AHS13 Colin Champ — Intermittent Fasting and Carbohydrate Restriction in Cancer Management
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AHS13 Colin Champ — Intermittent Fasting and Carbohydrate Restriction in Cancer Management

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Dietary manipulation, including intermittent fasting, carbohydrate restriction, and ketogenic diets, all ancestral in etiology, appear to increase the efficacy of radiation therapy for cancer......

Dietary manipulation, including intermittent fasting, carbohydrate restriction, and ketogenic diets, all ancestral in etiology, appear to increase the efficacy of radiation therapy for cancer treatment in preclinical and clinical trials. Clinical trials incorporating such dietary manipulation are necessary.

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  • My profession incorporates diet and exercise, including these topics, with cancer care, while my passion incorporates diet and exercise with cancer avoidance. In other words, I get paid for one and not for the other. But I do believe the importance clearly lies in prevention. However, over half of us in this room will be diagnosed with cancer, so methods to increase treatment efficacy while minimizing toxicity is greatly needed.
  • A am going to try to finish early and allow a generous amount of questions as I have prevented on this topic many times and there seems to always be audience questions that go unanswered
  • This mimics the human experiment that each and every one of us goes through every day, whether its BPA, pesticides, etc.
  • Taubes spoke of this last year
  • SAME PATHWAYS AS AUTOPHAGY, Discuss Baserga friends with Tannenbaum and discussed in Taubes book
  • This mimics the daily human experiment the experiment that each and every one of us goes through every day, whether its BPA, pesticides, etc.
  • However, this in in mice who eat well over their weight in day, have a remarkably higher metabolism than humans, and 30% CR in them is in no way equivalent to 30%CR in humans. N fact CR in humans does not ead to reductions in IGF either, Fontana
  • And this is probably closer to what happened in our mouse study, since according to many like Dr. Seyfried, a 30% calorie restriction in mice is closer to a prolonged fast in humans
  • More than enough data showing the effectiveness of carbohydrate restriction in noncancer populations and the effect on insulin/IGF
  • What about AMPK study in humans to answer both questions
  • study 1: 21 lean healthy individuals were overfed for 5 days study 2: 18 obese otherwise healthy individuals consumed a calorie-restricted diet for 5 days high fat/low carbohydrate (HF/LC) diet significantly increased phosphorylation of AMPK and deacetylation of PGC1α in skeletal muscle without affecting total amounts of AMPK, PGC1α, or SIRT 1. In contrast, low fat/high carbohydrate (LF/HC) hypocaloric diet reduced phosphorylation of AMPK and deacetylation of PGC1α. Our data indicate that a relative deficiency in carbohydrate intake or, albeit less likely, a relative excess of fat intake even in the absence of caloric deprivation is sufficient to activate the AMPK-SIRT 1-PGC1α energy-sensing cellular network in human skeletal muscle.
  • study 1: 21 lean healthy individuals were overfed for 5 days study 2: 18 obese otherwise healthy individuals consumed a calorie-restricted diet for 5 days high fat/low carbohydrate (HF/LC) diet significantly increased phosphorylation of AMPK and deacetylation of PGC1α in skeletal muscle without affecting total amounts of AMPK, PGC1α, or SIRT 1. In contrast, low fat/high carbohydrate (LF/HC) hypocaloric diet reduced phosphorylation of AMPK and deacetylation of PGC1α. Our data indicate that a relative deficiency in carbohydrate intake or, albeit less likely, a relative excess of fat intake even in the absence of caloric deprivation is sufficient to activate the AMPK-SIRT 1-PGC1α energy-sensing cellular network in human skeletal muscle.
  • study 1: 21 lean healthy individuals were overfed for 5 days study 2: 18 obese otherwise healthy individuals consumed a calorie-restricted diet for 5 days high fat/low carbohydrate (HF/LC) diet significantly increased phosphorylation of AMPK and deacetylation of PGC1α in skeletal muscle without affecting total amounts of AMPK, PGC1α, or SIRT 1. In contrast, low fat/high carbohydrate (LF/HC) hypocaloric diet reduced phosphorylation of AMPK and deacetylation of PGC1α. Our data indicate that a relative deficiency in carbohydrate intake or, albeit less likely, a relative excess of fat intake even in the absence of caloric deprivation is sufficient to activate the AMPK-SIRT 1-PGC1α energy-sensing cellular network in human skeletal muscle.
  • 1. Overconsumption of carbohydrates may inactivate AMPK regardless of caloric intake, 2. carb deprivation activates AMPK, less likley but fat consumption may activate it, 3. Potentially why high fat atkins type diets work so well in randomized trials
  • 1. Overconsumption of carbohydrates may inactivate AMPK regardless of caloric intake, 2. carb deprivation activates AMPK, less likley but fat consumption may activate it, 3. Potentially why high fat atkins type diets work so well in randomized trials
  • 1. Overconsumption of carbohydrates may inactivate AMPK regardless of caloric intake, 2. carb deprivation activates AMPK, less likley but fat consumption may activate it, 3. Potentially why high fat atkins type diets work so well in randomized trials
  • This mimics the daily human experiment the experiment that each and every one of us goes through every day, whether its BPA, pesticides, etc.
  • No metabolic flexibility
  • Not high protein
  • Based on amp-K, IGF ketogenic diet may be key
  • One mouse, no tumor at day 101, switched back for 200 days and was sacrificed with no evidence of disease on autopsy. 9/11 KD+RT mice appeared to be cured
  • II 94-109, 4 is greater than 137
  • Has nothing to do with molecular pathways and graphs…
  • Honestly may be the largest benefit, we have no clue abut the power of the human mind and psyche, and aspect of cancer care that has been ignored from day 1
  • The same way our ancestors did for millions of years
  • Whether its chemotherapy, radiation therapy, dietary intervention, or preventative measures, fighting cancer is about removing the weeds, not killing the grass in the process
  • Not the grass
  • So how do we increase ampK while lowering the insulin pathway to make cells more vulnerable to death. You have three options. The ancestral model and that of our history is a great one to fall back on. Like any model, it has its flaws, but the interconnection with the ancestral pathways that we have encountered over the past millions of years is remarkable. Most of these researchers are not ancestral health followers, but their data sure supports it.
  • Our society has gotten away from these three healthful measures, however, whether you are under treatment for cancer or simply trying to maintain your health these methods and been at the forefront for several million years and continue to be powerful tools to fight obesity, disease, and yes even cancer

Transcript

  • 1. Intermittent Fasting and Carbohydrate Restriction in Cancer Management Colin E. Champ, M.D. Assistant Professor and Physician Department of Radiation Oncology University of Pittsburgh Medical Center Cavemandoctor.com
  • 2. Disclosure • Conflicts of interest: None
  • 3. Overview • History of dietary manipulation in prevention and cancer care • Hypothesis and methods of action • Current methods of dietary intervention during treatment • Methods of implementation • Future directions
  • 4. Cancer • In this room: • Women: 1 in 8 will be diagnosed with breast cancer • Men: 1 in 6 with prostate cancer • Intense metabolic & cellular dysfunction • Diet/Lifestyle • Environment • Genetics • *Some increase due to diagnostic measures
  • 5. Introduction - History
  • 6. Conclusions thus far… • All studies: • 1. Placed mice on restricted diet (CR or carbohydrates) • 2. Applied a cancerous toxin/insult • 3. Observed: • Decrease in tumor formation/slowed tumor growth • Cancer not eliminated! • Can we harness the effects of nutrient restriction to aid in the treatment of cancer?
  • 7. Saleh A, et al. Caloric restriction augments radiation efficacy in breast cancer. Cell Cycle 2013
  • 8. Is it Calorie Restriction?
  • 9. If I were a mouse… 200 lbs. 40 lbs.
  • 10. Champ CE, Baserga R, et al. Nutrient Deprivation and Radiation Therapy – When Less is More. The Oncologist, 1:2012 How does it work? - Autophagy
  • 11. Conclusions thus far… • CR augments RT efficacy: • 1. Decreased IGF pathway • 2. Increases AMPK pathway • 3. Decreases mTOR pathway • Intermittent fasting = less weight loss • Calories restricted = primarily carbohydrates
  • 12. Insulin
  • 13. Can CR alone decrease the insulin pathway?
  • 14. Fontana L, Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. 2008 IGF and CR
  • 15. Halberg, N et al. Effect of intermittent fasting and refeeding on insulin action in healthy men. J Applied Phys 2005. Intermittent Fasting
  • 16. Ancel Keys Starvation Study • 1570 calories/day • “The major food items served were whole wheat bread, potatoes, cereals, and considerable amounts of turnips and cabbage.”
  • 17. Hite A H et al. Nutr Clin Pract 2011;26:300-308 Glucose/Insulin Pathway
  • 18. Fasting/Carbohydrate restriction better downregulate the insulin pathway… but what about the AMPK pathway?
  • 19. Amp Kinase Action Effect Increases glucose uptake Pulls glucose from circulation Increases glycolysis Glycogen and glucose burned Inhibit gluconeogenesis Decreases available glucose Increases fatty acid oxidation Inhibits fatty acid/cholesterol synthesis Increases mitochondrial biogenesis More mitochondria available Increases insulin sensitivity Per above Downregulates mTOR Per above
  • 20. Draznin, B., et al., Effect of Dietary Macronutrient Composition on AMPK and SIRT1 Expression and Activity in Human Skeletal Muscle. Horm Metab Res, 2012. 44(09): p. 650-655.
  • 21. Draznin, B., et al., Effect of Dietary Macronutrient Composition on AMPK and SIRT1 Expression and Activity in Human Skeletal Muscle. Horm Metab Res, 2012. 44(09): p. 650-655.
  • 22. Draznin, B., et al., Effect of Dietary Macronutrient Composition on AMPK and SIRT1 Expression and Activity in Human Skeletal Muscle. Horm Metab Res, 2012. 44(09): p. 650-655.
  • 23. Draznin, B., et al., Effect of Dietary Macronutrient Composition on AMPK and SIRT1 Expression and Activity in Human Skeletal Muscle. Horm Metab Res, 2012. 44(09): p. 650-655.
  • 24. Draznin, B., et al., Effect of Dietary Macronutrient Composition on AMPK and SIRT1 Expression and Activity in Human Skeletal Muscle. Horm Metab Res, 2012. 44(09): p. 650-655.
  • 25. Draznin, B., et al., Effect of Dietary Macronutrient Composition on AMPK and SIRT1 Expression and Activity in Human Skeletal Muscle. Horm Metab Res, 2012. 44(09): p. 650-655. Crossed-over
  • 26. Conclusions thus far… • Carbohydrate restriction/Intermittent fasting: • 1. Decreases IGF pathway • 2. Increases AMPK pathway • 3. Makes RT work more effectively • Intermittent fasting may provide similar benefits vs. CR • With less potentially detrimental weight loss • Increased downregulation of IGF
  • 27. Does carbohydrate restriction simply reduce available glucose for cancer cells?
  • 28. Kubicek G, Champ C, FDG-PET staging and importance of lymph node SUV in head and neck cancer. Head and Neck Onc. 2010
  • 29. Simone BA, Champ CE, Selectively starving cancer cells through dietary manipulation: Methods and clinical implications. Future Oncology, 2013. Metabolic Flexibility
  • 30. Ketogenic Diet • Ultimate lowering of blood glucose • Less than 20-50 g carbs/day & 70-80% fat • Aggressively lowers IGF and upregulates AMPK
  • 31. Fine E et. al. Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition 2012. ⬆ Ketones = Insulin⬇
  • 32. Blood Glucose Values KD Pts.
  • 33. Another Benefit…
  • 34. Illustrates the power of the mind and human spirit • Our patients must be involved in their care • Control & Autonomy • Diet and an ancestral lifestyle empowers patients to take control of their health • The days of medicine = sit back while we irradiate you and inject you with chemo must end! • In many cancers, cure is possible but futile without lifestyle changes • Future cancers/metabolic disorders will lead to significant morbidity and mortality
  • 35. Killing Weeds
  • 36. The Ancestral Solution
  • 37. In Conclusion & Going Further • Intermittent fasting/Ketogenic Diet • Potentially reduces risk of cancer in preclinical data • Aids current treatments like chemotherapy and radiotherapy • Does it work with all cancer types • ? • Does it replace current therapy • NO!!! – Available data points to synergy • Maybe (hopefully) one day
  • 38. Acknowledgements • Eugene M. Fine, M.D. • Albert Einstein College of Medicine • Jeff S. Volek, Ph.D., R.D. • University of Connecticut • Nicole L. Simone, M.D. • Kimmel Cancer Center of Thomas Jefferson University • Rainer Klement, Ph.D. • University of Würzburg • My amazing patients