Effects of a Very Low Carbohydrate Ketogenic Diet or Mediterranean Diet on Markers of Musculoskeletal Health in Older Adults

Aging Clinical Trial

Official title:

Effects of a Very Low Carbohydrate Ketogenic Diet Versus Mediterranean Diet on Markers of Bone Health and Muscle Function in Older Adults: A Pilot Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06203392
• Other study ID #: IRB202301329
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: University of Florida
• Contact: Cora Best, PhD, RDN
• Phone: 352-294-3751
• Email: corabest[@]ufl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Preclinical data indicate that very low carbohydrate ketogenic diets (KD) may prevent progression of age-related sarcopenia (skeletal muscle decline) but also may disturb bone metabolism. The investigators will pilot test a randomized trial comparing the effects of short-term adaptation to a well-formulated ketogenic diet and Mediterranean diet on markers of bone metabolism and muscle function in older adults. The expected results will help inform the benefit-risk assessment for older patients considering longer term use of KD therapy.

Description:

Eucaloric very low carbohydrate ketogenic diets (KD) are therapeutic diets that mimic fasting by generating ketones for metabolic fuel while meeting nutritional requirements (nutritional ketosis). Nutritional ketosis may broadly benefit healthspan through mechanisms such as suppression of inflammation or induction of autophagy, and preclinical and emerging clinical data indicate that KD therapy may help slow progression of age-related conditions including sarcopenia. However, questions remain about the benefits and risks of KD, especially relative to recommended therapeutic diets such as the Mediterranean Diet (MD) for which there is evidence of benefit for age-related conditions. For example, KD has shown efficacy for weight loss, which could reduce ectopic lipid accumulation that weakens muscle and bone. KD has been shown to increase skeletal muscle mitochondrial mass, mitochondrial activity, and strength in aged mice, possibly by increasing peroxisome proliferator-activated receptor activity and preserving fast-oxidative fibers that typically decline with age. However, long term use of KD may adversely impact bone. KD can cause deterioration of bone in juvenile mice without evidence of undernutrition and is associated with skeletal demineralization in children being treated for drug-resistant epilepsy.

Given the burden of musculoskeletal disease in older Americans, it is vital to understand the effects of KD on the musculoskeletal system of older adults to inform the benefit-risk assessment for an older patient and to optimize the effectiveness of KD for age-related conditions. The investigators are conducting a pilot test of a randomized clinical trial comparing the effects of short-term adaptation to a well-formulated KD and MD on markers of bone health and muscle function in older adults. The investigators will supply fresh prepared meals to achieve high adherence to the dietary interventions and adequate contrast in metabolic state between treatment groups.

Potential participants will complete a screening process so the investigators can determine whether potential participants are eligible to enroll in the study. At the first screening visit, the study team will measure blood pressure, height, and weight. Individuals will complete questionnaires that collect information about their health history, dietary intake, and physical activity habits. No more than 50 mL of blood will be collected from potential participants to run routine clinical lab tests to evaluate health status.

If an individual remains eligible after the first screening visit, they will be invited to complete a 24-hour urine collection (at home) and to schedule a second screening visit. At the second screening visit, a physician will conduct a physical exam and assess their body composition with an x-ray technology called dual-energy x-ray absorptiometry (DEXA or DXA).

If an individual remains eligible after the second screening visit, they will be invited to enroll in the dietary intervention study. Once enrolled, the participant will be assigned to either a very low carbohydrate ketogenic dietary pattern or a Mediterranean dietary pattern. The investigators will provide most of the food the participant will need each day in the form of a nutrition shake (breakfast) and two prepared meals (lunch and dinner). A study dietitian will be available to provide continuous support through a secure messaging app.

While in the dietary intervention phase of the study, participants will come to the UF Clinical and Translational Science Building once a week for 6 weeks. The study team will measure participant blood pressure and weight at each visit. At the first, middle, and final visits, the study team will collect a blood sample and urine sample from participants for lab testing, and participants will complete a short series of tests that measure physical performance.

Our ultimate research goal is to determine the effects of KD on body composition and clinically relevant measures of bone health and muscle function, as those data are needed to (1) inform the benefit-risk assessment for an older patient who is considering longer term adherence to KD therapy and (2) optimize the effectiveness of KD for age-related conditions.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: April 2026
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Postmenopausal

• BMI 20 to <35 kg/m2

• Weight stable for last 12 months

• Male or female biological sex

• Willing to eat supplied food and adhere to dietary advice

• Willing to document food intake

• Willing to maintain weight

• Willing to attend study visits

• Smartphone ownership

• Community-dwelling with permanent living arrangement

• Resides within 30 miles of Gainesville, FL

• Willing to avoid alcohol intake

• Estimated energy requirement = 2,600 kcal/day

• Have a refrigerator and means to reheat food within dwelling

• Bone mineral density tested within past 5 years or U.S. ethnicity-specific fracture risk assessment tool (FRAX) indicates ten year-probability of hip fracture <3% and ten year-probability of major osteoporotic fracture <20%

Exclusion Criteria:

• Pre- or peri-menopausal

• Fracture in past 6 months

• Circulating 25-hydroxyvitamin D < 20 ng/mL at screening

• History or prevalence of metabolic bone disease

• Chronic kidney disease diagnosis or eGFR <60 mL/min/1.73 m2 at screening

• Current or history of cancer excluding non-melanoma skin cancer

• Clinical cardiovascular disease, excluding current use of anti-hypertensive medication

• LDL cholesterol at screening that is elevated (= 160 mg/dL) or uncontrolled (= 100 mg/dL despise current statin treatment)

• History of recurrent kidney stones

• Current diabetes diagnosis or hemoglobin A1C = 6.5% at screening.

• Liver disease

• Pancreatic disease

• Alcoholism diagnosis or heavy drinking per CDC definition

• Currently smoke tobacco

• Malabsorption disease including celiac and inflammatory bowel disease

• Inborn error of metabolism including disorders of fatty acid transport or oxidation, organic aciduria, porphyria, or familial hyperlipidemia

• Dementia diagnosis

• Dietary restrictions including food allergy, vegetarianism, veganism or gluten, dairy, or seafood avoidance

• Current or history of diagnosed eating disorder

• Thyroid disorder

• Male hypogonadism

• Menopause before age 40 years

• Gender-affirming hormone therapy

• Currently eat a ketogenic or Mediterranean diet based on ASA 24-hour dietary recall and Mediterranean diet screener

• Currently consume > 500 mg/day supplemental calcium from all sources or the equivalent of = 2,000 IU/day supplemental vitamin D from all sources or any single oral dose of vitamin D = 14,000 IU on a regular basis

• Participation in concurrent research study

• Currently homeless

Related Conditions & MeSH terms

• Aging
• Musculoskeletal Diseases

Intervention

Other:
• Very low carbohydrate ketogenic diet
Very low carbohydrate ketogenic diet provided for six weeks
• Mediterranean diet
Mediterranean diet provided for six weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Bone turnover markers	Serum CTX, urine NTX, serum TRACP-5b, serum P1NP, serum BSAP, serum osteocalcin	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Body fat percentage	Body Fat Percentage measured by dual-energy x-ray absorptiometry	Pre-intervention; during the intervention (at 6 weeks into the intervention)
Other	Fat mass index	Fat Mass Index measured by dual-energy x-ray absorptiometry	Pre-intervention; during the intervention (at 6 weeks into the intervention)
Other	Visceral Adipose Tissue	Visceral Adipose Tissue (VAT) measured by dual-energy x-ray absorptiometry	Pre-intervention; during the intervention (at 6 weeks into the intervention)
Other	Fat Free Mass Index	Fat Free Mass Index measured by dual-energy x-ray absorptiometry	Pre-intervention; during the intervention (at 6 weeks into the intervention)
Other	Skeletal Muscle Mass	Skeletal Muscle Mass measured by dual-energy x-ray absorptiometry	Pre-intervention; during the intervention (at 6 weeks into the intervention)
Other	Appendicular Lean Mass to Height Ratio	Appendicular Lean Mass to Height Ratio measured by dual-energy x-ray absorptiometry	Pre-intervention; during the intervention (at 6 weeks into the intervention)
Other	Predicted resting metabolic rate	Resting Metabolic Rate estimated from dual-energy x-ray absorptiometry data	Pre-intervention; during the intervention (at 6 weeks into the intervention)
Other	24-hour urine analytes	A standardized report from 24-hour urine studies	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Handgrip strength	Handgrip strength measured by dynamometer	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Total balance test score	Results of balance tests performed as part of the short physical performance battery	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Gait speed test score	Results of gait speed tests performed as part of the short physical performance battery	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Chair stand test score	Results of chair stand tests performed as part of the short physical performance battery	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Circadian clock gene expression	Relative expression of circadian genes in whole blood collected in PAXgene blood RNA tubes	Pre-intervention; during the intervention (at 6 weeks into the intervention)
Other	Vitamin D status	Circulating concentrations of vitamin D metabolites	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Circulating parathyroid hormone (PTH) concentration	Circulating concentration of parathyroid hormone	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Anion gap	Anion gap from comprehensive metabolic panel	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Insulin	Circulating insulin concentration	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Glucagon	Circulating glucagon concentration	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	IGF-1	Circulating IGF-1 concentration	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Beta-hydroxybutyrate	Circulating beta-hydroxybutyrate concentration	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Blood lipids	Total Cholesterol, Triglycerides, HDL Cholesterol, LDL-Cholesterol, Non-HDL Cholesterol	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Other	Cystatin C	Serum cystatin C	Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Primary	Rate of enrollment	Number of participants enrolled in dietary intervention phase per month	Monthly. Up to 24 months.
Primary	Screen failure rate (percentage)	Number of participants deemed ineligible / number of participants screened * 100	Monthly. Up to 24 months.
Primary	Treatment-specific retention rates	Percentage of participants enrolled in dietary intervention phase who complete at least 6 intervention study visits including baseline, middle, and final visit.	Either after the endline visit or when participant is withdrawn or withdraws from study
Secondary	Treatment-specific adherence rates	Treatment-specific adherence rates to protocol as evidenced by (1) dietary intake (2) blood ketone concentrations	Either after the endline visit or when participant is withdrawn or withdraws from study