Effects of a fasting-mimicking 5-day program and a Longevity Diet on age-related risk factors and aging biomarkers

Follow up Study of the Effects of the Longevity and the Fasting Mimicking Diet on Body Composition, Age-related Risk Factors and Biomarkers of Aging in a Randomized Study 1 and 2

This trial will test whether a 5-day fasting-mimicking diet, alone or combined with a Longevity Diet, helps improve body weight, body composition, cardiovascular risk markers, and aging-related biomarkers in adults aged 30–65, many of whom are overweight or have metabolic risk.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 135 (estimated)
• Sex: All
• Sponsor: Fondazione Valter Longo (other)
• Locations: 1 site (Varapodio, Calabria, Italy)
• Trial ID: NCT07255300 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label, three-arm trial enrolling 501 adults aged 30–65 to compare a 5-day fasting-mimicking diet (FMD) given once every three months, FMD plus a Longevity Diet (FMD+LD), and a control group maintaining their usual diet. Participants are randomized 1:1:1 (approximately 167 per arm) and followed over a six-month period to measure changes in body composition, BMI, cardiovascular biomarkers, metabolic parameters, and epigenetic/aging biomarkers. The FMD is a structured five-day meal program developed to mimic the effects of prolonged fasting without severe nutrient deprivation. The trial excludes people with recent major cardiovascular events, recent cancer, insulin-dependent diabetes, certain severe hypertension, pregnancy, and specific food allergies; it is conducted at a clinic in Varapodio, Calabria, Italy.

Who should consider this trial

Good fit: Adults aged 30–65 who are overweight (BMI >25) or have cardiovascular/metabolic risk factors, who are not pregnant and do not have recent cancer, recent myocardial infarction or stroke, insulin-dependent diabetes, severe uncontrolled hypertension, or excluded food allergies, are the best candidates.

Not a fit: People who are pregnant, insulin-dependent, have had major cardiovascular events or cancer in the past five years, have severe uncontrolled hypertension, or have excluded food allergies are unlikely to be eligible or to benefit from these dietary interventions.

Why it matters

Potential benefit: If successful, the interventions could help reduce weight, improve cardiovascular and metabolic risk markers, and favorably shift biomarkers linked to biological aging.

How similar studies have performed: Preclinical work and smaller clinical studies, including NIH-supported research at the Longevity Institute, have shown promising effects of FMD on weight and biomarkers, but long-term randomized data are still limited.

Eligibility criteria

Inclusion Criteria:

Subjects of 30-65 years of age;

Exclusion Criteria:

individuals with a family member already included in the study; individuals who are allergic to tree nuts (macadamia, cashew, almond, pecan), soy, oats, sesame, or celery/celeriac; pregnant females; Individuals with any documented cancer diagnosis within the past 5 years; documented myocardial infarction within past 5 years; documented cerebrovascular accident within past 5 years; chronic steroid use (longer than 45 consecutive days); insulin-dependent diabetes mellitus; individuals taking insulin or insulin-like drugs and individuals taking hypoglycemic agents other than metformin. In this last case, close attention will therefore be paid to the self-monitoring of blood glucose during the FMD cycles; Individuals with severe hypertension (systolic greater than 200 mmHg and or diastolic greater than 105 mmHg.

Change in prescription medications, over-the-counter (OTC) medications, medical foods, and nutritional supplements within 30 days prior to the start and for the duration of the study.

Use of medications classified as narcotics 15 days prior start and for the duration of the study.

Use of prescription medications and/or over-the-counter medications for acute and semi- acute medical conditions 15 days prior to start and for the duration of the study.

Use of acetaminophen is permitted on an as-needed basis. Use of an investigational drug or participation in an investigational study within 30 days prior to the start and for the duration of the study.

Use of oral or injectable corticosteroids within 30 days prior to the start and for the duration of the study.

Use of anticoagulant medications (heparin compounds or warfarin) within 30 days prior to the start and for the duration of the study. Use of aspirin 81 mg or 325 mg once daily is permitted.

Use of neuroactive prescription medications including major and atypical antipsychotic medications, anti-depressants, anti-anxiolytics, and epilepsy medications within 30 days prior to the start and for the duration of the study.

(subjects will not be allowed to discontinue prohibited prescription medications to meet enrolment criteria).

A history of allergy or intolerance to study products. Detailed descriptions of study product are included in Section 4.1 and 4.2, appended to the Study Informed Consent.

Clinically significant vital sign abnormalities (systolic blood pressure \<90 mmHg or \>200 mmHg, diastolic blood pressure \<50 mmHg or \>105 mmHg or resting heart rate of \<50 or \>100 bpm) at screening visit.

A serious, unstable illness including cardiac, hepatic, renal, gastrointestinal, respiratory, endocrinologic, neurologic, immunologic, or hematologic disease.

Known infection with HIV, TB or Hepatitis B or C.

A current diagnosis or personal history of:

Any cardiovascular disease including myocardial infarction, angina, cardiovascular surgery (within 5 years), congestive heart failure, cardiac arrhythmias or conduction abnormalities, cerebrovascular accident, transient ischemic attack (TIA), or peripheral vascular disease, deep vein thrombosis or pulmonary embolus. Diabetes mellitus requiring inhaled or injected insulin.

Any autoimmune disease such as inflammatory bowel disease (including Crohn's disease and/or ulcerative colitis), multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, polymyositis, scleroderma and/or thyroiditis.

Any significant liver or kidney disease such as cirrhosis or non-alcoholic fatty liver disease, glomerulonephritis, and/or ongoing dialysis treatment.

Any malignancy (with the exception of adequately treated malignancies with no known recurrence for \>2 years).

Any serious mental illness including a history of attempted suicide. Any medical condition that in the opinion of the primary care doctor or a specialist would preclude safe participation in this study or interfere with compliance.

Use of drugs of abuse (such as marijuana, cocaine, phencyclidine \[PCP\] and methamphetamine) 15 days prior to Day 1 and for the duration of the study.

History of regular intake of \>14 alcoholic drinks per week for females, and \>21 drinks per week for males (1 drink = 35 cl. beer, 12 cl. wine, or 30 ml. hard liquor).

Technical reasons

Any condition in which bioelectrical impedance testing would be impossible or uninterpretable (e.g. prostheses in extremities on both sides, limb amputation, implanted pacemaker, inability to lay still or supine, or skin defects on preferred electrode placement sites.

Other Exclusion Criteria: Inability to comply with study and/or follow-up visits.

Any concurrent condition (including clinically significant abnormalities in medical history, physical examination or laboratory evaluations) which, in the opinion of the PI, would preclude safe participation in this study or interfere with compliance.

Any sound medical, psychiatric and/or social reason which, in the opinion of the PI, would preclude safe participation in this study or interfere with compliance.

Abnormal laboratory findings including: abnormal blood counts (hematocrit \< 33% or \> 47%; WBC \< 3.0 or \> 12.0 x10\^3/mm3; platelets \< 140 or \> 500 x 10\^9/L); abnormal kidney function test (creatinine \> 2.5 mg/dL) or liver function test(s) (AST, ALT, alkaline phosphatase) \> 1.5X the upper limit of normal; serum calcium \> 11 mg/dL); serum K \< 3.5 mEq/L; Na \< 134 or \> 148 mmolL-1 Women of Childbearing Potential Contraception: the effects of the study products on the developing human fetus have not been studied extensively. For this reason, women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Females of childbearing potential will have a pregnancy test prior to receiving study products. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform study staff and her primary care physician immediately.

Pregnancy: because there is an unknown but potential risk for adverse events in pregnant women during treatment with the study products, pregnant women are not eligible for study participation.

Breast-feeding: Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study products, breastfeeding mothers are not eligible for study participation.

Where this trial is running

Varapodio, Calabria, Italy

• Ambulatorio Medico presso Biblioteca Comunale — Varapodio, Calabria, Italy, Italy (RECRUITING)

Study contacts

• Study coordinator: Romina Inés Cervigni

Conditions: Fat Mass, Risk Factors Cardiovascular Disease, Epigenetic Aging, Metabolism Changes, Overweight (BMI &gt, 25), Risk Behavior, Obesity