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is there any medical basis to Freddd's protocol?

shah78

Senior Member
Messages
168
Location
st pete , florida
@PeterPositive I apprecriate your comments. But I didn't say or imply anything that you attribute to me. Methylation upstart is only one of ELEVEN"five star" modalities I've used to dig out of this cfs helhole. It isn't even one of the top tier. However it was a fast, cheap, very accessable modality with broad results. The "silver bullet" theory is no where to be found in my comments. In fact, Freddd never even says such a thing! People are always attributing this to him as well. He eats right, he practices his tantra alchemy et al. Please, the straw man aguements are a complete waste of everyone's time and energy. Cheers. :)
 

PeterPositive

Senior Member
Messages
1,426
@shah78
I am sorry for the straw men, but some of the ideas in your post are confusing.

You wrote this:
shah78 said:
No one (almost no one)is actually trying an actual protocol. They are simply fretting and spinning their wheels worrying about OVERMETHYLATION. Freddd would call this actual METYLATION! ie, the thing you actually want!...... Especially the COMT++ people and the people worried that they are COMT++. It is so sad.
That's the part I disagree with, and the oversimplification I was pointing out.

I have lots of respect for Freddd's protocol and the help he has given to people. Also I haven't got any desire to downplay the remarkable results that some people have had following it.

I don't think that most of the people who didn't find benefits from it automatically fall in the overmethylation-worriers category. It's even silly to argue about it. You would have to know every detail of every single case to claim such thing.

Cheers
 

shah78

Senior Member
Messages
168
Location
st pete , florida
I agree with you again! Please read the sentences closer. I'm claiming that the people weren't(aren't) even starting the (n=1) experiment! THEY WEREN"T OVERMTHYLATING, because the "experts" were fear mongering. They weren't doing anthing at all, but worring......They are treating Mb12/folate like its PLUTONIUUM :) And remember, I'm not talking about PR. I'm talking about the FB pages! Freddd does not exist over there. They are discussing Methylation in a special kind of vacuum. It's as if they are discussing the History of American Baseball and not mentioning Babe Ruth. :)
 
Messages
15,786
If it isn´t a too personal question, would you mind sharing what SNP´s you consider connected to metabolic and mitochondrial disorders worth looking at? And what SNP´s, except for MTHFR, you consider are affecting the folate and, I suppose, the methionine cycles? I assume those you are looking at, are not among the ones presented in a methylation panel from e.g. Yasko or GeneticGenie?
The SNPs causing the more severe sorts of problems are extremely rare ... so it's unlikely that Sea's would be helpful for you in seeing if you have the same ones. The alternative genotypes of the SNPs in the Yasko panel and such, on the other hand, are usually very common.

In my case, I'm a member of the H1b1 maternal haplogroup, which is actually defined by having a pathogenic missense mutation in the mitochondrial DNA - rs28357970 (i3002114) is G instead of A. It can result in adult-onset dystonia for some people, but obviously it doesn't always do so, and the gene (MT-DN1) is also associated with MELAS, LHON, and Leigh Syndrome, some of which have characteristics in common with ME/CFS.

Regarding other genes involved in folate production, transportation, etc, there are dozens. Also quite a few genes are involved in B12 absorption and transformation. The Yasko panel is really looking at a very tiny amount of SNPs involved in methylation, B12, or folate, and even those few are often completely irrelevant to gene function.
 

Helen

Senior Member
Messages
2,243
Hi @Valentijn
But what if the SNP´s that @Sea found connected to mitochondrial impairments are the same for other PWME;) ? I have gene test results from about 15 people who I know pretty well with their sick stories and it would be interesting to check the SNP´s also for them.

Though the actual SNP´s might be many I think it would be interesting to know what SNP´s that @Sea, probably for good reasons, thought where worth considering for B12 and folate metabolism. Sooner or later we hopefully will get to know from genome studies if the positive effects from extra B12 and folate for many PWME are connected to polymorphisms, or if another explanation has to be found. Probably Prof. Ruma Banerjee could sort this out.
 

Aerose91

Senior Member
Messages
1,400
But ,IT WAS THAT SIMPLE! ..... Suffer for 57 years, follow Freddd's protocol (at 1/30 his dosages!),derive a modest "brightening" of almost all aspects of life. Doesn't sound silly to me! Sounds like a f*cking miracle! :)

Awesome that you have seen relief with his protocol but I took 1/40th of his starting dose and got nothing but intolerable adrenaline. What would Freddd say to this, that these are just "startup reactions" and I should just increase my dose? There's obviously something else at play that Freddd is unaware of for some of us.
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
Hi @Valentijn
But what if the SNP´s that @Sea found connected to mitochondrial impairments are the same for other PWME;) ? I have gene test results from about 15 people who I know pretty well with their sick stories and it would be interesting to check the SNP´s also for them.

Though the actual SNP´s might be many I think it would be interesting to know what SNP´s that @Sea, probably for good reasons, thought where worth considering for B12 and folate metabolism. Sooner or later we hopefully will get to know from genome studies if the positive effects from extra B12 and folate for many PWME are connected to polymorphisms, or if another explanation has to be found. Probably Prof. Ruma Banerjee could sort this out.

Hi Helen, I'd be happy to share specifics if I thought it would be helpful but it would take me some work to dig them out and I honestly do not expect that anything I have found in me will apply to most or even any others. I have records, but they are in no way organised or easily summarised at this point in time.

One of them is a rare (0.009%) snp on the CPT2 gene which results in CPT2 deficiency. I have yet to follow this up fully because 23andme doesn't test enough relevant snps for me to know if I am a symptomatic carrier (which research has shown does happen with this snp) or a positive compound heterozygous. I would have to have the whole CPT2 gene sequenced to find this out, or a muscle biopsy to test the level/efficiency of the enzyme. It's hard to find a doctor who is keen to do that based on a 23andme test. My father had many episodes which fit the pattern of this disorder and died of kidney failure which is a known complication. His diagnosis of Myasthenia Gravis did not explain these events.

The mitochondrial snp I have is uncommon (I can't remember the prevalence) relevant to mitochondrial complex 1 deficiency. I googled OMIM mitochondrial and systematically went through all the listed snps for known mitochondrial deficiencies, ignoring the ones that are considered benign. There are a multitude! I did this because it is often said that our symptoms fit the patterns found in mitochondrial disorders.

B12 and folate I can't remember how I found them. I think I googled things like folate metabolism genes, B12 metabolism, B12 transport etc. and systematically looked at relevant snps. I don't know any way to short cut the process of finding out relevant info. I didn't keep any record of the genes that were relevant that I didn't find any snps on in my results.

Although research does show that common snps can lead to certain predispositions or benefits you need many hundreds or thousands of people's results to accurately determine such information. For example around 40% of people carry celiac predisposing genes but only around 1% of people are celiac. This is unlike some of the rare disorders where only the people with the rare snps have the the disorder. (eg Cystic Fibrosis) So I don't focus too much on the common ones but I look very carefully at any of the rare or relatively uncommon ones.
 
Messages
15,786
Hi @Valentijn
But what if the SNP´s that @Sea found connected to mitochondrial impairments are the same for other PWME;) ? I have gene test results from about 15 people who I know pretty well with their sick stories and it would be interesting to check the SNP´s also for them.
I've been comparing the rare and very rare results from the full 23andMe files of ME patients (43 so far, + 2 more definitely coming), and looking for similarities. I need to get a more powerful PC to process this much data in more useful ways, and to allow for incorporating data from various databases (minor allele frequencies, gene names/locations, pathogenic flags, missense/stop-gain mutation flags, maybe even gene keywords, etc).

One thing I want to do is automatically compare allele frequency for every SNP I have data for, with what is expected and what the "controls" have. I was (barely) able to do this when I had a much smaller sample several months ago, and eventually came up with a list of SNPs sorted based on which SNPs on which we differ the most from controls. As an example, at the top of the list is rs4557033 where we had 17 more instances of the "A" allele compared to the controls. that's quite a lot but the A allele has 38.1% prevalence in the general population. So we we have a MAF of 58.1%, which is a lot higher than the controls at 27.4%, but isn't a huge difference when compared to 38.1%, if you consider that 960,000 SNPs were processed in that way and some random big differences are likely to turn up.

Hence I need to get a statistics program talking nicely to a proper database program, so that statistical significance can be accurately determined, and give us a good idea of what is background noise and what might actually be relevant. Additionally, it is obvious that there's no single SNP in the 23andMe data which is effectively flipping a switch and causing ME/CFS. Hovever there might be a variety of SNPs on the same gene or on related genes which create the same susceptibility - but that involves more complexity to assess, and a need for the appropriate programs (database) and processing power.

Pending the ability to easily automate this sort of processing, I'm compiling lists of shared rare SNPs of ME patients, then using that to expand to looking at the entire gene involved with each shared rare SNP, and genes which share a similar function. Currently I'm doing this by starting with SNPs which have a 1% prevalence or less, with the list for each patient generated by http://sourceforge.net/projects/analyzemygenes/ and then the list for every patient added to the same excel sheet, where I can sort and tally the number of duplicate rare results. At the top of the list when I had data for 40 patients was rs11608105, which has an expected MAF of 1%, but we have at 25% (8 heterozygous patients, and 1 homozygous). Interesting! But the expected MAF in europeans is actually 7.5%, so not quite as impressive. But if I look at the 31 patients I currently have ethnically roughly-matched controls set up for, we have 22.6% MAF and those controls just have 6.5%. So definitely worth looking into the associated gene (CADM1) and such a bit further.

Anyhow, I am looking for associations in a variety of ways, but right now it's slow and tedious and requires my brain to be working fairly well. Except I'm getting fevers and intense hypotension for nearly the entirety of every day while on a couple antibiotics for Lyme, so I can't really handle it currently. But medical bills have been almost entirely paid and reimbursed now by my parents, so hopefully we can get a proper computer in the next week or so! The fiance actually brought it up last night, so fingers are crossed :D
 

justy

Donate Advocate Demonstrate
Messages
5,524
Location
U.K
Awesome that you have seen relief with his protocol but I took 1/40th of his starting dose and got nothing but intolerable adrenaline. What would Freddd say to this, that these are just "startup reactions" and I should just increase my dose? There's obviously something else at play that Freddd is unaware of for some of us.
This was my experience exactly - my M.E dr prescribed 500mcg a day of Mb12 - sub cut . I couldn't even tolerate half of this dose. I posted it on PR (not on Fredds thread) and he posted that it was a start up reaction, that I would never heal if I didn't push it and take a higher dose - I wasn't even looking at methylation at the time.

To be told you will never heal unless you do something that someone else suggests is not only rude, but also dangerous and plays with peoples minds.

I have always believed that if something makes me feel bad I stop or back off - I simply don't believe in pushing through anything. Another Dr told me the exact same thing when I reacted to Armour thyroid - I needed to take MORE not less and I simply wasn't taking enough - I increased my dose, because he was a dr and I thought he knew best, and I had paid him a lot of money to advise me and what happened? I crashed severely and have NEVER recovered to the level I was at before I even saw this Dr.

Rant over.
 

Aerose91

Senior Member
Messages
1,400
This was my experience exactly - my M.E dr prescribed 500mcg a day of Mb12 - sub cut . I couldn't even tolerate half of this dose. I posted it on PR (not on Fredds thread) and he posted that it was a start up reaction, that I would never heal if I didn't push it and take a higher dose - I wasn't even looking at methylation at the time.

To be told you will never heal unless you do something that someone else suggests is not only rude, but also dangerous and plays with peoples minds.

I have always believed that if something makes me feel bad I stop or back off - I simply don't believe in pushing through anything. Another Dr told me the exact same thing when I reacted to Armour thyroid - I needed to take MORE not less and I simply wasn't taking enough - I increased my dose, because he was a dr and I thought he knew best, and I had paid him a lot of money to advise me and what happened? I crashed severely and have NEVER recovered to the level I was at before I even saw this Dr.

Rant over.

Same thing happened to me with ativan; 3 years later I have never recovered.

However, though, I'm all for pushing through the hard times and getting past it but there's a difference in what Freddd calls start up reactions and being intolerant to mb12. I guess according to him we are never going to heal because we can't take high doses of mb12?
 

pemone

Senior Member
Messages
448
Thanks for that. So Freddd's protocol was just the protocol that worked for him? And he touts it like it's gospel and all of these doctors and research is wrong? He won't get 23and me either? I'm sorry but I'm having a hard time seeing how there's any merit at all to Freddd and his protocol. He's heavily pushing things that can be very dangerous to some of us.

Thanks for that PNG image showing forms of B12 to take with different SNPs.

I definitely get the feeling that methylation is an area people should NOT self-treat. You need to find a competent person who can read the SNPs and customize your approach to your biology.

Several people online are making the claim that glutathione will destroy MeCbl on contact and cause neurological damage. Yet when I search the scientific literature I don't find any support for that idea. The same people making these claims post small sample studies they conducted on their own, but at no point in their study do they measure MeCbl. So frankly you have to be very skeptical. Glutathione makes me very sick, but I think that is because I have a sulfur and thiol sensitivity. That may be partly attributable to poor methylation and may be partly attributable to mercury toxicity.

When people make factual claims, ask for the science. Personal experience isn't science, but personal observations can be very useful to form hypotheses to test.
 

pemone

Senior Member
Messages
448
SNPs are like a clue, but they aren't the full solution. There is a huge amount of redundancy in gene function and so you can have 1 that has a polymorphism but 5 others that do a same or similar thing that can compensate. Its extremely complicated. Nonetheless, the ones typically focused on, i.e. COMT, MTHFR, etc are examined in research for a reason and typically have a lot of data to support increased or decreased likelihoods of outcomes in various situations. But those are averages across groups, so everything is a tendency or a likelihood, not certainty.

I have COMT++ and it fits with how incredibly sensitive I am to many things. I struggled with methyl B-12 and it took a long time, but over time I've totally adapted to it. OTOH, I was unable to adapt to m-folate (or even folinic acid), even trying for a full year and taking a lot of elemental potassium, so had to abort that effort. I do take a combo adreno-hydroxy-methyl 1000 2x a day along with the methyl B-12.

Can you summarize what the COMT defect is? I have heard that some people with methylation problems have sulfur issues. Do you know what that is about and which SNPs are involved in that defect?
 

pemone

Senior Member
Messages
448
@Aerose91 Kruse just recently claimed (and I pretty much believe him) that enough DHA+electrons(ketosis) + cold thermogenesis(Magnetism) + no blue light after dark + limiting non native EMF will stop all heterogygous snps from expressing and most homozygous ones. Outrageous claim, but I'm all in on it for now. I'm not giving up my Mb12 /Ab12/folate just yet, but I can't wait to lower my already meager doses. Maybe as early as 2015!

What's really scary about Kruse is not that he makes these kinds of claims. What is really scary is that he never feels any need to test any claim he makes. And then he just works on the next blog, referring to the last untested theory as if it was foundational science.

I don't think these things will hurt (except maybe CT if you fall asleep in an ice tub and never wake up), but pretty hard to establish they they do or do not adjust SNP behavior.
 

pemone

Senior Member
Messages
448
The mitochondrial snp I have is uncommon (I can't remember the prevalence) relevant to mitochondrial complex 1 deficiency. I googled OMIM mitochondrial and systematically went through all the listed snps for known mitochondrial deficiencies, ignoring the ones that are considered benign. There are a multitude! I did this because it is often said that our symptoms fit the patterns found in mitochondrial disorders.

B12 and folate I can't remember how I found them. I think I googled things like folate metabolism genes, B12 metabolism, B12 transport etc. and systematically looked at relevant snps. I don't know any way to short cut the process of finding out relevant info. I didn't keep any record of the genes that were relevant that I didn't find any snps on in my results.

Although research does show that common snps can lead to certain predispositions or benefits you need many hundreds or thousands of people's results to accurately determine such information. For example around 40% of people carry celiac predisposing genes but only around 1% of people are celiac. This is unlike some of the rare disorders where only the people with the rare snps have the the disorder. (eg Cystic Fibrosis) So I don't focus too much on the common ones but I look very carefully at any of the rare or relatively uncommon ones.

I haven't even started to research the whole world of SNPs, and it sounds like you are getting fully immersed in this. Some broad questions:

1) Do you have an opinion about how long it will be until we have complete gene sequencing at a low price?

2) Isn't the whole world of SNP analysis changing so rapidly that effectively every year for the rest of your life you have to reanalyze the data?

I've been warned by two osteopaths that you can get completely lost in SNPs and most of them have no actionable information.
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
I haven't even started to research the whole world of SNPs, and it sounds like you are getting fully immersed in this. Some broad questions:

1) Do you have an opinion about how long it will be until we have complete gene sequencing at a low price?

No idea really, but I hope it is soon. At a guess I'd say within the next 5 years.
2) Isn't the whole world of SNP analysis changing so rapidly that effectively every year for the rest of your life you have to reanalyze the data?

There will always be new discoveries but once full genome sequencing is common it will not be unusual to know what snps we carry that are different to normal. So then we would only be following up on those ones. Especially interesting will be the rare ones.
I've been warned by two osteopaths that you can get completely lost in SNPs and most of them have no actionable information.

It is very true that you can get lost in snps. A little knowledge can be a dangerous thing and unfortunately there are many who really have no idea what they are doing who are trying to help others or making money off vulnerable people. It is also true that many snps are completely irrelevant. That however does not rule out that there is a wealth of information to be found in snps. Some of it is actionable. While sometimes we may find something that nothing can be done about I would still prefer to have as many answers as possible.
 

shah78

Senior Member
Messages
168
Location
st pete , florida
What's really scary about Kruse is not that he makes these kinds of claims. What is really scary is that he never feels any need to test any claim he makes. And then he just works on the next blog, referring to the last untested theory as if it was foundational science.

I don't think these things will hurt (except maybe CT if you fall asleep in an ice tub and never wake up), but pretty hard to establish they they do or do not adjust SNP behavior.
Its very easy to establish that they do "adjust snp behavior." You start to feel really good/healthy, really fast. :) As Lewis Black says," you don't feel like your head is in a airplane toilet anymore, while it is flushing". :) What test would you possibly need? Healthy people don't go for tests. No?
 

shah78

Senior Member
Messages
168
Location
st pete , florida
What's really scary about Kruse is not that he makes these kinds of claims. What is really scary is that he never feels any need to test any claim he makes. And then he just works on the next blog, referring to the last untested theory as if it was foundational science.

I don't think these things will hurt (except maybe CT if you fall asleep in an ice tub and never wake up), but pretty hard to establish they they do or do not adjust SNP behavior.
Why is Kruse "really scary"? Though you admit "these things won't hurt you". I feel this line of thinking and fearing comes about from our allopathy- medical conventional wisdom. All the allopathic cures (non cures) are dangerous and full of side effects and misery. So even something as benign as standing in the ocean is tainted with some "danger". A cure does not have to entail danger. A true cure involves getting rid of the danger with no danger attached. Aerose set me straight on that point in July.
 

pemone

Senior Member
Messages
448
It is very true that you can get lost in snps. A little knowledge can be a dangerous thing and unfortunately there are many who really have no idea what they are doing who are trying to help others or making money off vulnerable people. It is also true that many snps are completely irrelevant. That however does not rule out that there is a wealth of information to be found in snps. Some of it is actionable. While sometimes we may find something that nothing can be done about I would still prefer to have as many answers as possible.

Are there any practitioners that you can recommend who are extremely good with SNP analysis?
 

pemone

Senior Member
Messages
448
Its very easy to establish that they do "adjust snp behavior." You start to feel really good/healthy, really fast. :) As Lewis Black says," you don't feel like your head is in a airplane toilet anymore, while it is flushing". :) What test would you possibly need? Healthy people don't go for tests. No?

Establishing that Kruse's protocol is the cause of a specific chain of events requires more than just feeling good. The protocol might make you feel good for many reasons, most of which might have nothing to do with Kruse's theories.