Friday Favorites: Lycopene Supplements and Tomato Sauce vs. Prostate Cancer

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High doses of lycopene—the red pigment in tomatoes—were put to the test to see if it could prevent precancerous prostate lesions from turning into full-blown cancer. What happened when cancer patients were given three quarters of a cup of canned tomato sauce every day for three weeks?

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Lycopene is the phytonutrient that gives tomatoes their bright red color. It’s among the most potent of carotenoid antioxidants, so what happened when researchers pitted lycopene and whole tomatoes against prostate cancer? Check it out.

Back in the 80s, the Adventist Health Study found “[s]trong protective relationships [against prostate cancer] with increasing consumption of [legumes],…citrus…,…dried fruit, nuts, and tomatoes.” In the 90s, a Harvard study focused attention on tomatoes, which appeared to be “especially beneficial.” They suspected it might be the red pigment in tomatoes called lycopene, which has greater antioxidant power than some of the other pigments, like the orange beta-carotene pigment in carrots and cantaloupes. And, lycopene dramatically kills off prostate cancer cells in a petri dish—even way down at the levels one would expect in one’s bloodstream after just eating some tomatoes. So, of course, the Heinz ketchup company, along with manufacturers of lycopene supplements, petitioned the FDA to allow them to print health claims on their products.

They were essentially denied, with the FDA saying that the evidence was “very limited and preliminary,” with no endorsement allowed for ketchup or supplements. By that time, further population studies had cast doubt on the lycopene theory. Consumers of high dietary intakes of lycopene didn’t seem to have lower cancer rates, after all. But, who has high dietary intakes of lycopene? Those that eat the most pizza; so, maybe it’s no surprise there are mixed results. What we need is to put lycopene to the test.

It started with a case study. A 62-year old man with terminal prostate cancer; failed surgery, failed chemotherapy, metastases all over, spread to the bone. And so, he was sent to hospice to die. So, he took it upon himself to initiate “phytotherapy”—plant-based therapy, taking the amount of lycopene found in a quarter-cup of tomato sauce, or a tablespoon of tomato paste every day. His PSA, a measure of tumor bulk, started out at 365, dropped to 140 the next month, and then down to 8. His metastases started disappearing, and, as of his last follow-up, appeared to be living happily ever after.

But, when given in higher-dose pill form, it didn’t seem to work. A 2013 review of all such lycopene supplement trials “failed to support [the initial] optimism.” In fact, they were just happy that the lycopene pills didn’t end up causing more cancer, like beta-carotene pills did. But, then came 2014. Researchers in Italy had been giving the largest doses they could of lycopene, selenium, and isolated green tea compounds to men with precancerous prostate lesions, hoping they could prevent full-blown cancer. But, in 2014, the expanded results of a similar trial were published, in which selenium and vitamin E supplements resulted in more cancer. Yikes! So, these researchers stopped their trial, and broke the code to unblind the results, And indeed, those taking high doses of lycopene, green tea catechins, and selenium appeared to get more cancer than those who just got sugar pills.

“The potential implications are dramatic,” said the lead researcher, “given the current massive worldwide use of such compounds as alleged preventive supplementations in prostate and other cancers.” What went wrong?

Well, after the beta-carotene pill debacle, researchers measured cellular damage at different natural and unnatural doses of beta-carotene. At dietary doses, beta-carotene suppressed cellular damage, but at higher, supplemental doses, it not only appeared to stop working, but caused more damage. And, the same with lycopene. “Both lycopene and [beta]-carotene afforded protection against DNA damage” at the kinds of levels one might see in people eating lots of tomatoes or sweet potatoes—”levels…comparable with those seen in the [blood] of individuals who consume a carotenoid-rich healthy diet.” However, at the kind of blood concentrations that one might get taking pills, “the ability to protect the cells against such [free radical] damage was rapidly lost, and, indeed, the presence of [high levels of beta-carotene and lycopene] may actually serve to increase the extent of DNA damage.” So, no wonder high-dose lycopene pills didn’t work.

“Phytochemicals [may be] guardians of our health,” but “[t]he safety of consuming concentrated extracts…is unknown.” The protective benefits of a phytochemical-rich diet is best obtained [through whole plant foods].” The food industry has different ideas, though. Soon, there may be phytochemical-fortified bacon, martinis, and ice cream, says this article in the journal Food Technology. If they can find just the right mix of plant compounds, they hope to reconstruct “foods that once contributed to illness and disease…to offer significant health benefits.”

“Occasionally,… positive things happen in the field of cancer prevention science to popular, good-tasting foods.” Yes, broccoli family vegetables are wonderful, but may be “a hard food for the public to swallow.” By contrast, who doesn’t like tomatoes?

But, studies using high-dose supplements of lycopene, the antioxidant red pigment in tomatoes thought to be the active anticancer ingredient, failed over and over again to prevent or treat cancer, and may even end up promoting it—since at the high levels one can get with supplements, lycopene may actually act as a pro-oxidant. But, lycopene in supplement form doesn’t appear to be effective at lower doses, either. “There is a strong [protective] correlation between the intake of [actual whole] fruit[s] and vegetables and the incidence of certain cancers.” But when we supplement with only a single compound isolated in pill form, we may upset the healthy natural balance of antioxidants.

It does seem to be quite the human hubris to think we can reproduce “the beneficial effects of consuming entire fruits and vegetables” by giving supplements of a single phytochemical, which would normally interact with thousands of other compounds in “the natural matrix” Mother Nature intended. In addition to lycopene, other carotenoids in tomatoes include beta-carotene, gamma-carotene, zeta-carotene, phytofluene, and phytoene, all of which are known “to accumulate in human prostate tissue.” And, “there are also numerous non–carotenoid compounds in tomatoes that [may] have [anti-cancer] activity”—not to mention all the compounds we have yet to even characterize.

But, it’s not about finding the one magic bullet: “The anti-cancer effects of carotenoids and other phytonutrients may reside in [their] combined activity.” For example, at the low concentrations of the tomato compounds phytoene, phytofluene, and lycopene found in most people who eat normal amounts of tomatoes, there’s very little effect on cancer cell growth in vitro, used separately. But combine them all together, and a non-effective dose plus a non-effective dose becomes effective somehow, significantly suppressing prostate cancer cell growth.

And, the same synergy can be seen across foods. Curcumin, the yellow pigment in turmeric and curry powder, tomato extracts, and the vitamin E found in nuts and seeds do little to inhibit pro-growth signaling of prostate cancer cells—less than 10%. But all three together suppresses growth signaling like 70%. The whole is greater than the sum of its parts.

So, how about instead of giving cancer patients lycopene pills, we give them some tomato sauce? “Thirty-two patients with localized prostate [cancer]” were given three-quarters of a cup of canned tomato sauce every day “for 3 weeks…before their scheduled radical prostatectomy.” In their bloodstream, PSA levels dropped “by 17.5%.” PSA, prostate-specific antigen, is a protein produced by prostate gland cells, and elevated blood levels are routinely used “to monitor the success of [cancer] treatment. It was surprising to find that,” in just three weeks, a “tomato sauce-based dietary intervention” could decrease PSA concentrations in men with prostate cancer. Also, free radical damage of the DNA in their white blood cells dropped by 21%. Imagine how antioxidant-poor their diet must have been beforehand, if less than a cup of tomato sauce a day could reduce DNA damage by more than a fifth.

Okay, but what did they find in their prostates? “[H]uman prostate tissue [is thought to] be particularly vulnerable to oxidative DNA damage by free radicals, which are thought to play a critical role in all stages of [cancer formation].” This may be for a number of reasons, including “fewer DNA repair enzymes.” Well, the researchers had tissue samples taken before the tomato sauce from biopsies, and tissue samples after the three weeks of tomato sauce from the surgery, and resected tissues from tomato sauce-supplemented patients had 28% less free radical damage than expected. Here’s the DNA damage in the prostate before the tomato sauce, and here’s after. Just 20 days of sauce. And, what’s interesting is that “[t]here was no association between” the level of lycopene in the prostate and the protective effects. Tomatoes contain a whole bunch of things, some of which may be even more powerful than lycopene.

Regardless, in contrast to the lycopene supplements alone, “the whole-food intervention” seemed to help. To see if lycopene played any role at all, one would have to test a lycopene-free tomato—in other words, a yellow tomato. So, what if you compared red tomatoes to yellow tomatoes, which have all the non-lycopene tomato compounds, to straight lycopene in a pill? So, they fed people red tomato paste, yellow tomato paste, lycopene pills, or placebo pills, and then dripped their blood on prostate cancer cells growing in a petri dish.

Compared to those not eating anything, the red tomato serum, the blood from those who ate red tomato paste, significantly decreased the prostate cancer cell’s expression of a growth-promoting gene called cyclin D1. This downregulation of the gene by the red tomato consumption “may contribute to lower prostate cancer risk by limiting cell proliferation.” The red tomato seemed to work better than the yellow; so, maybe the lycopene helped, but not in pill form. “[T]his gene was not regulated by [the lycopene-pill serum],” indicating that maybe it’s something else. And, lycopene alone significantly upregulated “procarcinogenic genes. Therefore, it can be stated that tomato consumption may be preferable.”

So, what’s the best way? A spouse wrote in to the editor of the Harvard Men’s Health Watch saying his or her husband “wants to have pizza…for his prostate”—to which the doctor replied, fine, but how about “cheese-free pizza (with broccoli instead of pepperoni)”, or, he can just drink some “tomato juice.”

Please consider volunteering to help out on the site.

Icons created by Aetem Kovyazin, Alina Oleynik, Aleksandr Vector, Juraj Sedlák, and Setyo Ari Wibowo from The Noun Project.

Image credits: Kristina DeMuth and Daniel Means. Images have been modified.

Motion graphics by Avocado Video.

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Lycopene is the phytonutrient that gives tomatoes their bright red color. It’s among the most potent of carotenoid antioxidants, so what happened when researchers pitted lycopene and whole tomatoes against prostate cancer? Check it out.

Back in the 80s, the Adventist Health Study found “[s]trong protective relationships [against prostate cancer] with increasing consumption of [legumes],…citrus…,…dried fruit, nuts, and tomatoes.” In the 90s, a Harvard study focused attention on tomatoes, which appeared to be “especially beneficial.” They suspected it might be the red pigment in tomatoes called lycopene, which has greater antioxidant power than some of the other pigments, like the orange beta-carotene pigment in carrots and cantaloupes. And, lycopene dramatically kills off prostate cancer cells in a petri dish—even way down at the levels one would expect in one’s bloodstream after just eating some tomatoes. So, of course, the Heinz ketchup company, along with manufacturers of lycopene supplements, petitioned the FDA to allow them to print health claims on their products.

They were essentially denied, with the FDA saying that the evidence was “very limited and preliminary,” with no endorsement allowed for ketchup or supplements. By that time, further population studies had cast doubt on the lycopene theory. Consumers of high dietary intakes of lycopene didn’t seem to have lower cancer rates, after all. But, who has high dietary intakes of lycopene? Those that eat the most pizza; so, maybe it’s no surprise there are mixed results. What we need is to put lycopene to the test.

It started with a case study. A 62-year old man with terminal prostate cancer; failed surgery, failed chemotherapy, metastases all over, spread to the bone. And so, he was sent to hospice to die. So, he took it upon himself to initiate “phytotherapy”—plant-based therapy, taking the amount of lycopene found in a quarter-cup of tomato sauce, or a tablespoon of tomato paste every day. His PSA, a measure of tumor bulk, started out at 365, dropped to 140 the next month, and then down to 8. His metastases started disappearing, and, as of his last follow-up, appeared to be living happily ever after.

But, when given in higher-dose pill form, it didn’t seem to work. A 2013 review of all such lycopene supplement trials “failed to support [the initial] optimism.” In fact, they were just happy that the lycopene pills didn’t end up causing more cancer, like beta-carotene pills did. But, then came 2014. Researchers in Italy had been giving the largest doses they could of lycopene, selenium, and isolated green tea compounds to men with precancerous prostate lesions, hoping they could prevent full-blown cancer. But, in 2014, the expanded results of a similar trial were published, in which selenium and vitamin E supplements resulted in more cancer. Yikes! So, these researchers stopped their trial, and broke the code to unblind the results, And indeed, those taking high doses of lycopene, green tea catechins, and selenium appeared to get more cancer than those who just got sugar pills.

“The potential implications are dramatic,” said the lead researcher, “given the current massive worldwide use of such compounds as alleged preventive supplementations in prostate and other cancers.” What went wrong?

Well, after the beta-carotene pill debacle, researchers measured cellular damage at different natural and unnatural doses of beta-carotene. At dietary doses, beta-carotene suppressed cellular damage, but at higher, supplemental doses, it not only appeared to stop working, but caused more damage. And, the same with lycopene. “Both lycopene and [beta]-carotene afforded protection against DNA damage” at the kinds of levels one might see in people eating lots of tomatoes or sweet potatoes—”levels…comparable with those seen in the [blood] of individuals who consume a carotenoid-rich healthy diet.” However, at the kind of blood concentrations that one might get taking pills, “the ability to protect the cells against such [free radical] damage was rapidly lost, and, indeed, the presence of [high levels of beta-carotene and lycopene] may actually serve to increase the extent of DNA damage.” So, no wonder high-dose lycopene pills didn’t work.

“Phytochemicals [may be] guardians of our health,” but “[t]he safety of consuming concentrated extracts…is unknown.” The protective benefits of a phytochemical-rich diet is best obtained [through whole plant foods].” The food industry has different ideas, though. Soon, there may be phytochemical-fortified bacon, martinis, and ice cream, says this article in the journal Food Technology. If they can find just the right mix of plant compounds, they hope to reconstruct “foods that once contributed to illness and disease…to offer significant health benefits.”

“Occasionally,… positive things happen in the field of cancer prevention science to popular, good-tasting foods.” Yes, broccoli family vegetables are wonderful, but may be “a hard food for the public to swallow.” By contrast, who doesn’t like tomatoes?

But, studies using high-dose supplements of lycopene, the antioxidant red pigment in tomatoes thought to be the active anticancer ingredient, failed over and over again to prevent or treat cancer, and may even end up promoting it—since at the high levels one can get with supplements, lycopene may actually act as a pro-oxidant. But, lycopene in supplement form doesn’t appear to be effective at lower doses, either. “There is a strong [protective] correlation between the intake of [actual whole] fruit[s] and vegetables and the incidence of certain cancers.” But when we supplement with only a single compound isolated in pill form, we may upset the healthy natural balance of antioxidants.

It does seem to be quite the human hubris to think we can reproduce “the beneficial effects of consuming entire fruits and vegetables” by giving supplements of a single phytochemical, which would normally interact with thousands of other compounds in “the natural matrix” Mother Nature intended. In addition to lycopene, other carotenoids in tomatoes include beta-carotene, gamma-carotene, zeta-carotene, phytofluene, and phytoene, all of which are known “to accumulate in human prostate tissue.” And, “there are also numerous non–carotenoid compounds in tomatoes that [may] have [anti-cancer] activity”—not to mention all the compounds we have yet to even characterize.

But, it’s not about finding the one magic bullet: “The anti-cancer effects of carotenoids and other phytonutrients may reside in [their] combined activity.” For example, at the low concentrations of the tomato compounds phytoene, phytofluene, and lycopene found in most people who eat normal amounts of tomatoes, there’s very little effect on cancer cell growth in vitro, used separately. But combine them all together, and a non-effective dose plus a non-effective dose becomes effective somehow, significantly suppressing prostate cancer cell growth.

And, the same synergy can be seen across foods. Curcumin, the yellow pigment in turmeric and curry powder, tomato extracts, and the vitamin E found in nuts and seeds do little to inhibit pro-growth signaling of prostate cancer cells—less than 10%. But all three together suppresses growth signaling like 70%. The whole is greater than the sum of its parts.

So, how about instead of giving cancer patients lycopene pills, we give them some tomato sauce? “Thirty-two patients with localized prostate [cancer]” were given three-quarters of a cup of canned tomato sauce every day “for 3 weeks…before their scheduled radical prostatectomy.” In their bloodstream, PSA levels dropped “by 17.5%.” PSA, prostate-specific antigen, is a protein produced by prostate gland cells, and elevated blood levels are routinely used “to monitor the success of [cancer] treatment. It was surprising to find that,” in just three weeks, a “tomato sauce-based dietary intervention” could decrease PSA concentrations in men with prostate cancer. Also, free radical damage of the DNA in their white blood cells dropped by 21%. Imagine how antioxidant-poor their diet must have been beforehand, if less than a cup of tomato sauce a day could reduce DNA damage by more than a fifth.

Okay, but what did they find in their prostates? “[H]uman prostate tissue [is thought to] be particularly vulnerable to oxidative DNA damage by free radicals, which are thought to play a critical role in all stages of [cancer formation].” This may be for a number of reasons, including “fewer DNA repair enzymes.” Well, the researchers had tissue samples taken before the tomato sauce from biopsies, and tissue samples after the three weeks of tomato sauce from the surgery, and resected tissues from tomato sauce-supplemented patients had 28% less free radical damage than expected. Here’s the DNA damage in the prostate before the tomato sauce, and here’s after. Just 20 days of sauce. And, what’s interesting is that “[t]here was no association between” the level of lycopene in the prostate and the protective effects. Tomatoes contain a whole bunch of things, some of which may be even more powerful than lycopene.

Regardless, in contrast to the lycopene supplements alone, “the whole-food intervention” seemed to help. To see if lycopene played any role at all, one would have to test a lycopene-free tomato—in other words, a yellow tomato. So, what if you compared red tomatoes to yellow tomatoes, which have all the non-lycopene tomato compounds, to straight lycopene in a pill? So, they fed people red tomato paste, yellow tomato paste, lycopene pills, or placebo pills, and then dripped their blood on prostate cancer cells growing in a petri dish.

Compared to those not eating anything, the red tomato serum, the blood from those who ate red tomato paste, significantly decreased the prostate cancer cell’s expression of a growth-promoting gene called cyclin D1. This downregulation of the gene by the red tomato consumption “may contribute to lower prostate cancer risk by limiting cell proliferation.” The red tomato seemed to work better than the yellow; so, maybe the lycopene helped, but not in pill form. “[T]his gene was not regulated by [the lycopene-pill serum],” indicating that maybe it’s something else. And, lycopene alone significantly upregulated “procarcinogenic genes. Therefore, it can be stated that tomato consumption may be preferable.”

So, what’s the best way? A spouse wrote in to the editor of the Harvard Men’s Health Watch saying his or her husband “wants to have pizza…for his prostate”—to which the doctor replied, fine, but how about “cheese-free pizza (with broccoli instead of pepperoni)”, or, he can just drink some “tomato juice.”

Please consider volunteering to help out on the site.

Icons created by Aetem Kovyazin, Alina Oleynik, Aleksandr Vector, Juraj Sedlák, and Setyo Ari Wibowo from The Noun Project.

Image credits: Kristina DeMuth and Daniel Means. Images have been modified.

Motion graphics by Avocado Video.

Doctor's Note

So what are the Best Supplements for Prostate Cancer? Watch the video to find out!

More on natural treatments for prostate cancer in:

Are there any foods we should avoid? Check out, for example, Prostate Cancer Survival: The A/V Ratio and How Our Gut Bacteria Can Use Eggs to Accelerate Cancer.

We may be able to prevent cancer and even reverse the progression of cancer with diet. See:

It isn’t always easy to get guys to change, though. See Changing a Man’s Diet After a Prostate Cancer Diagnosis.

Check out the How Not to Die Cookbook for a bunch of green-light recipes! As always, all of my proceeds go to charity. Get a dose of tomato sauce with my Roasted Vegetable Lasagna.

The original videos aired on November 1 and 3, 2017

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