The Hormesis Files: Who’s Afraid of Unrefined Sugar?

Part 1: The Hormesis Files: Chronic Ketosis and The Case of The Missing Glutathione.

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.

Amazingly, both the Hadza and Masai co-evolved with the Greater Honeyguide bird, a wild bird that instinctively leads humans to sources of honey in exchange for honey combs (see video).

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.

honey cave painting
 

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.

US Patent#: 20060252725 A1 — Use of prebiotics for preventing or treating oxidation stress

"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:

From the Gastrointestinal Tract (GIT) to the Kidneys: Live Bacterial Cultures (Probiotics) Mediating Reductions of Uremic Toxin Levels via Free Radical Signaling, by Vitetta, et al. (2013)

"...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 [36]. 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 and Its Role in the Prevention of Human Colonic Muscle Cell Impairment Induced by Lipopolysaccharide Mucosal Exposure, by Stoyanova, et al. (2014)

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.

Achieving Homeostasis

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.

Gut microbes make dark chocolate healthy

...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.

From the Gastrointestinal Tract (GIT) to the Kidneys: Live Bacterial Cultures (Probiotics) Mediating Reductions of Uremic Toxin Levels via Free Radical Signaling, by Vitetta, et al. (2013)

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 [60] 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 [59]. Yan [61] 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 [64].

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.

Live probiotic cultures and the gastrointestinal tract: symbiotic preservation of tolerance whilst attenuating pathogenicity, by Vitetta, et al. (2014)

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.

Monterey Bay Outing

I've got  a major post coming tomorrow, part 2 in the hormesis series. In the meantime, just a couple of photos from the Monterey Bay area which is characteristically beautiful this time of year.

Yesterday we headed down to attend Holly's wedding at the Monterey Plaza Hotel on Cannery Row. Beatrice was her teacher for both 4th and 5th grades back in about 2000ish. Holly's mother and Bea are both teachers who've been good friends since before Holly was born.

This morning after checking out, we headed down the peninsula a bit and ended up at the Highlands Inn for breakfast—ending up booking a future 2-night stay. Here's a couple of reasons why (click for the HD versions).

IMG 2893
Unbelievable Views
IMG 2894
Good Food and Views

Bea had a nice zucchini frittata and I, a dungeness crab omelet with spinach and goat cheese.

...Until tomorrow.

Taking A Look At Medicinal Mushrooms: Chaga and Reishi

Trying to take an honest, objective look at anything that's within range of the SUPERFOOD!!! radar is a big PITA, let me tell you. There's 1,000 wide-eyed, hyped "articles" for every one that's measured and cautious.

...I get emails almost every day from people wanting to send me products to try, in the hope I'll like them, sign up for their affiliate deal, promote it here, etc. I don't even respond to 95% of them. You wouldn't believe some of the stuff people peddle, and the fact they're even asking me says that their first line—"I've been following your blog for a long time"—is a lie. Delete.

Being criticized for having the audacity to actually have this blog reimburse me for some of the time I spend at it (similar to having the audacity to demand your employer reimburse you for your time and efforts) can be irritating on that score alone, but doubly so because I think I do it in a decent way that's not nearly so annoying as having to sit through 3 minutes of commercials on the TV every 10 minutes.

  1. Every single thing I promote or have promoted to you directly in a post is something I use and like myself.
  2. Every other thing you purchase by going to My Amazon Link is something you have decided to buy anyway, and it doesn't cost a cent.
  3. The ads to the right are served up by Google and are largely based on your cookies, so a chance it's something you're interested in, like Bussian Rrides, for instance.

OK, onward. Here's what I'm guardedly promoting today.

IMG 2891
Proof that I actually use it

...About a month ago I got an email from Lari Laurikkala, one of the Finns that run Four Sigma Foods, asking if I'd be willing to try a couple of their medicinal mushroom products: Chaga (Inonotus obliquus) and Reishi (Lingzhi mushroom), to be exact. Before I hit the delete button (SUPERFOOD!!! radar) I recall Tim Steele mentioning something about a medicinal 'shroom he'd used for a long time, so I asked him and sure enough, Chaga is the one.

Alright, I'm in. Having used them for a week or so now I've decided to promote them and add them to My Amazon Store.

Four Sigma Foods Instant Chaga, 20 Count. For me, the taste is earthy and slight vanilla. I've had it in hot water, hot coffee, a smoothie and cold Tejava.

In terms of medicinal benefits, I really can't claim anything other than it seems soothing on the tummy, which is fine. There's some sign that it helps my morning back and leg pain (virtue of my L4-5 herniation) recede sooner for the day. Jury still out but, ibuprofen definitely helps for that and Chaga is supposed to have anti-inflammatory properties. Of course, there are a million medicinal claims. What's more relevant to me is that it has stood the centuries test of time in being a folk remedy in certain parts of the world. Anyway, here's one of the more objective pieces I found on it, from the Memorial Sloan Kettering Cancer Center.

Clinical Summary

Chaga mushroom, found on Birch and other trees in cold climates, has been used in folk medicine in Russia and other North European countries for generations. Chaga draws nutrients from the tree on which it grows and extracts are typically derived from the inner layers of the bark. The active constituents are thought to be a combination of triterpenes, such as betulinic acid, sterols, and polysaccharides. Chaga has demonstrated anticancer, antiviral, anti platelet, (2) anti-inflammatory, analgesic, (3) immune stimulating properties in vitro, and hypoglycemic effects in mice. (4) Chaga extract has inhibitory and proapoptotic effects against colon cancer (5) and hepatoma (1) cells. It also reduced toxicity associated with radiation (6) and inhibited tumor cell growth in animal models. (7) In some studies, Chaga demonstrates selective apoptosis in tumor cells with no effects on healthy cells. (1)

No clinical trials have been conducted to assess chaga's safety and efficacy for disease prevention or for the treatment of cancer, cardiovascular disease, or diabetes.

Constituents of chaga mushroom extract may interact with anticoagulant and antidiabetic drugs. [...]

Mechanism of Action

Chaga demonstrated hypoglycemic effects in mice with diabetes mellitus. (4) It's anti-inflammatory and pain relieving properties are thought to be via inhibition of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). (3) An extract of chaga reduced the oxidative stress in lymphocytes from patients with from inflammatory bowel disease. (8) Chaga also showed anti-mutagenic properties. (9) A hot water extract of chaga exhibited inhibitory and proapoptotic actions against colon cancer cell proliferation via up-regulation of Bax and caspase-3 and down-regulation of Bcl-2. (5) Aqueous extracts of chaga also inhibited growth of human hepatoma cells via arrest of the cell cycle in Go/G1 phase and inducing selective apoptosis. (1) The selectivity may also be a result of activation from a change in the pH of the tumor microenvironment. (11) Betulinic acid, a constituent of chaga, is cytotoxic and triggers apoptosis through a direct effect on the mitochondria of cancer cells. Other apoptosis-inducing factors result in cleavage of caspases and nuclear fragmentation. (7) Like many medicinal mushrooms, chaga is rich in beta glucans which have immunomodulating activities. Beta glucans bind to Complement Receptor 3 (CR3) that allows the immune cells to recognize cancer cells as “non-self.” (10)

Ok, now on to the next one.

Four Sigma Foods Instant Reishi, 20 Count. For me, the taste is pretty big anise (licorice). I've had it in hot water, hot coffee, a smoothie and cold Tejava.

In terms of the medicinal claims, let's see what the Life Extension Foundation has to say:

Over the past several decades, scientific research has intensified and focused on analyzing the hundreds of unique bio-active compounds found in the medicinal Reishi Mushroom. Just this year alone, three new compounds were discovered. With each new finding, intriguing medical applications for Reishi have emerged.

There is now a wealth of impressive data that demonstrates Reishi’s life extending properties [1, 2]  but also its significant ability to stimulate brain neurons, [3] search and destroy cancer cells [4] and prevent the development of new fat cells in obese individuals. [5]  As an example of growing science supporting Reishi, researchers using laboratory mice have detailed life span extension of 9% to more than 20% —the equivalent of 7 to nearly 16 years in human terms. [2, 6, 7]

As if these targeted benefits were not sufficient, Reishi’s numerous compounds show a therapeutic effect on asthma, [8] allergies, [9] autoimmune diseases, [10-15] Alzheimer’s [16] and Parkinson’s diseases, [17-21] diabetes, [22-26] liver disease, [27-36] and more.

Given Reishi’s complex composition of bioactive compounds, there is still more to discover. In this report, we will bring you up to date on how Reishi successfully targets a broad spectrum of deleterious factors of aging.

[See page 2 of the article for the references and fire up your Google Scholar.]

I've also combined the two of them in hot and cold ways, the latest discovery of that motivating me to actually promote it. Yesterday, I mixed the Chaga in a glass of Tejava, and though it flavors it, lots sinks to the bottom and ends up as kind of a gummy paste. So, I scraped with a spoon and swallowed it. There was still gummy sediment, so I just put a little water in the glass for soaking. Sure enough, in about 2 hours it was completely dissolved. So, this morning I took a fresh 1 Lt. bottle of Tejava and a funnel, and added 2 packets each of the Chaga and Reishi. Two hours later is was completely dissolved and wow do I have a smashing, dark, deep delicious tea.

In other words, the medicinal claims are what they are but ultimately, you should want to enjoy drinking it. That very much satisfied, I can recommend it to you with pride and in terms of medicinal benefit, that's just a bonus.

In terms of cost, soon after getting the boxes I checked on pricing and found they were about $25-30 per box, depending on where you source them. My first impression was that's expensive, but then I thought well, with 20 packets, it's $1.25 - $1.50 per serving—nowhere near Starbuck's profit margins (or bottled water companies, for that matter).

So, it shall remain an enjoyable deal for me. Give it a try. If you have, let us know what you think and by all means, if you have specific knowings of the medicinal aspects, those are welcome too.

Things I Grew Weary Of in 2014

I was really at a loss over what to blog about, New Year wise. Perhaps part of it is I've just never cared a wit about NY eve parties. I've probably slept through more ring ins than I've celebrated. So whilst driving to Whole Foods earlier today, listening to NPR, it hit me: 2014 was a year of getting really tired of lots of shit. In no particular order and probably not exhaustive:

~ I got completely tired of dietary dogma of every sort. "Paleoish" has been pretty decent as a framework, but has become largely meaningless to me with its endless array of products—many of them junk food, basically—in packages that are now "Paleo." Part of that is a weariness over static thinking when what people ought to be doing is embracing understanding in the context of real foods with a view toward getting better and better. For example, the idea that beans and lentils should be taboo, but here, "I've got 'Paleo' muffins, brownies and cookies," is ridiculous. Going forward, it's just real food in a context of mindful preparation and eating, without guilt or gluttony.

~ I got tired of all the narcissism inherent in social media, especially my own. When the first thing you often think about when doing anything is sharing it on Facebook, it's time to dump Facebook. Zero regrets. No return. Twitter serves most as an RSS alternative and a chance to put stuff out that doesn't call for a blog. Not a problem.

~ I got tired of caring about material things. In the last half of the year, where I bounced between an apartment in San Jose, a cabin in the mountains, and a trailer elsewhere in the mountains, I realized how very little I needed materially to be perfectly happy. No, happier, actually. Now I feel as though I have tons of stuff to get rid of.

~ I got ever so tired of the whole gay agenda, from top to bottom. It's like every time I turn on the TV or radio anymore, it's one more LGBT thing or another in some way or another, as though it's a perfectly "normal" thing. But it's not. It's a fringe thing, like a foot fetish, always will be. That's fine, what they do is none of my business, but that's kinda the point. I'm tired of an agenda that seems intent on making their business my business. I don't care and frankly, am tired of hearing about it.

~ I'm so tired of all versions of "support the troops" BS and I laf my head off every time someone talks about "the troops" in the context of "fighting" for our "freedoms."

Hopefully, 2015 will bring another handful of things to get over.

Teff Flour Has Resistant Starch

I've known Injera—made from teff, an ancient Ethiopian grain—are gluten free, but not that they have other benefits too.

Bob's Red Mill Whole Grain Teff Flour, 24-Ounce Packages (Pack of 4).

From an SBS piece: "Ms Radd said Teff is also nutritious and can be used for a variety of things.

'It tends to be a bit higher in a trace element called Manganese, and Copper and it does have the nutrients that all the other whole grains have, which is protein, good carbohydrates and fibre and so on. But it also includes something called resistant starch.'

'Now research on all whole grains has shown that fibre and resistant starch are incredibly important for our gut our bowel, because these components promote the growth of healthy bacteria which are known to be really important for our immunity. In fact they're now saying that about 80 percent of our immunity in our body occurs at the gut level,' she added."

If you do go to an Ethiopian restaurant, which I highly recommend, make sure they have injera made with teff and not wheat. The place I go to has both, so make sure you ask.

Is Resistant Starch By Means of Potato Starch Bad For You?

My thesis is that if it is, it's not because of anything Grace Liu of Animal Pharm is feverishly posting, in five parts so far. The time for vitriol and snark is over; so this time, it's just the facts, ma'am, and you can judge for yourselves.

...I mean, really. If she'd just say, "I don't recommend PS, I think there are better prebiotics," then fine. I'd still think it plays a role, but whatever. Chocolate. Vanilla. But this endless cycle of "proof" that "PS is destroying gutz!!!" is quite ridiculous, smelling a lot more like a campaign to discredit those of us who've been advocating it than honest, science-based inquiry.  Since I'm seeing little in the way of this "doctor's" conclusions being challenged, I guess it's time to do so semi-formally.

This addresses just the first part of the last of her posts on the topic: High Dose Potato Starch Can Make You Fatter, Insulin Resistant By Lowering GLP-1 AND ESPECIALLY If You Are Missing Bifidobacteria longum and Akkermansia mucinophila, aka SAD Microbial Fingerprint (Part V) NSFW (December 24, 2014).

First off, she cites Bodinham, 2014 and Table 1. Her take:

The drop in the gut hormone GLP1 was quite significant and was one of the few parameters that met statistically significance in this study.

Optimal gut health is supposed to yield better fat burning, leanness and metabolic improvements, no? Not high dosage RS2 it appears. Why? [emphasis added]

Then she lists everything from Table 1 as "proof" that RS2 is bad vis-a-vis gut health or downstream consequences. The problem is, almost everything on that table is labelled NS, meaning not statistically significant. The few things that are not labelled NS, she misinterprets as BAD!!!

For instance: "OMG GLP-1 decreased!" But what does Bodinham actually say?

Fasting GLP1 concentrations were significantly lower (P=0.049) following HAM-RS2 compared with placebo; however, there was a significantly greater meal GLP1 excursion with HAM-RS2 than with the placebo (P=0.009; Fig. 1C). [emphasis added]

...and

Indeed, GLP1, a well-defined incretin, was found to be elevated postprandially after HAM-RS2 intake, again a finding which was not found in our previous published work in those without diabetes (23) but has been reported in studies of RS in animal models (24). Interestingly, there was no effect of this elevated GLP1 on postprandial insulin levels and so any effect on postprandial glucose disposal may have been through insulin-independent mechanisms. GLP1 has been shown to directly increase muscle glucose uptake in rodent models (25), with the GLP1 receptor recently localized to human skeletal muscle (26). GLP1 acutely raises nitric oxide (NO) levels and so acute changes in both microvascular recruitment (27) and endothelial function (28) at the level of the muscle are believed to be involved in this effect. In the current study, glucose uptake across forearm muscle measured directly using A-V sampling was increased following HAM-RS2 intake and against a background of elevated GLP1 (Fig. 1) [emphasis added]

So, while fasting levels were lower, the after-meal effect was higher. GLP-1 has a half-life of 1-5 minutes in the blood. The lowered fasting GLP-1 is probably a good thing, but seen simply as a curiosity by Bodinham. To make a lesser point, her series is about potato starch, not HAM (high amylose maize RS2).

And just as an aside—a lesson in dishonest manipulation—here's the line item on pancreatic fat she makes a big—32.5% INCREASED, WTF!?!?!—deal of:

Screen Shot 2014 12 28 at 3 52 12 PM
 

Beyond the fact that the non-significant findings overlap in potential +/-, if you wanted to manipulate someone, would you tell them they were driving 13 in a 10 zone, or that they were breaking the speed limit by over 32%!

But here's the real kicker...this Bodinham 2014 study was conducted on "well-controlled T2 diabetics."

Bodinham's conclusion:

In conclusion, this is the first RS feeding study in human T2DM where the metabolic effects of RS (rather than a manipulation of dietary glycemic index/glycemic load (37)) have been investigated. HAM-RS2 intake improved meal glucose tolerance in patients with existing good diabetic-control due to a mechanism which appears to involve increased muscle uptake of FAs and increased S-IMCL. However, as a caveat, changes in both ectopic TG distribution and plasma TG were found, the clinical significance of which is unknown. Further work is now warranted to elucidate the molecular mechanisms within muscle tissue attributable to HAM-RS2, which would be vital in terms of recommending diet/exercise interventions to maximize the benefits for muscle glucose uptake. A larger scale intervention should now be undertaken in patients using high-fiber foods, with less well-controlled diabetes and over a longer time frame before a change to the evidenced-based dietary guidelines could be proposed. [emphasis added]

Bodinham is saying he thinks that RS2 has further improved T2D in these subjects —just like we've been saying here for 2 years in over 100 posts—not destroyed them in any way...but there were a few metabolic changes they were not expecting to see. These were not normal, healthy, people...they all had diabetes and were either taking meds (15 out of 17 participants) or being controlled through diet and exercise (2/17):

All participants had well-controlled diabetes (mean HbA1c levels of 46.6 (s.e.m. 2) mmol/mol at screening) and were diet and exercise controlled (2/17), taking metformin (13/17) or metformin and pioglitazone (2/17), were weight stable, and excluded if they had a history of gastrointestinal, cardiovascular, or other endocrine diseases.

OK. Then she invokes an older study, same dude, Bodinham 2012. She does the same thing: takes Table 1 and makes all of the NS items sound like a death sentence. Unfortunately for her, the only thing on Table 1 that was really significant was a reduction in fasting glucose. She explains this is really—trust her—a bad thing. Yes, you'll read that right:

Fasting glucose THIS TIME decreased BUT that is because all the spikes in post-prandial insulin is shoving all the glucose into adipose cells now and making them fatty which is clear by the increased TG and higher insulin-related consequences: higher systolic and diastolic blood pressures. wtf. I bet it lowered GLP1 where it is already low and lame in overweight and T2 diabetes subjects. [double emphasis added]

What did Bodinham say?

This study was designed to further explore the effects of HAM-RS2 on insulin secretion. To our knowledge this is the first study to demonstrate a significant improvement in first-phase insulin secretion following short-term supplementation with dietary fibre in the form of resistant starch (HAM-RS2). This work adds to our group’s previous findings of a positive effect of HAM-RS2 on insulin sensitivity. [emphasis added]

Let's take another look at her GLP-1 "theory."  In this 2012 study just cited, Bodinham said:

However, whilst there are data from rodent studies showing increases in GLP-1 following RS intake [15]–[17] data confirming this effect in humans are lacking, and indeed, one study in humans has shown that it may take a year of increased fibre intake (increase of 20 g/day) to increase GLP-1 secretion.

But just 2 years later, in 2014, he did show that RS2 raised postprandial GLP-1 in the human T2D subjects. So, all of this GLP-1 "proof" is completely wrong, and seems intentionally misleading.

Indeed, GLP1, a well-defined incretin, was found to be elevated postprandially after HAM-RS2 intake, again a finding which was not found in our previous published work in those without diabetes... (Bodinham, 2014) [emphasis added]

Yet, here's what she says says:

What is GLP1?

I love GLP-1.

It helps us to burn and remodel fat. "Glucagon-like peptide 1 (GLP-1), a gut-derived peptide, has been reported to have profound effects on metabolism and to reduce insulin resistance (Yang et al 2013)." High protein diets raise GLP-1 and satiating PYY gut hormones to cause nice fat burning. It appears that high dosage raw starches causes a downward trend of this fat-burning molecule. Ruh-OH. This time it does not depend on either the pre-existing gut or what human gut symbions are missing. It happens in healthy human subjects in several trials so far. [emphasis added]

So, she uses a guy's study to try and "prove" what's not proved, implying it's relevant to healthy people; is going to make them fat, when it actually involved diabetic people and improved their status on balance. Then, she finally acknowledges the diabetic point, but only to make a false distinction in healthy people, claiming results that don't actually exist.

OK, I think I've wasted enough time on this. Really, the whole post is a mess. The links don't jive with what she's saying. She's just making stuff up, as in the foregoing. I suspect that a similar close examination of her Parts 1-4 are going to yield similar poison fruit. And, if you have a good memory, you might even remember when she wrote this in her own comments:

(Akkermansia is good for us ;) lol unless overgrown in defective barriers

So...

Unfortunately, so very many just read post titles, skim—maybe check a few sycophant comments—and chalk it up to another "excellent post" by the "Gut Goddess" Fake Doctor. In contrast, there are over 130 posts here on RS and GutGeneral, over 10,000 comments, over two years. The positive anecdotes of N=1,000+ are legion.

I can only conclude that she wants to stop or inhibit that for her own selfish gain, because she has statistically insignificant relevance to do with any shred of it. She's made no long-term meaningful contributions—often inhibiting—but rather, only tried to dishonestly garner an unearned limelight.

Finally, she's spent five posts on a straw man, because except for diabetics and those who insist on remaining VLC, high dose potato starch was never touted as the be-all-cure-all. Not even from the very first post on RS. I've addressed this before.

Now, this simply serves as something linkable next time someone asks me to address her idiotic posts that they don't want to take the time to examine closely themselves.

Ina Garten’s Warm French Lentils

I watch quite a bit of Food Network when I don't really want to search for anything to watch, so it's whatever comes up. One of the shows I tend to like best is Ina Garten's Barefoot Contessa, at least when she prepares simple rustic cuisine.

So the other day, I saw her make a warm French lentil salad and had to give it a go myself. It's super easy. Most curious about it is boiling the lentils with a whole peeled onion stabbed with cloves and a turnip cut in half (which are both discarded after cooking).

IMG 2830
click to enlarge

A few key things to emphasize in terms of the preparation.

  1. Brining the lentils to a boil and immediately turning down to a light simmer, uncovered for 20 minutes, yielded perfect al dente lentils, ideal for a salad dish.
  2. Yes, only 3 minutes for the carrots and leek, then another minute with the garlic (I used 4 cloves). Remove and let sit in the same pan until the lentils are done.
  3. Soon as the lentils are done, drain and add them to the veggies, then stir in the dressing while it's still hot.
  4. If you taste it immediately it's going to taste salty. Patience. After it settles, it'll be perfect.
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Click to enlarge

I found salmon to be a nice pairing, and you don't even need to start it until the lentils are done and resting. Preheat your oven to 425. Pan fry the salmon on medium high, skin side down for 3 minutes. Then season with salt & pepper and drizzle some EVOO, and put the pan in the oven for 6 minutes.

Bon appétit!

Oral Glutathione Supplementation Is Bioavailable After All

Way back in 2007, Art De Vany used to talk about his glutathione supplements and upon looking into it, I heard from numerous sources that it's simply not bioavailable taken orally. Glutathione is generally regarded as the body's master anti-oxidant.

Glutathione (GSH) is an important antioxidant in plants, animals, fungi, and some bacteria and archaea, preventing damage to important cellular components caused by reactive oxygen species such as free radicals and peroxides.[2] It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side-chain and the amine group of cysteine (which is attached by normal peptide linkage to a glycine).

It's not an essential nutrient, since we synthesize it ourselves from the amino acids L-cysteine, L-glutamic acid, and glycine. So, two studies:

jf 2014 01338z 0007
 

Longtime reader and email correspondent Scott Miller excerpted this from the full text of the first study.

...Witschi et al. (1992) have observed no increase in plasma GSH levels after a single oral supplementation of GSH to healthy human volunteers at 0.15 mmol/kg body weight. The present study confirmed these results [Figure 5(a) and (b)]. Based on these results, it has been suggested that the oral supplementation of GSH does not affect blood GSH levels.

It has been demonstrated that plasma proteins, including albumin, can bind to low molecular weight thiol-compounds through a disulfide bond. Therefore, there is the possibility that supplemented GSH may be transported as a conjugate of protein in the blood, and this has not been examined. In the present study, the effects of the supplementation of GSH on plasma protein-bound GSH levels were examined...

...The present study also demonstrated that only a negligible amount of GSH was bound to plasma protein before the supplementation of GSH. However, the protein-bound GSH significantly (P < 0.01) increased from 60 to 120 min after the oral supplementation of GSH. This is the first report to demonstrate an increase in GSH in the human blood fraction by the oral supplementation of GSH. The protein bound form GSH level in plasma after supplementation of GSH is much higher (>1000 times) than other food-derived peptides such as Val-Tyr 25 and Ile-Pro-Pro 26, but less than the food-derived collagen peptides in human blood.

It has been thought that orally administered GSH is successively degraded to cysteinyl-glycine, cysteine, and glycine by γ-glutamyl-transferase and peptidase. Cysteine could be used for GSH synthesis in cells. Increased levels of protein-bound GSH might be derived from the newly synthesized GSH. The present study also detected fragment peptide (Cys-Gly) and precursor peptide (γGlu-Cys) as protein-bound form in human blood, which suggests some GSH is synthesized from degradation products of GSH.

However, an early study by Kubo (1968) that used 35S-labeled GSH and paper electrophoresis has suggested that GSH could be directly absorbed from the small intestine into rat portal blood. Therefore, there is a possibility that supplemented GSH is directly absorbed into human blood and bound to plasma protein. To solve these problems, further studies on the metabolic fate of supplemented GSH that use 13C-labeled GSH are in progress...

And from the second study.

GSH levels in blood increased after 1, 3 and 6 months versus baseline at both doses. At 6 months, mean GSH levels increased 30-35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells in the high-dose group (P < 0.05). GSH levels increased 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group (P < 0.05). In most cases, the increases were dose and time dependent, and levels returned to baseline after a 1-month washout period. A reduction in oxidative stress in both GSH dose groups was indicated by decreases in the oxidized to reduced glutathione ratio in whole blood after 6 months. Natural killer cytotoxicity increased >twofold in the high-dose group versus placebo (P < 0.05) at 3 months.

Life Extension Glutathione, Cysteine and C, 750 mg. The question is, how much do you need, and is there a potential downside? It's all very complicated, all intertwined—in my view—with hormesis, autophagy, apoptotic clearance, and the push-pull, yin-yang relationship between methylglyoxal and glutathione. I'm intuitively resistant to the idea that if some is good, more must be better. So many processes seem to have opposing counterparts—inflammation being a classic example. Yes, chronic inflammation is bad, but many forms of acute inflammation are beneficial. Negative feedback mechanisms are enhanced by opposing positive feedbacks, and vice-versa. It's the way nature operates to balance on the head of a pin.

Those keeping tabs might recognize that much of this kind of thinking was recently introduced in part 1 of a new series: The Hormesis Files: Chronic Ketosis and The Case of The Missing Glutathione. Part 2 is coming soon, probably first part of the new year. But here's one of the many relevant portions from that first post, which I encourage you to read.

Ketogenic Diets, Hormetic Oxidative Stress and Glutathione

What Dr. Eades couldn't have known, back in 2008, is that the same group of researchers (sans Jarrett) published another exciting paper in 2010—again with rats—showing that a ketogenic diet appears to produce its therapeutic benefits with a hormetic dose of oxidative stress, which activates the cytoprotective nuclear factor erythroid 2-related factor 2 (Nrf2)-signaling pathway. The Nrf2 pathway activates genes that are involved in detoxification of chemicals and antioxidant defense. That kind of stress is a good thing, at the right dose. The Nrf2 pathway itself is described by some as a key hormetic pathway and has been linked to longevity. And in fact, some studies suggest that trying to avoid low levels of oxidative stress is counterproductive.

However, the researchers stumbled onto a potential troubling side effect of ketogenic diets after a few weeks...

...If you didn't catch that, what this study showed is that chronic ketogenic diets (3 weeks) appear to deplete the liver of glutathione in the same way as taking Tylenol every day!

So, perhaps those most in need of supplementing glutathione, now that we know it's bioavailable, would be those on low carb and ketogenic diets—as well as those who take Tylenol, or perhaps other analgesics or NSAIDs.

Have Yourself A Merry Little Mythmas

I don't think anyone came up with the reference for Santa as God Lite before I did, in around 1993.

The Story of the WWI Christmas Truce

Last time I brought this up was a Christmas time post in 2006. Time to haul it out again.

640px Illustrated London News  Christmas Truce 1914
WWI Christmas Truce, 1914

From Wikipedia (a worthy cause to donate to this time of year)

The Christmas truce (German: Weihnachtsfrieden; French: Trêve de Noël) was a series of widespread but unofficial ceasefires along the Western Front around Christmas 1914. In the week leading up to the holiday, German and British soldiers crossed trenches to exchange seasonal greetings and talk. In areas, men from both sides ventured into no man's land on Christmas Eve and Christmas Day to mingle and exchange food and souvenirs. There were joint burial ceremonies and prisoner swaps, while several meetings ended in carol-singing. Men played games of football with one another, giving one of the most enduring images of the truce.

And: Soldiers Against War - The Story of the World War I Christmas Truce by John V. Denson; Quoting from Stanley Weintraub, Silent Night: The Story of the World War I Christmas Truce.

"Lieutenant Geoffrey Heinekey, new to the 2nd Queen’s Westminster Rifles, wrote to his mother, ‘A most extraordinary thing happened. . . Some Germans came out and held up their hands and began to take in some of their wounded and so we ourselves immediately got out of our trenches and began bringing in our wounded also. The Germans then beckoned to us and a lot of us went over and talked to them and they helped us to bury our dead. This lasted the whole morning and I talked to several of them and I must say they seemed extraordinarily fine men . . . . It seemed too ironical for words. There, the night before we had been having a terrific battle and the morning after, there we were smoking their cigarettes and they smoking ours."

"War is the health of the state," Randolph Bourne, 1918. From Wendy McElroy:

The thrust of Bourne's essays is to attack the sanctity of war by showing how it leads to the moral collapse of society by kicking out the props (the principles) of peaceful interaction upon which society rests.

In essence, Bourne addressed the moral consequences of war upon a post-war society which had abandoned individualism in favor of "the herd-machinery." He eloquently argued that post-war America would be morally, intellectually, and psychologically impoverished. By this observation, Bourne did not mean that peace time America would struggle under the increased bureaucracy that never seems to roll-back to pre-war levels. Many historians have made this point. Bourne addressed the less tangible, though arguably more significant, costs of war. For example, post-1918 America would be burdened by intellectuals who had "forgotten that the real enemy is War rather than imperial Germany." In converting World War I into a holy war, the intellectual and psychological groundwork was being laid for future instances of what he termed "the sport of the upper class" -- global conflict.

Merry Christmas spirit.

Update: Turns out there's a 2005 French film that tells the story. It's not on Netflix, but it's free streaming on Amazon Prime.