Nutri Sci Chapter 12: Phytonutrients – Flashcards

-non nutrient component of plants with physiological effects on humans -no individual phytonutrient is essential for the diet (we don't develop deficiency symptoms if we fail to consume one) -the effects of a low intake of phytonutrients generally take a lot longer to show up than the effect of a low intake of nutrients -if you have a chronically low intake, likelihood of cancer/heart disease may rise

-prior to the industrial revolution, it was hard to avoid eating a wide variety of phytonutrients so our bodies have become dependent on the physiological effects of high intake of plant chemicals (through long exposure to them)

-lower cholesterol -reduce the risk of cancer -may lower blood pressure

-specific chemical compound that we need but that our bodies CANNOT synthesize (aka we require them in our diet) -if we don't consume the particular substance, a role/function isn't fulfilled and we develop a deficiency symptom

-cancer and heart disease

-estimated 2/3 of cancers can be attributed to the environment -environment is made up of exposure to radiation, toxic chemicals, smoke, exercise, alcohol, and the food you eat -most of cancer is caused by smoking

-DON'T SMOKE -the 2nd most important thing is eat lots of fruits/veggies/whole grains/legumes

-protective effect of fruit and veggies against cancer is a well-studied phenomenon -been seen in 128 out of 156 studies -estimate: the lowest consumers of fruits and veggies have twice the risk of the highest consumers of getting cancer (eating fruits/veggies can cut your risk of cancer in half)

-lung, esophagus, colon, bladder, cervix, ovary, endometrium, breast, pancreas, prostate, stomach

-lettuce, leafy greens, onions, carrots, cabbage family, citrus, broccoli, potatoes, "raw and fresh" fruits and veggies

-show up a lot in diets of those who do not get cancer -cabbage, collards, kale, mustard greens, turnip greens, broccoli, cauliflower, kohlrabi, turnips, rutabagas

-fruits and veggies are good sources of vitamin A -form of vitamin A found in fruits and veggies isn't actually retinol (produce contains the PROVITAMIN FORM, mostly beta-carotene) -it doesn't look like retinol (active form of vitamin A) is the protective factor in produce

-Retinol is the active form of Vitamin A that has a role in cell differentiation -DIFFERENTIATION is the process by which newly-formed cells mature (a new liver cell for example cannot function as a liver cell until it develops the specialized structures and capacities to do its job-this is differentiation) -RETINOL is protective against cancer in cell culture studies (if you put cancer cells in a test tube with plenty of retinol, they don't grow) -Retinol deficiency enhances cancer risk in animals (deficient animals get more cancer) -however, blood levels of retinol are not correlated with cancer risk in humans. if retinol were protecting us against cancer, we'd expect to see cancer patients have lower blood levels of retinol. healthy people would have higher levels of retinol, which is why they are healthy-it protected them. HOWEVER, THIS IS NOT THE CASE. -BLOOD LEVELS OF RETINOL ARE UNRELATED TO CANCER STATUS. it doesn't look like retinol is the protective factor in produce

-cancer cells don't differentiate (or do so poorly) -cancer is distinguished by weird, misshapen, dysfunctional cells that grow out of control

-no -healthy people don't actually have higher levels of retinol proving that retinol is unrelated to cancer status and is NOT the protective factor in produce

-form of vitamin A found in fruits and veggies isn't actually retinol -produce contains the provitamin form of vitamin A (MOSTLY BETA-CAROTENE) -beta-carotene is a precursor to retinol -the body readily converts it into the active form of the vitamin -it is possible that it is beta-carotene, not retinol, that has anti-cancer activity (beta-carotene hypothesis)

-beta-carotene protects against cancer without conversion to retinol -blood levels of beta-carotene correlate with cancer risk, unlike the case for retinol, which is what we'd expect if it were protective -beta-carotene is also a powerful antioxidant which also fits nicely with the anti-oxidant hypothesis of cancer prevention

-suggests that anti-oxidant compounds, such as beta-carotene, protect the body from oxidative damage that could lead to cancer -oxidative damage is caused by free radical oxygen

-particularly reactive form of oxygen -body uses oxygen in chemical reactions that release energy from nutrients (thats why we breath) -oxygen exchanges electrons well with other atoms which makes it useful in chemical reactions. most of the time, there is an equal exchange of electrons, leaving pairs of them in the outer shells of the oxygen atom. sometimes, a reaction occurs that leaves a single, unpaired electron in that outer shell. this makes a free radical, a species of oxygen that is particularly unstable, making it highly reactive as it seeks to steal an electron by attacking another atom. when it does so, it reaches a stable equilibrium but the damaged atom that lost the electron is now unstable. it then seeks to steal an electron from another atom, and so it goes on down the line. the oxidative damage propagates itself.

-cell membranes, DNA, etc. can be harmed in this way -oxidative damage to the DNA can lead to cancer (if the genes that are damaged re the ones that control cell growth, you lose control over that growth and you may now have a cancer cell

FREE RADICAL OXYGEN

-smoking -oxygen bars -ozone pollution -excessive intakes of polyunsaturated fats or iron -too much sun -overdoing exercise -all of the above accelerate oxidative effects -even without these exposures though, even just breathing introduces free radicals into the body

-antioxidants! -"anti-oxidants quench free radicals" -anti-oxidants react with the free radical and donate an electron which stops the oxidative rampage -the hypothesis is that, although anti-oxidants are destroyed in the process, they block the DNA damage which prevents cancer

-vitamins C and E (ALSO FOUND IN PLANT FOODS) -perhaps the anti-oxidant hypothesis of cancer prevention fits well with the beta-carotene hypothesis

-less than 1/3 of the US vitamin A intake comes from carotenoids -most of our vitamin is in the form of retinol and it mostly comes from milk -there are 500 carotenoids to be found in nature and most do not have vitamin A activity -only about half a dozen can be used as precursors to retinol and of these, only beta-carotene is a significant source -the others may nonetheless be important contributors to cancer prevention and some are far more prevalent in the diet than in beta-carotene -diets rich in carotenoids seem to have a powerful protective effect against cancer

-yellow and orange fruits and vegetables -beta-carotene is an orange pigment so almost any yellow or orange plant food is a good source

-carotenoid -dark leafy greens are rich in lutein

-lycopene -lutein and lycopene are found in highest concentrations in blood

-prevention of cancer by use of phytochemicals

-a finnish study looked at 29,000 male smokers -smokers are a great group to study since they get so much cancer anyway (if carotenoids can help smokers, they can help anybody) -in this study, subjects received one of four treatments: a beta-carotene pill, a vitamin E pill, both, or a placebo -everyone fully expected to see beta-carotene and vitamin E reduce the cancer rate individually, compared to placebo, and reduce it even more taken together (both beta-carotene and vitamin E are antioxidants) -surprisingly, b-carotene and vitamin E failed to protect against lung cancer -one trial even showed that Beta-carotene enhanced carcinogenesis somewhat -CONCLUSION: taking anti-oxidant supplements doesn't help prevent cancer

-taking anti-oxidants in supplement form doesn't prevent cancer -there are two reasons for this: one has to do with dose. the benefits of anti-oxidants are found within a certain range of dosage. the amounts found in a healthy diet help you. amounts that exceed that may actually hurt you. aka, more is not better...supplements do not replace foods -the other reason has to do with context. there is weak evidence that nutrients are the primary plant factors responsible for cancer prevention. BUT there is solid evidence that some other plant constituents may explain the protective effects of plant foods (other plant constituents=PHYTONUTRIENTS)

-carotenoids are found in association with phytonutrients in fruits and veggies. therefore, to get high levels of carotenoids, you also have to eat a lot of phytonutrients -maybe the phytonutrients offer as much or more protection than the anti-oxidants do

-a diet rich in tomatoes will lower your risk of prostate cancer -tomatoes contain lycopene and we know that lycopene reduces the oxidative damage that can lead to cancer -there are 10,000 different chemicals in a tomato and it is very likely that some of the others also contribute to the tomato's protective effect (it is also possible that some of these are more powerful than lycopene and it is also possible that the interaction between these plant chemicals enhances the protective effect) -AKA, A TOMATO IS ALWAYS MORE POWERFUL THAN A PILL

-animal and cell-culture (test-tube) studies -we don't have many human studies as yet on individual phytonutrients -but by one count, 3000 such anti-carcinogens of varying strength have been indentified

-process by which cancer develops

-chemicals that damage DNA and initiate cancer development

-our original awareness of carcinogens came from occupational exposures -someone who worked with hazardous chemicals full-time in the age before modern worker safety measures, got ver high exposures and made a good guinea pig for finding out what certain chemicals could do to you -clusters of particular cancers would show up in particular industries -ex: lung cancer in asbestos workers or liver cancer among those working with vinyl chloride -occupational exposures are much less common nowadays and no longer account for a large percentage of cancers

-pollutants contribute to cancer but not as much as dietary factors -ex: pesticides, herbicides, auto emissions, and groundwater contaminants contain carcinogens

-some are naturally occurring, some are from contamination, and some have been added during processing

-nitrate compounds are added to cured meat like bacon or ham to preserve them and to maintain their characteristic flavor -nitrites are also a product of food processing, as has occurred in beer -nitrates are converted to nitrosamines in the body and can contribute to cancer risk -levels of these in meats and processed foods have been greatly reduced as a result of these concerns in the last few years, and now, their contribution to cancer is much less

-while most cancers have been on the rise in the U.S. since the beginning of the 20th century (early 1900s), one cancer that used to be very common has declined a lot (STOMACH CANCER) -this is thought to be because of better food safety. people are a lot less likely to eat spoiled food today -refrigeration is common/better food preservation techniques are used/a more efficient food distribution is in place so it is much less likely to consume rotten food -it is THOUGHT that the metabolites of the microbes involved in spoilage act as carcinogens on the lining of the stomach -there is also evidence that eating a lot of pickled food can do the same thing and for the same reason: the metabolites of the pickling organisms are carcinogenic. it is better to eat mostly fresh food. pickling LESS COMMON because there isn't a need for it due to refrigerators and fresh food at supermarkets

-mold toxins are thought to cause cancer -they make nerve gas from mold toxins -an example is aflatoxin -compared to the US, cancer rates in rural africa are generally much lower (with the exception of liver cancer) -it is thought that this is because of aflatoxin mold on food -food safety is much less closely monitored on the african continent than in north american, and in some places at least, climate favors mold growth -vulnerable foods, like peanuts, have been screened for aflatoxins in the US for some time

-some foods naturally have carcinogens present in them -these foods tend not to be very common in the US anymore -examples are bracken fern and sassafras

-we used to be able to identify carcinogens as the cause of many specific cancers in occupational exposures (lung cancer in asbestos workers) -massive exposures to single carcinogens are pretty rare with the widespread exception of tobacco -nowadays, it is rare to be able to point to an individual patient and figure out exactly where he/she got the cancer. there are many more factors now that make much smaller individual contributions to carcinogenesis -the focus today is no longer on avoiding carcinogens (because they are so diffuse) but on enhancing protective factors -without single prominent targets for cancer prevention, we need the many little factors that go into making us healthy -its not what you avoid, its what you include

-modern model for the development of cancer has three stages: initiation, promotion, and progression -each stage is marked by additional DNA damage -this damage could result from oxidative damage, a carcinogen, radiation, or another carcinogen -DNA damage could come from the same or a different source at each stage

-programmed cell death -process that separates a normal cell from a cancer cell -cells of any multicellular organism are good for around 50 to 100 cell divisions, and thats it -after that, they die. this is how the body protects itself against out-of-control division (which is what cancer is) -the stages of carcinogenesis remove the controls on cell division -in a cancer cell, the genes that program apoptosis are knocked out. with the controls removed, the cell goes wild. knock out other genes, and you have other problems. knock out genes controlling cell division, and you have cancer.

-first stage in carcinogenesis, marked by DNA damage which produces an initiated cell, which is neither normal nor cancerous -begins with a normal cell that receives a genetic insult resulting in a mutation -this damage to the DNA could come from a number of sources: oxidative damage from free radicals, a carcinogen, or radiation -initiation is a very common event, thought to happen to millions of cells per day in any individual. very few of these cells progress to cancer. -the cell has methods of genetic repair that restore much of the damage. a few cells escape repair. most of those just go on being dead cells, rather than cancer cells -some of this damage is more or less unavoidable. no matter what we do, there will always be some amount of exposure to carcinogens and some amount of oxidative damage -there is very little we can do to eliminate cosmic rays, which come from space -we can't eliminate damage but we can reduce its frequency -a vanishingly small percentage of initiated cells become cancerous. while it only takes one, any reduction in numbers improves your odds of avoiding the disease

-second stage in carcinogenesis marked by more DNA damage which takes the cell from being an initiated cell to being a cancer cell -additional insults occur to the genetic material of the initiated cell -these can come from the same sources responsible for the initial damage or they can come from other sources -many such insults are required to transform an initiated cell into a cancer cell -most initiated cells simply die, but if enough genes that control cell division are damaged, it's cancer

-final stage of three-stage model of carcinogenesis -you go from one cancer cell to many -cancer becomes dangerous and a tumor is formed -it takes a lot of cells to make a tumor. it is estimated that it takes 10^9 cells to be detectable. this is a pea sized lump, or enough bad cells to start doing some damage

-in order for a tumor to grow, angiogenesis needs to occur -this is the formation of new blood supply -without blood to supply nutrients and oxygen, tumor cells cannot grow

-cancerous tissues (tumor) -malignant tumors are invasive and they metastasize which means they grow into surrounding tissues, invading them, spreading into nearby organs

-the rapid spread of cancer cells to distant locations in the body -the tumor detaches tumor cells into the bloodstream, which carries them throughout the body, seeding new tumors -they are especially likely to end up in places with a good bloody supply, like the lungs, brain, or liver (all vital organs) -cancer can rapidly explore, showing up practically everywhere at once all from one original cell

-foreign lump in the body (which can interfere with the operation of organs) -stay in place unlike malignant tumors

-treatment is limited to slowing or halting progression -prevention of cancer happens in the initiation and progression stages -the prevention of cancer seeks to intervene against the damage to genetic material -phytonutrients can act at both of these stages

-phytonutrients are anti-carcinogens, capable of stopping genetic damage or otherwise interfering with initiation, promotion, and progression -most of these phytonutrients exhibit a blocking action against carcinogens -they stop carcinogens rom damaging DNA in the initiation and promotion stages -tomatoes contain compounds active against nitrates in the gut. they neutralize the carcinogen before it can be absorbed -mostly, anti-carcinogens block carcinogenesis by interaction with enzyme systems

-the body has enzymes that enable it to detoxify and eliminate dangerous chemicals, including carcinogens -enzymes break the toxin down into simpler, less dangerous substances that can be excreted in the urine. these are known as the cytochrome p-450 phase II enzymes -a diet rich in fruits and vegetables causes the body to increase its detoxification capacity, meaning that carcinogens will have less of an effect -there are many examples of these anti-carcinogens that induce higher levels of detoxification enzymes -these include a compound called Sulforaphane, found in broccoli and cabbages, and at least partly responsible for the fact that people who eat more vegetables in this family get less cancer -phenols are another example

-enzymes that enable the body to detoxify and eliminate dangerous chemicals, including carcinogens -they break the toxin down into simpler/less dangerous substances that can be excreted in the urine -certain F/V compounds induce the body to produce higher levels of the enzymes

-compounds found in all fruits and vegetables that have the beneficial effect of producing less cancer -a vegan diet, in fact, may be 10-20% phenols by dry weight, showing the enormous quantities of anti-carcinogens plant foods can supply

-substances in grapefruit juice also have effects of detoxification enzymes -sometimes you'll notice the package of medicine that says to not take the medicine with grapefruit juice. this is because the juice will induce such high levels of detoxification that you'll completely neutralize your expensive medication before it can do you any good

-some carcinogens are not ready-to-go when it comes to damaging DNA and they require activation -another set of enzymes, known as phase I enzymes, create or activate pro-carcinogens into actual carcinogens. while its not what they were intended for, they have exactly the opposite effect of the detoxification enzymes -fortunately, some plant compounds block this activation -ISOTHIOCYANATES, found in cabbages and broccoli, are an example. they are another reason why people who eat cabbage family vegetables have a lower incidence of cancer -most anti-carcinogens exhibit some type of blocking action, whether it is phase I or phase II enzymes. other anti-carcinogens use other mechanisms

-in high doses of isolated compounds, anti-oxidant vitamins and carotenoids do not seem to prevent cancer, and may even prevent it. this may be because in these large, unbalanced doses, they at as pro-oxidants or lower other anti-oxidant protection -as a component of food, anti-oxidants behave very differently -anti-oxidant rich DIETS DO LOWER CANCER RISK. Context is everything.

-other anti-carcinogenic phytonutrients may not block genetic damage, but that have other benefits, including in the promotion and progression stages

-some hormones promote the growth of some cancers. plant substances may reduce this effect -see next notecard on estrogen and cancer

-estrogen promotes the growth of breast, uterine, ovarian, endometrial and other cancers of tissues that (when healthy) respond to estrogen -estrogen normally regulates the function of these reproductive tissues -when the cells become cancerous, they continue to respond, even though the response is now uncontrolled growth -lifetime exposure to estrogen correlates to breast cancer risk in particular -anything that prolongs a woman's exposure increases the risk, such as early menarche or late menopause -pregnancies or breastfeeding lower estrogen levels temporarily and reduce the risk

-hormones, such as estrogen, interact with cells through the use of hormone-specific receptor on the surface of those cells -the receptors are very spefici as to what the bind to/interact with. only the hormone or a very similar compound can do it, and when they do bind the receptor, the hormone signals the cell to perform some action -the analogy usually made is "lock and key" the lock being the receptor, and the hormone being the key. only the right key will go into the lock, and when it does you can turn it and the door opens. the wrong key won't even go in the lock. receptors are that specific to the right hormone, and when the hormone binds, it triggers an action in the cell -a very close key, may go in the lock, but not be able to turn it. this triggers no action

-Genistein is a compound known as an isoflavone from soybeans -it is like a very close "key" to estrogen's receptor -it is a very weak estrogen, with about 0.01 percent of the activity of estradiol, the main form of estrogen. it has a very similar struggler to estrogen, close enough to bind the estrogen receptor, but not close enough to be able to turn the lock and make the door pop open. it triggers no response within the cell. -it does however, have a different effect. it blockades estrogen receptors. once genistein is bound to the receptor, estradiol cannot bind there. it is like taking that try close key which fits the lock, and trying to turn it until you snap the key off. it doesn't open the door, and now you can't insert the correct key even if you had it -IT COMPLETELY INHIBITS ESTROGEN -genistein is in fact, an anti-estrogen -it is not clear to what extent this occurs in humans but we do see that asian women get far less breast cancer than north american women. they also eat far more soy products. the anti-hormone effects of soy genistein could be why. -however, this can also be bad.. very high doses of isoflavones (like from supplements) may stimulate breast cell proliferation, not what you want if they are cancerous. doses of isoflavones found in the soy foods traditionally eaten in asian countries are probably much safer and more likely to be beneficial -tofu, tempeh, and soy milk are proven healthy additions to your diet. AVOID SUPPLEMENTS, which have not been shown to be so

-other dietary components also influence the effects of estrogen in other ways -lignans are made from the insoluble dietary fiber lignin by gut bacteria. lignans lower blood levels of estrogen -flax seed is a very god source of lignin

-indoles, other compounds also found in broccoli and other cabbage family plants, induce higher levels of enzymes that lower amounts of an estrogen precursor -with less precursor available, less estrogen will also be available to the body

-all of the above have the effect of reducing the effect of estrogen on all cells, including cancer cells, with an estrogen receptor -one could guess that estrogen production by the body is at a level that is meant to be tempered by plant factors (the body assumes that some of its estrogen production will be offset by these and similar factors) -diets that have too few of these offsetting substances from legumes, whole grains, and vegetables will allow estrogen effects on cells to be too great, potentially leading to cancer

-another way that plant compounds may reduce the risk of cancer is through suppression of the mevalonic acid pathway -this is a series of chemical reactions that synthesize cholesterol -some of the intermediate products of the pathway are diverted to produce other things as well, including a factor required for tumor growth in humans -when the body has synthesized enough cholesterol, an enzyme that facilitates an early step in the process shuts down any further synthesis. this is called the rate-limiting enzyme. -in plants, this pathway doesnt make cholesterol, but it does produce aroma and flavor compounds. these compounds share a parentage and some chemical characteristics with cholesterol. it turns our the plant compounds also suppress rate-limiting enzyme, just like cholesterol. taking in these plants flavors and aromas may slow the growth of tumors -experimentally, we see that many plant aroma and flavor compounds decrease cancer incidence in animal studies.

-genistein, our anti-estrogen, has another benefit -it blocks angiogenesis (the development of blood vessels) -restricting angiogenesis in tumors should slow their growth

-phytonutriets act through various mechanisms as anti-carcinogens, some of which have been discussed here -while the protective effect is hard to quantify, phytonutrients are likely among the most important factors in cancer prevention

-phytonutrients have been studied mostly for their role in cancer prevention, but there is evidence they also help prevent other chronic disease -heart disease -osteoporosis

-lowering the output of the mevalonate pathway as discussed earlier not only reduces tumor growth but also lowers cholesterol -these same plant compounds, known to us as aromas and flavors, will reduce cholesterol synthesis -other plant products of this pathway, known as phytosterols, will also suppress cholesterol production

-that same weak form of estrogen from soy and genistein that blockades estradiol, may give a boost to the bones of post-menopausal women -at that point, when there is no estradiol, its weak estrogenic effect may help to keep bone mineral in its place

-ecology is the interaction between individual organisms and between organisms and their environment -this interaction can be mediated by chemicals, thats why we have phytochemicals

-plants rely on chemicals to do things that animals do in other ways -one of the differences between plants and animals is that plants don't have an immune system -animals fight off infection with white blood cells and antibodies. plants cannot do that and instead they rely on chemical defense against infection. they synthesize chemicals to kill bacteria and fungi -plants are not mobile so if something wants to eat a plant, it cannot escape by running away like animals can. it falls back on chemicals instead and in doing so can produce a bad tasting or even toxic chemicals to repel the herbivore -for plants to exchange reproductive material, they may have to induce some mobile organism to carry it for them. thats why flowers smell good. they have to attract bees, ants, wasps, and so on to carry pollen from one plant to another. plants depend on insects for pollination -for the above reason, plants have a greater chemical diversity than animals. they do things with chemicals that animals do with mobility or with an immune system. there is a far wider variety of chemicals to be found in plant foods than in animal foods.

-humans are also attracted to flowers and nectar, just as insects are (also fruit and other plant materials) -many of the plant chemicals are familiar to humans as common flavors, aromas, and fragrances. even the bitter flavors we associated with coffee or brussels sprouts repel insects. phytonutrients are a key part of good-tasting food -one could even argue that when it comes to fruits and vegetables, better tasting produce is better for you, because it contains higher levels of phytonutrients, which give it the good taste

-the US average intake is only about 1.5 half-cup strings of vegetables per day and less than one serving of fruit per day -the food guide pyramid recommends as a minimum 5 servings of fruits and vegetables each day -because we don't eat as many plant foods as we should, it isn't surprising that cancer is the number 1 cause of death in the US

-eat more VEGETABLES, FRUITS, WHOLE GRAINS, LEGUMES, and herbs/spices (which make small contributions)

-phytonutrient supplements are not likely to be a big help -no one can tell you which phytonutrients are the best, let alone what dosage to take -all we know is that FOODS rich in phytonutrients keep you healthier -it might even be that massive supplemental doses behave entirely differently than the phytonutrient does when its taken as a component of a whole food, the way we saw with beta-carotene -large supplemental doses of beta-carotene actually enhance cancer risk, and, for all we know, that could be the case with other phytonutrients as well

-the approach with the highest degree of safety, and which has the most substantial research base to support it, is a diet rich in whole foods, like veggies, fruits, whole grains, and legumes -we know that works; we have no idea about supplements -there are no known risks to such a diet of whole foods, and there are many known benefits. it could be that the phytonutrient content of such a diet may be one of its biggest benefits -aka EAT A DIET OF WHOLE FOODS IT IS GOOD FOR U hehe

-don't smoke -get exercise -eat lots of fruits and veggies -learn to like fruits and veggies/learn convenient ways to eat them -find ways to get fresh local produce -eat whole grains -eat legumes -focus on minimally processed foods -don't waste time on supplements