Background: Study Details

Tan-Shalaby et al.
Nutrition & Metabolism (2016) 13:52 Page 2 of 12
Background that were measurable and avid on FDG PET/CT imaging.

Emerging evidence indicates that ketogenic diets can None were on chemotherapy at the time of enrollment,
have therapeutic potential for a broad range of cancers and all had good performance status (ECOG 0–2). Exclu-
in preclinical animal models and in patients [1–6]. A sion criteria included cases of active gout or kidney stones,
ketogenic diet is a high-fat low carbohydrate diet that active cardiac disease, cachexia, poorly controlled diabetes,
was developed originally to treat refractory epilepsy [7]. liver dysfunction (alanine/aspartate aminotransferase)
KDs create a metabolic state similar to that seen in ALT/AST >3 x upper limits of normal (ULN) if with liver
water-only fasting, where blood glucose levels are re- metastasis and > 5 x ULN if no liver metastases), renal
duced and blood ketone bodies (D-β-hydroxybutyrate failure (serum creatinine of > 2.0 mg/dl) or known brain
and acetoacetate) are elevated [7, 8]. Warburg first metastatic disease.
showed that aerobic fermentation (lactate production
in the presence of oxygen) was a hallmark feature of Study details
many cancers [9]. This unusual metabolism of tumor Primary endpoint was safety and feasibility. We investi-
cells later became known as the Warburg effect [10]. gated quality of life parameters and used a modified
Aerobic fermentation was considered a compensatory Atkins diet as the standard diet for this trial. Patients
response to an underlying deficiency in oxidative phos- were allowed 20 to 40 g of carbohydrates per day, during
phorylation that could arise from any number of deficien- a two-day screening period and were advised on grocery
cies in the structure, function or number of mitochondria shopping, and menu planning. We restricted consump-
[11]. Consequently, many tumor cells become addicted to tion of high carbohydrate foods such as cereal, bread,
glucose for survival and growth [8, 12, 13]. KDs could rice, pasta, potatoes and all fruits, but did not restrict
therefore put tumor cells under metabolic stress in calories, protein or fats (Table 1).
lowering the availability of glucose and in elevating Declining performance status, worsening disease,
blood ketone bodies that require functional mitochon- grade 3-weight loss, or inability to maintain at least trace
dria for metabolism [13, 14]. ketosis were criteria for removal. Eligible patients were
Most normal cells of the body readily metabolize evaluated at weeks 4, 8, 12 and 16 or until disease pro-
ketone bodies for energy especially when glucose levels gression or voluntarily termination. Patients used ver-
become reduced. Indeed, ketone bodies are considered a sion three of the European Organisation for Research
super fuel since they enhance the ΔG of Adenosine tri- and Treatment of Cancer Quality of Life Questionnaire-
phosphate ATP hydrolysis while reducing production of c30 (EORTC QLQ-c30). Periodic history and physical
reactive oxygen species (ROS) through the co-enzyme Q examinations included measures of height, weight and
couple [15]. In contrast to normal cells, the glucose- blood pressure. Blood was drawn (5 cc.) at mid-morning
dependent tumor cells cannot use ketone bodies effect- (between 10 AM-12 noon) during the appointed visit
ively for energy [16]. Ketone bodies can increase ROS in days, and was evaluated for a complete blood count,
tumor cells, which can be lethal to these cells [2]. Hence, metabolic panel 14, (including electrolytes, uric acid,
diets that can target glucose availability while elevating renal, liver and cholesterol profile), and for serum
circulating ketone bodies can be a non-toxic therapeutic ketone/beta-hydroxybutyrate determinations. All blood
strategy for managing those tumor cells that express the specimens were processed in the clinical pathology la-
Warburg effect. boratory (Pittsburgh VA Healthcare System) using 0.4 cc
The present study was conducted to evaluate the safety in Beckman DXC800 and DXH800 chemistry and cell
and tolerability of a modified Atkins diet on subjects with hematology analyzers. Patients were monitored for ad-
advanced cancers. Our secondary objective was to de- verse effects and diet tolerability. Tumors were evaluated
termine whether the diet influenced tumor stability or using PET /CT for heat imaging and RECIST version 1.1
progression based on changes in fluorodeoxyglucose criteria for size.
FDG and PET/CT imaging.
PET/CT scanning technique
Methods All patients with fasting blood glucose levels from 60 to
Recruitment and eligibility 180 mg/dl were included in the study group. The
This study was reviewed and approved by our hospi- patients received between 10–15 mCi of FDG intrave-
tal’s Independent Review Board (IRB) and listed on - nously, (~0.15 mCi/kg BW). An in-vivo incubation time
(https://clinicaltrials.gov/ct2/show/results/NCT01716468, of 60 min was allowed for optimal FDG accumulation to
Ketogenic Diet in Advanced Cancer). Patients were re- be seen in the tumor’s hypermetabolic areas. CT-PET
cruited from the Hematology Oncology outpatient clinic imaging was performed on a Philips-Gemini TF PET
of the Pittsburgh Veteran Affairs Healthcare System (Pitts- scanner. Time-of-Flight 3-D acquisition involved: 50 %
burgh, PA). All patients had advanced solid malignancies bed position overlap with acquisition time of 1.75 min

Background: Study Details

Uploaded by

Copyright:

Available Formats

Background: Study Details

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Background: Study Details

Uploaded by

Copyright:

Available Formats

Tan-Shalaby et al.

Nutrition & Metabolism (2016) 13:52 Page 2 of 12

Background that were measurable and avid on FDG PET/CT imaging.

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.