Food supplements and European regulation within a precautionary context: A critique and implications for nutritional, toxicological and regulatory consistency

Critical Reviews in Food Science and Nutrition

Volumn 47, Issue 3, 2007, Pages 267-285

  Hanekamp, J C ^a,c   Bast, A ^b  

^a HAN Research   (Turkey)

^b MAASTRICHT UNIVERSITY   (Netherlands)

^c NONE   (Netherlands)

Author keywords

European regulation; Food supplements; Intended Normal Use (INU); Micronutrients; Precautionary principle; Regulatory innovation

Indexed keywords

TRACE ELEMENT;

ARTICLE; DIET SUPPLEMENTATION; EUROPE; GENOMICS; HEALTH CARE POLICY; HEALTH PROMOTION; HUMAN; LAW; LEGAL ASPECT; NUTRITION; RISK ASSESSMENT;

DIETARY SUPPLEMENTS; EUROPE; GENOMICS; HEALTH PROMOTION; HUMANS; LEGISLATION, FOOD; MICRONUTRIENTS; NUTRITION PHYSIOLOGY; NUTRITION POLICY; RISK ASSESSMENT;

EID: 33947423935     PISSN: 10408398     EISSN: 15497852     Source Type: Journal    
DOI: 10.1080/10408390600737748     Document Type: Article

References (212)

1. De Vries, J. (Ed.). 1991. Food Safety and Toxicity. CRC Press, New York.
2. Anti-nutritives are food component that induce toxic effects by causing nutritional deficiencies of by interference with the functioning and utilization of nutrients. Examples are lectins, phytic acid, and oxalic acid. See further below.
3. Ashwell, M. 1990. How safe is our food? A report of the British Nutrition Foundation's eleventh annual conference. J. Royal. College. Phys., 24(3):233-237.
4. See for an extensive discussion of food safety issues: Notermans, S. 2006. Electronisch Dossier Voedselveiligheid. [Electronic Dossier Food-Safety.] (Prof. Notermans is a member of the EPSA Scientific Panel on Biohazards.)
5. Doll, R., and Peto, R. 1981. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer. Inst., 66(6): 1191-308.
6. Ames, B.N., Gold, L.S., and Willett, W.C., 1995. The causes and prevention of cancer. Proc. Natl. Acad. Sci. USA., 92:5258-5265.
7. Carcinogens and Anticarcinogens in the Human Diet. A Comparison of Naturally Occurring and Synthetic Substances. 1996. Committee on Comparative Toxicity of Naturally Occurring Carcinogens, Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council. National Academy Press, Washington D.C.
8. D'Mello, J.P.F., Duffus, C.M., and Duffus, J.H. (Eds.), 1991. Toxic Substances in Crop Plants. The Royal Society of Chemistry, Cambridge, UK.
9. See also: Van Genderen, H., Schoonhoven, L.M., and Fuchs, A. 1996. Chemisch-ecologische Flora. [Chemical-ecological Flora.] KNNV Uitgeverij, Utrecht, The Netherlands.
10. See further: Ames, B.N. 1983. Dietary Carcinogens and Anticarcinogens. Oxygen Radicals and Degenerative Diseases. Science., 221:1256- 1264.
11. See e.g.: Ames, B.N., and Wakimoto, P. 2002. Are vitamin and mineral deficiencies a major cancer risk? Nature. 2: 694-704.
12. Fenech, M. 2001. The role of folic acid and Vitamin B12 in genomic stability of human cells. Mut. Res., 475:57-67.
13. See e.g.: McKay, D. L., and Blumberg, J.B. 2002. The role of tea in human health: an update. J. Am. Coll. Nutr., 21:1-13.
14. See for scientific articles dealing with regulatory approaches for micronutrients (including botanical food compounds) within the food area: Meltzer, H.M., Aro, A., Andersen, N.L., Koch, B., and Alexander, J. 2002. Risk analysis applied to food fortification. Pub. Health. Nutr., 6(3):281-290.
15. Schilter, B., Andersson, C., Anton, R., Constable, A., Kleiner, J., O'Brien, J., Renwick, A.G., Korver, O., Smit, F., and Walker, R. 2003. Guidance for the safety assessment of botanicals and botanical preparations for use in food and food supplements. Food. Chem. Tox., 41:1625-1649.
16. Walker, R. 2004. Criteria for risk assessment of botanical food supplements. Tox Lett., 149:187-195.
17. Kroes, R., and Walker, R. 2004. Safety issues of botanicals and botanical preparations in functional foods. Toxicology. 198: 213-220.
18. See for a recent framework of risk assessment for nutrients and other substances: A Model for Establishing Upper Levels of Intake for Nutrients and Related Substances. (2006) Report of a Joint FAO/WHO Technical Workshop on Nutrient Risk Assessment. WHO Headquarters, Geneva, Switzerland 2-6 May 2005.
19. See e.g.: Rietjens, I.M.C.M., Boersma, M.G., Van der Woude, H., Jeurissen, S.M.F., Schutte, M.E., and Alink, G.M. 2005. Flavonoids and alkenylbenzenes: Mechanisms of mutagenic action and carcinogenic risk. Mut Res., 574:124-138.
20. See for the issue of consumption of herbal products and health (although this touches on the medicinal aspect not addressed in this review): Nortier, J. L., Muniz Martinez, M.-C., Schmeiser, H.H., Arlt, V.M., Bieler, C.A., Petein, M., Depierreux, M.F., De Paw, L., Abramowicz, D., Vereerstraeten, P., and Vanherwegheim, J.-L. 2000. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fanghi), N. Engl. J. Med., 342:1686-1692.
21. Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements. O. J. Eur. Comm., L183:51-57.
22. Directive2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. O. J. Eur. Comm., L311:67-128.
23. Bast, A., Chandler, R.F., Choy, P.C., Delmulle, L.M., Gruenwald, J., Halkes. S.B.A., Keller, K., Koeman, J.H., Peters, P., Przyrembel, H., De Ree, E.M., Renwick, A.G., and Vermeer, I.T.M. 2002. Botanical health products, positioning and requirements for effective and safe use. Env. Tox. Pharm., 12(4):195-211.
24. See note 12.
25. st 14th of February, 2007).
26. See note 16, p. 6.
27. Verwendung von Vitaminen in Lebensmitteln Toxikologische und ernährungsphysiologische Aspekte, Teil I. 2004. Bundesinstitut für Risikobewertung. This report can be downloaded from: http://www.bfr.bund.de/cm/ 238/verwendung _von_vitaminen_in_leben-smitteln.pdf (last visited on the 14th of February, 2007. See also: Verwendung von Mineralstoffen in Lebensmitteln. Toxikologische und ernährungsphysiologische Aspekte. Teil II. Bundesinstitut für Risikobewertung, 2004. This report can be downloaded from: http://www.bfr.bund.de/cm/238/verwendung_von_mineralstoften_in_leben- smitteln_bfr_wissenschaft_4_2004.pdf (last visited on the 14th of February, 2007).
28. See note 16.
29. Market failure, in economic theory, refers to the failure, in freely functioning markets, to deliver an efficient allocation of resources. The result is a loss of economic and social welfare. A number of reasons for market failure to arise are e. g. monopoly power (price is higher and output is lower under a monopoly than in a competitive market), and merit goods (goods and services that the government feels that people left to themselves will under-consume, and therefore needs to be subsidised at the point of use, examples being inoculations, public libraries, education and the like). In this particular case market failure is understood as the inadequate capability of a freely functioning market to generate a safe consumer environment for the production, marketing and consumption of food supplements.
30. Wildavsky, A. 1997. But is it True? A Citizen's Guide to Environmental Health and Safety Issues. Harvard University Press, Cambridge.
31. Fenech, M. 2001. Recommended dietary allowances (RDAs) for genomic stability. Mut Res., 480-481:51-54.
32. Cramer, G.M., Ford, R. A., and Hall, R.L. 1978. Estimation of toxic hazard - a decision tree approach. Food. Cosmet. Tox., 16:255-276.
33. Weinberg, A.M. 1972. Science and trans-science. Minerva., 10:209-222.
34. Weinberg quoted three examples that transcend science in three rather different senses. In the first case (low-level radiation insult), science is inadequate simply because to get answers would be unpractically expensive (the conundrum Cramer et al. discuss; see note 23). In the second case (social sciences), science is inadequate because the subject-matter is too variable to allow rationalisation according to the strict scientific canons established within the natural sciences. In the third case (choice in science), science is inadequate simply because the issues themselves involve moral and aesthetic judgements: they deal not with what is true or rational but rather with what is valuable.
35. Stenmark, M. 2001.Scientism. Science,Ethics and Religion. Ashgate Publishing Limited, Burlington. (Religion, here, is referred to in the wider context as worldviews.)
36. See also: Haack, S. 2003. Defending Science within Reason. Between Scientism and Cynicism. Prometheus Books, New York.
37. See e.g.: Wildavsky, A. 1991. Searching for Safety. Transaction Publishers, New Brinswick, USA.
38. The opposite of market failure is government failure. Even when good intentions of governments are taken for granted, governments only infrequently get their policy application correct. They can tax, control and regulate but the eventual outcome could be a deepening of the market failure or, even worse, a new failure may arise.
39. Stenmark, M. 2004. How to Relate Science and Religion. A Multidimensional Model. Wm. B. Eerdmans Publishing Co., Cambridge. (Religion, here again, is referred to in the wider context as worldviews.)
40. Power, M. 2004. The Risk Management of Everything. Rethinking the Politics of Uncertainty. Demos, UK.
41. Hanekamp, J.C., Frapporti, G., and Olieman, K. 2003. Chloramphenicol, food safety and precautionary thinking in Europe. Env. Liab. 6:209-221.
42. Hanekamp, J.C., and Kwakman, J. 2004. Beyond Zero-tolerance: A Novel and Global Outlook on Food-safety and Residues of Pharmacological Active Substances in Foodstuffs of Animal Origin. Env Liab., 1:33-39.
43. Hanekamp J.C., and Wijnands R.J., 2004. Analytical technology, risk analysis and residues of veterinary substances: A précis and a proposal for coherent and logical clinical residue legislation. In: Joint FAO/WHO Technical Workshop on Residues of Veterinary Drugs without ADI/MRL. 2004, 24-26 August, Bangkok, Thailand, p. 81-86.
44. Barnard, R.C. 1996. A New Approach to risk assessment integrating scientific evaluation and economic assessment of costs and benefits. Reg. Tox. Pharm., 24:121-125.
45. Feinstem, J.S. 1993. The relationship between socioeconomic status and health: A review of the literature. Milbank Q., 71:279-321.
46. Mackenbach, J.P. 1994. Ongezonde verschillen. Over sociale stratificatie en gezondheid in Nederland. [Unhealthy differences. Social stratification and health in the Netherlands.] Van Gorcum, The Netherlands.
47. Wagstaff, A., and van Doorslaer, E. 2000. Income Inequality and Health: What does the Literature Tell Us? Animal. Rev. Pub. Health., 21:543-567.
48. Keeney, R.L. 1994. Mortality Risks Induced by the Costs of Regulations. J Risk Uncertainty., 8:95-110.
49. Keeney, R.L. 1997. Estimating fatalities induced by the economic costs of regulations. J. Risk. Uncertainty., 14:5-23.
50. Kip Viscusi, W., and Aldy, J.E. 2003. The value of a statistical life: A critical review of market estimates throughout the world. J. Risk Uncertainty. 27(1):5-76.
51. Morrall III, J.F. 2003. Saving Lives: A Review of the Record. J. Risk. Uncertainty., 27(3):221-237.
52. Graham, J.D., and Wiener, J.B. 1995. Risk vs. Risk. Tradeoffs in Protecting Health and the Environment. Harvard University Press, Cambridge.
53. See e.g. the following seminal paper: Tengs, T.O., Adams, M.E., Pliskin, J.S., Safran, D.G., Siegel, J.E., Weinstein, M.C., and Graham, J.D. 1995. Five-hundred life-saving interventions and their cost-effectiveness. Risk. Anal., 15(3):369-390.
54. Hahn, R.W. (Ed.) 1996. Risks, Costs and Lives Saved. Getting Better Results from Regulation. Oxford University Press, Oxford.
55. Commission of the European Communities. 2000. Communication from the Commission on the Precautionary Principle. Brussels.
56. See for an illustrative and insightful risk-benefit analysis for vitamins and minerals: Renwick, A.G., Flynn, A., Fletcher, R.J., Müller, D.J.G., Tuijtelaars, S., and Verhagen, H. 2004. Risk-benefit analysis of micronutrients. Food Chem Tox. 42:1903-1922. This is in fact along the lines of the Healthy Life Years (HLY) Structural Indicator (that is the number of years a person can expect to live in good health) as put forward in the Communication from the Commission titled Healthier, safer, more confident citizens: a Health and Consumer protection Strategy. See: http://ec.europa.eu/health/ ph_overview/Documents/com_2005_0115_en. pdf (last visited on the 14th of February, 2007).
57. See note 16, p. 6.
58. See for instance: Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. A Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, Food and Nutrition Board, Institute of Medicine. 1998, National Acadamies Press, USA.
59. See note 16, p. 24.
60. Although for instance Schilter et al. (2003, note 10) refer to the few initiatives regarding the scientific data necessary to establish the safety of functional botanical products when used in food and dietary supplements, the cited references in relation to the issue of safety primarily deal with intoxications as a result of medicinal uses of supplements (herbs). See also Walker (2004), and Kroes and Walker, note 10.
61. See note 30.
62. Siegrist, M., and Cvetkovich, G. 2001. Better negative than positive? Evidence of a bias for negative information about possible health dangers. Risk. Anal., 21(1):199-206.
63. See for an explanation of negative bias: Taylor, S.E. 1991. Asymmetrical Effects of Positive and Negative Events: The Mobilization-Minimization Hypothesis. Psych Bull., 110(1):67-85.
64. See for a cultural-sociological perspective on risk selection: Douglas, M., Wildavsky, A. 1982. Risk and Culture. An Essay on the Selection of Technological and Environmental Dangers. Berkely University of California Press.
65. Wildavsky, A., and Dake, K. 1990. Theories of risk perception: Who fears what and why? Daedalus. 119(4):41-60.
66. See note 1, p. 93. This, however, should not be read as a generally extrapolative remark.
67. See note 1, p. 39-52.
68. Lips, P. 2003. Hypervitaminosis A and Fractures. N. Engl. J. Med., 348:347-349.
69. A unit is used to measure the activity (that is, the effect) of many vitamins and drugs. For each substance to which this unit applies, there is an international agreement specifying the biological effect expected with a dose of 1 IU. Other quantities of the substance are then expressed as multiples of this standard. Examples: l IU represents 45.5 micrograms of a standard preparation of insulin; the equivalent of 1 IU is 0.3 microgram (0.0003 mg) for vitamin A, 50 micrograms (0.05 mg) for vitamin C, and 25 nanograms (0.000025 mg) for vitamin D.
70. Taken from a lecture of Dr. M. Dourson et al., Toxicology Excellence for Risk Assessment.
71. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of DRIs, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board. National Academy Press: Washington DC, 2000, p. 284, p. 311-318.
72. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline A Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, Food and Nutrition Board, Institute of Medicine. National Academy Press: Washington DC, 1998, p. 370-371.
73. Akhilender Naidu, K. 2003. Vitamin C in human health and disease is still a mystery? An overview. Nutr. J., 2:7 p.
74. Abrams, S. A. 2002. Nutritional rickets: an old disease returns. Nutr. Rev., 60(4): 111-115.
75. See e. g.: Willett, W.C. 1994. Diet and health: What should we eat? Science. 264:532-537.
76. Borek, C. 2004. Dietary antioxidants and human cancer. Integr Cancer Ther. 3(4):333-341.
77. See e.g.: Steinmetz, K.A., and Potter, J.D. 1996. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc., 96:1027-1039.
78. Ness, A.R., and Powles, J.W. 1997. Fruit and vegetables and cardiovascular disease: a review. Int. J. Epidemiol., 26:1-13.
79. Block, G., Norkus, E., Hudes, M., Mandel, S., and Helzlsouer, K. 2001. Which plasma antioxidants are most related to fruit and vegetable consumption? Am. J. Epidemiol., 154:1113-1118.
80. Fenech, M. 2002. Micronutrients and genomic stability: a new paradigm for recommended dietary allowances (RDAs). Food Chem Tox. 40:1113-1117.
81. See also: Kaput, J., Ordovas, J.N., Ferguson, L., Van Ommen, B., Rodriguez, R.L., Allen, L., Ames, B.N., Dawson, K., German, B., Krauss, R., Malyj, W., Archer, M.C., Barnes, S., Bartholomew, A., Birk, R., Van Bladeren, P., Bradford, K.J., Brown, K.H., Caetano, R., Castle, D., Chadwick, R., Clarke, S., Clément, K., Craig A. Cooney, C.A., Corella, D., Da Cruz, I.B.M., Daniel, H., Duster, T., Ebbesson, S.O.E., Elliott, R., Fairweather-Tait, S., Felton, J., Fenech, M., Finley, J.W., Fogg-Johnson, N., Gill-Garrison, R., Gibney, M.J., Gillies, P.J., Gustafsson, J.-A., Hartman IV, J.L., He, L., Hwang, J.-K., Jais, J.-P., Jang, Y., Joost, H., Junien, C., Kanter, M., Kibbe, W.A., Koletzko, B., Korf, B.R., Kornman, K., Krempin, D.W., Langin, D., Lauren, D.R., Lee, J.H., Leveille, G.A., Lin, S.-J., Mathers, J., Mayne, M., McNabb, W., Milner, J.A., Morgan, P., Muller, M., Nikolsky, Y., Van der Ouderaa, F., Park, T., Pensel, N., Perez-Jimenez, F., Poutanen, K., Matthew Roberts, M., Saris, W.H.M., Schuster, G., Shelling, A.N., Simopoulos, A.P., Southon, S., Tai, E.S., Towne, B., Trayhurn, P., Uauy, R., Visek, W.J., Warden, C., Weiss, R., Wiencke, J., Winkler, J., Wolff, G.L., Zhao-Wilson, X., and Zucker, J.-D. 2005. The case for strategic international alliances to harness nutritional genomics for public and personal health. Br. J. Nutr., 94:623-632.
82. Fenech, M., and Ferguson, L.R. 2001. Vitamins/minerals and genomic stability in humans. Mut. Res., 475:1-6.
83. See for an introduction of the subject: Poortman, Y., Steegers, R., and Kluft, C. (Eds.) 2004. The Increasing Role of Nutrition and Genomics in the Prevention and Management of Disease. Aspekt, The Netherlands.
84. Ames, B.N., Atamna, H., and Killilea, D.W. 2005. Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging. Mol. Aspects Med., 26:363-378.
85. Fenech, M. 2003. Nutritional treatment of genome instability: a paradigm shift in disease prevention and in the setting of recommended dietary allowances. Nutr. Res. Rev., 16:109-122.
86. Wakimoto, P., and Block, G. 2001. Dietary intake, dietary patterns, and changes with age: an epidemiological perspective. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences., 56:65-80.
87. Ames, B.N. 2005. Increasing longevity by tuning up metabolism. EMBO reports. 6:S20-S24.
88. Courtemanche, C., Huang, A.C., Elson-Schwab, I., Kerry, N., Ng, B.Y., and Ames, B.N. 2004. Folate deficiency and ionizing radiation cause DNA breaks in primary human lymphocytes: a comparison. FASEB J., 18:209-211.
89. See note 56.
90. MRC Vitamin Study Group. 1991. Prevention of neural tube defects: results of the Medical Research Council vitamin study. Lancet., 338:131-137.
91. See further: Lucock, M. 2004. Is folio acid the ultimate functional food component for disease prevention? Brit. J. Med., 328:211-214.
92. Beck, M.A., Levander, O.A., Handy, J. 2003. Selenium Deficiency and Viral Infection. J. Nutr., 133: 1463S-1467S.
93. Ren, L.-Q., Li, X.J., Li, G.-S., Zhao, Z.-T., Sun, B., and Sun, F. 2004. Coxsackievirus B3 infection and its mutation in Keshan disease. World J. Gastroenterol, 10(22):3299-3302.
94. Ge, K., and Yang, G. 1993. The epidemiology of selenium deficiency in the etiological study of endemic diseases in China. Am. J. Clin Nutr., 57(2 Suppl): 259S-263S.
95. Tan, J., Zhu, W., Wang, W., Li, R., Hou, S., Wang, D., and Yang, L. 2002. Selenium in soil and endemic diseases in China. Sci. Total Env., 284:227-235.
96. See note 50.
97. Yang, G-Q., and Xia, Y.M. 1995. Studies on human dietary requirements and a safe range of dietary intakes of selenium and their application in the prevention of related endemic diseases. Biomed. Environ. Sci., 8:187-201.
98. See also: Yang, G., Zhou, R., Yin S., Gu, L., Yan, B., Liu, Y., Liu, Y., and Li, X. 1989a. Studies of safe maximal daily selenium intake in a seleniferous area in China. I. Selenium intake and tissue selenium levels of the inhabitants. J. Trace Elements Electrolytes Health Dis., 3:77-87.
99. Yang, G., Yin, S., Zhou, R., Gu, L., Yan, B., Liu, Y., and Liu, Y., 1989b. Studies of safe maximal daily selenium intake in a seleniferous area in China. II. Relation between selenium intake and the manifestation of clinical signs and certain biochemical alterations in blood and urine. J. Trace Elements Electrolytes Health Dis., 3:123-130.
100. See e. g.: Ip, C. 1998. Lessons from basic research in selenium and cancer prevention. J. Nutr., 128:1845-1854.
101. Rayman, M.P. 2000. The importance of selenium to human health. Lancet., 356:233-241.
102. Clark, L.C., Combs Jr, G.F., Turnbull, B.W., Slate, E.H., Chalker, D.K., Chow, J., Davis, L.S., Glover, R.A., Graham, G.E, Gross, E.G., Krongrad, A., Lesher Jr, J.L., Park, H.K., Sanders Jr, B.B., Smith, C.L., and Taylor, J.R. 1996. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA., 276:1957-1963.
103. Clark, L.C., Dalkin, B., Krongrad, A., Combs Jr, G.F., Turnbull, B.W., Slate, E.H., Witherington, R., Herlong, J.H., Janosko, E., Carpenter, D., Borosso, C., Falk, S., and Rounder, J. 1998. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol., 81:730-734.
104. See for a recent review: Thomson, C.D. 2004. Assessment of requirements for selenium and adequacy of selenium status: a review. Eur. J. Clin. Nutr., 58:391-402.
105. El-Bayoumy, K. 2001. The protective role of selenium on genetic damage and on cancer. Mut. Res., 475:123-139.
106. Ferguson, L.R. 2001. Role of plant polyphenols in genomic stability. Mut Res., 475:89-111.
107. Bagchi, D., Bagchi, M., Stohs, S.J., Ray, S.D., Sen, C. K., and Preuss, H.G. 2002. Cellular protection with proanthocyanidins derived from grape seeds. Ann N.Y. Acad Sci., 957:260-270.
108. Philpott, M., Gould, K.S., Markham, K.R., Lewthwaite, S.L., and Ferguson, L.R. 2003. Enhanced coloration reveals high antioxidant potential in new sweet potato cultivars. J. Sci. Food. Agric., 83:1076-1082.
109. Bartel, B., and Matsuda, S.P.T. 2003. Seeing Red. Science., 299:352-353.
110. Haenen, G.R.M.M., arts, M.J.T.J., Bast, A., and Coleman, M.D. 2006. Structure and activity in assessing antioxidant activity in vitro and in vivo. A critical appraisal illustrated with the flavonoids. Environm. Toxicol. Pharmacol., 21:191-198.
111. Bravo, L. 1998. Polyphenols: chemistry, dietary sources, metabolism and nutritional significance. Nutr. Rev., 56:317-333.
112. Augustin Scalbert, A., and Williamson, G. 2000. Dietary intake and bioavailability of polyphenols. J. Nutr., 130:20738-20858.
113. See e.g.: Mattivi, F., Zulian, C., Nicolini, G., and Valenti, L. 2002. Wine, biodiversity, technology, and Antioxidants. Ann N.Y. Acad Sci. 957:37-56.
114. Soleas, G.J., Grass, L., Josephy, P.D., Goldberg, D.M., and Diamandis, E.P. 2002. A comparison of the anticarcinogenic properties of four red wine polyphenols. Clin. Biochem., 35:119-124.
115. Manach, C., Williamson, G., Morand, C., Scalbert, A., and Rémésy, C. 2005. Bioavailability and bioefficacy of polyphenolsin humans I. Review of 97 Bioavailability Studies. Am J Clin Nutr., 81(suppl):230S-242S.
116. Williamson, G., and Manach, C. Bioavailability and Bioefficacy of Polyphenols in Humans II. Review of 93 Intervention Studies. Am. J. Clin. Nutr., 81(suppl):243S-2552S.
117. Li, H.-L., Huang, Y., Zhang, C.-N., Liu, G., Wei, Y.-S., Wang, A.-B., Liu, Y.-Q., Hui, R.-T, Wei, C., Williams, G.M., Liu, D.-P, and Liang, C.-C. 2006. Epigallocatechin-3 gallate inhibits cardiac hypertrophy through blocking reactive oxidative species-dependent and-independent signal pathways. Free. Rad. Biol. Med., doi:10.1016/j.freeradbiomed.2006.01.005.
118. Bagchi, D., Sen, C.K., Ray, S.D., Das, D.K., and Bagchi, M. 2003. Molecular mechanisme of cardioprotection by a novel grape seed proanthocyanidin extract. Mut. Res., 523-524:87-97.
119. Lambert, J.D., Hong, J., Yang, G., Liao, J., and Yang, C.S. 2005. Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am. J. Clin. Nutr., 81(suppl):284S-291S.
120. Heijnen, C.G.M., Haenen, G.R.M.M., Wiseman, S.A., and Tijburg, L.B.M. 2000. The interaction of tea flavonoids with the NO-system: discrimination between good and bad NO. Food Chem., 70:365-370.
121. Lee, J.-S., Oh, T.-Y., Young-Kyung Kim, Y.-K., Baik, J.-H., So, S., Hahm, K.-B., and Surh, Y.-J. 2005. Protective effects of green tea polyphenol extracts against ethanol-induced gastric mucosal damages in rats: Stress-responsive transcription factors and MAP kinases as potential targets. Mut. Res., 579:214-224.
122. Dolara, P., Luceri, C., De Filippo, C., Femia, A.P., Giovannelli, L., Caderni, G., Cecchini, C., Silvi, S., Orpianesi, C., and Cresci, A. 2005. Red wine polyphenols influence carcinogenesis, intestinal microflora, oxidative damage and gene expression profiles of colonic mucosa in F344 rats. Mut. Res., 591:237-246.
123. Schneider, Y., Vincent, F., Duranton, B., Badolo, L., Gossé, F., Bergmann, C., Seiler, N., and Raul, F. 2000. Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Lett., 158:85-91.
124. Da Silva, J., Herrmann, S.M., Heuser, V., Peres, W., Possa Marroni, N., Gonzáles-Gallego, J., and Erdtmann, B. 2002. Evaluation of the genotoxic effect of rutin and quercetin by comet assay and micronucleus test. Food Chem Tox., 40:941-947.
125. Stopper, H., Schmitt, E., and Kobras, K. 2005. Genotoxicity of phytoestrogens. Mut. Res., 574:139-155.
126. Galati, G., and O'Brien, P. J. 2004. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Rad. Biol. Med., 37:287-303.
127. Galati, G., Lin, A., Sultan, A.M., O'Brien, P.J. 2006. Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Rod. Biol. Med., 40:570-580.
128. Clifford, M.N., and Scalbert, A. 2000. Ellagitannins, occurrence in food, bioavailability and cancer prevention. J. Food Sci. Agric., 80:1118-1125.
129. Scalbert, A., Manach, C., Morand, C., Rémésy, C., and Jiménéz, L. 2005. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr. 45:287-306.
130. Matsuo, M., Sasaki, N., Saga, K., and Kaneko, T. 2005. Cytotoxicity of flavonoids toward cultured normal human cells. Biol Pharm Bull., 28(2):253-259.
131. De Boer, V.C.J., Dihal, A.A., Van der Woude, H., arts, I.C.W., Wolftram, S., Alink, G.M., Rietjens, I.M.C.M., Keijer, J., and Hollman, P.C.H. 2005. Tissue distribution of quercetin in rats and pigs. J. Nutr., 135:1718-1725.
132. Barotto, N.N., Lopez, C.B., Eynard, A.R., Fernandez Zapico, M.E., and Valentich, M.A. 1998. Quercetin enhances pretumorous lesions in the NMU model of rat pancreatic carcinogenesis. Cancer Lett., 129:1-6.
133. Pereira, M. A., Grubbs, C.J., Barnes, L.H., Li, H., Olson, G.R., Eto, I., Juliana, M., Whitaker, L.M., Kelloff, G.J., Steele, V.E., and Lubet, R.A. 1996. Effects of the phytochemicals, curcumin and quercetin, upon azoxymethane-induced colon cancer and 7,12-dimethylbenz[a]-anthracene-induced mammary cancer in rats. Carcinogenesis., 17:1305-1311.
134. See also note 11. The study of Baratto et al. cited here used 10 g quercetin/kgbw in their study, which, in terms of human diet exposure ranges reported on is unrealistically high. See the paper of Ames and Gold discussing the issue of the maximum tolerated dose approach in cancer research, and the flurry of responses generated by that paper: Ames, B.N., and Gold, L.S. 1990. Too Many Rodent Carcinogens: Mitogenesis Increases Mutagenesis. Science., 249:970-971.
135. See note 83.
136. Calvo, M.S., Whiting, S.J., and Barton, C.N. 2005. Vitamin D intake: A global perspective of current status. J Nutr., 135:310-316.
137. See also: Chatterjee, M. 2001. Vitamin D and Genomic stability. Mut Res., 475:69-88
138. Garland, C.F., Garland, F.C., Gorham, E.D., Lipkin, M., Newmark, H., Mohr, S.B., and Holick, M.F. 2006. The Role of vitamin D in cancer prevention. Am. J. Pub. Health., 96:252-261.
139. See e.g. also: Mehta, R.G., and Mehta, R.R. 2002. Vitamin D and cancer. J. Nutr. Biochem., 13:252-264.
140. See note 22.
141. See e.g.: Oakley Jr., G.P. 1998. Eat right and take a multivitamin. N. Engl. J. Med., 338:1060-1061.
142. Ocké, M. C., Buurma-Rethans, E.J.M., and Fransen, H.P. 2005. Dietary supplement use in the Netherlands. Current data and recommendations for future assessment. RIVM report 350100001/2005, Bilthoven, The Netherlands.
143. Lazarou, J., Pomeranz, B.H., and Coreym P.N. 1998. Incidence of adverse drug reactions in hospitalized patients. A meta-analysis of prospective studies. JAMA. 279(15): 1200-1205.
144. Linearity, both in terms of the threshold and non-threshold model, seems outdated with the advent and increasing acceptance of the hormesis model. See e.g.: Conolly, R.B., Gaylor, D.W., and Lutz, W.K. 2005. Population variability in biological adaptive responses to DNA damage and the shapes of carcinogen dose-response curves. Tox Appl. Pharm., 207:8570-8575.
145. Pollycove, M., and Feinendegen, L.E. 1999. Molecular biology, epidemiology, and the demise of the linear no-threshold (LNT) hypothesis. C. R. Acad. Sci. Paris, Sciences de la vie/Life Sciences., 322:197-204.
146. See also: Calabrese, E.J., and Baldwin, L.A. 2003. Toxicology rethinks its central belief. Hormesis demands a reappraisal of the way risks are assessed. Nature., 421:691-692.
147. Calabrese, E.J. 2004. Hormesis: from marginalization to mainstream. A case for hormesis as the default dose-response model in risk assessment. Tox Appl. Pharm., 197:125-136.
148. Tubiana, M., Aurengo, A., Averbeck, D., Bonnin, A., Le Guen, B., Masse, R., Monier, R., Valleron, A.J., and De Vathaire, F. 2005. Dose-effect relationships and estimation of the carcinogenic: effects of low doses of ionizing radiation. Académie des Sciences [Academy of Sciences], Académie Nationale de Médecine [National Academy of Medicine].
149. See e.g.: European Commission-Joint Research Centre Institute for Health and Consumer Protection European Chemicals Bureau (ECB), 2003. European Union Risk Assessment Report 12-Benzenedicarboxylic Acid, di-C8-10-Branched Alkyl Esters, C9-Rich and di-"Isononyl" Phthalate (DINP). Publications Office, Brussels.
150. Doelman, C.J.A., Borm, P.J.A., Bast, A. 1990. Plasticisers and bronchial hyperreactivity. Lancet., 335:725.
151. Dourson, M.L., Felter, S.P., and Robinson, D. 1996. Evolution of science-based uncertainty factors in noncancer risk assessment. Reg. Tox Pharm. 24(2): 108-120.
152. Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety. 2002. O J Eur Comm. L31:1-24.
153. Graham, J.D. 2001. Decision-analytic refinements of the precautionary principle. J. Risk. Res., 4(2):127-141.
154. Wiener, J.B. 2001. Precaution in a Multi-Risk World. Duke Law School Public Law and Legal Theory Working Paper Series, Working Paper No. 23.
155. See note 37, p. 5.
156. Christoforou, T. 2004. The regulation of genetically modified organisms in the european union: the interplay of science, law and politics. Common. Market. Law. Review., 41:637-709.
157. See on the issue of the scientific method and risk assessment: Seiler, F.A., and Alvarez, J.L. 1994. The Scientific Method in Risk Assessment. Technol. J. Franklin Inst., 331 A:53-58.
158. See e.g.: Westra, L. 1997. Post-normal Science, the Precautionary Principle and the Ethics of Integrity. Found Science., 2:237-262.
159. Funtowicz, S., Ravetz, J. 1999. Post-normal Science. Environmental Policy under Conditions of Complexity. See: http://www.nusap.net/sections.php?op= viewarticle&artid=13 (Last visited on the 14th of February, 2007).
160. See for criticism on relativism e. g.: Laudan, L. 1996. Beyond Positivism and Relativism. Theory, Method, and Evidence., Westview Press, Colorado.
161. Gellner. E. 1992. Reason and Culture. The Historic Role of Rationality and Rationalism., Blackwell, Oxford.
162. Raffensperger, C., and Tickner, J. (eds.) 1999. Protecting Public Health and the Environment: Implementing the Precautionary Principle. Island Press, Washington DC.
163. See note 97.
164. Cross, F.B. 1996. Paradoxical perils of the precautionary principle. Wash. Lee Law Rev., 53:851-925.
165. Sunstein, C.R. 2005. Laws of Fear: Beyond the Precautionary Principle. Cambridge University Press, Cambridge, U.K.
166. See for the issue of precautionary choices in a cultural and historical perspective: Hanekamp, J.C., Verstegen, S.W., and Vera-Navas, G. 2005. The historical roots of precautionary thinking: the cultural ecological critique and "The Limits to Growth". J. Risk. Res., 8(4):295-310.
167. Hanekamp, J.C. 2006. Precaution and Cholera: A Response to Thickner and Gouveia-Vigeant. Risk Anal., 26(4):1013-1019.
168. See also: Turvey, C.G., and Mojduszka, E.M. 2005. The Precautionary Principle and the law of unintended consequences. Food Pol. 30:145-161.
169. See further: Marchant, G.E., and Mossman, K.L. 2004. Arbitrary & Capricious: the Precautionary Principle in the European Union Courts. American Enterprise Institute, Washington D.C.
170. Furedi, E 2002. Culture of Fear. Risk-Taking and the Morality of Low Expectation. Continuum, London. See also: Hanekamp et al., note 107.
171. See further: Gori, G.B. 1996. Science, Imaginable Risks, and Public Policy: Anatomy of a Mirage. Reg Tox Pharm., 23:304-311.
172. See note 30.
173. See note 108.
174. See note 44.
175. Burgess, A. 2001. Flattering consumption, creating a Europe of the consumer. J. Consumer Cult., 1(1):93-117.
176. See further: Gori, G.B. 2001. The Costly Illusion of Regulating Unknowable Risks. Reg Tox Pharm., 34:205-212.
177. See: http://curia.eu.int/jurisp/cgi-bin/form.pl?lang=en&Submit= Submit&alldocs=alldocs&docj=docj&docop=docop&docor= docor&docjo=docjo&numaff=C-154%2F04&datefs=&datefe= &nomusuel=&domaine=&mots=&resmax=100.
178. See note 37, p. 11.
179. See e. g. for different critical perspectives: Stone, C.D. 2001. Is There a Precautionary Principle? Env Law Rep., 10789-10799.
180. Conko, G. 2003. Safety, risk and the precautionary principle: rethinking precautionary approaches to the regulation of transgenic plants. Trans Res. 12: 639-647.
181. Hahn, R.W., Sunstein, C.R. 2005. The precautionary principle as a basis for decision making. Econ Voice. 2(2) Article 8:1-9.
182. See note 61.
183. See Keeney, 1997, note 34.
184. Gerdtham, U.-G., and Johannesson, M. 2002. Do life-saving regulations save lives? J Risk Uncertainty., (24:3):231-249.
185. Shohaimi, S., Welch, A., Bingham, S., Luben, R., Day, N., Wareham, N., and Khaw, K.-T. 2004. Residential area deprivation predicts fruit and vegetable consumption independently of individual educational level and occupational social class: a cross sectional population study in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk). J. Epidemiol Community Health., 58:686-691.
186. James, W.P.T., Nelson, M., Ralph, A., and Leather, S. 1997. Socioeconomic determinants of health: The contribution of nutrition to inequalities in health. Brit. Med. J., 314:1545-1549.
187. Darmon, N., Ferguson, E.L., and Briend, A. 2002. A cost constrained alone has adverse effects on food selection and nutrient density: an analysis of human diets by linear programming. J. Nutr., 132:3764-3771.
188. Grosse, S.D., Waitzman, N.J., Romano, P. S., and Mulinare, J. 2005. Reevaluating the benefits of folic acid fortification in the united states: economic analysis, regulation, and public health. Am. J. Pub. Health., 95(11):1917-1922.
189. Grant, W.B., Cedric, F., Garland, C.F., Michael, F., and Holick, M.F. 2005. Comparisons of estimated economic burdens due to insufficient solar ultraviolet irradiance and vitamin D and excess solar UV irradiance for the United States. Photochem. Photobiol., 81:1276-1286.
190. Ames, B.N. 2003. The metabolic tune-Up: Metabolic harmony and disease prevention. J. Nutr., 133:1544S-1548S.
191. See note 26.
192. Barnard, R.C. 1994. Scientific Method and Risk Assessment. Reg Tox Pharm., 19:211-218.
193. Mill, J.S. 1859. On Liberty. Cited from http://www.utilitarianism. com/ol/five.html (last visited on the 14th of February, 2007).
194. See for a study on herbal medicinal products e.g.: Ernst, E. 2004. Risks of herbal medicinal products. Phamacoepi drug safety. 13:767-771.
195. Over-the-counter medication. 2005. British Medical Association Board of Science. This report can be downloaded from http://www.bma.org.uk/ap. nsf/AttachmentsByTitle/OTC0505/$FILE/OTC0505.pdf (last visited on the 14th of February, 2007).
196. See e.g. note 91.
197. Tacit knowledge, opposite to codified (usually scientific) knowledge, is part and parcel of our daily lives and is transmitted through interpersonal contact, not through schoolbooks or scientific publications. Skills and traditions formed in laboratories, for instance, are utilized extensively, yet are not part of the codified output, such as journal publications and books. Therefore, even scientific knowledge in the public domain needs to be found, interpreted by specialists, and reprocessed for actual use. See Mokyr, J. 2002. The Gifts of Athena. Historical Origins of the Knowledge Economy. Princeton University Press, Princeton.
198. Regulation (EC) No 258/97 of the European Parliament and the Council of 27 January 1997 concerning novel foods and novel ingredients. O. J. Eur. Comm. L43:1-7. In fact, this regulation defines a novel food or ingredient as novel when it is without a history of use in the EU (sic).
199. See e.g.: Wheeler, D.S., and Wheeler, W.J. 2004. The medicinal chemistry of tea. Drug Dev Res., 61:45-65.
200. See note 37, p. 11.
201. See note 38, 56.
202. See note 91.
203. See e.g.: Making Sense of Chemical Stories. A Briefing for the Lifestyle Sector on Misconceptions about Chemicals. 2006. Sense about Science, London, UK. The report can be downloaded on http://www. senseaboutscience.org.uk/pdf/Makaing Sense of Chemical Stories.pdf.
204. See note 29.
205. Weber, M. 1949. On the Methodology of the Social Sciences. Free Press, New York. In the justification phase of science, scientists try to convince the rest of the scientific community of the adequacy of the explanations they have put forward through the different (scientific) platforms of communication in order to have their theories accepted as a part of the corpus of scientific knowledge. Here, worldview influences on science are the most problematical and counter-productive, as it distorts the process of science fundamentally. Theories should only be accepted by the scientific community in the light of considerations that involve transparent and reproducible empirical data, other (accepted) theories, and cognitive values such as consistency, simplicity, and explicatory power. Worldview (political and ideological) considerations, but also appeals to authority, consequences, force, and popularity -to name some of the argumentation fallacies- are illegitimate ways of deciding between theories. See note 29.
206. See also: Polanyi, M. 1962. The republic of science: Its political and economic theory. Minerva., 1:54-73.
207. Polanyi, M. 1963. The Potential Theory of Adsorption. Authority in Science has its Uses and its Dangers. Science., 141:1010-1013.
208. See note 29.
209. See note 24.
210. Stern, P.C., and Fineberg, H.V. (eds.) 1996. Understanding Risk. Informing Decisions in a Democratic Society. National Research Council, National Academy Press, Washington, D.C.
211. Durodié, B. 2003. Limitations of public dialogue in science and the rise of new "Experts". Crit Rev Inter Soc Polit Phil., 6(4):8292.
212. Harris, J., and Holm, S. 2002. Extending human lifespan and the precautionary paradox. J Med Philos., 27:355-368.