From functional foods to neutraceuticals
Functional foods represent a concept rather than a specific and defined food category. ÔÇ£A food can be regarded as ‘functional’ if it is satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects in a way which is relevant to either an improved state of health and well-being and/or reduction of risk of disease. Functional foods must remain foods and they must demonstrate their effects in amounts which can normally be expected to be consumed in the diet. They are not pills or capsules, but part of a normal food patternÔÇØ 1
Diplock AT, Aggott PJ, Ashwell M, et. al. Scientific concepts of functional foods in Europe: consensus document. Br J Nutr. 1999; 81: 1-27. . The Mediterranean diet, of which the Cretan diet is the archetype, is recognised to be important in reducing chronic disease and some cancers 2 Simopoulos AP. The traditional diet of Greece and cancer. Eur J Cancer Prev. 2004; 13:219-30. 3 Simopoulos AP. What is so special about the diet of Greece? The scientific evidence. World Rev Nutr Diet. 2005; 95:80-92. . One of the main foods of the traditional Mediterranean diet is the tomato and its derivatives (sauces), of which lycopene is quantitatively the most important component 4 Itsiopoulos C, Hodge A, Kaimakamis M. Can the Mediterranean diet prevent prostate cancer? Mol Nutr Food Res. 2009; 53:227-39. . For a correct interpretation of the results of in vivo studies on lyco – pene, it must be remembered that these were carried out using toma- toes or their derivatives. In addition to lycopene, tomatoes contain many other micronutrients and phytochemicals, including other carotenoids, polyphenols, vitamin C and vitamin E, which may enhance their biological activity 5Mein JR, Lian F, Wang XD. Biological activity of lycopene metabolites: implications for cancer prevention. Nutr Rev. 2008; 66:667-83. .
*Patent for Industrial Invention No 0001354930 International Application Published under The Patent Cooperation Treaty WO 2008/015490 A1
For dietary action to have any effect on health, it must be constant and sufficient in terms of quantity. The current Western lifestyle allows little room for this ÔÇô hence the need for nutraceuticals. “Nutraceutical” is a made-up term coined in 1989 by Steven DeFelice by combining the terms “nutrition” and “pharmaceutical“; according to DeFelice’sdefinition “a food (or part of a food)that has a medical or health benefit including the prevention and/or treatment of disease” 6 Brower V. Nutraceuticals: poised for a healthy slice of the healthcare market? Nat Biotechnol. 1998; 16: 728-31. . Zeisel further specified that neutraceuticals are diet supplements that deliver a concentrated form of a presumed bioactive agent from a food, presented in a nonfood matrix, and used to enhance health in doses that exceed those that could be obtained from normal food 7 Zeisel SH. Regulation of ÔÇ£nutraceuticals.ÔÇØ Science. 1999; 285:1853-1855. . Lycopene fully satisfies the criteria and this has been the premise for developing a method of producing lycopene at industrial levels that can maintain its natural properties intact while also preserving the biochemical medium required for its effects on health.
Lycopene production methods
Lycopene production methods were recently described by Rescio, et al. 8
Rescio L, Di Maio A, Cazzola P. Lycopene, photoprotection and skin care: the benefits of or- ganic quality. J Plastic Dermatol. 2010; 6:37-47. . Lycopene used for the preparation of dietary supplements or other preparations can be produced by chemical synthesis (synthetic lycopene) or extracted from plants using two methods (natural lycopene, lycopene bio) (Figure 1).
Synthetic lycopene is produced from synthetic raw materials dissolved in organic solvents. The process normally used (Witting’s process) is long and complicated. In its final stages, it involves the condensation of two intermediate products (phosphonium methane- sulfonate and C10-dialdehyde), dissolved in toluene in the presence of sodium methyloxide to form crystals of crude lycopene that are then purified by filtration and recrystallisation. The resulting lycopene crystals are large, regularly-shaped and free of impurities. In the final product, the lycopene is very concentrated (90-95% by weight). It breaks down easily and has low bioavailability. It is known
that, all other conditions being equal, the bioavailability of lycopene increases with decreasing crystal size: reducing the size of lycopene crystals from 5 mm to 0.5 mm increases the bioavailability of lycopene by 30% 9 Richelle M, Bortlik K, Liardet S, et al. A food-based formulation provides lycopene with the same bioavailability to humans as that from tomato paste. J Nutr 2002; 132:404-408. .
Dietary supplements based on synthetic lycopene are obtained by diluting the product of synthesis to concentrations of between 1% and 10% by weight with lipids and adding preservatives and other exogenous chemical compounds. Synthetic lycopene may contain residues of organic solvents used in the manufacturing process and other impurities (unreacted raw materials, reaction intermediates, by- products) that are potentially toxic even at very low concentrations. C25-aldehyde (apo-12ÔÇÖ-licopenal) is a secondary product that is formed during the synthetic lycopene production process. Because this compound is very toxic, its concentration must be
minimised through purification processes to safeguard the quality and safety of the finished product.
Lycopene can be extracted from ripe tomato fruits using a traditional process that uses organic solvents that are toxic to human health and harmful to the environment (natural lycopene) or an innovative process that uses supercritical carbon dioxide as the sole extraction solvent (lycopene bio).
Natural lycopene is extracted from fresh tomato or residues of the tomato processing industry (skins) through the use of organic solvents (chloroform, hexane, etc.) from which it is then separated by crystallisation (Figure 2). The extraction is not selective and the resulting solution contains not only lycopene but also considerable quantities of other lipophilic substances present in tomatoes (b-carotene, lutein, zeaxanthin, astaxanthin, phytoene, phytofluene, tocopherols and tocotrienols, plant sterols, aromatic amino acids and polyunsaturated fatty acids). The substances co-extracted with lycopene present in the crystallisa- tion mother liquor partly co-precipitate and are included in the lyco- pene crystals as impurities. These impurities are of plant origin and, crucially, not toxic to the human body. They actually appear to act synergistically with the lycopene to enhance the antioxidant activity of the extract. They also give rise to the formation of smaller and less regular crystals than those of synthetic lycopene with a consequent improvement in bioavailability. The presence of impurities nevertheless gives rise to an increase in the toxicity of natural lycopene because residues of the solvents used to extract other contaminants (pesticides, dioxin, heavy metals, etc.) that may be present in the fresh tomato are absorbed/retained in the lycopene crystals in proportion to their quantity. This problem, which becomes more apparent when processing waste is used (pesticides and contaminants are concentrated in the skins), is due to the fact that tomato skins not subject to particular restrictions and/or production constraints may be used for the extraction of natural lycopene. Genetically modified tomato varieties (GMOs) and tomatoes containing residues of pesticides and heavy metals outside the limits per- mitted for human consumption may be used. Natural lycopene may be ÔÇ£purifiedÔÇØ and made less toxic by recrystallisation with a conse- quent loss of yield and most of the benefits of synergies due to the co-extracted substances. In this case too, the lycopene in the finished product is extremely concentrated (approximately 60% by weight) and must be diluted with lipids for the formulation of dietary supplements.
Lycopene bio is obtained through extraction with carbon dioxide under supercritical conditions 10 Rescio L, Ciurlia L, Vasapollo G, et al. Innovative supercritical CO2 extraction of lycopene in the presence of vegetable oil as co-solvent. Journal of Supercritical Fluids 2004; 29:87-96. 11 Rescio L, Ciurlia L, Bleve M. Supercritical carbon dioxide co-extraction of tomatoes (Lyco- persicum esculentum L.) and hazelnuts (Corilus avellana L.). A new procedure on obtaining a source of natural lycopene. Journal of Supercritical Fluids 2009; 49:338-344. from a freeze-dried matrix of ripe fruits grown organically.
Such methods exclude the use of genetically modified varieties and agrochemicals (fertilisers, antiparasitics and pesticides) and adopt strategies for biological control of plant diseases as established by EU Regulations EC 834/07 and EC 889/08. Figure 2
The absence of toxic and harmful organic solvents in the extraction process makes it impossible for the finished product to be contaminated (Figure 2).
For these reasons, the extract is 100% natural and completely free of residues of organic solvents and/or other toxic and harmful chemicals. Lycopene bio, like natural lycopene, contains other bioactive carotenoids and molecules present in the tomato that contribute synergistically to its beneficial effects and increase its stability and bioavailability 12
Fuhrman B, Volkova N, Rosenblat M, Aviram M. Lycopene synergistically inhibits LDL oxidation in combination with vitamin E, glabridin, rosmarinic . These substances, which may be present in quantities higher than that of lycopene, retain their biochemical properties and their biological activity in the extract. The antioxidant action of lycopene bio is therefore far higher than that of a solution of synthetic or natural lycopene of equal con- centration (unpublished CNR [Italian Research Council] data). Lycopene bio is maximally predisposed to the assimilation process because it is not present in crystalline form but as a super-saturated solution of lycopene in a vegetable oil rich in unsaturated fatty acids (oleoresin) (Figure 3).
This property is closely connected with the production technology. The extraction of lycopene from tomatoes using supercritical CO2 is promoted by the presence of lipids (from the extraction matrices). During separation of the solid phase from the supercritical phase, the lipids prevent the lycopene from clumping to form crystalline structures and thus give rise to a product where the lycopene is intimately and uniformly surrounded by lipids and other co-extracted compounds. The lipids also promote the formation of micelles/emulsions through which carotenoids are absorbed by enterocytes and conveyed to the tissues through the bloodstream. It has also been shown that, other conditions being equal, the bio- availability of lycopene is significantly higher when taken in the presence of b-carotene and plant lipids 13. The bioavailability of lycopene bio is further increased by the presence of higher quantities of cis forms than other isomers.
References [ + ]
Diplock AT, Aggott PJ, Ashwell M, et. al. Scientific concepts of functional foods in Europe: consensus document. Br J Nutr. 1999; 81: 1-27.
|2.||↑||Simopoulos AP. The traditional diet of Greece and cancer. Eur J Cancer Prev. 2004; 13:219-30.|
|3.||↑||Simopoulos AP. What is so special about the diet of Greece? The scientific evidence. World Rev Nutr Diet. 2005; 95:80-92.|
|4.||↑||Itsiopoulos C, Hodge A, Kaimakamis M. Can the Mediterranean diet prevent prostate cancer? Mol Nutr Food Res. 2009; 53:227-39.|
|5.||↑||Mein JR, Lian F, Wang XD. Biological activity of lycopene metabolites: implications for cancer prevention. Nutr Rev. 2008; 66:667-83.|
|6.||↑||Brower V. Nutraceuticals: poised for a healthy slice of the healthcare market? Nat Biotechnol. 1998; 16: 728-31.|
|7.||↑||Zeisel SH. Regulation of ÔÇ£nutraceuticals.ÔÇØ Science. 1999; 285:1853-1855.|
Rescio L, Di Maio A, Cazzola P. Lycopene, photoprotection and skin care: the benefits of or- ganic quality. J Plastic Dermatol. 2010; 6:37-47.
|9.||↑||Richelle M, Bortlik K, Liardet S, et al. A food-based formulation provides lycopene with the same bioavailability to humans as that from tomato paste. J Nutr 2002; 132:404-408.|
|10.||↑||Rescio L, Ciurlia L, Vasapollo G, et al. Innovative supercritical CO2 extraction of lycopene in the presence of vegetable oil as co-solvent. Journal of Supercritical Fluids 2004; 29:87-96.|
|11.||↑||Rescio L, Ciurlia L, Bleve M. Supercritical carbon dioxide co-extraction of tomatoes (Lyco- persicum esculentum L.) and hazelnuts (Corilus avellana L.). A new procedure on obtaining a source of natural lycopene. Journal of Supercritical Fluids 2009; 49:338-344.|
Fuhrman B, Volkova N, Rosenblat M, Aviram M. Lycopene synergistically inhibits LDL oxidation in combination with vitamin E, glabridin, rosmarinic