Saturday, June 13, 2009

Comparision of Protocols: Rigau, Mhyll, Konynenburg (Yasko)

Remember that this is just a post of my blog, and it evolves, so to see the full story go to: (English) or (Spanish)
My current doc: Josepa Rigau Av Catalunya, 12, 3º, 1ª 43002 Tarragona Spain +34977220358 (I do recommend! hoeopathy and biological medicine, significant improvement)
My previous docs: De Meirleir (, Dra Quintana (CMD), (Lots of medication, antibiotics etc... no significant improvement)

Please take into account that these protocols are taylor made to my particular case, which means that for every patient there are many variants on treatment that each doctor has to determine. Nevertheless these are general lines that gives you a clue of three different approaches to be taken into account because they are very much in the cutting edge of research of this illness.
These approaches are not compatible, either you do one or the other, specially Mhyll and Yasko. Rigau is a more soft approach that does not use heavy orthomolecular prescription that forces detox in the body, as Yasko protocol does for instance. The Methylation Cycle restoration is the hard one and can create toxicity and plenty of side effects, so do not try that without medical supervision, and only try it at a stage where you are strong, otherwise can be devastating. It is quite difficult to restore this cycle, and you need to run a methylation panel first to see if that is your problem.

Treatment of Dr. Rigau:

(Also reflected in Dr. Mhyll below)
1)Omega 3 (up to 6 a day) Eye Q
This is to prevent my propensity for inflammation and cardiovascular problems
2) Probiotics(1-0-0) Ferzym Plus (Specchiasol)
This is to restore folra, vitamins B, Managanesum, zinc, probiotics...

(exclusive from Dr. Rigau based on my genetic profile)
3)SOD from Douglas or Ageloss from Nature Import
This is for the lack of SOD that I show.
4)Milk Thistle (30 drops) or Coenzime Compositum (twice a week)
This is to slow phase I which is too fast, and activate Phase 2 which is too slow, as it shows the study.
5) Naturalith (2-0-2)
6) L Glutamine(1-0-1)
7) Mucosa Compositum
This is to reduce amonia and protect the mucosa from the intestines and colon
8) Homocysteine (Folic Acid and B6)
This is to lower my homocysteine levels
9) Malic Acid (Douglas) or espastrupel (homeopatic) and appe juice in the morning 10) Magnesium
This is to reduce my bilirrubine levels that were high
11) Nivelcol (Tongil) 2 in the morning
This is to help control cholesterol levels
12) Aminoacids: Glicina (2) & Prolina (1) Plus using the vibrating machine of the gym
This is to prevent osteoporosis which will be an issue in my case for the lack of colageno. I can also eat "manitas de cerdo", "codillo"

I can take a break of Labolife in the summer time, because with high temperatures, viruses are not very active.
My metilation pathway is partially bloqued, but the good thing is that the sulfuration pathway is not bloqued, and that offsets part of the problem with metilation.
I do not repair well my DNA, so I should be careful with the sun.
There are three things that are not completely ok in my case: COM (Hormones), MTHFR (metals) and CBS (Homocysteine)

Treatment of Dr. Mhyll

Standard for all Mitochondrial support Extra Anti-oxidants
1) In ½ to 1 pint of water/ Acetyl L-Carnitine 1 gram
2) some fruit juice dissolve: (1 small scoop)
-Ascorbic acid 1 g (1 small scoop) (Or BioCare Vit C 1 g = 2x 500mg caps)
-MMM 2 grams (2 small scoops)
-D-ribose 2.5 grams (½ teaspoon)

3)Swallow at breakfast with the below solution:
-BioCare Adult multivitamins x 1 capsule
-Igennus VegEPA x 4 capsules
-Vitamin Research Vit D3 x 2 caps
-Co-Enzyme Q10 100mg x 2 capsules
-Niacinamide 500mg x 1 capsule
-Magnesium 300mg daily orally (more if tolerated – up to 600mgs)

4)-Subcutaneous injection Evans 50% magnesium sulphate ½ ml (0.05ml lignocaine with 0.5ml magnesium)
5)-Subcutaneous injection B12 ½ ml methylcobalamin daily initially for two months and adjust according to clinical response.

Mid morning
6)D-ribose ½ a teaspoon in tea or coffee
7)Swallow: Co-enzyme Q10 100mg x 1 capsule
Midday – lunchtime
8)Dissolve in ½ pint of water D-ribose ½ a teaspoon
9)MMM 1gram 1 scoop
10)Swallow: Co-enzyme Q10 100mg x 1 capsule
Start on 300mg daily split in three dose for 3 months, then a maintenance dose of 100mg daily.
11)Dissolve D-ribose ½ a teaspoon in tea or coffee
Three teaspoonfuls daily (15gms) should be taken in small doses throughout the day in drinks taking it with green tea, coffee, tea or whatever (hot or cold).
12)Dissolve in ½ to 1 pint of water/ Acetyl L-carnitine 1 gram
13)some fruit juice:
-Ascorbic acid 1 gram (Or BioCare Vit C 1 g = 2x 500mg caps)
-MMM 2 grams
-D-ribose ½ a teaspoon (or adjust to complete your daily dose of 3 teaspoon per day -15mg)
14)With the above solution swallow the following caps with food:
-Co-enzyme Q10 100mg 1 capsule (after 3 months reduce dose to 100mg daily)
-Igennus VegEPA x 4 capsules
After 3 months VegEPA can be reduced to 2-4 capsules daily
At night
15)Take in water/fruit juice
-D-ribose ½ teaspoon
-Selenium 300mcg 3 drops
-(for 4 months) – GSH-px

-Eat a Stone Age Diet, Low carbohydrate intake and high dose of "do it yourself" probiotics including Kefir. Some people also need herbal antifungals and some people systemic prescription antifungals to get on top of their yeast problem.
-Sleep between 9.30pm and 6.30am – more in winter, less in summer.
-Avoid chemicals and do a good clean up of the environment to try to reduce the total load and this will also reduce the allergic burden.
-Epsom salts in the bath (a double handful) will improve magnesium status since magnesium is absorbed through the skin. The bath needs to be as warm as can be tolerated for at least 15 minutes.
-Run microrespirometry studies which look at oxidative phosphorylation in more detail.
-Far Infra Red saunaing at least two sessions a week. Another method of detoxing is to take high dose essential fatty acids and other oils.Interestingly many people who take VegEPA report much improved sleep.

PROTOCOL Richard A. Van Konynenburg

FolaPro [2]: ¼ tablet (200mcg) daily (5-methyl tetrahydrofolate)
Actifolate [3]: ¼ tablet daily
General Vitamin Neurological Health Formula [4]: start with ¼ tablet and work up dosage as tolerated to 2 tablets daily (multivitamin, multimineral supplement including antioxidants, trimethylglycine, nucleotides, supplements to support the sulfur metabolism, a high ratio of magnesium to calcium, and no iron or copper) starting with ¼ tablet and increasing the dosage as tolerated, to 2 tablets daily
Phosphatidyl Serine Complex [5]: 1 softgel capsule daily (phospholipids and fatty acids)
Activated B12 Guard (hydroxocobalamin)[6]: 1 sublingual lozenge (2,000 micrograms) daily

Here is hard to tell, wether is included in Dr. rigau or Dr Mhyll strategy: Folic Acid is prescribed in Dr.Rigau's protcol to reduce homocisteyn. Multivitamins and Minerals is included in Dr. Mhyll and Dr. Rigau as a general thing. Phospholipids and fatty acids, could be included as the omegas prescribed by Dr. Rigau and Dr. Mhyll. And B12 is included by Dr. Mhyll. The key question is to know which format, and dose is the better advice...

I guess I will discuss the three protocols with Dr. rigau and will come up with something out of it. To be continued...

Martin Pall questions the Richard Konynenburg Protocol


There has been a movement arguing that a deficiency in methylation activity is central to the causation of both autism and chronic fatigue syndrome/myalgic encephalomyelitis. Many have argued that lowered methylation of DNA leads to epigenetic changes that may be responsible for the development of these diseases. While there has been published evidence for lowered DNA methyation, there is no evidence that this has any epigenetic role and an animal model study suggests that is does not. Dr. Richard Van Konynenburg has argued repeatedly that such methylation deficiency leads to lowered levels of reduced glutathione levels which he argues lead, in turn to the symptoms of CFS. My own view is that both of these views are mostly wrong. There is, however, a modest decrease in methylation cycle activity that is a consequence of the NO/ONOO- cycle. Whether this modest decrease in methylation cycle activity has any importance in the pathophysiology of CFS or other NO/ONOO- cycle! diseases is uncertain.

Let me outline my own views on this:

1. 5-methyltetrahydrofolate (5-MTHF) the methyl donor derived from the B vitamin folic acid, has been shown to be a potent scavenger for peroxynitrite. I am aware of some unpublished data that has shown that the levels of 5-MTHF are quite low in the plasma of CFS/ME patients, typically something like 60 to 70% lower than in normal controls. Other folate derivatives are also low, but not as low relative to normals as 5-MTHF. The only interpretation of this that I am aware of is that peroxynitrite, presumably elevated as a consequence of the NO/ONOO- cycle, is leading to the oxidation of 5-MTHF and subsequently some loss of total folate as well. A precursor of 5-MTHF, tetrahydrolate, also has a role as a peroxynitrite scavenger but is considerably less active in this process. The loss of 5-MTHF is opposite what might be expected from the Van Konynenburg model which assumes that lowered methylation is caused by a lowered activity of the enzyme methionine synthase and! lowered vitamin B12 activity. However, both of these mechanisms will produce a lowered utilization of 5-MTHF and should, therefore cause 5-MTHF to accumulate to higher levels. This is the opposite of what is found. So the pattern of changes in folate pools is consistent with the prediction that it is caused by excessive peroxynitrite, reacting with 5-MTHF and to a lesser extent with tetrahydrofolate but is not consistent with the Van Konynenburg model.

2. The same set of data showed that there was a modest decrease (circa 10-15% lower) in the levels of S-adenosylmethionine (SAM)in CFS/ME patients. SAM is the downstream methyl donor produced in the methylation cycle that is used, in turn, to methylate many compounds in cells. It has been estimated that about 20% of the methyl donors going into the methylation cycle to produce S-adenosylmethionine comes from 5-MTHF with the other 80% coming from betaine (trimethylglycine) and methionine. It is reasonable, therefore, that a 60-70% decrease in 5-MTHF could produce a 10 to 15% lowering of S-adenosylmethionine and thus a modest lowering of methylation cycle activity. The question is whether this modest lowering has any substantial role in the pathophysiology of CFS and other multisystem illnesses? I don't know the answer to that but suspect if it has a role, it is a relatively modest one. In any case, those of you who are taking the whole Allergy Research Gro! up nutritional support protocol including the betaine found within the NAC enhanced antioxidant formula and the hydroxocobalamin form of vitamin B12 found in the MVMA, have probably already normalized methylation activity so I doubt that this is a problem for you.

3. Dr. Neil Nathan and Dr. Van Konynenburg have developed an treatment protocol that they argue should act to increase methylation cycle activity. I believe that this does produce substantial improvements in most CFS/ME patients who have been treated by it and I think this may be an effective treatment approach. However I think that their interpretation of how it works in wrong.

4. Their protocol includes about 300 micrograms per day of 5-MTHF, which they argue is effective because of its role in introducing methyl groups into the methylation cycle. However this amount of 5-MTHF only supplies roughly 1/80,000 of the daily methyl donors in the human diet, almost all of which do go into the methylation cycle. It follows, therefore that the 5-MTHF is probably on the order of 1/10,000th of what is needed to produce anything like a normalization of methylation cycle activity. One can conclude, therefore, that Dr. Van Konynenburg is wrong in ascribing the action of the 5-MTHF in this protocol to acting to introduce methyl groups into the methylation cycle. How can it be acting? It can be acting as a peroxynitrite scavenger, lowering the activity of peroxynitrite and therefore lowering the NO/ONOO- cycle. You may recall that at the heart of the NO/ONOO- cycle is what I call the central couplet, where peroxynitrite oxidized the compound tetrahydrobio! pterin (BH4) and a BH4 deficiency leads to partial uncoupling of the nitric oxide synthases, leading to more peroxynitrite. It has been known for a while that high dose folate supplements lead to increased availability of BH4. It seems likely, now, that the high dose folate acts as a precursor of 5-MTHF, leading to peroxynitrite scavenging and therefore to increased BH4 availability.

5. Dr. Van Konynenburg has told me that if they used doses of 5-MTHF substantially higher than 300 micrograms per day, they have some toxic reactions to it. I have gotten similar information from a physician treating fibromyalgia patients. My guess is that there may be oxidation products produced by the reaction of peroxynitrite with 5-MTHF that may be toxic - this is just a guess, but it makes sense given what we know about the overall mechanism.

6. They have in their protocol both intrinsic factor, a glycoprotein that greatly increases vitamin B12 absorption and also substantial amounts of the hydroxocobalamin form of vitamin B12, which is a potent nitric oxide scavenger. This combination should lead to much higher levels of absorption of hydroxocobalamin than we get just using strait oral hydroxocobalamin in the MVMA component of our protocol, without intrinsic factor. This may be responsible, in part for the clinical response that they see. We have known all along that the amount of hydroxocobalamin absorbed from the Allergy Research Group nutritional support protocol is inadequate to get the full effect of the hydroxocobalamin scavenging of the nitric oxide and many have gone to using hydroxocobalamin IM injections, inhaled nebulized material, nasal spray or other approaches to increase the hydroxocobalamin blood levels. Using intrinsic factor may be another approach that may be useful for this as well, base! d on their observations.

7. We have, then, in their protocol, two agents that should be effective in acting to lower peroxynitrite, the most central element in the NO/ONOO- cycle. High dose hydroxocobalamin whose absorption is greatly stimulated by the presence of intrinsic factor and which serves to lower one of the precursors of peroxynitrite, nitric oxide. The other is the 5-MTHF which serves as a potent peroxynitrite scavenger. I think that the roles of both of these are telling us some useful things, which is part of the rationale for this post.

8. They have a number of things in their protocol which I am sure are useful when used as a stand alone approach. These include a number of antioxidants and also a high dose B vitamins. My guess is that the Allergy Research Group nutritional support protocol is at least as good in these areas and probably better.

9. Unfortunately, we do not have any direct comparisons of the two protocols. My guess is that they are roughly similar. I do think that adding 5-MTHF to the Allergy Research Group nutritional support protocol may be quite useful however, based on the reasoning presented above. We already had reason to believe that increasing the hydroxocobalamin levels in the body over that produced by the Allergy Research Group protocol is useful.

I want to add that I am a PhD, not an MD and none of this should be viewed as medical advice.

Martin L. (Marty) Pall

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