Chapter 4
Yeasts and Fungi: How to Control Them
By Dr. William Shaw


Since byproducts of yeast and fungi are frequently elevated in urine samples of people with autism, 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 diseases causing species of yeast 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: 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 in the vast majority of hospital laboratories but only by advanced research 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 the urine samples of children with autism, leads me to suspect that Aspergillus or similar species of mold are producing these compounds in their gastrointestinal tract.

Even ordinary household yeast, which is called Saccharomyces cerevisiae, might cause disease in susceptible individuals. 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).  This type of yeast is being investigated for its role in the intestinal disorder called Crohn’s disease (11), and it 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 the urine samples of many children with autism indicates 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 into 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 these patients used both dietary restriction and antifungals, 78% (116 of 149) of the patients were negative on re-test, indicating that this therapy was highly successful in the treatment of intestinal yeast overgrowth.  

Yeast is 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 acid in 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. Both humans and yeast use this chemical compound 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 yeast do not colonize the intestinal tract in an uniform fashion, but instead, 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) of the intestinal tract does not rule out their presence (16). There are several ways of diagnosing such a condition including the stool culture, the organic acid test, and the blood test.


 Stool Testing

The problem with stool cultures is that many people have a small number of Candida present 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 and the 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 an individual has Candida, but rather how much Candida is there? Even though the stool culture is not perfect, I have examined a large number of reports in which both the organic acid and stool culture tests were done and two techniques compliment each other. The Great Plains Laboratory now offers a combination test profile (Combo test) that includes a stool test for yeast as well as the urine organic acid test for yeast and bacteria metabolites. The stool test includes testing to determine which antifungal drugs are most effective for the particular yeast strain in stool.


 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. The organic acid test screens for many genetic diseases such as PKU and nutritional deficiencies as well. In addition, the organic acid test will also detect byproducts of bacteria that may also be important in a subgroup of children with autism.

This testing is available from:

The Great Plains Laboratory Phone: 913 341-8949
11813 W. 77th St. Fax: 913 341-6207
Lenexa, KS 66214  www.greatplainslaboratory.com
E-mail: GPL4U@aol.com  


 Blood tests for Candida

Severe Candida infection, called systemic Candidiasis, is a serious illness with severe symptoms like high fever, which can even be fatal in individuals with weakened immune systems. Candida infection of the brain, called Candida meningitis, can also be fatal (18) but this is a very rare condition that sometimes occurs in HIV-positive individuals or infants with extreme 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 (and this 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.

What is the reason for the failure of these blood tests in detecting systemic candidiasis?  It is possible that Candida is a fastidious organism that doesn’t grow if it doesn’t “like” the particular culture of the media in which it is placed or perhaps 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 whether this antibody test can pick up the intestinal yeast overgrowth because most of the time, the yeast are not in the blood stream. 

However, with yeast overgrowth in the intestinal tract, fever rarely occurs. Symptoms of intestinal yeast may include behavioral changes such as hyperactivity, psychosis, depression and non-specific complaints such as fatigue, achy joints and muscles, sleep disturbance, increased allergies, chemical sensitivity, and 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, into the body, and can invade the organs.  It can invade virtually any organ of the body including the blood, the lungs, the bones, the 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 both synergy or cooperation and competition between the species. For example, studies have shown that Candida albicans has supported the establishment of Staphylococcus aureus infection in mice, (21). In addition, the treatment of yeast overgrowth with antifungals leads to bacterial overgrowth if beneficial bacteria are not used at the same time. Furthermore, it has been shown that E. coli, a common intestinal bacteria and Saccharomyces can exchange genetic information through 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 bacterium could be developed.


 Antifungal Therapies

The major therapies for treating yeast overgrowth in autism include probiotics, anti-yeast diet and non-prescription and prescription anti-fungal products.


 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 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 most children with autism are sensitive to the peptides derived from milk, it may be wise to choose a dairy-free brand.

I generally recommend Lactobacillus acidophilus GG, a special strain of Lactobacillus acidophilus that was formulated and patented specifically for controlling Clostridia overgrowth of the gastrointestinal tract. I generally recommend a dose of at least 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 good 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 would advise caution since there have been some reports of hypoglycemia with this agent. 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.


 Diet to Control Yeast Overgrowth

Numerous popular books by William Crook M.D. (18), John Trowbridge M.D. (19), and others have addressed the importance of sugar elimination to control intestinal yeast overgrowth because of the stimulatory effect of simple sugars on yeast.  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, which may or may not be essential but who can argue with success. It is true that complex carbohydrates are broken down to simple sugars in the intestinal tract, which then “feeds” the yeast. Therefore, diet alone may be insufficient to control a significant yeast overgrowth and it may be necessary to also use 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 abnormal organic acids or other toxic byproducts during the yeast die off phase. The yeast is 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 increases when antifungals are first given (Figure 1) and then begin to drop as the yeast are all killed and the toxic organic acids are no longer released. 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 and it also occurs when certain bacteria overgrowths of the intestinal tract are treated as well.

In cases of severe yeast overgrowth, Herxheimer or yeast die-off reaction can last as long as a week, though normally lasting 3 to 4 days. Some of the affects can be lethargy, fever, and an increase in stereotypical behaviors. Symptoms may also include bloating, nausea, vomiting, eczema, aching, headache, and stuffiness. In addition, children with autism or PDD may experience an intensification of symptoms such as craving sweets, self-stimulation, arm flapping, and hyperactivity. For example, if a child with autism normally does a lot of hand flapping, there may be an intensification of this behavior during this yeast die-off period. Some of the parents of children with autism tried nystatin years ago for their children and gave up on it because of adverse effects during the die-off reaction.


Figure 1
Biochemical Basis of Herxheimer Reaction
Figure-1

Four approaches can be taken to reduce the intensity of the yeast die-off reaction:

  • Use nutritional approaches to cut down on yeast burden prior to using an antifungal drug. Eliminate sugar containing foods from the diet for two weeks prior to the use of an antifungal drug. Even this dietary change alone may cause a slight to moderate yeast die-off reaction. It doesn’t matter whether or not a sugar is natural or artificial. Any simple sugar (glucose, fructose, sucrose, or galactose) will serve as yeast food. In addition, sugared drinks and fruit juices may have more sugar than foods.  It is important to give your child vitamin C during this period (500-1000 mg per day is recommended). Sugar substitutes include stevia, xylitol, fructooligosaccharides and FOS. FOS is not digested until it is acted on by gas forming anaerobic bacteria in the lower gastrointestinal tract. A lot of parents noticed excessive gas and abdominal pain in their children after ingesting FOS so it may not be the ideal sugar substitute. Aspartame can cause headaches and other symptoms. It appears stevia and xylitol may be the best choices for sugar substitutes.   
  • Since many of the yeast products are acids, release of these acids, which are absorbed into the body, may cause a condition called metabolic acidosis. An extremely simple therapy used by physicians who treat autism is to supply a mild antidote that neutralizes the excess acids. The most convenient product is a nonprescription drug called AlkaSeltzer Gold. Do not use any other kind of Alka-Seltzer. Alka-Seltzer Gold is simply a very safe product called bicarbonate that helps to neutralize excess acids of any kind. The dose for children is on the label. Do not exceed the number of recommended doses.
  • If the organic acid test indicates your child has high concentrations of tartaric acid, the tartaric acid may be inhibiting the production of malic acid. Malic acid is essential for the efficient operation of the Krebs cycle and for providing raw material that the body can use to produce its own sugar between meals. The use of malic acid supplements will probably help during the yeast die-off reaction and may also be useful until the tartaric acid from the yeast is eliminated through a combination of a low sugar diet and antifungal therapy.  The use of malic acid supplements must be under the close supervision of a dietitian and/or physician because malic acid supplements frequently contain magnesium. Some multi-vitamins have high amounts of magnesium and other supplements may also contain magnesium. It is possible to ingest too much magnesium if combining different magnesium containing supplements leading to magnesium toxicity, which can be fatal. Since vitamin B-6 has the ability to prevent the formation of the harmful pentosidines, I would strongly urge the use of Vitamin B-6 prior to starting antifungal therapy.

 Nonprescription Antifungal Products

Antifungal supplements that are available without a prescription from health food stores and New Beginnings Nutritionals (www.nbnus.com) include garlic or garlic extract, grapefruit seed extract, oregano, caprylic acid and its oil form MCT oil, Samento, goldenseal, monolaurin, and lactoferrin. These products are also combined into different formulations. Even though these supplements 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 supplements can cause the yeast die-off reaction that is just as severe as the one caused by prescription drugs. There have been many positive reports from parents of children with autism who have successfully treated with all of these supplements. Some of these people undertook therapy on their own because they lived in a remote area where alternative health professionals were not available and their family doctor would not prescribe antifungal drugs.  Others used these supplements in the belief that they were safer than prescription drugs because they 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 supplements.


 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 lbs. If your child weighs 50 lbs., 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 called fats while liquid triglycerides are called oils. Triglycerides containing predominantly the medium chain length fatty acids are called 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. When MCT oil reaches the intestine, it is broken down by lipases to form caprylic acid and glycerol. Since many children with autism have defective production of pancreatic enzymes, another positive benefit of MCT oil is in the fact that it is a medium chain triglycerides.  Medium chain triglycerides are broken down to form caprylic acid at a much more rapid rate than long chain triglycerides (35) so this compound can be broken down effectively when the pancreas is producing low levels of lipase (a digestive enzyme). Coconut oil also contains caprylic acid in a lesser concentration. 

Caprylic acid is safe with the following exception. Children with the rare genetic disorder called 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 when a patient with MCAD was given a high dose of MCT oil. MCT oil is found in a variety of foods and infant formulas.  A dose of up to one teaspoon twice a day for children over two years old and half that amount for infants would most likely 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, it is not recommended to use 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) It is a heavy metal and 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 which is 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.


 Lactoferrin

Lactoferrin is a protein found in many mammals including humans which possesses the ability to bind iron. Studies have shown that both human and cow lactoferrin kills Candida albicans and Candida krusei (39, 40). Lactoferrin is only active against Candida when it is free of iron since its mechanism of killing Candida is most likely by starving it from iron. Lactoferrin is available as a supplement but because of the iron inactivation and digestion by the body’s enzymes, it is difficult to determine an appropriate dosing. A piece of the lactoferrin molecule called lactoferricin B can also kill Candida. Interestingly, this molecule also possesses potent antiviral activity as well (41). Since this product controls yeast by removing iron, an evaluation of your child’s iron intake might be important. If a blood test shows that your child has high iron and high iron binding capacity, it might be beneficial to use vitamins that do not have additional iron when using lactoferrin for yeast control.


 Combination Products

A large number of different combinations of antifungal products are available. There may be differences in the potency of each of these products as antifungals but there are few large studies with these products since the small profits generated by these products cannot support expensive clinical trials. One product called Candida Defense Formula contains Pau D’Arco extract, oregano, gentian extract, caprylic acid, grapefruit seed extract, berberine, ginger, cinnamon, chamomile, and biotin.


 Biotin

Biotin is one of the essential vitamins (termed vitamin H. Biotin) and it is commonly found in most multivitamin supplements but is usually present in doses well below the recommended daily allowance (RDA). In addition, biotin is one of the vitamins that is produced by good bacteria in the intestinal tract (42). The use of antibiotics can eliminate this bacterial production of biotin leading to biotin deficiency.

I had a personal experience in my own family with this vitamin. When one of my sons was small, he was on antibiotics for an ear infection. He lost his appetite, began to lose weight, developed red eczema on the cheeks, became withdrawn, and then his hair began to fall out in large clumps. He began to look like a starved concentration-camp victim. Unfortunately, the role of yeast in such cases was unknown at that time. However, I knew that biotin deficiency could cause hair loss probably due to killing off the beneficial germs in the intestine, which produce it there. Supplementation with biotin started his hair growing back within a couple of days and he began to look better overall. This was the first episode that focused my attention on the negative side effects of the “miracle” antibiotic drugs and stimulated my interest in the role microorganisms play in our human biochemistry. 

In addition to its nutritional role in humans, biotin is also needed by most other creatures including yeast. However, when yeast are exposed to biotin, they are stimulated to grow but are less likely to convert to their mycelium form, which is the form in which they invade the tissues (19).  My recommendation is a supplement of 800-1000 micrograms per day for any person with a yeast-related condition. Biotin is a water-soluble vitamin and is completely safe at this dose. To minimize yeast overgrowth, it might be best to introduce biotin and other vitamins a week after beginning antifungal therapy.


 Biotinidase Deficiency

Biotinidase deficiency is a genetic inborn error of metabolism that has been found both in autism (43) and in Rett’s syndrome (44), a disorder in girls in which many autistic traits are present. Biotinidase deficiency is frequently associated with yeast and fungal infection (42). Biotin from the diet becomes chemically bonded to many of the body’s enzymes that require it. Biotin is attached to enzymes by combining specifically with the free amino group of the amino acid lysine (42). If acetaldehyde or arabinose produced by yeast has previously reacted with these lysine sites, as discussed in other chapters, biotin will not be able to attach to these critical sites and cannot function properly. When the body eventually breaks down these enzymes, biotinidase is needed to chemically release biotin from its degraded enzyme.

When biotinidase is deficient, this bound biotin cannot be recycled in the body and, as a consequence, biotin is lost rapidly from the body. The symptoms of biotinidase deficiency are very similar to those in biotin deficiency. The therapy for this disorder is to give large doses of biotin daily: 5000-20,000 micrograms (mcg) per day. Defective regulation of the immune system has been reported in several patients with biotinidase deficiency (42). Some of the patients had Candida dermatitis and some showed defective cellular immunity against Candida. One patient had reduced white blood cell killing against Candida and myeloperoxidase deficiency (see chapter on immune system) that were normalized by biotin supplementation. Developmental delay is also common in biotinidase deficiency (42).

Biotinidase may be especially important in autism because it has been found that the biotinidase enzyme also helps to break down peptides including those with opiate-type activity (45, 46).  Therefore, patients with a biotinidase deficiency may be over-stimulated by endorphins and other peptides. It is also possible that the conversion of biocytin to free biotin by biotinidase might be inhibited by the high amount of undigested peptides from wheat and milk so that biotin might not be properly recycled even when biotinidase is present at normal values. Therefore, people with autism who are not on a gluten and casein free diet may need additional amounts of biotin in their diet. This enzyme is zinc dependent so it is possible that this enzyme may not function well if zinc is deficient, which is often the case in many children with autism.

Biotinidase deficiency is tested in only a handful of laboratories in the world and requires a blood test. This test is performed in the laboratory of Dr. Barry Wolf at the Genetics Dept at the Medical University of Virginia in Richmond, Virginia.  The phone number is 804-828-9632. The easiest way to arrange for this test is to have your doctor request the test and then have a local pediatric hospital skilled in drawing blood from children take the blood sample and ship it to Dr. Wolf’s lab.


 Prescription Antifungal Products

Nystatin is one of the oldest and safest antifungal drugs. Its safety is largely due to the fact that it’s not absorbed into the blood stream at the doses most commonly prescribed. Your entire intestinal tract is a long tube with your mouth at one end of the tube and your anus at the other end of the tube. Virtually 100% of nystatin is eliminated in the feces. Since nystatin does not enter the blood stream to any appreciable extent, it’s very safe and can’t cause any serious side effects. Nystatin is so safe that it is available in Germany without a prescription. Nystatin was named after the New York (NY) research laboratory in which it was discovered in the 1940’s (NY=New York; stat = state; in).  I know of no serious side effects that have ever been documented with the use of nystatin.

Most children with autism cannot swallow capsules so that the liquid suspensions of nystatin are sometimes the best options. The two brand names of nystatin suspensions are Mycostatin made by Squibb and Nilstat made by Lederle. William Crook M.D. advises against the use of these products because they contain both food dyes and sugar (18). However, most children with autism will not take capsules or plain nystatin powder that is measured out in scoops because of its bitterness. A good option is to find a compounding pharmacist who will mix it with stevia (a natural sweetener that can be bought at health food stores) and dye-free flavorings. All antifungal drugs cause the Herxheimer reaction or yeast die-off reaction.

Amphotericin B, which may be very toxic when given intravenously, is very safe given orally. When it is given orally, its safety is comparable to that of nystatin because like nystatin it is poorly absorbed from the GI tract.  But to get this in a prescription in the United States that is suitable for oral use, you have to contact one of the special pharmacies that dispense this product including Wellness Health and Pharmaceuticals (1-800-227-2627) or College Pharmacy (1-800 855-9538). This drug is widely available for oral use in European pharmacies. The other prescription antifungal drugs are different from amphotericin and nystatin in that they are appreciably or completely absorbed from the intestinal tract into the bloodstream. There is a slight incidence of liver toxicity with all of these drugs that is not a factor with oral nystatin or amphotericin B. When these absorbed antifungal drugs are used, it is necessary to do a liver function test to make sure that the liver is not damaged. These absorbed antifungal drugs include Diflucan (fluconazole), Nizoral (ketoconazole), Sporanox (itraconazole), and Lamisil (terbinafine). Even though these drugs can be considered safe for the most part, they are not as safe as nystatin or amphotericin B.

An increase in the activity of liver enzymes due to leakage from a damaged liver is usually an indicator of liver toxicity. However, a moderate increase in the activity of these enzymes after vitamin B-6 supplementation is not an indicator of liver toxicity. Vitamin B-6 increases the activity of certain of the transaminases or liver function enzymes called AST (SGOT) and ALT (SGPT).  Vitamin B-6 is an essential cofactor for these enzymes and simply activates these enzymes. You need to be aware of this effect since you might be using these tests to monitor liver function when using systemic antifungal drugs. If B-6 supplementation was started at the same time as the drug, a moderate liver enzyme increase may be due to the B-6 activation of the enzymes rather than the release of these enzymes by a damaged liver.

When these absorbed drugs are used, it is necessary to check other medications that may be processed by similar liver detoxification mechanisms. Such drugs include anti-seizure medications, neuroleptics like phenothiazines and haloperidol, and antidepressants like amitriptyline. Other drug metabolism may also be affected and you should check with both your physician and pharmacist before using these drugs for your child. When these drugs are used with the absorbed antifungal drugs, the metabolism of both drugs may be slowed and the systemic amounts of these drugs may increase. Therefore, dosages for both drugs may have to be adjusted downwards. Sporanox has another undesirable side effect in that it inhibits testosterone production at higher doses and might affect a male’s sexual development. The reason is that this antifungal drug works by preventing the synthesis of the fungal steroid ergosterol by yeast and fungus. Unfortunately, this drug also inhibits the human system that produces the human steroid testosterone. Diflucan does not have this effect at normal doses.
 
If there are so many concerns with these absorbed antifungals, why use them at all? The simple answer is that some of the yeasts and fungi are resistant to nystatin or oral amphotericin B or the yeast may be inside the deeper layers of the lining of the intestinal tract where nystatin cannot act. Nystatin and oral amphotericin B, which act mainly on intestinal yeast, may also be ineffective in treating persons with more severe fungal infections of the skin and nails.


 How to Administer Nystatin

I am including more detail about nystatin because it is the most commonly used drug and it is one of the safest and most effective. The most common suspensions of nystatin are formulated to have 100,000 units per cc or ml. (1 cc equals 1 ml for water-based drugs.) Five cc or five ml is the amount in a teaspoon. In administering the doses, it is advisable to use a medicine dropper. There is too much variation in using a plain spoon.

The main consideration in using nystatin is how to avoid the side-effects of the yeast die-off reaction. This can be accomplished by increasing the dosage of nystatin gradually so that the severity of the yeast die-off is minimized. When this approach is used, the yeast are killed over a longer time period instead of during a very short time period. A typical dosing for 2-8 year olds is given in Table 1.  If the symptoms of the die-off reaction are too severe, the dose may be held at the lower level for a day or two before going up to the next dose. If the concentrations of yeast metabolites are predominantly in the normal range when re-tested at 30 days, this dosage is continued. If the yeast metabolites are significantly elevated after 30 days of therapy, the dose of nystatin could be increased by 50-100 % or other antifungal drugs might be added. The die-off reaction may occur again when the medication is increased. Doses for children 8-12 years would be about 50% higher than those in Table 1 and for adults and children older than 13, the dose would be double the above schedule. These doses are my own suggestions. Your physician may want to prescribe a somewhat different regimen and Dr. Semon has suggested a somewhat different dosage schedule in Chapter 12.

Although there is no reason that the higher doses of nystatin might cause increased aggression, reports of such aggression have been fairly common when 4-8 times the dosages recommended above are given. I suspect that nystatin at high doses causes this side-effect although it is possible that the food colors or contaminants in the medication may be responsible. Nystatin is a biological product derived from a mold.


Table 1
 Typical Dosage of Nystatin to Minimize Yeast Die-Off Reaction

 

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6 on

Total daily dose (Units)

50,000

100,000

200,000

300,000

400,00

400,000

Divided daily into

1 dose

2 doses

2 doses

3 doses

4 doses

4 doses



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