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Methylation

Jody

Senior Member
Messages
4,636
Location
Canada
No problem, dreambirdie

Cold? Here, let's just pull this blanket up a bit more. There.

Better? :)
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
DIFFERENTIAL B12 STARTUP REACTIONS

The word “startup” is only used to convey timing. There is a period at the initiation of B12 usage during which a wide variety of symptoms appears, changes, intensifies or is otherwise apparent. These may occur starting within 5 minutes of a sublingual of tested absorbtion and may continue for days, weeks or rarely more than a few months. Most of these appear to be literally stalled processes starting up, of which methylation is only one though that has dozens of secondary blocked processes as a result. As there are hundreds of these stalled processes, the number of possible symptoms is very large and of many varied types. Over a period of time these symptoms settle down, most either disappearing or changing to something else and the rate of change of symptoms and intensity subsides dramatically. The symptoms themselves are usually ones that the person has or has had; often reverting to an earlier form though sometimes unrecognized symptoms occur. As the rapid inflow of active b12s into the nervous system changes the very means of perception it is often difficult to know what is occurring. Rapid changes in mitochondrial, neurological and other functioning often causes mood changes ranging from euphoria to anxiety and sometimes panic attacks. Those who respond to changes with anxiety will usually do so with these changes.


DOSE RELATED CHRACTERISTICS OF STARTUP SYMPTOMS


There are several groups of characteristics that apply to the startup symptoms across type of symptoms and specific symptoms.


1. All the startup symptoms and continued symptoms observed so far to b12 appear to have a ceiling to the effect; they do not increase without limit unlike drugs such as methamphetamine or morphine.


2. Some startup symptoms are binary, either on or off. When these “turn on” they turn on full blast with no moderation. Titrating keeps them from happening until their threshold is reached and then they are ON in full force. More b12 makes no difference at all to these.


3. Some startup symptoms appear to have a dose proportionate response, but not a linear dose proportionate response. The biggest change occurs with a small dose and intensity of symptoms increases more slowly than dose. Some have a noticeable increment of intensity at each doubling of b12 dose that decreases as it approaches the ceiling and disappears. Some approach a ceiling more rapidly than others but all appear to have a ceiling. After the ceiling is reached, more b12 has no perceivable effects. It’s like the hero’s paradox, always going halfway to the tortoise.


4. Larger doses at one time may have a different effect than the same dose spread across the day. They appear to trigger more startup symptoms at one time and penetrate deeper into tissues. More frequent smaller doses appear to penetrate more broadly and allow some startup symptoms to subside before triggering others.


5. Larger more frequent doses appear to trigger more separate startup symptoms but also to bring some to completion more quickly.


6. Very small doses subject to binding limits cause fewer startup symptoms because of limiting cellular access to active b12s and can take years to a lifetime to startup all systems. Larger doses of active b12s makes active b12 available to all cells very rapidly way beyond the limits of the binding and transport system.


7. In those with the hypothesized CNS/CSF depressed cobalamin levels as measured in some studies, 50mg single doses of selected sublinguals triggers a CNS startup reaction for each active cobalamin separately. These are not as long lasting or intense as the body level startup, presuming that the body level startup has already reached saturation.



DIFFERENTIAL EFFECTS OF DIFFERENT FORMS OF B12 AND FOLATE

In a population of people with a variety of subsets of symptoms as listed 100% inclusive of but not limited to, the symptoms of FMS, CFS, CFIDS, ME and possibly MCS most will respond to both active b12s separately regardless of previous usage of cyanob12 and/or hydroxyb12 or presumed genetic conditions or lack there of.


Starting with methylb12

If the person starts with methylb12 and reaches a state of saturated equilibrium in which startup symptoms have subsided and no further perceptible startup reactions occur with an increase of dose in the normal body range many persons will then have a separate startup reaction, usually milder than mb12 and of somewhat different characteristics to adenosylb12 at normal dosages.


Starting with adenosylb12


If the person starts with adenosylb12 and reaches a state of saturated equilibrium in which startup symptoms have subsided and no further perceptible startup reactions occur with an increase of dose in the normal body range most persons will then have a separate startup reaction of somewhat different characteristics to methylb12 at normal dosages. The mb12 startup reactions tend to be broader, more intense, and more inclusive and last longer.


Starting with hydroxyb12

If the person starts with hydroxyb12 and reaches a state of saturated equilibrium in which startup symptoms have subsided and no further perceptible startup reactions occur with an increase of dose in the normal body range most persons will then have a separate startup reaction of somewhat different characteristics to methylb12 at normal dosages and to adenosylb12 at normal dosages. These mb12 startup reactions tend to be broader, more inclusive and last longer. The previous inclusion of hydroxyb12 appears to make some of the startup reactions to each kind of active b12 significantly more severe than would otherwise have been noted.


Starting with cyanob12

If the person starts with cyanob12 and reaches a state of saturated equilibrium in which startup symptoms have subsided and no further perceptible startup reactions occur with an increase of dose in the normal body range most persons will then have a separate startup reaction of somewhat different characteristics to methylb12 at normal dosages and to adenosylb12 at normal dosages. These mb12 startup reactions tend to be broader, more inclusive and last longer. The previous inclusion of cyanob12 appears to make some of the startup reactions to each kind of active b12 significantly more severe than would otherwise have been noted.


After active b12 startup symptoms

Once startup reactions to both adenosylb12 and methylb12 have subsided they generally don’t reoccur unless the dose of active b12s is reduced below maintenance level. Additional substances such as methylfolate, SAM-e, l-carnitine-fumarate most commonly; vitamin D, Zinc, magnesium, Omega3 oils more rarely, and a number of other supplements may induce startup symptoms of their own as their presence allows certain pathways to function.



After saturated equilibrium with active b12s

If a person has reached saturated equilibrium with both active b12s and then changes to inactive b12s for maintenance, after a period of time generally deficiency symptoms will reappear and startup symptoms will occur all over again.

Once a body level saturated equilibrium is reached higher doses produce no differential affects except when the single dose level reaches a high enough level there is an additional threshold effect. This is at a dose in the area of 7.5mg subcutaneous injection or 50mgs of a tested sublingual and is suggested by Japanese research and is noted as an “up regulation of neurological healing”. This does not seem to appear in everybody but too few have tried it to be clear. There are potentially 2 separate effects, one to methylb12 and one to adenosylb12. This occurs after saturation is reached by repeated doses of the other. The general startup effects are minor but the neurological healing can be dramatic.



Separate active b12 reactivity

The separate reactivity to each active b12 in most responding people appears over a range of relative intensities. Some have huge responses to both, some a huge response to one and a mild or moderate response to the other. Some degree of separate response appears to happen in most people having any response to either. This happens far in excess of the estimates for genetic causes of such. It may be that these disease patterns themselves select for persons with these genetic patterns or it may be that the ceiling of conversion in normal people is normally below the level needed for restoring health.

People without any of these many b12 and folate related symptoms normally have no perceptible effects from either active b12 or methylfolate. People who have 1 noticeable characteristic deficiency symptom will usually have many more when a thorough history is taken.


SUMMARY – When will startup symptoms appear

This applies only to people with symptoms from the list of symptoms and similar and related symptoms. Those without symptoms rarely notice anything when starting active b12s or folate.


1. Persons not taking any form of b12 will have startup symptoms a large part of the time when starting methylb12.

2. Persons not taking any form of b12 will have startup symptoms a large part of the time when starting adenosylb12.

3. Persons not taking any form of b12 will have startup symptoms part of the time when starting hydroxyb12.

4. Persons not taking any form of b12 will have startup symptoms occasionally when starting cyanob12.

5. Persons taking cyanob12 will have startup symptoms a large part of the time when starting methylb12.

6. Persons taking cyanob12 will have startup symptoms a large part of the time when starting adenosylb12.

7. Persons taking cyanob12 will have startup symptoms part of the time when starting hydroxyb12.

8. Persons taking hydroxyb12 will have startup symptoms a large part of the time when starting methylb12.

9. Persons taking hydroxyb12 will have startup symptoms a large part of the time when starting adenosylb12.

10. Persons taking hydroxyb12 will rarely have startup symptoms when starting cyanob12 though they may experience induced deficiency symptoms.

11. Persons taking methylb12 will almost never have startup symptoms starting cyanob12 though they may experience induced deficiency symptoms.

12. Persons taking methylb12 will almost never have startup symptoms starting hydroxyb12 though they may experience induced deficiency symptoms.

13. Persons taking methylb12 will often have different startup symptoms starting adenosylb12.

14. Persons taking some methylb12 brands will often have startup symptoms when changing to a 5 star methylb12 sublingual or injection.

15. Persons taking adenosylb12 will almost never have startup symptoms starting hydroxb12 though they may experience induced deficiency symptoms.

16. Persons taking adenosylb12 will almost never have startup symptoms starting cyanob12 though they may experience induced deficiency symptoms.

17. Persons taking adenosyllb12 will often have different startup symptoms starting methylb12.

18. Persons taking some adenosylb12 brands will often have startup symptoms when changing to a 5 star adenosylb12 sublingual.
 

brenda

Senior Member
Messages
2,266
Location
UK
Fredd

I believe that some people are too sick for their bodies to cope with a start up - i believe that I am one of them. I am not denying anything you have said - you may well be right and the fact that some have healed following this procedure would certainly indicate this.

My issue with you is that you are denying that some being too sick could be true and not warning people about the severity of the effects of trying the procedure if indeed they are too sick at that time to cope with it. It is interesting that two others ie dreambirdie and klutzo who are both at a similar level to me have stopped the treatment through listening to what their bodies were telling them and not listening to you say that everything was fine when it obviously was not.

I think that an endo system can be too knackered to cope and what is needed first is some basic healing so that the body can be brought up to the point where perhaps your protocol can be tried out again. I am certainly willing to try it again one day.

I get the impression that perhaps you are thinking that we have 'chickened out' and would not see it through to the end. Again it is rather arrogant of you to assume you know our bodies better than we do or that we are really to soft to cope with a bit of discomfort. I am sure that I can speak for the other two in saying that we have already been through hell and would go back there is we thought we could be healed this time.

I would really love to see you listening to somebody and being a bit more responsible in giving a warning.

Brenda
 

jenbooks

Guest
Messages
1,270
I am not sure it is about being too sick. It could be for instance releasing metals. It can *also* *be* genetic variation. Maybe too much methylb12 is not good in an overmethylator (according to Yasko). Maybe a good converter needs the building block of hydroxy and then be very careful about "startup." We're individuals. Unfortunately there are not necessarily sophisticated tests for each of us and even when there is some testing available its expensive. Therefore we have to start very gingerly and carefully.
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
I would really love to see you listening to somebody and being a bit more responsible in giving a warning.

Yes Freddd--I agree with Brenda. And I have something to add as well.

REMEDY BECOMES OBSESSION
I have seen this quite a number of times, where people find a remedy that heals them or makes them significantly better, and then they get completely OBSESSED with it to the point of losing all objectivity in regard to other people's not quite so miraculous reactions.

REMEDY BECOMES SAVIOR
The remedy/diet/protocol soon becomes the end all and be all, the answer for every malfunction in the body, the "savior" that can do no wrong.


REMEDY BECOMES DOGMA
A dogma of reasons (often marinated in scientific lingo to make it sound more justifiable) as to WHY the remedy is the "savior" follows suit. (sort of like the 10 commandments of the given agenda) This is intended to prove, among other things, why the remedy/diet/protocol, being the end all and be all, could not possibly be causing any adverse effects, and reducing all aforementioned adverse effects to either "discharge" "herx" "die-off" "start up" etc. (pick your word).


REMEDY NEEDS TO CONVERT OTHERS
During this missionary phase, when the "savior" is taken out on the road in order to convert and "save" others, there is a strange religious fervor that develops around the remedy/diet/protocol. This divides those experimenting with it into the "believers" (for whom the remedy works and causes few negative effects), and "non-believers," (who experience A LOT of negative effects and begin to DOUBT :eek: it).

REMEDY CREATES ITS OWN INSANITY
This makes for an interesting bunch of tension. How can you possibly tell someone that their "savior" made them SICK, without experiencing a lot of resistance? The truth is you can't, because beliefs like this go WAY BEYOND scientific explanation, to places where reason doesn't exist.
 

jenbooks

Guest
Messages
1,270
Dreambirdie

You really hit the bullseye with that post. How do you make font colors on these posts?

I've suffered long term consequences (severe MCS and other consequences that eventually ameliorated after lots of suffering) as detailed in other posts, when I was more trusting/naive.
 

jenbooks

Guest
Messages
1,270
Cool. Whaddya know.Hmmm. What next?Anyway. I often think back on these turning points for the worse for me and wonder why I was naive, but then I see people here, veterans of this kind of illness making similar innocent errors.

Still, I often get angry at myself. And tired.
 

jenbooks

Guest
Messages
1,270
Wiser

Yes. Don't worry I won't become color mad just for tonight :D Anyway. The problem is also that our particular bodies are so 'brittle'--our reactions so overwhelming. And one issue with me is I never really *know* whether a particular reaction is minor or serious. I can think something is minor and it's serious and visa versa. That uncertainty is very demoralizing
 
Messages
84
no i will not do it .. i m not sick/fatigued enough to be let to have fun with people ..
if the difference of making fun and putting someone down (or hoplessly tring to ) is , in that the person laughs with u or not , do u plan to ask freddd if he enjoys this ?
or u r senior here enough not to obey newcomers rules ?
and if this is a game r u tough enough to take a beat from someone some 50 iq higher ?
he came with a protocol and and even some who dont use it , live some adverse effects .. this is more than placebo i think
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
questions for Sushi--

SIMPLIFIED TREATMENT APPROACH FOR LIFTING THE METHYLATION CYCLE BLOCK IN CHRONIC FATIGUE SYNDROME (Revised)

(Extracted from the full treatment program developed by Amy Yasko, Ph.D., N.D. which is used primarily in treating autism [1])

SUPPLEMENTS
1. FolaPro [2]: tablet (200mcg) daily
2. Actifolate [3]: tablet daily
3. General Vitamin Neurological Health Formula [4]: start with tablet and work up dosage as tolerated to 2 tablets daily
4. Phosphatidyl Serine Complex [5]: 1 softgel capsule daily
5. Activated B12 Guard [6]: 1 sublingual lozenge daily


Hi Sushi--
I know you have benefitted from the above, and I have some questions for you about it.

I'm wondering why there are 2 different folates in this protocol? Do you know, and have you experienced it to be easier, (in terms of less detoxing) to start with one or the other?

And is it easier to take the B12 for a while BEFORE starting the folates, or after? Or did you feel it was best to take them all together?

Also, that General Vitamin Neurological Health Formula--WOW! that has a LOT of stuff in it! Some of which I already take, and some that I don't really want to take. Is it essential to this protocol, or can it be replaced with a self-created nutrient combo alternative?

I have already spent SO much money on supplements... I want to get only what I really need.
Let me know what you think.

It sure is fun to play the COLOR GAME. :):):):)
 

jenbooks

Guest
Messages
1,270
Colors

The designer on cort's site is so talented!

Anyway I'm sure Sushi will answer and maybe Rich but my own personal understanding is they are two different active forms. Folinic acid, and 5-methyltetrahydrafolate. I personally from my genetics think I needt he latter more than the former but sort of like the b12's you'd supply both to your body. I think that's the general idea.

RE: Yasko's multi I don't like multi's. They assume one fits all and you might react adversely to a percentage and not know which. It generally covers the bases but I was just going to do hydroxy and folates (active). Because those are the essence.

I do know this is very strong. You could start with a sprinkle. Like 1/256th. Starting low is safest--you can always titrate UP but you can't always easily get over a bad over-reaction as we well know!

I'm sorry that the supplements have NOXIOUS fillers!!! That is an issue across the industry tho.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Fredd

I believe that some people are too sick for their bodies to cope with a start up - i believe that I am one of them. I am not denying anything you have said - you may well be right and the fact that some have healed following this procedure would certainly indicate this.

My issue with you is that you are denying that some being too sick could be true and not warning people about the severity of the effects of trying the procedure if indeed they are too sick at that time to cope with it. It is interesting that two others ie dreambirdie and klutzo who are both at a similar level to me have stopped the treatment through listening to what their bodies were telling them and not listening to you say that everything was fine when it obviously was not.

I think that an endo system can be too knackered to cope and what is needed first is some basic healing so that the body can be brought up to the point where perhaps your protocol can be tried out again. I am certainly willing to try it again one day.

I get the impression that perhaps you are thinking that we have 'chickened out' and would not see it through to the end. Again it is rather arrogant of you to assume you know our bodies better than we do or that we are really to soft to cope with a bit of discomfort. I am sure that I can speak for the other two in saying that we have already been through hell and would go back there is we thought we could be healed this time.

I would really love to see you listening to somebody and being a bit more responsible in giving a warning.

Brenda

Hi Brenda,

I am by no means trying to avoid warning people of the intensity of symptoms. It isn't my intention to avoid warning people. If you were to go back and look at previous posts I use terms like "emotionally volitile", "knock your socks off", "severe", "floored", "52 pickup", "intensification", "paranoia", "depression", "severely painful", "extreme continous nausea", "too weak and dizzy to walk" and many others over and over again. If you would like to contribute addtional descriptive terms I would be glad to include them. I have expressed the intensification of neuro-psychiatric symptoms as "Mr Hyde" coming out, and Mr Hyde was a homicidal maniac, not a pleasant mild happy character.

I very specifically specify potassium because a quite a few people undergo induced hypokalemia at startup and that can range from unpleasant to deadly. I also warn of the possible problems of CoQ10 during the startup period until healing has progressed enough, and how far that is is unknown, because it can trigger a dramatic increase in blood pressure which again can be dangerous for all sorts of reasons. It has happened often enough in some people to be a repeatable and predictable occurance. From time to time I also warn of occult tetanus (Clostridium tetani) as methylb12 protects against the obvious neurotoxic effects of tetanus without stopping the infection and can delay diagnosis considerably because it is usually diagnosed based on the characteristic neurotoxic effect. Those are all included in the BASICS postings which I hope people read. It also protects against the neurotoxic effects of a related clostridium bacteria, botulism (Clostridium botulinum). That's only a problem usually if somebody is receiving Botox theraputically and the mb12 reverses it.

In fact, if you would like to make up a listing of all the startup symptoms you and others experienced, which ones are dangerous rather than unpleasant or miserable, and why they are dangerous, I would incorporate them into a much larger compsite list contributed to by all interested. In the marking of dangerous, if it isn't something like BP that is known dangerous, please include links to articles and/or specify that it is based on a theoretical or hypothetical concern.

As this entire b12 and/or methylation treatment of all varieties, active, inactive or whatever, is still in the theoretical or hypothetical basis stage with various degrees of demonstration which is not proof, and we are all still trying to figure it out, in giving guidence we need make it as clear and easy for people as we can. In my last posting I attemped to break up large text areas with headings and color coding to make it easier to read and understand.
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
Hi Dreambirdie,

Yes, color makes forums and life fun!:)

I think the easiest way to answer some of these questions is to quote from previous posts Rich has done on other forums. He has always OK'ed us sharing information this way in the past.

And yes, Rich's Simplified Protocol has helped me a lot. I know it has corrected some basic things--like my diurnal cortisol curve was normal for the first time after being on the protocol for about 9 months. Generally I don't crash much now--the main problem is getting into heavy-duty detox reactions as I have been sick for decades and have accumulated a big mess of toxins. I am now sweating though (what a weird and wonderful thing to rejoice at being able to sweat!:p) and use FIR saunas and epsom salts baths to help move on out all the gems that my newly active detox system has started to deal with.

OK, actifolate: Rich used to recommend something by metagenics called Intrinsi/B12/folate because he feels that it is important to get the right amount of folinic acid. Metagenics changed this product, so now he recommends actifolate for the same reason. To quote Rich:

"I've learned that Metagenics has recently changed the formulation of its product Intrinsi/B12/folate without changing the name of the product. It no longer contains folinic acid (5-formyl tetrahydrofolate). Metagenics also supplies Actifolate, which does continue to contain folinic acid, as well as folic and 5-methyl tetrahydrofolate. So I'm suggesting that in the future, people doing the simplified treatment approach should substitute Actifolate for Intrinsi/B12/folate, using the same dosage, i.e. one-quarter of a tablet. FolaPro should continue to be used also, as in the past."

Both these forms of folate are necessary to restore methylation.

And the order to start taking the supplements--Rich wrote this in June 09, so it should still be current:

"I generally suggest starting with the multi and the phos. serine complex, because they support the basic metabolism and help to correct any deficiencies that might be present in the essential nutrients.

"Then I generally suggest that people start a few days later with the folate-containing supplements, at the suggested dosages, and then add the hydroxocobalamin a few days later. If the detox symptoms become intolerable, it's O.K. to stop all the supplements to calm them down, and then proceed. People seem to need different dosages, and have to experiment a little to see what works for them. I do not recommend going higher than the recommended dosages for the folate-containing supplements, at least until a person has been on the treatment for a while, because some people have experienced detox symptoms that have momentum, and do not stop right away when they stop the supplements, if the dosage has been high.

"As always, I want to state my position that it's necessary for a person to be monitored by a physician while on this treatment, even though it consists only of food supplements, because it can have profound effects, especially in people who have some other conditions along with CFS, and a few people have had some serious adverse effects, as I have written."


Most people find it is best to start with a tiny, tiny doses (a sprinkle or a crumb) of the folates, the B12, and the multi. I think it is best to start the supplements in the order he suggests and take each one for a few days to make sure you are not reacting to it--sometimes the reactions appear only after a few days. When you feel stable with all the supps, you can start raising the doses, one by one and monitoring your response. I think it took me about 3 months to get up to the recommended doses.

As far as costs and the multi, Rich recommends this multi because it has several key ingredients that support methylation that will not be found in other multis. Also, you do not want to take a multi that has any folic acid or B12 as it is likely to be a different form and can "grab" the receptors for that nutrient and prevent the bioactive ones in the protocol from getting a chance at the receptors.

The costs are really minimal as you cut up the pills and take tiny doses. I think the first 3 months of supplements cost me about $100. And the only one that you need to get from Holistic Heal is the multi--there are less expensive sources on the internet for the others.

After being on these supps for nearly 2 years
, I have found that I need to reduce the doses from the recommended ones--presumably because methylation is working better now and I don't need as much. (Rich confirmed this as likely--at least in my case) So I spend very little still on these supplements.

Because you don't get enough of the basic nutrients from the multi, most of us supplement other vitamins separately--like some of the B's, D3, etc.

Hope this helps! Everyone responds differently to these supps, so if you try it, just go very slowly and watch your body.

Best wishes,
Sushi