Thursday, February 24, 2011

Polyphenols, Hormesis and Disease: Part II

In the last post, I explained that the body treats polyphenols as potentially harmful foreign chemicals, or "xenobiotics". How can we reconcile this with the growing evidence that at least a subset of polyphenols have health benefits?

Clues from Ionizing Radiation

One of the more curious things that has been reported in the scientific literature is that although high-dose ionizing radiation (such as X-rays) is clearly harmful, leading to cancer, premature aging and other problems, under some conditions low-dose ionizing radiation can actually decrease cancer risk and increase resistance to other stressors (1, 2, 3, 4, 5). It does so by triggering a protective cellular response, increasing cellular defenses out of proportion to the minor threat posed by the radiation itself. The ability of mild stressors to increase stress resistance is called "hormesis." Exercise is a common example. I've written about this phenomenon in the past (6).

The Case of Resveratrol

Resveratrol is perhaps the most widely known polyphenol, available in supplement stores nationwide. It's seen a lot of hype, being hailed as a "calorie restriction mimetic" and the reason for the "French paradox."* But there is quite a large body of evidence suggesting that resveratrol functions in the same manner as low-dose ionizing radiation and other bioactive polyphenols: by acting as a mild toxin that triggers a hormetic response (7). Just as in the case of radiation, high doses of resveratrol are harmful rather than helpful. This has obvious implications for the supplementation of resveratrol and other polyphenols. A recent review article on polyphenols stated that while dietary polyphenols may be protective, "high-dose fortified foods or dietary supplements are of unproven efficacy and possibly harmful" (8).

The Cellular Response to Oxidants

Although it may not be obvious, radiation and polyphenols activate a cellular response that is similar in many ways. Both activate the transcription factor Nrf2, which activates genes that are involved in detoxification of chemicals and antioxidant defense**(9, 10, 11, 12). This is thought to be due to the fact that polyphenols, just like radiation, may temporarily increase the level of oxidative stress inside cells. Here's a quote from the polyphenol review article quoted above (13):
We have found that [polyphenols] are potentially far more than 'just antioxidants', but that they are probably insignificant players as 'conventional' antioxidants. They appear, under most circumstances, to be just the opposite, i.e. prooxidants, that nevertheless appear to contribute strongly to protection from oxidative stress by inducing cellular endogenous enzymic protective mechanisms. They appear to be able to regulate not only antioxidant gene transcription but also numerous aspects of intracellular signaling cascades involved in the regulation of cell growth, inflammation and many other processes.
It's worth noting that this is essentially the opposite of what you'll hear on the evening news, that polyphenols are direct antioxidants. The scientific cutting edge has largely discarded that hypothesis, but the mainstream has not yet caught on.

Nrf2 is one of the main pathways by which polyphenols increase stress resistance and antioxidant defenses, including the key cellular antioxidant glutathione (14). Nrf2 activity is correlated with longevity across species (15). Inducing Nrf2 activity via polyphenols or by other means substantially reduces the risk of common lifestyle disorders in animal models, including cardiovascular disease, diabetes and cancer (16, 17, 18), although Nrf2 isn't necessarily the only mechanism. The human evidence is broadly consistent with the studies in animals, although not as well developed.

One of the most interesting effects of hormesis is that exposure to one stressor can increase resistance to other stressors. For example, long-term consumption of high-polyphenol chocolate increases sunburn resistance in humans, implying that it induces a hormetic response in skin (19). Polyphenol-rich foods such as green tea reduce sunburn and skin cancer development in animals (20, 21).

Chris Masterjohn first introduced me to Nrf2 and the idea that polyphenols act through hormesis. Chris studies the effects of green tea on health, which seem to be mediated by polyphenols.

A Second Mechanism

There is a place in the body where polyphenols are concentrated enough to be direct antioxidants: in the digestive tract after consuming polyphenol-rich foods. Digestion is a chemically harsh process that readily oxidizes ingested substances such as polyunsaturated fats (22). Oxidized fat is neither healthy when it's formed in the deep fryer, nor when it's formed in the digestive tract (23, 24). Eating polyphenol-rich foods effectively prevents these fats from being oxidized during digestion (25). One consequence of this appears to be better absorption and assimilation of the exceptionally fragile omega-3 polyunsaturated fatty acids (26).

What does it all Mean?

I think that overall, the evidence suggests that polyphenol-rich foods are healthy in moderation, and eating them on a regular basis is generally a good idea. Certain other plant chemicals, such as suforaphane found in cruciferous vegetables, and allicin found in garlic, exhibit similar effects and may also act by hormesis (27). Some of the best-studied polyphenol-rich foods are tea (particularly green tea), blueberries, extra-virgin olive oil, red wine, citrus fruits, hibiscus tea, soy, dark chocolate, coffee, turmeric and other herbs and spices, and a number of traditional medicinal herbs. A good rule of thumb is to "eat the rainbow", choosing foods with a variety of colors.

Supplementing with polyphenols and other plant chemicals in amounts that would not be achievable by eating food is probably not a good idea.


* The "paradox" whereby the French eat a diet rich in saturated fat, yet have a low heart attack risk compared to other affluent Western nations.

** Genes containing an antioxidant response element (ARE) in the promoter region. ARE is also sometimes called the electrophile response element (EpRE).

71 comments:

David said...

I think you nailed it. Of course, there is a lot yet to be understood, but once again your claims do not exceed the evidence. And, I'm glad to see the mention of sulforphane. I'm surprised you didn't mention that there is no French Paradox, if one is a regular reader of Whole Health Source. Thanks again!

Todd Hargrove said...

Thanks for a great post.

Why a rainbow? Does this ensure that you are getting a diversity of different types of polyphenols? Couldn't you get quite a diversity without eating different colors?

Alex said...

Hi Steve, Great post.

I like your second mechanism and the idea of thinking about how food components interact with each other.

I wonder if there is an additional mechanism by which polyphenols afford protection. Namely, do they mitigate the autoimmune effects of various proteins by binding with them during digestion or even sooner, when cooking and preparing foods. In winemaking we use a variety of proteins (casein, albumin, gelatin, isinglass) to remove excess or undesirable polyphenols.

I heard about one study in the popular press that talked about how adding milk to tea prevented the beneficial affects of tea consumption (polyphenols and casein again). To think about it in another light, does tea make milk safer to drink for people sensitive to casein?

Do we have any information on whether gluten readily binds with polyphenols?

Alex J

gunther gatherer said...

Thanks for this!

The ionizing radiation benefits you mention make me think then: Perhaps the purported benefits of vitamin D are actually not from the vitamin itself, but from the hormetic processes the sun's radiation sets in motion?

dum3z said...

David,
There's still a French paradox, though. They eat a ton of bread and live long lives.

Gunther,
Given what Stephan was talking about in the post, that could be possible. I think the vitamin D is probably still an important part, though.

douglis said...

So after all....is the french paradox explained(or at least partialy) by red wine?

Brad Hurley said...

Personally I think the French Paradox boils down to genetics. Having lived with a French woman for the past decade and having spent quite a bit of time in France, I'd say there is some truth to the stereotype of the high-strung, high-metabolism French man or woman; in a nutshell French people are different from the rest of us. You can take a thin French person and transplant him or her to America with a typical American diet and lifestyle, and he or she will probably not gain weight. There are exceptions to everything of course, but my hunch is that the general observation that French people tend to be excitable and highly strung may translate to a trait for high baseline metabolism. My French girlfriend and I eat the same diet and similar portion sizes; I have to watch my weight but if anything she has to be careful to avoid becoming dangerously underweight.

john said...
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malpaz said...

had the exact same thought as gunther about vitamin D... a quick search shows me that the Yerba Mate tea drink is very potent in antioxidants?

john said...

Hi Stephan,

Ref 24 is interesting: what is going on with the HO group? They did have somewhat higher serum glucose, but they had less body fat and weight gain [to other high fat]. The serum glucose was a bit higher, but their serum leptin, insulin, and liver trigs were way lower. Note that although the HO group and low fat group has similar body fat, the low fat group had larger yet fewer adipocytes. So, who's healthier?

Just so you know, reference 27 is the same as 10 and, at least in the abstract, doesn't mention suforaphane or allicin.

douglis and Brad,

The French paradox is only a paradox with incorrect thoughts about saturated fat.

Paul Jaminet said...

Hi Stephan,

I like your two mechanisms, but here's a third: modulation of gut flora.

Toxin levels are much higher in the gut than the body. So they can be hormetic in the body, but deadly to microbes in the gut.

Many of these compounds are part of plant immune defenses against microbes. So they evolved activity against microbes.

Best, Paul

Chris Masterjohn said...

Great post. I think it's pretty funny that the ARE is alternatively called the "antioxidant response element" or the "electrophile response element," because the latter is usually used when it is toxic reactive drug metabolites and such things activating the response element. That commonality seems to emphasize that these are "well-behaved toxins," even though they are referred to as "antioxidants" in this context.

rob said...

That seems to be a pretty big misconception of the pharmacological effects of reservatol. http://www.ncbi.nlm.nih.gov/pubmed/19843076

Barry said...

We assume that if something is highly toxic at high doses, it's slightly toxic at low doses. Hormesis says this is not necessarily the case.

The notorious poisons dioxin and PCBs may have a hormetic effect:

http://www.ncbi.nlm.nih.gov/pubmed/18648613

The study found, counter-intuitively, "The highest risk of sarcoma was found in the septile with the lowest body burden...".

When plotting incidence of soft tissue sarcoma, the study suggested the possibility of a J-shaped response curve. That is, the risk of cancer is higher at the lowest concentrations. Then, as concentrations increase, the risk declines before going higher again. The implication is that there is a body-burden of this toxin, above the minimum, that is ‘healthier’ (my term) than having little or none at all.

A lot of substances have been banned because, since they appear to cause cancer at high doses, they are assumed to cause cancer at low doses. This assumes a linear dose-response curve. If, however, the dose-response curve is non-linear, low concentrations may have no health effects or, if hormetic, may even be beneficial.

Now, what other substances might have a hormetic effect at low to moderate doses? Carbohydrates? Food additives? Vegetable oils? Processed food?

Hormesis is an area that deserves a great deal more study: We may have to change the way we think about toxins.

Stephan said...

Hi Todd,

Yes, it's to ensure a diversity of polyphenols and other substances such as carotenoids.

Hi Alex,

My thinking is that polyphenols binding proteins in the digestive tract probably isn't a good thing. It inhibits digestive enzymes, which is probably why we secrete protective polyphenol-binding proteins in saliva and increase gastric secretions in response to bitter foods.

Hi Gunther,

That could be, although the vitamin D itself is important as well.

Hi Douglis,

I don't think so. First of all, there is no paradox. If you adjust for diagnostic bias, the French have a similar CHD rate to other countries in Southern Europe. The fact that they eat a lot of SFA is irrelevant because it has never been convincingly associated with CHD.

Hi Brad,

I don't think it's genetics. Most of the French people I know who moved to the US gained weight unless they cooked all their own food. Same for people from other European countries.

Stephan said...

Hi John,

Yes, that is curious. Perhaps the HO group wasn't that unhealthy after all.

About the references, I do give the same ref different numbers within the same post sometimes. I number refs sequentially because it would be a pain in the butt to do otherwise.

If you read the full text of ref 10/27, you will see that they used both sulforaphane and compounds from garlic.

Hi Paul,

Thanks.

Hi Chris,

Interesting observation.

Hi Barry,

I agree, hormesis does throw a wrench in the way we typically think about toxins. But I think the things most likely to have a beneficial hormetic effect are those that we evolved to deal with. Natural stimuli are probably going to be the most effective hormetic inducers.

water said...

any thoughts on salicylate intolerance/food chemical intolerance? Some children have dramatic improvements in behavior when they eat foods that are less polyphenol rich, for example. Plenty of adults do well on the Failsafe diet.

Stephan said...

Hi water,

Yes, you raise a good point. Some people are intolerant of certain plant chemicals. That's one of the reasons why I wasn't stronger in my recommendation to eat polyphenol-rich foods.

"Guppy" Honaker said...

Hey Stephen,

It's been a while since I've left a comment (though I read your blog nearly everyday).

You mentioned x-rays. It's important that when people go to their dentist that, if an x-ray is suggested (and NEEDED - which in most cases it is), ask for a "Thyroid Guard." In most cases, they have one but don't even think to put it over your throat for protection unless you specifically ask for it.

- David

Top 10 Aloe Vera Juice Benefits
Holistic Nutrition and Health

JML said...
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JML said...
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Might-o'chondri-AL said...
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Helen said...

I'll have the broccoli sprouts with a side of dental x-rays, please.

Might-o'chondri-AL said...
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David L said...

Stephan,

I understand the argument against high dose supplements and the related J-curve argument. However, when I look at some of these polyphenol studies, I am seeing relatively high levels of food items. For example, the Japanese drink four to six glasses of green tea a day. The common belief is that two glasses of red wine are optimum.

I don't necessarily want to high dose the nutrient, but wonder why green tea solids and resveratrol supplements,for example, in a moderate amounts would not be ok. I'm just not in the position to drink six cups of green tea and two glasses of wine every day,

joetheplumber said...

You're right about the hormesis response, but you're still ignoring a large body of evidence showing that polyphenol health benefits are also due to reinforcing beneficial gene expression that degrades during the aging process. Ignoring this point seems premature.

成卓伦 said...

dum3z: I was going to second your question on bread and perhaps the real French paradox, but I found the comments on the China Study on Wheat. Take a look at some possible explanations.

Might-o'chondri-AL said...
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Steve said...

Hi Stephen,

How does the stressor effect of hormesis from these compounds fit into an already stressed out body and lifestyle. In the context of the SAD where our cells and system wide anti-oxident systems are already likely overworked from excess processed foods, sugars, pufa's etc, does stressing them out even more with plant chemicals still provide a benifit, or does this then come down on the other side of the 'J' curve and add to the pro-oxidant effect?
Or is the method completely seperate and still provides a hormetic effect regardless of other stressors?
Is this related to the possible negative effects of other high dose nutrients?

Thanks for your time

Steve

morten_g said...

Aren't the French still doing well despite drinking too much and smoking too much?

My two guesses are these:
1) French healthcare system is simply best.
2) French skip breakfast more than others (intermittent fasting effects)

John said...

@Might-o'chondri-AL

I like the rigor of the information you're telling us, but I am rather skeptical of how EGCG gets from your food to your cells in the first place. The impression I've gotten from various literature is we really don't know how antioxidants affect our cells. As in we don't know how a bunch of ingested EGCG can not run into a bunch of free oxygen in our stomach, make it into our bloodstream and be evenly distributed to our cells (not to mention those that picture antioxidants getting into mitochondria to quell free radical DNA damage). If anything it seems more reasonable to me that ingesting excess antioxidants might cause a net gain in antioxidants that your body naturally makes and subsequently has a positive effect.

John

Might-o'chondri-AL said...
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David said...

Another class of sometimes beneficial plant chemicals are some of the bewildering array of terpenes. Do you think, when there it appears that they are of benefit to us, that it is usually, often, or occasionally through hormetic mechanisms?

LeonRover said...

I don't get the the notion that there is a "French Paradox".

What an absurd con-struction (a la J P Sartre), or by contrast a Derrida-ist de-construction.

There is an implicit assumption in the "American Orthodox", and that non-American is therefore the "Paradox".

Not only is there a "French Paradox" but there is also a similar "Swiss Paradox", not explained by a Mediterranean diet.

Even further afield there a "Kitavan Paradox", while
within North America, there are many sub-populations, an example being the "Amish Paradox".

From a European perspective, North American descriptions are the Paradox, while European descriptions are Orthodox, so what gives?

Get with the notion that American perspectives are the Paradox and the rest of us reflect the Orthodox.

Come on, Stephen, you are more International, are you not?

Stephan said...

Hi David L,

I doubt polyphenol supplements are inherently toxic, it probably just depends on the dose. I'm not sure you can just "scale up" from rodent studies for a variety of reasons. Polyphenols are metabolized differently in humans (i.e. different pharmacokinetics), and rodent studies typically use a low-polyphenol background diet with added polyphenols. In humans, adding an equivalent dose to a diet that already contains significant polyphenols could be too much. I'm just speculating here, but my main point is that I'm pretty sure polyphenol-rich foods are safe, whereas I can't be confident that supplements are safe because no one has long-term data in humans. If you're supplementing with an amount that can be obtained from food, I doubt it will do any harm, but that's just a guess.

Hi joetheplumber,

I'm not intentionally ignoring anything. What makes you think that the gene expression changes you're referring to are not caused by a hormesis response? Enhancing antioxidant defenses and repair mechanisms counts as "reinforcing beneficial gene expression that degrades during the aging process". Since polyphenols are so diverse in structure, I'm sure there are specific polyphenols that have drug-like effects, and perhaps a small subset of those are beneficial. I'm not familiar enough with the literature to know if there are polyphenols that have effects through non-hormetic mechanisms (except the phytoestrogens like genistein, which are of dubious value to health IMO).

Hi Steve,

That's a good question, and I can't answer it with 100% confidence. But I do think that mildly stressing the body in certain specific ways can be helpful for most people even in the context of a modern lifestyle that's already stressful in other ways. Exercise is a good example. I think a good exercise regimen coupled with adequate rest increases your resistance to other stressors, such as physical and emotional stress. But perhaps there are some people who wouldn't benefit from exercise because their bodies are already on the edge.

Hi David,

I haven't looked into terpenes, but I suspect there are many types of plant chemicals that can act by hormesis.

Chris Masterjohn said...

Leon,

There's an "American Paradox" too:

http://www.ncbi.nlm.nih.gov/pubmed/15531654

Chris

Kurt G. Harris MD said...

Another excellent post. You have provided the science to my own intuitions. I've never believed it made sense that we evolved to require specific plants in our diet, nor that the human body can be "improved" with supplements derived from them. But it makes sense that we evolved to derive a hormetic benefit from a suite of plant compounds that will show up with the plants we are evolved (as omnivores) to eat.

My palette is probably smaller than yours, but I do consume dark chocolate, coffee, tea and green tea in pretty decent amounts, in addition to colorful veggies like sweet potato, tomato and "atkins vegetables" like salad greens.

The idea that a variety of different polyphenols is good, but big doses are as therapeutic as too much radiation makes a lot of sense on an evolutionary basis.

I like the comparison with hormesis from low level radiation. Interestingly, the CW is just as confused about that as about the benefits of polyphenols from plants. When you hear stories in the MSM about how a single CT scan causes cancer, you can remember 2 things:

1) There is no epidemiologic evidence whatever for cancer caused by CT scans.

2) Estimates of cancer rates are interpolations from data derived from massive doses - atomic bombs. They assume a linear dose-response rate model - a model that REJECTS the possibility of hormesis.

And to the other posters worried about dental xrays, the way to reduce dose with dental is to make sure your dentist has a true digital x-ray unit. This will be only 1/3 the dose from film radiography (the old fashioned kind). There is no need for lead shielding. If your thyroid or lungs are getting a dose, they aren't be taking a picture of your teeth! (The beam is very highly collimated in dental xrays.)

Kurt G. Harris MD said...

@Gunther

I also think sunshine is hormetic, but probably only up to the minimal erythemal dose, beyond which there is no more vitamin D made anyway.

jnktangent said...

Received my hibiscus tea in the mail this week. Very nice treat.

Dr. Curmudgeon Gee said...

awesome! thanks.

Stanley said...

I think it's a mistake to think of polyphenols as mere (anti)oxidants of various strengths. Resveratrol, for instance, is thought to target a very specific metabolic pathway:

http://www.longecity.org/forum/topic/27350-resveratrol-and-nampt-what-is-resveratrols-true-target

There may be coursely similar properties in this chemical class, probably due to the polyphenols' hydroxyl groups, but we shouldn't forget that individual ones may target very specific pathways for molecular morphological reasons unrelated to the mere presence of hydroxyl groups. I'm not saying you made this error, Stephan, but I think the general public has a tendency to do so.

I also wouldn't encourage people to simply accept the notion that concentrated polyphenol pills are bad simply because they're processed foods. Butter, cheese, and chocolate also processed foods, but appear to be somewhat beneficial. So too might be certain concentrated polyphenols in certain doses. I think what is needed is more research. What we have at present is a preponderance of compelling evidence and a relative absence of longterm human data, insofar as polyphenol supplements are concerned.

douglis said...

Most of the polyphenols are phytoestrogens(revestratol is also one) and their consuption has as effect the elevation of HDL.Isn't this another possible way(non hormetic) that polyphenols improve health?
I really wonder about their effect on sex hormones though.

EL 66K said...

Very interesting post Stephan. What are your thoughts about food chemical intolerance? If someone can't defend himself of minute amounts of chemicals like phenols in plants, wouldn't that point to reduced ability to mount a response to a variety of stresses?

Might-o'chondri-AL said...
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Mark L said...

Questions:
If we make a hormetic stress continuous (instead of episodic), does it lose its hormetic effect? What are the optimum doses and optimum frequencies of blueberries, strawberries, garlic, turmeric, radiation, etc.? Do some homeopathic remedies induce the body to respond hormetically as if the original substance were present? Is there a hormetic effect when simply visualizing the consumption of hormetic polyphenols?

Amy said...

I saw this article in Science Daily (link)
I won't even pretend that I understand it.
How does heparin fit in to all of this? Are there natural forms of heparin?

A lot of people that have food allergies and intolerances have trouble with different polyphenols.

Thank you for your help in advance.

Amy

Katya said...

Hi Stephan,
Thanks for all the info, great food for thought as always.

I was wondering, off the top of your head, could you recommend any graduate programs in nutrition that don't follow the mainstream line of thought on this topic? Or perhaps any organizations or universities which do insightful/valuable work? I have a background in molecular biology and am continually fascinated by the developments and insights into this field, but am skeptical about the types of career opportunities available for those wanting to study it. (For example, one could pay 80k and go to Columbia's school of nutrition for a year, and learn a lot about nothing).

Thanks for any advice you may have : )

Tim Lundeen said...

Re homesis and the value of exercise, have you seen this NY Times blog about how high levels (400IU/day) of Vitamin E prevent the beneficial effects of exercise on glucose metabolism?

http://well.blogs.nytimes.com/2010/10/06/phys-ed-free-the-free-radicals/

The original research is at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680430/

The paper used Vitamin C (1000mg/day) and Vitamin E (400IU/day) together, but 1000mg/day of Vit C is readily achievable from food, so is in the normal range; I think the effects they saw were from the high Vit E levels. Unfortunately, most multi-vitamins contain 400IU of Vitamin E.

gunther gatherer said...

Morten G., maybe drinking and smoking are hormetic too, at least in moderation. And the French seem to be pretty moderate with both.

Don't forget they also ingest lots of bacteria in their wine, vinegar and stinky raw cheeses. Bacteria give off lipopolysaccharides which cause hormesis too, since they stimulate the immune system and other anti-inflammatory pathways.

gunther gatherer said...

And if extra virgin olive oil causes hormesis, the French are getting a lot of that as well.

water said...

Dr. Harris - I very much appreciate your putting the dental x-rays in perspective. Dentists have thyroid guards; are they for thyroid patients? I tend to avoid the dentist anyway; just don't need to go as often after changing the diet. My main question is about the radiation from an airplane flight. How does that relate to what is being discussed here?

Might-o'chondri-AL said...
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Morris said...

@Al
According to CDC, radiation exposure from a x-country flight is 0.03mS or 1/3 that of a chest X-ray. Quite different from what you said. Sieverts replace Rem as standard units, 1S=100Rem.

Might-o'chondri-AL said...
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Jack said...

@Al -

How come you don't create your own forum? You seem to have so much knowledge about dang near every topic under the sun. I read through your posts and I am just amazed at the complexity of your comments. I consider myself to be at least reasonably intelligent, yet I cannot grasp much of what you put down. And I am beginning to think that maybe you are just a brilliant mind that could be of even greater help if you had your own site that could draw some like minded (BIG minded) folks to your circle.

Ever considered the possibilty?

Might-o'chondri-AL said...
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Kurt G. Harris MD said...

@Al

Barium is absolutely not radioactive. Flouroscopy is just a video x-ray and the dose depends on the length of procedure.

Jack said...

jeez i should hope barium is not radioactive. i think i drank that stuff when i did a CT scan or something. or was it an MRI. I can't remember.

John said...

For those interested (from Am J Clin Nutr May 1, 2004 vol. 79 no. 5 727-747 ):
Polyphenols: food sources and bioavailability

TABLE 1 Polyphenols in foods

Source (serving size) Polyphenol content
By wt or vol By serving
mg/kg fresh wt (or mg/L) mg/serving
Hydroxybenzoic acids (2, 6) Blackberry (100 g) 80–270 8–27
Protocatechuic acid Raspberry (100 g) 60–100 6–10
Gallic acid Black currant (100 g) 40–130 4–13
p-Hydroxybenzoic acid Strawberry (200 g) 20–90 4–18
Hydroxycinnamic acids (2, 5–7) Blueberry (100 g) 2000–2200 200–220
Caffeic acid Kiwi (100 g) 600–1000 60–100
Chlorogenic acid Cherry (200 g) 180–1150 36–230
Coumaric acid Plum (200 g) 140–1150 28–230
Ferulic acid Aubergine (200 g) 600–660 120–132
Sinapic acid Apple (200 g) 50–600 10–120
Pear (200 g) 15–600 3–120
Chicory (200 g) 200–500 40–100
Artichoke (100 g) 450 45
Potato (200 g) 100–190 20–38
Corn flour (75 g) 310 23
Flour: wheat, rice, oat (75 g) 70–90 5–7
Cider (200 mL) 10–500 2–100
Coffee (200 mL) 350–1750 70–350
Anthocyanins (8–10) Aubergine (200 g) 7500 1500
Cyanidin Blackberry (100 g) 1000–4000 100–400
Pelargonidin Black currant (100 g) 1300–4000 130–400
Peonidin Blueberry (100 g) 250–5000 25–500
Delphinidin Black grape (200 g) 300–7500 60–1500
Malvidin Cherry (200 g) 350–4500 70–900
Rhubarb (100 g) 2000 200
Strawberry (200 g) 150–750 30–150
Red wine (100 mL) 200–350 20–35
Plum (200 g) 20–250 4–50
Red cabbage (200 g) 250 50
Flavonols (11–18) Yellow onion (100 g) 350–1200 35–120
Quercetin Curly kale (200 g) 300–600 60–120
Kaempferol Leek (200 g) 30–225 6–45
Myricetin Cherry tomato (200 g) 15–200 3–40
Broccoli (200 g) 40–100 8–20
Blueberry (100 g) 30–160 3–16
Black currant (100 g) 30–70 3–7
Apricot (200 g) 25–50 5–10
Apple (200 g) 20–40 4–8
Beans, green or white (200 g) 10–50 2–10
Black grape (200 g) 15–40 3–8
Tomato (200 g) 2–15 0.4–3.0
Black tea infusion (200 mL) 30–45 6–9
Green tea infusion (200 mL) 20–35 4–7
Red wine (100 mL) 2–30 0.2–3
Flavones (11–12, 14, 18) Parsley (5 g) 240–1850 1.2–9.2
Apigenin Celery (200 g) 20–140 4–28
Luteolin Capsicum pepper (100 g) 5–10 0.5–1
Flavanones (19–21) Orange juice (200 mL) 215–685 40–140
Hesperetin Grapefruit juice (200 mL) 100–650 20–130
Naringenin Lemon juice (200 mL) 50–300 10–60
Eriodictyol
Isoflavones (22–25) Soy flour (75 g) 800–1800 60–135
Daidzein Soybeans, boiled (200 g) 200–900 40–180
Genistein Miso (100 g) 250–900 25–90
Glycitein Tofu (100 g) 80–700 8–70
Tempeh (100 g) 430–530 43–53
Soy milk (200 mL) 30–175 6–35
Monomeric flavanols (6, 17, 26, 27) Chocolate (50 g) 460–610 23–30
Catechin Beans (200 g) 350–550 70–110
Epicatechin Apricot (200 g) 100–250 20–50
Cherry (200 g) 50–220 10–44
Grape (200 g) 30–175 6–35
Peach (200 g) 50–140 10–28
Blackberry (100 g) 130 13
Apple (200 g) 20–120 4–24
Green tea (200 mL) 100–800 20–160
Black tea (200 mL) 60–500 12–100
Red wine (100 mL) 80–300 8–30
Cider (200 mL) 40 8

John said...

^eat some eggplant (aubergine)!!

Razwell said...

Great points and questions, Stephan and Steve.


Some vegans think plants are a panacea, and they definitely are not. There are potentially harmful compounds in them.


A balanced diet is important, but some people think as long as they are eating plants they are completely protected from coronary disease and cancer.


As far as exercise ,I agree. People with diseases who are physically stressed will not benefit from too much exercise.They should move some - but light.

Pretty In Primal said...

@ Alex- I don't know if polyphenols bind with anything to mitigate autoimmune effects, but I do know that they can be used to balance TH1 cell-mediated dominant autoimmune conditions like Crohn's, Hashimoto's (which I have) and Rheumatoid Arthritis by action of stimulating a TH2 humoral immunity response. I'm on a TH1 balancing protocol that uses a combo of polyphenols (resveratrol, green tea, pine bark, grape seed). This is not advisable if you have an autoimmune condition unless you know for sure that you're TH1 dominant (you can find out through blood testing for CD4/CD8 ratio).

Pedro said...

Great post Stephan as usual.

Caloric Restriction, Exercise (as you said), thermal stress, Intermittent fasting, etc. All have hormetic actions.

Another phytochemical with an hormetic action is curcumin http://www.ncbi.nlm.nih.gov/pubmed/19343114

And there are various studies with curcumin in various cancer cell lines. Personally, I know a physician who uses it in colon cancer with great success.

Keep up the great work.

Pedro

Jeffrey of Troy said...

Perhaps these substances are read by your body as a signal that it is summer, and so time to turn on the appetite, fat-burning, muscle-building, and sex hormones?

benn686 said...

are polyphenols and flavonoids the same thing?

flavonids are shown to increase leukemia cancer!

http://www.ncbi.nlm.nih.gov/pubmed/20025993

Ian said...

Here is a clue that certain dye-like substances such as in turmeric, red wine and blueberries cling to or penetrate defective proteins in plaques and possibly mark them for destruction. Their minor toxicity also alerts homeostatic defences.
http://www.researchals.org/page/4746/6722/
The big question seems to be optimal doses. Another would be whether combinations are more effective.

Bill Rowles said...

You might like to check out Michael Ristow, who's done a fair bit of research into ROS induced hormesis, and the effect of antioxidants in its inhibition. Here's a couple of links:

http://www.sciencedirect.com/science/article/pii/S1550413107002562

http://www.pnas.org/content/early/2009/05/11/0903485106.abstract

hopeful geranium said...

"For example, long-term consumption of high-polyphenol chocolate increases sunburn resistance in humans, implying that it induces a hormetic response in skin (19). Polyphenol-rich foods such as green tea reduce sunburn and skin cancer development in animals"

Here I think you might be heading into "uneccesary hypothesis" territory. Plants evolved polyphenols to (in part) protect against UV radiation. Is it so crazy that they have the same effect in animals that consume them for the same reasons (resonance structure plus hydroxyl groups, as in synthetic sunblock?)
I also note the structural similarity between polyphenols and the tanning compounds formed in human skin on exposure to UV; both are polymer derivatives of aromatic amino acids.
And where do carotenoids fit into the hormesis theory of the rainbow?
They are not metabolised as toxins, yet have very similar effects on UV and cancer to polyphenols.
Are polyphenols hormetic to the plants that make them?

hopeful geranium said...

About salicylate intolerance; salicilate is detoxified by the acetyl-coA and glycine type 2 detox pathways, so could be a sign of co-enzyme A deficiency. Does salicylate intolerance correlate with lupus? A quick search shows it does: www.bmj.com/content/2/6151/1532.2.full.pdf+html
Pantethine, or high-dose B5 and sulfur amino acids, or a high-fat, high protein diet are indicated in either condition.
Megadose B5 is the standard orthomolecular treatment for lupus. This tells us something about what is going on in both conditions.

hopeful geranium said...

Specific polyphenols can affect cells via pathways that are no different from those by which drugs (or in some cases hormones operate). Do pharmaceuticals then deliver their benefits through hormesis? Is this how, for example, low dose aspirin works?
This is the reductio ad absurdum of the hormetic polyphenol hypothesis. I think the hypothesis does have merit, but I also think you need to revisit the definition of hormesis, and study some of the specific actions of particular polyphenols - any hypothesis is but a starting point.
An alternative or complementary hypothesis; polyphenols are low-dose drugs, their effect is medicinal rather than nutritional.
Most traditional herbal medicines are polyphenol-based, and the majority of the polyphenols in a large proprotion of the world's diets are actually taken in drug form; coffee, tea, mate, coca, wine, or in spices, or in traditional medicines (e.g. hibiscus tea in Mexico)

marcus volke said...

Hi stephan, I noticed one thing you left out.
There have been studies done on certain supplements used at doses far too high to achieve from a normal diet which have shown beneficial effects. Reservratrol, curcumin and astaxanthin come to mind.
How do you explain high doses of these supplements having therapeutic effects if they work by hormesis? thanks.