Kurt G. Harris MD

PāNu means paleonutrition. The "paleo" here signifies "old" and not necessarily paleolithic. The PāNu approach to nutrition is grounded on clinical medicine and basic sciences disciplined by knowledge of evolutionary biology and paleoanthropology. The best evidence from multiple disciplines supports eating a pastoral (animal-based) diet rather than a grain-based agricultural one, while avoiding what I call the neolithic agents of disease - wheat, excess fructose and excess linoleic acid.

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Polyphenol Hormesis follow-up


Reader Joe has posted the following in the comments on "William Munny eats his vegetables".

It's kind of a dissertation, but has some very good questions, so I'll use it to expand on the original post.

Hi Dr. Harris,

I've read both of Stephan's posts and this one several times, and I had a couple of quick questions I was hoping to get your thoughts on.

First, I was wondering just how "strong" you consider the hormetic effect from plant compounds to really be. I've read Peter's "Fruits and Vegetables" series of posts, and he makes several good arguments that decreasing antioxidant consumption can sometimes be beneficial (such as the study (6) you quoted in this post), while increasing consumption probably doesn't have any significant effects (like (1), (2),and (3) above).

As I alluded to in the post, but maybe didn’t make explicit enough, I interpret Stephan’s idea to be good support for some veggies and fruits being better than none, but in no way support for “the more the better”. Think of the typical j-curve here, but with the ordinate representing harm, not benefit. Like for lipoprotein (a)- could be bad if high, but zero is worse than none. The attractive thing about the hormesis idea is exactly that it then makes no sense to think “the more the better”, anymore than it does for radiation or exercise or sunlight. Perhaps exercise is a bad example, as most people are deluded into thinking that relationship is both continuously linear, and positive! It’s might be fair to say that some of Peter’s posts argue that zero is the best level of polyphenols/antioxidants. If so, I am here speculating that some might well be better than none.

 I very much like Stephen's ideas on the hormesis model of how plant compounds may be beneficial, and I think it (along your thoughts in this post) explains a lot, not just about vegetables but about moderation in life in general: exercise, sunlight, fasting, etc... At the same time, though, I thought some of the beneficial results Stephan used to illustrate the effects of polyphenols in particular were actually rather small in the grand scheme of things - such as a slight reduction in blood pressure from drinking a half liter of OJ every day.

If you are looking for gross physiologic changes as evidence for hormesis in vivo, they are going to be small if even detectable almost by definition. The point is cumulative benefits from the whole suite of toxins you are exposed to in small quantities. The orange juice thing may even be a red herring and of course I would not recommend that. That is the whole point I am making, is not to pick and choose and then “load up” on particular compounds like hesperiden, even via food.

I thought the benefits in most of the examples Stephan used just didn't seem as large or as beneficial as some of Peter's examples in limiting antioxidants, making me wonder just how good hormesis from polyphenols can really be, relatively speaking.

So let’s imagine the j curve again. Here I am speculating, but the way I would synthesize Peter and Stephan is to guess (it is just a guess) is that the right hand side of the curve is steeper than the left. Reducing huge consumption of polyphenol containing plants down to reasonable -lets’ say 5 servings a day down to 5 a week- might be of more benefit than the jump from zero to one a day. The lack of benefit of plants in prospective trials may be confounding of actual harm from more plant compounds with benefits from eating less wheat and sugar – the displacement effect. The same is probably true in the observational data re: veg and meat consumption.

My question really boils down to the recommendation you make to "include a moderate variety of colorful plants". I definitely accept that this can be beneficial due to hormesis, and I would never argue to avoid vegetables; my question is about the phrase "moderate variety".

I meant moderate in variety, not quantity. Like all my recommendations, it is just meant as a reasonable guideline and it is not very quantitative on purpose as I hate to tell people what to eat (I’m more comfortable saying what not to eat and I limit that, too).

Is this mostly aimed towards those who would claim that all vegetables are poisonous and should be avoided, which is clearly unreasonable?

Yes, somewhat. You might say I am synthesizing Peter and Stephan to say that in addition to starchy vegetables as a staple, there may be positive benefit to including a variety of other less caloric vegetables and plant compounds in some quantity, but my intuitive skepticism of 3-5 servings a day and antioxidant supplementations seems to be well-founded.

Or is this a stronger recommendation - should someone like me, who regularly consumes only a small variety of polyphenols (from coffee, chocolate, tomatoes, and sweet potatoes, plus limited fruit and green leafy veggies) actually make a deliberate effort to include a wider range of plants, solely to induce hormetic effects?

I know if I say what I eat that there will be threads everywhere discussing my “new recommendation”. Let me be clear that I have no clue where the exact nadir of the polyphenol j-curve lies. It could be three Mark Sisson big-ass salads a day, or one a week. I have no idea. I just doubt it is either really high or zero. I would say that if you are a meat-and-water zero-carber, to start eating colorful tubers and root veggies with starch in them first. If you are getting a modicum of starch – my back of the envelope is 2K – twice the Kwasniewksi number of 10% of calories – 20%, then maybe add a few green salads a week. Personally, my polyphenol consumption sounds about like yours. I eat green salads and salsas and avocados, tomatoes, sweet and russet potatoes, green beans, etc. I also drink plenty of coffee and cold brewed white and green tea (just for the flavor) and dark chocolate makes the cut as well. I don’t plan to change or add to any of this, and if Stephan is wrong and Peter is right (no plants besides potatoes is best, e.g.) I would not change it anyway.

(Note: I am not representing Peter’s views here. I don’t know what his exact position is, I am just using his ideas to illustrate the left side of the plant spectrum.)

Is the question of polyphenol consumption, like the macronutrient ratio, just a wide spectrum of healthfulness - something like "it's healthier to eat at least some variety of plants than none at all, but stupid to take supplemental megadoses of plant compounds; anything in between is probably good". Would you agree with that sentiment, or am I off base?

Yes, I would basically agree.

Second, I would love to hear your thoughts on Stephan's "Second Mechanism", concerning the action of antioxidants consumed concurrently with fats to prevent oxidation of n-3 fatty acids during digestion. This caught my attention quickly, because it seems to be potentially significant; I remembered you stating that n-3 fatty acids are one of the least stable fats and are prone to oxidation in the gut. I try to eat high-GRAF (mostly from butter and cream), but most of the meat I eat is factory-farmed, bringing with it sometimes a fair amount of IRAF or NRAF as well, and I sometimes worry about getting enough n-3.

Grass fed butter and cream will give you plenty of n-3. You don’t need much. DHA levels in vivo are determined more by lack of excess n-6. I would worry more about the oxidation if you are eating too much n-3, not if you are eating very little.

 Will doing something as simple as drinking a glass of red wine with dinner increase the amount of n-3 that makes it through digestion? Do you think this effect is significant enough to keep it in mind when eating, or do you think it is relatively small and unimportant?

Whenever I eat grass-fed lambchops, with the very first first bite I always get the urge for a bottle of cabernet. Maybe that's instinctive behavior? What goes better with red meat than red wine?

But seriously, you can probably guess what I would think of obsessing over particular food combinations in order to protect your ingested n-3s.

Thanks again for writing a great blog and taking the time to participate in discussion!


You’re welcome!

Reader Comments (14)

Hi Dr. Harris,

Thank you for this lengthy response; I appreciate you taking the time to write it! Everything you wrote here makes a lot of sense, and I'm glad to see I understand your points. I'm also happy to see you say "I don't know" with regards to some theoretical optimal level of veggie consumption; too many people out there claim to have the one and only revealed truth about exactly what we should eat, and your rational skepticism is always good to see.

I agree with you on another point, too - even if zero plants besides potato turned out to be the best, I would still eat some of the tastier ones anyway.

I'm glad to see you open up comments, at least on some posts. If it works out well this time, I hope you'll consider continuing the practice occasionally.

Thanks again for writing a great blog - I'm very much looking forward to the next "No such thing as a macronutrient" post!


March 1, 2011 | Unregistered CommenterJoe

"Grass fed butter and cream will give you plenty of n-3."

I tried to do some research into the different n-3/n-6 profiles of grass vs grain fed cows and cream and came up with zilch. Here in Prague, I don't have the option of buying grass fed butter or cream and I don't worry about it that much. But I'd be interested to know in what ballpark I'm playing in.

I ran the numbers for myself on beef (http://praguestepchild.blogspot.com/2010/09/omega-3-and-grass-fed-beef.html) and decided it doesn't matter all that much but isn't necessarily negligible. I'd really be obliged if someone had some hard data on grass fed and grain fed cream and butter.


I can't give you the exact amount but my GF butter is around 4% PUFA, and that is a 1:1 ratio. My eggs are all pastured and also around 1:1 or 1.5:1. My GRAF beef is probably 10% n-6 and 5% n-3. IRAF will exchange n-3 for MUFA and have about the same n-6 (percentages are of the total fat content)

The n-3 in IRAF will be about 1-2% at best, the n-6 about the same at maybe 10%. Still not terrible, really, if not EM2.

So I guess between butter and GRAF meats and IRAF cream, my 6:3 ratio (dietary) is somewhere around 2:1 or a little less, with total PUFA less than 4%. Easily fits the EM2. Easily ruined by eating nuts and chicken!

Maybe you could have Kerrygold shipped to you from elsewhere on the continent?

A very good review here:


IRAF - industrial ruminant animal fat

GRAF = grass fed ruminant animal fat

March 1, 2011 | Unregistered CommenterSean

Thanks Kurt, we actually can get Kerrygold here, but it's the cream and eggs I'm really wondering about (we go through a lot of heavy cream). It would be interesting to see some hard data on them. My wife was talking about the huge difference in quality from store bought eggs and her grandmother's eggs way back before I knew anything about "real food". Except for the butter it's all just theoretical for us but I'd really be interested in finding some figures on the differences.

March 1, 2011 | Unregistered CommenterSean

My approach is to eat food based on the perhaps naive theory that our bodies have reasonable instincts for what to eat, once we eliminate the option of neolithic agents of disease (e.g. the 'breakfast danish'). Even butterflies know to lick water off of mineralized rocks.

Based on that idea, I start my meal planning with meat, usually red meat, and perhaps eggs. Then I add some safe starch and whatever I think will make the meat taste good. Sometimes that's salt and black pepper, sometimes that's a marinade or sauce, sometimes it's a huge pot of salad, sometimes it's onions, garlic, and peppers, sometimes blueberries after the meal, and sometimes nothing at all.

I don't spend too much time thinking about it. I figure a few million years of evolution has optimized me for instinctually gravitating towards the right microdoses of plant toxins.


March 1, 2011 | Unregistered CommenterJ. Stanton

Dr. Harris, I'm just loving the last two posts and how you relate it to Stephan G.'s recent series.

Slightly off topic, can you (or others) elaborate on why zero Lp(a) is worse than low Lp(a)? I've seen Peter mention this too but cannot find details anywhere. (My Lp(a) was nondetectable when tested last year). Is it possible to raise or is it a gene that I carry and permanent? My doctor said I'll likely never have a heart attack because of it...

thanks, Kelly

KGH: The first thing to understand is that Lp (a) is not something you can do much about, other than if its high you can reduce it a bit with saturated fat intake.

This is my version of the theory:

Lp(a) is genetically determined in that some have the increased kringle repeats and some don't. Lp(a) seems to function as a repair molecule - including vascular repair, and may relate to infection control as well.

There are two reasons you could have high Lpa levels.

1) You could have lots of vascular damage going on, and the high levels would reflect lots of repair activity being required. You are the United States, with lots of crappy asphalt highways that are falling apart, so Lpa is the repair crews, and seeing a lot of them reflects high levels of road repair. You have repair crews and as many of them as you can muster are our fixing things because the roads are crap.

2) You could be born with a very high level, and if there is not much vascular damage going on, the high levels just mean you have a lot of Lp(a) available. You are Germany, where the roads are well-engineered high quality concrete, and the DOT has repair crews are all hanging around and waiting for something to fix, just in case.

3) You could be born with low or very little Lp (a). As long as little vascular damage occurs you might need much. As long as you have good roads and keep the overweight 18 wheelers off them, you might not need a lot of road repair crews. But having some Lpa or some road repair crews is going to be better than none, no matter how good condition your arteries or roads start out in.

This little cartoon and road metaphor for Lpa fits perfectly with what the epidemiologic data tell us about Lpa and with the known genetics and putative actions of Lpa are in humans and hedgehogs.

You are in category 3. The evidence I have so far is that I am in category 2. I have Lp(a) of 85 but my calcium score at age 49 is 0, my CIMT is the same as a typical 30 year old and ancestors who don't smoke (and even some with up to 50 pack years or more) typically live to the 9th decade with no coronary events. It's worth mentioning that all my relatives eat the SAD and no one has ever been diagnosed with diabetes at any age, either.

Lp(a) is a good model for how something can be a statistical risk factor for coronary events, but be relatively meaningless when applied to single individual. Of course, in my model, it is not "causing" heart attacks or anything else.

March 1, 2011 | Unregistered CommenterKelly A.

I live in the same E2M2 (east-european metabolic milieu)as praguestepchild, --with Kerrygold but no decent eggs, lots of nice-tasting sour cream but never grass fed. This is what I do: not much cream, substitue butter (often also enrich cream with butter), forget the eggs, use more liver instead.

March 2, 2011 | Unregistered Commenterdonat


I used to live in Prague for a few years. Though I did not prioritise grass fed over industrial fed then or had a faint idea why I should do it, I think that cattle in Czech did get a fair amount of grass feeding. On the other hand there are some large farms and lots of imported dairy in supermarkets, so usually you can't tell if the particular product is GRAF or not.

You might try to ask in your local Billa - now they are introducing the Heumilch campaign in Austria http://www.billa.at/Layouts/dd_bi_subseite2008.aspx?pageId=1146462&folderid=130212&ProdId=3111
The butter is "silofrei" (basically meaning grain-free) and "gentechnikfrei", exactly what you want.

March 2, 2011 | Unregistered CommenterTomas

Hi Dr. Harris,

Quick thanks for enabling some comments, i find that in the older posts a lot of the comments can be just as interesting as the articles themselves.

I had a slightly off topic question about veg/fruit intake that i don't believe you have covered previously but is one of those paleo dogmas that i have never really understood. Maybe if its not as simple as a quick response, you could write a future article on this topic. My question is about the PH balancing effects of a high intake of veg/fruit is supposed to have and that it is one of the biggest reasons people like Cordain say you cant get too much of them. Since our way of eating (EM2) must be on the acidic side, what are you thoughts on heavy veg/fruit in terms of PH balance?

Thanks for any thoughts you can give, i am really looking forward to your Paleo Solution episode!

KGH: Forget balancing your PH, it's probably nonsense.

March 2, 2011 | Unregistered CommenterZach

I've read Peter's "Fruits and Vegetables" series of posts, and he makes several good arguments that decreasing antioxidant consumption can sometimes be beneficial (such as the study (6) you quoted in this post)

I disagree with Joe that Peter makes a good argument about this green tea/flavonoid-free study.
That study failed to show a reduction in oxidative damage to DNA, blood proteins and lipids by green tea extract. So post-hoc they also treated it as a 10 week flavonoid-free diet trial. Result: oxidative damage decreased.

So it seems fair to conclude that oxidative damage can be reduced without fruit and vegetables. And if the paper had specified the diet prior to the intervention, we might conclude something about the cause of the oxidative reduction. But the paper didn't. So claiming that the oxidation went down due to the removal of fruit and vegetables is pure speculation.

Looking at the intervention diet (table 1), to me it seems low in PUFA. So the following subtitle appears suitable too: "lasting antioxidant effect of a diet low in PUFA". Seems like a more plausible explanation to me, but this is also pure speculation (I have no pre-trial diet info either).

I think that there is a more convincing antioxidant study1, by some of the same investigators. The basis was a flavonoid-free diet plus 600 grams of fruit and vegetables, or antioxidant/vitamin/mineral tablets plus a sugar drink, or placebo tables puls a sugar drink. Result: oxidative DNA damage was similar in all 3 groups. So regarding DNA damage, natural whole food plant matter seems equally protective/damaging as neolithic supplements, and as a placebo.

Just too bad that they didn't add a fourth group where they replaced the sugar drink by some starch. That way it would be possible to evaluate the effect of the fructose on the DNA damage.


1 Møller P., et al. No effect of 600 grams fruit and vegetables per day on oxidative DNA damage and repair in healthy nonsmokers. Cancer Epidemiol Biomarkers Prev. 2003 Oct;12(10):1016-22. http://pmid.us/14578137

March 2, 2011 | Unregistered CommenterJohn

John, I find both studies to be convincing. They have a lot of similarities, but some key differences as well. Neither specify how much PUFA was in the diet prior to intervention (although the "600 grams study" does note that subjects recorded an average daily consumption of 280g of fruits and vegetables in the 4 days beforehand, though this is all we know...) Both studies seem to use a very similar intervention diet of common Danish foods (lots of gluten!), so I think it's fair to assume that if these were low in PUFA, then the subjects prior diet must have been similarly low as well. Really, you'd have to know if it is common to use butter, rather than soy oil, in bread rolls and sponge cake in Denmark? I doubt the researchers specifically requested a cake recipe that was lower in PUFA than the norm without noting it.

The main difference I see is that the "green tea study" had subjects on a flavonoid/ascorbate restricted diet during both the intervention and wash-out periods, so they ended up with a total of 10 consecutive weeks rather than only 24 days allowing plasma levels of antioxidants to fall much lower. (The average plasma ascorbate after 10 weeks of deprivation was 10 μm/l, whereas after 24 days in the other study it was 21.1 μm/l.) Another factor to consider is that the subjects in the "green tea study" were younger (men ages 20-31, as opposed to men and women ages 21-56 in the other study) so any positive benefits that were going to happen might have appeared quicker on average. It's hard to know if 10 weeks in the "600 g study" with young men wouldn't have shown significantly less oxidative damage in the flavonoid/antioxidant depleted group.

What I find fascinating about both studies is how insignificant they show even the necessary antioxidant vitamins (like ascorbate) to be. It makes me wonder if there is any benefit at all to getting even 1 mg more vit. C than it takes to prevent scurvy? Part of the problem may be that unlike other novel plant compounds (whether it's catechins, theaflavins, caffeine, theobromine, solanine, nicotine, fructose, resveratrol, anthocyanins, I3C, lycopene, genistein, lutein, carotene, etc, etc...) the body doesn't recognize ascorbate or tocopherols as outright toxins and so rather than a hormetic effect where the body ramps up its own endogenous defenses, you have the opposite, seen clearly in those studies Kurt linked in the post below, where high doses of C&E blunt the body's beneficial adaptations to exercise. Maybe getting ascorbate especially low is another thing we should be aiming for? Thoughts?

KGH: "What I find fascinating about both studies is how insignificant they show even the necessary antioxidant vitamins (like ascorbate) to be." I agree.

March 3, 2011 | Unregistered CommenterOwen

I wanted to add a quick thought regarding the pH issue of eating lots of fruits and vegetables: am I being too simple with this theory in thinking that the idea of something like acidic citrus fruit having a "positive alkalizing effect" on the body is ridiculous nonsense? Isn't it just a matter of forcing the use of more bicarbonate to balance the extra bit of citric acid added to gastric HCl when it hits the small intestine? Somehow this ends up appearing to have created a more alkaline state than meat and dairy which don't require the waste of bicarbonate? This all seems like pretending that something that is probably a metabolic burden is actually a boon...

KGH: Your kidneys are smart. Trust them.

March 3, 2011 | Unregistered CommenterOwen

Do animal/non-plant sources of antioxidant essential vitamins also work via hormesis (like animal vitamin A or selenium obtained from eating a slice of liver)?

Does the hormetic effect begin AFTER essential nutritional needs are met (so does the dose of the essential compound have to be higher than the minimum used for basic metabolic needs to be hormetic)?

Can an 'anti-oxidant' be both hormetic and usable by the body at the same time (and even if it is non-essential, like caretenoid storage in the skin)?

Please and thank you. I can't be the only one confused in this way.


Most vitamins are not "antioxidant". Vitamins are essential compounds that work because they are necessary for cellular function, not via hormesis. Fat soluble vitamins like A D E and K and B vitamins are all quite different and only have in common that they are essential.

Alleged "antioxidants" might include vitamins like C, but most of the plant polyphenols we are talking about here are not vitamins, they are plant compounds that are somewhat toxic.

Vitamins are quite heterogeneous and hard to generalize about, but generally there is no benefit to taking vitamin supplements - just get them in food.

The point we are making about polyphenols working via hormesis is not to seek them out specifically, but to say they explain why eating some variety of plants may be good for you, yet taking supplements made from plant polyphenols is likely counterproductive and harmful.

So, polyphenols in general are not vitamins, they are toxins.

Still clear as mud?

March 3, 2011 | Unregistered CommenterKatie

Dr Harris, I've been reading your blog for some time now and enjoy your practical attitude to eating. I'm lucky enough to have access to grass-fed organic meat and even raw organic milk, cheese, butter and cream. I'd be interested to know whether anyone has looked at the effect of a paleo-type diet on people who've had a transplant. I had a liver and kidney transplant ten years ago and was doing OK but putting on weight. A couple of years ago, my husband and I cut right back on the carbs and now my hepatologist and nephrologist are extremely puzzled by the huge improvement in my health. I'm no longer gaining weight and have even lost some. My liver and kidney function is completely normal, despite having had surgery on my transplanted kidney which they thought might cause it to fail. I take the minimum amount of medication my doctors will allow me to get away with (tacrolimus, MMF and irbesartan). I've cut down on my blood pressure medication recently despite working harder than I've done in a long time. I'm sure my improved health is due to my high-animal fat low-carb way of eating, which, in fact, is the way I always wanted to eat but was told was unhealthy! My husband tells me that I look much healthier and slimmer than most of the other kidney transplant recipients we see on visits to the hospital (I'm totally blind so can't judge for myself). I'm trying to persuade my doctors that my way of eating should be recommended to other transplant patients, but I don't think it's going to happen any time soon. I'll just have to live to the age of 100 to convince them! Oh well, not much over 40 years to go, then.

March 3, 2011 | Unregistered CommenterAnne Robertson

Based on my (limited) knowledge at this moment, it seems to me that the water soluble antioxidant defence system of our body is "on-demand", i.e., an appropriate defence is mounted when needed (e.g., Nrf2 is activated). If true, then eating more water soluble antioxidants will have little effect: the antioxidant demand didn't change. Also, in case our body simply makes most/all water soluble antioxidants it actually uses itself (e.g., glutathione), it's even more pointless. And it would make more evolutionary sense not to be that dependent on dietary antioxidants.

Fat soluble antioxidants seems to be treated differently. In LDL, CoQ10 and vitamin E appear to be added as "preventative measure" antioxidants rather than "on-demand". The amount seems dependent on supply (the liver trying to get rid of it). If true, eating more fat soluble antioxidants could be helpful. A study Stephan mentioned in his post on red palm oil appears to confirm this. The CoQ10 and vitamin E rich oil reduced oxLDL by 69%.

So, the water soluble antioxidant defence seems difficult to "override" with diet. For the fat soluble antioxidant defence this seems easier.

(Note: all of the above is of course pure speculation.)

@ Owen, I also find the green tea study convincing in showing the insignificance of dietary antioxidants. I just think that as a flavonoid depletion study it was poorly controlled, due to a lack of info on the habitual diet. In that sense, I felt that the 600 gram study was more convincing. I agree with the points you bring up about that study.


March 3, 2011 | Unregistered CommenterJohn

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