Biological Treatments for Autism and PDD Online > Chapter 4: Part I | Part II

Buy The newest version (2002) of this book online!

Lactoferrin.

Lactoferrin is a protein found in many mammals including humans and 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 probably by starving it from iron. Lactoferrin is available as a supplement but because of the iron inactivation and digestion by the body's enzymes, I am unsure as to 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 your child has high iron and high iron binding capacity by a blood test, it might be beneficial for yeast control to use vitamins that do not have additional iron.

Top

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 Candicyn (not an endorsement) contains Pau D'Arco extract, oregano, gentian extract, caprylic acid, grapefruit seed extract, barberry extract, goldenseal extract, ginger, cinnamon, chamomile, and biotin.

Top

Biotin

Biotin is one of the essential vitamins. It was termed vitamin H. Biotin is commonly found in most multivitamin supplements but is usually present in doses well below the recommended daily allowance or RDA even in the most expensive vitamins. In addition, biotin is one of the vitamins that is produced by 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 He lost his appetite, began to lose weight, developed a red eczema on the cheeks, became withdrawn, and then his hair began to fall out in large clumps.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 inmate.

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 episode first brought my attention to the less than miraculous results 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.

Top

Biotinidase deficiency

Biotinidase deficiency is a genetic inborn error of metabolism that has been found in both autism(43) and another defect of biotin metabolism has been reported 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 can not function properly. When these enzymes are eventually broken down by the body, 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 enzyme biotinidase 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 absorbed by the person with autism so that biotin might not be properly recycled even when biotinidase was 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 as is 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.

Top

Prescription antifungal products.

Nystatinis 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 get into 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 won't take capsules so that the liquid suspensions of nystatin are sometimes the best options. The 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, I feel that most children with autism will not take capsules or plain nystatin powder which is measured out in scoops because of its bitterness. Another option would be to add a natural sweetener like FOS (fructo-oligosaccharides) or Stevia to the dose of plain powder All antifungal drugs cause the Herxheimer reaction or yeast die-off reaction.

I have encountered a significant number of reports of increased aggression of children with autism when doses 4-8 times the recommended dose of nystatin were given. One particular behavior that was reported by several different parents was that the child would pinch women on the breast, even women who were strangers. I suspect that this behavior may have been due to the food dye used in the nystatin.

Top

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-6supplementation 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 detoxification mechanisms by the liver. 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 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, the human system that produces the human steroid testosterone is also inhibited by this drug. 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.

Top

How to administer nystatin

I am including more detail about nystatin because it is the most commonly used drug and because 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. Since most people use a regular spoon instead of a measuring spoon to give liquid drugs, I would advise using a precise dropper or other device be used for greater accuracy. 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. 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 concentration 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.

 

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
50,000
100,000
200,000
300,000
400,000
400,000
Divided daily into
1 dose
2 doses
2 doses
3 doses
4 doses
4 doses

 

Although there is no reason that the higher doses of nystatin might cause increased aggression, reports to me 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. A physician who uses nystatin quite frequently in his practice stated to me that he gets better results with the Lederle brand of nystatin (Nilstat). He suspects that other brands of nystatin may be contaminated with other byproducts of the mold that produces nystatin. Furthermore, he attributes some adverse reactions of nystatin to the effects of these contaminants rather than to the yeast die-off reaction.

Top

References

  1. Naugle E. Candida & Dysbiosis Foundation Newsletter Vol 2, No 2, p8, 1996.
  2. Nolting S et al. Mykosen des Verdauungstraktes, Max Simon KG, Hamburg,Germany, 1994.
  3. Trowbridge J and Walker M. The Yeast Syndrome. Bantam Books, NY, 1986.
  4. Kasckin P. Some aspects of the candidosis problem. Mycopathologia et Mycologia applicata 53:173-181, 1974.
  5. Mattman L. Cell Wall Deficient Forms. Stealth Pathogens. Second Edition. CRC Press. pg 245-246, 1993.
  6. Ionescu G et al. Zirkulierende immunokomplexe, spezifisches IgE gegen Nahrungsmittel. Immuno Infekt 13:147-155, 1985.
  7. Sumiki Y. Fermentation products of mold fungi. IV. Aspergillus glaucus. J Agr Chem Soc Jap 5 : 10, 1929.
  8. Sumuki Y. Fermentation products of molds. J Agr Chem Soc Jap 7 : 819, 1931.
  9. Kawarda A, Takahoshi N, Kitamura H, Seta Y, Takai M, and Tamura S. Biochemical studies on bakanae fungus. Bull Agr Soc Jap 19: 84, 1955.
  10. Sobel J et al. Vaginitis due to Saccharomyces cerevisiae: epidemiology, clinical aspects, and therapy. Clinical Infectious Diseases 16:93-99, 1993.
  11. McKensie H et al. Antigenic heterogeneity of strains of Saccharomyces cerevisiae and Candida albicans recognized by serum antibodies from patient's with Crohn's disease. FEMS Microbio. Immunol 89: 219-224, 1992.
  12. Sternberg S. The emerging fungal threat. Science 266:1832-1834, 1994.
  13. Eaton K et al. Abnormal gut fermentation: Laboratory studies reveal deficiency of B vitamins, zinc, and magnesium. J Nutr Biochem 4: 49-52, 1993.
  14. Humnisett A et al. Gut fermentation(or the autobrewery syndrome): a clinical test with initial observations and discussions. J Nutr Med 1:33-38, 1990.
  15. Sweetman L. Branched chain organic acidurias. In : The Metabolic Basis of Inherited Disease. Sixth Edition. Volume 1. C. Scriver et al, editors. McGraw-Hill, New York, pgs 791-819, 1989.
  16. Hauss R. Gastrointestinal mycoses: Insights and clinical pearls from the German experience. Proceedings of the American Academy of Environmental Medicine in Boston MA. pgs 281-285, 1996.
  17. Conway P. Microbial ecology of the human large intestine. In: Human Colonic Bacteria. Role in Nutrition, Physiology, and Pathology. CRC Press. Ann Arbor. Gibson and MacFarlane, editors. pgs 1-24.
  18. Hughes, WT. Candidiasis. In: Textbook of Pediatric Infectious Diseases. Third edition. Volume II.W.B. Saunders Co., Philadelphia, pgs.1907-1915, 1991.
  19. Crook,W. The Yeast Connection Handbook. Professional Books, Jackson, TN, 1996.
  20. Yeast-related mental disturbances. Psychiatric symptoms elicited through biological (physical) mechanisms. An interview with Richard G Jaeckle M.D.. Mastering Food Allergies. 10(1): 1-4, 1995.
  21. Ruchel R et al. Bacteria accompanying clinical Candida isolates from respiratory secretions and the genitourinary tract. Mycoses 34: 235-238, 1991.
  22. Heinemann J and Sprague G. Bacterial conjugative plasmids mobilize DNA transfer between bacteria and yeast. Nature 340: 205-209, 1989.
  23. Crook W. The Yeast Connection and the Woman. Professional Books. Jackson, TN, pgs. 442-445.
  24. Gorbach S et al. Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG. Lancet ii: 1519, 1987.
  25. Bergogne-Berezin E. Ecologic impact of antibiotherapy. Role of substitution microorganisms in the control of antibiotic-related diarrhea and colitis. Presse Med 24:145-148, 151-152, 155-156, 1995.
  26. Vargas S et al. Modulating effect of dietary carbohydrate supplementation on Candida albicans, colonization and invasion in a neutropenic mouse model. Infection and Immunity 61: 619-626, 1993.
  27. Miles M et al. Recurrent vaginal Candidiasis: importance of an intestinal reservoir. JAMA 238:1836-1837, 1977.
  28. Reed B et al. The association between dietary intake and history of vulvovaginitis. J Family Practice 29:509-515, 1989.
  29. Horowitz B, Edelstein S, and Lipman L. Sugar chromatography studies in recurrent vulvovaginitis. J Reproductive Medicine 29:441-443, 1984.
  30. Appleton J and Tansey M. Inhibition of growth of zoopathogenic fungi by garlic extract. Mycologia 67: 882-885, 1975.
  31. Stiles JC, et al. The inhibition of Candida albicans by oregano. J Appl Nutr 1995; 47 (4):96-102.)
  32. Keeney EL. Sodium caprylate: a new and effective treatment of moniliasis of the skin and mucous membranes. Bull John Hopkins Hosp 78:333-339, 1946.
  33. Neuhauser I and Gustus EL: Successful treatment of intestinal moniliasis with fatty acid resin complex. Arch Int Med 93: 53-60, 1954.
  34. Rotmistrov M et al. Study of the antifungal properties of ammonium caprylate. Mikrobiol Zh 32: 780-787, 1970.
  35. Bartley J. Lipid metabolism and its disorders. In: Clinical Biochemistry of Domestic Animals. Third Edition. J Kaneko, editor. Academic Press, NY, pgs 53-96, 1980.
  36. Roe C and Coates P. Acyl CoA dehydrogenase deficiencies. In: The Metabolic Basis of Inherited Disease. Volume I. Sixth edition. C. Scriver et al, eds. McGraw Hill, NY, pgs 889-914, 1989.
  37. Duran M et al. Cis-4-decenoic acid in plasma: a characteristic metabolite in medium chain acyl-CoA dehydrogenase deficiency. Clin Chem 34:548-551, 1988.
  38. Carlsen G. The Candida Yeast Answer. pg 17, 1997. The Candida Wellness Center, Provo, Utah.
  39. Nikawa H et al. The fungicidal effect of human lactoferrin on Candida albicans and Candida krusei. Archives of Oral Biology 38:1057-1063, 1993.
  40. Bellamy W et al. Killing of Candida albicans by lactoferricin B, a potent antimicrobial peptide derived from the N-terminal region of bovine lactoferrin. Med Microbiol and Immun 182:97-105, 1993.
  41. Hasegawa K et al. Inhibition with lactoferrin of in vitro infection with human herpes virus. Jap J of Med Sci and Biol 47:73-85, 1994.
  42. Wolf B and Heard G. Disorders of biotin metabolism. In: The Metabolic Basis of Inherited Disease. Volume II. Sixth edition. C. Scriver et al, eds. McGraw Hill, NY, pgs 2093-2103, 1989.
  43. Personal communications with both parents and physicians of children with autism, which included examination of medical records.
  44. Bachmann C et al. Rett syndrome revisited: a patient with biotin dependency. Eur J Pediat 144: 563-566,1986.
  45. Oizumi J. Hayakawa K. Enkephalin hydrolysis by human serum biotinidase. Biochimica et Biophysica Acta. 1074: 433-8, 1991.
  46. De Felice C, Hayakawa K, Nihei K, Higuchi S, Tanaka T, and Watanabe T. Changes in cerebrospinal fluid biotinidase activity in Staphylococcus aureus meningitis. Brain & Development 16: 156-8, 1994.

Buy The newest version (2002) of this book online!

Top

Biological Treatments for Autism and PDD Online > Chapter 4: Part I | Part II