1. Barbara A. Gower, PhD UAB Department of Nutrition Sciences
“You can’t run from a bad diet*.” A dietary approach to prevention and treatment of cancer
Barbara A. Gower, PhD
UAB Department of Nutrition Sciences *

2. Obesity and Cancer
“Obesity is a major under-recognized contributor to the nation’s cancer toll and is quickly overtaking tobacco as the leading preventable cause of cancer.”
“As many as 84,000 cancer diagnoses each year are attributed to obesity, and overweight and obesity are implicated in 15% to 20% of total cancer-related mortality.”
J. Clin. Oncol. 32:3568, American Society of Clinical
Oncology Position Statement

3. Why is obesity associated with cancer?
High blood insulin,
High blood sugar, inflammation
Genes
Diet
Obesity
Diabetes
CVD
PCOS AD
Cancer
Obesity is a MARKER for a metabolic environment that predisposes to chronic diseases including cancer

4. Insulin (not obesity!) predicts breast cancer
Sub-cohort (n=2830) of WHI with fasting sera
497 incident cases of breast cancer over ~8 yr follow-up
Cancer Research :270

5. Insulin is commonly elevated in obesity; only insulin predicts BC* **
Adjusted for age, ethnicity, age at menarche and menopause, parity, 1st degree relative,
education, alcohol, physical activity, site, arm, study, assignment.

6. Insulin and cancer “Mitogenic”: causes cancer cells to divide
Promotes glucose (blood sugar) uptake
Cancer cells burn sugar as a fuel
Damaged “engines” (mitochondri)a
“Warburg effect” (aerobic glycolysis)
↑oxidative stress/inflammation/mutations
Prevents burning fat as a fuel
Normal products of fat burning inhibit cancer cell metabolism

7. Insulin is secreted in response to carbohydrate foods: sugar, starch, grain

8. Diet quality affects blood sugar and insulin
High glycemic load (standard)
vs.
Low glycemic load
(reduced carbohydrate) diet
Chandler-Laney and Gower 2014
Appetite, 80:236-41

9. Carbohydrate quality associated with breast density
5-yr longitudinal study; n=1668
Tested hypothesis that total carbohydrate (CHO), starches, sugars, or Glycemic Index, Glycemic load would increase risk for high mammographic breast density
Breast density is a risk factor for cancer
Masala G et al PLoS1 8:e70943

10. >Glycemic load = denser breast
Dietary Glycemic Load
>GL, total CHO, and simple sugar intake = >breast density

11. Our Model Genetic Oxidative Changes Stress CH3 Insulin Glucose
“Engines” of the cells;
Burn fuel, produce energy
(ATP)
Insulin
Glucose
Mitochondria
Genetic
Changes
Oxidative
Stress
Gene expression
↑Fermentation genes
↑Oncogenes
Myc
TOR
NFKB
CHOP
Ras
↓DNA repair genes
Mutations
CH3
Genomic instability

12. Summary: Obesity-cancer connection
Obesity is a “marker” for high blood sugar and high insulin
Cancer cells need sugar and insulin
Reducing sugar and insulin may reduce cancer risk
Reducing sugar and insulin could be used to treat cancer

13. Treatment of cancer with a carbohydrate restricted diet
10 cancer patients
Different types of cancer (lung, ovarian, etc.)
9/10 with progressive disease
28-d diet intervention (26-28 d)
“Ketogenic” diet
PET scan for glucose uptake
Serum insulin and ketones
Fine et al 2012 Nutrition 28:

14. What is a ketogenic diet?
Carbohydrate <5% total energy
Healthy cells burn mainly fat
Fat burning by the liver produces ketones
Ketones are used as a fuel for the brain
Ketones inhibit cancer cell metabolism X

15. Higher ketone production = stable disease and partial remission

16. Current (ongoing) cancer project UAB CCC support
Recurrent ovarian cancer
12 weeks of ketogenic diet (KD)
Outcomes related to cancer, metabolic health, quality of life

17. UAB Ketogenic diet prescription Transition to fat oxidation and ketone production
<20 g/d CHO
2 cup/day salad greens
1 cup/day non-starchy vegetables
<100 g/d protein (poultry, fish, red meat, pork, eggs)
Unlimited fat
Olive oil, coconut oil, coconut milk, butter, meat fat
Limited fat
Cheese (4 oz/d)
Olives (6/d); ½ avocado
Mayonnaise and cream (2 Tb/d)
This diet will “starve” cancer cells

18. Sample menu Calories Fat (g) Carbohydrates (g) Protein (g) Breakfast
Coffee 2
0.1
0.2
Cream
117
10.3
3.9
2.7
Three eggs
262
20.3
1.3
18.7
Bacon 54
4.2
3.7
Broccoli, cooked 16
0.8
2.1
0.7
Lunch
Greek salad
212
14.6
6.7 14
Olive oil
239 27
Dinner
Coconut oil
234
27.2
Kale, cooked
138
8.4
14.7
4.9
Salmon, cooked
118
19.9
Snack
Macadamia nuts
406
43.1
7.3
4.4
Total
1,799
159.6
36.2
69.3

19. Preliminary data 9 patients enrolled 1 completed Patient 1:
22 lb weight loss
Decrease in CA-125: (-245 units/mL)
Smaller tumor
20x17mm to 7x5 mm (one-tenth)
Decrease in total cholesterol (-30 mg/dL)
Elected to stay on the diet

20. Upcoming cancer project Funded by the AICR
Recurrent ovarian or endometrial cancer
60 patients (30 KD + 30 AICR diet)
12 weeks of diet therapy
Outcomes:

21. Body composition by DXA
GE-Lunar Prodigy

22. Body composition by impedance analysis

23. Blood work Markers of inflammation Blood sugar (glucose) Insulin IGF-1
Cholesterol and triglycerides

24. Quality of Life Questionnaires: Hunger and satiety
Fatigue and perceived energy
Depression

25. Cancer outcomes Tumor size by CT scan Blood cancer markers
RECIST criteria
Blood cancer markers
CA-125 marker

26. More information Treatment Ketogenic diet 2-bromo-pyruvate
(blocks glucose metabolism)
Hyperbaric oxygen

27. 3-bromo-pyruvate to treat cancer
Hexokinase 2 (glucose→ G6P) inhibitor
The pivotal player in the Warburg effect
Complete eradication (19 mice); normal life span
1 case report
No toxicity