Lecture 23 - Ketogenic Diets

what is the ketogenic diet

A diet enriched in calories from fat with minimal calories from carbohydrates and protein that promotes ketogenesis (ketosis)

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

what are ketone bodies

Fatty acids need to be converted into acyl-CoAs in order to be oxidized

Hence, fatty acid oxidation is required for ketogenesis

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

what are the 3 ketone bodies found in our circulation

βOHB, Acetoacetate, Acetone

Why do our bodies undergo adaptive ketogenesis physiologically?

1) Our body has small reserves of carbohydrate (glycogen)

2) Our body has limited protein stores

3) Our body has plentiful fat stores as triacylglycerol in adipose tissue

4) Our brains are unable to oxidize fatty acids for energy

what are normal vs fasting circulating ketone levels

Normal = 0.2 mM

Fasting = 1 – 3 mM

what are ketone levels like in DKA

levels can be >25 mM (blood pH: 7.25-7.3 [mild], 7-7.25 [moderate], <7.00 [severe])

what blood glucose levels are considered a risk of DKA

if blood glucose > 16.7 mM and blood ketones > 1.5 mM

What Happens When you Eat Some Carbohydrates?

Insulin inhibits adipose tissue lipolysis and fatty acid metabolism

Insulin promotes glucose uptake into the muscle, heart, adipose tissue and liver

Hence, insulin shuts off ketogenesis!

what is the effect of the ketogenic diet on the bdy

Makes the body behave like it’s fasting and continually produces ketones

what is the mechanism of the ketogenic diet

1) The low carbohydrate intake keeps insulin levels low

2) Low insulin levels activate mobilization of triglyceride stores in the adipose tissue

3) The liver will oxidize the fatty acids in the diet and convert them into ketones

4) Overtime consumption of this diet can promote weight loss

• Continuous mobilization and loss of adipose tissuederived fat that the liver continually turns into ketones

what are variations of the ketogenic diet

Standard ketogenic diet: 90% of calories derived from fat and 10% calories from carbs/proteins. In general 20- 50 grams of carbs per day

Targeted ketogenic diet: consumption of 25-50 grams of carbs 30-60 min prior to exercise

Medium-chain triglyceride diet: majority of fat intake comes from medium-chain triglycerides

Modified Atkins diet: carbohydrate intake remains limited at 10%, but protein content is increased to 30%

Low glycemic index diet: Carbohydrate intake is limited to foods with a glycemic index < 50

what is the aim of variations of the ketogenic diet

increasing carbohydrate and/or protein content in order to improve palatability of the diet (an important consideration from the pediatric perspective)

Where is a Ketogenic Diet Used in Medicine

Children with drug-resistant epilepsy (DRE)

Individuals with glucose transporter 1 (GLUT1) deficiency

what are the benefits of the ketogenic diet in children with DRE

Studies show that children with DRE may have as high as a 50% reduction in seizure frequency after 6-months of ketogenic diet consumption.

Reversal of protective effect rapidly diminishes following discontinuation of the diet.

Mechanism of action for this benefit is unknown

When should a ketogenic be avoided?

In people with carnitine deficiency

In people with inborn errors of metabolism

Any situation where fat metabolism is impaired

what are adverse effects of the ketogenic diet

Metabolic abnormalities → Hypoglycemia, Excessive ketosis (metabolic acidosis), Electrolyte Imbalances

Dehydration → More common in ketogenic diet protocols that include fasting

Gastrointestinal symptoms → Abdominal pain, Vomiting, Constipation

Kidney stones → Ketogenic diet-associated risk of kidney stones ranges from 2 – 6%

“Fruity” breath → We eliminate acetone mainly via respiration in the lungs

what is something important to consider to avoid reversing ketosis with the ketogenic diet

Over-the-counter medications may contain carbohydrates - e.g. cough syrups

Can reverse ketosis and precipitate seizures again in children taking a ketogenic diet for their drugresistant epilepsy

Is the Ketogenic Diet Actually Beneficial for our Everyday Health?

In general, the ketogenic diets reduces seizure frequency, but the overall quality of evidence is low.

All studies have been done in children, need further research for adults with DRE

What Is The Role of the Ketogenic Diet in People Trying to Manage their Type 2 Diabetes?

Low carbohydrate intake will help combat elevated blood sugar levels that characterize the type 2 diabetes phenotype

Low carbohydrate levels will promote less islet beta cell insulin secretion, thereby reducing potential beta cell stress (beta-cell rest hypothesis)

what were the outcomes of the Hallberg Study

The Hallberg Study demonstrated that a ketogenic diet significantly improved glycemic control, reduced diabetes medications, and led to weight loss in participants with type 2 diabetes.

how does the ketogenic diet compare to a low fat/high carb plant-based diet

better glycemic control in ketogenic diet

what is the role of the ketogenic diet in people trying to manage their body weight

Meta-analyses of 13 studies with follow up of 1-year or greater and carbohydrate intake <10%, indicated a mean weight loss of 0.91 kg

There was also a mean increase in LDL cholesterol of 0.12 mM

• Associated with decreases in circulating triacylglycerol levels

• Associated with increases in HDL cholesterol levels

Weight loss may actually be due to the ketogenic diet promoting enhanced satiety

We don’t have enough clinical evidence!

what is the evidence surrounding the ketogenic diet in people with cancer

It has been suggested that a ketogenic diet may act synergistically with and enhance the effectiveness of oncology therapies

what is a strategy used to try to help with ketogenic diet adherence

ketone ester drinks (based on the theory that the ketones themselves are responsible for the benefits of the ketogenic diet)

contain (R)-β-hydroxybutyrate is transesterified to ethyl (R)- 1,3-butanediol

Non-specific gut esterases hydrolyze the ketone ester into D-β-hydroxybutyrate and (R)-1,3-butanediol