"Occult" Calcium and Copper in "Gums" and Other Soluble and Insoluble Fibers: Relevance to the Adjunctive Management of Depression

These articles [Fang et al., 2007: (http://www.ncbi.nlm.nih.gov/pubmed/17910512); Debon and Tester, 2001: (http://cat.inist.fr/?aModele=afficheN&cpsidt=987245); Leroux et al., 2003: (http://cat.inist.fr/?aModele=afficheN&cpsidt=14819835); Nasir et al., 2008: (http://www.ncbi.nlm.nih.gov/pubmed/18267216)] show that gum arabic and other gums (comprising high-molecular-weight polysaccharides and glycoproteins, etc.) contain significant amounts of "occult" calcium (Ca2+) and magnesium, primarily, and also small amounts of copper and zinc. The amounts of zinc and copper listed in the table on page 4 of Debon and Tester (2001) are actually (ug zinc or iron)/(g of "gum") (micrograms Zn or Cu/g gum), not mg/g. The authors mention that in the text on that page, and those values are consistent with the values reported in other articles. Debon and Tester (2001) found that the gum arabic (also known as gum acacia or acacia fiber, etc.) samples contained a mean of 7.82 mg Ca2+/g gum, and the values for pectin, guar gum, and carrageenan are, respectively, 1.53 mg Ca2+/g, 0.79 mg Ca2+/g gum, and 30.3 mg Ca2+/g gum. Fang et al. (2007) found that a 20 % (w/w) aqueous solution (20 g gum arabic/100 g solution) of gum arabic contained 1417 ppm Ca2+. One ppm = 1 ug/g. So that works out to about 7.1 mg Ca2+/g gum arabic. Leroux et al. (2003) found that sugar beet pectin contained 5700 ppm Ca2+, and that's 5.7 mg Ca2+/g sugar beet pectin. That gives one an idea of the amounts of unlabeled calcium that some of these things might contain. If one applies the 7.82 mg/g number, for example, one sees that 30 g of gum arabic might contain up to about 235 mg Ca2+. There's also magnesium, but there's research that implies that some of these gums may sequester magnesium and increase the gums' intestinal (and urinary) excretion [Eby and Eby, 2009: (http://www.ncbi.nlm.nih.gov/pubmed/19944540); Nasir et al., 2008]. Acacia gums of the family Gummiferae (similar to gum acacia, which is from the family Leguminosae) contained mean copper contents of 4.36 and 13.0 ug copper/g of Acacia gum (4.36 and 13.0 ppm) and 6 and 9.5 mg calcium/g gum [Mhinzi, Mghweno, and Buchweishaija, 2008: (http://linkinghub.elsevier.com/retrieve/pii/S0308814607009983)] . That works out to about 131-390 ug copper per 30 g of gum acacia or gum arabic, assuming that the "inter-family" similarities in calcium contents imply that the two families contain similar copper concentrations. Harmuth-Hoene and Schelenz (1980) [Harmuth-Hoene and Schelenz, 1980: (http://www.ncbi.nlm.nih.gov/pubmed/6251185)] found that the endogenous copper concentration in guar gum was 0.40 ppm (0.40 ug/g), and it looks like guar gum might contain less copper than some of these other fibers. In general, however, it looks like some of these soluble fibers might contain smaller amounts of copper (and, perhaps, also calcium) per gram of fiber (insoluble or soluble) than even some of the "best" commercial "whole-grain" "goodness-filled" cereals contain. There's nothing terrible about cereal, but some of these cereals that are "healthy" in relation to their glycemic indices have unsettlingly-large amounts of copper in them, in my opinion. The USDA nutrient tables are useful for estimating one's copper intake (http://www.nal.usda.gov/fnic/foodcomp/Data/SR17/wtrank/sr17a312.pdf), but there's a typo in that document on the copper contents of foods. The numbers given are in milligrams, not micrograms. For example, a number like 0.345 means 345 micrograms (mcg) of copper per mass given, and that's equivalent to 0.345 milligrams copper. (To find the USDA documents for other nutrients/minerals, search on google with the terms USDA copper content" or whatever other nutrient, and the title will be something God-awful, along the lines of "release 18 December 23rd 1993" or the like.) It's appalling that one has to keep trying to check to see what the RDA is now, and I don't even know if they mean for males or females. I personally make every attempt to avoid dealing with numbers that are based on the RDAs, given that, for example, the RDA for copper for adult males is different from the RDA for adult females. The way to use a USDA table is to convert all of the numbers into ug nutrient/g food (mcg/g) or mg nutrient/g food. Take a copper content of 345 mcg or whatever, and divide by the mass of the serving of food in question. When one does that, the numbers are relatively consistent across similar foods. If I'm looking at a nutrition label on a food and can't tell what RDA "thing" the label is referring to, I'll just type the name of the food into google scholar and add the words "copper content" or whatever. The articles usually provide the concentrations in ppm (ug/g) or mg/g or % (w/w) (which is g nutrient/g food, or g/g, unless otherwise specified).

These types of issues could be relevant to the treatment of depression or other psychiatric disorders, given the potential that exists, in my opinion, for small changes in dietary calcium and copper to produce low-level hemostatic effects and, by that and other mechanisms, in my view, to exacerbate depression or brain functioning in a more general sense, at least in some people. It's worthwhile to note that the soluble fibers can sequester small amounts of metals, and that effect could, in theory, offset the supposed increases in copper or calcium absorption that one might expect to see in response to the ingestion of one or more of the fibers. I was going to discuss some of the research on depression and psychiatric symptoms in relation to copper and calcium metabolism, but this posting is getting too long. One of the points I was going to make is that one could replace a healthy cereal with some source of soluble fiber and conceivably get less copper, less calcium, and substantially more soluble fiber than one would get from the cereal itself, with milk. Another downside of milk is that manufacturers are still adding preformed vitamin A to it, and preformed vitamin A can produce toxic effects on the liver and parts of the brain, among other tissues, in relatively small amounts. Another approach would be to dilute the milk with water. I'm not suggesting that these are likely to be practical approaches for most people, but I just throw the ideas out. As discussed in past postings, there's research that suggests that excesses of dietary calcium can produce increases in platelet activation, either by increasing the rates of calcium influx into platelets or simply serving its functions in the coagulation cascade. In my opinion, excesses of dietary copper have the potential to exacerbate depression, in part by producing hemostatic effects. Copper is incorporated into coagulation factor V and factor VIII during the post-translational processing of those proteins (http://scholar.google.com/scholar?hl=en&q=copper+%22factor+VIII%22+OR+%22factor+V%22&btnG=Search&as_sdt=2000&as_ylo=&as_vis=0), and there's abundant evidence that excesses of intracellular copper have been associated with exacerbaions of symptoms of depresssion and other psychiatric conditions, etc. Essentially, it's well-known, and I'm not going to collect a lot of references at this point. But it's interesting that there's all this research focusing on the increases in platelet activation that can occur in association with depression (http://scholar.google.com/scholar?hl=en&q=depression+platelet&btnG=Search&as_sdt=2000&as_ylo=&as_vis=0), and the assumption seems to generally be that this platelet activation is going to mainly have relevance as an explanation for the association of heart disease with depression [for example, see Nemeroff and Musselman, 2000: (http://www.ncbi.nlm.nih.gov/pubmed/11011349)]. But there's a lot of research showing, for example, that elevations in serum antiphospholipid autoantibody titers can occur in people who have been diagnosed with depression or some other disorder (http://scholar.google.com/scholar?hl=en&q=depression+antiphospholipid&btnG=Search&as_sdt=2000&as_ylo=&as_vis=0); (http://scholar.google.com/scholar?hl=en&q=antiphospholipid+psychiatry&btnG=Search&as_sdt=2000&as_ylo=&as_vis=0)]. Elevations in serum antiphospholipid autoantibody titers are very well known to produce hemostasis and increases in platelet activation or platelet-dependent thrombosis (http://scholar.google.com/scholar?hl=en&q=antiphospholipid+hemostatic+OR+hemostasis+OR+platelet+OR+thrombogenic+OR+thrombosis&btnG=Search&as_sdt=2000&as_ylo=&as_vis=0). Thus, the increases in platelet activation could be a cause of the depression. I want to emphasize, however, that using any old platelet-anti-aggregatory approach is likely to be problematic, at best, and could be disastrous, given the association of a lot of these plant (herb)-derived or other antiplatelet compounds with hemorrhages and whatnot. There's a lot of other indirect evidence that I'm not going to get into now.

Rambler on L-Methylfolate and Tetrahydrobiopterin, in Relation to the Brain and to Influenza-Induced Hemostasis

I was just going to mention that the use of L-methylfolate could be another approach to the management of post-influenza hemostatic effects, given that L-methylfolate and other reduced folates appear to be active as cofactors for tetrahydrobiopterin (BH4)-dependent enzymes. It's something that researchers could investigate and that one would want to discuss with one's doctor. I think it might primarily be useful, conceivably, after the acute illness has abated, in part because BH4 is a cofactor for inducible nitric oxide synthase (iNOS) enzymes and not just eNOS. I think the higher dosage range of L-methylfolate might be useful under certain circumstances, such as in the "aftermath" of a viral illness and the oxidative stress that is associated with viral illnesses. Oxidative stress would tend to increase the rate of degradation of BH4 and to potentially increase the neopterin/biopterin ratio, thereby potentially leading to further, functional inhibition of either the formation of BH4 or of BH4-dependent enzymes (eNOS, tyrosine hydroxylase, and tryptophan hydroxylase). For example, Mittermayer et al. (2005) [Mittermayer et al., 2005: (http://ajpheart.physiology.org/cgi/reprint/289/4/H1752.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/15964928?dopt=Abstract)] found that the intra-arterial administration of BH4 counteracted the detrimental effects of intravenous endotoxin on eNOS activity, basically (or it might have acted as an antioxidant, without enhancing eNOS activity). There's a large amount of research on BH4 in humans, now, and most of it shows that BH4 does increase eNOS-dependent blood flow responses (http://scholar.google.com/scholar?q=tetrahydrobiopterin+oral+OR+orally+OR+peroral+OR+supplement&hl=en&as_sdt=2001&as_sdtp=on). It's being tested in trials in the treatment of peripheral arterial disease, and maybe it'll be covered by insurance then. It's been approved to treat phenylketonuria, but I checked the out-of-pocket cost of it. It's prohibitively expensive. There's research showing it can pretty dramatically decrease blood pressure in people who are hypertensive. If only they'd started testing it 30 years ago, in 1981 or so, when some of the first research showing its biological effects was published. In the context of Alzheimer's disease, some researchers discussed the potential for an increase in BH4 availability to limit the uncoupling of eNOS activity (and nNOS and iNOS activities) to NO formation (or to uncouple the formation of citrulline, from arginine, from the formation of NO) and thereby decrease peroxynitrite formation [Foxton et al., 2007: (http://www.ncbi.nlm.nih.gov/pubmed/17191137)].

From the standpoint of the effects of methylfolate or BH4 on the brain, I think that L-methylfolate could initially increase, for example, iNOS activity in astrocytes or microglia or even increase nNOS activity excessively and produce effects on mood or cognitive functioning that would initially but not "ultimately" be counterproductive. For example, the administration of L-arginine via microdialysis into the caudal ventrolateral medulla (CVLM) augmented the pressor response to muscle contractions, but the arginine produced the opposite effect when administered into the rostral ventrolateral medulla (RVLM) [Freda et al., 1999: (http://www.ncbi.nlm.nih.gov/pubmed/10320724)]. Those effects could be explained in terms of differences in the anatomical "localization" of nitrergic inputs to glutamatergic neurons that provide excitatory inputs to the preganglionic sympathetic neurons in the RVLM, but most of these articles don't provide many details on the anatomy [Zanzinger et al., 1998: (http://ajpregu.physiology.org/cgi/reprint/275/1/R33.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/9688957?dopt=Abstract)]. Another article found a pressor effect of arginine in the CVLM [Rampin and Giuliano, 2000: (http://www.ncbi.nlm.nih.gov/pubmed/10899272)] (I just glanced over part of that and thought that was on cardiovascular reflexes only). But the general idea is that nNOS-derived NO tends to be excitatory and to bind directly to NMDA receptors or to otherwise increase glutamatergic transmission, such as by amplifying the excitatory effects of NMDA receptor activation. But that's not really the way BH4 behaves in models of hypoxia or ischemia. There's some research showing that it worsens the damage, but a lot of it shows neutral or beneficial effects. Those parts of the medulla are mainly involved in cardiovascular reflexes, but the same type of concept applies to the nitrergic regulation of the firing rates of noradrenergic neurons in the locus ceruleus or of dopaminergic neurons, etc. BH4 or methylfolate could enhance nNOS activity and, by that mechanism and its function as a cofactor of tyrosine hydroxylase, exert an excitatory influence on dopaminergic and noradrenergic transmission (and serotonergic transmission), but there could be an initial enhancement of nNOS (and eNOS and iNOS) activity/activities and then a subsequent "normalization" of the nitrergic transmission. The increases in NO release, induced by BH4 or methylfolate, could, relatively rapidly, lead to a kind of new, equilibrium state and restore the normal extent to which nNOS-derived (and iNOS-derived) NO produces autoinhibition of nNOS and iNOS activities. For example, these authors [Galijasevic et al., 2003: (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=299800)(http://www.ncbi.nlm.nih.gov/pubmed/14657339)] found that the presence of myeloperoxidase, a heme-containing enzyme present in neutrophils and other cell types, could function as a nitric oxide scavenger but paradoxically disinhibit iNOS activity by relieving the constitutive, autoinhibitory influence that iNOS-derived NO exerts on iNOS activity and that is thought to be largely responsible for the maintenance of iNOS activity at between 20 and 30 percent of its maximal rate (Galijasevic et al., 2003). The autoinhibition phenomena is a real phenomenon and isn't just a theoretical mechanism. I actually observed that type of phenomenon (in my opinion) when I took significant dosages of methylcobalamin during infectious mono, and it was mainly apparent when I increased the dosage (these were reasonable but sort of large dosages, as in 10 mg/d, even though there are 15 mg dosage forms of methylcobalamin now) and took it on an empty stomach. It always took 2 hours+ to be absorbed on an empty stomach (apparently because it's all bound to B12 binding proteins or forms some sorts of insoluble complexes?), and it behaved, initially, like a nitric oxide donor but then rapidly ceased to produce that type of effect (the migrating myoelectric complexes that drive gastric motility in the fasted state occur every 1.5 to 2 hours, incidentally, and "reset" upon the ingestion of small amounts of food, meaning it would take about 2 hours for the small amount of food to begin entering the small intestine, assuming it was part of a molecule too large to be transported into the small intestine in solution, by solvent drag or whatever, between the cells). It was possible to tell these things because of all the upregulation of iNOS activity, in response to the viral illness, etc. The point is that nitrergic effects, in response to something like methylfolate, seem to exhibit a kind of tachyphylaxis, and that's consistent with the transience of the inhibitory effects of high dosages of nitrate-derived NO on platelet function. There's an initial inhibition of platelet activation and platelet functions, but there's rapid adaptation/tolerance to the effect. But there still is a nitrergic effect of higher dosages of methylfolate, in the longer term, that's less pronounced than the effects that occur in the short term, in my opinion. In this article on the use of BH4 in the treatment of depression [Curtius et al., 1983: (http://www.ncbi.nlm.nih.gov/pubmed/6131342)], there was a delay of a couple of days until the maximal mood-elevating effect emerged, and the dosage regimes used in the articles on the use of BH4 itself, in treating depression, are bizarre. The authors (Curtius et al., 1983) used a dose that was probably excessively-high (1 g once and then a 100 mg/d maintenance dosage) and that could have compromised the efficacy of the BH4, in my view, given the potentially counterproductive effects that excesses of NO can have on glutamatergic and monoaminergic transmission, etc., in relation to mood or cognitive functioning. But the authors also were using tyrosine at a high dosage, and tyrosine has the potential to worsen depression, in my opinion, particularly at the high dosages that can allow for the autoinhibition of tyrosine hydroxylase activity by tyrosine itself to become significant. But the point is that the 100 mg/d dosage (used in other case reports, also) is similar to the highest dosage (90 mg/d) of methylfolate that's been used in small trials, in the treatment of depression. And the timecourse with which the changes in mood (or, by extension, in something like blood flow, etc.) emerged are consistent with some sort of adaptation to a change in nitrergic transmission. I generally haven't found that Rx L-methylfolate produces any more benefits at dosages above ~50 mg/day, but this hasn't always been the case. I just think that one has to work with one's doctor and try to individualize the dosage in a way that's appropriate for oneself, as an individual. In other words, there may be a significant need to individualize the dosage, and an awareness of some of the mechanisms by which BH4 acts, in the brain, may be useful in...the individualization of the dosage, etc.

Another Commentary on Childhood Bipolar Disorder

http://www.youtube.com/watch?v=a9nScu00E7I

Lactobacillus Bacteremia, Endotoxemia, & Effects of Indigestible Polysaccharides on Bacterial Proliferation & on Liver & Exocrine Pancreatic Function

These are some of the articles [Salminen et al., 2002: (http://toxicology.usu.edu/endnote/Lactobacillus-safety-humans-Fin.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/12410474); Land et al., 2005: (http://www.ncbi.nlm.nih.gov/pubmed/15629999); Kunz et al., 2004: (http://www.ncbi.nlm.nih.gov/pubmed/15085028); De Groote et al., 2005: (http://www.ncbi.nlm.nih.gov/pubmed/15750472); (http://scholar.google.com/scholar?hl=en&q=bacteremia+probiotic+OR+prebiotic+OR+yogurt&as_sdt=2000&as_ylo=&as_vis=0)] whose authors have discussed evidence that the use of the preformed, live strains of Lactobacillus bacteria or other bacteria can cause bacterial endocarditis or sepsis, etc. So-called Lactobacillus bacteremia can occur in a person who isn't taking any "probiotic" supplement, but the point is that disease states in which intestinal permeability has been increased could increase a person's susceptibility to this kind of dramatic, potentially devastating event. It's important to realize that portal endotoxemia, in which there's an abnormally-elevated concentration of endotoxin(s) in the portal venous blood but not in the systemic circulation, in many cases, is not something that only occurs in severe disease states, in which a person is falling on the floor and so forth. There's evidence that portal endotoxemia occurs in some obese people and may contribute to nonalcoholic fatty liver disease in people who may or may not be obese [see Brun et al. (2007) and others: (http://scholar.google.com/scholar?hl=en&q=portal+endotoxemia+%22fatty+liver%22&as_sdt=2000)], and some researchers have estimated that 20-30 percent of people in the US have fatty liver disease [Cave et al., 2007: (http://www.ncbi.nlm.nih.gov/pubmed/17296492); (http://hardcorephysiologyfun.blogspot.com/2009/03/nonalcoholic-fatty-liver-disease-nafld.html)]. It's important to note that bacteremia or sepsis or bacterial endocarditis are not minor events but could permanently devastate a person's intellectual capacity, leaving the person mentally disabled, lead to kidney or liver failure leading to death or transplantation, etc.

The other side of the issue is that there are lots and lots of articles showing that Lactobacillus bacteria can reduce endotoxemia in the context of liver diseases or a variety of traumas (http://scholar.google.com/scholar?q=lactobacillus+endotoxin&hl=en&as_sdt=2001&as_sdtp=on). Even though the use of any old oligosaccharide doesn't sound good to me, Wang et al. (1998) [Wang et al., 1998: (http://www.ncbi.nlm.nih.gov/pubmed/9757556)] found that the administration of a "soluble fiber" polysaccharide reduced the liver damage in D-galactosamine-induced liver failure in rats. The polysaccharide doesn't have to leave the GI tract to exert these effects, and Wang et al. (1998) found evidence that the increases in numbers of Bifidobacteria can reduce the numbers of gram-negative bacteria that endotoxin can be derived from. Cherbut et al. (2003) [Cherbut et al., 2003: (http://cat.inist.fr/?aModele=afficheN&cpsidt=15118468)] found that people were able to tolerate gum acacia (from a commercial standpoint, this is the same thing as "acacia fiber," "gum arabic," or "acacia gum," etc.) easily, and gum acacia promoted the proliferation of Bifidobacteria, etc. There are many reasons that acacia gum and, for example, guar gum would be superior to something like inulin, in my view, in many contexts, but that's just my opinion. I've probably been too inclined toward caution with something like "apple pectin" or "grapefruit pectin" (I'm not sure how that differs from apple pectin), but the low-molecular weight fraction might just be glycoproteins or something. I can't imagine how apples would be innocuous and apple pectin would be "poisonous" or "horrendous." There's a ton of research on pectin, incidentally, and some other mechanisms basically have to do with the overlapping of these effects of soluble fibers with the effects of cholestyramine, a resin that sequesters bile acids. Pectin and some of these other polysaccharides can sequester bile acids but can also promote the reabsorption of the bile acids and act as generalized emulsifiers/surfactants/cosurfactants. Cholestyramine is not really a surfacant (http://scholar.google.com/scholar?hl=en&q=cholestyramine+surfactant&as_sdt=2000&as_ylo=&as_vis=0) and has been associated with various side effects, such as steatorrhea (http://scholar.google.com/scholar?hl=en&q=cholestyramine+steatorrhea&as_sdt=2000&as_ylo=&as_vis=0), in which there's malabsorption of dietary fats (potentially as a consequence of the sequestration of bile acids), and hyperchloremic, normal-anion-gap, metabolic acidosis (http://scholar.google.com/scholar?hl=en&q=cholestyramine+%22metabolic+acidosis%22&as_sdt=2000&as_ylo=&as_vis=0). Arginine hydrochloride can also cause that type of hyperchloremic metabolic acidosis (http://hardcorephysiologyfun.blogspot.com/2009/03/arginine-hydrochloride-and.html). Either pectin or cholestyramine can increase cholesterol 7alpha-hydroxylase activity in hepatocytes and increase the overall pool of bile acids [(http://scholar.google.com/scholar?hl=en&q=pectin+hydroxylase+cholesterol+bile&as_sdt=2000&as_ylo=&as_vis=0); (http://scholar.google.com/scholar?hl=en&q=pectin+hydroxylase+cholesterol+bile+cholestyramine&as_sdt=2000&as_ylo=&as_vis=0)]. Pectins can also decrease the activities of bacterial beta-glucuronidase enzymes and thereby lead to a decrease in the rate at which unconjugated bilirubin is formed in the large intestine [(http://scholar.google.com/scholar?hl=en&q=pectin+glucuronidase&as_sdt=2000&as_ylo=&as_vis=0); Kim et al., 1996: (http://kmbase.medric.or.kr/Main.aspx?d=KMBASE&m=VIEW&i=1007519960050020124)], and that effect could reduce the enterohepatic recycling of bilirubin, potentially (http://scholar.google.com/scholar?q=glucuronidase+bacteria+enterohepatic+recycling+bilirubin&hl=en&as_sdt=2001&as_sdtp=on). Only about half of the articles on pectin and glucuronidase activity have shown a decrease. Some of those have shown increases. But increases in the enterohepatic recycling of bilirubin are thought to contribute to the development of some types of gallstones in adults [Brink et al. (1999) and Vitek et al. (2003), shown here: (http://scholar.google.com/scholar?hl=en&q=enterohepatic+bilirubin&as_sdt=2000&as_ylo=&as_vis=0)]. It's important to note that the complex effects of these polysaccharides on bile acid reabsorption could account for those effects, but the research showing that pectin or guar gum, etc., can inhibit gallstone formation or the like, such as in animals or in association studies in humans, could be explained in terms of the polysaccharides' effects on bile acids or on the enterohepatic recycling of bilirubin [(http://scholar.google.com/scholar?hl=en&q=pectin+gallstone&as_sdt=2000&as_ylo=&as_vis=0); (http://scholar.google.com/scholar?hl=en&q=gallstone+pectin+OR+%22guar+gum%22&as_sdt=2000&as_ylo=&as_vis=0)]. There's also the whole pancreatic cancer risk-reduction-association stuff (http://scholar.google.com/scholar?hl=en&q=%22soluble+fiber%22+pancreatic+cancer&as_sdt=2000&as_ylo=&as_vis=0), and some of these soluble, indigestible, high-molecular weight polysaccharides can increase pancreatic exocrine function (http://scholar.google.com/scholar?hl=en&q=pancreatic+exocrine+acacia+OR+pectin+OR+%22guar+gum%22&as_sdt=2000&as_ylo=&as_vis=0). I discussed some of the risks of some of these things in a previous posting (http://hardcorephysiologyfun.blogspot.com/2009/12/potential-effects-of-soluble-fibers-as.html), and those things are worth keeping in mind, in my opinion. But hey, it's no skin off my nose. Have a nice trip, as they say. In any case, the research is a bit chaotic, but there's a large amount of it. The main point is that I think the use of specific indigestible polysaccharides would potentially pose a less extreme range of possible outcomes than the use of the actual bacteria would, particularly since the supplements, as opposed to the foods sold in groceries or whatever, contain larger amounts of bacteria and need to be shipped with ice. I dunno. That doesn't sound so good to me. I used to think the main problem would be the destruction of the bacteria by stomach acid, but apparently it's not even the most important issue, necessarily. Then I thought that the products might be contaminated. That's not even the issue. It's the "good" bacteria themselves that are thought to have entered the bloodstream in some of these cases. The quality control in the realm of the actual baterial supplements seems to be lacking, as discussed in this article [Hamilton-Miller et al., 2002: (http://www.ncbi.nlm.nih.gov/pubmed/11852901)]. It seems really chaotic to me, in the context of the actual bacterial supplements (as opposed to the soluble fibers that are fuel sources for the existing bacteria). But even some of these lowly foods may pose risks to vulnerable individuals [Presterl et al., 2001: (http://scholar.google.com/scholar?hl=en&q=lactobacillus+bacteremia+yogurt&as_sdt=2000&as_ylo=&as_vis=0)]. A person should discuss this type of thing with one's doctor, however, and I obviously can't make any statements about the safety or lack of safety of any product or supplement.