From the Guidelines
Elevation of beta hydroxybutyrate (BHB) levels is primarily caused by states of ketosis, which can occur due to various factors including prolonged fasting, very low-carbohydrate or ketogenic diets, intense exercise, uncontrolled diabetes, and certain metabolic conditions. The most common causes of elevated BHB include:
- Prolonged fasting (typically beyond 12-24 hours)
- Following a very low-carbohydrate or ketogenic diet (usually less than 50g of carbohydrates daily) 1
- Prolonged intense exercise that depletes glycogen stores
- Uncontrolled diabetes, particularly type 1 diabetes with insulin deficiency leading to diabetic ketoacidosis 1 Certain metabolic conditions like alcoholic ketoacidosis and some inborn errors of metabolism can also raise BHB levels. Additionally, exogenous ketone supplements containing BHB salts or esters will directly increase blood BHB levels when consumed. Physiologically, when glucose availability is limited, the liver converts fatty acids into ketone bodies, including BHB, which serves as an alternative fuel source, particularly for the brain, as described in the context of ketogenic diets 1. This metabolic adaptation is a normal response to carbohydrate restriction but can become dangerous in pathological states like diabetic ketoacidosis where extremely high levels may develop alongside metabolic acidosis 1. The production of BHB from fatty acids by the liver during carbohydrate restriction typically results in BHB levels varying between 0.3 up to 4 mmol/L 1. It's essential to differentiate between physiological ketosis, characterized by normal pH, low but within physiological ranges of both insulin and blood glucose, and pathological ketosis, which is marked by low systemic pH, no insulin, hyperglycemia, and very high levels of ketone bodies 1.
From the Research
Causes of Beta Hydroxybutyrate Elevation
- Beta hydroxybutyrate (BHB) elevation can be caused by various factors, including the use of sodium glucose cotransporter inhibitors, such as sotagliflozin, in patients with type 1 diabetes 2.
- Physiological conditions like exercise, fasting state, and acute illness can also increase BHB levels 3.
- A ketogenic diet, which is a very low-carbohydrate and high-fat diet, can lead to ketoacidosis and elevated BHB levels, particularly in individuals with unrecognized type 1 diabetes 4.
- Genetic factors, such as the ablation of CNDP2, can affect BHB metabolism and lead to changes in BHB levels 5, 6.
- Energy balance and metabolic pathways, including a previously undescribed secondary BHB metabolic pathway, can also influence BHB levels 5, 6.
Associated Factors
- Baseline BHB levels and changes in BHB levels over time can be associated with an increased risk of diabetic ketoacidosis (DKA) 2.
- Age, insulin pump use, and sotagliflozin use can also be associated with DKA episodes 2.
- The levels of BHB can be correlated with energy metabolism of myocardial cells, and increased BHB levels can be observed in patients with heart failure 3.