Type 1 Keto

Metabolism for HCP education

Essential Metabolic Health Module. 

Metabolism involves all energy pathways that maintain function in the body 

It is a process that is always in equilibrium, but that equilibrium is not necessarily balanced towards a healthy state 

Factors which can affect metabolism include : 

Energy sources: Carbohydrate, Protein and Fat 

Physical activity ( might increase muscle mass which will improve insulin sensitivity) 

The wider environment: light (affects sleep, vitamin D), stress (emotional, physical, toxins) 

Microbiome 

Genetics including epigenetics 

Adjusting any of these variables will alter the equilibrium of metabolism. It will attempt restoration of a healthy balance, but this might not be possible because of the type and persistence of the stressor.  

Energy Sources 

Current dietary recommendations are that fat makes up 35% of the energy intake, of which 10% is limited to saturated fat, carbohydrate 55%, and protein, 15% 

Energy form 1g carbohydrate and protein =4cals Energy from 1g fat =9cals 

A 2000calorie diet, therefore, needs 275g carbohydrate, 75g protein and 78g fat 

Protein. It is absorbed into the portal system as amino acids. Protein provides structure (muscle), function, intracellular organelles, cell surface receptors, hormones and enzymes, energy. Protein cannot be stored, but the amino acids can be used to make proteins which includes structural materials such as muscle, and cellular components such as cell surface receptors and enzymes.  It can also be converted to glucose ( glucogenic proteins), ketone bodies (ketogenic proteins), and the glycerol backbone of triglycerides.  

There are essential amino acids, and therefore protein is an essential dietary component. 

Fat. Dietary fat is absorbed into lymphatics as ULDL ( ultra-low density lipoproteins). These are also known as chylomicrons.  Chylomicrons enter the bloodstream via the thoracic duct. Dietary fatty acids are therefore absorbed directly into tissue without modification. Hence the importance of the correct type of nutritional fat.  

Fats are integral to cell structure, including cell membranes and organelles. 60% of the brain is made of fatty substance.  Fats can provide energy through fatty acid oxidation and ketone bodies. Energy providing fats are primarily saturated, medium-chain, fatty acids of chain length 16-18 units. Long-chain polyunsaturated fatty acids (omega fats) are usually involved in cell processes other than energy and are considered anti-inflammatory if in the right ratio of omega 6 to omega 3. It is ideally a 1:1 ratio. Essential fats are omega -3 and omega-6. Plant-derived essential fats need a modification process to make them bioactive in humans. The process is around 10% efficient but is sufficient for the tiny daily amounts required.   

Fats and glycogen make up the energy storage substances in the body. Fat can be made from fat itself, from the conversion of glucose or the conversion of protein. Glycogen is synthesised from glucose.  

Carbohydrates. Provide energy but have other functions such as cell-signalling through glycans. All dietary carbohydrate is absorbed into the portal system as one of 3 monosaccharides, glucose lactose, fructose. Starch is simply a glucose chain. Lactose can provide energy directly; fructose can do this too, but preferentially this is indirect by conversion to fat first.  

Glucose is maintained within a narrow range in the bloodstream. There are just 5g of glucose in the total blood volume. Glucose in excess is cleared by conversion to glycogen, cell uptake of glucose or conversion to fat. The first 2 of these are limited by cellular energy requirements. When the cells are replete in energy, the surplus is converted to fat.  

There are no essential carbohydrates.  

Metabolism. 

General Principles. Every human likely has a unique metabolism based on their genetics and the environment.  

The body is multi-fuel and can use all types of macro-nutrients equally well. Most energy is derived from the Krebs cycle or TCA cycle. This takes place across the mitochondrial cell wall.  

Glycolysis happens in the cytoplasm except in red blood cells where it is in the cell wall. 

 Parts of the brain and red blood cells are solely dependent on glucose as fuel as they have no mitochondria. These needs can easily be met through gluconeogenesis in the liver, kidney and probably gut, using glycerol from fats and proteins. There is no minimum amount of carbohydrate ingestion needed to meet the daily requirement. 

The Laws of Thermodynamics apply only to closed systems. Biological systems are not closed systems for practical purposes ( unless you count the whole universe, assuming there is no multiverse!)  

Calories-In does not equal Calories-Out ultimately because the Basal Metabolic Rate changes to compensate after a few months. The body adapts to its environment. This phenomenon is seen in yo-yo dieting.  

Metabolism in Insulin Resistance 

There is no agreement on the exact mechanism of insulin resistance, but it is present in those who cannot process carbohydrates effectively. Studies have shown that more insulin is needed to handle a set amount of carbohydrates in these people compared to those with carbohydrate tolerance. Raised glucose cannot be cleared from the blood leading to fat deposition and chronic hyper-insulinaemia in the presence of too many carbohydrates.  

Functions of Insulin. 

Enhance the function of Glut 4 receptors to clear glucose into the muscle.  

Reduce the rate of renal sodium excretion leading to hypertension. 

Up-regulating HMGCoA reductase leading to cholesterol production 

Increasing production  of inflammatory cytokines 

 IL6 TNF leading to inflammation 

Neuroendocrine effects in the brain to regulate appetite and weight. 

  Chronic hyper-insulinaemia will cause weight gain, inflammation, hypertension, and unfavourable changes in lipid profiles if left untreated. Current treatments include negating the individual effects with medication such as anti-hypertensives, anti-obesity medication, statins and glucose-lowering agents. Another way is to reduce insulin levels. Insulin needs to be present at low doses, and this can be achieved by dietary change by removing carbohydrates from the diet. 

Summary  

There are some essential macro-nutrients in protein and fat but none in carbohydrates 

Healthy fats are crucial because they are absorbed before entering the portal circulation. 

Not all calories are equal, and this is because of their effects on metabolism 

The body is a multi-fuel organism 

Metabolism will adjust according to dietary nutrients, but this is not always in favour of health. 

Insulin has many harmful effects in high concentration. Insulin resistance can be resolved by altering metabolism  

Calories-In does not equal Calories-Out in biological systems.