Monday, March 17, 2014

Persorption of Resistant Starch Granules: Should We Be Worried?

I recently wrote a piece that I thought I would try to publish in one of the main-line nutritional journals on a topic in the field of starch that no one in my field seemed to know anything about when I brought up the subject to them. However, when I cast about looking for a journal that would publish the piece, which was not quite long enough for a mini-review, too long for a brief communication, and certainly was no new research paper in its own right, I found only rigid requirements that would not bend and high publishing fees that I can not afford at the time of writing this piece. Thus, I am instead publishing the piece online for all eyes to see.

Credit must be given to Doctor Ray Peat for first introducing me to the persorption phenomenon, which is really a very old discovery. The term refers to the paracellular transport of solid particulates across the intestinal “barrier” – which, coming from someone with numerous food allergies, is a laughable term in itself – and into the lymphatic and circulatory systems, including our main topic of discussion over these last few posts, the starch granule.

Because the research on starch granules was mostly old, not to mention in German, I believe that it has largely failed to cross the Atlantic and penetrate the consciousness of the larger food science and nutrition communities who have investigated the effects of dietary fibres, such as the various forms of resistant starch, ad nauseum. What little has crossed over has been in the pharmaceutical and medical journals, and so I set out to write a short piece on the matter to apprise my fellow food scientists of the phenomenon. I uncovered enough disturbing effects of persorbed starch granules and solid bodies that make their way into the tissues that this post will not be easily accepted. Let the reader judge for himself.

The paper can be found below the break.

Persorption of “Resistant” Starch: Should We Be Worried?

Moore, S. A.

1006 Lincoln Way, Unit #101, Ames, IA 50011, Phone: (540) 834-8924,


The fact that a portion of starch survives digestion under conditions of in vitro digestion with porcine pancreatic α-amylase as an analogue for the human enzyme was first noted by Englyst and co-workers (1982). This fraction of starch was later found to have physical significance in that it also survives in vivo digestion and thereby “resists” absorption in the small intestine of human ileostomy patients (Englyst and Cummings 1987) and was termed “resistant starch” (RS). In following years, the form, morphology, and chemical characteristics of native and chemically-modified starches that qualify as RS were elaborated.

Because RS has a functional, rather than chemical, definition, a number of different classifications or “types” of RS have been enumerated (Englyst and Hudson 1996). RS Type 1 (RS1) is that which is inaccessible to the peptic enzymes, such as in whole grains or coarse meal; RS Type 2 (RS2) is raw starch granules that resist enzyme hydrolysis based on structural characteristics, although some authors (e.g. Alsaffar 2011) make a distinction between thermally stable granules with elevated amylose contents (i.e. ≥ 50% amylose, RS2a) that survive most cooking processes and those with normal amylose contents, such as starch from raw potato or green banana (RS2b); RS3 is retrograded starch crystallites formed by the reassociation of starch chains disordered during cooking; RS4 covers a number of chemical modifications of starch granules that resist digestive enzymes based on chemical characteristics; finally, RS5 is the helical inclusion complex formed between starch chains and lipids and may be either endogenous in the starch source or produced industrially (Hasjim and others 2010). RS has attracted considerable attention for its potential in diabetic therapy, in weight management, and for improving and modulating the microbial constitution of the intestinal microbiome. These aspects have been recently and thoroughly reviewed elsewhere (Birt and others 2013).

Yet prior to and concurrent with the development of the definition of RS, a different phenomenon relating to ingestion of starch was also investigated. The process by which intact solid microparticles on the order of several micrometers exhibit paracellular translocation across the intestinal epithelium into the portal blood, lymph, and eventually into the urine, organs, and capillaries was first noted by Herbst (1844) in the dog and confirmed by Donders (1851) in the frog and rabbit using starch granules as a solid particle. The phenomenon was thus originally termed the “Herbst effect”. Hirsch (1906) was the first researcher to confirm that this effect is also observed in humans, finding that starch granules were present in the urine of volunteers ingesting raw starches of multiple botanical sources several hours post-prandium. This phenomenon came to be termed “persorption” of the particle to distinguish from absorption of dietary components, such as simple sugars. The effect in man was independently confirmed by Verzàr (1911) after attempting to disprove the earlier observations and was not thoroughly treated until a series of reports by Volkheimer investigated the physiological effects and end destination of many types of persorbed particles, including starch granules (Volkheimer 2001). The mechanism for the translocation of solid particles across the intestinal barrier is a combination of kneading into the mucosa via peristalsis and the compression and suction of villous “pumping” action (Volkheimer 2001). To date, raw starch granules have been found in blood (Volkheimer 1974), urine (Hirch 1906, Verzàr 1911), as embolisms in small arterioles (Volkheimer 1974, Freedman 1991), in cerebrospinal fluid (Volkheimer and others 1962), in mesenteric lymph nodes (Hodges and others 1995, Hazzard and others 1996), in the chyle (Volkheimer 1974), and in the lungs (Lamb and Robert 1972). The presence of starch granules in all of these systems suggests that persorbed particles may enter the circulation via the portal vein or lymphatic system. Freedman (1991) hypothesized that starch granules embolizing arterioles in the brain could result in the death of local neurons. Giltzelmann and Spycher (1993) likewise expressed concern over the use of cornstarch in the treatment of glycogen storage diseases in juveniles (Lee and others 1996), which they considered potentially problematic due to the isolated starch granules being very readily absorbed in their young patients.

While unmodified starch is itself relatively inert, any solid microparticle may elicit an inflammatory, immunological response termed a foreign-body giant cell in which macrophages are recruited and fused around the foreign body. Foreign-body giant cells are observed in lungs, lymph nodes, and peritoneal tissue in which intact starch granules have penetrated (Michowitz, Ilie, and Stavorovsky 1983, Lamb and Robert 1972).

Contemporary investigations of the persorption mechanism have shown that microparticles up to 150 μm are transported across the endothelium, although microparticles from 7 – 70 μm are most readily absorbed (Volkheimer 2001). Notably, many common food starches lie in this optimum size range for persorption (Table 1).

Table 1. Particle size range and distribution of common food starches

Particle Size (μm), long axis
3 – 8, compound
2 – 15, compound
5 – 20
High-Amylose Maize
6 – 15
<10, 22 – 36, bimodal
15 – 75
Latex Microspheresb
aJane and others 1994
bMcMinn, Hodges, and Carr 1996

Because the lines of inquiry into starch properties and persorption of solid microparticles have advanced independently, and because previous studies have assumed an effective spherical shape of starch granules for sake of simplicity, no report on the persorption of asymmetric starch granules has yet appeared. This dearth of research becomes much more significant in the context of high-amylose maize starches (RS2a), which present elongated granules formed by the fusion of nascent starch granules in amyloplasts due to amylose-amylose helical interactions and are not fully dispersed in normal cooking conditions due to their elevated conclusion gelatinization temperature above the boiling point of water (Jiang and others 2008, Jiang and others 2010). Whether the persorption rate of these long granules corresponds more closely with that of the shorter or the longer axis (6 - 15 μm) is not known (Jane and others 1994).

No study has appeared differentiating between the susceptibility of the different types of RS to persorption. However, encapsulation, as in food matrices constituting RS1, is no protection against persorption after the motions of chewing and peristalsis; starch granules from corn, rolled oats, and cold cereals, such as muesli, have been observed in the blood of human subjects 30 min after ingestion (Nagele and others 2013).

To date, no survey of the persorption of any non-native starch has been reported in the literature. As such, questions as to the toxic effects or intensity of the foreign-body response to chemically modified starch transported to peripheral tissues via the persorptive mechanism remain unanswered. A strong foreign-body response and inflammation of the peritoneal cavity due to infiltration of the highly-cross linked corn starch used as a lubricant in surgical gloves has been reported in the medical literature (Michowitz, Ilie, and Stavorovsky 1983).

Saturated free fatty acids exert a lipotoxic, apoptotic effect on a number of tissues and cell types in vivo and in culture, including the pancreas (Weinberg 2006), muscle (Artwohl and others 2009), sex organs (Mu and others 2001, Lu and others 2003), heart (Vandervusse and others 1992), vascular endothelium (Artwohl and others 2008), and kidney (Weinberg 2006). The debranched high-amylose maize-palmitic or stearic acid complex described by Hasjim (2010) and termed RS5 shows a coating of crystalline fatty acids on the surface of starch granules (Reed, personal communication); whether these crystalline fatty acids may elicit an inflammatory or foreign-body response in peripheral tissue is not known. Similarly, no report has appeared on the quantity of chemically modified starch granules that appear in bodily fluids compared to native counterparts.

Removal of persorbed starch granules from the tissues in which they come to rest appears to be a time-critical process. The predominant means of removal of persorbed particles is via the veinous blood and urine, up to 90% within the first 4 h after ingestion (Volkheimer 2001). Starch particles that remain are largely those embolized in small arterioles or peripheral organs and may therefore participate in foreign-body giant cell reactions. Because the only modified starch granulatoma reported in the medical literature arise from the cross-linked starch used in gloves (Michowitz, Ilie, and Stovorovsky 1983) and condoms (Saxén, Kassinen, and Saxén 1963), the question of whether other types of chemical modifications influence the residence time of persorbed starch granules in tissues should be investigated.

As the benefits of resistant starches in the management of chronic conditions become more widely known and find increasing use in food products as a dietary fibre supplement, the phenomenon of persorption has been largely neglected. Because the starch science community has not conducted any significant research in this area, leaving the advancement of our knowledge of the mechanisms of persorption to the medical and pharmaceutical industries, the technologies and knowledge of the one field have not crossed over to the other, leaving significant gaps in our knowledge of how resistant starches may behave in the body outside of the confines of the alimentary canal. To summarize, the following areas appear to be most in need of further investigation:

1)      Whether the nature of chemical modifications of starch granules, as in RS4, may result in increased dispersion across the intestinal membrane and deposition in peripheral tissues;
2)      Whether chemical modifications of starch granules may increase residence time of persorbed starch granules in peripheral tissues;
3)      Whether observations that glove starch induces inflammatory giant-cell reactions commute to persorbed “resistant” starch granules;
4)      Whether chemical modifications of RS4 or RS5 may cause local excitation and cytotoxicity by auxiliary mechanisms.

Works Cited

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Artwohl, M.; Lindenmair, A.; Sexl, V.; Maier, C.; Rainer, G.; Freudenthaler, A.; Huttary, N.; Wolzt, M.; Nowotny, P.; Luger, A.; Baumgartner-Parzer, S. M. Different mechanisms of saturated versus polyunsaturated FFA-induced apoptosis in human endothelial cells. Journal of Lipid Research. 2008 49, 12, 2627 – 2640

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  1. I researched this awhile back and thought I would share my notes, in case this actually were to concern anybody…

    Volkheimer used 200g of potato starch to cause embolisms in his subjects. Think about that for a moment. That’s an enormous dose of starch granules. Even people who eat raw potato starch—for the resistant starch—rarely consume more than 40-50g per day. And it would be a challenge to eat more than 8-12g of starch granules in a day from food.

    Volkheimer believed that persorption was some kind of flaw in the gut that allowed starch granules to leak through. And if starch granules that were larger than a red blood cell (6-8 microns in diameter) could get stuck in the blood vessels and cause blockages and embolisms. This was theorized because some blood vessels are so tiny that the red blood cells must travel single-file to pass through. However, it’s highly unlikely that the lymph and blood vessels are not prepared to handle such intrusions. If not, I doubt our species would have been able to tolerate Underground Storage Organs (USOs). Furthermore, it’s well recognized that the liver is specifically designed to filter such particles from the blood.

    If we are going to worry about starch granules—which are often larger than the diameter of a red blood cell—then we must also worry about anything else that fits this criteria:

    Activated charcoal, has a particle size range of 1-150 microns, and seems to have the ability to detoxify the blood. These are surely persorbed as Volkheimer specifically mentions “charcoal” being persorbed in his subjects.

    As pointed out, above, carrots have a starch granule size of 4-26 microns, and should therefore cause embolisms according to Volkheimer.

    Raw unfiltered honey, contains pollen that range from 2.5 to 1,000 microns! Most honey producers will filter the pollen out their honey with sieves that range from 50 microns (heavily filtered) to 600 microns (lightly filtered). But, as we know, Hunter Gatherer populations tend to eat a lot of honey and they didn’t filter their honey with modern sieves. So, I can imagine lots of large and small pollen getting persorbed by Hunter Gatherers every day.

    It would seem that persorption probably isn’t some kind of design flaw in our bodies. Combine that with the practice of geophagy (eating dirts and clays) and you get the picture that these particles are probably supposed to temporarily roam through our blood vessels. Persorption appears to be an intentional mechanism with a purpose.

    Obligate carnivores consume raw meat, which is rich in glycans (glycolipids, glycoproteins, etc.), which is what we know of as animal fiber. Animal fiber is persorbed as well, and likely has a very wide range. Some of these glycans are probably used throughout the body. In fact, any fiber particle that is eaten from any food will surely become persorbed in the same manner.

    Glycosaminoglycans (GAGs) from blueberries literally 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....

    1. ...Beta-glucans—usually acquired from mushrooms—are are considered to be “keys” that turn on the body’s macrophage defense (immune) system. David Wolfe describes how they work, like this:

      David Wolfe said: “Specifically, here is how it works: the beta glucans found in [mushrooms], other herbs, foods, or supplements enter the body via the small intestine and are captured by the macrophages. To be activated by beta glucans, the macrophages must first “ingest” the beta glucans through specific beta glucan receptor sites on these cells’ membranes. Then the macrophages internalize and fragment the beta glucans within themselves and transport these fragments to the bone marrow (helping stimulate more stem cells) and to the reticuloendothelial system (RES). The beta glucans fragments are eventually released by the macrophages and taken up by other immune cells, including neutrophils , monocytes, natural killer cells, and dendritic cells, leading to numerous enhanced immune responses, 19 including adaptability against and deactivation of foreign pathogens, genotoxicity (toxins harmful to genetics), cancerous growth formations, and environmental toxicity.

      According to a study that appeared in the Journal of Hematology and Oconology in 2009, “animals pretreated with purified glucan particles are subsequently more resistant to bacterial, viral, fungal, and protozoan challenge, reject antigenically incompatible grafts more rapidly and produce higher titers of serum antibodies to specific antigens.”

      SOURCE: Wolfe, David (2012-09-11).

      When you put it all together, you can sort of see the big picture of what the body does with persorption. It selectively persorbs particles, perhaps based on their size, so that these particles can get exposed to the entire body and the immune system in a matter of minutes. And then the unneeded particles disappear — often filtered out by the liver or lymphatic system.

      I suspect as long as you are eating quantities of particles that are within the range of normal human consumption, you are fine. The amount of RS that most people consume supplementally (5g to 40g) is within the normal limits that would have been eaten by Andean indians or even Asians consuming Dioscorea opposita (a tuber high in resistant starch granules). I don’t see how that could be especially problematic within the context of the naturally occurring persorption that we have always been exposed to.

      The concern with persorption, if there is one, is likely from man made particles that the body may not be prepared to filter.