1. 1 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Combinations of Natural Products Opportunities and Dangers Dr. Paul F. Davis Bioactivity Investigation Group (BIG) Wellington School of Medicine and Health Sciences Wellington New Zealand

2. 2 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Natural Products Long History –Prevention –Therapeutics

3. 3 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 In Early Times Achieved Via Food Derived preparations from: –Animal –Plants –Fish –Birds Becomes a tradition

4. 4 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Traditional Chinese Medicine 3,500 years ago-origins 2,700 years ago (Zhou Dynasty)-regularly prescribed

5. 5 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Arabian Medicine 1,800 years ago –Drugs –Many conditions 1,100 years ago –Samanids –Muhamad Zakariyya Razu –Abu Ali Ibn Sina Records kept

6. 6 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 South American Medicine Incas –Bolivia –Kallaways (1500 years at least)

7. 7 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Long history suggests efficacy Recognised by current consumers

8. 8 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Currently Increasing use of Natural Products –Preventative –Therapeutic Nutraceuticals Functional Food Food Supplements Medicinal Food US Market-$18 billion in 2001- 20% per annum growth

9. 9 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Tendency to use multiple products, multiple conditions Anecdotal Information Basis

10. 10 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Combinations Natural Products-Natural Products Natural Products-Prescription medicines

11. 11 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Examples Garlic –used for hypertension, cardiovascular conditions, neoplasms and infections Cod Liver Oil- used for B-cell lymphoma, prostate cancer, breast cancer, hypertension, hypertryglycerdemia, arthritis, cardio vascular conditions Garlic + Cod Liver Oil- used for anti-coagulant (andecdotal)

12. 12 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Examples Ginger –Has over 30 uses including inhibition of platlet aggregation –Regarded as safe Potential Risks –Concurrent use with anti-coagulant prescriptions or natural products –When combined with angelica, garlic, ginseg panax, red clover, tumeric

13. 13 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Risks for: Individuals Producers Marketers (international sales)

14. 14 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Risks occur when: Consumer does the combining Marketer does the combining

15. 15 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Beneficial or Detrimental Product available in Korea, Japan, and China Oil derived from shark –Anti-angiogenic –Anti-inflammatory Mushroom Extract (b-glucan rich) –Immune enhancing

16. 16 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Shark Oil +Mushroom extract –Reduction in proliferation of primary tumours –Reduction in metastases Effect of combination is synergistic Neither of them or combination is anti-tumour Beneficial or Detrimental

17. 17 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Echinachea-Immune enhancing (Cichoric acid) –Echinachea+Herbal Supplements-No reported adverse effect –Echinachea+Other Immune Stimulants-Additive effect –Echinachea+Other Immune Stimulants-Suppresseive effect Examples of these are commercially available Beneficial or Detrimental

18. 18 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Examples From BIG Research Lipid-rich extract from sharks is anti-angiogenic Potency meant dilution required Cooking oil (olive oil)-inactive Combination –2x more active invitro –6x more active invivo Synergistic Activity-Beneficial Outcome

19. 19 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Risks of Prescription Pharmaceutical Widely Publicised Recent publicity on Cox-2 inhibitors Also risk of combining 2 pharmaceuticals (regulatory authority requirment) Frequently these combinations are for chronic conditions-Elderly often have several medical conditions

20. 20 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Possible that Patients are Taking: Over the counter remedies + Prescribed therapies –Combination often not revealed at time of prescribing –Non-prescription item commenced subsequent to prescription Risky Little research information

21. 21 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Example-Warfarin An anti-thrombotic, anti-coagulant Activity decreased by: –American Ginseng –St John`s Wort –CoQ10 No data on ginseng (Siberian)

22. 22 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Example-Warfarin Not all combinations are detrimental Activity increased by combining with: –Garlic –Ginger –Ginkgo Biloba –Fish Oils –60 other products

23. 23 BIG@wnmeds.ac.nzBIG@wnmeds.ac.nz or +64 (04) 918 5611 Summary All Natural Products: Biologically active Can interact with cells, pathways, like drugs Modulate other activities Own activities altered Care and caution needed Similar approach to that with pharmaceuticals Significant lack of data and information Need for Research is Urgent