LIFE HACK #2
Tomatoes & Lycopenes
Familiar and powerful friends - tomatoes are rich in
antioxidants and vitamins that help combat cancer
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July 2020 | by Dr. Benny Gavi
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Common in many cuisines and even considered part of the "comfort foods"
that we often eat, tomatoes should be part of a healthy diet. Here's why:
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Snapshot of tomatoes
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Did you know that tomatoes are the second most commonly consumed vegetable in the US due to our high consumption of pizza sauce? This is definitely within the realm of possibilities.
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Did you know that tomatoes are packed with phytochemicals and micronutrients such as potassium, folate, and vitamins A, C, and E. This is more elusive to most people unless you have some background in nutrition.
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But, did you know that tomatoes get their red color from lycopene, a powerful antioxidant? Lycopene is a carotenid pigment like what beta-carotene is to carrots, and can also be found in watermelon and pink grapefruit.
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Although humans do not produce lycopenes ourselves, we can enjoy a diet rich in lycopenes from consuming fresh tomatoes, spaghetti sauce, and comfort food such as pizza.
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Let's look at some research​
One note before we begin. Scientists are great people. How they live as individuals varies with each person, of course, but how they approach the scientific method of research is singular. Truth is found after lengthy research and this truth is subjected to peer review and must be able to be replicated by other scientists. When any inconsistency arises, the hypothesis is re-examined. This process enables us to continuously refine our understanding of the world as it evolves. Here is a short video explaining the scientific method from Khan Academy, an American non-profit organization dedicated to online learning:
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Is there a connection between tomato consumption & reduced cancer risk?
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Background: Dr. Edward Giovannucci noticed that some data from the Health Professionals Follow-Up Study (HPFS) between 1986 to 1992 suggest that frequent intake of tomato products - lycopene - is associated with reduced risk of prostate cancer. But overall, the total body of research remained inconclusive.
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Methods: Data from 47,365 participants were collected over a 12-year period via dietary questionnaires every 4 years in 1986, 1990, and 1994. The research team used pooled logistic regression to compute multivariate relative risks and 95% confidence intervals. All statistical tests were two-sided.
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Results: Researchers noted that 2,481 men in the study developed prostate cancer from 1986 through January 31, 1998. They found that consumption of tomato sauce, the primary source of bioavailable lycopene, was associated with reduced risk of prostate cancer, especially for extraprostatic cancers. The researchers wrote that their findings were true in analyses controlling for fruit and vegetable consumption and for olive oil use, a marker for Mediterranean diet, and were observed separately in men of Southern European or other Caucasian ancestry.
Conclusion: This study found that men who had the highest consumption of tomatoes enjoyed a 23% reduced risk for prostate cancer and a 35% reduced risk for aggressive prostate cancer compared with men who had the lowest consumption. Due to the moderate association between tomato consumption and prostate cancer risk, this finding could be missed in a smaller study, with substantial errors in measurement, or in assessments based on a single dietary assessment.
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Click here to see Dr. Giovannucci's full article, "A Prospective Study of Tomato Products, Lycopene, and Prostate Cancer Risk." Published in 2002 by the Journal of the National Cancer Institute.
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Do lycopenes prevent prostate cancer? ​
We have wonderful news for the pasta lovers among us! Dr. Giovannucci discovered that when fresh tomatoes are processed into tomato sauce, the amount of lycopene increases. Studies suggest that lycopene from tomato paste is 2.5 times more bioavailable in humans than lycopene from fresh tomatoes. This happens because cooking or processing tomatoes breaks down cell walls, which in turn makes lycopene more accessible to the body when consumed. The body's absorption of lycopene is even better when you consume it with a small amount of fat - such as adding heart healthy olive oil - or some of the wonderful dishes found in Italian cuisine.
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But still, one of the many questions hanging over researcher's heads has been the role of lycopene in prostate cancer prevention. The advent of more sensitive screening tools, such as the prostate-specific antigen (PSA) test, means that cancers are detected earlier and at asymptomatic stages that would have remained undiagnosed before.
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Also, the risk factors for prostate cancer might be different depending on the subtype of cancer and might even act differently at various stages of the disease. So, epidemiological studies of prostate cancer from different settings might produce different results. Don't throw out the baby with the bath water yet. More refined research can update our understanding of the biochemistry of lycopene and its role in cancer prevention. With this in mind, Dr. Ke (Kirsten) Zu updated the work done earlier by Dr. Giovannucci.
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Background: This study re-examines the associations between dietary lycopene (as opposed to supplemental lycopene) and prostate cancer, specifically keeping an eye on the influence of PSA screening. In addition, this study looks at tissue biomarkers in prostate cancer with relation to lycopene consumption.
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Methods: Among 49,898 screened, male health professionals who participated in the study, researchers obtained dietary information through questionnaires given every 4 years from 1986 through January 31, 2010. The overall number of prostate cancer cases and the subset of lethal cases were tallied. Cox regression was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Tissue microarrays and immunohistochemistry were used to assess tumor biomarker expression in a subset of men.
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for a
refresher
course in
statistics,
watch a free video-based course on interpreting multivariable Cox regression models, offered by Coursera, an American company revolutionizing online learning.
You made it back from the online statistics class! Let's continue with the lycopene study...
Results: Dr. Zu noted that higher lycopene consumption was inversely associated with total prostate cancer and more strongly with lethal prostate cancer. In other words, the more lycopene-containing foods you consume (such as watermelon, pink grapefruit, and fresh tomatoes), the lower your risk for prostate cancer overall. There is an even stronger potential to lower your risk for the lethal forms of prostate cancer from a diet rich in lycopenes. The research team wrote, "Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential."
Conclusion: Diets rich in lycopene were associated with reduced risk of lethal prostate cancer and with a lesser degree of angiogenesis in the tumor. This is the first epidemiological study to report the potential antiangiogenic effect of lycopene-rich foods. Although all observational studies have the limitation of uncontrolled confounding by unknown factors, the potential is low for all of the results on lycopene and postate cancer to be completely explained by unknown factors.
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Click here to see Dr. Zu's full article, "Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the Prostate-Specific Antigen Era." Published in 2014 by the Journal of the National Cancer Institute.
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Why are antioxidants important?
Antioxidants seem like a marketing buzzword that will never fly away. From skincare products and dark chocolate to superfoods such as blueberries and goji berries, the "A" word shows up almost everywhere. What does this really mean? The term antioxidant refers to molecules that can protect other molecules in our bodies from a chemical process called oxidation.
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Oxidation can sometimes damage the important molecules in our cells, such as proteins, lipids, and DNA, that are responsible for many bodily processes. When cells get damaged, they often overcome the small changes and return to their original state. But, trouble begins when they malfunction or die due to oxidative damage.
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Here's some food for thought. Oxidation is a common chemical reaction where electrons are transferred from one molecule to another. The movement of electrons breaks bonds within the molecule and changes its structure. Copper oxidation is a well-known example of how the Statue of Liberty got its blue-green patina, which formed between the Statue's unveiling in 1886 and the fully-oxidized green color by 1906. Within the human body, oxidation processes aren't always as mischievous because the oxidation of glucose and oxygen is what gives us energy.
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When oxidation occurs, free radicals are created. Free radicals are simply molecules with unpaired electrons, which is an unstable environment because electrons like to be in pairs. This is where antioxidants can save the day by donating an electron to the free radical, stabilizing it, and stopping any further damage. But, lifestyle factors such as stress, poor diet, pollution, smoking, and alcohol consumption that can increase the amount of free radicals in our bodies.
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The hero of this story is antioxidants and they are powerful friends. If free radical damage brings about unstable environments leading to disease, then antioxidants in appropriate quantities can help save the day.
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3 life hacks:
Antioxidants are found in fruits and vegetables. Eating tomatoes give you Vitamins A, C, E, potassium, folate, polyphenols, and lycopene - all excellent antioxidants.
Whole foods are powerful: they contain many important antioxidants and micronutrients that cannot be engineered into lycopene extracts or other supplements.
Why do
tomatoes have
more powerful
anticancer effects
than lycopene
supplements?
What mechanisms of lycopenes drive results?
Dr. Gary Williams wrote that about 50% of all cancers can be attributed to diet. In the animal models and human studies we reviewed below, the results demonstrate that lycopenes in whole foods can decrease the risk of chronic diseases such as cancer and cardiovascular disease.
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The antioxidant mechanism of lycopenes is thought to drive powerful health benefits, but evidence is accumulating that maybe other mechanisms are involved too. In 2000, Dr. Sanjiv Agarwal from the University of Toronto published a meta-analysis to evaluate lycopene mechanisms that are thought to fight cancer. He first sets the table by offering definitions of reactive oxygen species, antioxidants, and lycopene. Then, he evaluates the major mechanisms of tomato phytochemicals, which can be categorized into (1) oxidative processes and (2) non-oxidative processes.
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Oxidative processes have the mechanisms of reducing reactive oxygen species, decreasing oxidative damage, and increasing antioxidant potential. Non-oxidative processes have the mechanisms of modulating hormone and immune systems, regulating gene function, and gap-junction communication. This study provides guidance on dietary lycopene, including watermelons, pink grapefruits, and pink guava as well as the tomato products with the highest lycopene bioavailability, such as tomato soup, juice, ketchup, tomato sauce, and tomato paste.
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Please click here to see Dr. Agarwal's article, "Tomato lycopene and its role in human health and chronic diseases." Published in 2000 in Canadian Medical Association Journal.
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American food supply and consumption: everything increased
In 2017, the USDA published a report that examined food-based commodities in the domestic market as well as shifts in the food supply to consumers. Potatoes won top billing for the most commonly consumed vegetable. Second place went to tomatoes, especially enjoyed in the U.S. as pizza sauce. The USDA researchers found that since 1970, the U.S. obesity rate has almost tripled for adults and more than tripled for children and adolescents.
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Click here to view the full report online or download the PDF of the USDA's "U.S. Trends in Food Availability and a Dietary Assessment of Loss-Adjusted Food Availability, 1970-2014." Published in 2017 by the U.S. Department of Agriculture. Or jump right in and play our food consumption game below. Please click on the small white brackets in the lower right corner of the quiz (below) to render this in your browser.
Broccoli + Tomatoes = Powerful Cancer Prevention
Nutrition can seem intangible because we do not have a real-time view of ourselves at a cellular level. We know our weight and can make BMI calculations, and beyond that we go for an annual checkup under normal circumstances. Early warning detection does not exist for many diseases. So, we have a subjective understanding of the food we eat as it relates to our health. After a large dinner, a night out drinking, or a week of business travel, you might experience a more snug waistband on your trousers. But that's it, right? Not really.
The gains of healthy eating accumulate over time, so the entire picture of your nutritional profile is greater than the sum of its parts. If eating broccoli is good cancer prevention and if eating tomatoes is also good cancer prevention, then putting these vegetables together into your diet ends up being more powerful than eating only one or the other. Let's take a look at research that quantifies the effects of eating broccoli and tomatoes using an in vivo study of prostate tumor sizes and weight.
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Background: The recommendation of consuming 2 cups of fruit daily and 2 1/2 cups of vegetables daily for adults is a cornerstone of healthy eating. But, the concept had not been tested until Dr. Kirstie Canene-Adams published an article in 2007 examining this. She realized that live experiments with animal subjects could help us understand the role of nutrition in cancer beyond health questionnaires or reviews of existing medical literature. Dr. Canene-Adams and her team hypothesized that the combination of broccoli and tomato consumption would contribute to greater impact in cancer tumor reduction than either alone.
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Methods: 206 male Copenhagen rats were fed 1 of 5 diets. See below. These diets continued for approximately 22 weeks starting 1 month prior to receiving subcutaneous Dunning R3327-H prostate tumor implants. The effects of diet were compared to surgical castration or finasteride to simulate androgen deprivation.
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10% tomato diet
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10% broccoli
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5% tomato plus 5% broccoli
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10% tomato plus 10% broccoli powders, or
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lycopene supplements
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Results: The first method of androgen deprivation was castration, which had the dramatic and immediate effect of decreasing tumors by >56% in 2 weeks. The second method of androgen deprivation was the administration of finasteride, which yielded no differences in tumor growth compared with the control animal subjects. The wonderful findings happened in the animal subjects who experienced the 5 different diets prior to prostate tumor implantation. In all animal subjects, the size of their tumor areas began to shrink:
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the 10% tomato diet subjects saw tumor shrinkage by week 12
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10% broccoli diet subjects saw tumor shrinkage by week 13
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5% tomato plus 5% broccoli subjects saw tumor shrinkage by week 13
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10% tomato plus 10% broccoli powders subjects saw tumor shrinkage by week 12
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lycopene supplement subjects saw tumor shrinkage by week 15
Also, the subjects' tumor weight began to decrease across the different diet groups compared with the control group. Table 2 below describes tumor weight results from the study with a link to the full article and attribution at the bottom of this discussion. The blue circled area begins with control subjects, and then continuing down through this list, you can see how effective each method is compared with the control group. Lycopene supplementation did not have a large effect at 93% tumor weight compared with control subjects for the 23 nmol lycopene/gram diet and then 82% tumor weight compared with control subjects for the 224 nmol lycopene/gram diet.
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Does it surprise you that the most effective diet was the 10:10 combination diet of broccoli and tomato with a 48% tumor weight compared with control? That result is astonishing because it means there is a significant contribution of tumor reduction from eating a healthy diet. The second most effective diet was the 10% broccoli diet where tumor weight was 58% that of control. The third most effective diet was the 10% tomato group.
Castration and finasteride results are shown in rows 2 and 3, but are meant for research purposes in understanding different mechanisms and possibly different pathyways than diet that can help achieve tumor reduction. In her paper,
Dr. Canene-Adams shows that tomato or broccoli exposure, alone or in combination, was more effective than finasteride which has shown a 24% reduction in prostate tumor detection in a 7-year human study, "The Influence of Finasteride on the Development of Prostate Cancer" published by Dr. Ian Thompson in 2003 in the New England Journal of Medicine.
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Conclusion: This study confirms previous epidemiologic studies that pointed to the benefits of eating diets rich in tomatoes and broccoli to protect against prostate cancer. The priceless finding from this study is that consuming both vegetables has the significant effect of decreasing the size and weight of prostate tumors.
Interestingly, researchers and purveyors of anticancer supplements consider lycopene the powerful ingredient of tomato products. But in comparing supplemental lycopene versus tomato-based diets, Dr. Canene-Adams found that you cannot cheat the system and take lycopene supplements to bypass eating real tomato-based food.
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Click here to view Dr. Canene-Adams' article online or click the PDF icon to download the file, "Combinations of Tomato and Broccoli Enhance Antitumor Activity in Dunning R3327-H Prostate Adenocarcinomas." Published in 2007 by the American Association for Cancer Research.
Lycopenes protect against heart attacks too!
It is an ongoing quest to understand the drivers of diseases such as cancer and many of the conditions that continue to stalk our species. You know carotenoids for their bright red, yellow, and orange pigments in many fruits and vegetables such as squash, carrots, apricots, and oranges. The most famous carotenoid is carotene, which gives carrots their bright orange color. Did you know that carotenoids also contribute color and flavor to flour? But, did you know that carotenoids have been destroyed in bleached flour?
Studies have explored beta-carotene as a panacea for many diseases through ecologic studies, cross-sectional studies, case-control studies, and cohort studies. However, several large-scale trials have not been able to confirm the protective effect of beta-carotene, so it is still unproven whether it prevents cancer or cardiovascular disease.
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Epidemiologic studies still suggest a protective effect of high vegetable consumption. So then, what is the magic bullet? We know that beta-carotene often occurs naturally with other carotenoids such as alpha-carotene and lycopene. We also know that lycopene supplements have not been successful. The study above by
Dr. Canene-Adams demonstrates that lycopene supplements at different concentrations did little to decrease prostate cancer tumors in the animal model.
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Background: Carotenoids are fat-soluble nutrients with antioxidants, and researchers have hypothesized that naturally-occurring antioxidants might slow the progression of atherosclerosis by inhibiting the oxidation processes of bad cholesterol known as low density lipoprotein (LDL). Dr. Lenore (Kohlmeier) Arab set out to tease apart the protective effects of alpha-carotene, beta-carotene, and lycopene on heart attack risk. In 1997, she published an article in the American Journal of Epidemiology noting that even 2 decades ago coronary heart disease remains a major cause of mortality in developed countries and is increasingly recognized as an important cause of morbidity in the developing world as well.
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Methods: Participating hospitals in 10 European countries recruited cases of first acute myocardial infarction in men under 70 years of age. Researchers recruited 662 participants and 717 controls. Informed consent was obtained for all participants in accordance with the EU requirements of responsible committees on human experimentation. Samples of adipose tissue were taken from the buttock by needle aspiration, and carotenoid concentrations were based on the amount of fat in the sample. SAS, the statistical analysis software package, was used for the regression models in this study. Creating models is a topic for a better person to write about than me, but you can find a treasure trove of information online about examining data, assumptions, outliers, and testing.
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Results: Findings revealed that lycopene was the only carotenoid to be inversely associated with a person's risk for myocardial infarction. Analyzing the 3 carotenoids simultaneously showed that lycopene remained independently protective. Interestingly, lycopene remained independently protective even when researchers controlled for age, body mass index, socioeconomic status, smoking, hypertension, and maternal and paternal history of disease. The associations for alpha- and beta-carotene were eliminated.
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Conclusion: The lycopenes in tomatoes have demonstrated a protective effect against myocardial infarctions in this research study. Comparing the 90th percentile of lycopene consumption to the 10th percentile, the participants in the 90th percentile saw a 50% reduced risk of getting a heart attack.
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Please click here to see Dr. Kohlmeier's article, "Lycopene and Myocardial Infarction Risk in the EURAMIC Study." Published in 1997 by the American Journal of Epidemiology.
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Paywalled medical journals
Many established publishers of medical research are moving to an open access model for all. This is happening because studies are often publicly funded by government grants to researchers, who still have to pay journals to publish their article, then pay to subscribe to those very journals, and yet the potentially lifesaving knowledge never benefits taxpaying citizens. It was estimated in 2016 that American taxpayers spent $171.8 billion to support research they can't easily access.
In 2013, the Obama administration announced that all research they funded had to be publicly available 1 year after publication. The Bill and Melinda Gates Foundation, a private American foundation created by Microsoft co-founder Bill Gates, announced an open access policy in 2014 that all research they fund must be open immediately and easily discoverable online. In 2018, the European Commission and the national research grant organizations in Austria, France, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Slovenia, Sweden, and the UK required all funded research to be published in journals that enable anybody to view, reuse, and distribute the material. So, scientific publishing is becoming more open and accessible despite the journals that put up expensive paywalls. If you are interested in this topic, please take a look at the European Parliament's article, "Europe leads the way in the transition to open access publishing: what is at stake?"
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Lycopenes decrease your risk of stroke
The body of knowledge continues to grow as medical research is conducted on various aspects of the protective effect of nutrition. In October 2012, Dr. Jouni Karppi published an article, "Serum lycopene decreases risk of stroke in men: A population-based follow-up study" in Neurology, a journal of the American Academy of Neurology (AAN). In this case, a brief abstract is publicly available on the AAN website and the full article is available for download for $39.
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Objective: Intake of fruits and vegetables and levels of serum carotenoids have been associated with decreased risk of stroke, but the results have been inconsistent. The aim of the present study was to examine whether serum concentrations of major carotenoids, alpha-tocopherol and retinol, are related to any stroke and ischemic stroke in men.
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Methods: The study population consisted of 1,031 Finnish men aged 46−65 years in the Kuopio Ischaemic Heart Disease Risk Factor cohort. Serum concentrations of carotenoids retinol and alpha-tocopherol were measured by high-performance liquid chromatography. The association between the serum concentrations of lycopene alpha-carotene, beta-carotene, beta-tocopherol, and retinol and the risk of strokes was studied by using Cox proportional hazards models.
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Results: A total of 67 strokes occurred, and 50 of these were ischemic strokes during a median of 12.1 follow-up years. After adjustment for age, examination year, BMI, systolic blood pressure, smoking, serum low-density lipoprotein cholesterol, diabetes, and history of stroke, men in the highest quartile of serum lycopene concentrations had 59% and 55% lower risks of ischemic stroke and any stroke, compared with men in the lowest quartile (hazard ratio [HR] = 0.45, 95% confidence interval [CI] 0.25−0.95, p = 0.036 for any stroke and HR = 0.41; 95% CI 0.17−0.97, p = 0.042 for ischemic stroke). alpha-Carotene, beta-carotene, alpha-tocopherol, and retinol were not related to the risk of strokes.
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Conclusions: This prospective study shows that high serum concentrations of lycopene, as a marker of intake of tomatoes and tomato-based products, decrease the risk of any stroke and ischemic stroke in men.
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You really can't go wrong
These studies demonstrate that lycopenes in tomatoes can reduce your risk for many chronic and life threatening diseases, such as prostate cancer, heart disease, and stroke. Many studies on this topic support this view, but not all studies on tomatoes and prostate cancer are unanimous in their findings.
For example, some studies have not found an association between tomatoes and prostate cancer risk. While it is important to recognize this, it is equally important to note that our research has not identified research that found detrimental effects from eating tomatoes. This leaves us with a best case scenario where current research indicates that eating tomatoes can significantly reduce your risk for prostate cancer and a worst case scenario where you are simply eating more of a delicious and nutritious food. In order to arm you with a balanced view, we found research of the "worst case scenario" where eating tomatoes is certainly good for you, but might not conclusively prevent cancer.
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Please click here to see: Kolonel, L.N., Hankin, J.H., Whittemore, A.S., Wu, A.H., Gallagher, R.P, Wilkens, L.R. John, E.M., et al. (2000). "Vegetables, fruits, legumes, and prostate cancer: a multiethnic case-control study," Cancer Epidemiology, Biomarkers & Prevention, 9(8):795-804. PMID: 10952096.
Please click here to see: Kirsh, V.A., Mayne, S.T., Peters, U., Chatterjee, N., Leitzmann, M.F., Dixon, L.B, Urban, D.A., et al. (2006). "A prospective study of lycopene and tomato product intake and risk of prostate cancer," Cancer Epidemiology, Biomarkers & Prevention, 15(1):92-98.
