosis associated with ketogenic diets.Benign dietary ketosis is a controlled, insulin regulated process which results in a mild release of fatty acids and ketone body production in response to low carbohydrate intake, and higher fat consumption. On the other hand, Ketoacidosis is a condition in which abnormal quantities of ketones are produced in an unregulated biochemical situation. In order to reach a state of ketoacidosis, the body has to be in a state of not producing enough insulin to regulate the flow of fatty acids and the creation of ketone bodies.



Ketogenic diet in metabolic disease management:



Source: A Paoli, A Rubini, J S Volek and K A Grimaldi. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition (2013) 67, 789–796



Cancer

Normal cells have the metabolic flexibility to adapt in the absence of glucose surviving on other sources of metabolic fuel. Cancer cells lack this ability because of their broken metabolism; cancer cells are vulnerable to any diet which sharply lowers blood sugar. This is the main idea behind the use of a ketogenic diet to treat cancer - to deprive the cancer cells of the glucose they need to survive, and provide alternative fuel to support the mitochondrial respiratory processes in healthy tissues. Dr. Otto Warburg, one of the twentieth century's leading biochemists, discovered this about cancer and the hypothesis that cancer cells are only able to use glucose (blood sugar) for fuel is today called the Warburg Hypothesis.

Neurological diseases

The keto diet is also being increasingly considered for the treatment of many neurological diseases and injuries, a list that includes Parkinson’s, Alzheimer’s, stroke, and even traumatic brain injuries. The keto diet can also improve memory function in older adults with increased risk for Alzheimer’s disease. Neuroscientists attribute the keto diet’s brain-protective qualities to a number of things:

Ketone bodies serve as an alternative source of energy during metabolic stress
Ketosis diminishes the toxicity produced by glutamate acid, a problem when a brain injury happens
It enhances GABA levels (γ-Aminobutyric acid) — an important inhibitory neurotransmitter
It has antioxidant and anti-inflammatory qualities
The diet protects against various forms of cell death
Restricting carbs protects against oxidative- and glutamate-stress, among other things

Diabetes

Ketogenic diet works very well for people with type 2 diabetes because it is a low carbohydrate diet. It is effective at improving glycemic control in diabetic patients, and it "has a significant beneficial effect in ameliorating the diabetic state and helping to stabilize hyperglycemia. Some studies also show that ketosis help reverse hepatic insulin resistance.

Side effects:

As every other diet used to address metabolic diseases ketogenic diet also has its limitations. Therefore, it is important that any person considering the diet should consult a dietician or a doctor who can advice him or her on the best way to approach it. Some of the side effects of this diet include constipation, hypoglycemia, hypercholesterolemia, hyperacidosis, osteoporosis, and kidney Stones.

Other negative symptoms occur during the first week the diet is introduced; they include fatigue, weakness, light-headedness, headaches, and mild irritability but they usually can be eased fairly easily. Most are over by the first week of a ketogenic diet, though some symptoms may extend to two weeks.