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Glutathione: It’s Your Gut

glutathione levelsSome things are so grossly unconventional that we think they’ll never get off the ground. To the contrary is the ultimate use of waste water, but not the kind you’re thinking of. This is olive water, the leftovers from the olive grinding mill. It seems that this material is able to influence some measures of oxidative stress in humans by affecting levels of glutathione, the body’s premier endogenous (self-made) antioxidant, able to be synthesized by all cells of the body.

It has already been accepted that plant phenols are beneficial compounds. Because of increasingly sophisticated testing techniques, those in olives are receiving more and more attention as amplifiers of the body’s antioxidant capacity. A French study performed in 2009 discovered that olive mill waste water has a positive effect on plasma antioxidant potency. Ingesting a mere 2 milliliters of this benevolent elixir contributed to,”…a significant increase in total plasma glutathione concentration…,” involving, “…both the reduced and oxidized forms…”  (Visioli. 2009)  It is widely recognized that specific groups of individuals benefit substantially from increased glutathione levels, most notably the geriatric population. Research has robustly demonstrated that the natural compounds in olives and now, apparently, their waste, play important roles within the living organism.

Glutathione is made from three amino acids—cysteine, glycine, and glutamine—none of which is absolutely essential.  In times of great physical stress, such as major surgery, however, glutamine may be conditionally essential, meaning it has to come from a food or a supplement. Glutathione is your personal antioxidant powerhouse, and it pays super dividends to keep stores as healthy as possible. It’s the presence of a sulfur group on the cysteine portion of the molecule that’s at the foundation of its powerful antioxidant capacity.

Widely found in all forms of life, glutathione plays an essential role in the health of an organism. Cysteine, the businessman of the molecule, but itself a relatively insoluble entity at normal pH, needs to be part of the glutathione tripeptide to do its work. Glutathione synthesizes and repairs DNA, transports amino acids, metabolizes toxins and carcinogens, strengthens the immune system, prevents oxidative damage, and activates enzymes.  It’s pretty busy, don’t you think? Levels of glutathione increase during exercise, but fall with old age, and are found to be deficient in age-related macular degeneration, diabetes, lung and gastrointestinal disease, pre-eclampsia, Parkinson’s disease, and other neurological maladies.

Glutathione exists within cells in its reduced form (GSH), meaning it has an extra electron. In the process of neutralizing reactive oxygen species it becomes oxidized (GSSG), but reacts with another oxidized glutathione to become glutathione disulfide.  Because of enzymatic activity, glutathione is self-healing, particularly in the presence of available cysteine.  (Miller. 2002)  In healthy cells, more than ninety percent is the reduced form…and it should stay that way.  (Owen. 2010) This has strong implications for dietary habits.

Raising GSH through direct supplementation is difficult.  Research suggests that oral glutathione is not well-absorbed across the gastrointestinal tract, since it may be inactivated by peptidase enzymes in the gut.  (Witschi. 1992)  At least in the brain, GSH may be elevated by vitamin D. (Garcion. 2001)   However, the supplements, N-acetyl cysteine (NAC) and lipoic acid can increase GSH levels.  (Gross.1993)   (Busse. 1992)   (Shay. 2009) Ongoing research will determine the true bioavailability of oral supplementation.  In cases of Acetaminophen (Tylenol) poisoning, the number one cause of emergency room poisoning visits, the hospital will likely use NAC as an antidote.  Among health care providers, at least a little speculation has focused on the inclusion of NAC in acetaminophen tablets and capsules.

Although no specific foods contain glutathione, there are some that can elevate levels, most by virtue of their sulfur content, including animal products, red peppers, cabbage, broccoli, Brussels sprouts, onions, oats, lentils, beets, eggs, and parsley.  Because it is fundamental to a raft of physiological process, especially as an antioxidant, it’s wise to eat the foods that will ramp it up, including olives.

References

Visioli F, Wolfram R, Richard D, Abdullah MI, Crea R.
Olive phenolics increase glutathione levels in healthy volunteers.

J Agric Food Chem. 2009 Mar 11; 57(5):1793-6.

Lauren T. Miller, Walter H. Watso, Ward G. Kirlin, Thomas R. Ziegler and Dean P. Jones
Oxidation of the Glutathione/Glutathione Disulfide Redox State Is Induced by Cysteine Deficiency in Human Colon Carcinoma HT29 Cells
J. Nutr. 132:2303-2306, 2002

Owen JB, Butterfield DA.
Measurement of oxidized/reduced glutathione ratio.
Methods Mol Biol. 2010;648:269-77.

Witschi A, Reddy S, Stofer B, Lauterburg BH.
The systemic availability of oral glutathione.
Eur J Clin Pharmacol. 1992;43(6):667-9.

Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D.
New clues about vitamin D functions in the nervous system.
Trends Endocrinol Metab. 2002 Apr;13(3):100-5.

Gross CL, Innace JK, Hovatter RC, Meier HL, Smith WJ.
Biochemical manipulation of intracellular glutathione levels influences cytotoxicity to isolated human lymphocytes by sulfur mustard.
Cell Biol Toxicol. 1993 Jul-Sep;9(3):259-67.

Busse E, Zimmer G, Schopohl B, Kornhuber B.
Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo.
Arzneimittelforschung. 1992 Jun;42(6):829-31.

Kate Petersen Shay, Régis F. Moreau, Eric J. Smith, Anthony R. Smith, and Tory M. Hagen
Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
Biochim Biophys Acta. 2009 October; 1790(10): 1149–1160.

Wu G, Fang YZ, Yang S, Lupton JR, Turner ND.
Glutathione metabolism and its implications for health.
J Nutr. 2004 Mar;134(3):489-92.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Gallstones: An Ounce Of Prevention Is Worth…

basic-food-groupIf you have some gall, we hope it’s the kind that causes you to exasperate others, and not the kind that hurts in the center of your upper belly, under the ribs, and occasionally spreads to your right upper back or shoulder.  Gallstone disease is the most common and costly of all the digestive conditions in the United States, accounting for nearly a million hospitalizations a year.  It can interfere with breathing and become severe enough to wake you from sleep…if you can get there in the first place.  Sometimes a person will vomit and relieve the pain; at other times he’ll get feverish from an outright blockage of the bile duct that connects the liver and gall bladder to the small intestine.  With a blockage, urine turns dark, stools are clay-colored, and the whites of the eyes may yellow.  We hope it never gets this far.

While allopathic medicine preaches no sure way to prevent gallstones, it allows that there are means to reduce risk.  Staying close to your ideal weight is important.  A real concern with this is that, lately, everybody is jumping onto the “lose weight fast” bandwagon.  It seems that gallstones can form from such a regimen and even from gastric bypass surgery (Shiffman, 1991).   In obesity, bile tends to stand still and cholesterol saturation increases.  Stones can form within a month of severe caloric restriction, as much as twenty-five times more likely than in obese persons who lose weight gradually (Weinsier, 1993).  Once in a while a person gets lucky, and there are no symptoms, despite the fact that most middle-agers probably have small stones.

Whether it was intended to be a mnemonic or not, the association of the “Five F’s” with gallbladder disease has been around for a time.  Female, fair (hair and skin), forty-ish, fertile (gallbladder trouble is associated with high estrogen), and owning too much fat risk gallstones.  But alcohol intake, a high-fat diet (especially fried foods) and sedentary lifestyle are contributing factors.  In an acute gallbladder attack, people will generally go to the ER, where they will get antibiotics and medicine for the pain, which will probably go away.  If an obstruction is noted, surgery will be done.  In a chronic gallbladder condition, surgery, either traditional or laparoscopic, will remove the gallbladder.  In circumstances that can be pinpointed only by a physician, medications called chenodeoxycholic acids or ursodeoxycholic acids can be given to help dissolve the stones.  But this can take as long as two years and the stones often reappear after treatment is stopped.

It is advisable that, if you are prone to gallbladder problems, you eat a low-fat, low-sugar, high fiber diet.  Decreasing fat limits the amount of work the gallbladder has to do every day.  Increasing fiber helps the liver to eliminate toxins faster. Besides, anything that supports liver function also helps it to make more bile.  Alternative treatment of gallbladder disease relies on increased bile production, liquefaction of bile to help get rid of gallbladder sludge, and dissolution of stones so they can be reduced to a size that can pass naturally. Production of bile can be increased with foods that reduce toxic burden on the whole body, including beets, artichokes (Saénz Rodriguez, 2002), greens, and cruciferous vegetables (Tsai, 2006).  Acidulated water also stimulates liver function. Even a shot of unfiltered apple cider vinegar can help.

Since an ounce or prevention is worth more than a ton of cure, take a look at what coffee does for gallbladder disease.  Harvard scientists found that increased intake of caffeinated beverages reduces the risk of symptomatic gallbladder disease in men, while decaf demonstrated no such effect (Leitzmann, 1999).  In a ten-year study of male healthcare professionals, the incidence of gallbladder attacks was significantly lower in those consuming coffee regularly.   A novice coffee drinker might get the jitters and act like Barney Fife charging his cylinder, but the tradeoff is worth it.  Later study by the same researcher discovered a parallel benefit for women (Leitzmann, 2002).  Using ultra-sound to document gallbladder disease, the Third National Health and Nutrition Examination found that, among women, there was a decreased prevalence of previously diagnosed gallbladder disease with increased coffee drinking (Ruhl, 2000).

Primates and guinea pigs are unable to create vitamin C from diet, so supplementation is required.  The enzyme needed to convert glucose into ascorbic acid was lost eons ago.  Without vitamin C, even guinea pigs get gallstones, although we have never seen tiny guinea pig ambulances in our neighborhood.  From the same health and nutrition exam cited earlier, which ran from 1988 to 1994, researchers from the V.A. Center in San Francisco saw an inverse relationship between vitamin C intake and gallstones, strongly so among women, less so among men (Simon, 1998, 2000).  Vitamin C, by the way, affects the catabolism of cholesterol to bile acids.  Using guinea pigs as, well, guinea pigs, Swedish investigators learned that deficiency of vitamin C causes supersaturation of bile and the subsequent formation of cholesterol gallstones.  But they also found an interesting side story in humans.  Increasing ascorbic acid also increases phospholipid concentrations, leading to a strong inverse association with the conditions that lead to stone formation (Gstafsson, 1997).  German scientists came to the same conclusion about ascorbic acid when they found half the incidence of gallstones in a female population that supplemented with vitamin C regularly (Walcher, 2009) (Lammert, 2004).

So far, prevention has addressed measures that are readily available, off the shelf.  An important strategy to prevent stone formation if one is susceptible is to alter the conditions that promote it.  That can be done with phosphatidylcholine (PC), the chief phospholipid from which the cell membrane is made.  Enriching your diet with PC can directly affect cholesterol solubilization and reduce or eliminate the probability of gallstone formation (Kasbo, 2003) (Vakhrushev, 2005) (Lammert, 2004).

Anecdotal reports about healing protocols abound.  But some of them are surprisingly supportable.  When a person is hospitalized for gallbladder disease, his food is typically replaced with intravenous fluids.  In a while, the pain goes away, after which time you’re allowed to eat.  It’s believed that some foods invoke an allergic response that is at the root of gallbladder attacks.  In a casual test done in the late 1960’s, Dr. James Breneman, the chair of the Food Allergy Committee of the American College of Allergists, asked 69 people suffering from gallbladder pain to try an elimination diet to determine food allergies.  After the identified foods were taken from their diets, symptoms disappeared.  The offending foods were tagged.  Eggs, pork, onions, chicken and turkey, milk, coffee, and oranges were most bothersome, followed by corn, beans, nuts, spices, peanuts, fish and rye.  In addition to foods, twenty percent of the group had attacks caused by medications (Wright, 2004).

Pain and the fear of surgery will direct a person to the least invasive solution he can find, whether it’s clinically proven or not.  There is at least one such remedy for gallstone dissolution that seems to be popular outside the U.S.—a gallbladder cleanse purportedly designed by a Korean chemist named Dr. Lai Chiu Nan.  It entails drinking four glasses of apple juice (or eating four-five apples) daily for five days.  The juice is supposed to soften the stones.  Maintain a normal diet during this time.  On day six, no dinner is enjoyed.  At 6 PM, a teaspoon of Epsom salts in a glass of warm water is consumed, followed by a second such cocktail two hours later.  Magnesium sulfate opens the gallbladder ducts (Harvey, 1973).  At 10 PM, swallow a half cup of olive oil mixed with a half cup of fresh lemon juice, to lubricate the stones and to ease their passage.  Green stones are supposed to drop into the toilet the next day.  If they don’t, use the olive oil and lemon juice to make vinaigrette.  If they do, a gemologist might make you an offer.  Hey, sometimes folk medicine really works, as in the oatmeal baths for itchy skin or lemon juice and honey for a sore throat.

Bile synthesis has been improved and increased by taking essential fatty acids, most notably fish oil.  In a head-to-head contest with fibrates (drugs used to lower triglycerides and cholesterol), fish oil was found to up the ante on bile acids and to alter their distribution (Jonkers, 2006).  But this wasn’t the first time that fish oil stood in the limelight.  Gall bladder emptying increases with fish oil, as gall bladder motility improves and triglyceride levels drop (Jonkers, 2003).  And it sure works on monkeys (Scobey, 1991).  In prairie dogs, who must be kin to guinea pigs because they are prone to gallstones, menhaden oil (an occasional source of commercial fish oil) increased levels of EPA and DHA and reduced incidence of cholesterol crystals (Booker, 1990).

We normally think of solvents as able to dissolve things, but almost never relate them to the human body except in old Vincent Price movies.  Some scientists might disagree with this neglect because they have learned that gallstones can sometimes be dissolved by plant-sourced solvents, especially a terpene called limonene, common to citrus fruits and recognized as a safe flavoring agent in foods and beverages.  An unsaturated hydrocarbon from plants, limonene has been tried and proven to be a dissolver of cholesterol stones (Sun, 2007), while a welcome side effect is the relief of heartburn and GERD (Ibid.).  In a trial dating back to the 1970’s, a blend of limonene and polysorbate 80 (an emulsifier) was found safe and effective in the lab and the clinic (Igimi, 1976).  Occasionally following gallbladder surgery, stones are retained in the duct.  Injecting a limonene preparation directly to the biliary system was able to dissolve retained stones (Igmini, 1991).  Efficacy was enhanced when limonene was mixed with a medium-chain triglyceride in a Japanese study done toward the end of the last century (Shionogi, 1992).  Besides citrus, a readily available source of such solvent is peppermint oil.  Whether it works orally to dissolve gallstones is under investigation.  It’s doubtful that some of us can wait for the results to be printed.

References

Baranyai T, Terzin V, Vajda A, Wittmann T, Czakó L.
[Acute pancreatitis caused by hypertriglyceridemia].  [Article in Hungarian]
Orv Hetil. 2010 Nov 7;151(45):1869-74.

Booker ML, Scott TE, La Morte WW.
Effects of dietary fish oil on biliary phospholipids and prostaglandin synthesis in the cholesterol-fed prairie dog.
Lipids. 1990 Jan;25(1):27-32.

Doran J, Keighley MR, Bell GD.
Rowachol–a possible treatment for cholesterol gallstones.
Gut. 1979 Apr;20(4):312-7.

Gaby AR.
Nutritional approaches to prevention and treatment of gallstones.
Altern Med Rev. 2009 Sep;14(3):258-67.

Gilat T, Leikin-Frenkel A, Goldiner L, Laufer H, Halpern Z, Konikoff FM.
Arachidyl amido cholanoic acid (Aramchol) is a cholesterol solubilizer and prevents the formation of cholesterol gallstones in inbred mice.
Lipids. 2001 Oct;36(10):1135-40.

Gustafsson U, Wang FH, Axelson M, Kallner A, Sahlin S, Einarsson K.
The effect of vitamin C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time.
Eur J Clin Invest. 1997 May;27(5):387-91

R. F. HARVEY AND A. E. READ
Effects of oral magnesium sulphate on colonic motility in patients with the irritable bowel syndrome’
Gut, 1973, 14, 983-987

Igimi H, Hisatsugu T, Nishimura M.
The use of d-limonene preparation as a dissolving agent of gallstones
Am J Dig Dis. 1976 Nov;21(11):926-39.

Igimi H, Tamura R, Toraishi K, Yamamoto F, Kataoka A, Ikejiri Y, Hisatsugu T, Shimura H.
Medical dissolution of gallstones. Clinical experience of d-limonene as a simple, safe, and effective solvent.
Dig Dis Sci. 1991 Feb;36(2):200-8.

Igimi H, Watanabe D, Yamamoto F, Asakawa S, Toraishi K, Shimura H.
A useful cholesterol solvent for medical dissolution of gallstones.
Gastroenterol Jpn. 1992 Aug;27(4):536-45.

Jonkers IJ, Smelt AH, Ledeboer M, Hollum ME, Biemond I, Kuipers F, Stellaard F, Boverhof R, Meinders AE, Lamers CH, Masclee AA.
Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil.
Gut. 2003 Jan;52(1):109-15.

Jonkers IJ, Smelt AH, Princen HM, Kuipers F, Romijn JA, Boverhof R, Masclee AA, Stellaard F.
Fish oil increases bile acid synthesis in male patients with hypertriglyceridemia.
J Nutr. 2006 Apr;136(4):987-91.

Kasbo J, Tuchweber B, Perwaiz S, Bouchard G, Lafont H, Domingo N, Chanussot F, Yousef IM
Phosphatidylcholine-enriched diet prevents gallstone formation in mice susceptible to cholelithiasis.
J Lipid Res. 2003 Dec;44(12):2297-303. Epub 2003 Jul 1.

Kraft K.
Artichoke leaf extract- recent findings reflecting effects on lipid metabolism, liver and gastrointestinal tracts.
Phytomedicine 1997;4:369-78.

Lammert F, Matern S.
Evidence-based prevention of cholecystolithiasis.
Dtsch Med Wochenschr. 2004 Jul 9;129(28-29):1548-50.

Leitzmann MF, Willett WC, Rimm EB, Stampfer MJ, Spiegelman D, Colditz GA, Giovannucci E.
A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.
JAMA. 1999 Jun 9;281(22):2106-12.

Leitzmann MF, Stampfer MJ, Willett WC, Spiegelman D, Colditz GA, Giovannucci EL.
Coffee intake is associated with lower risk of symptomatic gallstone disease in women.
Gastroenterology. 2002 Dec;123(6):1823-30.

Riber C, Hojgaard L, Madsen JL, Rehfeld JF, Olsen O.
Gallbladder emptying and cholecystokinin response to fish oil and trioleate ingestion.
Digestion. 1996;57(3):161-4.

Ruhl CE, Everhart JE.
Association of coffee consumption with gallbladder disease.
Am J Epidemiol. 2000 Dec 1;152(11):1034-8.

Saénz Rodriguez T, García Giménez D, de la Puerta Vázquez R.
Choleretic activity and biliary elimination of lipids and bile acids induced by an artichoke leaf extract in rats.
Phytomedicine. 2002 Dec;9(8):687-93.

Scobey MW, Johnson FL, Parks JS, Rudel LL.
Dietary fish oil effects on biliary lipid secretion and cholesterol gallstone formation in the African green monkey.
Hepatology. 1991 Oct;14(4 Pt 1):679-84.

Shiffman ML, Sugerman HJ, Kellum JM, Brewer WH, Moore EW.
Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity.
Am J Gastroenterol. 1991 Aug;86(8):1000-5.

Simon JA, Hudes ES.
Serum ascorbic acid and gallbladder disease prevalence among US adults: the Third National Health and Nutrition Examination Survey (NHANES III).
Arch Intern Med. 2000 Apr 10;160(7):931-6.

Simon JA, Hudes ES.
Serum ascorbic acid and other correlates of gallbladder disease among US adults.
Am J Public Health. 1998 Aug;88(8):1208-12.

Sun J.
D-Limonene: safety and clinical applications.
Altern Med Rev. 2007 Sep;12(3):259-64.

Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL.
Fruit and vegetable consumption and risk of cholecystectomy in women.
Am J Med. 2006 Sep;119(9):760-7.

Vakhrushev IaM, Suchkova EV.
Use of essentiale and cholagogum in prevention of cholelithiasis in fat hepatosis with concomitant cholecystitis 
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von Bergmann K, Beck A, Engel C, Leiss O.
Administration of a terpene mixture inhibits cholesterol nucleation in bile from patients with cholesterol gallstones.
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Walcher T, Haenle MM, Kron M, Hay B, Mason RA, Walcher D, Steinbach G, Kern P, Piechotowski I, Adler G, Boehm BO, Koenig W, Kratzer W; EMIL study group.
Vitamin C supplement use may protect against gallstones: an observational study on a randomly selected population.
BMC Gastroenterol. 2009 Oct 8;9:74.

Weinsier RL, Ullmann DO.
Gallstone formation and weight loss.
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Williams CA, Goldstone F, Greenham J.
Flavonoids, cinnamic acids and coumarins from the different tissues and medicinal preparations of Taraxacum officinale.
Phytochemistry. 1996 May;42(1):121-7.

Wright, Jonathan V.
The 99.9 percent effective technique for eliminating gallbladder attacks forever
Nutrition and Healing. 2004; 11(9):1

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Gut Health, Body Health

stomachThe large intestine is seldom the topic of conversation, with the possible exception of surgeons and gastroenterologists. Most “civilians” don’t pay attention to it until it isn’t working right. The inability to move material out of it is one reason. Unusual egesta might be another. Regardless of its laid back persona, the colon is actually an interesting character. It runs from the cecum (the beginning of the large intestine, where the appendix hangs) to the rectum (the dumpster), and extends about five or six feet. If you want to be technical, the colon runs between these two points. The large intestine has no digestive function, but lubricates wastes and absorbs water and remaining salts, and stores useless stuff for eventual removal. It takes about sixteen hours to evacuate the hold. You need to know that the large intestine absorbs vitamins made by colonic bacteria, such as vitamin K and the vitamin A converted from beta-carotene.

Despite that the colon is known for removal of material, there exists inside a raft of bacteria that keep a permanent residence. In fact, there are more bacteria in the colon than cells in the body. If you have ten trillion cells in your body, you have ten times that many microbes, weighing from two to five pounds. This microflora is sometimes called the microbiome or microbiota. Whichever term is used, the activities performed by these bacteria parallel that of an organ, rivaling the metabolic capacity of the liver (MacFarlane, 2010). For example, carbohydrates are fermented to form short-chain fatty acids that support epithelial cell growth, which helps to reduce the absorption of toxic products. The flora recycle carbon and nitrogen, manufacture methane, metabolize steroids, convert lignans and phytoestrogens to other compounds and fight invasion by unwelcome species. Although people can survive without them, these bacteria are among the best of friends. Damaged or abnormal gut flora is the cause of much human agony as a prime factor in disease. Treating the microbiome with dignity and respect may prevent, or even reverse, disorders that include heart disease, autoimmune conditions, allergies and cancer (deVrese, 2008) (Garcovich, 2012).

There are hundreds of different species of micro-organisms living in the gut, more than 95% of which are anaerobic and genetically diverse. A lactobacillus is more different from a bifidobacterium than a human is from a rabbit. Identification of all species is difficult because not all can be cultured, but you can rest assured that your bacteria belong to you, remaining fairly constant throughout your life time. Talk about close friends!  The healthy bacteria provide a natural barrier against pathogenic bacteria, parasites, fungi, viruses, toxins and whatever else would wreak havoc with our health. Basically, there are half a dozen main groups:  Bacteroides, Firmicutes (Clostridia, Lactobacilli, Streptococci), Actinobacteria (Bifido-), Proteobacteria (Entero-), Fusobacteria and Verrucomicrobia. Not all of these offer salubrity. Some are so complex they almost defy taxonomy, but to our benefit, the good control the evil (Vedantam, 2003) (Beaugerie, 2004).

Analyses have determined that specific gut microbes are associated with what we eat. Some are associated with carbohydrates and some with animal proteins, fats and amino acids. It appears they come to the front of the class when it’s their turn to perform. Changing diet from one type of macro-nutrient to another can alter which bacterial strain is on stage at the time. A baby’s gut is clean and sterile until it entertains bacteria from its mother. Vaginal birth may afford bacterial strains directly from mom’s gastrointestinal tract, while caesarean might present strains from the ambient environs, including the air and the attending medical folks. The infant doesn’t establish his own microbiota for up to six months after caesarean delivery, only one month for normal birth. In any case, the microbiota shapes the development of the immune system, and the immune system in turn shapes the composition of the microbiota (Nicholson, 2012).

The influence of gut microbes on immunity is profound and, therefore, associated with long-term health, particularly since microflora is relatively stable throughout adulthood. The dynamics of the gut environment are subject to perturbations, though, such as from stresses or dietary changes. It’s comforting to know that there is considerable interest in developing modalities that can manipulate biome composition to benefit the host through a kind of metabolic communication, such as would affect obesity and type 2 diabetes (Kootte, 2012). In these matters, therapeutic pathways may be designed by enlisting short-chain fatty acids, prebiotics, bile acids and probiotics. Realizing that antibiotics are non-selective in destroying bacteria—they kill the good as well as the bad—this give us the means for resolution of myriad complaints. In general, the host immune system can prevent the overgrowth of pathogens, which, upon ingestion, fall to this complex integrated structure.

Probiotics are helpful in many cases, but are not silver bullets. When used as part of a broad nutritional protocol, they are likely effective in establishing or re-establishing a healthy microbiome. Stress management, elimination of detrimental medications and dietary interventions need to be included in such a protocol. Because they are many and varied in their composition, probiotics are often viewed tentatively until they are administered and monitored for efficacy. Eating fermented foods, like sauerkraut, yogurt and kefir, fosters a nurturing environment for your own microbiome. The florae best known are the Lactobacilli (there are more than 50 strains) and Bifidobacteria (there are more than thirty). Lacto-, in one strain or another, have been used to treat and to prevent a variety of conditions, from bacterial vaginosis to childhood abdominal distress and diarrhea, to childhood respiratory infections. Bifidobacteria comprise about 90% of the intestinal community, and appear in an infant’s gut within days of parturition, especially if breastfed. The Bifido- species has been used to address irritable bowel syndrome, dental caries, blood lipids and glucose tolerance.  A knowledgeable nutrition professional can guide you in the choice of probiotics to meet a specific need if you have one. Oh, yeah, there is a yeast probiotic, called Saccharomyces boulardii, which is quite effective in treating diarrhea associated with antibiotic use, and may even be helpful with Clostridium difficile and acne.

Hey, what about short-chain fatty acids (SCFA), especially butyrate?  We’re glad you asked. Butyrate is derived from the bacterial fermentation of resistant starches and fibers. Its multiple beneficial effects have been demonstrated beyond the colon, mostly because SCFA can be absorbed across the colonic epithelium. Now that gut health has its own fan club, what with renewed interest in the GI barrier defense system, SCFAs are the darlings of moneyed research. These 2-carbons to 5-carbons fatty acids include acetate, propionate, butyrate and valerate, but the 4-carbon butyrate is the featured performer due to its multiplicity of virtues. Among butyrate’s mechanisms of action are the regulation of gene expression, inhibition of histone deacetylase (an action which helps to make copies of DNA), sequestration of ammonia (ammonia causes cloudy thinking), mobilization of renegade fats, and clearance of biotoxins (Soret, 2010) (Fusunyan, 1999) (Yin, 2001). Because butyrate availability in the colon is lower than the other SCFAs, supplementation is highly recommended. You can’t eat enough resistant starches to make enough butyrate to be physiologically significant. However, even at low concentrations, butyrate can inhibit cell proliferation of several colon cancer lines. At high concentrations, it works like gangbusters against cancer cells while leaving healthy cells alone (Omaida, 1996) (Gamet, 1992).

The extraordinary complexity of the human microbiome is only recently revealed, despite having been known for decades. The interdependence between beneficial bacteria and the immune system demands recognition. If the florae can fight the inflammation that threatens them, they can fight whatever threatens their host.

References

Arora T, Sharma R, Frost G.
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Bäckhed F, Fraser CM, Ringel Y, Sanders ME, Sartor RB, Sherman PM, Versalovic J, Young V, Finlay BB.
Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications.
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Beaugerie L, Petit JC.
Microbial-gut interactions in health and disease. Antibiotic-associated diarrhoea.
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Bischoff SC.
‘Gut health’: a new objective in medicine?
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Early nutrition and immunity – progress and perspectives.
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Roberto Berni Canani, Margherita Di Costanzo, and Ludovica Leone
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Cummings JH, Antoine JM, Azpiroz F, Bourdet-Sicard R, Brandtzaeg P, Calder PC, Gibson GR, et al
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de Vrese M, Schrezenmeir J.
Probiotics, prebiotics, and synbiotics.
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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Gut Bacteria And The Brain

brain-gears

They’re called flora. Their name comes from the Roman goddess of plants, flowers and fertility, and refers to the plant life occurring in a particular region. The region in this case is the intestine, and the florae that occupy it are micro-organisms that total almost a hundred trillion, a number considerably larger than the number of cells in the human body. So phenomenal are the metabolic activities of these bacteria that they are considered an organ (O’Hara, 2006). Gut bacteria are so influential that they affect more than just a few bodily functions, from immunity to weight control to behavior and concentration (Bravo, 2011). And without them we couldn’t make biotin, vitamin K, or the short-chain fatty acids that energize intestinal cells. An absence of intestinal bacteria is associated with reduction in mucus cell turnover, muscle wall thickness, cytokine production (regulatory proteins), and of course, digestion. The micro-organism population begins in the mouth, where about two hundred different kinds live. They bypass the almost-sterile stomach and then increase on their way to the colon, where several hundred species thrive (Canny, 2008). For all that we know about the body, this area is not completely understood.

Gut diversity is more pronounced in adults than in children and, once developed, tends to remain stable unless dietary changes are dramatic. Generally, those who consume lots of vegetables and fiber have a different composition from those whose diets typify the Western regimens that are high in unwholesome fats and carbohydrates. Studies have demonstrated that what happens in the gut affects what happens in other areas of the body as well, including those that manage mood, anxiety, and possibly the onset of chronic and degenerative diseases (Tillisch, 2013). Suppose we could manipulate intestinal conditions to address health issues, either one at a time or as a group, by using probiotics.

Lactic acid bacteria and Bifidus bacteria are the most common ones used as probiotics, but others may also be employed. The WHO recognizes probiotics as living micro-organisms that confer a health benefit when taken in adequate amounts. The “health benefit,” however, is undefined. What is defined is that specific strains of a beneficent bacteria offer specific effects that cannot be ascribed to other strains, even in the same variety. Therefore, the probiotic used to treat irritable bowel syndrome will be different from the one used for pediatric diarrhea (Verna, 2010). What’s more, the optimal remedial number of colony forming units (CFU’s) for each bacterial strain is still uncertain; and the doses used in animal studies do not necessarily translate to humans. Then there’s the delivery system. Do we use yogurt, milk or a capsule? The gut environs make a difference, too. If too acidic or alkaline, some bacteria cannot survive.

One micro-organism has shown significant promise as a therapeutic agent in the matter of hypertension. It’s called Lactobacillus helveticus, a bacterium used to add a nutty flavor to American Swiss cheese and to prevent bitterness, although it lends character to other cheeses, including cheddar and various Italian varieties. The name helveticus derives from a Gallic tribe that occupied Switzerland in the first century B.C.

L. helvicus produces a compound called a tripeptide. A peptide consists of two or more amino acids linked end to end, sort of like joining batteries in series (That would be positive to negative in order to increase voltage.)  They always hook up between the oxygen-bearing carbon end of one amino and the nitrogen-bearing end of the other. When you get ten or more amino acids in this parade, it’s called a polypeptide; fifty or more give you a protein. That’s the stuff we’re made from. Some peptides, though, are hormones. The biological synthesis of protein depends on messenger RNA that lives on ribosomes; that of peptides doesn’t. A tripeptide has three amino acids. A familiar one is glutathione, an antioxidant made by the body to shield itself from reactive oxygen species. When L. helveticus is used to make a fermented milk product, it forms a tripeptide called IPP, or isoleucine-proline-proline, which acts like an ACE inhibitor.

Without getting too complicated, an ACE inhibitor deals with angiotensin-converting enzyme, a substance that makes angiotensin, which narrows blood vessels after the lub-dub and consequently raises blood pressure. Most of these drugs end in “-pril,” but have different brand names, such as Univasc, Altace or Vasotec. As with all pharmaceuticals, there are side effects, the most common being a bothersome cough. With L. helveticus there are none.  The Finns realized this after conducting a gold-standard clinical trial—randomized, double-blind, placebo-controlled—in which one hypertensive group received no intervention and the other received 150 milliliters (5 oz.) of L. helveticus fermented milk twice a day for ten weeks. There was a four-point difference in systolic pressure and a two-point difference in diastolic pressure between groups, indicating efficacy of the IPP tripeptide (Jauhiainen, 2005). Though these numbers don’t seem like much, they are, indeed, significant. If you prefer higher numbers, another, earlier, Finnish study reported six point and four point differences (Seppo, 2003). Contributing to this positive outcome is a reduction in the arterial stiffness that contributes to hypertension, particularly as we age. Additional study along these lines found that L. helveticus dairy wrought moderate changes in gene expression in the aorta, which you know to be the main artery leading away from the heart (Ehlers, 2011).

Finland is not the only venue enjoying the anti-hypertensive nature of fermented dairy. The Sant’Orsola-Malpighi University Hospital, in Bologna, Italy, noticed that subjects with high-normal blood pressure experienced a drop in numbers, while those with normal readings were unaffected, which is not a surprise (Cicero, 2010). To make this enterprise even more affable, the Japanese used powdered fermented milk to draw similar results, adding a kind of portability to the protocol (Aihara, 2005).

It’s almost hard to bridle one’s encouragement at the prospect of a hypertension management system based on functional food. A few probiotics already contain the strain: Dr. Stephen Langer’s, Garden of Life, and New Chapter are three. Spectra Probiotic by Integrative Therapeutics is another. Kefir, a probiotic drink available in the supermarket, contains L. helveticus, as well as other beneficent micro-organisms. Be advised not to stop any medications. Just know that any decrease in BP is welcome.

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*These statements have not been evaluated by the FDA.
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Colon and Butyrate: The Colon Beyond Punctuation

crammed-jarQuite a lot of people do not like to share their space. It’s understandable that some are uncomfortable when a conversation, as with a stranger, is carried on nose to nose. In Arab countries, it is offensive to step or lean away during such an encounter. There is, however, an instance where closeness cannot be avoided with the microbiome that occupies not only our space, but also us. The human body holds ten times more microbes than human cells, some on the outside, and others on the inside. The skin, the largest organ of the body, houses a range of microbes that live in distinct communities yet work together to protect us from attack by sickness and disease (Grice, 2009). But our attention here is to those on the inside, the microbiota that weigh up to three pounds and contain tens of trillions of members. There might even be more than a thousand different species, about a third of which are common to most of us. The other two-thirds belong only to you.

Though we have a tailor-made personal microbiome, all perform the same physiological functions and have a direct impact on our health. Besides completing digestion by absorbing water and storing wastes, the gut microbes help to make biotin and vitamin K while fighting aggression from the pathogenic gang of bugs and bolstering the immune system. Each of our gut communities remains stable throughout our lives, unless dietary changes are dramatic. Those who consume lots of vegetables and fiber have a different composition from those who live on fatty meats and simple carbohydrates. What happens in the gut telegraphs to what happens in other areas of the body, including areas that manage mood and possibly the onset of chronic and degenerative diseases (Tillisch, 2013).

The neonatal biome starts to form right after birth, when the digestive tract becomes colonized by micro-organisms that come from the mother and from the environment into which it is born. In about three years the biome becomes stable. To keep it that way, we need to take measures that transcend dietary behavior and the mere swallowing of probiotics as adults. Probiotics are micro-organisms. To analogize, they’re like police whose local precinct needs a workplace conducive to efficiency.  If a probiotic, or any array of gut bacteria for that matter, is to augment or to enhance the native population, it needs a favorable place to work. The problem with the typical Western diet is that we feed the upper GI tract without feeding the gut. One way to do that is with resistant starch, the fermentation of which manufactures short-chain fatty acids, notably butyrate. Butyrate nourishes the gut barrier and helps to prevent inflammation.  Very often, however, dietary intake of resistant starch is insufficient to make enough butyrate to be physiologically significant.

What does butyrate do?  It has powerful effects on several colonic functions, not the least of which is the inhibition of inflammation and carcinogenesis, and the reinforcement of the defenses that fight infection and oxidative stress (Hamer, 2008). Butyrate has partners and precursors in the form of acetates and propionates, likewise made by the bacterial fermentation of resistant starch and fiber.  In the company of acetate, butyrate is reported to protect against diet-induced obesity without causing hypophagia, while propionate may reduce food intake. Unfortunately, there is little understanding why this works (Hua, 2012). What distinguishes one from another?  The number of carbons it holds. Acetic acid has two, propionic acid has three and butyric acid has four. The first of these has the scent of vinegar. Propionic acid is found in sweat; butyric acid in rancid butter and vomit.

Butyrate, joined with calcium, magnesium, potassium, sodium or a combination of these minerals inhibits histone deacetylase enzymes, helping butyric acid to enhance the transcription activity of DNA. Sodium butyrate, for example, has been found to increase lifespan in animal experiments (Zhang, 2009). Of the three short-chain fatty acids mentioned, butyrate is more potent than the others at inhibiting invasive colon cancers (Emenaker, 1998). If this activity of the butyrate molecule has been known since the late 1990’s, why has it not received the publicity that newly-concocted drugs, with their hosts of nasty side effects, have?

The reasons for paying attention to your gut go beyond what you read while seated. Some problems can be attenuated with an occasional laxative, although increasing dietary fiber is a better technique. Even the orange-flavored stuff in the plastic canister, used every day, is an improvement. But a butyrate supplement, despite its pungency, is the best thing going, especially as we get older.

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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.