The power of lycopene

Prostate support, cardio protection, repair from UV radiation — lycopene can do it all.

Mark J Tallon, PhD, uncovers the growing body of science behind this multi-faceted ingredient

The lovable tomato has caused quite a stir scientifically speaking over the past few years. Recent market projections by the Business Communication Co (BCC)1 suggest the carotenoid market will breach the $1 billion mark by 2009 and lycopene sales will surpass $26 million, according to Frost & Sullivan.2

Although at present the food colourant market is the leading carotenoid outlet, the fastest-growing segment for carotenoid sales is poised to boom from dietary supplements and fortified foods. These rapid upturns in possible market revenue have not gone unnoticed.

Such is the case for European behemoths DSM (Roche) and BASF, who at present control three-fourths of the global carotenoid market. Word on the street, as reported by BCC, suggests these market statistics are unlikely to change for at least the next five years.

So how have these statistics been impacted by the scientific turnover of lycopene research over the past 10 years? Where is the research heading? And what are the immediate and long-term challenges facing both the carotenoid and lycopene market?

Over the past 10 years, we have seen some remarkable growth in the academic interest in tomatoes, carotanoids, and, ultimately, lycopene. The yearly lycopene publication number over the past 10 years has increased by more than 400 per cent (tomatoes and carotenoids by 80 and 170 per cent, respectively).

This vast increase in research is reflective of the global growth of carotenoids sales for the enhancement of health. From the early beginnings of Dr Giovannuchi?s epidemiological-based insights, the antioxidant activities of carotenoid intake3 has now been confirmed by clinically validated, double-blinded and randomized interventions.

But where is this latter research taking the supply and manufacturing chain? And what opportunities are emerging for hooking new public interest in tomato-based extracts for enhancing health and slowing deleterious disease states?

I would be remiss without giving an overview of a defining disease state regarding lycopene?s action: prostate health. Prostate cancer is a worldwide health problem, with an estimated 230,000 new cases occurring in the US in 2004 and 30,000 deaths.4 This places prostate cancer as the second-leading cause of cancer death in US men.4

The prostate health crisis led to a search for a prevention strategy that was effective from a clinical and fiscal basis. Soon, epidemiological evidence of the protective role of tomatoes in the US diet provided a possible answer 3,5 as men who consumed the most tomato products had significantly lower risk of developing prostate cancer. Following these initial observations, many studies have investigated the effects of tomato product extracts, including lycopene, on diseases of the prostate.6,7

One of the most interesting studies over the last year is that by Ulrich Siler?s group at Charité University Hospital, Humboldt-University Berlin.8 Although lycopene research has been primarily epidemiological and/or looking into disease states, this current study answers the fundamentals about disease prevention as well as its actions on health issues.

Copenhagen male rats were supplemented with 200ug lycopene/g diet and every two weeks starting at day 0 until week 8, groups of 6-8 rats were killed and their prostates analysed for lycopene accumulation and distribution, changes in gene expression, and prostate lobe weight.

In comparison to placebo following the same dietary intake, less lycopene showed increased lycopene in primarily the alltrans isoform with the highest distribution/uptake observed in the lateral lobe of the prostate. Further analysis went on to show that factors involved in prostate cancer prevention were significantly affected including a reduction in androgenic enzymes, IGF-1, and a selection of inflammatory cytokines. These very insightful results suggest lycopene may offer a long-term strategy in reducing the risk of prostate cancers.

Of greater interest is the effectiveness of lycopene as a treatment strategy, which may depend on where prostate cancers occur (ie, which lobe) due to the localized accumulation of lycopene in the prostate. Re-analysis of epidemiological studies should be able to shed light on this and may be an interesting factor in treatment outcomes.

Antioxidants have been shown time and again to slow the progression of atherosclerosis because of their ability to neutralize damaging oxidative processes.9,10 The oxidation of low-density lipoproteins, which transport cholesterol into the blood stream, is thought to play an integral role in the etiology of cardiovascular diseases including heart attack and ischemic strokes.11,12

The logical therapeutic step was to look for antioxidants, which were powerful oxidant quenchers. One of the answers came in the form of the most potent singlet oxygen quencher among carotenoids: lycopene.13

Following on from studies suggesting lycopene may affect risk factors of coronary heart disease, new research sought to systematically examine the effects of lycopene in the prevention of platelet aggregation and thrombus formation.14

Lycopene is known to inhibit sunburn and delay light-induced skin ageing
Researchers found a dose-dependency relationship between lycopene and inhibited platelet aggregation (a risk factor in blood-clot formation and stroke). The biochemical pathways suggested to bring about this effect were inhibition of intra-cellular Ca+2 mobilization and activation of cyclic GMP/nitrate in human platelets, resulting in the inhibition of platelet aggregation.

The results may imply that tomato-based foods such as lycopene are especially beneficial in the prevention of platelet aggregation and thrombosis.14 Extensive human trials are still required to confirm these results.

The US cosmeceuticals industry is projected to grow to $4.7 billion by 202015 and as such, functional foods competitors have been scrambling to carve out their share of the personal health industry over the past decade. One of the most lucrative and under-exploited niches in this category is dermal health.

Dr Karin Wertz, laboratory head at DSM Nutritionals, also believes this is a very important growth area. "In addition to prostate cancer prevention, lycopene has interesting benefits for skin health, such as inhibition of sunburn and delay of light-induced skin ageing," he says.

Exposure to UV light brings about a series of photo-oxidative reactions that can negatively impact dermal health.16 The biochemical reactions brought about via photo-oxidation damage the integrity of skin cells leading to premature ageing and in some cases melanomas. One initial skin damage sign visible upon excessive exposure to UV light is erythema (redness or inflammation of the skin or mucous membranes) of which the impact of carotenoids and lycopene have been assessed as a method of decreasing photo-damage.17,18

Investigators assessed the photoprotective properties of synthetic lycopene in comparison with a tomato extract (Lyc-o-Mato) and a drink containing solubilized tomato extracts (Lyc-o-Guard-Drink).18 These three different sources amounted to about 10mg/day of lycopene. Following 12 weeks of supplementation, significant increases in serum lycopene levels and total skin carotenoids were observed in all groups.

At weeks 0, 4 and 12, erythema was induced with a solar light simulator. A decrease in erythema formation was observed in all groups from weeks 0-12. Compared to week 0, the reduction in erythema was significantly lower (25 per cent) in the synthetic lycopene group. However, the protective effect was more pronounced in the Lyc-o-Mato (38 per cent) and Lyc-o-Guard-Drink (48 per cent) groups.

In the two latter groups, phytofluene and phytoene may have contributed to protection.18 Both phytofluene and phytoene exhibit absorption maxima at wavelengths of UV light giving additional protection. Absorption of UV light protects skin from photo-damage and might explain the differences observed between groups.18

Based on these results, a combination of tomato extracts including lycopene may be the most effective way to protect the skin from UV damage. However, topical applications may give different results and are worth further investigation.

Frost & Sullivan forecasts the European carotenoid market will rise to $419.6 million in 20102 driven by health and ageing issues. But with all the science available on carotenoids and lycopene, public awareness seems to be lagging.

In fact, health claims might even confuse consumers and actively turn them away from purchases, according to the UK?s Food Standards Agency (FSA), which last year conducted extensive research into how consumers understand claims.19 The agency concluded that consumers respond to them in a nonscientific way.

An example of claims typically misinterpreted are those that refer to cholesterol-lowering effects. These claims were viewed as being for sick people and not the average consumer — and in the worst cases, many consumers didn?t even notice them on the packaging. The FSA concluded that issues of brand familiarity, taste, overall product appeal and ?naturalness? of ingredients were much more important to decision-making.

One point to consider in the future exploitation of the growing carotenoid market is to take a lesson from functional foods brands that are highly successful, yet carry no health claims at all. Yakult, for example, a $2.3 billion brand, talks only about ?wellness from the inside.? We already have some focus of noningredient health claims in lycopene marketing such as Redivivo by DSM.

"Imagine a beverage with a red tomato color and providing a health benefit (a healthy red)," explains Dr Wiltrud Baier, global marketing manager at DSM Nutritional Products. "Redivivo, DSM?s lycopene-based products, is optimal for these applications, as it has excellent stability and performance, as well as the highest quality standards."

DSM may try to use the image and color of the healthy tomato as an integral branding tool rather than relying only on science-based claims.

The science behind lycopene has grown radically over the past decade with no immediate slowdown in academic interest. The fields of research have far surpassed its prostate-based roots, leading to new marketing for a host of health and disease conditions including macular degeneration, infertility, high blood pressure (preeclampsia), asthma, drug-induced carotenoid depletion and ameliorating the decline in oxidative stress during intense fatiguing exercise.

Some of the most relevant issues to food technologists and research scientists are primarily issues of bioavailability and of which cis isomers of lycopene are the most effective in providing a positive impact in specific disease cases.

Following the establishment of lycopene as a positive nutrient in food, scientists are now assessing and searching for new sources of lycopene (ie, red carrots, passionflower fruit, red palm oil) and their influence on human health.

Together, peer-reviewed research and increasing public education of tomato-based extracts will surely provide a sustainable and lucrative niche in the carotenoid industry to 2010 and well beyond.

Mark J Tallon, PhD, is chief science officer of OxygeniX, a London-based consultancy firm specialising in claims substantiation, product development and technical Dr Tallon is also co-founder of Cr-Technologies, a raw-ingredients supplier.

1. The Global Market for Carotenoids. Connecticut: Business Communications Co Inc, 2001, p117.
2. Frost & Sullivan. European Carotenoids Market (B260). New York, 2003.
3. Giovannucci E, Ascherio A, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. J. Natl Cancer Inst 1995; 87; 23:1767-76.
4. American Cancer Society, Cancer Facts and Figures 2004, National Home Office. Atlanta, p1-56.
5. Mills PK, Beeson WL, et al. Cohort study of diet, lifestyle and prostate cancer in Adventist men. Cancer; 1989; 64:598-604.
6. Agarwal S, Rao AV. Tomato lycopene and low-density lipoprotein oxidation: A human dietary intervention study. Lipids 1998; 33:981-4.
7. Kucuk O, Sakr, FH, et al. Lycopene supplementation in men with prostate cancer (PCa) reduces grade and of preneoplasia (PIN) and tumor, decreases serum prostate specific antigen and modulates biomarkers of growth and differentiation [Abstract P1.13]. International Conference on Diet and Prevention of Cancer; 1999 Tampere, Finland.
8. Siler U, Herzog A, et al. Lycopene effects on rat normal prostate and prostate tumor tissue. J.Nutr. 2005; 135(8):2050S-2S.
9. Parthasarathy S. Mechanisms by which dietary antioxidants may prevent cardiovascular diseases. J Med Food 1998; 1:45-51.
10. Morris DL, Kritchevsky SB, et al. Serum carotenoids and coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study. JAMA 1994; 272(18):1439-41.
11. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet. 1994; 344: 793-795.
12. Parthasarathy S, Steinberg D, et al. The role of oxidized low-density lipoproteins in the pathogenesis of atherosclerosis. Annu Rev Med 1992; 43:219-25.
13. Di Mascio P, Kaiser S, et al. Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch Biochem Biophys 1998; 274(2):532-8.
14. Hsiao G, Wang, Y, et al. Inhibitory effects of lycopene on in vitro platelet activation and in vivo prevention of thrombus formation. J.Lab.Clin.Med. 2005; 146(4):216-26.
15. Freedonia Group. World Nutraceuticals Report. 2001, Cleveland, Ohio
16. Ribaya-Mercado JD, Garmyn M, et al. Skin lycopene is destroyed preferentially over beta-carotene during ultraviolet irradiation in humans. J.Nutr. 1995; 125(7):1854-9.
17. Fazekas Z., Gao D., et al. Protective effects of lycopene against ultraviolet B-induced photodamage. Nutr Cancer 2003; 47(2):181-7.
18. Aust O, Stahl W, et al. Supplementation with tomato-based products increases lycopene, phytofluene, and phytoene levels in human serum and protects against UV-light-induced erythema. Int J Vitam Nutr Res 2005; 75(1):54-60.
19. Food Standard Agency. Consumer attitudes to food standards: UK report. 2004, London, UK p1-130.

Mark J Tallon, PhD, is chief science officer of OxygeniX, a London-based consultancy firm specialising in claims substantiation, product development and technical writing. Dr. Tallon is also co-founder of Cr-Technologies, a raw-ingredients supplier.

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