Level Best Study

EFFECT OF A NEW NUTRITIONAL SUPPLEMENT (LEVEL BESTä) ON BLOOD GLUCOSE AND BLOOD LIPID PARAMETERS

Study #10

Principal Investigator:

Steve Freed, RPh, Diabetes Educator,

DiabetesInControl.com

Deerfield, IL 60006

800 798-6972 

Patient Enrollment Begins: March 15, 2001

Patient Enrollment Ends: May 1, 2001

Conclusions of Study: September, 2001 

1.      PURPOSE OF PROTOCOL: 

A new food beverage/tablet combination has been developed, which contains ingredients that may favorably modulate blood parameters in patients with diabetes mellitus.  The product contains nutrients, which have been shown in clinical studies to lower both fasting and postprandial blood glucose concentrations.  These include low-glycemic-index carbohydrates (Liu S, et al. Am J Clin Nutr 2000; 71:1455), chromium (Anderson RA. Diabetes 1997; 46:1786), and ginseng (Sotaniemi EA. Diab Care 1995; 18:1373).  Other ingredients are included which lower the risk of developing cardiovascular disease.  These include red yeast rice (a natural source of HMG-CoA reductase inhibitors), which lowers total and LDL-cholesterol concentrations (Heber D. Am J Clin Nutr 1999; 69:231), and willow bark, which contains salicin and dosed to provide 80 mg per day, to lessen platelet aggregation. 

The specific aim of this study is to determine if consuming this new beverage/tablet combination, twice a day with lunch and dinner, will favorably improve blood glucose and blood lipid parameters. 

2.      STUDY DESIGN: 

Hypothesis. We hypothesize that consumption of a new beverage/tablet combination twice a day will significantly lower fasting blood glucose concentrations and favorably improve blood lipids (lower total cholesterol and LDL-cholesterol levels).  The study design uses each patient as their own control, with baseline data serving as the control data.  

Inclusion criteria. Patient inclusion criteria are: 1) type 2 diabetes mellitus, which is managed by diet, diet and oral agents, or insulin; 2) hypercholesterolemia, fasting total cholesterol > 200 mg/dL; 3) fasting LDL-cholesterol > 100 mg/dL, 4) 21 years old or older. 

Exclusion criteria include: 1) using insulin; 2) s/p major cardiac co-morbidities (e.g. surgery); 3) renal insufficiency, BUN > 100 mg/dL and creatinine > 2.0 mg/dL; 4) significant gastroparesis; 5) currently taking any dietary supplements, not including a multi-vitamin and minerals tablet; 6) pregnant or nursing; 7) abnormal liver functions test; 8) taking cholesterol-lowering drugs, 9) type 1 diabetes. 

Study design. This is an open-label, prospective study.  Two weeks before the study starts, patients who meet the Inclusion Criteria, will have to monitor daily fasting blood glucose levels, and postprandial blood glucose after lunch and dinner. These data will be presented to the Study Coordinator at the patients’ clinic.  The patients will also need to have a total cholesterol and LDL-cholesterol level within in the past 6 months. Then, baseline blood tests will be drawn, and the patients provided the diet, Level Best. 

Patients will be instructed to keep a dairy of when they took the product and of any gastrointestinal side effects.  At week 4, patients need to go to their clinic in order to get more Level Best, and have laboratory measurements made for the second blood drawing.  The patient returns on week 8 for the final blood drawing. 

Blood measurements. Baseline fasting blood data will be obtained which include: total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and Hgb A_1C.  All of these parameters, except Hgb A_1C, will be assessed again at week 4 and week 8.  During the study, patients will be instructed to measure and record daily fasting blood glucose concentrations and 2 to 3-hour postprandial lunch and dinner levels throughout the 8-week study at home. 

The Diagnostics.  Patients will be provided with a HbA1c test at the onset and the conclusion of the study.  They will also be supplied with a Total Cholesterol Panel at the onset, at 4 weeks and at the conclusion in 8 weeks.  These tests can be used in the office or by the patient at home.  These tests are supplied at no cost to the patient.

The Diet. The test diet consists of a beverage, which is made by mixing 11 g of dry powder in 8 ounces of water, and 3 tablets.  All ingredients are non-pharmaceutical and are presently sold as dietary supplements or foods. The beverage and tablets are to be consumed with lunch and dinner.  The nutritional composition of the product is: 

One serving of the beverage provides: (1/2 carbohydrate exchange according to the American Dietetic Association) 

45 kcal (11 g and reconstituted in 8 ounces of water)

Carbohydrate = 7 g from fructose, psyllium, and barley

Protein = 2 g from whey protein

Fat = 1 g from partially hydrogenated vegetable oil (cottonseed and soy) 

3 tablets provide: 

100 mcg elemental chromium (the Estimated Safe and adequate dietary intake is 50 to 200 mcg/d; based on the RDA, National Academy of Science, Washington, D.C.)

50 mg ginseng

267 willow bark (equal to 40 mg salicin)

1,200 mg red yeast rice 

3.      DATA ANALYSIS / SUBJECT SELECTION 

We desire to test for a significant difference between the mean serum cholesterol levels of persons using this beverage and tablet combination to determine the power calculation (i.e., minimum number of people to include in the study).  In another published study (Heber D, Am J Clin Nutr 1999; 69:231), eighty-three subjects consumed 2.4 g of red yeast rice for 8 weeks.  The total serum cholesterol concentrations decreased from 254 ± 36 mg/dL to 208 ± 31 mg/dL and LDL-cholesterol concentrations from 179 ± 15 mg/dL to 134 ± 27 mg/dL.  We wish to test at the 0.05 level for significance with a 90% chance of detecting a true difference between population means as small as 40 mg/dL.  The estimated standard deviation is 33 mg/dL. 

Then, according to the equation of (1) of:

n ³ (2 (SD)²/d²) (t 0.05V + t 0.1V)²

Assuming a required significant level of a = 0.05, a power level of b = 1 – 0.10 = 0.90.  If the degree of freedom v = 19 (n = 20), then (from the t-distribution table): t 0.05, 19 = 2.093 and t 0.01 = 1.729.  n ³ (2* 1089)/1600) * (2.093 + 1.729)² = 19.85. 

Therefore, we consider that the study should contain at least 20 subjects, because each patient is serving as his own control.  The key variables needed to show product efficacy are:

·        fasting blood glucose

·        total cholesterol

·        LDL-cholesterol.

The overall significance of these variables will be made by one way repeated measurements of ANOVA with least significant difference test as the post-hoc correction.  At each time point, the results will also be analyzed by paired Student t-test to compare the differences between basal and 4 weeks, and between basal and 8 weeks after treatment (2). 

1. Reference: Zar JH. Biostatistical Analysis (2^nd ed.). Prentice-Hall, Inc., Englewood Cliffs, NJ, 1984, p 133

2. Statistical assistance provided by Dr. Pei-ra Ling, Beth Israel Deaconess Medical Center, Department of Nutrition, Boston, Massachusetts

4.      POSSIBLE BENEFITS: 

Patients who participate in this study may see reductions in fasting blood glucose levels, total serum cholesterol, and LDL-cholesterol concentrations.  Platelet aggregation may lessen.  If these changes occur, they will do so with nutrients and not additional medications. The implication is that additional benefit can be derived from a nutritional supplement in terms of improving abnormal blood parameters (glucose and lipids). The cost and associated side effects of dietary therapy are less than pharmaceutical management. 

5.      POSSIBLE RISKS: 

Possible side effects may occur like mild gastrointestinal pain, gas and bloating, and potentially, but unlikely diarrhea.  There may be interactions between prescribed or over-the-counter medications with the nutritional compounds found in the food product. The red yeast rice contains the active compound (HMG CoA reductase) found in many statins.  This may adversely affect liver function tests. 

6.  FLOW DIAGRAM FOR STUDY OF LEVEL BEST

Step 1/Pre-Monitoring: Patient screening to determine if they meet Inclusion Criteria. If so, patients need to collect 2 weeks of data for the following:

·        Daily fasting blood glucose

·        Daily postprandial (2-3 hours) blood glucose after lunch

·        Daily postprandial (2-3 hours) blood glucose after dinner

·        Need total and LDL-cholesterol level within past 6 months

Once these are collected, the following schedule is applicable.

 If you read the protocols and would like to participate, you can apply to enroll by clicking below.    

diabetesincontrol@home.com and 800-798-6972