Lecture 21 Ketogenic diet

Question 1

What is the ketogenic diet?

Answer 1

diet enriched in calories from fat with minimal from carbs and protein ⇒ promotes ketogenesis (ketosis)

standard one has 90% calories from fat, remaining 10% from carbs and proteins (about 20-50 g carbs per day)

4:1 ratio by weight (fat:carbs/protein)

makes body behave like its fasting and continually produces ketones ⇒ low carbs keeps insulin low ⇒ activates mobilization of TG stores in adipose ⇒ liver oxidizes fatty acids into ketones ⇒ overtime this diet can promote weight loss

Question 2

What is ketogenesis and why does our body do it?

Answer 2

under normal conditions our body ⇒ 1. has small reserves of carbs (glycogen), 2. our body has limited protein stores, 3. our body has plentiful fat stores as triacylglycerol in adipose, 4. our brains can’t oxidize fatty acids for energy

THEREFORE a ketone body is a pre-catabolized fatty acid that can be metabolized/oxidized by brain

Insulin SHUTS OFF KETOGENESIS as it inhibits tissue lipolysis and fatty acid metabolism, and promotes glucose uptake into muscle, heart, adipose, and liver ⇒ INGESTING CARBS SHUTS OFF KETOGENESIS

Question 3

What are normal levels for ketones, and what is ketoacidosis?

Answer 3

Normal = 0.2 mM, fasting = 1-3 mM, ketoacidosis = can be >25 mM

considered at risk of ketoacidosis if BG >16.7 mM and blood ketones >1.5 mM

Question 4

What is the MOA of insulin shutting off ketogenesis?

Answer 4

insulin activates Akt leading to increased phosphodiesterase 3B ⇒ degrades cAMP ⇒ reduces lipolysis ⇒ reduces circulating FFA delivery to liver ⇒ reduced ketone production

insulin activates acetyl CoA carboxylase (ACC) in liver which produces malonyl CoA ⇒ inhibits fatty acid oxidation, promotes fatty acid biosynthesis

Question 5

What are different variations of the keto diet?

Answer 5

Targeted: consumption of the 20-50 g of carbs 30-60 min before exercise

Medium-chain TG: majority of fat comes from medium-chain TGs

Modified Atkins: carb intake remains at 10% but protein increased to 30%

Low glycemic index: carb intake limited to foods with glycemic index <50

Question 6

Where is a keto diet used in medicine, and when should it not be used?

Answer 6

Children with drug-resistant epilepsy (DRE) - studies show that children may have 50% reduction in seizure frequency after 6 months of diet, reversal of this happens rapidly following stoppage of diet, MOA unknown

Individuals with GLUT1 deficiency - rare genetic disorder characterized by seizures, developmental delay, movement disorders, as this transporter gets glucose through BBB

DIET SHOULD BE AVOIDED IN PEOPLE WITH CARNITINE DEFICIENC

Question 7

What are AEs of a ketogenic diet?

Answer 7

metabolic abnormalities: hypoglycemia, excessive ketosis (metabolic acidosis), electrolyte imbalances

dehydration: more common in protocols involving fasting

GI: ab pain, vomiting, constipation

Kidney stones: associated with 2-6% risk

‘fruity’ breath: we eliminate acetone mainly via respiration

Question 8

How might a ketogenic diet be applied for someone with diabetes, is there any evidence?

Answer 8

low carb intake will help combat elevated BG levels, and will promote less islet beta-cell insulin secretion thereby reducing beta-cell stress (hypothesis)

Evidence: Hallberg study, 262 people for 1 year, 87 in control ⇒ noted improved A1c levels, reduction in diabetes meds, lower mean insulin dose used, most patients on the diet saw weight reductions ⇒ was open label non-randomized and keto diet patients received extra counselling and tools