Health through stressing fruits and vegetables – the Xenohormetic Live Food Hypothesis (updated)

By Vince Giuliano and Melody Winnig

Update , October 17, 2013: 

The purpose of this blog entry is to lay out a hypothesis that could turn out to be very significant for health and longevity if it were practically applied. We originally thought that the hypothesis was original to the authors here.   However, feedback from our posts and additional research have helped us come to realize that the concepts we put forward are already familiar to a number of researchers, and that there is a growing body of studies related to  many of the ideas presented below.  Still, we believe that the central concept could be of great importance if embraced in agriculture and in the chain of food delivery, so we plan to continue to expand on it in subsequent blog entries.

The hypothesis is summarized in eleven points:

  1. Most of the cells and even much of the organic structure of many fruits and vegetables remain alive right up to the point where they are destroyed by stomach acid or bacteria and are digested in our gut.  Of course, as fruits and vegetables decay their cells will die.
  2. These still-live cells remain capable of producing the same plant-based stress responses that they produce in live plants.
  3. In many cases for fruits and vegetables, the stress responses include plant cells producing phytochemicals such as  pterostilbene in the case of blueberries, and allicin in the case of garlic. Many such phytochemicals can be thought of as plant stress-responsive hormones.
  4. In many instances, stress can increase the production of such health-producing phytochemicals by an order of magnitude or more.
  5. Such phytochemicals produced as a result of plant cell stress have numerous documented health benefits for humans, and possibly also longevity benefits.  Numerous entries in this blog have discussed these benefits in various contexts.
  6. The phytochemicals address evolutionarily conserved pathways in us working via xenohormesis. That is, we respond to many plant stress-produced phytochemicals in similar ways to how the plants themselves respond.
  7. Besides upregulated production of health-inducing phytochemicals, stresses on live fruit and vegetable cells have a second mode of health-producing action.  In the process of eating plants, miRNA components are released in microvesicles which enter and show up in the circulatory systems of animals who eat them. These micro RNAs encode for multiple epigenetic impacts including health-producing ones
  8. Therefore, stresses experienced by fruits and vegetables experienced from the point of cultivation to the point of digestion in the gut may have major impacts on the health-producing properties of such fruits and vegetables for us humans.  Xenohormetic activity of a consumed fruit or vegetable cell could result from stress responses in a plant cell right up to a point where that cell is digested and dies.
  9. Stresses on fruits or vegetables associated with cultivation, storage, transportation, industrial processing, cooking, freezing, and other forms of food preparation and even chewing and encounters with the gut bacteria might have significant impacts on either degrading or enhancing the contributions of these foods to human health. Stresses on fruits and vegetables that activate known stress responses include heat, cold, UV exposure, desiccation, cutting and slicing, exposure to bacteria, viruses, chewing, and acid exposure. Experienced stresses can be many and vary by specific fruit and vegetable. Our hypothesis is that in many cases such stresses may greatly enhance or denigrate the healthiness associated with consumption.
  10. Such stresses are mostly open for manipulation by us, allowing us to decrease or increase them or change the timing for when they occur.  We believe that applying knowledge of such stresses at critical points in the food delivery chain – including cooking – might result in significant increases of the nutritional value of many fruits and vegetables.
  11. The economic consequences of our learning how to manage these stresses to benefit humans could be enormous, involving trillions of dollars.

Beyond what is contained here, Jim Watson has weighed in with a second blog entry on the topic which considerably expands what is laid out here.  For example, he identifies a number of additional plant stresses that upgrade polyphenol production either pre or post harvesting, and describes several transcription factors that are key in plant polyphenol production. More on the xenohormetic live food hypothesis – synergies among polyphenols, additional post-harvest plant stressors and stress responses, plant polyphenol transcription factors, and more.

A third blog entry Further extensions to and implications of the Xenohormetic live food hypothesis goes on to revisit xenohormesis in a little more theoretical depth and covers additional topics such as pre-harvest plant stressing, and how pre or post-harvest stressing may be used to induce additional benefits such as crop mold resistance and reduced food spoilage.  It cites a number of other findings from the literature related to stressing plants.  And it describes a simple and practical approach that ordinary consumers could use to further preserve and enhance nutritional values of fruits and vegetables while they sit in the refrigerator.

Reviewing xenohormesis

From the blog entry Part 1: Slaying two dragons with one stone: “Xenohormesis is the concept that different species such as plants and animals have common stress signaling molecules, and that such molecules can be harvested from plants and used to increase stress adaptation pathways in animals(ref)(ref)(ref).  Plants cannot run away from predators, parasites, infectious agents, hot weather, cold weather or dryness.  For this reason, plants have evolved a large number of molecular stress coping pathways that are activated by compounds that are actively synthesized in response to the stressor.  Some of these compounds ward off predators with bitter tasting compounds. Others ward off potential organisms that would eat the plant by synthesizing poisons that would kill the predator (i.e. natural pesticides). Others – the ones of main interest to us – strengthen the plant and allow survival in the face of the stress.   Although there are many toxic compounds in this arsenal of phytochemicals, there is a large family of molecules called polyphenols that are non-toxic and appear to have great benefits in humans. Approximately 14,000 of these plant-based stress-signaler polyphenol compounds have been discovered so far in plants.  They are found in the leaves, stems, flowers, seeds, fruits, nuts, and shells surrounding the nuts.  These plant polyphenols appear to be xenohormetic compounds in that they also upregulate stress coping pathways in mammalian cells.  These xenohormetic compounds appear to prevent aging and cancer through a large number of pathways.  For this reason, their mechanism of action is multifactorial or pleiotropic.  Xenohormetic compounds include resveratrol, curcumin, EGCG, isothiocyanates, secoiridoids, genistein, gallic acid, lycopene, allyl mercaptan, plumbagin, etc. Multiple plant polyphenols and their mechanisms of action have been reviewed in past entries in this blog.  See for example ref, ref, ref, ref, ref, ref, ref and ref.


Image source

“A surprising number of plant molecules in our diet interact with key regulators of mammalian physiology to provide health benefits. Shown are three examples: resveratrol found in numerous plants and concentrated in red wine; curcumin from turmeric; and epigallocatechin-3-gallate (EGCG) in green tea. These compounds modulate key pathways that control inflammation, the energy status of cells, and cellular stress responses in a way that is predicted to increase health and survival of the organism. Such observations raise the question: are these biochemical interactions merely a remnant of what existed in the common ancestor of plants and animals, or is selection maintaining interactions between the molecules of plants and animals? Some interactions activate signaling pathways (arrows) whereas others inhibit them (bars). Solid arrows or bars indicate instances where there is some evidence of a direct interaction of the plant metabolite with a mammalian protein(ref)”  A mechanism of xenohormesis appears to be animal gene regulation mediated by plant micro RNAs acquired through food intake.” More yet on xenohormesis can be found in that blog entry.

There is another health action of eating live fruit and vegetable cells: Beneficial miRNAs and microvesicle communications from plant cells

So far, we have discussed how stresses on fruits and vegetables, say induced in the processes of cooking or slicing, could greatly increase the content of health producing phytochemicals that are ingested upon eating the fruits and vegetables. Presumably, a human being could get the same substances in dietary supplement pills and capsules. However, there is an additional part of the story that goes beyond the actions of phytochemicals. That part involves plant-based miRNAs which are likely to be communicated directly from live plant cells via secreted vesicles. It turns out that a significant fraction of our circulating miRNAs are plant-based.  Again from a recent blog entry: The 2011 publication Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA reports: “Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.”  The miRNAs are present in microvesicles in the plasma where they are circulated to various cell types and serve as intercellular signaling molecules.  “Our further studies demonstrated that miRNAs could be selectively packaged into MVs and actively delivered into recipient cells where the exogenous miRNAs can regulate target gene expression and recipient cell function15. Thus, secreted miRNAs can serve as a novel class of signaling molecules in mediating intercellular communication15. The novel and important functions of the secreted miRNAs were also reported by many other groups18,19,20,21. The identification of circulating miRNAs, mainly delivered by cell-secreted MVs, as stable and active signaling molecules opens a new field of research in intercellular and interorganelle signal transduction.”

The implication of microvesicle-communicated plant-based miRNAs for epigenetic regulation of human gene expression are profound.  “MicroRNAs (miRNAs), a class of 19-24 nucleotide long non-coding RNAs derived from hairpin precursors, mediate the post-transcriptional silencing of an estimated 30% of protein-coding genes in mammals by pairing with complementary sites in the 3′ untranslated regions (UTRs) of target genes1,2. miRNAs have been widely shown to modulate various critical biological processes, including differentiation, apoptosis, proliferation, the immune response, and the maintenance of cell and tissue identity1,2. Dysregulation of miRNAs has been linked to cancer and other diseases3,4. Recently, we and others found that mammalian miRNAs exist stably in the sera and plasma of humans and animals5,6. – We next characterized the possible carrier of circulating miRNAs. Microvesicles (MVs) are small vesicles that are shed from almost all cell types under both normal and pathological conditions13,14. They bear surface receptors/ligands of the original cells and have the potential to selectively interact with specific target cells and mediate intercellular communication by transporting bioactive lipids, mRNA, or proteins between cells13,14. Our recent results demonstrated that MVs from human plasma are a mixture of microparticles, exosomes, and other vesicular structures and that many types of MVs in human plasma contain miRNAs15. These findings were in agreement with the recent reports by other investigators that exosomes from cultured cells served as physiological carriers of miRNAs16,17. — miRNAs are present in human and animal sera and organsUpon investigation of the global miRNA expression profile in human serum, we found that exogenous plant miRNAs were consistently present in the serum of healthy Chinese men and women. As shown in Figure 1A and Supplementary information, Table S1, Solexa sequencing revealed ~30 known plant miRNAs in Chinese healthy donors, among which MIR156a and MIR168a showed considerable levels of expression(ref).”

Because they are packaged in microvesicles, the plant miRNAs in food can go where they will in the body.  They can pass unharmed through the GI track resisting gut bacterial action and stomach acids, enter the sera and organs and pass through the blood-brain barrier.

Microvesicles, like their human cousin exosomes, are generated in live cells and released under stress conditions.

So, there appears to be two operating mechanisms of stress-induced xenohormesis connected with eating fruits and vegetables: production of beneficial phytochemicals, and release of micro-vesicles containing beneficial miRNAs.  The second mechanism requires our direct contact with live fruit and vegetable cells.

About phytochemicals and how they work

The benefits of consuming fruits and vegetables have universally been attributed to unique phytochemicals they contain: plant polyphenols involving substances like flavonoids, anthocyanins, Isoflavones, indoles, saponins, isocynates, sesquiterpene lactones, anacardic acid. etc. –  along with minerals and essential micro-nutrients.  These substances produce beneficial effects and activate stress-response pathways like Nrf2.  This is well and good.  However we are suggesting that there may be an additional and deeper level of explanation for the health-producing actions of fruits and vegetables,  That level of explanation goes beyond the chemical-action theory and could provide us with insights that allows us new forms of control over the health benefits of foods we consume.

Our concept is an extension of xenohormesis, the notion that evolutionarily-conserved plant-based stress responses can be elicited in humans who eat the plants.  The essence of our new idea is that the plant cells in fruits and vegetables are mostly alive before we cook, eat or digest them, and are therefore likely to be stress-responsive.  Our manipulation of such stresses can enhance the healthfulness of many fruits and vegetables.  Below, we cite some examples that show foods are stress-responsive to steps in cooking and preparation.

Preliminary evidence for the hypothesis: On food preparation and stress-induced impacts relating to healthfulness

Indeed, there appears to be evidence that food preparation and cooking can both positively and negatively impact human health. The following examples and quotes are drawn from the book Eating on the Wild Side – a Field Guide to Nutritious Foods.

Garlic:  Allicin is a key cancer-fighting component of garlic.  Allicin is created when two substances in garlic come into contact with each other: a protein fragment alliin and a heat sensitive enzyme alliinase.  “in an intact clove of garlic these compounds are isolated in separate compartments.  They do not commingle until you slice, press or mince the garlic.”  Then the allicin-producing reaction occurs.  “Israelis discovered that heating garlic shortly after crushing it or slicing it destroys the heat-sensitive enzyme that triggers the reaction.  As a result no allicin is created.”  Two minutes in the frying pan or 30 seconds of microwaving wipes out allicin production and ability to thin blood almost completely.  The best way to get the benefits of garlic are to chop and mash it and then let it sit for 10 minutes away from heat. This creates the maximum amount of allicin. After the allicin is created, the heat-sensitive enzyme is no longer needed and the garlic may be cooked without losing the allicin and its beneficial properties.  In this case, the stress producing a beneficial result is chopping or mincing.  We wonder if the allicin production is an adaptive stress response, say to a garlic plant being eaten by an animal.  Allicin gives garlic its strong taste and smell.

Onions:  Here, we have a different but still interesting situation.  An important health-producing ingredient in onions is quercetin. “Studies have shown that baking, sautéing roasting or frying onions increases their quercetin content.  It is not clear to me whether this is due to a heat-induced chemical reaction or due to a hormetic heat-shock response in the onion cells. Boiling is the only cooking method that reduces quercetin content.  The quercetin leaches out into the water when onions are boiled.  Strong pungent onions have the most phyto-nutrients but these can be neutralized by boiling.” Here, the upgraded adaptive stress response in onions appears to be due to heat shock in response to cooking.

Corn:  Canning can enhance phytonutrient content, the opposite of what is commonly assumed.  “It is now clear that vitamin C provides only a fraction of the antioxidant power in most fruits and vegetables.  The majority comes from phytonutrients.” (We of course now know that the phytonutrients are not themselves antioxidants but that they active production of endogenous antioxidants via the Nrf2 and possibly other pathways.  Moreover, there is the recent paper to the effects that some of these “antioxidants” are in fact ROS-inducing pro-oxidants)  “ – many phytonutrients maintain their antioxidant properties when they are heated.  Some even become even more potent because the heat transforms them into more-active forms or easier to absorb.  This explains why canned corn is higher in carotenoids than fresh corn.”  Again, to us  this explanation falls flat.  It is not clear to us  whether the impact on corn is due to a heat-induced chemical reaction or due to a hormetic heat-shock response in the corn cells.

Tomatoes:  Tomatoes  provide a particularly interesting case-in-point. A key health-producing phytochemical in tomatoes is lycopene. “Tomatoes, like a few other fruits, are better for you cooked than raw.  In fact, the longer you cook them, the more health benefits you get.  They heat increases the food value in two ways.  First, it breaks down the fruit’s cell walls, making their nutrients more bioavailable. Second, it twists the lycopene molecule into a new configuration that is easier to absorb. — Thirty minutes of cooking can more than double their lycopene content — .”  The explanation given in the book is that the heat converts trans lycopene into cis-lycopene, the more bioavailable form.  Again, it is not clear to us  whether this is purely a chemical reaction or involves a tomato cell heat stress response, or perhaps both. In any event, it is yet another example of how stress in food preparation can improve the health producing-properties of a food or vegetable.  Continuing from the book:  the most nutritious tomatoes in the supermarket are not in the produce section – they’re in the canned goods aisle. Processed tomatoes, whether canned or cooked into a paste or sauce, are the richest known sources of lycopene. The reason is that the heat of the canning process makes the lycopene more bioavailable. — Tomato paste, the most concentrated form of processed tomato, has up to 10 times more lycopene than raw tomatoes. Tomatoes produce lycopene to protect themselves from UV rays.”  (Production of lycopene is clearly a stress response.)  As to the xenohormetic affect, “eating tomato paste has the same effect on us. In a German study, volunteers were divided into two groups. Half the participants made no changes in their eating habits. The other half added 3 tablespoons of tomato paste to their daily diets. When the volunteers were exposed to enough UV rays to produce a modest sunburn, the people who had been consuming tomato paste were 40% less red overall.”  Tomatoes provide an excellent example of xenohormesis at work.  See the 2001 publication Dietary tomato paste protects against ultraviolet light-induced erythema in humans.

The 2002 study Thermal Processing Enhances the Nutritional Value of Tomatoes by Increasing Total Antioxidant Activity documents the increase in lycopene in tomatoes due to cooking them. “Processed fruits and vegetables have been long considered to have lower nutritional value than their fresh commodities due to the loss of vitamin C during processing. This research group found vitamin C in apples contributed <0.4% of total antioxidant activity, indicating most of the activity comes from the natural combination of phytochemicals. This suggests that processed fruits and vegetables may retain their antioxidant activity despite the loss of vitamin C. Here it is shown that thermal processing elevated total antioxidant activity and bioaccessible lycopene content in tomatoes and produced no significant changes in the total phenolics and total flavonoids content, although loss of vitamin C was observed. The raw tomato had 0.76 ± 0.03 μmol of vitamin C/g of tomato. After 2, 15, and 30 min of heating at 88 °C, the vitamin C content significantly dropped to 0.68 ± 0.02, 0.64 ± 0.01, and 0.54 ± 0.02 μmol of vitamin C/g of tomato, respectively (p < 0.01). The raw tomato had 2.01 ± 0.04 mg of trans-lycopene/g of tomato. After 2, 15, and 30 min of heating at 88 °C, the trans-lycopene content had increased to 3.11± 0.04, 5.45 ± 0.02, and 5.32 ± 0.05 mg of trans-lycopene/g of tomato (p < 0.01). The antioxidant activity of raw tomatoes was 4.13 ± 0.36 μmol of vitamin C equiv/g of tomato. With heat treatment at 88 °C for 2, 15, and 30 min, the total antioxidant activity significantly increased to 5.29 ± 0.26, 5.53 ± 0.24, and 6.70 ± 0.25 μmol of vitamin C equiv/g of tomato, respectively (p < 0.01). There were no significant changes in either total phenolics or total flavonoids.”  This is a good example of a plant phytochemical(lycopene) being induced by cooking heat stress.

Tomatoes also provide an example of where industrial processing increases food value, the kind of situation we would like to see more of.  See the NYT opinion Not all industrial foods are evil.

Blueberries:  Blueberries are another example where the cooked fruit offers more phyto nutrients than the raw fruit. We trust the description of what happens here and in other cases in the Eating on the Wild Side book, but not necessarily the explanations given of why it happens.   “Cooked blueberries, believe it or not, have greater antioxidant levels than fresh berries. Even canned blueberries are better for you than fresh packed fruit, providing you consume the canning liquid along with the berries. The reason that cooking and canning increases their nutritional content is that the heat rearranges the structure of the phyto nutrients and also makes them more bioavailable. Many other berries respond in a similar fashion.”  Again, the phytochemicals in blueberries are not themselves antioxidants; they are activators of the Nrf2 pathway in humans which turn on our endogenous antioxidant-producing genes.  It is those stress-responsive phytochemicals which are increased due to heat stress in cooking and canning.

How convenient in this and several others of these examples that the heat “rearranges the structure of the phytonutrients!”  We strongly suspect this is a heat-stress response in the blueberry cells mediated by heat shock proteins.  It probably happens when cooking is just started before the plant cells die.

Broccoli:  From a 2007 Science Daily article reporting research results, Culinary Shocker: Cooking Can Preserve, Boost Nutrient Content Of Vegetables: “In the new study, the researchers evaluated the effects of three commonly-used Italian cooking practices — boiling, steaming, and frying — on the nutritional content of carrots, zucchini and broccoli. Boiling and steaming maintained the antioxidant compounds of the vegetables, whereas frying caused a significantly higher loss of antioxidants in comparison to the water-based cooking methods, they say. For broccoli, steaming actually increased its content of glucosinolates, a group of plant compounds touted for their cancer-fighting abilities. The findings suggest that it may be possible to select a cooking method for each vegetable that can best preserve or improve its nutritional quality, the researchers say.”  Here again, the so-called “antioxidant compounds” are no doubt the stress-induced phytochemicals which activate endogenous antioxidant pathways, and are not themselves actual antioxidants.

There are more such examples of where cooking stress induces health-producing phytochemical content. The 2006 publication Content of redox-active compounds (ie, antioxidants) in foods consumed in the United States provides the following table.  The titles of the article and table are misleading.  By “antioxidant content” the article is referring to  content of beneficial polyphenols which upgrade endogenous body antioxidant responses.  It was fashionable back in 2006 to call these “antioxidants” though in fact some are chemically pro-oxidants.

Effects   of Processing on Antioxidant Content in Foods


Type   of Processing

Antioxidant   Content % Compared to Non-Processed Food

Apples Peeling (-)33-66%
Carrots Steaming (+)291%
Carrots Boiling (+)121-159%
Cucumbers Peeling (-)50%
Asparagus Steaming (+)205%
Broccoli Steaming (+)122-654%
Cabbage, green Steaming (+)448%
Cabbage, red Steaming (+)270%
Green pepper Steaming (+)467
Red pepper Steaming (+)180%
Potatoes Steaming (+)105-242%
Tomatoes Steaming (+)112-164%
Spinach Boiling (+)84-114%
Sweet potatoes Steaming (+)418%

The heat-shock stress response encountered in cooking appears to be very powerful in generating healthful phytochemicals.  Since plant stress responses are generally concentrated on or near the skins, another general theme is that peeling reduces beneficial polyphenol content.  So, whole carrots are better nutritionally than baby peeled carrots and peeling apples or cucumbers is not a good idea.

Light exposure is another stress that can increase phytosubstance content and nutritional value in several  fruits and vegetables.  It is particularly effective when the light is synchronized to original plant circadian response.

An additional dimension of evidence for our hypothesis is that after harvesting, fruits and vegetables continue to produce polyphenols as driven by a daily circadian rhythm.  This happens best if the fruits or vegetables are exposed to light according to the daily rhthym thay are used to.  We are grateful to Dan Campagnoli, a reader of this blog, who responded in a comment below mentioning two citations.

One of these citations is the June 2013  publication Postharvest Circadian Entrainment Enhances Crop Pest Resistance and Phytochemical Cycling.  “The modular design of plants enables individual plant organs to manifest autonomous functions [1] and continue aspects of metabolism, such as respiration, even after separation from the parent plant [2]. Therefore, we hypothesized that harvested vegetables and fruits may retain capacity to perceive and respond to external stimuli. For example, the fitness advantage of plant circadian clock function is recognized [3,4]; however, whether the clock continues to influence postharvest physiology is unclear. Here we demonstrate that the circadian clock of postharvest cabbage (Brassica oleracea) is entrainable by light-dark cycles and results in enhanced herbivore resistance. In addition, entrainment of Arabidopsis plants and postharvest cabbage causes cyclical accumulation of metabolites that function in plant defense; in edible crops, these metabolites also have potent anticancer properties [5]. Finally, we show that the phenomena of postharvest entrainment and enhanced herbivore resistance are widespread among diverse crops. Therefore, sustained clock entrainment of postharvest crops may be a simple mechanism to promote pest resistance and nutritional value of plant-derived food.”  Entrainment here involves the synchronization of the internal rhythm of responsiveness (which occurs, say, in cabbage after harvesting) with the light-cycle external environment.

The document says this entrainment works even after harvesting in some plants to increase phytochemical content.  The light stress produces protective polyphenols and facilitates the process of the fruit or vegetable ripening.  For experienced cooks, there is little here of practical importance that is new. Of course, tomatoes that fall off the vine continue to ripen on the ground.  And you can leave green tomatoes out of the refrigerator and out in the light where they wlll ripen and turn red – at the same t so what you want to do is good library get a book while and go to the Mexican restaurant and then go before cooking and I felt that has to be beautiful young you what were well right now what were doing ime increase their lycopene content.

The other item citation by Dan is Does your salad know what time it is?  This is a recent press release on research at Rice University.  “Vegetables and fruits don’t die the moment they are harvested,” said Rice biologist Janet Braam, the lead researcher on a new study this week in Current Biology. “They respond to their environment for days, and we found we could use light to coax them to make more cancer-fighting antioxidants at certain times of day.” Braam is professor and chair of Rice’s Department of Biochemistry and Cell Biology. — Braam’s team simulated day-night cycles of light and dark to control the internal clocks of fruits and vegetables, including cabbage, carrots, squash and blueberries. The research is a follow-up to her team’s award-winning 2012 study of the ways that plants use their internal circadian clocks to defend themselves from hungry insects. That study found that Arabidopsis thaliana — a widely used model organism for plant studies — begins ramping up production of insect-fighting chemicals a few hours before sunrise, the time that hungry insects begin to feed.”

The examples and data cited are sufficient to make our point with respect to cooking and light stresses.  Other stresses also probably strongly impact phytochemical content and plant cell microvesicle production, such as cropping, refrigeration, supermarket preparation and even chewing, but the possible positive impacts of such stresses appear to be little studied.  We believe further studies related to such stresses might reveal important new insights.  Finally, there is a whole question of how live consumed fruit and vegetable cells produce stress reactions in response to stomach acids and gut biome microbial constituents – another potentially fruitful area for new research.

Consumption of fruits and vegetables could have an enormous economic impact

The Union Of Concerned Scientists has just put out a report THE $11 TRILLION REWARD arguing that the economic value of people consuming even slightly more fruits and vegetables would have incredible economic value for the society.  Among the report’s findings are:

  1. More than 127,000 deaths per year from cardiovascular diseases could be prevented, and $17 billion in annual national medical costs could be saved, if Americans increased their consumption of fruits and vegetables to meet existing dietary recommendations.
  2. Using estimates of how much people are willing to invest in measures to reduce cardiovascular disease mortality, the present value of lives saved in the above-bulleted way would exceed $11 trillion.

And, of course, there are many other positive health impacts to consuming fruits and vegetables besides those on the cardiovascular system, implications for the reduction of cancer, diabetes, neurodegenerative diseases and wound healing.  So the ultimate health and economic benefits would be much greater yet. We are here suggesting the possibility that even greater benefits could be realized through careful management of the stresses experienced by fruits and vegetables before they are digested.


Our concept is that cells in fruits and vegetables often remain alive and active until cooked or digested, and can generate stress responses at every stage along the way from cultivation to digestion. These stresses could be associated with separation from the original soil and plant biome, physical picking, packing, cleaning and storage, movement during transportation, cold shock due to refrigeration or freezing, food preparation steps as above, cooking, chewing, and encounters with our gut biome.  These stressors could include physical maceration and cutting, heat, cold, UV exposure and xenobiotic exposure.  Stress responses in plant cells can include enhanced production of beneficial phytochemicals and production and dissemination of microvesicles containing plant-based miRNAs.  Both can have major impacts on human gene expression.  Therefore, we suggest that stresses encountered along the way by these foods from field to gut can make major contributions to enhancing or degrading the ultimate xenohormetic responses of humans. Finally, it is likely possible that we can manipulate and control these stresses so as to produce optimal health impacts.  These ideas suggest new areas for possibly important research.

That cooking and light exposure can increase the nutritional values of several fruits and vegetables has been known for some time and have been regarded as partial paradoxes.  We believe that the live-cell stress hypothesis laid out in this blog entry explains why these happen.

What we are suggesting is that steps in the food delivery and preparation chain for humans pre-condition the healthfulness of fruits and vegetables in specific ways due to live plant cell stress responses.  Food scientists have largely been oblivious to the molecular mechanisms of such stress preconditioning on foods.  And they understand the net results of such preconditioniong only in special cases, such as related in the examples given above connected with food preparation and cooking.  Further research could possibly assist us in improving such pre-conditioning, giving us fruits and vegetables which produce enhanced health benefits.  The health consequences and economic benefits of doing so could be very large.

Melody Winnig has been pursuing research related to beneficial effects and mechanisms of action of plant polyphenols and factors affecting the longevity of centenarians and super-centenarians.  She has contributed significantly to surfacing and interpreting relevant research that has been reported in this blog.  She is CEO of Vivace Associates, a consulting company concerned with realization of the practical health benefits achievable through science-informed consumption of plant polyphenols.

About Vince Giuliano

Being a follower, connoisseur, and interpreter of longevity research is my latest career, since 2007. I believe I am unique among the researchers and writers in the aging sciences community in one critical respect. That is, I personally practice the anti-aging interventions that I preach and that has kept me healthy, young, active and highly involved at my age, now 93. I am as productive as I was at age 45. I don’t know of anybody else active in that community in my age bracket. In particular, I have focused on the importance of controlling chronic inflammation for healthy aging, and have written a number of articles on that subject in this blog. In 2014, I created a dietary supplement to further this objective. In 2019, two family colleagues and I started up Synergy Bioherbals, a dietary supplement company that is now selling this product. In earlier reincarnations of my career. I was Founding Dean of a graduate school and a full University Professor at the State University of New York, a senior consultant working in a variety of fields at Arthur D. Little, Inc., Chief Scientist and C00 of Mirror Systems, a software company, and an international Internet consultant. I got off the ground with one of the earliest PhD's from Harvard in a field later to become known as computer science. Because there was no academic field of computer science at the time, to get through I had to qualify myself in hard sciences, so my studies focused heavily on quantum physics. In various ways I contributed to the Computer Revolution starting in the 1950s and the Internet Revolution starting in the late 1980s. I am now engaged in doing the same for The Longevity Revolution. I have published something like 200 books and papers as well as over 430 substantive.entries in this blog, and have enjoyed various periods of notoriety. If you do a Google search on Vincent E. Giuliano, most if not all of the entries on the first few pages that come up will be ones relating to me. I have a general writings site at and an extensive site of my art at Please note that I have recently changed my mailbox to
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11 Responses to Health through stressing fruits and vegetables – the Xenohormetic Live Food Hypothesis (updated)

  1. Dan Campagnoli says:

    Hi Vince,
    Here’s a couple of studies which support the concept of post-harvest modification of phytochemical concentrations. Previously the researchers had shown that Arabidopsis thaliana begins ramping up production of insect-fighting (and anti-cancer) chemicals a few hours before sunrise, the time that hungry insects begin to feed. Now they have been able to continue this cycle post-harvest with controlled lighting.

    New item: Does your salad know what time it is?
    Article: Postharvest Circadian Entrainment Enhances Crop Pest Resistance and Phytochemical Cycling

    • Dan Campagnoli

      Thanks for your contribution. Fascinating circadian involvement we need to think about further. The additional evidence helps, Further contributions are most welcome.

      As a matter of fact, Dan, the new information you pointed us to is so important that we have now rolled it into the body of the blog body itself.

      Vince and Melody

  2. Pingback: More on the xenohormetic live food hypothesis – synergies among polyphenols, additional post-harvest plant stressors and stress responses, plant polyphenol transcription factors, and more | AGING SCIENCES – Anti-Aging Firewalls

  3. gabarton says:

    Dear Vincent,

    Excellent article as usual. I have a question though. The studies that show cooking raises certain anti-oxidant levels compare the levels of raw versus cooked. But does this give us any understanding of the anti-oxidant levels of raw food that is exposed to digestion and thus the stress that produces more anti-oxidants? It seems that in order to rightly compare raw and cooked we would have to measure the stressed response of raw food in the digestion system against cooked. Or, better yet I suppose, measure the level of key anti-oxidants in the blood stream after consumption of raw versus cooked. Or am I missing something here?

    • gabarton:

      Your points are excellent. What is important are the end results – which polyphenols are active in which organs after consumption of the food concerned? At present, I think we know relatively little about such matters as:

      * Whether bacteria in the gut biome stress live fruit and vegetable cells so as to enhance or degrade their polyphenol content. Which bacteria do this, if any? How do these possibly condition transmission of such polyphenols through the gut wall and into the bloodstream?
      * The same question with respect to stomach acids and enzymes?

      Perhaps a good approach as you suggest is to measure polyphenol levels after consumption.

      There is much still to be learned.


  4. Dan Campagnoli says:

    Hi Vince and Melody,

    Another plant stressor mechanism to consider is simulating plant-to-plant communication of defense signals. Plants communicate through underground Mycorrhizal networks
    Interplant Communication of Tomato Plants through Underground Common Mycorrhizal Networks

    “This finding indicates that CMNs may function as a plant-plant underground communication conduit whereby disease resistance and induced defence signals can be transferred between the healthy and pathogen-infected neighbouring plants, suggesting that plants can ‘eavesdrop’ on defence signals from the pathogen-challenged neighbours through CMNs to activate defences before being attacked themselves.”

    And also through airborne through volatile compounds.
    Airborne signals prime plants against insect herbivore attack
    “Green leafy volatiles (GLV), six-carbon aldehydes, alcohols, and esters commonly emitted by plants in response to mechanical damage or herbivory, induced intact undamaged corn seedlings to rapidly produce jasmonic acid (JA) and emit sesquiterpenes.”

    I haven’t looked into jasmonic acid before, a quick search turns up
    Jasmonates in cancer therapy
    Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria
    Jasmonates–a new family of anti-cancer agents

    In terms of potential practical applications, in the prior link on GLV’s says:
    “The use of pure synthetic chemicals revealed that (Z)-3-hexenal, (Z)-3-hexen-1-ol, and (Z)-3-hexenyl acetate have nearly identical priming activity.”

  5. Dan Campagnoli

    Thanks to you again to this very relevant comment regarding plant signaling. I wonder about the role interplant stress signaling may play in food preservation, or whether the signaling plays a role when one piece of spoiling fruit or vegetable leads to a whole contiguous batch of fruits or vegetables spoiling too. Signaling could be a very useful way for thinking about food preservation. Instead of keeping your apples together in a bag on the counter, might it be better to scatter them around the kitchen? As is well known, one bad apple in the bag will spoil them all. Circulating air is important too – possibly to keep airborne signaling molecules from reaching from a bad piece of produce to its companion good ones.
    I had never previously heard of the Jasmonate family of phytochemicals. In fact, I did not appreciate the extent of research that has been done on plant stress hormones by plant scientists. It seems that the researchers concerned with the health benefits of certain phytochemicals (which by-and-large are stress hormones), and researchers looking at stress hormones from a plant biology and agricultural viewpoint belong to largely non-interacting communities and are concerned with different phenomena. If we are going to understand xenohormesis (how stress responses in plants can lead to health benefits in humans), we need to draw on research from both camps.


  6. eric25001 says:

    Seems like short lived species like the fly and worm could show the extent of plant stress on aging of the eating of the plants.

    Hard to see how this overcomes glucose, insulin, and ketone on aging! Eric

  7. Melody says:

    Here is an update on cooking with blueberries and how that affects polyphenols “Accumulating evidence suggests that diets rich in (poly)phenols may have positive effects on human health. Currently there is limited information regarding the effects of processing on the (poly)phenolic content of berries, in particular in processes related to the baking industry. This study investigated the impact of cooking, proving, and baking on the anthocyanin, procyanidin, flavonol, and phenolic acid contents of wild blueberry using HPLC with UV and fluorescence detection. Anthocyanin levels decreased during cooking, proving, and baking, whereas no significant changes were observed for total procyanidins. However, lower molecular weight procyanidins increased and high molecular weight oligomers decreased during the process. Quercetin and ferulic and caffeic acid levels remained constant, whereas increases were found for chlorogenic acid. Due to their possible health benefits, a better understanding of the impact of processing is important to maximize the retention of these phytochemicals in berry-containing products.” The article Impact of Cooking, Proving, and Baking on the (Poly)phenol Content of Wild Blueberry was just publishing in The Journal of Agricultural and Food Chemistry.

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