Here we have Part 2, an in-depth look at unrefined, whole-food sugar in an evolutionary context—an enormous blind spot in "Paleo" going back to the very beginning. "Duck Dodgers" is once again the lead man for the piece, with lots of research work by three other collaborators who wish to remain anonymous such that credentials and employment don't get in the way. Took the four of them 2 months to put this together. There was also some proofing help by a couple of others.
Here are the topics:
- Sugarcane Is A Superfood
- Revisiting Oxidative Stress
- Honey Is A Superfood
- The Secret of Honey: Fiber and Fructose
- Purified Antioxidants Are Counterproductive
- Plants Use Sugars To Counteract Stress and Inflammation
- Can Starch and Fibers Scavenge ROS?
- Achieving Homeostasis
- Hormesis from Antioxidants Acting As Prooxidants?
- The Riddle of Persorption
- Gut Flora and Homeostasis
- Brief Overview of Part 3
In her 2011 book, "Primal Body, Primal Mind," Nora Gedgaudas made an irresponsible statement that caused a great number of people to have anxiety about food.
"Primal Body, Primal Mind: Beyond the Paleo Diet for Total Health and a Longer Life," by Nora Gedgaudas (2011)
"Glycation and its damage is ultimately a cumulative process, so every bit of sugar or starch we eat eventually counts. Every piece of candy, cookie, bread, or potato, every spoonful of honey, and every drop of soda effectively shortens your life—something to think about."
No, I'm afraid it doesn't quite work like that. Refined sugars like HFCS or table sugar are intensely processed with heat, vacuums, chemicals, centrifuges, and filtering—which are designed to remove the naturally occurring cofactors, like prebiotic fibers, antioxidants, minerals and microbes. Ignoring that major difference is sloppy and disingenuous.
Sugarcane Is A Superfood
Sugarcane and sugar beet are major sources of refined sugar in the modern world. But, it might surprise you to learn that many traditional cultures in the tropics chewed raw sugarcane and drank sugarcane juice as a medicinal. Not only did the ancients utilize unrefined sugar for its medicinal qualities, but sugarcane juice is still considered to be a medicinal and a health-promoting beverage in some parts of the world. Interestingly, some of the earliest soda recipes, including Coca-Cola and Moxie, were initially concocted as medicinals before they were ever marketed to the public.
Sugar beets are considered to be a medicinal herb, where the fresh roots and leaves are used as garnish in traditional Asian dishes and have been shown to have potent hypoglycemic activity. More recently, sugarcane juice is being recognized as a low glycemic superfood. Sugarcane juice and sugarcane and sugar beet molasses was shown to have antioxidant and free-radical scavenging activity, as well as the ability to to reduce iron complex and inhibit lipid peroxidation. Sugarcane is rich in calcium, chromium, cobalt, copper, magnesium, manganese, phosphorous, potassium and zinc, and contains essential vitamins such as B1, B2, B3, B5 along with soluble fiber and proteins. Incredibly, it's also believed to protect your teeth from decay.
Sugarcane molasses—the waste product of sugar refining—has anti-diabetic compounds, is rich in minerals like manganese, magnesium and potassium, and sugarcane molasses concentrate even lowers glycemic response when added to carbohydrate-rich foods.
Carbophobes like to classify potatoes as bags of sugar, but the potato happens to be loaded with antioxidants and other phytochemicals. Purple and red potatoes are very high in measured antioxidants, but potato varieties with yellow and white flesh were found to have greater antioxidant activity than colored potatoes. One of the more impressive antioxidants in potatoes is Alpha Lipoic Acid, which improves insulin sensitivity and is beneficial for diabetics. Amazingly, potatoes and their processed products, such as French fries and chips, are reported to be good sources of glutathione, the master antioxidant.
Revisiting Oxidative Stress
Now the damaging oxidative stress that Nora was referring to, above, is mainly due to Reactive Oxygen Species (ROS) and Advanced Glycation Endproducts (AGEs). The word "glycation" is really a misnomer—a relic of early diabetes research and the discovery of spontaneous glucose reaction products. However, scientists now know that most glycation products are a result of dicarbonyls, which are 20,000 times more reactive than glucose and can be derived equally from fatty acid and carbohydrate metabolism. The same is true of both ROS and Reactive nitrogen species (RNS). And as we learned in Part I, chronic ketosis—the metabolic state Nora recommends to avoid the glycation—is believed to generate large amounts of these highly reactive dicarbonyls.
We also learned in Part I that normal and unavoidable levels of ROS and oxidative stress act as signals for cellular metabolism—like traffic lights for our bodies that tell us, among other things, when to upregulate our own hormetic anti-oxidant pathways.
Furthermore, as Chris Masterjohn tells us, Insulin signaling is highly protective against glycation and ROS, so its loss in conditions like diabetes is a major contributor to damage.
Nora's notion that every spoonful of honey and every bite of potato shortens our life is not backed by any science. Nor is it backed up by any real-world examples from cultures who relied heavily on those whole foods. It's nothing more than fear-mongering to encourage people to embrace an unnatural diet under the guise of a faux "Paleo™" lifestyle.
It's the false narratives, like Nora's, that promote eating disorders such as orthorexia nervosa (an unhealthy obsession avoiding foods perceived to be unhealthy), which have become rampant in the Paleosphere. Our Paleolithic ancestors ate whatever energy-positive staples they could find. They certainly didn't fear sweets, like honey or starchy tubers. And as we will see below, plants natively provide the very compounds necessary to help regulate oxidative stress because they too need to regulate their own oxidative stress.
Honey Is A Superfood
Honey is one of the most energy-dense foods in nature, in terms of absorbable calories. (Fat is more energy-dense, but isolated fat is not classified as a "whole food"). More importantly, anthropologists now believe that starchy C4 sedge tubers and honey played a significant role in our evolution. Honey, in particular, was a prime source of energy for many indigenous cultures throughout the world. And with an unlimited shelf life, it never spoils.
A few of the well known honey hunters include the Rai people of Nepal, who scale cliffs in the foothills of the Himalayas that are home to the world's largest honeybee, Apis laboriosa. The Magars—also of Nepal—were honey hunters as well. Others include the Shenko Honeymen of Ethiopia, the Aka, Mbuti and Efe pygmies of the Congo. Honey is the favorite food of the Mbuti. At times, during the rainy season up to 80% of the calories in their diet come from honey.
In Paraguay, the Aché tribe, consider honey and bee larvae to be the second most important food in their diet, after large game meat, and at times they will consume as much as 1,100 calories from honey a day.
Other notable honey hunters include the Masai, the Hadza of Tanzania, Australian aborigines like the Aranda, the Batek of Malaysia and the Yanomami of Venezuela. The Hadza consume about 15% of their calories from honey.
Bees are the only the only animals in nature to create enormous surpluses of food—apparently evolving to have its own honey stolen by hungry humans, and other animals.
The lengths some cultures, like the Gurung Nepalese and the Aka will go to obtain honey are breath-taking.
Note that they eat the indigestible honeycomb (beeswax) too. And interestingly, some people consider bee venom, from bee stings, to be hormetic (see apitherapy).
Rock art depicting honey collecting has been dated to 40,000 years ago—found in Africa, Europe, Asia and Australia. One of the most famous honey-collection cave paintings is "Man of Bicorp", an 8,000 year-old Epipaleolithic painting from the Araña Caves, shown climbing lianas and gathering honey from wild bees.
Those are the cave paintings low carb Paleos, like Nora, don't want you to see. How someone can write a book on the benefits of Paleolithic diets while also claiming every drop of honey shortens lifespans is absolutely mind-boggling.
Honey is now being investigated as an anti-diabetic agent. By this point we shouldn't be surprised that it's the oligosaccharides in honey that contribute to this anti-diabetic effect. But honey is more than fiber. It's also a good source of antioxidants, and it is also being studied for its ability to significantly modulate gene expression differently than refined sugars. For example, in bees, honey up-regulates detoxification and immunity genes. Suddenly, fructose within the context of naturally occurring fiber and antioxidants isn't quite so scary anymore. But don't tell that to The Paleo Diet™ author, Loren Cordain, who's team recently gave honey a big thumbs down solely because it is a good source of fructose. We know refined fructose is inflammatory, so therefore honey must be bad for you. There's your modern Paleo™ "logic" in a honeynut-shell. [Update: see this 2014 study: Effect of honey in preventing gingivitis and dental caries in patients undergoing orthodontic treatment.]
To top it off, evidence shows that honey may have been consumed in much greater quantities than previously believed.
Honey revisited: a reappraisal of honey in pre-industrial diets, by Allsop & Miller (1996) (Free Download)
A reappraisal of the evidence from the Stone Age, Antiquity, the Middle Ages and early Modern times suggests that ordinary people ate much larger quantities of honey than has previously been acknowledged. Intakes at various times during history may well have rivaled our current consumption of refined sugar. There are implications therefore for the role of sugar in modern diets. Refined sugar may not have displaced more nutrient-rich items from our present-day diets but only the nutritionally comparable food, honey.
And it doesn't take much digging to find paradoxes that defy Nora's unsupported claims of death by carbohydrates. For instance, super-centenarians in the Longevity Villages and "Blue Zones" of the world eat lots of carbohydrates and legumes—basically the polar opposite of her version of Paleo™. In Bama, China and Yuzurihara, Japan they eat lots of potatoes. If you do your homework, you won't find a single low carb longevity village. How can this be if Nora tells us that carbohydrates shorten our lives?
Another paradox we've seen more recently is that eating spoonfuls of prebiotic fibers seems to make people look younger and improve their body composition. Somehow eating spoonfuls of raw (prebiotic) starch appears to reduce inflammation. It seems as though fibers help reduce inflammation. Let's keep looking.
The Secret of Honey: Fiber and Fructose
Perhaps carbophobes, like Nora, never took the time to look into what makes natural carbohydrates, such as honey, so special. But with a little bit of digging we can find some clues. A group of researchers fed honey to a group of rats and purified fructose to another group of rats to observe the difference. The honey protected the rats from much of the prooxidative effects of fructose.
Substituting Honey for Refined Carbohydrates Protects Rats from Hypertriglyceridemic and Prooxidative Effects of Fructose, by Busserolles, et al. (2002)
Because honey is rich in fructose, the aim of this study was to assess the effect of substituting honey for refined carbohydrates on lipid metabolism and oxidative stress...Compared with those fed fructose, honey-fed rats had a...lower susceptibility of heart to lipid peroxidation. Further studies are required to identify the mechanism underlying the antioxidant effect of honey but the data suggest a potential nutritional benefit of substituting honey for fructose in the diet.
Incredibly, the same researchers figured out one of the underlying mechanisms that significantly reduced the oxidative stress in the rats, but they withheld their findings so they could patent it.
"A subject of the invention is also the use of prebiotics as compounds with an anti-aging effect linked to an effect which protects the cells of the organism against the action of free radicals...These results indicate that the animals following the fructose diet are subjected to a significantly greater oxidative stress than that of the control animals (subjected to the starch diet) and that the addition of FOS allows significant reduction in the oxidative stress linked to the consumption of fructose."
The patent filing reads like a study—explaining the experiments they ran to determine the antioxidant role of prebiotics in honey. Between the study and the data presented in the patent, we can see that while a purified fructose diet resulted in higer levels of inflammation, the prebiotics alongside fructose resulted in oxidative stress that was not significantly different over that of the starch + prebiotics diet. Another study in rats, the following year and using oligofructose, showed similar results. And in 2008, a third study showed that inulin protects from the harmful effects of fructose.
Purified Antioxidants Are Counterproductive
In Part I we learned that low levels of ROS and oxidative stress can activate powerful hormetic responses. We also learned that taking too many anti-oxidants may suppress the ROS signals that activate our hormetic pathways and can be counter-productive to health. Ironically, it seems that by avoiding oxidative stress, we become more fragile and susceptible to oxidative stress. The scientific community is finally starting to grasp this:
"...The concept of oxidative stress being a major deleterious player in all manner of situations has been massively supported by a vast literature [31,32,33]. The data presented in these reports has formed the basis for pre-clinical and clinical trials of antioxidant therapies [34,35], most of which have disappointing outcomes. We assert that the conclusion of a need for antioxidant therapy is based on misinterpretation of these data. Reactive oxygen species (ROS) are central to normal metabolism. They give rise to physiological levels of peroxide, which then acts as a second messenger in maintaining normal physiological function . Thus, ROS at physiological levels are essential for health"
Therefore, it may be reasonable to deduce that a combination of antioxidants and pro-oxidants may result in a mild inflammation, or homeostasis, that provides us with hormetic benefits, such as up-regulated antioxidant status.
Given the important role honey plays for so many indigenous cultures, it's possible that honey promotes that kind of homeostasis—a mild and hormetic inflammation without the harmful effects of refined fructose. If nothing else, the large amounts of honey many indigenous cultures consume at certain times of the year should encourage us to consider honey as yet another ideal source of carbohydrarates.
Plants Use Sugars To Counteract Stress and Inflammation
You may have noticed a correlation between plants becoming sweeter as the weather turns cold. Apples become sweeter during the Fall. Carrots increase their sugar or brix content as frost starts to appear. Sugars accumulate as plants undergo stress (drought, cold, salinity, lack of nutrients). This is not an accident. Sugars help plants tolerate and respond to stresses, like the cold. And the accumulated sugars allow for rapid growth once the stress is removed.
These "sugars" or "glycans" include the complex polysaccharides we think of as prebiotics (starch, inulin, FOS, GOS, etc.) as well as the carbohydrates attached to larger molecules like proteins (glycoproteins) or fats (glycolipids, triglycerides, etc). Thus, "carbohydrate", "glycan", "saccharide", and "sugar" are generic terms that are used interchangeably. Plants and animals each have millions upon millions of their own special kinds of sugars/glycans. For instance, our gut linings are composed of mucin-2, a glycoprotein that's 80% sugar by weight. And it's no accident that most of the known prebiotics are glycans. That's because if a glycan is packed too tightly (like resistant starch) or has β-glycosidic bonds (like β-glucans) they cannot be degraded by our own enzymes. But, our microbiota specializes in metabolizing glycans. So, virtually every complex sugar or glycan has the potential to be a prebiotic. That's how our gut bugs survive. If you have the right gut bugs that can degrade some of these glycans, those glycans become what is referred to as Microbiota-accessible carbohydrates (MACs).
In plant cells, sugar goes beyond stress tolerance and energy—sugar is also used for signalling genes and signaling antioxidant network connections. Recent studies have investigated how sugars help plants balance their internal signals and responses to oxidative stress from ROS—to achieve homeostasis. In both animals and plants, tolerable and hormetic levels of sugar appears to up-regulate ROS scavenging pathways.
Furthermore, researchers are also investigating how sugars can have true antioxidant effects in plants and animals. For instance, sucrose can act as a powerful antioxidant in plants. Of course, animals have enzymes to rapidly degrade sucrose into the monosaccharides glucose and fructose, for energy. When sucrose is eaten in its refined form, without fiber or antioxidants, it obviously increases oxidative stress.
If you've read Jo Robinson's "Eating on the Wild Side," you know that stressed and damaged plants will be higher in natural antioxidants. It seems that sugars and antioxidants tend to go hand in hand in nature.
Can Starch and Fibers Scavenge ROS?
Feeding diabetic rats RS-rich white rice, can decrease inflammation and improve antioxidant status. The same is true of other prebiotic fibers. The most common explanation for this is that the prebiotics are inert and the gut bugs or their metabolites are upregulating our anti-inflammatory responses. That alone would explain why people look younger while eating spoonfuls of prebiotics and why honey and inulin protects against the inflammation from fructose.
But, if plants use sugars for balancing hormetic ROS production/signaling with ROS-scavenging, might the sugars and indigestible polysaccharides/prebiotics have a similar effect in animals as well? Some researchers seem to think so.
The food additives inulin and stevioside counteract oxidative stress, by Stoyanova, et al. (2011)
Prebiotics such as inulin (Inu)-type fructans and alternative natural sweeteners such as stevioside (Ste) become more popular as food ingredients. Evidence is accumulating that carbohydrates and carbohydrate-containing biomolecules can be considered true antioxidants, capable of scavenging reactive oxygen species (ROS). Here, we report on the ROS scavenging abilities of Inu and Ste in comparison with other sugars, sugar derivatives and arbutin. It is found that Inu and Ste are superior scavengers of both hydroxyl and superoxide radicals, more effective than mannitol and sucrose. Other compounds, such as 1-kestotriose, trehalose, raffinose and l-malic acid, also showed good reactivity to at least one of the two oxygen free radicals. The strong antioxidant properties of Inu and Ste are discussed.
Even raffinose family oligosaccharides (RFOs) and other sugars may act as antioxidants in both plants and animals. Even pine bark, a medicinal prebiotic fiber used by some indigenous cultures, has free radical-scavenging abilities targeted for humans.
Researchers are now considering the theoretical antioxidant functions of all prebiotic glycans. However, in theory many should be inert, and only a limited direct scavenging ability may be theoretically plausible. Nevertheless, researchers such as molecular plant biologist, Wim Van den Ende, has raised some eyebrows:
Disease prevention by natural antioxidants and prebiotics acting as ROS scavengers in the gastrointestinal tract, by Van den Ende, et al. (2011)
An increasing amount of data point to a combined antioxidant and immuno-modulatory effect for prebiotics, suggesting that the underlying mechanisms might be identical. The finding that both AXOS and inulin-type fructans can act as antioxidants themselves (Broekaert et al., 2011; Stoyanova et al., 2011), raises the question whether they could act directly as ROS scavengers (instead of indirectly through SCFAs and GSTs)
And this past year, researchers further explored the antioxidant scavenging ability of fructans, like inulin:
Antioxidant activity of inulin, which was significantly higher compared to simple sugars, remained unaltered despite cooking and digestion processes. Inulin protected the mucosal and submucosal layers against protein oxidation...Inulin protects the human colon mucosa from LPS-induced damage and this effect appears to be related to the protective effect of inulin against LPS-induced oxidative stress.
The RS in sweet potatoes are being investigated for ROS-scavenging properties. So is Buckwheat. Chitosan, a prebiotic glycan found in insects, crustaceans, and fungi has stronger scavenging activity than Vitamin C on highly chemically reactive ROS hydroxyl radicals. Moreover, RS has been shown to prevent the depletion of glutathione.
And just like the glycans in fibers and polysaccharides, polyphenols have glycosidic linkages that can be metabolized by gut bugs. This explains why red wine polyphenols can bloom certain kinds of bacteria.
In fact, polyphenols, fructans, and fibers like RS appear to be synergistic. One study showed that tea polyphenols modulate RS to produce a more slowly digestible starch that is beneficial to postprandial glycemic control. Fructans are not only prebiotics, but when combined with co-existing phenolic compounds they too can exhibit anti-inflammatory, antioxidant and immunomodulatory properties.
And it seems that plant-derived polyphenols can act in collaboration with whole saliva, human red blood cells, platelets, and also with catalase-positive microorganisms to decompose reactive oxygen species (ROS). Amazingly, polyphenols can adhere to mucosal surfaces, and are retained there for long periods to possibly act as a "slow-release devices" capable of affecting the redox status in the oral cavity.
In Western medicine, and culture, there's a misconception that things can only be "good" or "bad." We think that a pathogen must be "bad," even though there is some evidence that pathogenic parasites can up-regulate hormetic responses. So, we try to kill and eradicate all pathogens and anything perceived to be "bad" and we over-indulge in anything that is "good." Meanwhile, indigenous cultures such as the Hadza co-exist with some pathogens. Could it be that in the West we tend to turn our attention to the extremes?
In traditional Eastern medicine, there is a belief in achieving homeostasis—a harmonious balance between what some may perceive as good and bad. All diseases are considered to involve a disturbance of homeostasis. There is also a belief in taking something that is bad and turning it into something good. Think for a moment how this stands in contrast to Western medicine, and how this applies to what we've learned above and about hormesis. If we look closer, we see that even the antioxidants themselves may have dual roles in this game.
Hormesis from Antioxidants Acting As Prooxidants?
As Stephan Guyenet explained in his excellent hormesis posts (Parts I and II), while antioxidants, as polyphenols, may have the ability to scavenge free radicals in a test tube, and inside of our guts, their role as they travel throughout the body may actually be hormetic as prooxidants which can activate hormetic pathways.
Polyphenols, Hormesis and Disease: Part II, by Stephan Guyenet
...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.
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.
Evidence also suggests that the increase in antioxidant capacity of blood seen after the consumption of polyphenol-rich (ORAC-rich) foods is not caused directly by the polyphenols, but most likely results from increased uric acid levels derived from metabolism of the antioxidants. The health benefits from fruits, vegetables, and even chocolate, may be that they activate our hormetic pathways.
The Riddle of Persorption
As Guyenet pointed out, when polyphenols enter the bloodstream, they are seen as foreign compounds—or xenobiotics—and the body does everything it can to get rid of those foreign particles. Moreover, he explains that the concentration of these particles is not great enough to reduce much oxidative stress. More likely, the particles in the blood appear to be a temporary hormetic stressor that can upregulate the powerful antioxidant pathways in the body—known as xenohormesis. Guyenet says the reason may be that diversity and chemical structure of polyphenols makes them potentially bioactive. But there's another interesting reason why the body has to get rid of them. Many polyphenols (and starch particles) can be too large to fit through small blood vessels (arterioles).
Gerhard Volkheimer showed this phenomenon when he asked test subjects to drink an excessive 200g of raw potato starch, without chewing, and he observed how the large starch granules found in potatoes and other foods entered the bloodstream and caused embolisms in small blood vessels. Ray Peat made it sound rather frightening. What happens is that the gut lining preferentially persorbs particles into the bloodstream that range from 5 μm (microns) to 150 μm in diameter. What Volkheimer discovered is that it's possible to overwhelm the natural defenses of the human body.
Since red blood cells have to squeeze through tight arterioles, persorbed particles that are larger than a red blood cell (which are only 6-8 μm in diameter) could potentially get stuck and cause blockages and embolisms. So, you can see why the body would want to get rid of those large particles once they are done doing their job.
A sampling of some of these large nanoparticles include raw mature potato starch granules (8 to 140 μm), cellulose in vegetables (>30-50 μm), carrots (4-26 μm), drip coffee (filtered to <25 μm), activated charcoal (1-150 μm), pollen in raw unfiltered honey (2.5-1,000 μm), dirt (0μm up to small pebbles), antioxidant-containing particles in cocoa solids (5-150 μm), machine ground cocoa bean shells (>90 μm), flavanols in green tea (average 715 μm), ascorbic acid particles (10-160 μm), and α-Tocopherol (10-80 μm). Even animal fibers have been implicated too. When particles are too large, our microbiota metabolize them and make sure they are small enough to enter the bloodstream.
...Bacteria break down some specific components contained in cocoa, called polyphenols. These molecules are too big to be absorbed into the blood, but gut bacteria break them down into smaller chemicals that can pass to the blood. These chemicals have the property of reducing inflammation in cardiovascular tissues.
Given the wide array of large particles we persorb on a daily basis, the lymph and blood vessels are prepared to handle such intrusions. For instance, it's well recognized that the liver is specifically designed to filter such particles from the blood. Volkheimer also acknowledged various elimination pathways (urine, bile, enzymatic degradation, cerebrospinal fluid, milk production, phagocytosis by macrophages).
There are three lines of defense to prevent obstructions and embolisms from ingestion of starch granules—salivary amylase, pancreatic amylase and plasma/serum amylase (see also this paper). And the blockages appear to be temporary. Full disclosure: if someone has liver, pancreatic or other health issues, serum amylase may be compromised.
But, one has to wonder why a healthy gut epithelium would selectively persorb particles into the bloodstream, ranging up to 120μm, only to then get rid of them a few hours later. There are other reasons besides hormesis.
For instance, β-glucans—a fiber/glycan found in mushrooms and oats—stimulate the immune system when they are delivered into the blood and ingested by macrophages (macrophages themselves are 21 μm). Starch granules have shown the ability to catch pathogens like Cholera. Mannose-binding lectins can scavenge Ebola and other microorganisms like HIV (so can polyphenols). Edible plant exosome-like nanoparticles can "talk" to animal cells, to promote Healing—an amazing example of interspecies communication. Glycosaminoglycans (GAGs) from blueberries get transported to your blood vessels and play a role in maintaining their health. Without persorption, there would be no way for GAGs to contribute to the health of blood vessels, there would be no way for polyphenols, ascorbic acid particles, and α-Tocopherol particles to do their jobs.
In other words, it's not an accident that the body lets those large particles into the bloodstream and lymphatic system. Our bodies want those large particles to interact with the body. And then it wants them gone.
Gut Flora and Homeostasis
As many who read this blog already know, we are constantly learning about new roles that our gut flora play in our health. It's impossible to do the topic the justice it deserves, but I hope some of these recent discoveries will change the way we think about inflammation and ROS signaling going forward.
One interesting example is that bacteria coated by polyphenols acquire potent oxidant-scavenging capacities. Suddenly we can see how using sterile test tubes doesn't give us the full story on antioxidants.
But remember, optimal health appears to be a balance of mild inflammation (ROS signaling), combined with antioxidants, which seems to provide a kind of homeostasis in both plants and animals.
So, how can our gut flora help modulate this homeostasis? Believe it or not, your gut bugs can contribute to hormetic levels of inflammation.
A recent study has demonstrated that some genera of human GIT bacteria can induce a rapid increase of ROS, eliciting a physiological response through the activation of epithelial NADPH oxidase-1 (Nox1) [57,58]. In addition, reports site in vitro experiments with epithelial cells that, when co-cultured with specific probiotic bacteria, show an increased and rapid oxidation reaction of soluble redox sinks, namely glutathione and thioredoxin [57,58] that indicate the presence of a regulated process. This effect was demonstrated as an increase in the oxido-reductase reaction of transcriptional factor activations such as nuclear factor kappa B (NFκB), NrF2 and the antioxidant response element, reflecting a cellular response to increased ROS production that is regulated [57, 58]. This effect must be decisive in order to elicit a restrained anti-infective response with a minimal chance of pro-inflammatory damage to the tissue. These reactions define potent regulatory effects on host physiological functions that include immune function and intracellular signaling.
Furthermore, probiotic strains have also been reported to generate a range of anti-microbial substances and to positively affect and modulate immune system function. Lee  has reported that the enteric commensal bacteria by rapidly generating ROS negotiate an acceptance by the GIT epithelia. Different strains of commensal bacteria can elicit markedly different levels of ROS from contacted cells. Lactobacilli are especially potent inducers of ROS generation in cultured cells and in vivo, though all bacteria tested have some ability to alter the intracellular oxido-reductase environment . Yan  has reported that there are soluble factors that are produced by strains of lactobacilli that are capable of mediating beneficial effects in in vivo inflammatory models. This result expands our understanding that there are ROS-stimulating bacteria that possess effective specific membrane components and or secreted factors that activate cellular ROS production to maintain homeostasis.
These reports focus our understanding on the importance of second messenger functionality for the maintenance of homeostasis and brings into serious question the annulment of ROS by antioxidant supplements for the amelioration of chronic diseases such as CKD. The established importance of recent investigations regarding probiotic/microbial-elicited ROS teaches that stimulated cellular proliferation and motility is strictly controlled and is a regulated signaling process for proper innate immunity and gut barrier functionality [59,62,63]. The observations that the vertebrate epithelia of the intestinal tract supports a tolerable low-level inflammatory response toward the GIT microflora can be viewed as an adaptive activity that maintains homeostasis .
Probiotics demonstrate properties that can promote and rescue deviations in intestinal redox metabolism through the activity of ROS in a similar manner as somatic cells signal metabolic function
It's rather curious that our gut bugs evolved to help us manage oxidative stress. How can this be? Well, it turns out that the creation of animal guts appears to have coincided with the oxygenation of the Earth's atmosphere—forging major alliances between animals and microbes. And in this alliance, we find that our microbial inhabitants actively program our bodies and our genes to manage oxidative stress.
These reports focus our understanding on the importance of second messenger functionality for the maintenance of homeostasis and brings into serious question the annulment of ROS by antioxidant supplements for the amelioration of chronic diseases. The established importance of recent investigations regarding probiotic/microbial-elicited ROS teaches that stimulated cellular proliferation and motility is strictly controlled and is a regulated signaling process for proper innate immunity and gut barrier functionality (Collier-Hyams et al., 2005; Lin et al., 2009). The observations that the vertebrate epithelia of the intestinal tract, supports a tolerable low-level inflammatory response toward the GIT microflora, can be viewed as an adaptive activity that maintains homeostasis (Neish et al., 2000).
These [bacterial] endosymbionts providing a functional duality, that is control of homeostasis for growth and protection from the deleterious effects of an oxygen rich atmosphere that is analogous to the deleterious effects of oxidative stress.
...An ancient endosymbiotic event that gave rise to mitochondria also evolved regulated ROS signaling pathways that are widely distributed in diverse environments from soils to commensal and probiotic bacteria found in the human gastrointestinal tract (Neish, 2013).
...Mechanistically probiotic bacteria may rescue mitochondrial dysfunction by linking a biologically plausible cellular signaling program (ROS dependent) between the human host and its microbiome cohort for a continued co-operative symbiosis that maintains homeostasis favorable to both.
Our gut bugs evolved to co-exist with us. We provide them with shelter from the oxygenated atmosphere, as well as food, while they help us manage our oxidative stress by programming our genes and helping to stimulating ROS-signaling in order to maintain homeostasis.
After investigating hormesis on the cellular and microbial levels, perhaps the ancient Eastern medicine concept of promoting homeostasis may be more sound than the Western approach of purification, over-sanitation, and eradication of all pathogens and microbes as well as suppressing inflammation through potent pharmaceuticals and purified antioxidants. Ironically, Mother Nature—as well as our gut bugs—provides us with a wide range of ways to achieve homeostasis. And the best part of all is that our tastebuds help us navigate the entire process.
That wraps up Part II of our hormesis series. In Part III we'll investigate how the recent "Paleo™" trend of trying to avoid all naturally occurring toxins is not only anthropologically incorrect, but is likely counterproductive to optimal health.