Types of the ketogenic diet

 

The KD is defined as a high-fat, low-carbohydrate diet. So far, several variants of KD have been created that exhibit similar efficacy to the original form and allow flexibility to promote compliance with the regimens. 24,25 The original long-chain triglyceride (LCT) KD, medium-chain triglyceride (MCT) KD, modified Atkins diet (MAD), and low glycemic index therapy are the four basic forms of KD with demonstrated efficacy (Fig. 1). 24

The classic LCT KD is the most traditional type of KD and is widely used in clinical settings. It contains a 4:1 fat (in grams) to protein plus carbohydrate ratio (in grams). 26,27 Fat supplies 90% of the calories, and the most common source is food-derived LCT, which can be employed in a 3:1 or lower ratio. 24. Furthermore, low ratios are optimal for KD beginning in newborns; however, in older children, a 4:1 ratio followed by a lower ratio may be more successful. 24,28 Furthermore, there is evidence that calorie and fluid restrictions are unnecessary because there is no benefit impact with these two parameters.24,29

The LCT KD is unappealing, difficult to prepare, and hence difficult to maintain because of the significant carbohydrate limitation. 30. The MCT (C6-C12) KD was developed in 1971. 30. MCT oil is more tolerable and ketogenic than LCTs in the diet. 30,31,32,33 The MCT KD provides greater diet ratio flexibility than the LCT KD, and calorie intake is determined depending on the percentage of energy produced from MCT. 24, 31. Furthermore, there is clinical evidence that the MCT and LCT KD have equal effectiveness. 12,32 The MCT KD, on the other hand, is usually associated with gastrointestinal adverse effects. 24,31

The MAD is based on the Atkins diet, which was widely used to lose weight. 34,35,36 and has similar cuisine options to the original KD, but without the requirement for exact ingredient weighing. The MAD lacks a precise ketogenic ratio, which normally fluctuates from 1:1 to 1.5:1 and can occasionally approach 4:1.35. Furthermore, the MAD does not impose any protein, drink, or calorie limits. The MAD restricts carbohydrate consumption to 10–15 g/day for the first month, then increases to 20 g/day. 37, 38 There is clinical evidence that the MAD is effective in children with intractable epilepsy.

The low glycemic index treatment is based on the idea that the KD's protective effect is dependent on stable glucose levels, 45 but it has a liberalized regimen with low-carbohydrate composition to minimize glycemic increases (glycemic indices of 50), 45 and is an effective antiepileptic intervention in children with intractable epilepsy. 44,45,46,47,48,49

Despite the evidence that the four forms of KD have equal effectiveness, it is unclear if the mechanisms of action of these diets differ.

The impact of the ketogenic diet on metabolism

The breakdown of lipids

The metabolism of blood lipids during KD is frequently a source of concern. In the presence of oxygen, the majority of cellular energy is generated through glycolysis from glucose-metabolized pyruvate, which is subsequently oxidatively phosphorylated inside mitochondria. In the absence of glucose, cellular energy is generated by the breakdown of fatty acids. 50 A low-carbohydrate, high-protein, and high-fat diet can be harmful because it raises circulation levels of low-density lipoprotein (LDL), cholesterol, and triglyceride (TG). In terms of liver fat metabolism, a low total and saturated fat/high carbohydrate diet can effectively regulate hepatic fat accumulation by reducing exogenous fats.

On the other hand, the KD offers potential health advantages in terms of these cardiovascular risk factors, and recent animal and clinical research has shown strong evidence that limiting carbohydrates can really lower total cholesterol, boost high-density lipoprotein (HDL), and lower blood TG levels. 52, 53 The KD, based on the notion of maintaining constant total calorie intake, reduces carbohydrate consumption, lowers serum insulin levels, increases insulin sensitivity, and improves fat catabolism, lowering blood lipids. 14. Higher carbohydrate consumption may be harmful to net hepatic fat reduction due to increased de novo lipogenesis, reduced fatty acid oxidation, and/or ketone generation.

Low-carbohydrate/high-fat KD, on the other hand, greatly enhances the rate of whole-body fatty acid oxidation and hepatic ketogenesis. As a result, KD has been demonstrated to lower liver fat. 56,57 Furthermore, the KD improves the hepatic clearance of TGs by inducing the production of fibroblast growth factor-1. 58 Furthermore, the KD has the ability to increase the size and volume of LDL-C particles59, which is thought to minimize the risk of cardiovascular disease since smaller LDL particles have higher atherogenic activity. In addition, the KD has an effect on endogenous cholesterol production. Insulin activates -Hydroxy-methylglutaryl-CoA reductase, a crucial enzyme in cholesterol production. As a result, increasing blood glucose levels and insulin levels result in increased endogenous cholesterol production. As a result, lowering dietary carbs and increasing cholesterol consumption will result in the suppression of cholesterol biosynthesis.

Glucose metabolism

In humans, there are two sources of glucose: glycogenic amino acids and glycerol, which are produced through TG lysis. 60, 61 During ketosis, the importance of the latter source grows. During the first few days of the KD, glycogenesis from amino acids is the primary source of glucose. As a result, the contribution of amino acids decreases while the quantity of glucose derived from glycerol increases. In fact, TG-hydrolysis-induced glycerol can generate more than 16% glucose in the liver during the KD, compared to 60% glucose after several days of complete fasting. 62) The KD's effect on blood sugar levels is still debatable.

After several days of fasting or carbohydrate restriction, the body's glucose stores are inadequate to create oxaloacetate in the Krebs cycle for normal fat oxidation and glucose delivery to the central nervous system. 63) As a result, most studies think that the KD causes lower blood sugar concentrations and a lower insulin-to-glucagon ratio, which is advantageous for glycemic management in diabetics. 20,64 Elevated glucagon levels are linked to increased hepatic glucose mobilization. A recent study looked at the effects of KDs in both active and sedentary rats. 65. When compared to the conventional meal, KD reduced insulin levels by 80%, blood sugar by 50%, TGs by 55%, and cholesterol by 20% after 6 weeks, although exercise had no effect.

KD has no effect on inhibiting or improving cell function or insulin secretion. Individual differences and treatment conditions should be considered in the practical use of KD.

In the liver, excessive production of acetyl-coenzyme A (acetyl-CoA) and oxidation of fatty acids lead to the production of ketone bodies (KB). Then it spontaneously converts to acetone or 3--hydroxybutyrate by 3--hydroxybutyrate dehydrogenase. 70.71 kB then enters the bloodstream and can be used in the brain, heart, and muscles, where they transmit cellular energy in the mitochondria to generate 7,72,73 Higher levels of circulating KB lead to ketonemia and ketonuria.74. Under physiological conditions, the concentration of KB in the blood during long-term fasting is usually 5–7 mM, while the glucose concentration can be reduced to less than 1 mM without convulsions or any mental limitations. In diabetic ketoacidosis, plasma KB levels may increase by up to 25 mM due to insulin deficiency, resulting in increased plasma glucose levels and lower blood pH. 74. KB con can be a more efficient source of energy than glucose, metabolizes faster than glucose, and can bypass the glycolytic pathway by entering the Krebs cycle directly. while glucose must undergo glycolysis.76. In addition, they cause fatty acid-mediated activation of the peroxisome proliferator-activated receptor. as well as inhibition of glycolysis and fatty acids. 77 KB thus reduces glycolytic adenosine triphosphate (ATP) production and increases ATP production induced by mitochondrial oxidation, thereby promoting mitochondrial oxidative metabolism and leading to beneficial metabolic changes.