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Dr Nina Fuller-Shavel 2021 Systems approach to cancer metabolic and mitochondrial health
SYSTEMS APPROACH TO CANCER - MONTH 4
DR NINA FULLER-SHAVEL
MA HONS (CANTAB) MB BCHIR IFMCP DIPIM PG CERT DIPION RYT200 Disclaimer
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Dr Nina Fuller-Shavel Ltd provides healthcare information to registered healthcare practitioners and offers the opportunity to hear the views, recommendations and experiences of other practitioners. Research discussed in this course on cancer and the application of nutrients, herbs and other health-related information regarding cancer is not a substitute for medical advice and standard of care treatment.
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Dr Nina Fuller-Shavel Ltd has not evaluated the legal status of herbs, products, services or recommendations with respect to individual scope of practice. Practitioners are advised to consult their professional association for further guidance. Dr Nina Fuller-Shavel Ltd does not and cannot accept responsibility for errors or omissions or for any consequences from applications of the information provided and makes no warranty, expressed or implied, with respect to the information provided.
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This education programme is not intended to diagnose, treat or cure any disease.
> Dr Nina Fuller-Shavel 2021
## Dr Ninas systems approach to cancer
Dr Nina Fuller-Shavel 2021
Systems approach to cancer
Healthy microbiome balance and GI function
Balanced immune function
Effective detoxification
Healthy circulation and tissue architecture
Mitochondrial and metabolic health
Hormone balance
Balanced methylation and genomic stability
Mental/ emotional/ spiritual health and biorhythms Supporting metabolic and mitochondrial health
Key aims:
Reduce growth factor drivers, e.g. normalise insulin and IGF-1, PI3K/Akt/mTOR etc
Balanced metabolism autophagy/mitophagy, glucose/glutamine pathways, Warburg/reverse Warburg
> Dr Nina Fuller-Shavel 2021
## Metabolic dysregulation and cancer
Key aspects:
Obesity
Insulin resistance/diabetes
Raised IGF-1
Meta-inflammation is important!
> Dr Nina Fuller-Shavel 2021
## Insulin more than just metabolism
> Dr Nina Fuller-Shavel 2021
# Obesity and cancer
Dr Nina Fuller-Shavel 2021 IGF-1 and cancer
Dr Nina Fuller-Shavel 2021 IGF-1R and therapy resistance
Dr Nina Fuller-Shavel 2021 Dietary factors in managing the IGF-1 axis
Low GL/GI diet
Mediterranean diet
RCT in BRCA carriers - Mediterranean dietary intervention with moderate protein restriction is effective in reducing IGF-I and other potential modulators of BRCA penetrance (anthropometrics)
Protein restriction sticking to max 1.2-1.4 g/kg
Calorie restriction not a feasible strategy in humans intake needs to be reduced by 50%+
Fasting
Dairy intake avoidance or small amounts of organic fermented only
Each 400 g increment in daily dairy intake was associated with 16.8 g/L (95% CI 6.9, 26.7) higher IGF-1 concentrations. Each 200 g increment in milk per day was associated with 10.0 g/L (95% CI 4.2, 15.8) higher IGF-1. Interestingly, yoghurt did not show the same association.
> Dr Nina Fuller-Shavel 2021
PI3K/AKT/mTOR
Dr Nina Fuller-Shavel 2021 PI3K/AKT/mTOR
Dr Nina Fuller-Shavel 2021 Counter-regulators - AMPK
Dr Nina Fuller-Shavel 2021 Glucose in mitochondrial dysfunction
> Dr Nina Fuller-Shavel 2021
Mitochondrial reprogramming in cancer
> Dr Nina Fuller-Shavel 2021
## Key aspects to consider during intake
Medical history and family history, e.g. T2DM, early CVD, PCOS etc
Current medications
Nutrition SAD/SBD, high GL, alcohol, sweet fat, pro-inflammatory, low antioxidant intake
Lifestyle sedentary/lack of physical activity, chronic stress, sleep deprivation
Anthropometrics, e.g. BMI and WHR
Recent blood test results
> Dr Nina Fuller-Shavel 2021
## Testing
Bloods:
Basic HbA1c and fasting glucose, fasting lipids
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Fasting glucose, fasting insulin HOMA-IR
Inflammatory markers are relevant, e.g. CRP
Specialist tests as needed, e.g. IGF-1
Genetics SNPs, e.g. TCF7L2, PPARgamma etc
DNA Health
May want to monitor anthropometrics
> Dr Nina Fuller-Shavel 2021
## Interventions - foundations
Low GL anti-inflammatory colourful high phytonutrient wholefood-based diet
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Moderate, not high, protein
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Healthy anti-inflammatory fat balance focus on EVOO/avocado oil, avocadoes, nuts/seeds, small wild oily fish
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Limited amounts of organic fermented dairy if any
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May require a short period on anti-inflammatory KD if very dysregulated
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Avoidance of alcohol and minimise/avoid refined sugar (completely avoid artificial sweeteners and avoid any fructose not in fresh fruit)
Overnight fasting a minimum 13 hours, in metabolically dysregulated individuals 16:8 TRF
Manage sleep and stress re: cortisol/cravings
Regular physical activity excellent insulin sensitizer
Healthy weight maintenance and decrease in abdominal and visceral fat
> Dr Nina Fuller-Shavel 2021
## Interventions - insulin
Insulin sensitivity berberine, chromium, citrus bergamot, omega-3, bitter melon, cinnamon, green tea extract
Note berberine long-term use at high doses will deplete the gut microbiome
Herbs Panax ginseng and tulsi (Ocimum sanctum) are commonly used
Gymnema good for cravings but supports more insulin release from the pancreas, so would usually avoid long-term in cancer
> Dr Nina Fuller-Shavel 2021
## Interventions IGF-1
Dr Nina Fuller-Shavel 2021 Natural AMPK activators
Dr Nina Fuller-Shavel 2021 Natural PI3K/AKT/mTOR pathway inhibitors
> Dr Nina Fuller-Shavel 2021
Natural PI3K/AKT/mTOR pathway inhibitors
> Dr Nina Fuller-Shavel 2021
## Targeting mitochondrial dysfunction
> Dr Nina Fuller-Shavel 2021
## Summary metabolic and mitochondrial health
Assess metabolic status history and anthropometrics, testing (repeat to monitor)
Nutrition and lifestyle first foundational and crucial!
Anti-inflammatory wholefood low GL high phytonutrient diet moderate in protein
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Avoidance of added fructose and refined sugar and alcohol
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Minimise dairy to organic fermented in small amounts only or avoid in sensitive individuals
Fasting, exercise, stress, sleep
Healthy weight and reduce of visceral adiposity
Can consider supplementation personalised to individual but be aware of limited evidence base and do not overstate this
> Dr Nina Fuller-Shavel 2021
## References
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Adhami VM, Afaq F, Mukhtar H. Insulin-like growth factor-I axis as a pathway for cancer chemoprevention. Clin Cancer Res. 2006 Oct 1;12(19):5611-4.
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Ben-Sahra I, Manning BD. mTORC1 signaling and the metabolic control of cell growth. Curr Opin Cell Biol. 2017 Apr;45:72-82.
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Bruno E, Oliverio A, Paradiso AV, Daniele A, Tommasi S, Tufaro A, Terribile DA, Magno S, Filippone A, Venturelli E, Morelli D, Baldassari I, Cravana ML, Manoukian S, Pasanisi P. A Mediterranean Dietary Intervention in Female Carriers of BRCA Mutations: Results from an Italian Prospective Randomized Controlled Trial. Cancers (Basel). 2020 Dec 11;12(12):3732.
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Burris J, Shikany JM, Rietkerk W, Woolf K. A Low Glycemic Index and Glycemic Load Diet Decreases Insulin-like Growth Factor-1 among Adults with Moderate and Severe Acne: A Short-Duration, 2-Week Randomized Controlled Trial. J Acad Nutr Diet. 2018 Oct;118(10):1874-1885.
> Dr Nina Fuller-Shavel 2021
## References
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Carresi C, Gliozzi M, Musolino V, Scicchitano M, Scarano F, Bosco F, Nucera S, Maiuolo J, Macr R, Ruga S, Oppedisano F, Zito MC, Guarnieri L, Mollace R, Tavernese A, Palma E, Bombardelli E, Fini M, Mollace V. The Effect of Natural Antioxidants in the Development of Metabolic Syndrome: Focus on Bergamot Polyphenolic Fraction. Nutrients. 2020 May 21;12(5):1504.
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Cerella C, Radogna F, Dicato M, Diederich M. Natural compounds as regulators of the cancer cell metabolism. Int J Cell Biol. 2013;2013:639401.
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Denduluri SK, Idowu O, Wang Z, Liao Z, Yan Z, Mohammed MK, Ye J, Wei Q, Wang J, Zhao L, Luu HH. Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance. Genes Dis. 2015 Mar 1;2(1):13-25.
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Goodwin PJ, Stambolic V. Impact of the obesity epidemic on cancer. Annu Rev Med. 2015;66:281-96.
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Grasso D, Zampieri LX, Capela T, Van de Velde JA, Sonveaux P. Mitochondria in cancer. Cell Stress. 2020 May 11;4(6):114-146.
> Dr Nina Fuller-Shavel 2021
## References
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Hardie DG. AMPK: a target for drugs and natural products with effects on both diabetes and cancer. Diabetes. 2013 Jul;62(7):2164-72.
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Key TJ. Diet, insulin-like growth factor-1 and cancer risk. Proc Nutr Soc. 2011 May 3:1-4.
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Lyons CL, Roche HM. Nutritional Modulation of AMPK-Impact upon Metabolic-Inflammation. Int J Mol Sci. 2018 Oct 9;19(10):3092.
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Mendelsohn, J., In Gray, J. W., In Howley, P. M., In Israel, M. A., & In Thompson, C. (2015). The molecular basis of cancer.
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O'Donnell JS, Massi D, Teng MWL, Mandala M. PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux. Semin Cancer Biol. 2018 Feb;48:91-103.
> Dr Nina Fuller-Shavel 2021
## References
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Rahmani J, Kord Varkaneh H, Clark C, Zand H, Bawadi H, Ryan PM, Fatahi S, Zhang Y. The influence of fasting and energy restricting diets on IGF-1 levels in humans: A systematic review and meta-analysis. Ageing Res Rev. 2019 Aug;53:100910.
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Romo Ventura E, Konigorski S, Rohrmann S, Schneider H, Stalla GK, Pischon T, Linseisen J, Nimptsch K. Association of dietary intake of milk and dairy products with blood concentrations of insulin-like growth factor 1 (IGF-1) in Bavarian adults. Eur J Nutr. 2020 Jun;59(4):1413-1420.
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Suvarna V, Murahari M, Khan T, Chaubey P, Sangave P. Phytochemicals and PI3K Inhibitors in Cancer-An Insight. Front Pharmacol. 2017 Dec 14;8:916.
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Varghese E, Samuel SM, Lkov A, Samec M, Kubatka P, Bsselberg D. Targeting Glucose Metabolism to Overcome Resistance to Anticancer Chemotherapy in Breast Cancer. Cancers (Basel). 2020 Aug 12;12(8):2252.
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Yee LD, Mortimer JE, Natarajan R, Dietze EC, Seewaldt VL. Metabolic Health, Insulin, and Breast Cancer: Why Oncologists Should Care About Insulin. Front Endocrinol (Lausanne). 2020 Feb 20;11:58.