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Low Carbohydrate Dietary Intervention Improves Insulin, Hormonal Levels and Inflammatory Markers in Early Stage, Postmenopausal Breast Cancer Survivors

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Conference Paper

Low Carbohydrate Dietary Intervention Improves Insulin, Hormonal Levels and Inflammatory Markers in Early Stage, Postmenopausal Breast Cancer Survivors

Abstract

Background: Obesity has been associated with decreased disease free survival and overall survival in postmenopausal breast cancer survivors. Proposed mechanisms for this finding include elevated estradiol levels, hyperinsulinemia, and increased inflammatory mediators. This feasibility study evaluated whether a low carbohydrate, calorie restricted dietary intervention could achieve weight loss and measurable metabolic changes in a group of obese postmenopausal breast cancer survivors. Methods: Twenty-three early stage estrogen receptor positive breast cancer survivors were enrolled on a low carbohydrate, calorie-restricted dietary intervention. At time of enrollment the patient had to be deemed postmenopausal and have a BMI >28. Patients were not allowed to have an underlying inflammatory condition or be receiving treatment for diabetes. The mean age was 57 years old (42-68) with a mean weight of 220 lbs (171-300) and mean BMI of 37 (28-48.5). All subjects had completed surgery and adjuvant chemotherapy. The majority of patients were on endocrine therapy with 61% on an AI and 35% on tamoxifen. The dietary intervention utilized 0.5g protein/pound (actual body weight), less than 40 grams of carbohydrates and 800-1200 calories per day. The program provided weekly coaching, meal replacement protein products and nutritional supplements. Subjects were medically monitored with brief physical exams and labs done every 2 weeks for the first 12 weeks, then monthly thereafter. Subjects were seen by a health coach every week. The average weight loss period spanned 23 weeks (7-59 weeks) due to the variance in weight loss goals aimed at a BMI ≤28. Results: The mean weight loss was 19.9% of total body weight, the equivalent of 43.7 pounds. Total body fat lost was 6.86%. Weight loss averaged 5.4 pounds in week one and 2.14 pounds per week in weeks 2-19. Statistically significant declines in the total estrogen level (p = 0.0345), estrone (p = 0.0296), and estradiol serum levels (p = 0.0296) were demonstrated. A rapid decline in fasting insulin level was seen with a 23% decline by Week 3 (p = 0.0959), 26% by Week 7 (p = 0.0139), and 42% by Week 19 (p = 0.0071). A statistically significant improvement in the CRP level compared to baseline was also demonstrated with a 40% decrease at Week 19 (p = 0.0272). Conclusions: Our results support that a low carbohydrate dietary intervention can be used to successfully achieve weight loss and improve metabolic parameters. This feasibility study provides additional support for larger trials evaluating the role of carbohydrate restriction in breast cancer survivors. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD2-5.
Objectives
Low Carbohydrate Dietary Intervention Improves Insulin, Hormonal Levels and Inflammatory
Markers in Early Stage, Postmenopausal Breast Cancer Survivors
Amy K. Krie, MD,1Krista N. Bohlen, PharmD,1,2 Yueshan Hu, PhD,2Cheryl Ageton, RN,1,2 Heidi Nickles, MS,1,2
Daniel Norfolk, RN,1,2 BSN,1,2 Julie Kittelsrud, RN, C-NP,2Reggie Thomes, BS,2Adam Fahrendorf, BA,2Jessica Muth, RD, LD,1
Luis A. Rojas-Espaillat, MD,1and Gareth E. Davies, PhD2
1Avera Cancer Institute, Sioux Falls, SD, 2Avera Research Institute, Sioux Falls, SD
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 10-14, 2013
Background
Conclusions
1. Body mass index of 25.0 kg/m2 or greater. Source: Behavioral Risk Factor Surveillance System, CD-ROM (1984-1995, 1998) and Public Use Data Tape (2004, 2006),
National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 1997, 2000, 2005, 2007.
2. Chlebowski, R, G Blackburn, C Thomson, et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study. J Natl
Cancer Inst 2006; 98: 1767-1776.
3. Demark-Wahnefried W, Peterson BL, Winer EP, et al: Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer
patients receiving adjuvant chemotherapy. J Clin Oncol 19: 2381-2389, 2001.
4. Ewertz, M, M-B Jensen, K Gunnarsdottir, et al. Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol 29:25-31, 2011.
5. McTiernan A, Rajan KB, Tworoger SS, et al: Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol 2003; 21: 1961-1966.
6. Sinicrope, F, A Dannenberg. Obesity and Breast Cancer Prognosis: Weight of the Evidence. JCO 2010; 4-7.
7. Jen, K, Z Djuric, N DiLaura, et al. Improvement of metabolism among obese breast cancer survivors in differing weight loss regimens. Obes Res 2004; 12:306-312.
8. Duggan, C, M Irwin, et al. Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer. JCO 2010; 29:32-39.
9. Samaha, F, N Iqbal, et al. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity. N Engl J Med 2003; 348 (21): 2074-2081.
10.Yancy, W, M Olsen, et al. A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet to Treat Obesity and Hyperlipidemia. Ann of Int Med 2004; 140:769-777.
1. Determine if patients could comply with dietary intervention and achieve weight loss.
2. Evaluate efficacy of dietary intervention on decreasing serum hormone levels.
3. Evaluate efficacy of dietary intervention on decreasing serum insulin and
inflammatory markers.
Obesity has been associated with decreased disease free survival and overall survival
in postmenopausal breast cancer survivors. Proposed mechanisms for this finding
include elevated estradiol levels, hyperinsulinemia, and increased inflammatory
mediators. This feasibility study evaluated whether a low carbohydrate, calorie restricted
dietary intervention could achieve weight loss and measurable metabolic changes in a
group of obese postmenopausal breast cancer survivors.
Results (cont.)
This presentation is the intellectual property of the author/presenter. Contact amy.krie@avera.org for permission to reprint and/or distribute. Printed by
Methods
Results
Decline in serum estradiol levels were approaching statistical significance (p=0.056).
1. A low carbohydrate dietary intervention can successfully be implemented in a group
of overweight breast cancer survivors to achieve significant amounts of weight loss.
2. A rapid and significant reduction in serum hormonal levels and serum inflammatory
markers can be achieved with dietary intervention.
3. This feasibility study provides additional support for larger trials evaluating the role of
carbohydrate restriction in cancer survivors.
170
190
210
230
250
012345678910 11 12 13 14 15 16 17 18 19 20
Average body weight
(lb)
Dietary intervention time (week)
Weekly Weight Loss
*
*****
**
The mean weight loss was
19.9% of total body weight, the
equivalent of 43.7
pounds. Total body fat lost was
6.86%. Weight loss averaged
5.4 pounds in week one and
2.14 pounds per week in weeks
2-19.
A rapid decline in fasting insulin level was seen with a 23% decline by
Week 3 (p=0.0959), 26% by Week 7 (p=0.0139), and 42% by Week 19 (p=0.0071). References
Demographics
N= 24
Mean (range)
Age
57 years (42-68)
Weight (pre-diet)
220 lbs (171-300)
BMI (pre-diet)
37 (28-48.5)
Endocrine Therapy
AI (61%)
Tamoxifen (35%)
Weight Loss Period
23 weeks (5-59)
Eligibility Criteria
Early Stage ER+ breast cancer survivor
Postmenopausal
BMI >28
Completed surgery & adjuvant chemotherapy
No underlying inflammatory condition
No treatment for diabetes
0
1
2
3
4
5
6
7
8
0
5
9
11
15
19
Serum Estradiol levels (pg/mL)
Dietary Intervention time (weeks)
Serum Estradiol Levels
** *
0
2
4
6
8
10
12
14
3
7
11
15
19
Average fasting insulin level
(μUnits/ml)
Dietary Intervention time (weeks)
Serum Fasting Insulin Levels
Protein Meal
Product
Replacements
(0.5 g protein/lb
actual body
weight),
<40 gm carbs,
800-1200
calories/day
Weekly Session
with Health
Coach
Medical
Monitoring (brief
physical exam)
Labs every 2
weeks x 12
weeks, then
every month
** * *
A statistically significant improvement in the CRP level compared to baseline was also
demonstrated with a 40% decrease at Week 19 (p=0.0272).
0
1
2
3
4
5
6
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Serum CRP (mg/L)
Dietary intervention time (weeks)
Serum C-Reactive Protein Levels
* * * * *
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