Effect of Diet Induced Ketosis on LDL Turnover Rates

NCT05103761 | Unknown

• 1 other identifier: Keto study 21-5376
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

There have been concerning case reports of marked elevations of LDL-c in some individuals consuming a KD and Dr. Lewis has been referred a number of these cases to his lipid clinic, some of whom have had extreme elevations of LDL that mimic familial hypercholesterolemia. These marked elevations of LDLc are unique to a ketogenic diet and far exceed the typical mild elevations seen in those consuming a high fat, low carbohydrate LGIT. The degree of elevation of LDL-c suggests that ketosis per se may impair LDL receptor-mediated LDL particle clearance. This clinical observation is a concerning and clinically important issue since millions of people are consuming this popular diet. There are currently no studies that have examined the mechanism of the LDL-raising effect of a ketogenic diet.

Conditions

Ketosis, Metabolic

Keywords

keto diet; ketosis; LDL metabolism; hyperlipidemia; cardiovascular disease

Outcome Measures

Primary Outcomes (1)

• LDL apoB turnover rates

  The primary objective is to quantitate LDL apoB turnover rates in response to eight weeks of KD-induced ketosis in healthy individuals.

  8 weeks

Study Arms (2)

Ketogenic diet

ACTIVE COMPARATOR

Diet administered to induce ketosis.

Other: Study diet

Low glycemic index treatment diet

PLACEBO COMPARATOR

Diet matched with a ketogenic diet with added carbohydrates to avoid ketosis.

Other: Low glycemic index treatment diet

Interventions

Study diet OTHER

A low carbohydrate diet (\<20g/day) is administered to achieve diet-induced ketosis.

Also known as: Nutritional intervention

Ketogenic diet

Low glycemic index treatment diet OTHER

A diet matched with the study diet with added carbohydrates (40-60g/day) to avoid ketosis.

Also known as: Control

Low glycemic index treatment diet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18 to 65 years
• Normolipidemic
• Plasma TG \<2.0 mmol/L (\~175 mg/dL)
• HDL \>1.0 mmol/L (\~40 mg/dL) ) in men or \>1.3 mmol/L (50 mg/dL) in women
• LDLc \<4.0 mmol/L (\~150 mg/dL)
• Total cholesterol \<5.0 mmol/L (\~200 mg/dL)
• Blood pressure ≤ 140/90 mmHg
• Fasting plasma glucose ≤ 6.3 mmol/L (125 mg/dL)
• HbA1c within ≥ 4.0% to ≤ 6.0%
• Hb \> 130
• BMI between 18-30 kg/m2
• Participant agrees to maintain their usual lifestyle and not make any significant changes to activity levels while enrolled in the study
• Cr \< 110 umol
• Able to speak and read English
• Agrees to consume each study diet for eight weeks

You may not qualify if:

• Patients on active treatment using lipid-lowering medications, such as statins, ezetimibe, or bile acid sequestrants
• Use of medications that interfere with protein, carbohydrate, or lipid metabolism (e.g., fish oil capsules)
• Patients who have unstable weight in the past three months (weight loss)
• Patients with a history of gout
• Patients who have had major surgeries
• Abnormal thyroid function or known liver disease
• Patients with chronic kidney disease, decompensated liver disease, unstable cardiac or respiratory disease, or GFR
• Uncontrolled hypertension
• Patients who are pregnant or breastfeeding or peri-menopausal
• Actively attempting to get pregnant or pregnant. Low dose estrogen-containing pill if taken for \> 3 months and continued throughout the study is acceptable. Women will be required to use adequate contraception and a pregnancy test will be performed on all women at the time of screening and immediately before each kinetics study.
• Participant has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose additional risk to the participant by their participation in the study.
• Abnormal bleeding, frequent headaches, arthritis, stomach problems, SOB, migraines, black outs/fainting, epilepsy, chest pain, asthma
• Participants who consume vegan diet
• Participant consumes excessive amounts of alcohol, defined as \>70 g/wk (5 standard drink/wk) for female, and \>140 g/wk (10 standard drink/wk) for male.
• One standard drink contains roughly 14 grams of pure alcohol, which is found in: 12 ounces of regular beer, 5 ounces of wine or 1.5 ounces of distilled spirits. Vigorous-intensity physical activity, defined as more than 150 minutes per week of moderate-intensity, or 75 minutes a week of vigorous-intensity aerobic physical activity, or an equivalent combination of both.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Tornto General Hospital, UHN

Toronto, Ontario, M5G 1L7, Canada

RECRUITING

MeSH Terms

Conditions

Ketosis; Hyperlipidemias; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders

Study Officials

• Gary F Lewis, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gary F Lewis, MD

CONTACT

416-340-4270; gary.lewis@uhn.ca

Majid Mufaqam Syed Abdul, PhD

CONTACT

416-581-7487; MajidMufaqam.SyedAbdul@uhnresearch.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to either the ketogenic diet or the LGIT diet for 8 weeks. Once they complete the first diet, they will go under a washout period for 8 weeks before they start the second diet.

Study Record Dates

• First Submitted: October 21, 2021
• First Posted: November 2, 2021
• Study Start: October 12, 2021
• Primary Completion: December 31, 2022
• Study Completion: June 30, 2023
• Last Updated: November 9, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)