Swiss Re AG · SIX:SREN
Swiss Re — Technical Presentation (October 2023)
33 slides from Swiss Re's technical presentation, October 2023
Slide 1: Ketogenic Diets for Mental Health: Clinical Trials
Ketogenic Diets for Mental Health: Clinical Trials Georgia Ede MD Nutritional and Metabolic Psychiatry www.diagnosisdiet.com
Slide 2: Insulin Resistance and/or Cerebral Glucose Hypometabolism
Insulin Resistance and/or Cerebral Glucose Hypometabolism Depression1 Borderline personality disorder6 Post-traumatic stress disorder2 Obsessive compulsive disorder (hoarding type)7 Bipolar disorder3 Anxiety disorders in children with Schizophrenia4 obesity8 Attention deficit hyperactivity disorder
Slide 3: Metabolic Dysfunction and Mental Health
Metabolic Dysfunction and Mental Health Newly diagnosed Newly diagnosed Pre-diabetes bipolar disorder schizophrenia 2.7 X 3.5 X 3.7 X more likely to develop more likely to have more likely to have major depression1 metabolic syndrome2 insulin resistance3 1. Watson KT et al. Am J Psychiatry 2021; 2.
Slide 4: IR Associated with Bipolar Severity
IR Associated with Bipolar Severity Bipolar (types 1 and 2) n=121 patients, age 30’s–50’s 32% 22% More likely: Rapid cycling Chronic symptoms IR DMII Lithium-refractory (BMI predictive) Calkin CV, Alda M. Bipolar Disord. 2015.
Slide 5: IR Reversal Eases Bipolar Depression
IR Reversal Eases Bipolar Depression N=45 patients with bipolar disorder and insulin resistance 20 received Metformin 25 received placebo IR resolved in 10/20 IR resolved in 1/25 34 remained IR 11 resolved IR MADRS Score HAM-D Score CGI-BP 35 20 4.5 18 4 30 16 IR 3.5 IR 25 IR 14 3 12 20 2.5 10 15 2
Slide 6: Almost 90% of the patients in the TRIO-BD study had not had a single remission
Almost 90% of the patients in the TRIO-BD study had not had a single remission in 25 years. It has been a relief to discover a new mechanism-based treatment that can get these patients better. —Dr. Cynthia Calkin
Slide 7: Ketogenic Diets for Schizophrenia
Ketogenic Diets for Schizophrenia 1965: 10 hospitalized women, KD x 2 wks1 “Significant improvement” ……………………………………………………………………….…………………… 2009: 70-yo woman with lifelong schizophrenia KD x 12 mos 2 Long-term resolution of visual/auditory hallucinations, medications discontinued 2017: 33-yo man, 31-y
Slide 8: Ketogenic Diets for Binge Eating
Ketogenic Diets for Binge Eating 30g carbohydrate per day: Binge episodes/week Binge episodes/week Patient Weight loss at start after 6 months 54 yo woman 14+ 0 37 lbs 34 yo man 8-11 0 44 lbs 62 yo woman 8-10 0 22 lbs Carmen M et al. J Eating Disorders. 2020.
Slide 9: Ketogenic Diet for Anorexia
Ketogenic Diet for Anorexia Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity https://doi.org/10.1007/s40519-022-01455-x BRIEF REPORT ® Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study
Slide 10: Carnivore Diet for Anorexia
Carnivore Diet for Anorexia NG Norwitz et al. J Ins Resist. 2023
Slide 11: Alcohol Dependence
Alcohol Dependence 2021 Randomized controlled trial 3-week inpatient alcohol withdrawal management program 19 pts on classic 4:1 KD vs 14 pts on SAD (serum BHB 1.6 mM rising to >4 mM) Fewer cravings and Required ~50% less benzodiazepine (oxazepam/Serax) Wiers et al. Sci Adv. 2021.
Slide 12: Autism Spectrum Conditions
Autism Spectrum Conditions Three 6-month clinical trials (plus two case reports1,2) • 2003: n=30, cyclical KD. 18/23 completers experienced 10 – 33% improvement3 (serum BHB 0.8 to 2.2 mM) • 2017 RCT: n = 45. KD outperformed a gluten-free/casein-free diet vs. no benefit on balanced diet4 (in ketosis
Slide 13: Mild Cognitive Impairment / Early Alzheimer's
Mild Cognitive Impairment /Early Alzheimer’s 2012: 23 pts w MCI; ~34g CHO/day x 6wks1 Small, statistically significant improvement on long-term memory tests 2018: 10 pts w early AD; ~45g CHO/day + MCT oil x 6wks 2 Small, statistically significant improvements on cognitive tests in 9/10 2019: n=27 pt
Slide 14: Dementia in the Context of Down Syndrome
Dementia in the Context of Down Syndrome 47 yo woman with Down Syndrome KD x 6 wks and obesity (BMI 47) (BHB 0.8 mM – 3.0 mM): Rapidly progressing dementia, • Seizures stopped paranoia, and seizures x 4 years • Paranoia resolved ADL dropped from 57/78 to 34/78 • ADL score 58 • Vocabulary expanded Bo
Slide 15: VIRTA: Ketogenic Diet for Depression
VIRTA: Ketogenic Diet for Depression Non-randomized, uncontrolled study 262 outpatients with T2DM; 36 with mild clinical depression Depressive symptoms score Mildly ketogenic diet Mood improved modestly in all patients More than half with clinical depression had achieved remission at week 10 Adams R
Slide 16: KD for Serious Mental Illness (2022)
KD for Serious Mental Illness (2022) Clinique du Castelviel Castelmarou, France
Slide 17: KD for Serious Mental Illness (2022)
KD for Serious Mental Illness (2022)
Slide 18: Study Participants
Study Participants Bipolar disorder n=12 Schizophrenia 31 28 n=10 enrolled >2 weeks on the Major Depression keto diet n=6 Average hospital stay: 85 days Average diet duration: 59 days
Slide 19: Study Participants
Study Participants 71% female; 29% male Average age: 50 years old (27-73) Average duration of care : 10 years (5 mos – 30 years) Average number of medications: 5 (25/28 taking at least one antipsychotic medication) All had at least one marker of poor metabolic health
Slide 20: Dietary Intervention
Dietary Intervention 15-20% Protein • Meat, seafood, poultry, eggs 5% Carbohydrate • 2 cups salad vegetables per day (20g) • 1 cup cooked non-starchy vegetables per day 75-80% Fat • 1 snack box (e.g. nuts, cheese, boiled egg)
Slide 21: Mental Health Measures
Mental Health Measures Hamilton Depression Montgomery-Åsberg Positive and Negative Rating Scale Depression Rating Scale Syndrome Scale (HAM-D) (MADRS) (PANSS) 35 40 120 30 35 100 25 30 80 25 20 20 60 15 15 40 10 10 5 20 5 0 0 0 start end start end start end Scale of 0 – 52 Scale of 0 – 60 Scale of 3
Slide 22: Effect Sizes Compared to Medication
Effect Sizes Compared to Medication MADRS PANSS 3.6 3.5 HAM-D 3.1 Cohen’s d effect size:3 0.5 0.8 large 0.3 0.5 medium 0.2 small Antidepressants1 Ketogenic Diet Antipsychotics2 Ketogenic Diet 1. Hengartner MP, Plöderl M. Front Psychiatry. 2018; 2. Leucht S et al.Schizophr Bull. 2022; 3. Lakens D. Fr
Slide 23: Clinical Global Impressions Severity Scale (CGI-S)
Clinical Global Impressions Severity Scale (CGI-S) 100% participants improved (within ~3 weeks) CGI-S score 44% reached CGI-S = 1 (clinical remission) Number of days on ketogenic diet
Slide 24: Metabolic Health Measures
Metabolic Health Measures FBG: 8.1% Trig: 14.8% AST: 9.0% HbA1c: 3.5% Total Chol: 4.4% GGT: 21.0% SBP: 7.6% LDL-C: 0.5% ALT: 1.4% DBP: 7.4% HDL-C: 8.4% Weight: 5.3% Values in bold are statistically significant
Slide 25: Change in Medication
Change in Medication ag oF Bipolar disorder n=12 =6 disorder n =10 Schizoaffective disorder n =28 Overall n MM Adjusted (No change [Ml Increased MM Reduced
Slide 26: Limitation
Limitation Study treatment conditions Prior treatment conditions No control group + KD – KD
Slide 27: What Can We Say?
What Can We Say? Feasible Safe Well-Tolerated* Low-Risk, High Potential Benefit *mild keto flu symptoms <2 wks 2/28 pts experienced GI upset <4 weeks
Slide 28: Studies Under Way
Studies Under Way Bipolar Disorder Alzheimer’s Disease S. Sethi, Stanford Univ R. Swerdlow, Univ of Kansas H. & I. Campbell, Univ of Edinburgh S. Craft, Wake Forest Univ M. Lilimand, Hôpitaux de Paris Psychosis A. Ruusunun, Finland Substance Abuse Z. Sarnyai, James Cook University C. Wiers, U Penn J
Slide 29: Everyone Deserves a Metabolic Evaluation
Everyone Deserves a Metabolic Evaluation Fasting glucose (<90 mg/dl, <5.0 mM) Hemoglobin A1c (<5.7% ideal) Fasting total insulin (single digits mIU/L ideal) Waist : height ratio (<0.5 ideal) Triglycerides (<100 mg/dl or <1.1 mM) Triglyceride : HDL ratio (< 1.5 ideal) HOMA-IR (<1 ideal, >3 poor)
Slide 30: Look Before You Leap
Look Before You Leap Learn more about: Absolute and relative contraindications Medication management Safe navigation of keto-adaptation phase Medical care coordination
Slide 31: Learn More
Learn More January 23, 2024 Learn more at diagnosisdiet.com/training
Slide 32: Ketogenic Diets for Mental Health Resources
Ketogenic Diets for Mental Health Resources MetabolicMind.org
Slide 33: A Promising Alternative or Adjunctive Therapy
A Promising Alternative or Adjunctive Therapy