developed by: Richard A. Van Konynenburg, Ph.D
Richard A. Van Konynenburg, Ph.D presented the Glutathione Depletion—Methylation Cycle Block Hypothesis for the pathogenesis of CFS in a poster paper at the 8th international conference of the International Association for Chronic Fatigue Syndrome in Ft. Lauderdale, Florida, on January 10-14, 2007. Due to subsequent requests from clinicians for a description of a treatment approach based on this hypothesis, Van Konynenburg came up with a Simple Approach Part I, Part II and a more Customized Approach, based on what he perceives to be the most successful treatment approaches currently used in autism, which he believes shares the same basic pathogenetic mechanism with CFS. In most cases, it will be necessary for the physician to use the Customized Approach and tailor the treatment program to the individual patient. He has since updated his approach and added some cautions. Please note that some people who have tried this approach have had adverse effects, sometimes of a serious nature.
Van Konynenburg believes that the fundamental biochemical issue in a large subset of the CFS patients is that the methylation cycle is blocked. The main goal of this treatment approach is to remove this block and restore the methylation cycle. He also believes that glutathione depletion is directly responsible for many of the features of CFS, but that it is usually not possible to normalize the glutathione levels on a permanent basis by direct approaches of glutathione supplementation. Rather, the methylation cycle block must be corrected first, to break the vicious circle that is holding down the glutathione levels. In addition to this, about one-third of CFS patients, because of particular genetic polymorphisms, cannot tolerate supplementation with glutathione or other substances intended to help them directly to build glutathione.
Based on what is being done in autism by the Defeat Autism Now! (DAN!) researchers and clinicians and independently by Dr. Amy Yasko, N.D., Ph.D., he suggests two treatment approaches for CFS. The first is a simplified approach better suited to patients who have been ill a relatively short time and are not disabled. Use of this simplified approach would be based on the hope that the patient does not have certain genetic polymorphisms, which would not be known in this simplified approach.
If the patient does in fact have these polymorphisms, the simplified approach will not be successful, and the customized program should be followed. This simpler treatment approach is based partly on the treatment that was used by Dr. S. Jill James, Ph.D., et al. in the study that found the connection between the methylation cycle block and glutathione depletion in autism (Ref. 2 in his pathogenesis paper), but it makes use of supplements that are part of Dr. Amy Yasko’s treatment program.
The second treatment approach is much more involved and is based on Dr. Yasko’s complete autism treatment. Van Konynenburg believes that the second approach is the treatment that will be necessary for most CFS patients, especially those who are more debilitated/disabled, as well as those with certain genetic polymorphisms.
Protocol: The simplified approach includes taking the following oral supplements daily, all of which are available from Dr. Yasko’s supplement website at http://www.holisticheal.com
- 1/4 tablet (200 micrograms) Folapro (Folapro is 5-methyl tetrahydrofolate, an active form of folate, which is sold by Metagenics with a license from Merck, which holds the patent on synthesis).
- 1/4 tablet Intrinsic B12/folate (This includes 200 micrograms of folate as a combination of folic acid, 5-methyl tetrahydrofolate, and 5-formyl tetrahydrofolate, aka folinic acid or leucovorin (another active form of folate), 125 micrograms of vitamin B12 as cyanocobalamin, 22.5 milligrams of calcium, 17.25 milligrams of phosphorus, and 5 milligrams of intrinsic factor)
- (up to) 2 tablets (It’s best to start with 1/4 tablet and work up as tolerated) complete vitamin and ultra-antioxidant from Holistic Health Consultants (This is a multivitamin, multimineral supplement with some additional ingredients. It does not contain iron or copper, and it has a high ratio of magnesium to calcium. It contains antioxidants, some trimethylglycine, some nucleotides, and several supplements to support the sulfur metabolism.)
- 1 softgel capsule Phosphatidyl Serine Complex (This includes the phospholipids and some fatty acids)
- 1 sublingual lozenge Perque B12 (2,000 micrograms hydroxocobalamin with some mannitol, sucanat, magnesium and cherry extract)
- 1 capsule SAMe (200 mg S-adenosylmethionine)
- 1/3 dropper, 2X/day Methylation Support Nutriswitch Formula (This is an RNA mixture designed to help the methylation cycle. It is not essential, but is reported to be helpful.)
Note that hydroxocobalamin is specified rather than methylcobalamin as the main supplemental form of vitamin B12, to accommodate patients who may have downregulating polymorphisms in their COMT (catechol-O-methyltransferase) enzyme, which many CFS patients seem to have. If they do not have these polymorphisms, methylcobalamin would be more effective, but in this simplified treatment, the patient’s polymorphisms will not be known.
This simplified approach also includes a small amount of SAMe, which is also a compromise, since the amount needed will again depend on COMT polymorphisms, which will not be known for this simplified treatment. The amount of B12 specified is also a compromise, since those with certain polymorphisms will benefit from a higher dosage than will those without them.
Treatment Course: Once treatment begins, the patient may feel worse initially. It is best to determine whether this is occurring because the treatment is working and the patient’s body is beginning to detox and kill viruses, or whether it is occurring because the patient does in fact have upregulation polymorphisms in their CBS (cystathionine beta synthase) enzyme, in which case you will have to move on to the more complicated complete treatment regimen.
Which of these is the case can be determined by taking spot urine samples for a urine toxic metals test and a urine amino acids test from Doctor’s Data Laboratories. These can be ordered through Dr. Yasko (at http://www.testing4health.com) if you would like to receive her interpretation of the results, or they can be ordered directly from Doctor’s Data Laboratories (http://www.doctorsdata.com).
If the toxic metals are elevated on the urine toxic metals test, this will indicate that the patient has begun to detox, which is desirable. If taurine and ammonia are elevated on the urine amino acids test, this will suggest that the patient does have CBS upregulation polymorphisms, in which case you will have to stop this treatment and move to the more complicated approach described below.
It would be best to do this treatment for a week or two before doing the urine tests, so that meaningful results can be obtained on these tests, unless the patient cannot tolerate it. If the latter is the case, then you will have to go on to the more complicated Customized Approach.
A yahoogroup has been started for those wanting to explore Dr. Amy Yasko’s protocol and Rich Van Konynenburg’s treatment plans in depth: http://health.groups.yahoo.com/group/CFS_Yasko/. Please note, this is a treatment group and not a support group.
see also: Dr. Amy Yasko’s Nutrigenomics Protocol
source(s): Suggestions for Treatment of Chronic Fatigue Syndrome (CFS): The Simple Approach based on the Glutathione Depletion—Methylation Cycle Block Hypothesis for the Pathogenesis of CFS by Richard A. Van Konynenburg, Ph.D.