POTENTIAL HEALTH BENEFITS OF WATERCRESS

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1 POTENTIAL HEALTH BENEFITS OF WATERCRESS Hippocrates was one of the first to recognize the potential health benefits of watercress. Today, good intakes of nutrient and phytochemicals-dense green leafy and/or cruciferous vegetables has been associated with a decreased risk of conditions such as certain cancers, coronary heart disease, age-related macular degeneration and skin photo damage. A prospective study of over 6000 adults found that a higher intake of cruciferous vegetables was linked to a lower risk of all cause mortality (32). However, epidemiological associations do not show causality. Ongoing laboratory, animal and human intervention studies are helping to increase our understanding of why vegetables, including watercress, offer potential health benefits. Antioxidant potential of watercress It is hypothesized that consuming foods rich in antioxidants may help to prevent or slow the oxidative stress induced by free radicals. Since there is still much to understand about phytochemicals, interest is moving towards assessing the antioxidant activity and in vivo effects of whole foods. The in vivo evidence that fruit and vegetables actually reduce markers of oxidative damage have been limited. Null findings may be influenced by many factors including absorption and metabolism of phytochemicals, study length and design, and individual variation in antioxidant status and responsiveness to dietary antioxidants. Nevertheless, studies have shown that eating fruit and/or vegetables can reduce the amount of damage free radicals cause to the blood. For example, it has been associated with markers such as a reduction in serum oxidizability, enhanced resistance of plasma lipoproteins to oxidation and increased red blood cell glutathione peroxidase. Specifically, fruit and vegetable consumption can reduce DNA damage (a precursor to the development of cancer) in blood cells. The effect in blood cells is an indicator of what is happening to tissues less accessible for sampling and testing. Responsiveness may be greater for people who are under a higher level of oxidative stress, such as smokers (34). The University of Ulster study (24) found that daily watercress consumption resulted in a 100% increase in plasma lutein, and 33% increase in beta-carotene and a significant decrease in oxidative damage to white blood cell (lymphocyte) DNA, especially amongst smokers (see page 6). CANCER Cancer ultimately stems from damage to cellular DNA, mostly caused by some form of carcinogen (cancer causing agent) or virus. Faulty genetic material can also be inherited. If not repaired, damaged cells have the potential to proliferate uncontrollably to form a tumour. Cancerous cells may also spread to and invade other tissues (known as metastasis ). Many diet and lifestyle factors can influence the development of cancer, a disease that is expected to affect more than 1 in 3 people in the UK at some stage of their lives. This section focuses on the potential benefits of watercress. Population studies associate an increased intake of cruciferous vegetables with reduced risk of cancers at several sites. In1977, one of the first papers identifying the potential of phenylethyl isothiocyanate (PEITC) to inhibit carcinogenesis (the development of normal cells into cancerous cells) in laboratory animals was published (39). In 1995, it was demonstrated that eating watercress protected smokers from a

2 key tobacco carcinogen implicated in lung cancer (40). In 2000, UK scientists identified a number of active isothiocyanates in watercress and found that watercress extract has more powerful anticarcinogenic activity than PEITC alone (41). In 2007 an important study with watercress adds to the few human intervention studies investigating the effects of cruciferous vegetable consumption on cancer risk. Isothiocyanates proposed anti-cancer mechanisms Many studies from laboratory and cell culture studies, through animal models and into human trials have indicated that isothiocyanates such as PEITC and MEITCs can inhibit cancer development by: preventing carcinogen activation by inhibiting phase I enzymes such as cytochrome P450s - thus stopping a potential carcinogen becoming a carcinogen. increasing the ability of cells to resist attack from carcinogens by increasing the activity of detoxifying/antioxidant enzymes known as phase II enzymes - such as quinone reductase, glutathione S- transferases and UDPglucuronosyltransferases. inhibiting cell cycle progression - which inhibits the uncontrolled growth of cancer cells. inducing apoptosis (the death of damaged or cancer cells). Mechanisms of other Components of Watercress Studies using a watercress extract, which result in antigenotoxic (reduction in damage to DNA) effects, indicate that PEITC/other isothiocyanates are not always directly identified as the potentially active components. Flavonols such as quercetin can accumulate in the plasma and have been shown to modulate DNA damage from genotoxins in vitro and have anti-proliferative effects. The hydroxycinnamic acids ferulic acid and p-coumaric acid have been found to offer free radical scavenging activity, protection against DNA breakage in mammalian cells and inhibition of phase I enzyme activity. Watercress is also a good source of lutein and beta-carotene. Lutein has been shown to have anticarcinogenic activities in vitro. A placebo-controlled trial in post menopausal women by Zhao and colleagues with carotenoid supplements (lutein, β-carotene, lycopene and as mixed carotenoids, at levels achievable with diet) found a decrease in endogenous lymphocyte DNA damage as a result of the supplementation. Although borderline, a recent pooled analysis of 11 cohort studies investigating intakes of dietary carotenoids and colorectal cancer risk identified lutein plus zeaxanthin as the only carotenoids to show any significance. 6 COLORECTAL CANCER Epidemiological studies link cruciferous vegetable intake with a reduced risk of colorectal cancer. However, recent cohort studies appear to question the strength of these findings, despite plausible mechanisms for anti-carcinogenic activity of cruciferous vegetables. These inconsistencies may be explained by factors such as the sensitivity of measuring vegetable intake, amounts of cruciferous vegetables

3 needed to be consumed to achieve an effect, and differences in response according to glutathione S-transferase genotype (sub-grouping populations according to glutathione S-transferase genotype appears to strengthen the relationship). Further supportive evidence comes from a recent investigation into potential anti-carcinogenic mechanisms for the cruciferous vegetable watercress, led by scientists at the University of Ulster. They showed for the first time that an extract of watercress juice can inhibit the three key stages of carcinogenesis. Namely: initiation (the DNA damage that triggers cancer cell development); proliferation (uncontrolled growth) of cancer cells; and metastasis (the spread of cancer cells). The study involved incubating human colon cancer cells (HT29) with watercress extract, prepared using watercress bought from local supermarkets. The cells were then either exposed to toxins (H202, 4-Hydroxy nonenal and faecal water) known to promote the DNA damage and abnormal changes that initiate carcinogenesis, or had their ability to proliferate assessed. Metastasis (their ability to invade tissues) was assessed by studying attachment and penetration of HT115, human colorectal adenocarcinoma, cells through Matrigel. The watercress extract significantly inhibited DNA damage induced by oxidative stress from H202 (by 28%) and by faecal water (by 19%), delayed the cell cycle of the colon cancer cells, which in turn delays their growth, and significantly blocked the cells invasive or metastatic actions. The study differed from many others in that it used extracts of whole watercress rather than individual phytochemicals found in watercress to test for anticarcinogenic effects. This provided information on the overall effect of identified, and still to be identified compounds in watercress, and how they might work together. The authors concluded that their studies support the view that watercress may be effective in helping to reduce cancer risk in humans, and further studies are warranted. BREAST CANCER Inverse associations between vegetable intake, particularly cruciferous vegetables, and breast cancer have been noted in some but not all studies. To investigate possible reasons for these positive associations, Rose et al (56) used a watercress extract to assess its effects on chemically induced cancer cell invasion in human breast cancer cells (MDA-MB-23). Matrix metalloproteinase are enzymes that break down proteins such as collagen found in the extracellular matrix, which acts as a primary barrier to tumor growth and metastasis. Cancer cells can stimulate abnormally high activity of matrix metalloproteinase (including metalloproteinase-9), which is associated with increased invasive and metastatic potential. There is therefore much interest in agents that may block their action. The watercress extract (and also a broccoli extract) inhibited metalloproteinase-9 activities in vitro and also suppressed the invasive potential of human breast cancer cells. Analysis of the extracts revealed that the inhibitory effects of each vegetable were associated with the presence of 7-methylsulphinylheptyl isothiocyanates (MEITCs) and 4-methysulphinylbutyl (sulphoraphane). PROSTATE CANCER A number of epidemiological studies link consumption of diets rich in cruciferous vegetables with a reduced incidence of prostate cancer (57, 58). One prospective study found a weak association but suggested that the potential benefits of cruciferous vegetables may emerge only after many years and consumption from an early age is recommended. Direct studies with watercress have not been carried out. However, mechanisms to explain positive associations with cruciferous vegetables are being investigated. PEITC, the major isothiocyanate in watercress, has

4 recognized anticarcinogenic effects. More recent in vivo work suggests a potential effect on tumor growth. After finding that in vitro exposure of human prostate cancer cells to the N-acetylcysteine (NAC) conjugate of phenethyl isothiocyanate (PEITC-NAC), significantly inhibited their growth, Chiao et al (60) assessed the in vivo affects of a PEITC-NAC supplemented diet versus a nonsupplemented diet on tumors of human prostate cancer cells grafted on to mice. After a 9-week treatment period, there was a significant reduction in tumor size in 100% of the mice on the supplemented diet. Tumor weight was reduced by 50% compared with mice on the diet without PEITC- NAC. Mechanisms identified in this study suggest that PEITC-NAC may reduce tumor growth by inhibiting proliferation (uncontrolled cell growth) via cell cycle regulators, and inducing apoptosis (externally triggered cell death). LUNG CANCER Regular consumption of cruciferous vegetables and associated isothiocyanates has been linked to a reduced risk of lung cancer, with stronger effects noted for GST null individuals (who therefore have no potential protection from the phase II enzymes, glutathione S-transferases) after sub-grouping according to GST genotype. Anti lung cancer mechanisms for isothiocyanates have been attributed to the inhibition of phase I enzymes (so neutralizing potential carcinogens) and/or to the induction of the activity of phase II enzymes which can detoxify carcinogens. Other possible mechanisms include acting at the post initiation stage of lung tumor development via cell-cycle arrest and induction of apoptosis. Hecht and colleagues (40) had already observed significant benefits of PEITC for cancer protection in animals and wanted to assess its potential in humans. Unable to obtain a license for a human study using pharmaceutical PEITC, Hecht used watercress, the richest known food source. Eleven smokers volunteered to expose themselves to the lungspecific tobacco carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for 3 days, while consuming 2 ounces (56.8 g) of watercress at each meal. The result was a highly significant increase in urinary NNK breakdown products during days 2 and 3 which correlated with the intake of PEITC from watercress during this period. This linked PEITC and watercress consumption to the metabolism and secretion/neutralization of the lung carcinogen NNK. CARDIOVASCULAR HEALTH It has been estimated that eating at least 5 portions of a variety of fruit and vegetables a day could reduce the risk of deaths from chronic diseases such as heart disease and stroke by up to 20%. Causal mechanisms are still being clarified, but may involve reduced lipoprotein oxidation and lipid, homocysteine and blood pressure reductions. Proposed beneficial components of vegetables and fruit include: antioxidant nutrients including vitamin C, folate, flavonoids, lutein, glucosinolates, fiber and minerals such as potassium and vitamin B6. The EPIC (European Prospective Investigation into Cancer and Nutrition) Norfolk population study found that plasma ascorbic acid (vitamin C) concentration was inversely related to all-cause mortality, and from cardiovascular disease and ischemic heart disease in men and women (69). A rise in plasma ascorbic acid, equivalent to 50g of fruit or vegetable intake, was independently associated with about a 20% reduction in all-cause mortality. While no studies have been carried out with watercress to specifically assess its potential to help maintain cardiovascular health, watercress is rich in vitamin C and a good source of most of the identified beneficial components. In addition, Gill et al found that blood triglyceride levels were reduced by about 10% after the 8-week test period of watercress consumption (85g, equivalent to a vegetable portion, daily). Raised blood triglyceride levels can be a risk factor for cardiovascular disease. In the same study blood levels of lutein increased by 100%.

5 EYE HEALTH Watercress is a source of nutrients associated with the maintenance of normal vision and eye health, including vitamin A, vitamins C and E, alpha-linolenic acid and the carotenoids lutein and zeaxanthin, and beta-carotene. Higher intakes of lutein and zeaxanthin-rich foods have been associated with a lower incidence of the eye diseases such as cataract and age-related macular degeneration (50, 70-72) - the most common cause of poor vision and blindness in people over 60 in the UK. Diet is the sole source of lutein and zeaxanthin, and they are the only carotenoids concentrated in the lens and macular pigment (which protects the macula from the damaging photo-oxidative effects of blue light). Gradual deterioration of the macular can cause oxidative stress within the retina, leading to a loss of central vision. However, it is not currently possible to make clear conclusions about the distinct role of lutein and zeaxanthin without more prospective studies. In addition, many other physiological, lifestyle and dietary factors (such as omega-3 fatty acids, zinc and the antioxidants vitamins C and E and betacarotene) may be associated with the development of these conditions. Nevertheless, a regular intake of luteinrich green, leafy vegetables, and other antioxidant rich foods, as part of a healthy diet and lifestyle (including not smoking) remains a key recommendation for the maintenance of eye health. The Ulster study showed a 100% increase in plasma lutein levels in subjects regularly eating watercress. SKIN HEALTH Watercress contains a range of nutrients and phytochemicals associated with the maintenance of skin health, including vitamins A (from beta-carotene), C and E, polyphenols and carotenoids. Phytochemicals such as carotenoids and flavonoids are part of the light-protecting systems in plants and appear to contribute to the prevention of UV damage in humans. Free radicals can be produced in the skin as a result of UV radiation from sun exposure and pollution, which over time can damage skin DNA, proteins and lipids, with the potential for skin ageing, immune suppression and possibly skin cancer. Associations have been found between higher intakes of carotenoids (from fruit and vegetables) and reduced risk of melanoma and higher intakes of green leafy vegetables and reduced risk of recurrence of squamous cell carcinoma (skin cancer). The skin has internal antioxidant defense systems but also appears to make use of dietary antioxidants, including carotenoids such as beta-carotene, lutein and lycopene, which can accumulate in the skin. Methods such as Raman resonance spectroscopy have been used to measure the uptake of carotenoids in the skin, and high levels have been associated with skin protection and reduced wrinkling (81). While no direct research has been done with watercress, human intervention studies with supplements or a carotenoidrich diet have shown evidence of skin photo-protection after intervention periods of at least 10 weeks. An animal study found that compared to a standard diet, a lutein-supplemented diet resulted in lutein accumulation and a decrease in reactive oxygen species (free radicals) in the skin and a significant inhibition of skin photo damage. WEIGHT CONTROL Almost two-thirds of adults are overweight and 23% of men and 24% of women are obese. Based on recent trends, 12 million adults (33% of men and 28% of women) are predicted to be obese by Most fruit and vegetables have a low energy density, which can contribute to feelings of fullness and may help with weight control. Higher

6 intakes of fruit and vegetables have been associated with better body weight control in women. Watercress is low in fat and calories with 18 calories per 80g portion. As a salad vegetable it is most often eaten as part of a mixed salad. Like most vegetables it has a high water content (93%) and low energy density. Research carried out at Pennsylvania State University (87) found that eating a large, mixed low fat salad as a starter resulted in subjects eating 12% fewer calories (a saving of more than 100 calories) overall at that meal, compared to when they didn t start their meals with the salad. LIFECYCLE NUTRITION The mix of nutrients and phytochemicals found in watercress make it a valuable food that can help to support the body s natural defenses and contribute to health and well being throughout life. As a salad vegetable it can contribute to the nutritional benefits associated with daily salad consumption. A recent analysis found that salad consumers tended to have more favourable intakes of vitamins C and E, folate and carotenoids and consistently higher serum values of these nutrients. All essential nutrients support growth and development. Watercress is an especially good provider of vitamins A (via beta-carotene), C and K, folate, iron and vitamin E. Calcium is important to build and maintain strong bones, and vitamin K contributes to normal bone structure. During pregnancy requirements increase for vitamins A and C. Folate is needed for the normal development of the neural tube so helping to prevent neural tube defects such as spina bifida. Folate also plays a role in maintaining blood and circulation. Eating plenty of vegetables (around 3 portions daily), especially green leafy, yellow and cruciferous vegetables, has been associated with a slower rate of cognitive decline amongst people aged 65 or over.