Gut healing, Intestinal Permeability, Biofilm

Beyond Probiotics
Hidden Causes of GI Dysfunction
By Chris D. Meletis, ND
Often, in the absence of overt disease, the extent of an individual’s colon-supporting supplement regimen consists exclusively of consuming a good probiotic. Yet, in order for the good bacteria found in probiotics to flourish in the colonic environment, there are other steps we need to take to ensure our gut is hospitable to the friendly bacteria our bodies need to thrive—regardless of whether an individual is healthy or whether that individual suffers from irritable bowel syndrome or another gastrointestinal disease. The colon is essentially our body’s compost pile, used to nurture our garden of friendly flora.

There are two often-overlooked aspects of gut health that are essential to keeping our colon healthy and to ensure it remains a hospitable environment where good bacteria can thrive. First, gut health is linked to a substance called butyrate. If the intestine isn’t working at its optimal best, levels of butyrate can undergo a decline, putting individuals at risk for colon cancer. Butyrate levels are closely tied to the health of the intestine and to levels of friendly flora found in the gut.

A second aspect of gut health is known as intestinal permeability. This can be a huge factor, even in seemingly healthy individuals. Intestinal permeability refers to the potential for nutrients and bacteria to escape through a weakened intestinal wall. When intestinal permeability is increased, food and nutrient absorption is impaired. Dysfunction in intestinal permeability can result in leaky gut syndrome, where larger molecules in the intestines pass through into the blood. This can trigger immediate damage and immune system reactions since these large molecules are perceived as foreign. Progressive damage occurs to the intestinal lining, eventually allowing disease-causing bacteria, undigested food particles, and toxins to pass directly into the bloodstream.

Dysfunctions in intestinal permeability are associated not only with intestinal diseases such as ulcerative colitis, irritable bowel syndrome and Crohn’s disease, but also with chronic fatigue syndrome, psoriasis, food allergies, autoimmune disease and arthritis. Impaired intestinal permeability also occurs in patients undergoing chemotherapy and in heart disease patients.

I briefly discussed intestinal permeability in my last article on GI health. In this article, I will go into further detail about this damaging aspect of intestinal health and explain how increasing butyrate can be a powerful tool in not only restoring ideal colon function but also improving energy levels and the overall health of the body.

Building Butyrate for Colonic Health

Butyrate, a major short-chain fatty acid produced in the human gut by bacterial fermentation of dietary fiber, exhibits strong tumor suppressing activity. Butyrate is an important energy source for cells lining the intestine and plays a role in the maintenance of colonic balance. Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis. Butyrate also reinforces various components that play a role in the colonic defense barrier and decrease oxidative stress. In addition, butyrate may promote satiety.1

Low levels of butyrate are linked to increased risk of colon cancer. A loss of balance in the colon caused by either genetic mutations or environmental factors such as dietary habits can increase the risk for the formation of aberrant crypt foci (the earliest identifiable cancerous lesions in the colon) and ultimately the development of colon cancer. Evidence exists that butyrate reduces the number and the size of aberrant crypt foci in the colon.2

Butyrate’s inhibition of colon cancer is thought to arise from its ability to act as a natural histone deacetylase inhibitor, which results in activation of certain genes known to induce apoptosis (cell death) in cancer cells.2

Low butyrate levels occur in healthy humans prior to the onset of disease, often in response to a poor diet high in sugar and low in fiber. Low butyrate levels also are found in disease states such as ulcerative colitis and Crohn’s disease, especially in patients with moderate to severe mucosal inflammation.3 The monocarboxylate transporter helps colon cells uptake butyrate and during inflammatory bowel disease the monocarboxylate transporter is impaired, preventing the butyrate from getting to the cells.4

The Colonic Barrier and Overall Health

Abnormal intestinal permeability, like low butyrate levels, is another concern that can serve as a hidden reason why we might not be feeling our optimal best. A dysfunction can present in intestinal permeability when an individual is consuming a less than optimal diet or due to other factors such as psychological stress.5

Intestinal permeability, in fact, may be the main cause behind why the body becomes sensitive to a particular type of food. One group of researchers evaluated the intestinal permeability in subjects with adverse reactions to food. Twenty-one subjects with a food allergy and 20 with food hypersensitivity who were on allergen-free diets were enrolled and divided into four groups according to the seriousness of their referred clinical symptoms. The study authors found statistically significant differences in intestinal permeability in subjects with food allergy or hypersensitivity compared to control patients. The worse the intestinal permeability, the more serious the clinical symptoms in patients with food allergy and hypersensitivity.6

According to the researchers, “The present data demonstrate that impaired intestinal permeability, measured in our conditions, is present in all subjects with adverse reactions to food. In addition, for the first time, we report a statistically significant association between the severity of referred clinical symptoms and the increasing of Intestinal Permeability Index. These data reveal that intestinal permeability is not strictly dependent on IgE-mediated processes but could better be related to other mechanisms involved in early food sensitization, as breast-feeding, or microbial environment that influence the development of oral tolerance in early infancy.”

Impaired intestinal permeability is often linked with GI diseases such as ulcerative colitis and Crohn’s. However, new research is unearthing a surprising link between malfunctions in the colonic barrier and a number of non-gastrointestinal conditions such as heart disease.

In a recent study, scientists evaluated the function of the gut in 22 patients with chronic heart failure (CHF) and 22 control subjects. Chronic heart failure patients, compared with control patients, had a 35 percent increase of small intestinal permeability and a 210 percent increase of large intestinal permeability. Additionally, higher concentrations of adherent bacteria were found within mucus of CHF patients compared to control subjects.7

The researchers determined, “Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified. Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition.”

Strengthening the Colon

Raising butyrate levels and reducing the permeability of the intestinal barrier can have far reaching consequences for our health that extend beyond the gastrointestinal tract. Consequently, nutritional support is key.

Increasing fiber intake through consumption of a fiber supplement is one of the easiest ways to increase butyrate levels in the body. Fiber is well known for its ability to protect against colon cancer and its ability to raise butyrate levels is thought to be one of the main ways in which it protects the colon. The benefits of dietary fiber on inflammatory bowel disease may also be related to the production of butyrate that occurs when fiber is fermented in the colon. Butyrate appears to decrease the inflammatory response.8

Combining fiber and a good probiotic with specific botanicals, amino acids and fatty acids known to reduce intestinal permeability can provide additional support for the colon. Phosphatidylcholine, for example, can enhance butyrate’s ability to inhibit colon cancer cells, and therefore works well with fiber to strengthen the intestinal environment.9

The amino acid glutamine is one of the most powerful tools for reducing intestinal permeability, thereby protecting the body against the negative consequences of a leaky gut. In a recent review, researchers studied the medical literature to determine if glutamine was effective in reducing intestinal permeability in critically ill patients. In this group of patients, intestinal permeability can have particularly lethal consequences, causing bacteremia, sepsis, and multiple organ failure syndrome. After studying the medical literature, the scientists concluded that glutamine administration by the intravenous or oral route has a protective effect that prevents or reduces the intensity of the increase in intestinal permeability. Glutamine also reduces the frequency of systemic infections.10

Another group of researchers drew a similar conclusion after studying chemotherapy patients with gastrointestinal cancer. In this group of subjects, oral glutamine decreased intestinal permeability and maintained the intestinal barrier.11

Berberine is another substance that can help reduce intestinal permeability and stop beneficial nutrients from escaping through the intestinal wall.12 Berberine also is highly effective at inhibiting the growth of pathogens that invade the colon.

In my clinical practice, I have found that the best way to improve butyrate levels and reduce intestinal permeability is to combine a good fiber supplement with a supplement that contains phosphatidylcholine, L-glutamine, berberine, deglycyrrhizinated licorice (DGL), N-acetyl glucosamine, marshmallow (Althaea officinalis) root, cabbage powder, slippery elm (Ulmus rubra) bark, and gamma oryzanol. This often results in an increased level of friendly flora in the gut and maximizes the effectiveness of any probiotic supplement consumed. After undertaking this approach, patients often report improvement in their gastrointestinal tract and increased overall health and energy.

Conclusion

The gut uses a disproportionate amount of energy (about 25 percent of total oxygen consumption) for the size of the tissue (about 6 percent of body weight).13 Consequently, it’s especially important to provide this part of the body with as much support as possible. Fiber, probiotics, the amino acid L-glutamine, the fatty acid phosphatidylcholine, N-acetyl glucosamine, deglycyrrhizinated licorice and select botanicals such as marshmallow, berberine, cabbage powder and slippery elm can help raise levels of butyrate and reduce intestinal permeability. This approach can result in a healthier colon, improved energy and enhanced overall health.

References


1. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19.
2. Kim YS, Milner JA. Dietary modulation of colon cancer risk. J Nutr. 2007 Nov;137(11 Suppl):2576S-2579S.
3. Duffy MM, Regan MC, Ravichandran P, O’Keane C, Harrington MG, Fitzpatrick JM, O’Connell PR. Mucosal metabolism in ulcerative colitis and Crohn’s disease. Dis Colon Rectum. 1998 Nov;41(11):1399-405.
4. Thibault R, De Coppet P, Daly K, Bourreille A, Cuff M, Bonnet C, Mosnier JF, Galmiche JP, Shirazi-Beechey S, Segain JP. Down-regulation of the monocarboxylate transporter 1 is involved in butyrate deficiency during intestinal inflammation. Gastroenterology. 2007 Dec;133(6):1916-27.
5. Zareie M, Johnson-Henry K, Jury J, Yang PC, Ngan BY, McKay DM, Soderholm JD, Perdue MH, Sherman PM. Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress. Gut. 2006 Nov;55(11):1553-60. Epub 2006 Apr 25.
6. Ventura MT, Polimeno L, Amoruso AC, Gatti F, Annoscia E, Marinaro M, Di Leo E, Matino MG, Buquicchio R, Bonini S, Tursi A, Francavilla A. Intestinal permeability in patients with adverse reactions to food. Dig Liver Dis. 2006 Oct;38(10):732-6.
7. Sandek A, Bauditz J, Swidsinski A, Buhner S, Weber-Eibel J, von Haehling S, Schroedl W, Karhausen T, Doehner W, Rauchhaus M, Poole-Wilson P, Volk HD, Lochs H, Anker SD. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007 Oct 16;50(16):1561-9.
8. Rose DJ, DeMeo MT, Keshavarzian A, Hamaker BR. Influence of dietary fiber on inflammatory bowel disease and colon cancer: importance of fermentation pattern. Nutr Rev. 2007 Feb;65(2):51-62.
9. Hossain Z, Konishi M, Hosokawa M, Takahashi K. Effect of polyunsaturated fatty acid-enriched phosphatidylcholine and phosphatidylserine on butyrate-induced growth inhibition, differentiation and apoptosis in Caco-2 cells. Cell Biochem Funct. 2006 Mar-Apr;24(2):159-65.
10. De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Crit Care Med. 2005 May;33(5):1175-8.
11. Zhonghua Wei Chang Wai Ke Za Zhi. 2006 Jan;9(1):59-61. [Protective effect of glutamine on intestinal barrier function in patients receiving chemotherapy] [Article in Chinese]. Jiang HP, Liu CA.
12. Taylor CT, Winter DC, Skelly MM, O’Donoghue DP, O’Sullivan GC, Harvey BJ, Baird AW. Berberine inhibits ion transport in human colonic epithelia. Eur J Pharmacol. 1999 Feb 26;368(1):111-8.
13. Britton R, Krehbiel C. Nutrient metabolism by gut tissues. J Dairy Sci. 1993 Jul;76(7):2125-31.

Gut Healing 1

HEALING A LEAKY GUT © What Doctors Don't Tell You (Volume 8, Issue 5) It's possible to cure a leaky gut with a nutrient dense diet and appropriate supplements. Many natural substances help repair the intestinal mucosal surface or support the liver when stressed by toxins. Your vitamin and mineral supplements should include all the B vitamins, vitamin A, C and E, zinc, selenium, molybdenum, manganese, and magnesium. Because of the association between increased gut permeability and pancreatic dysfunction, pancreatic enzymes may also be needed.Avoid drugs which damage the gut. Test for and get treated intestinal infection or dysfunction. If you haven't discovered all your allergies, follow a highly nutritious elimination diet, tailor made for you. The following substances can repair the gut wall: Epidermal growth factor (EGF), a polypeptide that stimulates growth and repair of epithelial tissue, is widely distributed in the body, with high concentrations detectable in saliva. Chew your food thoroughly, to increase salivary EGF. Also, purified EGF has been shown to heal ulceration of the small intestine (Lancet, 1993; 341: 843-8). Saccharomyces boulardii, a non pathogenic yeast originally isolated from the surface of lichee nuts, has been widely used in Europe to treat diarrhea. In France it is popularly called "Yeast against yeast" and is thought to help clear the skin in addition to the gut. Clinical trials have demonstrated the effectiveness of Saccharomyces boulardii in the treatment or prevention of diarrhea (Am J Gastroenterol, 1989; 84: 1285-7; Gastroenterol, 1989; 96; 981-8). Lactobacillus caseii var GG, a strain of lactobacillus isolated and purified in Finland, has been shown effective in the prevention of diarrhea and in the treatment of colitis. It also improves the gut permeability associated with rotavirus infection (Ann Med, 1990; 22: 57-9). Although the ability of other lactobacillus preparations to improve leaky gut has not been directly tested, it is suggested by the ability of live cultures of L acidophilus to diminish radiation induced diarrhea, a condition directly produced by the loss of mucosal integrity. Glutamine, the amino acid needed for the maintenance of intestinal metabolism, structure and function, has been shown to reverse all the gut abnormalities in patients fed intravenously. Glutamine also repairs gut lining damage caused by chemotherapy or radiation (Arch Surg, 1990; 125: 1040-5). Glutathione (GSH) is an important antioxidant. Lowered levels of liver glutathione is a common occurrence in leaky gut syndromes, contributing to liver dysfunction and liver necrosis among alcoholics and immune impairment in patients with AIDS. The most effective way to raise liver glutathione is to take its dietary precursors, systeine or methionine; the best supplements for leaky gut are GSH and N-acetyl cysteine. Avoid taking during treatment of parasite infection, especially with Artemisia. Take flavonoids before eating. They may block allergic reactions which increase permeability. Catechins have been used in Europe to treat gastric ulcerations; the flavonoids in milk thistle (silymarin) and in dandelion root (taraxacum) can protect the liver. Take essential fatty acids (EFAs), particularly gammalinolenic acid (GLA). In laboratory experiments, fish oil was able to prevent intestinal mucosal injury produced by methotrexate and protect the body from the toxins produced in the gut (Am J Clin Nutr, 1991; 54: 346-50). Take these in their most concentrated and physiologically active form to avoid exposure to large quantities of polyunsaturated fatty acids. If you are supplementing with dietary fibre, make sure you are taking hypoallergenic insoluble fibre and watch the amount. Too much may increase gut permeability (J Nutr, 1983; 113: 2300-7). Gamma oryzanol, derived from rice bran, has been extensively researched in Japan for its healing effects in the treatment of gastric and duodenal ulcers and potent antioxidant activity (Rep Hokaido Inst Pub Health, 1966; 16: 111).

Supplements for ADHD

ADD & ADHD ADD & ADHD Natural Control of ADD & ADHD Billie J. Sahley, Ph.D., CNC In Toxic Psychiatry, Peter Breggin, MD states, Hyperactivity is the most frequent justification for drugging children. Difficult-to-control children are certainly not a new phenomenon, but attempts to give them a medical diagnosis are the product of modern psychology and psychiatry. At first, psychiatrists called hyperactivity a brain disease: minimal brain dysfunction (MBD). When no minimal brain dysfunction could be demonstrated, the label became attention deficit disorder (ADD). Six million children in this country suffer some type of learning disability, ADD, or ADD with hyperactivity (ADHD). Over two million children currently take Ritalin for ADD/ADHD. ADD and ADHD may be caused by psychological problems, including trauma and abuse, nutritional deficiencies, chemical imbalances, allergic responses to food and chemicals, or a poor diet. A failure in the brains inhibitory system (the ability of the brain to inhibit and control itself) may also cause ADD/ADHD. Ritalin, the most commonly used drug for ADD and ADHD, is an amphetamine and a Schedule II class drug (other Schedule II drugs are morphine, opium, and medicinal cocaine). Doctors prescribe Ritalin for many children who do not need it, causing a number of adverse mental and physical side effects. Yet this potent, toxic drug is being used as a quick fix to quiet children. Surprisingly, prescription rates for Ritalin doubled between 1992 and 1996. Children demonstrating symptoms of anxiety, ADHD or ADD often have an imbalance in their brains biochemistry. A biochemical imbalance results from a deficiency of neurotransmitters, the chemical messengers of the brain. If a biochemical imbalance goes untreated, a child can display maladaptive behavior, followed by possible long-term physical and emotional problems. A childs state of health reflects his or her state of nutrition. When minerals, vitamins, amino acids, enzymes, or even hormones are deficient in a childs system, the result can be a disturbed biochemical homeostasis causing impaired functions in the brain. This, in turn, can cause an inability to focus, concentrate, and stay on task. At the Pain and Stress Center in San Antonio, we have successfully treated numerous children with orthomolecular therapy. Orthomolecular therapy corrects the brains biochemical imbalance, without toxic drugs that can produce adverse side effects. ADD/ADHD presents a major problem facing parents today. Most people think of hyperactivity as some type of behavioral problem (a child who is impatient, impulsive, and constantly moving); but not all hyperactive children are aggressive. Some are very passive, withdrawn, and find it hard to communicate their feelings. ADD/ADHD is not a condition that can be measured in precise scientific terms. Nor is it a situation with a quick fix, especially with powerful and addictive drugs such as Ritalin. ADD/ADHD is a complex and intricate condition in which children demonstrate maladaptive or disorganized behaviors, which put them out of sync with the world around them. Numerous clinical studies established that hyperactive children often have low serotonin levels. A proper combination of tryptophan or 5-HTP and B6, elevates the serotonin level and balances the brain; the childs symptoms diminish. The dosage, of course, depends on the childs age, weight, and the degree of hyperactivity. Effectiveness of Amino Acids Neurotransmitters affect behavior and learning. A neurotransmitter deficiency consequently has a dramatic effect on childrens or adults abilities to learn and function in an orderly manner. Most hyperactive and ADD children are born with a shortage of neurotransmitters, establishing a genetic link, most often on the male side. These children also do not manufacture the needed amount of these chemical messengers. Where do we get neurotransmitters? From the amino acids, GABA, glycine, taurine, tyrosine, glutamine and tryptophan. Do children or adults get enough aminos through diet? NO! Balanced amino-acid doses, in the right combination and formulas, produce the needed neurotransmitters naturally. Using a stimulant medication to try to produce neurotransmitters is like a shotgun going off in the childs brain. Our children were not born with Ritalin in their brain, so how can they have a Ritalin deficiency? Approximately fifty different neurotransmitters exist in the human brain, but communication between brain cells uses only ten (approximately) major neurotransmitters. How we feed the brain directly affects our production of neurotransmitters. With proper nutrition and supplementation, we can correct or enhance mind, mood, memory, and behavior. All major neurotransmitters are made from amino acids and dietary protein. One of the dangers of a low-protein diet is not ingesting enough amino acids to make adequate brain neurotransmitters. Apathy, lethargy, difficulty concentrating, loss of interest, and insomnia all result when the diet does not include adequate amounts of amino acids. Drugs do not produce or increase production of neurotransmitters. Drugs only address symptoms. Amino acids restore the balance nature intended. Some of the major symptoms of neurotransmitter deficiencies are ADD, ADHD, brain fog, mood swings, increased stress, anxiety, depression, insomnia, irritability, and aggression. Stress plays a major role in the depletion of neurotransmitters. Inhibitory neurotransmitters are the keys to behavior, emotions, and pain. Inhibitory amino acids include tryptophan, taurine, GABA, and glycine. Millions of people have turned to drugs known as SSRIs (Selective Serotonin Reuptake Inhibitors). These drugs, such as Prozac, Paxil, Zoloft, and Effexor work by selective enhancement of serotonin levels. SSRIs prevent the presynaptic nerve from reabsorbing serotonin that it previously secreted. Prozac causes an increase in brain serotonin levels; but Prozac and other prescription drugs do not increase neurotransmitters. (See Figure 1). 5-HTP is synergistic with other supplements that enhance neurotransmitters such as GABA, glutamine, tyrosine, phenylalanine, and glycine. Magnesium prolongs the benefits of 5-HTP. Chronic stress depletes available serotonin, as well as interferes with serotonins ability to control behavior. Research demonstrates that low serotonin levels can change brain function and impair learning. Low serotonin may be responsible for an increase in depression and drug use among teens and children. Most teens with low serotonin levels are more prone to try recreational drugs or even prescription drugs, for relief. A low brain serotonin level impairs the ability to focus and reason. 5-HTP shows a lot of promise as a natural answer to a multitude of problems that plague adults and children. Use caution with 5-HTP if your child is taking prescription antidepressant medications. GABA (Gamma-aminobutyric acid) GABA, an inhibitory neurotransmitter, is found throughout the central nervous system. GABA assumes an ever-enlarging role as a significant influence on ADD, ADHD, stress, anxiety, and depression, as well as stress-induced illnesses. According to Candace Pert, a neuroscientist who discovered the GABA receptor, every cell in the body has a GABA receptor, which is one reason why GABA has such positive effects. GABA inhibits the cells from firing, diminishing anxiety-related messages. Tranquilizers provide only temporary relief. We have seen many patients on Xanax that still experience anxiety. They have been told it is not addictive: it is! THERE IS NO SUCH THING AS A TRANQUILIZER DEFICIENCY! Nutrient deficiencies do occur, however; and they can and do change behavior. GABA, glutamine, and glycine prove vital for energy and the smooth running of brain functions. We have successfully used these three amino acids with patients to ease anxiety, irritability, and ADD. Research demonstrates a large number of children who display ADD/ADHD behavior actually experience anxiety. If they use all available GABA, then the receptors in the brain become empty, allowing the brain to be bombarded with random firings of excitatory messages. However, when adequate amounts of GABA are present, the reception of multiple random firings are blocked, so the brain does not become overwhelmed. At the Pain & Stress Center we regularly combine GABA and other amino acids to achieve positive results. Dose amounts vary, depending on the age and weight of the child. GABA now takes its place as a major influence on those taking drugs, and in many cases, replacing the drugs. We have found that, when combined with other amino acids, GABA works exceptionally well with ADD children. L-Glutamine Glutamine, along with GABA and Glycine, is rapidly becoming an important therapeutic amino acid of the 21st century. Glutamine, found in many foods, is the third most abundant amino acid in the blood and brain. It also provides a major alternative fuel source for the brain when blood sugar levels are low. Glutamine functions as an inhibitory neurotransmitter, and is the precursor for GABA, the antianxiety amino acid. The amino acid trio of Glutamine, GABA, and Glycine plus B6 are among the major inhibitory neurotransmitters in the brain. Glutamine is found in the nerves of the hippocampus, the memory center of the brain, in the cranial nerves, and in many other areas of the brain. These three amino acids work together as inhibitory neurotransmitters. Anyone taking amino acids must take B6 to metabolize the amino acids. Intellectually impaired children and adults often show an increase in IQ after taking glutamine in combination with Ginkgo biloba and B6. Dr. Roger Williams demonstrated that children and adults diagnosed with ADHD showed a marked improvement when taking 250 mg to 1,000 mg of glutamine daily. GABA and glutamine are not only found in the brain, but also in the receptor sites throughout the body. Glutamine is the memory and concentration amino acid. Seventy five percent of hyperactive and ADD childrens blood tests showed low levels of glutamine. Dr. C. Fredericks research also demonstrated a definite increase in the IQs of children given glutamine. When glutamine was given daily, children showed impressive improvements in their abilities to learn, to retain, and to recall. Glutamine is a major part of my orthomolecular program for hyperactive and ADHD children. Glutamine is one of the amino acids that create the neurotransmitters in the brain that enhance learning and memory. Hyperactive and ADD children have low neurotransmitter levels, especially glutamine. Adding glutamine increases the level of neurotransmitters. Start with 500 mg of glutamine and gradually increase until you reach the optimal dose for your child, to a maximum of 3,000 mg per day. Taurine Taurine is now classified as a conditionally essential amino acid in the adult. In infants and children, however, taurine is an essential amino acid. As one of the sulfur amino acids, adults synthesize taurine from cysteine and methionine, provided B6 and zinc are present. Taurine is found abundantly throughout the body in the heart, olfactory bulb, central nervous system, and brain (hippocampus and pineal gland). As an inhibitory neurotransmitter, taurine, after GABA, is the second-most important inhibitory transmitter in the brain. Taurines inhibitory action in the brain equals that of GABA and glycine. Its inhibitory effect is one source of taurines anticonvulsant and antianxiety properties. Some children with Downs syndrome have shown an increase in IQ levels when taurine was added to their diet along with glutamine, B6, and vitamin E. The need for taurine increases whenever you experience more stress than usual, or have an illness. Tyrosine Tyrosine is the amino acid and inhibitory neurotransmitter that often helps overcome depression. Clinical studies show that tyrosine controls medication-resistant depression. In a 1980 issue of the American Journal of Psychiatry, a study by Dr. Alan Gelenberg of Harvard Medical School discussed the role of tyrosine in the control of anxiety and depression. Dr. Gelenberg postulated that the lack of available tyrosine results in deficiency of the hormone norepinephrine at a specific location in the brain that relates to mood problems such as depression. Children given tyrosine supplementation demonstrated a marked improvement in mental performance and mood stability. Tyrosine, because of its role in assisting the body to cope physiologically with stress and building the bodys natural store of adrenaline, deserves to be called the stress amino acid. Stress exhaustion requires tyrosine. During periods of stress, in order to continue coping with stress physiologically, the brain requires tyrosine. Tyrosine aids children and young teens, as well as adults, with recurrent depression and mood disorders. In children, dosage ranges from 200 to 500 mg daily. Glycine Glycine is a nonessential amino acid, with the simplest structure of all the amino acids resembling glucose (blood sugar) and glycogen (excess sugar converted in the liver for storage). Glycine is sweet to the taste, can be used as a sweetener, and can mask bitterness and saltiness. Pure glycine dissolves readily in water. As the third major inhibitory neurotransmitter in the brain, glycine readily passes the blood-brain barrier. Studies by the late Carl Pfeiffer, MD, Ph.D., demonstrated glycine as an important factor in psychiatric disorders. Glycine decreases the craving for sugar, and, in many cases, can replace sugar on foods such as cereal. Glycine calms aggression in both children and adults. When combined with GABA and glutamine, glycine influences brain function by slowing down anxiety-related messages from the limbic system. As a very nontoxic amino acid, both children and adults can use glycine. Glycine can be mixed with other amino acids. Doses for a child range between 500 to 2,000 mg daily, divided. Magnesium Hyperactive or ADD children are almost always deficient in magnesium. Magnesium proves necessary for proper brain energy and is the first mineral depleted when anyone (child or adult) is under stress. Magnesium is a stress mineral, and deficiency can lead to hyperactive or ADD behavior. Magnesium plays a significant role in sugar metabolism and in the proper utilization of carbohydrates to create energy. Magnesium is so very important in a childs diet, especially if he displays hyperactive behavior, ADD, or other behavioral problems. Magnesium can be taken in liquid form, tablet, or capsule. When added to the ADD/ADHD diet, calming effects sometimes occur immediately. Most magnesium exists inside the cells where it activates enzymes necessary for the metabolism of carbohydrates and amino acids. In 1988, a study published in Alternative Medicine Review linked the development of ADHD to low blood-serum magnesium levels. A group of children followed for six months were given 200 mg of magnesium a day. Researchers noted remarkably decreased hyperactivity in the children. As a major nutrient needed by ADD/ADHD children and adults, magnesium is the number one stress mineral needed by the body. Magnesium is responsible for over three hundred enzyme functions. It cannot be stored by the body, and it must be taken daily. Symptoms of magnesium deficiency include asthma, migraines, eye twitches, anxiety, confusion, muscle spasms, irritability, depression, nervousness, fatigue, mood swings, PMS, hypertension, and insomnia. Calcium A calcium deficiency can also induce ADD/ADHD behavior. A child deficient in calcium exhibits irritability, sleep disturbances, anger, and inattentiveness. The first signs of a calcium deficiency include nervous stomach, cramps, tingling in the arms and legs, and painful joints. A calcium deficiency can also lead to ADD/ADHD behavior. Children sensitive to dairy products must receive daily calcium supplementation in capsule, chewable, or liquid form. Children up to 10 years of age need 1000 mg of calcium daily; adolescents need 1,200 to 1,500 mg daily. For those involved in sports activities, calcium supplementation is a must. Huperzine Recent research reports that Huperzine A improves mental function and learning in adolescents. Chinese researchers designed a study to determine the efficiency of Huperzine on memory and learning. The clinical study included 34 matched pairs of junior middle school students that had significant complaints of poor memory and difficulty in learning. In the double blind trial, half of the students received a placebo while the other half received Huperzine A for four weeks. Academic performance was measured before and after the clinical trial. The Huperzine group scored significantly better on standard memory tests without side effects. Huperzine A is an extract derived from Chinese club moss. Huperzine can be combined with amino acids and other nutrients. The suggested dosage is one 50 mcg capsule in the morning and in the evening for children aged 12 and over. This information is excerpted from my book Control Hyperactivity/ADD Naturally. Other resources include Is Ritalin Necessary? Both are available through: Pain & Stress Center 5282 Medical Dr. #160 San Antonio, TX 78229-6023

Urinary neutotransmitters

Neurorelief.com * Increased glutamate, epinephrine, norepinephrine, or PEA levels are observed in patients with anxiety disorders. * Anxiety may result from inefficient GABA or Glycine receptors. * High GABA, Glycine, and frequently Taurine levels are observed in patients with anxiety disorders. * Neurotransmitter tests can help identify chemical imbalances that underlie anxiety. * Reducing excitatory neurotransmitters glutamate, norepinephrine, PEA, epinephrine etc., will reduce anxiety and GABA and Glycine levels. * Patients with high GABA levels need GABA support.

Oxidative stress and neurochemicals

Oxidative stress and chronic fatigue syndrome Another speaker, Christian Renna, DO, presented an interesting thesis that without sufficient serotonin and antioxidant defenses, the brain decides that it's not safe to produce dopamine and norepinephrine—hence chronic fatigue and related neurosomatic disorders. A central feature of chronic fatigue-like disorders is a deficiency of norepinephrine. But simply increasing norepinephrine through pharmacological means is not appropriate, since the brain is already overwhelmed with stress, and thus with free radicals. In Renna's view, both stress reduction and antioxidant supplements are absolutely necessary to help the brain produce and maintain inhibitory and excitatory neurotransmitters in proper ratios. This applies not only to those diagnosed with chronic fatigue, but to all of us, especially as we age. In the presence of excess free radicals, the brain seeks to protect itself by lowering its activity. This means lower production of excitatory neurotransmitters such as dopamine, and less energy production in the mitochondria. Every neuron has an excitatory threshold beyond which it will not fire, Renna explained. Instead, the overstimulated neuron shifts to an “escape pathway,” preventing the synthesis of dopamine and norepinephrine. In chronic fatigue, the neuroexcitatory threshold is set too low. Raising it requires increasing the brain's safety mechanisms: serotonin and antioxidants. “If the cell doesn't need to fear oxidative stress, the mitochondria light up like Las Vegas,” Renna said. He also pointed out that many chronic fatigue patients responded well to fen/phen, which was a combination of a serotonin-raising drug and an amphetamine analogue. “Overcoming serotonin deficiency allows the brain to tolerate more norepinephrine,” Renna said. He didn't favor long-term use of antidepressants, however. He felt such use prevented the patient from achieving a more complete recovery. The point is to help the brain produce more of its own serotonin. Thus, we need to address the necessity of lowering stress—not only emotional stress, but also stress coming from chronic low-grade infections, toxins (including endotoxins [toxins produced within the body] originating in the gut under conditions of dysbiosis, meaning an overgrowth of harmful intestinal flora), excess calories, insufficient sleep or any other source. “The more gentle the stimulation, the better,” Renna said. “So don't rush.” In addition, we must make sure the patient's antioxidant defenses are adequate before we use any kind of stimulant. “If a person is not energetic, maybe it's not safe for them to be energetic,” Renna said, again reinforcing the point about low serotonin and depleted antioxidant defenses. Both need to be corrected through stress reduction, diet, the right exercise and supplements. The brain will produce more dopamine when it becomes safe to do so. Dopamine is a very energizing, feel-good neurotransmitter; in addition, dopamine stimulates the release of nerve growth factors. But dopamine has its dark side. “Dopamine is the most dangerous of all neurotransmitters because the brain needs to defend itself against overstimulation,” Renna explained. When serotonin is low, the threshold for what constitutes overstimulation is also set low. Low serotonin, low dopamine, and low energy production in cerebral mitochondria all lead to a cascade of harmful consequences. Since the brain is in constant chemical communication with the rest of the body, including the endocrine system and the immune system (in fact Renna calls the immune system “morcelized brain”), the whole body suffers. We see this not only in the chronic fatigue syndrome, but above all in aging. Tofu has recently come under suspicion as deleterious to the brain. In an ironic reversal of our previous beliefs, coffee and tea are now seen as neuroprotective, while tofu is increasingly under attack. Renna also discussed neuroprotective supplements. His special emphasis was on flavonoids as particularly effective antioxidants and neuroprotectants. Flavonoids (such as those present in blueberries and bilberries, green tea, grape seed extract, and various fruits and vegetables) not only raise glutathione levels, but also help prevent inflammation by inhibiting the enzymes in the lipoxygenase family (LOX), which NSAIDs and COX-2 inhibitors cannot do. Renna added folic acid, SAMe and acetyl-l-carnitine to the list of essential neuroprotective supplements. As for the so-called smart drugs, such as deprenyl and piracetam, these too are worth looking into, according to Renna. They increase energy production while reducing oxidative stress (acetyl-l-carnitine works the same way). Tofu has recently come under suspicion as deleterious to the brain. In an ironic reversal of our previous beliefs, coffee and tea are now seen as neuroprotective, while tofu is increasingly under attack. Renna takes his patients off tofu, at least until there is some solid new evidence of its safety. Both Perlmutter and Renna covered a huge territory, at times overwhelming the audience. Permutter focused on the “anti-inflammatory breakthrough”: preventing and fighting inflammation in the prevention and treatment of Alzheimer's disease, as well as on the use of intravenous glutathione, the body's chief detoxifying compound, as a new and potentially revolutionary treatment for Parkinson's disease. Perlmutter also touched on the production of energy in the cerebral mitochondria, a subject developed more fully by Renna. The main message was clear: we already know a great deal about preventing and treating brain diseases and age-related cognitive and motor dysfunction. Relatively simple measures such as reducing caloric intake and taking fish oil, NSAIDs, lipoic acid and CoQ10 could save millions from terrible brain diseases. It is high time to start implementing this knowledge on a much broader scale. Antioxidants against vitamins: lipoic acid and selenium improve the survival of AIDS patients The excitement over the new anti-retroviral drugs designed to fight the AIDS virus is yielding to a sober assessment of their limitations. By now it has been shown that these drugs do not fully restore immune function. They are not the long-awaited cure. Their side effects are so severe that many AIDS patients drop out of treatment. In addition, the majority of the virus is in the latent stage in the nuclei of T cells, and antiviral drugs cannot affect latent viruses. Are there effective alternative treatments? An affirmative answer was compellingly presented by two speakers: Raxit Jariwalla, PhD, a research scientist at California Institute for Medical Research in San Jose, and Lynn Patrick, ND, medical director of HIV Wellness Program in Tucson, Arizona. The speakers cited study after study showing improved survival rate for AIDS patients who used certain critical supplements known to reduce oxidative stress (a major factor in the progression of the disease) and, in some cases, to significantly suppress viral reproduction. Both presenters singled out lipoic acid as particularly important. All antioxidants are also anti-inflammatory agents, but lipoic acid is regarded as an especially effective anti-inflammatory. It has been known for almost a decade that lipoic acid effectively inhibits the replication of the AIDS virus in vitro. This is not surprising in view of our knowledge that lipoic acid inhibits the activation of Nuclear Factor kappa B (NFkB), which is believed to play an important role in the activation of the HIV virus. Essentially, the latent virus is activated by certain inflammatory cytokines that result from the activation of NFkB. These cytokines include Tumor Necrosis Factor alpha (TNF alpha)—hence the goal of reducing TNF alpha, and the similarity between alternative treatments against AIDS and hepatitis, Dr. Patrick pointed out. Both protocols emphasize lipoic acid, selenium and a combination of various other antioxidants. In addition, many AIDS patients are co-infected with Hepatitis C. “All AIDS patients need liver support,” Patrick said. In addition to 500 mg of lipoic acid/day, she also uses silymarin, shown to be remarkably effective in restoring liver health. Lyn Patrick largely confirmed Dr. Jariwalla's primary emphasis on lipoic acid, stating that “lipoic acid is of extreme importance for HIV patients.” She reinforced this with some added details. Studies have found that lipoic acid inhibits reverse transcriptase (a viral enzyme needed for replication), and makes AZT significantly more effective. Another obvious reason for the importance of lipoic acid for HIV patients is its ability to raise glutathione, our chief detoxifier and a crucial endogenous antioxidant. Glutathione is low in all serious illnesses. When the levels of glutathione rise, the result is reduced oxidative stress. The role of oxidative stress has been neglected in the discussion of AIDS, with the public getting the impression that the sole factor in the progression of this disease is the presence of AIDS virus, commonly referred to as HIV. Yet oxidative stress and consequent inflammation play a major role in whether symptoms of AIDS will appear at all, and in the rate of progression. Some people who are HIV positive do not show any symptoms of AIDS. Interestingly, this group tends to have a higher intake of antioxidants, from diet or supplements or both. Even merely taking a multivitamin turned out to reduce the risk of developing the symptoms of AIDS by 33% in HIV-positive individuals. While lipoic acid plays a starring role in the alternative treatment for HIV patients, another thiol (i.e. sulfur-containing) antioxidant, the acetylated form of cysteine known as NAC, appears to be somewhat helpful as well. NAC too helps raise the levels of glutathione, but by itself it is not likely to have enough effect in AIDS patients; lipoic acid is far more efficient at raising glutathione and blocking NFkB. The special effectiveness of lipoic acid may derive from the fact that it's a dithiol (it has two sulfur groups), while NAC is a monothiol. NAC is more effective when used with other antioxidants. In particular, it synergizes with high-dose ascorbate. High-dose ascorbate, Dr. Jariwalla stated, is unique in that it recycles itself to the reduced state. It also produces “dramatic dose-dependent suppression of viral reproduction.” It is believed that high-dose ascorbate suppresses viral replication through a different mechanism than thiol antioxidants (lipoic acid and NAC) and selenium. Some participants suggested that intravenous delivery of ascorbate would be most effective, due to the large dose required (6 to 12 grams if taken orally). Selenium also plays a starring role in anti-viral regimens. It too inhibits NFkB. But the main reason that selenium is known as “birth control for viruses” derives from the fact that many viruses, including HIV, need selenium to replicate. Interestingly, in a selenium-rich milieu the viral genes that control replication stay turned off. In addition, selenium is required by T cells, and potentiates the action of interleukin-2. An AIDS patient is ten times more likely to die if s/he is selenium-deficient, according to Dr. Patrick. She uses the dose of 400 mcg per day. Vitamin E is known to play an important part in bolstering immunity and reducing inflammation. Like lipoic acid, vitamin E also inhibits NFkB, essential for viral replication. Dr. Patrick stressed that only the succinate form of vitamin E inhibits both the activation of NFkB and the binding of activated NFkB to DNA, as shown by the research of Dr. Lester Packer in the early nineties. Vitamin E has also been shown to enhance the action of AZT. Thus, the form of vitamin E known as alpha-tocopheryl-succinate (“dry E” in popular parlance) is of crucial importance for HIV patients. It is possible, however, that gamma-tocopherol, being a COX-2 inhibitor, is also of value. Vitamin A and beta carotene have been found helpful, as has zinc—but only in small doses. Zinc supplements in excess of 10 to 15 mg appear to increase disease progression. We don't know very much about zinc and HIV, but we do know that zinc is important for the immune system. Zinc activates the thymus hormone thymulin, which plays a part in the differentiation of T cells. Zinc is also involved in protease and integrase enzymes. It seems that supplementing with 12 mg of elemental zinc works best, according to Patrick. HIV infection has also been linked to deficiencies in B6, B12 and folate—the methylating factors. There is a “rampant deficiency” of B12 among AIDS patients, according to Dr. Patrick. Such nutritional deficiencies in patients with full-blown AIDS result mainly from their poor absorption of nutrients due to gut problems, Patrick explained. Thus doses need to be especially large. Most HIV patients are also glutamine-deficient, Patrick said. This is true of anyone under chronic severe stress, even though glutamine is abundant in any protein-rich diet (interestingly, the immune dysfunction seen in AIDS resembles the symptoms of protein-calorie malnutrition). Glutamine helps stop diarrhea and prevents muscle wasting. Large doses are needed (Patrick uses 40 g/day in four divided doses), but the cost is only $31 per week versus $1000 a week it would take for growth hormone treatment, another therapy aimed at preventing wasting. Patrick mentioned yet another supplement: acetyl-l-carnitine. AZT is a mitochondrial toxin. It turns out that the combination of acetyl-l-carnitine and lipoic acid can reverse this toxicity. After learning about the effectiveness of lipoic acid, NAC, Vitamin E, high-dose ascorbate and other supplements in fighting the HIV virus and improving the survival rate of AIDS patients, it was sad to hear that AIDS activists have largely lost interest in alternative therapies and are mostly waiting for the next “miracle drug.” So far, the drugs have proven highly toxic and not effective in many patients. We need to seriously consider the preventive and therapeutic use of supplements such as lipoic acid. In Dr. Jariwalla's words, “nutrients are compelling candidates for treatment of immune dysfunction underlying AIDS.” Much is to be gained from paying attention to the developments in the alternative treatment for AIDS. Cellular immunity decreases not only in the course of AIDS, but also during aging. It is of utmost importance that we learn how to sustain a healthy immune system that can fight viruses and bacteria. Thus, the results presented in the lectures on AIDS are of special interest for anti-aging medicine. Antioxidants, with special emphasis on lipoic acid and selenium, once again show their amazing potential.

Posted on Autism-Mercury

"Precursors to glutathione are glycine, glutamine, and NAC. In Amalgam Illness, Andy recommends taking 4 parts NAC, 2 parts glutamine, and 1 part glycine on an empty stomach to help boost glutathione levels."

Lead inhibits the formation of GABA and increases the concentration of Glutamate/glutamine in the synapse.

Pubmed Laboratory of Pathobiochemistry of the Central Nervous System, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego str., 02-106 Warsaw, Poland. lidkas@cmdik.pan.pl

Glutamine (Gln), glutamate (Glu) and gamma-amino butyric acid (GABA) are essential amino acids for brain metabolism and function. Astrocytic-derived glutamine is the precursor of the two most important neurotransmitters: glutamate, an excitatory neurotransmitter, and GABA, an inhibitory neurotransmitter. In addition to their roles in neurotransmission these neurotransmitters act as alternative metabolic substrates that enable metabolic coupling between astrocytes and neurons. The relationships between Gln, Glu and GABA were studied under lead (Pb) toxicity conditions using synaptosomal fractions obtained from adult rat brains to investigate the cause of Pb neurotoxicity-induced seizures. We have found that diminished transport of [(14)C]GABA occurs after Pb treatment. Both uptake and depolarization-evoked release decrease by 40% and 30%, respectively, relative to controls. Lower expression of glutamate decarboxylase (GAD), the GABA synthesizing enzyme, is also observed. In contrast to impaired synaptosomal GABA function, the GABA transporter GAT-1 protein is overexpressed (possibly as a compensative mechanism).

Furthermore, similar decreases in synaptosomal uptake of radioactive glutamine and glutamate are observed. However, the K(+)-evoked release of Glu increases by 20% over control values and the quantity of neuronal EAAC1 transporter for glutamate reaches remarkably higher levels after Pb treatment. In addition, Pb induces decreased activity of phosphate-activated glutaminase (PAG), which plays a role in glutamate metabolism. Most noteworthy is that the overexpression and reversed action of the EAAC1 transporter may be the cause of the elevated extracellular glutamate levels. In addition to the impairment of synaptosomal processes of glutamatergic and GABAergic transport, the results indicate perturbed relationships between Gln, Glu and GABA that may be the cause of altered neuronal-astrocytic interactions under conditions of Pb neurotoxicity.