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Yeasts and fungi. How to control them.
By William Shaw Ph.D.
Since byproducts of yeast and fungi are frequently elevated in urine samples of people with autism, a knowledge of the biology of these organisms and the therapies to control them are essential.
Fungi is a biological group of organisms that include yeasts, molds, and mushrooms. Thus, all yeast are fungi but many fungi are not yeast. One of the most common disease causing species of yeasts is Candida albicans. Other species of Candida include Candida tropicalis, Candida glabrata, Candida pseudotropicalis, Candida guilliermondii, and Candida parapsolis. Probably all of these species can cause disease especially if the immune system is weak (1). Candida albicans can exist in four forms: a yeast or single cell form, a colony of cells or mycelium, a chlamydospore or cyst-like form, and a cell-wall deficient form (2). Both the mycelium type and the chlamydospore are capable of tissue invasion (2). The vitamin biotin is thought to prevent the transformation of Candida from the yeast to the mycelium form and is sometimes included in nonprescription antifungal medications such as Candicyn (3).
The cell-wall deficient Candida may even be able to conceal itself inside of cells and may be the reason that complete elimination of Candida is difficult (2). These cell-wall deficient forms are extremely small-0.15 millionths of a meter. These cell-wall deficient organisms are extremely difficult to identify and would probably not be detected except in advanced research laboratories and not in the vast majority of hospital laboratories. Certain yeast may actually grow faster when antibiotics are included in the growth media (4,5). Aspergillus is a common food-borne mold which is capable of living and reproducing in the gastrointestinal tract (6). The furan compounds, 5-hydroxymethylfuroic and furan-2,5-dicarboxylic which are frequently elevated in urine samples of children with autism (see chapter on organic acids) are known products of Aspergillus species (7-9). The closely related compound furancarbonylglycine is probably a detoxification product of the other furan compounds which is combined with glycine in the liver. The fact that antifungal drugs decrease the concentration of these products in urine samples of children with autism leads me to suspect that Aspergillus or similar species of mold are producing these compounds in the gastrointestinal tract of many children with autism.
Even ordinary household yeast might cause disease in susceptible individuals. This ordinary yeast is called Saccharomyces cerevisiae. Different strains of this same species are used in both the baking and brewing (alcoholic beverage) industries. Saccharomyces cerevisiae can also exist in the yeast or mycelium form and, like Candida, can cause vaginal yeast infections (10), is being investigated for a role in Crohn's disease (11), an intestinal disorder, and can cause systemic infection in individuals with impaired immune systems (12). The finding of high concentrations of tartaric acid, a product of Saccharomyces cerevisiae, in many urine samples of children with autism, indicates to me a strong possibility that Saccharomyces cerevisiae or a closely related organism may play a role in autism.
Since yeast have the ability to ferment sugar to alcohol, an increase in blood alcohol after intake of sugar can be used as an indicator of yeast overgrowth of the intestine. Dr. Eaton and his colleagues (13,14) at The London Medical Centre in England found that blood alcohol concentrations in patients with suspected yeast overgrowth increased one hour after ingestion of glucose. Furthermore, they found that after dietary restriction of carbohydrates, 42% (27 of 64) of patients were negative on re-test (13). When both dietary restriction and antifungals were used by these patients, 78%(116 of 149) of the patients were negative on re-test, indicating (to me) that this therapy was highly successful in the treatment of the intestinal yeast overgrowth.
Yeast are more complex than bacteria on the evolutionary scale. They are eukaryotic organisms that have cells with defined structures like mitochondria, nuclei, and chromosomes. Many yeast biochemicals are exactly the same as those produced by humans. In many children with autism, there is increased excretion of the compound called 3-hydroxy-3-methylglutaric acidin the urine. Increased 3-hydroxy-3-methylglutaric acid in the urine may be due to a genetic disease called 3-hydroxy-3-methylglutaric acidemia (15). However, the elevated values of urinary 3-hydroxy-3-methylglutaric acid in children with autism are much lower than the values in children with the genetic disease. This chemical compound is used by both humans and yeast to make steroids. I suspect that high values in children with autism are due to yeast overgrowth of the gastrointestinal tract and that it is unlikely (but still possible) that some children with autism have a mild form of the genetic disease 3-hydroxy-3-methylglutaric acidemia.
Diagnosis of yeast disorders.
Why is Candida such a problem to diagnose? The condition that occurs in most children with autism is not technically an infection; it is really an overgrowth of the intestinal tract. Furthermore, the yeasts do not colonize the intestinal tract in an uniform fashion. Instead, they usually form clusters or nests. Sometimes, they settle in the crypts of the intestine, which are small out of the way "side pockets". Therefore, failure to detect these organisms by endoscopy examination(examination with a long tube into the intestinal tract) of the intestinal tract does not rule out their presence (16). There are several ways of diagnosing such a condition. One of the ways is the stool culture. The problems with stool cultures is that many people have a small number of Candida in them in their stool at any given time (17). Furthermore, if the yeast are in their hyphal or colony form, most of the cells are physically attached to the intestinal lining. Stool culture can only detect the cells that have broken off. If you get a positive test result on a stool culture for yeast, it really doesn't convey much information unless it is a quantitative one. The real question is not whether or not an individual has Candida, but rather how much Candida is there. Even though stool culture is not perfect, I have examined a large number of reports in which the organic acid test and stool testing were done and there is general agreement in the two techniques.
Organic acid test for yeast and bacterial byproducts.
The organic acid test is valuable because it detects byproducts of yeast and fungi produced in the intestinal tract. These byproducts are then absorbed into the blood stream from the intestinal tract and are eventually filtered into the urine. The sample is easy to collect and only a small amount of first morning urine is required. In addition the organic acid test screens for genetic illnesses such as PKU and many other genetic diseases as well as many nutritional deficiencies. In addition, the organic acid test also detects byproducts of bacteria that may also be important in a subgroup of children with autism. This testing can be ordered online or by contacting us at:
The Great Plains Laboratory
9335 W 75 Street
Overland Park, KS 66204
Phone: 913 341-8949
FAX: 913 341-6207
E-mail: Williamsha@aol.com
Blood tests for Candida
Severe Candida infection, called systemic Candidiasis is a serious illness with severe symptoms like fever and can even be fatal in individuals with weakened immune systems. Candida infection of the brain called Candida meningitis can be fatal(18). I don't want to alarm anyone since this is a very rare condition that sometimes occurs in HIV-positive individuals or infants with immune deficiency. Finding Candida by blood culture is considered the definitive test for systemic yeast infection. However, in one of the most intensive studies done (18), there was a very high incidence of false negatives using blood cultures for Candida. In children who really did have yeast invasion of their organs including brain, liver, or heart that was confirmed by autopsy, only 17% of the children's blood samples tested positive for yeast even though they had been tested repeatedly (an average of ten times) for Candida.
The reason for the failure of these blood tests may be that the Candida is a fastidious organism and doesn't grow if it doesn't "like" the particular culture of the media in which it is placed or the antibiotics given to the patients may have induced the development of cell-wall deficient forms that could not be detected by ordinary culture methods. Another explanation may be that yeast implanted in the tissues are not shedding very many cells into the blood where they can be detected. Antibodies can be used to detect Candida but such antibodies measure old infections. Even with Candida IgM antibodies that measure recent infections, it is not clear that such an antibody test can pick up the yeast overgrowth of the intestinal tract because most of the time the yeast are not in the blood stream.
However, with a yeast overgrowth in the intestinal tract, fever rarely occurs. Symptoms of yeast overgrowth of the intestinal tract may include behavioral changes such as hyperactivity, psychosis, or depression and non-specific complaints such as fatigue, achy joints and muscles, sleep disturbance, increased allergies and sensitivity to chemicals at home and at work, increased incidence of vaginal yeast infections in women and "jock itch" in males (3,19,20).
There are several places that fungal infections can exist. There can be external or superficial infections which involve the mouth, skin or vagina. Athlete's foot is one of the common kinds of fungal infections. Some people get fungal infections under the nails called onychomycosis. Internal or systemic yeast infection can be life threatening. In this type, the yeast has escaped from the intestinal tract, is inside the body, and can be in the organs. It can invade virtually any organ of the body including the blood, the lungs, bones, kidneys, the liver, the heart, the eyes, and the brain (18).
Interactions of yeast and other bacteria.
Yeast and bacteria live together in the intestinal tract and it is not surprising that sometimes there is synergy or cooperation and competition between the species. For example, a supporting role of Candida albicans in the establishment of Staphylococcus aureus infection with mice has been reported (21). I have also found that treatment of yeast overgrowth with antifungal treatment leads to bacterial overgrowth if beneficial bacteria are not used at the same time as the antifungals. Furthermore, it has been shown that E. coli, a common intestinal bacteria and Saccharomyces can exchange genetic information by exchange of a piece of DNA called a plasmid (22), leading to the possibility that the genetic makeup of common yeast might eventually be contaminated by the genes of intestinal bacteria. An inhibitory effect of Pseudomonas bacteria on Candida growth has been reported(21) and might be evaluated as a potential therapy if a suitable safe species of this bacteria could be developed.
Antifungal Therapies
The major therapies for autism are antifungal products, probiotics to control both yeast and bacteria overgrowth, immune therapies, and nutritional therapies.
Probiotics
Probiotics(pro=for + biotic=life) are microorganisms that are used therapeutically to control abnormal overgrowth of yeasts, fungi, and bacteria in the intestinal tract. Probiotics were first recommended by the Russian immunologist Metchnikoff who received the Nobel Prize in Medicine for his discovery of the role of the white blood cells in fighting infection. In the early 1900's, Metchnikoff proposed that many human diseases were caused by abnormal overgrowth of harmful bacteria in the intestinal tract. He noted the good health of a European community that included large amounts of yogurt in the diet. Yogurt contains bacteria of the Lactobacillus family and Metchnikoff concluded that the Lactobacillus family was controlling the harmful bacteria that produced harmful "ptomaines". Metchnikoff's observations probably were a major impetus to the development of the health food industry.
There are now over a hundred different brands of beneficial bacteria that are available in mail order supply houses, pharmacies, and health food stores. Some of the common species of bacteria are Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus bulgaricus, Lactobacillus salivarius, Lactobacillus thermophilus, and Lactobacillus plantarum. Other beneficial species include Bifidobacterium bifidum and Streptococcus faecium (not to be confused with Streptococcus faecalis, a pathogen.) In addition to these different species, these bacteria are found in many different formulations as well including suspensions, loose powder, capsules, and flavored chewable tablets. Some of these organisms are grown on dairy products as a source of nutrition while others are dairy-free. Because of the sensitivity of most children with autism to the peptides derived from milk, it may be wise to choose a dairy-free brand.
I do not recommend a particular brand but I generally recommend a dose of 10 billion cells per day for any child over three and half that amount for younger children. These products may help to control both yeast (23) and abnormal bacteria such as Clostridia (24) in the intestinal tract. In addition to probiotics which are bacteria, there is increasing interest in a beneficial yeast called Saccharomyces boulardi (25) to control both yeast and Clostridia overgrowth of the intestinal tract. However, I have very little experience with this yeast and would advise caution until more evaluation has been done especially since a related species Saccharomyces cerevisiae can cause medically significant conditions. I recommend the simultaneous use of a probiotic product any time an antifungal drug is used. Yeast are part of the intestinal ecosystem and hold other organisms in check. Overgrowth of harmful bacteria may occur unless probiotics are taken simultaneously with prescription or nonprescription antifungal products.
Nonprescription Antifungal Products.
Antifungal products that are available from a health food store and mail order supply companies without a prescription include garlic or garlic extract, grapefruit seed extract, oregano, caprylic acid and its oil form MCT oil, Tanalbit, goldenseal, aloe vera gel, and lactoferrin. These products are also combined into different formulations. Even though these products do not require a prescription for their use and common experience indicates they are safe, they are best used under the supervision of a health care professional who is familiar with their side effects. All of these products can cause the yeast die-off reaction that is just as severe as the one caused by prescription drugs. One of the difficulties in using these products is that dosing information for children is not usually provided. I have received positive reports from parents of children with autism treated with all of these products. Some of these people undertook therapy on their own because they lived in a remote area where no alternative health professional was available and their family doctor would not prescribe antifungal drugs. Others used these products in the belief that these products were safer than prescription drugs because these products were "natural". I would like to emphasize that nystatin is a very safe prescription drug and that it is probably just as safe as any of these natural products.
Diet to control yeast overgrowth.
Numerous popular books by William Crook MD (18), John Trowbridge M.D. (19), and others have addressed the importance of sugar elimination to control yeast overgrowth of the intestinal tract because of the stimulatory effect of simple sugars on yeast overgrowth. Vargas and his colleagues found that mice given sugar water had 200 times the amount of Candida yeast in the intestine compared to mice given plain water (26). Similar results have also been reported in the treatment of humans for yeast-related illnesses(27-29). The rule of thumb for sugar elimination is simple: If it's sweet, don't eat. The list of restricted foods includes candy, ice cream, cake, pie, soda pop, Kool-Aid, and even fruit juices. Since your child may be on a dairy-free diet as well, water may become your child's main drink. To ease the transition, you might want to dilute fruit juice ten-fold with water during the transition.
All types of sugar, both "natural" and refined, should be eliminated including honey, syrup, fruit sugar, and refined sugars. You will find some difference of opinion on sugar elimination. Some authorities recommend complete elimination while others allow occasional sugar in the diet. A vitamin C supplement may be needed if your child gets a lot of his daily vitamin C from orange juice. Fruits may have to be eliminated from the diet for a period of about a month to accelerate the yeast elimination. The high-sugar dessert foods may have to be eliminated indefinitely.
What is left to eat since wheat and dairy products may have also been eliminated for the casein and gluten-free diet? Major sources of carbohydrates may include potatoes, corn. rice, yams, and other vegetables such as beans, peas, broccoli, etc. All meat and fish are acceptable although both Pam Scott and Dr. Semon are concerned about antibiotic residues and fungal byproducts in commercial meat. Pam Scott went the extra mile to obtain antibiotic-free sources of these meats. I don't know if this is essential but it couldn't hurt and I am not going to argue with success. It is true that complex carbohydrates are broken down to simple sugars in the intestinal tract that can be utilized by the yeast so that diet alone may be insufficient to control a significant yeast overgrowth and will have to be combined with some kind of antifungal therapy. Eaton's data (mentioned earlier in the chapter) indicates that combining diet and antifungals is nearly double the effectiveness of diet alone in eliminating intestinal yeast overgrowth. I always recommend combining the two therapies. No formal assessment of these combined therapies is available but the experience of many physicians who treat for yeast-related illnesses indicates better response when both diet and antifungal products are used simultaneously.
The Yeast die-off or Herxheimer reaction
The Herxheimer reaction is also called the yeast die off reaction (3,19). Usually for about 3 or 4 days after starting antifungal drugs the person may feel a little bit worse during that time. There may be symptoms of extreme tiredness and even fever. The Herxheimer reaction is probably due to the abnormal release of these abnormal organic acids during the yeast die off phase. The yeast are like water balloons filled with toxins. When you give the antifungal drugs, the water balloons burst and the contents of the water balloons are then absorbed into your body and are eventually excreted into the urine. Therefore, the concentration of abnormal urine organic acids rises when antifungals are first given (Figure 1) and then begin to drop as the yeast are all killed and there are no more toxic organic acids to release. This reaction was presumed to be due to the release of toxic compounds by the yeast when they die after exposure to antifungal agents. My research is the first to document a marked increase in certain organic acids for several days after beginning an antifungal drug. The Herxheimer reaction is not limited to yeast. It also occurs when certain of the bacteria overgrowths of the intestinal tract are treated as well.
The Herxheimer or yeast die off reaction lasts 3 to 4 days and sometimes as long as a week if the person has a severe yeast overgrowth. Some of the affects can be lethargy, fever, and an increase in stereotypical behaviors. Symptoms may include bloating, nausea, vomiting, eczema, aching, headache, and stuffiness. In addition, children with autism or PDD may experience an intensification of symptoms during this period including intense craving for sweets, more self-stimulation, more arm flapping, or more hyperactivity. If the child with autism does a lot of hand flapping normally, during the yeast die-off period, there may be an intensification of this behavior. Some of the parents of autistic children who tried nystatin years ago for their children gave up on it because of adverse effects during the die-off reaction.
Four approaches can be taken to reduce the intensity of the yeast die-off reaction:
Garlic.
Garlic is a potent antifungal product that also leaves a strong odor on the breath. Fortunately, it has been found that deodorized garlic has essentially the same antifungal activity as fresh garlic. Of course, fresh garlic is cheap and effective if you don't mind the smell. Allylsulfinyl alanine is a major constituent(3) of garlic that is converted to a compound called allicin when the garlic is crushed or eaten. Allicin and some of its byproducts contain sulfur its characteristic odor. When garlic is allowed to age for an extended time period, the odor dissipates. At lower doses, allicin is fungistatic meaning that it slows the growth of yeast or fungus. At higher doses the allicin actually will kill Candida albicans(30). The recommended dosage of Kyolic brand garlic for antifungal therapy for adults is three capsules per day. A child's dose would be proportionally less on a weight basis. Assume an average adult weight of 150 lb. If your child weighs 50 lb., the garlic dosage would be 50 lb/150 lb. or one-third the adult dosage.
Oregano.
Oregano oil inhibited the growth of Candida albicans in vitro (31) The minimum inhibitory concentration (MIC) was less than 0.1mcg/ml when tested with 3 different strains of Candida; 0.1% survival occurred at a concentration of 45 mg/ml. Carvacrol, a major phenolic constituent of oregano oil, inhibited Candida as effectively as did the oil itself. Parents have indicated to me that oregano was sometimes helpful in their child with autism when nystatin was ineffective in killing the yeast. This killing of yeast by oregano was confirmed by stool yeast evaluation.
Caprylic acid and MCT oil.
Caprylic acid is a fatty acid and is present in a wide variety of foods. Fatty acids have different numbers of carbon atoms ranging from two in acetic acid to twenty-four or more. Caprylic acid has six carbon atoms and thus is considered to be a medium chain length fatty acid. Caprylic acid eventually is just burned up by the body for fuel or may be stored as fat. Caprylic acid was found to have antifungal activity over 40 years ago (32-34). When three molecules of caprylic acid are combined with one molecule of glycerol, the compound is called a triglyceride. Triglycerides are also called fats or oils. Solid triglycerides are frequently termed fats while liquid triglycerides are termed oils. Triglycerides containing predominantly the medium chain length fatty acids are termed medium chain triglycerides or MCT oil.
Caprylic acid is the predominant fatty acid in most commercially available MCT oil. MCT oil is a liquid at room temperature and thus can be administered to a child who cannot or will not take capsules or tablets of caprylic acid. The taste of MCT oil is fairly bland and it tastes very much like corn oil or other vegetable oils. Flavored MCT oil is also available for use as well. When MCT oil reaches the intestine, it is broken down by lipases to form caprylic acid and glycerol. Since children with autism may have defective production of pancreatic enzymes, another property of MCT oil is very important. Medium chain triglycerides are broken down to form caprylic acid at a much more rapid rate than long chain triglycerides (35) so that this compound will be broken down effectively even in children whose pancreas is producing low levels of lipase. Coconut oil is a major natural source of caprylic acid.
Caprylic acid is safe with the following exception. Children with the rare genetic disorder medium chain acyl dehydrogenase (MCAD) deficiency cannot biochemically process caprylic acid (36). Theoretically, caprylic acid could be harmful to these children. The organic acid screen performed in the Great Plains Laboratory checks for MCAD but it is possible that it might not be detected in its dormant form by the organic acid screen. The probability of a child having MCAD is low, probably less than one in six thousand. However, Duran and colleagues (37) reported that no harmful effects were caused by a high MCT oil load in a patient with MCAD at a high dose. MCT oil is found in a variety of foods and in infant formulas and a dose of up to one teaspoon twice a day for children over two years old and half that amount for infants would seem to be completely safe even for a child with MCAD. However, if your child has MCAD or has ever had a lapse into a coma-like state, I would advise against using products containing MCT oil or caprylic acid since other effective antifungal agents are available.
Colloidal silver.
Silver is a metal that is used for jewelry and dinnerware. Solutions of silver have been used as a germicide since the early 1900's. In the Old West, prior to refrigeration. a silver dollar would be put in the milk container to prevent spoilage by microorganisms. Colloidal silver is a suspension of silver that kills almost all intestinal microorganisms including yeast, bacteria, protozoa, viruses, and parasites. My major concerns with this product are: (1) It essentially kills every living thing in the intestine including any beneficial bacteria. (2) Silver is a heavy metal. If the size of the silver particles are too large, the absorbed silver particles may lodge in the body causing a graying of the skin due to the deposited silver, a condition called argyria (38). Most heavy metals that kill microorganisms indiscriminately like mercury and arsenic are also toxic to humans. Although the claim is made that certain products are safe because the particles of silver are too small to be lodged in the capillaries of the skin and organs (38), I would be extremely cautious about these products and would not use them except under close medical supervision of a physician who has used these products for a long time and is certain of the product's safety. (Continue to Part II.)
Buy The newest version (2002) of this book online!
Biological Treatments for Autism and PDD Online > Chapter 4: Part I | Part II