P.024 A multi-faceted lifestyle intervention for mitochondrial A8344G associated multiple symmetric lipomatosis (MSL): a successful patient initiated novel therapy

Background: A female carrying the common MERRF mitochondrial DNA A8344G mutation had multiple symmetric lipomatosis (MSL) as the primary disease manifestation. Methods: Case report of a mitochondrial disease patient treating her severe lipomas by lifestyle modifications including a modified ketogenic diet. Results: The patient required lipoma reduction surgery after a rapid rate of lipoma progression. Following a difficult recovery, the patient independently researched an alternative therapy for her disease. The intervention was multi-faceted (dietary, physical activity, meditation) and progressive over two years. A carbohydrate reduced (5–10% of calories) modified ketogenic diet was a major part of the treatment owing to its incidental success in MSL management in her brother for management of glioblastoma multiforme. The outcome of her intervention was positive: weight loss, lipoma size reduction, improvement in physical activity/strength, laboratory markers of insulin resistance, and sense of well including a return to full time work. Conclusions: A potential non-surgical therapy for mitochondrial disease associated MSL appears feasible over the short term. The success of the lifestyle intervention in MSL therapy is unprecedented and, importantly, was fully patient initiated. This novel therapy provides potential insight into the mechanism of MSL exacerbation: suggesting insulin resistance or other lifestyle modifiable factors as mediators of disease progression.

Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease

Background Brain energy metabolism is impaired in Alzheimer’s disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine whether a 12-week modified ketogenic diet improved cognition, daily function, or quality of life in a hospital clinic of AD patients. Methods We randomly assigned patients with clinically confirmed diagnoses of AD to a modified ketogenic diet or usual diet supplemented with low-fat healthy-eating guidelines and enrolled them in a single-phase, assessor-blinded, two-period crossover trial (two 12-week treatment periods, separated by a 10-week washout period). Primary outcomes were mean within-individual changes in the Addenbrookes Cognitive Examination - III (ACE-III) scale, AD Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory, and Quality of Life in AD (QOL-AD) questionnaire over 12 weeks. Secondary outcomes considered changes in cardiovascular risk factors and adverse effects. Results We randomized 26 patients, of whom 21 (81%) completed the ketogenic diet; only one withdrawal was attributed to the ketogenic diet. While on the ketogenic diet, patients achieved sustained physiological ketosis (12-week mean beta-hydroxybutyrate level: 0.95 ± 0.34 mmol/L). Compared with usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL (+ 3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+ 3.37 ± 6.86 points, P = 0.023) scores; the ACE-III also increased, but not significantly (+ 2.12 ± 8.70 points, P = 0.24). Changes in cardiovascular risk factors were mostly favourable, and adverse effects were mild. Conclusions This is the first randomized trial to investigate the impact of a ketogenic diet in patients with uniform diagnoses of AD. High rates of retention, adherence, and safety appear to be achievable in applying a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life, two factors of great importance to people living with dementia. Trial registration This trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202. The trial was registered on August 28, 2018.

Modified ketogenic diet in solid tumors: A Veteran Affairs Pittsburgh Healthcare System case series.

e14217 Background: Cancers prefer glucose due to mitochondrial dysfunction. Ketogenic diets fuel normal cells while starving cancer. Sparse data exists on ketogenic diets in solid tumors. Methods: Studied 5 advanced solid tumor patients on a modified ketogenic diet plus standard of care chemotherapy. Daily carbohydrate limited to 20-40 grams, no sweets or starch. Histories and clinical courses are presented. Results: Case 1: 70 year old male, medically inoperable Stage IIIA poorly differentiated squamous cell lung cancer and non-hodgkins lymphoma. Treated with radiation and paclitaxel/carboplatin. After 5 months, lung cancer relapsed in a neck mass, treated with chemoradiation plus the diet. At 46 months, scans and blood counts were normal. Case 2: 42 year old, 417 lb. male diabetic stage IV colon cancer, spread to lungs and liver. Progressed on 5FU/bevacizumab/oxaliplatin, irinotecan, tipiracil/trifluridine, regorafenib but responded to 5FU/irinotecan rechallenge plus liver chemoembolization. Dieted, mild ketosis but lost 64 lbs, stable disease at 6.5 years. Case 3: 42 year old male, Stage III BRAF V600 E melanoma, Vemurafenib intolerant. Bulky axillary nodes resected plus diet for 3 years. Complete remission at 7 yrs 9 months. Case 4: 57 year old male, medically inoperable liver cancer, normal AFP values and normal scans after 5 months of sorafenib. AFP later increased to 690 ng/ml. Advised to change treatment but he refused and started the ketogenic diet with the sorafenib. After 5 months, AFP improved to 445 ng/ml. Sorafenib and diet interrupted for 3 months, AFP rose to 1017. At 7 yrs, 4 months, back on sorafenib and diet, AFP 1520 mg/ml, negative scans. Case 5: 49 year old male, aggressive digital papillary skin adenocarcinoma, multi-organ metastases. Had side-effects with many chemotherapies (paclitaxel/bevacizumab/carboplatin, sorafenib, gemcitabine, oxaliplatin/5FU, cyclophosphamide) Stable disease on diet despite multiple therapy changes. At 34 months, he was off the diet, tumors grew plus new brain lesions (resected). Alive on atezolizumab at 36 months. Conclusions: Ketogenic diets in human solid tumors seem well tolerated and may improve response and survival after standard therapy.