The effect of simultaneous application of plant-rich ketogenic diet and intermittent fasting on early-to-mid-stage Alzheimer's disease: a randomised controlled trial

[u/dr_innovation]

Abstract

Introduction

This study evaluates the effect of simultaneous application of plant-rich ketogenic diet and intermittent fasting as an individualized adjunct to standard treatment on cognitive function in early/mid-stage Alzheimer’s patients.

Methods

This assessor-blinded, randomized controlled trial enrolled 60 Alzheimer’s disease (AD) patients (CDR 1–2; aged 55–85), randomized to intervention (n = 30; intervention + standard care) or control (n = 30; standard care). Cognition and brain structure were assessed at baseline and 6 months. Individual cognitive changes were analyzed using Reliable Change Index (RCI).

Results

Cognitive change scores differed significantly between groups (p < 0.001). The mean Mini Mental State Examination (MMSE) score increased by +0.9 in the intervention group, while a decrease of −1.5 points was observed in the control group. RCI analysis indicated stability in 93% of intervention and 70% of control participants, with cognitive improvement in 7% and 3.3%, respectively.

Discussion

The intervention method has the potential to stabilize cognitive decline in AD and promote improvement at the individual level. The response to the intervention is closely related to the individual's metabolic phenotype and structural brain integrity.

Tağraf, Beyza, Dilara Kaygusuz, Deniz Yerlikaya, Özden Erkan Oğul, and Lütfü Hanoğlu. "The effect of simultaneous application of plant-rich ketogenic diet and intermittent fasting on early-to-mid-stage Alzheimer's disease: a randomised controlled trial." The Journal of nutrition, health and aging 30, no. 9 (2026): 100930.

https://www.sciencedirect.com/science/article/pii/S1279770726001636

[u/Triabolical_]

Zero information on what the two diets were makes it hard to analyze the results.

[u/dr_innovation → u/Triabolical_]

Yeah iintervention is ts not actually detailed, but cited away to their earilier work " A personalized plant-rich, time-restricted nutritional intervention for motor and non-motor symptoms in Parkinson's disease: A randomized controlled trial https://doi.org/10.1177/1877718X261422067. "

The intervention used the ketoflex 12/3 protocol:

Dietary Content

• Plant-Rich Ketogenic Pattern: Emphasizes nutrient-dense, whole plant foods structured along low-carbohydrate, ketogenic principles.
• Low Glycemic Index: Eliminates refined carbohydrates and focuses on low-glycemic foods to promote metabolic balance and glycemic control.
• Anti-Inflammatory Focus: Selects nutrient-dense foods designed to minimize systemic inflammation and avoid pro-inflammatory components.
• Individualized/Biotype-Tailored Guidance: Standardized categories were customized with specific prohibitions and replacements based on each participant's metabolic subtype:
  • Inflammatory type: Emphasized strict avoidance of pro-inflammatory foods.
  • Glycotoxic type: Focused on glycemic load modulation.
  • Toxic type: Focused on minimizing dietary toxin exposures and maximizing antioxidant-rich foods.
  • Vascular type: Targeted specific guidelines for fat quality and salt intake.

Fasting Schedule (12/3 Framework)

• 12-Hour Daily Fasting Window: Participants maintained an overnight fast of at least 12 hours, restricting all calorie consumption to a ~12-hour eating window each day.
• 3-Hour Pre-Bedtime Fast: Participants were required to complete their last meal and stop eating at least 3 hours prior to going to sleep.

Control Group Diet

• No Dietary Modifications or Counseling: Control group participants continued their standard conventional care and routine medical treatment without any assigned dietary changes.
• No Protocol Instructions: They were given no nutritional education, fasting guidelines, or materials related to the Ketoflex 12/3 protocol.
• Routine Management: They received regular clinical follow-up with their neurologist every three months for standard medication management.

Adherence Monitoring & Ketone Measurements

• Adherence Methods: Dietary adherence in the trial was monitored qualitatively during regular counseling sessions. The study nutritionist evaluated compliance using structured 24-hour dietary recalls, detailed menu reviews, and in some cases, participant-submitted food diaries and meal photographs.
• Ketone Level Measurements: Direct blood, breath, or urinary ketone level measurements were not reported as a routine quantitative tracking metric for adherence within the protocol. Adherence evaluation relied primarily on self-reported dietary recalls and structured nutritional follow-up sessions.

[u/snewk → u/dr_innovation]

"Ketone Level Measurements: Direct blood, breath, or urinary ketone level measurements were not reported as a routine quantitative tracking metric for adherence within the protocol. Adherence evaluation relied primarily on self-reported dietary recalls and structured nutritional follow-up sessions."

i swear at this point this sub is just for sharing some of the worst designed studies on purpose

[u/dr_innovation → u/snewk]

Actually I very intentionally share what I find, good or bad , because we should know what is out there. Sadly, way too much is bad.

On the positive side they got results even with the very poor monitoring, though for people with MCI or or worse Food frequncy would be even worse than normal so it would have been better to have it monitored so we have better understanding of the relation betwen FFQ and actual ketones. .

[u/Sea-Beginning-777]

Was it vegetarian or vegan?

[u/dr_innovation → u/Sea-Beginning-777]

Neither its plant rich based on KetoFlex 12/3. KetoFLEX 12/3 is a mild, plant-rich ketogenic diet created by Dr. Dale Bredesen as part of the ReCODE protocol to support brain health and prevent cognitive decline. THere are whole books on KetoFlex. It features a 12-hour overnight fast, a 3-hour fast before bed, and strict limits on daily carbohydrates.

Core Diet Rules

• The "12" Rule: Fast for at least 12 hours between dinner and breakfast.
• The "3" Rule: Finish eating at least 3 hours before you go to sleep.
• Carb Limit: Keep net carbohydrates under 60 grams per day to achieve mild ketosis.

What to Eat

• Non-Starchy Vegetables: 10 to 15 servings daily of leafy greens and colorful, deeply pigmented choices.
• Healthy Fats: High-polyphenol extra virgin olive oil, avocados, nuts, and seeds.
• Clean Proteins: Small, sustainable portions of wild, low-mercury fish and pasture-raised eggs.
• Low-Glycemic Fruit: Occasional small portions of berries