Health

The Biochemistry of Ketosis: How a Low-Carb Diet Affects Metabolism and Health

Students often become fascinated with the idea of diets that promote weight loss through nutritional ketosis. This sparks their interest in metabolic pathways such as the citric acid cycle, glycogen metabolism, fatty acid oxidation and hormonal regulation.

Low-carbohydrate diets suppress insulin secretion and trigger compensatory processes of gluconeogenesis and ketogenesis; in turn, ketone bodies like b-hydroxybutyrate and acetoacetate can quickly be transported to other tissues where they provide significant energy sources.

Metabolism

A very low-carb diet results in depletion of the body’s glucose stores and subsequent depletion of glycogen reserves, prompting liver cells to convert fat to energy through processes known as gluconeogenesis and fatty acid oxidation or ketogenesis, producing acetone and beta-hydroxybutyrate, two types of ketones which can be measured either blood or breath tests and which give off fruity or slightly sweet breath odors, popularly referred to as “keto flu.”

Nutritional ketosis encourages the breakdown of excess triglycerides while sparing muscle, and increasing insulin sensitivity. Ketones are an efficient respiratory fuel and cross the blood-brain barrier to provide energy directly to the brain – one reason research shows a very low-carbohydrate diet can bring long-term improvements in HbA1c, fasting glucose and HOMA-IR for those living with type 2 diabetes; similar benefits have also been observed with diets currently popular with the general population.

Thyroid

Normaly, our bodies rely on blood sugar (glucose) as fuel and store excess in our livers as glycogen. When carb intake falls significantly below what is required to maintain metabolic ketosis – producing acetone, acetoacetate and beta-hydroxybutyrate from fatty acids as fuel for our bodies and minds alike. Ketone bodies also serve as energy stores in their own right.

Nutritional ketosis involves maintaining low insulin levels to facilitate fat breakdown as fuel for muscle use and promote de novo gluconeogenesis if necessary.

At first, a low-carb diet may lead to digestive issues like constipation and gas. This is likely caused by decreased water weight due to decreased carb intake and ketosis; furthermore, decreased thyroid hormone production is possible since active T3 production relies upon gut bacteria for sulfation and glucuronidation (*). Furthermore, ketogenic diets increase your risk for gut infections that could further compromise thyroid health.

Adrenal Stress

Ketogenic diets induce the body to break down fat for energy. This produces fatty acids and ketones (or ketone bodies), which provide energy for brain functions. Acetone released during this process is excreted via urine; thus giving rise to bad breath – commonly referred to as “keto flu.”

Low-carb diets activate the hypothalamic pituitary adrenal (HPA) axis and increase stress hormones such as cortisol and adrenaline to protect the body against perceived threats, raising both blood pressure and heart rate in response to them. Adrenals also respond by increasing sodium metabolism while stimulating kidneys to release salt to normalize blood pressure.

Nutritional ketosis has been found to significantly improve metabolic and inflammatory markers in the body, such as HbA1c, fasting glucose and insulin levels, lipid profiles and HOMA-IR scores. Although further research needs to be conducted into long-term adherence and practicality of VLCKD diets for weight loss and metabolic health is warranted, the evidence supporting VLCKD as an approach is compelling.

Health

When glucose becomes scarce, the body starts breaking down fats and proteins for energy – this process is known as gluconeogenesis and results in glucose being created from fat molecules like triglycerides as well as amino acids forming proteins. Ketone bodies, similar to glucose but created using different mechanisms than traditional methods – can also provide fuel for brain activity.

The ketogenic diet stimulates several metabolic and hormonal adaptations that improve fat oxidation while sparing glycogen in exercising skeletal muscle, as well as increasing citric acid cycle intermediate concentrations to support carbohydrate and lipid metabolism.

Ketone bodies can pass across the blood-brain barrier and into brain cells where they serve as an alternative fuel source to glucose. Ketone bodies compete with glucose for entry into mitochondrial citric acid cycle via phosphorylation process allowing brain cells to use energy directly without recourse to glycolysis process or insulin levels causing any side effects of action.

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