Slowly the poison the whole blood stream fills

It is not the effort nor the failure tires

The waste remains, the waste remains and kills.

–William Epson, Poet

or centuries, traditional systems of healing have recognized the fundamental role of digestive health in overall wellness. These traditional systems displayed an understanding of how the body’s organs are integrated together; and how, for example, the functioning of the digestive system can directly impact the rest of the body, including the functioning of the brain, joints, muscles, or nervous system.

And, as is becoming increasingly common, modern research is beginning to lend scientific validity to the wisdom of such holistic views. We now understand many of the reasons why a healthy gastrointestinal tract is important for so much more than just absorbing nutrients. It’s become well accepted that healthy intestines are the bodies’ first line of defense against a whole host of infectious organisms and cellular toxins; and by some estimates, a full 80% of our immune system’s resources are localized in our gastrointestinal tract.

So, when harmful intestinal bacteria are left to flourish unabated, or when we’re under the influence of stress, injury, or food-toxins, our enteric (located in the intestines) immune system springs into action. As a result, the GI tract can often become a chronic hotbed of inflammation. Of course, such inflammation is well-known to be involved with increasingly common GI disorders such as ulcerative colitis, Crohn’s disease, and irritable bowel syndrome - but what’s not so well-known is the role intestinal inflammation may play in seemingly unrelated, and body-wide inflammatory disorders – conditions like arthritis, psoriasis, allergies, chronic fatigue, heart failure, cachexia (muscle wasting), hepatitis, cirrhosis, and fibromyalgia.

Inflammation in the gastrointestinal tract leads to an increase in intestinal permeability, or a “leaky gut,” which sets the stage for massive body-wide disruption. As the intestines become more permeable, undigested foods, bacterial toxins, and various microbes “leak” across the mucosal barrier of the intestines, not only placing enormous strain on the detoxifying ability of the liver, but simultaneously stimulating the internal immune system into an inflammatory frenzy, as it attacks the foreign matter which has breached our intestinal defenses.

This chronic low-level poisoning by intestinal contents places continued strain on all of the detoxifying systems of the body. It also causes the immune system to be chronically stimulated to the point of exhaustion. This is probably the major reason why the immune dysfunction associated with a leaky gut has been associated with the development of allergies and autoimmune disorders like rheumatoid arthritis and lupus.

But even in the absence of noticeable symptoms, it’s a safe bet that the majority of us have digestive systems which are more “leaky” than we may imagine. Environmental factors like the widespread use of antibiotics, along with dietary factors like the use of certain food additives and processed foods serve to put our intestines under nearly constant assault; exacerbating the chronic body-wide inflammation which is a driving force behind every degenerative disease of aging.

In this edition of the Integrated Supplements Newsletter, we’ll take a look at some of the common dietary factors which pose a threat to our gastrointestinal health, as well as some simple dietary strategies to maintain the proper structure and function of our intestines.

With these strategies, we’ll be able to rid our body of the major toxic burden which results from excessive intestinal permeability, and we’ll see just how supporting digestive health is ultimately a major part of the nutritional solution for pain and inflammation.

Intestinal Inflammation and Permeability

Intestinal permeability can be dangerously increased by anything which irritates, and damages the integrity of the intestinal lining - and the list of potential offenders in this regard is numerous:

• Infectious microbes (viruses, bacteria, fungi, parasites)

• Alcohol

• Exercise (especially endurance exercise)

• Stress (physical or psychological)

• Anti-Inflammatory Drugs

• Oxygen-reactive substances (iron, polyunsaturated fats)

• Food Additives (carrageenan, sucralose, artificial colors)

• A Low-Fiber Diet

• Oral Contraceptives

And for as common as these offending elements are, it’s not exactly comforting to know that our protective defenses are often in short supply as well.

Right now, in our digestive tracts, live approximately 100 trillion bacteria – 3 to 5 pounds-worth by some estimates. Ideally, a significant portion of these bacteria will be the “friendly” type – bacterial species like lactobacillus and bifidobacterium which can aid in digestion and protect us from infection by harmful organisms. Friendly bacteria are unique in that they produce substances called short chain fatty acids (SCFAs) as a natural byproduct of their metabolism. These SCFAs have far reaching benefits for our entire body, but they are especially well known for nourishing intestinal cells and maintaining the strength of the intestinal barrier.

But commonly, the balance of bacteria in our intestines is skewed towards a preponderance of the harmful type. Scientists have begun to categorize such an imbalance by the term intestinal dysbiosis.

Study Link - The causes of intestinal dysbiosis: a review

Quote from the above study:

Alterations in the bowel flora and its activities are now believed to be contributing factors to many chronic and degenerative diseases. Irritable bowel syndrome, inflammatory bowel disease, rheumatoid arthritis, and ankylosing spondylitis have all been linked to alterations in the intestinal microflora. The intestinal dysbiosis hypothesis suggests a number of factors associated with modern Western living have a detrimental impact on the microflora of the gastrointestinal tract. Factors such as antibiotics, psychological and physical stress, and certain dietary components have been found to contribute to intestinal dysbiosis.

Harmful bacteria in the intestines can cause physical damage to the delicate intestinal lining, and when the intestinal barrier is compromised, these harmful bacteria from the intestines can be absorbed. Scientists refer to the toxic and inflammation-producing components of these harmful bacteria generally as endotoxins and one common endotoxin is called lipopolysaccaride. When bacteria from the intestinal tract breach the intestinal barrier, this phenomenon is known as bacterial translocation.

And if even small amounts of endotoxin are able to bypass detoxification by the liver, and are absorbed into the bloodstream, this could trigger massive system-wide inflammation. We saw in the May 2008 issue of the Integrated Supplements newsletter how the omega-6 fat known as arachidonic acid is the driving force behind the inflammatory cascade in the entire body. Studies have shown that absorbed bacterial toxins from the gastrointestinal tract trigger inflammation by stimulating the massive release of arachidonic acid from immune cells called macrophages.

Study Link - Bacterial lipopolysaccharides prime macrophages for enhanced release of arachidonic acid metabolites.

Of course, full-blown endotoxemia, or sepsis – where large amounts of bacteria enter the bloodstream – is usually considered to be an issue only under periods of trauma, surgery, or extreme immunodeficiency. But, researchers are beginning to realize that the gradual and continuous leakage of harmful bacteria across the intestinal barrier can lead to a chronic low-level toxic burden with far-reaching consequences.

Healthy individuals often have strong enough liver function to filter out the endotoxins which are absorbed from the intestines before they find their way into general circulation, but with so many factors leading to increased intestinal permeability, even healthy people may, at the very least, have chronically impaired liver function as a result of absorbed intestinal toxins (and we saw in the previous Integrated Supplements Newsletter how important the detoxification system of the liver is in pain syndromes and inflammatory disorders).

For example, research has clearly shown that the toxic effects of alcohol on the liver may not be due to the toxicity of alcohol itself, but may be due to the fact that alcohol increases intestinal permeability, and leads to the absorption of endotoxin:

Study Link - The leaky gut of alcoholism: possible route of entry for toxic compounds.

Quote from the above study:

Patients abstaining from alcohol for less than 4 days almost invariably had higher intestinal permeability than controls, and in many the abnormality persisted for up to 2 weeks after cessation of drinking. The presence of gastritis did not correlate with the presence of increased permeability. The site of altered intestinal permeability was shown by an in-vitro permeability test to be the small bowel. The increased intestinal permeability to toxic "non-absorbable" compounds of less than 5000 molecular weight may account for some of the extraintestinal tissue damage common in alcoholic patients.

(Note: The above study makes an important point – that an increase in intestinal permeability was not associated with noticeable gastrointestinal symptoms. This may be a major reason why the common presence of a “leaky gut,” while widely supported by the medical literature, is rarely diagnosed or addressed by conventional medical practitioners.)

Study Link - Mechanisms of Hepatic Toxicity - Alcoholic liver injury involves activation of Kupffer cells by endotoxin.

Quote from the above study:

These findings led to the hypothesis that alcohol-induced liver injury involves increases in circulating endotoxin, leading to activation of Kupffer cells, which causes a hypoxia-reoxygenation injury.

It has even been well documented that endurance athletes have a particularly high prevalence of gastrointestinal disorders; and that the stress of intense exercise, while certainly not life-threatening, is enough to substantially increase intestinal permeability:

Study Link - Effect of running intensity on intestinal permeability.

Quote from the above study:

Running at 80% VO2 peak increased (P < 0.05) small intestinal permeability compared with rest, 40, and 60% VO2 peak. . .

And bacterial translocation is increasingly being investigated as a contributing factor in many puzzling disorders of unknown origin – disorders such as arthritis, chronic fatigue, fibromyalgia, autism and even heart disease:

Study Link - Are intestinal bacteria involved in the etiology of rheumatoid arthritis? Review article.

Quote from the above study:

We feel that the immunoreaction against PG peptides [from intestinal bacteria] plays a pivotal role in experimental and human arthritis of an unknown etiology.

Study Link - Altered intestinal permeability in patients with primary fibromyalgia (FM) and in patients with complex regional pain syndrome (CRPS).

Quote from the above study:

The [intestinal permeability] in primary [fibromyalgia] and, unexpectedly, [complex regional pain syndrome] are increased. This study should stimulate further research to determine the implication of altered [intestinal permeability] in the disease pathophysiology of FM and CRPS.

Autism, an increasingly common neurological disorder in children may also be associated with a leaky gut. It’s interesting to note that a diet free of food additives, especially those known to damage the gastrointestinal tract like artificial colors and sweeteners, is often recommended for autistic children.

Study Link - Abnormal intestinal permeability in children with autism.

Quote from the above study:

We determined the occurrence of gut mucosal damage using the intestinal permeability test in 21 autistic children who had no clinical and laboratory findings consistent with known intestinal disorders. An altered intestinal permeability was found in 9 of the 21 (43%) autistic patients, but in none of the 40 controls.

Cachexia, the muscle-wasting disorder associated with degenerative diseases like AIDS and cancer, is largely inflammatory in nature, and may be caused or exacerbated by increased intestinal permeability and bacterial translocation:

Study Link - Role of intestinal function in cachexia.

Quote from the above study:

There is increasing evidence that catabolic diseases such as liver cirrhosis and chronic heart failure are associated with increased gut permeability, endotoxemia and enhanced expression of proinflammatory cytokines. . . Recent data support the hypothesis that impaired gut barrier function and increased permeability further translocation of endotoxins. Increased endotoxemia might be a potent trigger of systemic inflammatory response which is involved in the pathogenesis of the cachexia syndrome.

And even cardiovascular disease, the number one killer in the industrialized world, has been associated with the presence of a leaky gut. At first, the connection may not be obvious, but it’s logical when you think about it – the authors of the following study point out that decreased cardiac function leads to poor circulation to the intestines. This leads to increased intestinal permeability, and this permeability causes the translocation of intestinal bacteria which stimulate chronic inflammation – exacerbating heart disease further. Like so much else in the biology of disease and aging, it’s a classic example of a self-perpetuating downward spiral.

Study Link - The importance of the gastrointestinal system in the pathogenesis of heart failure.

Quote from the above study:

In recent research, the gut has received very little attention from cardiologists as its role in the pathogenesis of cardiovascular disease is poorly understood. Intestinal ischaemia may play an important role in bacterial translocation by increasing bowel permeability. Decreased cardiac function can reduce bowel perfusion and so clearly impairs the function of the intestinal barrier. There is an increasing evidence to suggest that a 'leaky' bowel wall may lead to translocation of bacteria and/or endotoxin, which may be an important stimulus for inflammatory cytokine activation in [chronic heart failure].

It’s unlikely that many of us will ever be officially diagnosed with it, but the fact that it’s being implicated in so many common disorders of aging is evidence that the presence of a “leaky gut” is something to which none of us are immune. As further evidence of this fact, one need only to investigate the many potent intestinal irritants which have found their way into our modern food supply.

Food Ingredients Which Cause a Leaky Gut

In researching the ingredients in many processed foods, it becomes frighteningly clear that, if we’re not careful, our modern food supply is almost certain to decimate our digestive health. We’ve written previously in the Integrated Supplements Newsletter about the potential of artificial colors, and the artificial sweetener, sucralose to cause damage to the gastrointestinal tract. Such damage not only increases intestinal permeability in the short-term, but may also predispose us to gastrointestinal cancer with long-term use. As just one example, the following study found that many common food additives caused genotoxic (DNA-damaging) changes to the gastrointestinal organs of mice. Such DNA damage is generally thought to be indicative of the process which initiates cancer, and many researchers have noted that the increased consumption of such food additives has closely paralleled an increase in the incidence of colon and other gastrointestinal cancers in developed nations in recent decades.

Study Link - The comet assay with 8 mouse organs: results with 39 currently used food additives.

Quote from the above study:

[W]e believe that more extensive assessment of food additives in current use is warranted.

Fats and Intestinal Permeability

The composition of fats in our modern diet may make us particularly susceptible to the toxic effects of a leaky gut as well. We wrote in the May 2008 edition of the Integrated Supplements Newsletter, about the omega-6 precursors of arachidonic acid and their primary role in inflammation. We also commented on how dangerously overrated the omega-3 fats have become in recent years as a therapeutic tool for “balancing” omega-6s. While omega-3 fats are certainly less inflammatory than omega-6s, over-consumption of omega-3s isn’t without potential drawbacks. Omega-3s are some of the most chemically fragile fats, and are known to form harmful lipid peroxides easily. The lipid peroxides produced from omega-3s may be particularly apt to damage the delicate cells of the intestinal lining.

Our recommendation is to reduce the consumption of omega-6 fats as much as reasonably possible, thus letting the trace amounts of omega-3s in the diet exert their benefit without predisposing us to the lipid peroxides which often form when omega-3s are consumed in excess (i.e., when omega-3 supplements are taken, for example). When looking at the effects both of these fatty acids have on gastrointestinal health, and our susceptibility to endotoxin in particular, this recommendation seems all the more reasonable.

The “anti-inflammatory” action of omega-3 oils has been exploited therapeutically in various inflammatory intestinal disorders, but as could be predicted from a biochemical understanding of these fatty acids, the ability of omega-3s to reduce inflammation appears to be temporary, while potentially causing more tissue destruction in the long run.

Such was the case in the following study in which omega-3 oils were shown to only temporarily delay the relapse of ulcerative colitis:

Study Link - N-3 fatty acids only delay early relapse of ulcerative colitis in remission.

Quote from the above study:

Omega-3 fatty acids temporarily retard, but do not prevent relapse of ulcerative colitis

The following study looked at levels of lipid peroxidation in the small intestines of rats given ethanol (alcohol) in conjunction with different types of dietary fats. The levels of lipid peroxides and of oxidative stress were highest in the rats fed omega-3s from fish oil, and these markers increased when ethanol was given.

Study Link - Ethanol effects on lipid peroxidation and glutathione-mediated defense in rat small intestine: role of dietary fats.

Quote from the above study:

Highest rate of iron/ascorbate-induced lipid peroxidation was observed in intestinal mucosa of [fish oil]-fed rats, which was further elevated (p < 0.05) upon ethanol administration. . . ethanol exposes the small intestinal mucosa to oxidative stress. The effects were more pronounced in rats fed n-3 fatty acid-rich [fish oil] diet.

And in the following study, omega-3 fish oil was shown to increase intestinal permeability sufficiently to allow macromolecules (large molecules) to be absorbed, triggering an anaphylactic allergic reaction.

Study Link - Effects of dietary fat on permeability of the protective intestinal barrier to macromolecules in experimental anaphylaxis.

Quote from the above study:

The deleterious effect on intestinal protective barrier efficiency against polyethyleneglycol 4000 macromolecules was noticed in rats fed with [fish oil] containing large amounts of n-3 PUFA.

Interestingly, numerous studies have shown that rats fed a diet which is extremely low in both omega-3 and omega-6 fats, are remarkably resistant to the harmful effects of endotoxin. In the following study, 100% of rats given arachidonic acid died when endotoxin was administered, 40% of rats fed omega-3 DHA died when endotoxin was administered, but only 24% of the low omega-3, low omega-6, essential fatty acid-deficient (EFAD) rats died when exposed to endotoxin:

Study Link - Essential fatty acid deficient rats: a new model for evaluating arachidonate metabolism in shock.

Quote from the above study:

Essential fatty acid deficient (EFAD) rats are significantly more resistant to the lethal effects of S. enteritidis endotoxin (20 mg/kg, IV) than normal control rats. Compared to endotoxin-treated normal rats, EFAD rats also manifested less severe alterations of hepatic and lysosomal integrity and became less hypoglycemic.

Of course, it’s probably impossible to become “essential fatty acid-deficient,” like the animals in this study when eating a diet of fresh, unprocessed foods, but the results of the above studies are probably further reason to consciously limit our consumption of omega-6 and omega-3 oils to trace amounts. It seems that an excess of these oils not only primes the body for excessive inflammation and tissue destruction, but it may also have particularly detrimental effects on the delicate cells of the intestines as well.

Carrageenan

While some food additives like artificial sweeteners and colors have amassed particularly vocal detractors in recent years, there are some particularly harmful food additives which have almost completely slipped by the radar screens of even the most health-conscious consumers. Carrageenan is one such example. In fact, even though most people never suspect it, there may be no more insidious destroyer of gastrointestinal health in our modern food supply than carrageenan.

Carrageenan is an extract from red seaweed which is commonly used to give processed foods a creamy or pleasing texture. This “natural” substance can be found in an amazingly wide array of foods and nutritional supplements including such things as: milk (cow’s milk, soy milk, almond milk, rice milk), cottage cheese, protein drinks, protein powders, meal replacement powders, puddings, baked goods, ice cream, processed cheese, luncheon meats, hot dogs, sauces, pie fillings, jellies, frosting, and coffee creamer.

Where carrageenan is so widely used by the food industry (again, it’s even used in many “natural” foods and nutritional supplements) many people, if they notice its presence in food items at all, simply assume that it has been proven safe. But after decades of study, the scientific literature on carrageenan reveals many reasons for any health-conscious person to be concerned about this particular additive. To put it bluntly, carageenan can be hell on the gastrointestinal tract.

Carrageenan’s use in food products has been the subject of ongoing controversy for decades, as some types of carrageenan have repeatedly and conclusively been shown to cause immune suppression, inflammation, liver enlargement, gastrointestinal ulcerations (with subsequent endotoxemia), and both pre-cancerous and cancerous growths in the intestines of a variety of animal species.

Study Link - Harmful effects of carrageenan fed to animals.

Quote from the above study:

An increased number of reports have appeared in the literature describing the harmful effects of degraded and undegraded carrageenan supplied to several animal species in their diet or drinking fluid. The harmful effects include foetal toxicity, teratogenicity, birth defects, pulmonary lesions, hepatomegaly, prolonged storage in Kupffer cells, ulcerative disease of the large bowel with hyperplastic, metaplastic, and polypoidal mucosal changes, enhancement of neoplasia by carcinogens, and, more ominously, colorectal carcinoma. Degraded carrageenan as a drug or food additive has been restricted in the United States by the FDA, but undegraded carrageenan is still widely used throughout the world as a food additive. Its harmful effects in animals are almost certainly associated with its degradation during passage through the gastrointestinal tract. There is a need for extreme caution in the use of carrageenan or carrageenan-like products as food additives in our diet, and particularly in slimming recipes.

Technically speaking, carrageenan belongs to a group of chemicals known as sulfated polysaccharides. And, as a polysaccharide (literally a chain of sugar molecules), carageenan can exist in varying sizes (molecular weights) depending upon how many such sugar molecules happen to be linked together. The smaller the carrageenan structure, the more of it is likely to be taken up by the intestinal epithelial cells (cells lining the intestines). The more carrageenan is taken up by the epithelial cells, the more inflammation and damage it can cause. So, the crux of the carrageenan controversy revolves around the molecular weight of the carrageenan being used in food products. While it’s undisputed that degraded carrageenan (carrageenan with a molecular weight of less than 100,000) is a potent carcinogen which induces ulcerations and cancer in the gastrointestinal tracts of numerous animal species, the food industry stance is that undegraded, “food-grade” carrageenan (generally, though not officially defined as carrageenan with an average molecular weight above 100,000), is a safe food additive.

But when we look a little closer at the existing scientific research, we see how incredibly flimsy such a defense really is. It’s certainly true that degraded carrageenan is much more toxic than native, undegraded carrageenan. But if, as is generally accepted in the case of carrageenan, the only thing preventing this common food additive from becoming a potent carcinogen is its molecular size, then several questions naturally arise.

The first of which is: can carrageenan be degraded into its toxic form by the acids used in processing carrageenan-containing products, or by the acids secreted during digestion?

The research offers evidence that it can. The following study found considerable degradation of carrageenan in a research model which stimulated the acid environment of digestion:

Study Link - Molecular-weight-distribution and the behaviour of kappa-carrageenan on hydrolysis.

Quote from the above study:

The rate of degradation of kappa-carrageenan in simulated gastric juice was considerable at pH 1.9.

And indeed, animal studies show clearly that even undegraded carrageenan does increase intestinal permeability. The following study looked at the appearance of the food dye, phenol red, in the urine as evidence of intestinal permeability in response to several different diets, including those containing carrageenan:

Study Link - Effects of certain dietary fibers on apparent permeability of the rat intestine.

Quote from the above study:

At 2 wk urinary recoveries of phenol red were high in rats fed fiber-free and carrageenan type II diets, indicating increased apparent permeability.

One proposed mechanism for carrageenan’s toxicity is that smaller particles of carrageenan are able to be taken up by the intestinal epithelial cells. Soon thereafter, something “foreign” about carrageenan’s molecular structure triggers immune cells called macrophages to infiltrate the area, and to “attack” the foreign carrageenan. Macrophages (whose name literally means “big eater”) attempt to engulf and digest carrageenan as they would any other foreign invader. But carrageenan is unable to be broken down by the macrophages.

Interestingly, the fate of macrophages in their attack against carrageenan in the intestinal epithelium is stunningly similar to the phenomenon which occurs when macrophages attack oxidized cholesterol in the vascular epithelium (cells lining the blood vessels). In both instances, the foreign molecules (carrageenan and oxidized cholesterol) disable the normal “digestive” function of the macrophages. As a result, these immune cells “stuff” themselves with the respective offending compound until they burst – spewing a toxic cellular mess of digestive and inflammatory substances into the surrounding area. This causes a vicious cycle of further macrophage-infiltration, and increased inflammation. In the artery, this is how oxidized cholesterol triggers the plaque build-up of heart disease, and in the intestines, this is how carrageenan may trigger ulcerations, increased intestinal permeability and even the formation of cancer.

Carrageenan’s ability to incapacitate massive numbers of macrophages in this way has been shown to greatly suppress the immune system. When large numbers of macrophages are recruited to attack carrageenan, fewer macrophages are available to handle other pathogens. But even though carrageenan has been entertained for use as an immunosuppressive drug (to prevent rejection in organ transplants, for example), it’s tendency to thicken the blood, promote tumor growth, and it’s toxic effects on the kidney and liver have prevented even its use as an immune suppressant:

Study Link - Carrageenan: a review of its effects on the immune system.

Quote from the above study:

The mechanism responsible for carrageenan-induced immune suppression is believed to be its selective cytopathic effect on macrophages. This property of carrageenan has led to its adoption as a tool for analysing the role of these cells in the induction and expression of immune reactivity. Systemic administration of carrageenan may, however, induce disseminated intravascular coagulation and inflict damage on both the liver and kidney. This is an important consideration in the interpretation of the effects of carrageenan in vivo and precludes its use as a clinical immune suppressant.

We’ll have more to say about carragenan in the coming months, but for now even this brief look at the relevant research should make one point clear: Dietary strategies aimed at reducing systemic inflammation by maintaining the integrity of the gastrointestinal tract should include the strict avoidance of carrageenan-containing foods and supplements.

Protective Substances for the GI Tract

And now that we’ve taken a look at some of the common substances which can harm our intestinal barrier, we’ll also take a look at some of the most important substances for supporting the integrity and overall health of the GI tract.

Glutamine

Many people, especially workout enthusiasts, know glutamine as a major free amino acid in muscle tissue. But glutamine is, first and foremost, the major fuel for the cells called enterocytes which form the lining of the small intestine. In fact, the enterocytes proliferate so rapidly, that the small intestine exhibits the largest glutamine usage of any organ in the body. We’ve seen how all types of stress can contribute to increasing gastrointestinal permeability, and interestingly, it has been proposed that the major reason that stress hormones (cortisol, adrenalin) cause the release of glutamine from muscle, is so that this glutamine can serve the more pressing needs of the intestines under periods of injury, trauma, or intense exercise. Supplying the body with additional glutamine may be able to prevent the vicious cycle of stress-induced intestinal hyperpermeability, endotoxemia, systemic inflammation and infection commonly seen in critically ill patients.

Study Link - Intestinal permeability and systemic infections in critically ill patients: effect of glutamine.

Quote from the above study:

Glutamine administration improves the prognosis of critically ill patients presumably by maintaining the physiologic intestinal barrier and by reducing the frequency of infections.

While its effects have been studied mostly on the critically ill, and patients receiving total parenteral nutrition (intravenous feeding), there is reason to believe that low doses of oral glutamine may represent a reasonable strategy for ensuring gastrointestinal integrity, even in healthy individuals.

For example, glutamine has been shown in animal studies to prevent the gastrointestinal damage caused by both aspirin and bile acids.

Study Link - Effects of L-glutamine of acetylsalicylic acid or taurocholic acid-induced gastric lesions and secretory changes in pylorus-ligated rats under normal or stress conditions.

Quote from the above study:

L-glutamine, given together with SAS or TCA, significantly prevented the potentiated development of SAS- or TCA-induced gastric lesions in stressed rats.

(Note: For the generally healthy person, it’s probably prudent to stick with relatively low doses of supplemental glutamine, along the lines of 1 to 2 grams per day. Doses which overwhelm the gastrointestinal tract are prone to increase free glutamate in the bloodstream and brain, and as we saw in the previous Integrated Supplements Newsletter, free glutamate may exacerbate pain syndromes and inflammation – exactly the phenomena we’re trying to prevent. Athletes who train intensely may be able to take higher amounts of glutamine, but doses above 5 grams per day are probably ill-advised until more is known about the safety of such an intake.)

Whey Protein Isolate

Perhaps an even more effective strategy than glutamine for supporting intestinal integrity would be the regular use of undenatured whey protein isolate. Not only does whey protein contain abundant precursors to glutamine, but whey protein also contains several other substances which have been shown to support GI integrity as well.

Whey contains a protein fraction called glycomacropeptide which has been shown to increase the levels of cholecystokinin (CCK) in the intestines. Cholesystokinin has been shown to protect the gastric mucosa against the damage caused by alcohol:

Study Link - Exogenous and endogenous cholecystokinin protects gastric mucosa against the damage caused by ethanol in rats.

Quote from the above study:

We conclude that CCK exerts protective activity against ethanol-induced damage and that this effect is mediated through specific CCKA receptors and hyperemia involving NO.

Whey protein also contains the iron-binding protein called lactoferrin. Lactoferrin has been shown to significantly reduce the toxic effects of bacterial endotoxin:

Study Link - Treatment of enterogenic endotoxinemia with lactoferrin in rats.

Quote from the above study:

There was a dose-dependent improvement of the endotoxin activity in plasma and the bacterial contamination of the peritoneum cavity and mesenteric lymph nodes after lactoferrin administration. The maximum plasma endotoxin activity could be reduced by 89% with 80 mg/kg lactoferrin.

And undenatured whey protein is among the most effective substances available for increasing the multi-faceted antioxidant glutathione. Adding to the list of glutathione’s many benefits, glutathione appears to be integral in maintaining the integrity of the epithelial cells of both the small and large intestine:

Study Link - Glutathione is required for intestinal function.

Quote from the above study:

Glutathione (GSH) deficiency produced in mice by giving buthionine sulfoximine leads to severe degeneration of the epithelial cells of the jejunum and colon. This is prevented by giving GSH monoester (orally or i.p.) and also by giving GSH (orally, but not i.p.).

Soluble Fiber

Where the cells of the small intestine use glutamine as their primary fuel source, the cells of the large intestine, or colon, use a short chain fatty acid produced from the fermentation of soluble fiber, called butyric acid, as their primary fuel source. Certain types of soluble fibers are able to feed, and support the growth of beneficial probiotic bacteria in the intestines, and it’s these beneficial bacteria which produce butyric acid as part of their normal metabolism. It’s for this reason that soluble fiber and/or probiotics are increasingly being recognized as remarkable tools for supporting the integrity of the large intestines, and reducing both intestinal and systemic inflammation. In fact, a low-fiber diet, in and of itself, is sufficient to cause a dangerous increase in intestinal permeability. Without a constant supply of fiber to feed the good bacteria, bad bacteria which can damage the gastrointestinal wall are left to run amok in the GI tract.

From the study we referenced previously in relation to carrageenan:

Study Link - Effects of certain dietary fibers on apparent permeability of the rat intestine.

Quote from the above study:

The ratio of phenol red recovery from urine to that from feces, another index of apparentintestinal permeability, was higher in the fiber-free diet group than in all the other groups. Rats fed 15% dietary fiber had higher average ratios than those fed the same fiber at 5%.

And, due to their effectiveness in supporting the growth of beneficial bacteria certain types of soluble fiber, now being called prebiotics, may offer exceptional benefits in supporting gastrointestinal integrity.

The related fibers, inulin and oligofructose (collectively called inulin-type fructans in the following study) are two such examples:

Study Link - Studies with inulin-type fructans on intestinal infections, permeability, and inflammation.

Quote from the above study:

Symbiosis between host and gut bacteria can be optimized by prebiotics. Inulin-type fructans have been shown to improve the microbial balance of the intestinal ecosystem by stimulating the growth of bifidobacteria and lactobacilli. These changes have been associated with several health benefits, including the prevention of gastrointestinal and systemic infections in animal models and human studies. Inulin-type fructans induce changes of the intestinal mucosa characterized by higher villi, deeper crypts, increased number of goblet cells, and a thicker mucus layer on the colonic epithelium.

Oat Fiber

The fiber from oats, most notably the soluble fiber called beta glucan, may also be particularly effective in reducing systemic inflammation caused by endotoxin. In the following study, oats administered to rats receiving increasing doses of alcohol were able to reduce gut leakiness, and prevent alcoholic liver damage – further evidence, as was mentioned earlier, that the liver damage associated with alcohol ingestion may have more to do with the effects of endotoxin rather than alcohol itself.

Study Link - Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats.

Quote from the above study:

Since the gut is the main source of endotoxin, we sought to determine whether an increase in intestinal permeability (leaky gut) is required for alcohol-induced endotoxemia and liver injury and whether the gut leakiness is preventable. For 10 weeks, rats received by gavage increasing alcohol doses (to 8 g/kg/day) and either oats (10 g/kg) or chow b.i.d. Intestinal permeability was then assessed by urinary excretion of lactulose and mannitol. Liver injury was evaluated histologically, biochemically (liver fat content), and by serum aminotransferase. Alcohol caused gut leakiness that was associated with both endotoxemia and liver injury. Oats prevented these changes.

Resistant Starch

Resistant starch is a term used to encompass a type of fiber which doesn’t necessarily fit into the classical categories of soluble or insoluble fiber. But much like soluble fibers, resistant starches are able to support the production of butyric acid by feeding the beneficial bacteria. For our purposes here, it’s important to note that resistant starches have been shown to have profound protective effects on the integrity of the gastrointestinal tract – thus reducing inflammation throughout the entire body:

Study Link - Long-term intake of resistant starch improves colonic mucosal integrity and reduces gut apoptosis and blood immune cells.

Quote from the above study:

Long-term intake of [resistant starch] induces pronounced changes in the colonic environment, reduces damage to colonocytes, and improves mucosal integrity, reducing colonic and systemic immune reactivity, for which health benefits in inflammatory conditions are likely to be associated.

In a study of particular interest to us here at Integrated Supplements, researchers looked at the effects of several types of supplemental protein on DNA damage and barrier function of the intestines of rats. The researchers also examined how this damage was affected by the inclusion of resistant starch in the diet.

First off, it has been well documented in other studies that casein, soy protein, and red meat are known to cause DNA damage of the colon cells, and to thin the colonic barrier, when consumed in the absence of fiber or fermentable carbohydrates like resistant starch. With protein supplements comprised of soy and/or casein being hyped so heavily these days, it’s important to note the fact that the vast majority of protein supplements containing these protein sources may slowly be causing long-term damage to the gastrointestinal tract.

(Note: As if to add insult to injury, many protein supplements and meal replacement powders use carrageenan as a “fiber source,” which, as we now know, is worse for gastrointestinal health than no “fiber” at all.)

The researchers who conducted the study below found that casein and soy (but not whey, probably due to the many protective substances in whey which we mentioned earlier) caused DNA damage to the cells of the colon. And while resistant starch is able to attenuate this damage somewhat when casein is consumed, protein-induced DNA damage remained significantly higher in the rats fed large amounts of soy protein, even if resistant starch was added.

Study Link - Differential effects of dietary whey, casein and soya on colonic DNA damage and large bowel SCFA in rats fed diets low and high in resistant starch.

Quote from the above study:

Feeding higher levels of dietary animal protein (as casein or red meat) increases colonic DNA damage and thins the colonic mucus barrier in rats. Feeding resistant starch (RS) reverses these changes and increases large bowel SCFA . . . Higher dietary casein and soya (but not whey) increased colonocyte DNA damage. DNA damage was highest with soya when fed at 15 or 25% protein without RS. Dietary RS attenuated protein-induced colonocyte DNA damage in all groups but it remained significantly higher in rats fed 25% soya compared with those fed 15% protein . . . Dietary protein level did not affect colonic mucus thickness overall but the barrier was thinner in rats fed high dietary casein.

With studies like these in the literature, you may be beginning to see why we at Integrated Supplements chose to formulate our protein supplement with only undenatured CFM® Whey Protein Isolate. The scientific literature makes it very clear that protein supplements such as casein and soy (and whey concentrate, for that matter) while extremely common, are simply not suitable for the health-conscious supplement user.

You may also be beginning to see our reasons for producing Fiber Balance™. Fiber Balance™ is a concentrated source of 5 types of fiber including those we believe to be most likely to support digestive health for a lifetime - inulin, oligofructose, oat fiber, and Fibersol 2™, a digestion-resistant starch.

Hopefully, it’s now clear why we specifically avoid certain ingredients which have become frustratingly common in nutritional supplements - things like artificial sweeteners, artificial colors, soy protein, casein (and caseinate), carrageenan, and flaxseed meal (a “fiber” source, which, as we’ve mentioned else where, is destined to contain peroxidized fats).

For any person looking to enjoy a lifetime free from debilitating pain and chronic inflammation, it’s clear that the health of the gastrointestinal tract is of the utmost importance. But the sad irony is that even many natural foods and nutritional supplements may be destined to slowly decimate our digestive health, as the ingredients they contain are dictated more by the profit motive than by sound nutritional principles.

But, as has been our goal since our inception, Integrated Supplements is dedicated to bringing you the research and the products you need to see through the hype and finally reach your full human potential. With the strategies you’ve learned in the Integrated Supplements Newletter in the past few months, we hope you’re now well on your way to finding a lasting nutritional solution for pain and inflammation.

About Us: At Integrated Supplements, our goal is to bring you the wellness information and products you need to live your life to the fullest. We are dedicated to producing the highest quality, all natural nutritional supplements; and to educating the world on the health promoting power of proper nutrition. You can find out more by visiting: www.IntegratedSupplements.com

These statements have not been evaluated by the FDA. No Integrated Supplements product is intended to diagnose, treat, cure or prevent any disease.