B-12 - The Hidden Story

[maddietod]

Is there an amount of vegetables that's typically OK to eat, if pre-loading with metafolin, per meal or per day?

I'm just wondering if there's a safe place to start, or if I should completely avoid fruits/vegetables for a period of time while I figure this out.

[I went off all folic/folinic acid a week ago. Within 24 hours my tight muscles relaxed and my brain-fog cleared. My sleep immediately became deranged; I wake up about every hour. I am taking 2 B-Complex a day, breakfast and lunch.]

Madie

 

[Freddd]

Is there an amount of vegetables that's typically OK to eat, if pre-loading with metafolin, per meal or per day?

I'm just wondering if there's a safe place to start, or if I should completely avoid fruits/vegetables for a period of time while I figure this out.

[I went off all folic/folinic acid a week ago. Within 24 hours my tight muscles relaxed and my brain-fog cleared. My sleep immediately became deranged; I wake up about every hour. I am taking 2 B-Complex a day, breakfast and lunch.]

Madie

Hi Madie,

As to vegetable consumption, I am experimenting. I know of no way to elliminate them and have any kind of a healthful and pleasurable diet. Total quantity makes a difference. Possibly even frequency during the day makes adifference. preloading with Metafolin makes a difference. As I have some symptoms that come and go in days, I can experiment and back off before things get severe.

The b-complex might be better off breakfast and dinner, more like 10-12 hours apart. The slepp wil normalize after a bit. Good luck in your experiments and keep us posted witg what works, now that you have some rapidly repsponding symptoms that can alert you.

 

[Valentijn]

Selenium and melatonin, given together, give me an autoimmune reaction similar to ms (limb weakness, poor coordination).

Another possibility is an aggravation of orthostatic intolerance, which can be caused by melatonin.

 

[richvank]

Hi, Freddd.

I think we agree that the way your protocol works is that methyl B12 and adenosyl B12 are able to diffuse through cell membranes in sufficient quantity to supply these active coenzyme forms of B12 directly to the cells without needing the normal intracellular processing, provided the levels of these B12 forms in the blood are raised high enough by injection or sublingual application of these forms.

As I understand it, there are also people (including yourself) who may have difficulty getting enough of these forms of B12 into their brain. As you have noted, the study that Bo Regland et al. carried out in Sweden some years ago indicated that this may be an issue in many people who have ME/CFS.

In view of these things, it has occurred to me that using a liposomal form of these active coenzyme forms of B12 may be a more effective way to get them into both the cells of the body in general as well as getting them into the brain. Perhaps lower dosages could be used, and less would be dumped in the urine. There are several published papers indicating that liposomes will cross the blood-brain barrier. I found one published paper from Korea in which adenosyl B12 had been prepared in liposomal form for transdermal use in a skin problem. See below. I didn't find any papers mentioning liposomal methyl B12. It may be more difficult to make, given the greater chemical instability of this form of B12, but probably could still be done. There are commercial outfits that will prepare liposomal forms of just about any substance, I think, and there are now amateur methods on the internet using ultrasonic cleaners. I think it would be very important to make sure that very pure substances were used, and that careful attention be paid to dosages, if this approach is used, because it would bypass the usual protective barriers of the gut and the cell membranes. It would be important not to be creating "Trojan horses" with this method.

What do you think about this?

Best regards,

Rich


Pharmazie. 2011 Jun;66(6):430-5.
Topical application of liposomal cobalamin hydrogel for atopic dermatitis therapy.
Jung SH, Cho YS, Jun SS, Koo JS, Cheon HG, Shin BC.
Source

Korea Research Institute of Chemical Technology, Daejeon, Korea.
Abstract

Topical vitamin B12 was shown to be effective for atopic dermatitis. However, vitamin B12 itself is light sensitive and has low skin permeability, thus reducing its therapeutic effectiveness. In the present study, we prepared a liposomal hydrogel of adenosylcobalamin (AdCbl), a vitamin B12 derivative, and investigated possible beneficial effects of AdCbl on atopic dermatitis using an NC/Nga murine atopic dermatitis model. AdCbl was loaded into liposomes prepared by a thin film hydration method using a pH gradient method that employed citric acid buffer solution. This resulted in AdCbl-loaded liposomes that were 106.4 +/- 2.2 nm in size. The loading efficiency was 40% (of the initial AdCbl amount). Lipo-AdCbl had enhanced skin permeability, being about 17-fold compared with AdCbl-gel. Topical administration of Lipo-AdCbl-gel to 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like skin lesions in NC/Nga mice ameliorated lesion intensity scores, dorsal skin thickness, and total serum IgE in a concentration-dependent manner. Other preparations, including AdCbl solution, AdCbl cream, liposomes alone, and a mixture of AdCbl solution and liposomes had little effect. Taken together, our findings indicate that Lipo-AdCbl-gel has protective effects against atopic dermatitis symptoms, and suggest that it may be of benefit in the treatment of human inflammatory skin diseases.

PMID:
21699082

 

[Freddd]

Hi, Freddd.

I think we agree that the way your protocol works is that methyl B12 and adenosyl B12 are able to diffuse through cell membranes in sufficient quantity to supply these active coenzyme forms of B12 directly to the cells without needing the normal intracellular processing, provided the levels of these B12 forms in the blood are raised high enough by injection or sublingual application of these forms.

As I understand it, there are also people (including yourself) who may have difficulty getting enough of these forms of B12 into their brain. As you have noted, the study that Bo Regland et al. carried out in Sweden some years ago indicated that this may be an issue in many people who have ME/CFS.

In view of these things, it has occurred to me that using a liposomal form of these active coenzyme forms of B12 may be a more effective way to get them into both the cells of the body in general as well as getting them into the brain. Perhaps lower dosages could be used, and less would be dumped in the urine. There are several published papers indicating that liposomes will cross the blood-brain barrier. I found one published paper from Korea in which adenosyl B12 had been prepared in liposomal form for transdermal use in a skin problem. See below. I didn't find any papers mentioning liposomal methyl B12. It may be more difficult to make, given the greater chemical instability of this form of B12, but probably could still be done. There are commercial outfits that will prepare liposomal forms of just about any substance, I think, and there are now amateur methods on the internet using ultrasonic cleaners. I think it would be very important to make sure that very pure substances were used, and that careful attention be paid to dosages, if this approach is used, because it would bypass the usual protective barriers of the gut and the cell membranes. It would be important not to be creating "Trojan horses" with this method.

What do you think about this?

Best regards,

Rich


Pharmazie. 2011 Jun;66(6):430-5.
Topical application of liposomal cobalamin hydrogel for atopic dermatitis therapy.
Jung SH, Cho YS, Jun SS, Koo JS, Cheon HG, Shin BC.
Source

Korea Research Institute of Chemical Technology, Daejeon, Korea.
Abstract

Topical vitamin B12 was shown to be effective for atopic dermatitis. However, vitamin B12 itself is light sensitive and has low skin permeability, thus reducing its therapeutic effectiveness. In the present study, we prepared a liposomal hydrogel of adenosylcobalamin (AdCbl), a vitamin B12 derivative, and investigated possible beneficial effects of AdCbl on atopic dermatitis using an NC/Nga murine atopic dermatitis model. AdCbl was loaded into liposomes prepared by a thin film hydration method using a pH gradient method that employed citric acid buffer solution. This resulted in AdCbl-loaded liposomes that were 106.4 +/- 2.2 nm in size. The loading efficiency was 40% (of the initial AdCbl amount). Lipo-AdCbl had enhanced skin permeability, being about 17-fold compared with AdCbl-gel. Topical administration of Lipo-AdCbl-gel to 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like skin lesions in NC/Nga mice ameliorated lesion intensity scores, dorsal skin thickness, and total serum IgE in a concentration-dependent manner. Other preparations, including AdCbl solution, AdCbl cream, liposomes alone, and a mixture of AdCbl solution and liposomes had little effect. Taken together, our findings indicate that Lipo-AdCbl-gel has protective effects against atopic dermatitis symptoms, and suggest that it may be of benefit in the treatment of human inflammatory skin diseases.

PMID:
21699082

Hi Rich,

Yes, bypassing all the assumptions about transport and conversion and going straight into cells with diffusion is a very important aspect for some. Based on my own private trials and another person's private trials with adb12, I would be inclined to say it is far more fragile than mb12. A solution of adb12, mixed under safelight conditions and darkness, stored in the fridge in foil wrapped vial, started changing noticably in 5-6 days and worthless in 10 days leading to the same acne. Mb12 is stable for months under those conditions. I haven't had any mb12 breakdown when protected from light and kept cool. I put one vial aside and left it in those conditions for 6 months. No problem.

My BIG question about is whether the topical works as well as the kind of doses we have been using sublingually and injection. For skin lesions and problems the big payoff appears to happen with 3mg absorbed dose of mb12 with metafolin and omega3 oils and cofactors. I guess I mean, standardize the cofactors and test diffusion from inside vs diffusion of liposomal from exterior.

Topical mb12 application for psoriosis as been tried for some years with mixed effects but NEVER with the cofactors that might have aided success and never compared to even modest daily injection of mb12 or equiv sublingual. So much of what is done is based on incorrect assumptions based on cyancbl, hydrocbl and folic acid.

I will mention that my skin had a multitude of problems all my life until the last few years. Now it is the best in my life.


The CNS is a different story since the difference in effect between heroin and morphine on the brain is very noticable and based on fat soluability of heroin in fats.


It would be very interesting to see. I would want to have the right 5 star qualified mb12 crystal to start with because anything else might not work for reasons of the invisible qualitative differences in mb12.

In countries where adb12 is packeged for sale for injection the crystal is in a vial into which saline is injected for mixing, containg 2 days worth, and the directions say to discard in 5 days.

 

[adreno]

In view of these things, it has occurred to me that using a liposomal form of these active coenzyme forms of B12 may be a more effective way to get them into both the cells of the body in general as well as getting them into the brain. Perhaps lower dosages could be used, and less would be dumped in the urine. There are several published papers indicating that liposomes will cross the blood-brain barrier. I found one published paper from Korea in which adenosyl B12 had been prepared in liposomal form for transdermal use in a skin problem. See below. I didn't find any papers mentioning liposomal methyl B12. It may be more difficult to make, given the greater chemical instability of this form of B12, but probably could still be done. There are commercial outfits that will prepare liposomal forms of just about any substance, I think, and there are now amateur methods on the internet using ultrasonic cleaners. I think it would be very important to make sure that very pure substances were used, and that careful attention be paid to dosages, if this approach is used, because it would bypass the usual protective barriers of the gut and the cell membranes. It would be important not to be creating "Trojan horses" with this method.

Like this?

http://www.readisorb.com/readisorb_methyl_b12_spray.html
http://www.amazon.com/Ecological-Formulas-Dibencozide-Health-Beauty/dp/B003TVD4BO

 

[Freddd]

Like this?

http://www.readisorb.com/readisorb_methyl_b12_spray.html
http://www.amazon.com/Ecological-Formulas-Dibencozide-Health-Beauty/dp/B003TVD4BO

Hi Adreno,

No, not like either of these two. Nobody has been able to duplicate the verifiable absorbtion of mb12 to about 7.5mg absorbed by any spray. It is easy to do with Jarrow mb12 and injections. Further to achieve the same thing with oral adb12 would require about 700mg taken orally to equal the 7.5mg validated absorbtion form the sublingual dibencozides. Further it has folic acid and is a disaster for many. Absorbing 10mcg from the 1mg of adb12 and 400mcg of folic acid is a disaster waiting to happen where the blocking of methylfolate by folic acid is dose related. It might take 100 sprays or more over 3 hours to attempt to document the absorbtion

 

[richvank]

Hi, Freddd and Adreno.

Freddd, sorry I wasn't clear, I didn't mean to suggest a transdermally applied liposome, though that's what the abstract is about. I meant one taken orally. The key thing is the liposomal containment, which allows the substance to go right through lipid membranes. The liposomes are thought to pass through the wall of the stomach, into the blood stream. From there, they can enter peripheral cells or go through the blood-brain barrier, delivering their cargo. This is not the same as an ordinary oral supplement.

Adreno, thanks, I wasn't aware that these products are available. I think they might work for some PWMEs. I realize that folic acid is a problem for Freddd and some others, and for them it would be better just to have the B12 forms in the liposomes, I think.

I still think this is a viable concept, worth trying. Incidentally, Readisorb is Dr. Tim Guilford's company. He's the pioneer of putting glutathione into liposomal form. I met him several years ago. He will be speaking at the OHM meeting in San Francisco in late February, and I plan to attend. Maybe I'll have a chance to talk to him about this stuff.

Best regards,

Rich

 

[adreno]

Hi Adreno,

No, not like either of these two. Nobody has been able to duplicate the verifiable absorbtion of mb12 to about 7.5mg absorbed by any spray. It is easy to do with Jarrow mb12 and injections. Further to achieve the same thing with oral adb12 would require about 700mg taken orally to equal the 7.5mg validated absorbtion form the sublingual dibencozides. Further it has folic acid and is a disaster for many. Absorbing 10mcg from the 1mg of adb12 and 400mcg of folic acid is a disaster waiting to happen where the blocking of methylfolate by folic acid is dose related. It might take 100 sprays or more over 3 hours to attempt to document the absorbtion

I know the adb12 has folic acid and that you don't like that, but that is not the point. I'm not saying these are optimal formulations.

Have you seen data for the absorption of B12 through liposomal encapsulation? If not, how did you arrive at the 100x dose required? The whole point of liposomal encapsulation is that it dramatically enhances absorption into cells, not just serum.

Could you point me to some research showing that sublingual absorption of B12 is better than oral, because I can't find any?

J Altern Complement Med. 2006 Nov;12(9):881-5.
A single-center, double-blinded, randomized controlled study to evaluate the relative efficacy of sublingual and oral vitamin B-complex administration in reducing total serum homocysteine levels.
Yazaki Y, Chow G, Mattie M.
Source

College of Naturopathic Medicine, University of Bridgeport, Bridgeport, CT, USA.
Abstract
OBJECTIVE:

Reports correlating total homocysteine (tHcy) concentrations with arteriosclerosis have become a matter of interest amongst healthcare professionals and the public. Several commercial preparations of vitamin B complexes have been marketed as supplements intended to reduce elevated levels of tHcy. Among these preparations are those that have been specifically designed for sublingual administration. This study is designed to evaluate the relative efficacy of sublingually versus orally delivered vitamin B complex in reducing serum tHcy levels.
DESIGN:

Forty-one (41) subjects, between the ages of 50 and 80 years with total serum tHcy concentrations exceeding 11 micromol/L, were treated with a six-week regimen of vitamin B complex. Each B complex consisted of 1000 microg vitamin B12 (as methylcobalamin), 400 microg folate (as folic acid), and 5 mg vitamin B6 (as pyridoxine HCl). Participants in the study were randomized into two groups designated, retrospectively, as SL and PO. Members of group SL were given a sublingually delivered vitamin B complex and a matching orally delivered placebo. Members of group PO were given an orally delivered vitamin complex and a matching sublingually delivered placebo. A statistically significant reduction in tHcy values was observed in both groups upon completion of the 6-week protocol.
RESULTS:

There was no statistically significant difference in serum tHcy concentrations between SL and PO groups either before or after treatment, substantiating the idea that there is no difference in efficacy between the two methods of vitamin complex delivery.

PMID:
17109579

Br J Clin Pharmacol. 2003 Dec;56(6):635-8.
Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route.
Sharabi A, Cohen E, Sulkes J, Garty M.
Source

Recanati Center for Medicine and Research and Clinical Pharmacology Unit, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
AIMS:

To compare the efficacy of sublingual and oral administration of 500 micro g of cobalamin in subjects with cobalamin deficiency.
MATERIALS AND RESULTS:

Thirty subjects with low serum concentrations of cobalamin participated in the study. Subjects were randomly allocated to receive one tablet daily of 500 micro g cobalamin sublingually or orally, or two tablets daily of a vitamin B complex. Serum cobalamin concentrations before treatment were 94 +/- 30 pmol l-1, 108 +/- 17 pmol l-1 and 98 +/- 14 pmol l-1 in the sublingual B12, oral B12 and oral B-complex groups, respectively. After 4 weeks, concentrations rose to 288 +/- 74 pmol l-1, 286 +/- 87 pmol l-1 and 293 +/- 78 pmol l-1, respectively. The increase in each group across time was statistically significant (P = 0.0001, differences [95% confidence intervals] 194.2 (114.5, 273.9), 178.3 (104.2, 252.4), and 195.1 (135.0, 255.2) pmol l-1, respectively). There was no significant difference in concentrations between the treatment groups.
CONCLUSION:

A dose of 500 micro g of cobalamin given either sublingually or orally is effective in correcting cobalamin deficiency.

PMID:
14616423

 

[Freddd]

I know the adb12 has folic acid and that you don't like that, but that is not the point. I'm not saying these are optimal formulations.

Have you seen data for the absorption of B12 through liposomal encapsulation? If not, how did you arrive at the 100x dose required? The whole point of liposomal encapsulation is that it dramatically enhances absorption into cells, not just serum.

Could you point me to some research showing that sublingual absorption of B12 is better than oral, because I can't find any?

Hi Adreno,

Have you seen data for the absorption of B12 through liposomal encapsulation? If not, how did you arrive at the 100x dose required? The whole point of liposomal encapsulation is that it dramatically enhances absorption into cells, not just serum.

When one swallows a pill or eats b12 in food or vitamins, stomach acid separates it from fats and proteins, then it is absorbed via HTC1 and intrinsic factor. The rate of absorbtion in that mode is 2-3 mcg per incidence AT NEAR 100%, and then percentage falls off fast. Oral cobalamins in excess of 100mcg input or so is passively absorbed at 1% according to lots of studies that have looked at it from many directions. There is no evidence at all that any liposomal encapsulation survivrs the digestive proecess. If it does, then run a series of absorbtion tests and tell me how much you have to take oraly in order to see it in your urine comparable to a 7.5mg injection. That's enough to leave no doubt of what you are seeing.


Could you point me to some research showing that sublingual absorption of B12 is better than oral, because I can't find any?

Oral has a known absorbtion rate maxing out at about 1%. You can demonstrate the difference yourself. Take 10 Jarrow 5mg tablests and swallow them. Observe you urine. The the next day take the same 10 x 5mg tablets and take them sublingually, 4 to start with, 3 more at 30 minutes and 3 more at anotyher 30 minutes and keep as much as possible there at least past the end of the third hour, or even 4th. Then observe your urine. Collect the 5 hour (or more) urine output to make sure you get most of the visible b12. If you want to take it one step further do the same with a 7.5mg sc injection.

I did hundreds of such tests with various brands but mostly Jarrow b12 once I settled on it, with doses from 5mg to 100mg sublingually. I also did the same series with injections from 1mg to 100mg and compared. The 1-25mg was one series of injections and 25mg to 100mg another series.


I don't know of any peer reviewed studies doing this however you can easily duplicate it for yourself. This is science fair level difficulty, very easy. You KNOW it has been absorbed because there is no other way for it to get into the urine, whether from oral tissues, intestinal tissues or injection.

adb12 has folic acid and that you don't like that, but that is not the point

Actually it is part of the point. It isn't a usuable product for some unknow percentage of persons. With the folic acid if the folic acid, to the degree that it blocks metafolin, the amount excreted by the kidneys goes up very much, 2x or more. The same with glutathione. It increases the urine excretion several fold over metafolin without glutathione. ANd this has nothing to do with the blocking of methylfolate but a simple chemical reaction of making glutathionylcobalamin out of mb12 and adb12 and immediately excreting it, also a test you can easily duplicate.

 

[adreno]

When one swallows a pill or eats b12 in food or vitamins, stomach acid separates it from fats and proteins, then it is absorbed via HTC1 and intrinsic factor. The rate of absorbtion in that mode is 2-3 mcg per incidence AT NEAR 100%, and then percentage falls off fast. Oral cobalamins in excess of 100mcg input or so is passively absorbed at 1% according to lots of studies that have looked at it from many directions. There is no evidence at all that any liposomal encapsulation survivrs the digestive proecess. If it does, then run a series of absorbtion tests and tell me how much you have to take oraly in order to see it in your urine comparable to a 7.5mg injection. That's enough to leave no doubt of what you are seeing.

There is evidence from peer-reviewed studies of enhanced absorption through liposomal encapsulation. Here is one example showing a 29-fold increase in absorption of a liposomal encapsulated formula of curcumin:


J Nat Prod. 2011 Apr 25;74(4):664-9. Epub 2011 Mar 17.
Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation.
Cuomo J, Appendino G, Dern AS, Schneider E, McKinnon TP, Brown MJ, Togni S, Dixon BM.
Source

USANA Health Sciences, Inc., 3838 West Parkway Boulevard, Salt Lake City, Utah 84120, USA. john.cuomo@us.usana.com
Abstract

The relative absorption of a standardized curcuminoid mixture and its corresponding lecithin formulation (Meriva) was investigated in a randomized, double-blind, crossover human study. Clinically validated dosages were used for both products, and plasma levels of all three major curcuminoids [curcumin (1a), demethoxycurcumin (1b), and bisdemethoxycurcumin (1c)] were evaluated. Total curcuminoid absorption was about 29-fold higher for Meriva than for its corresponding unformulated curcuminoid mixture, but only phase-2 metabolites could be detected, and plasma concentrations were still significantly lower than those required for the inhibition of most anti-inflammatory targets of curcumin. Remarkably, phospholipid formulation increased the absorption of demethoxylated curcuminoids much more than that of curcumin (1a), with significant differences in plasma curcuminoid profile between Meriva and its corresponding unformulated curcuminoid mixture. Thus, the major plasma curcuminoid after administration of Meriva was not curcumin (1a), but demethoxycurcumin (1b), a more potent analogue in many in vitro anti-inflammatory assays. The improved absorption, and possibly also a better plasma curcuminoid profile, might underlie the clinical efficacy of Meriva at doses significantly lower than unformulated curcuminoid mixtures.

PMID:
21413691

Oral has a known absorbtion rate maxing out at about 1%. You can demonstrate the difference yourself. Take 10 Jarrow 5mg tablests and swallow them. Observe you urine. The the next day take the same 10 x 5mg tablets and take them sublingually, 4 to start with, 3 more at 30 minutes and 3 more at anotyher 30 minutes and keep as much as possible there at least past the end of the third hour, or even 4th. Then observe your urine. Collect the 5 hour (or more) urine output to make sure you get most of the visible b12. If you want to take it one step further do the same with a 7.5mg sc injection.

I did hundreds of such tests with various brands but mostly Jarrow b12 once I settled on it, with doses from 5mg to 100mg sublingually. I also did the same series with injections from 1mg to 100mg and compared. The 1-25mg was one series of injections and 25mg to 100mg another series.


I don't know of any peer reviewed studies doing this however you can easily duplicate it for yourself. This is science fair level difficulty, very easy. You KNOW it has been absorbed because there is no other way for it to get into the urine, whether from oral tissues, intestinal tissues or injection.

Sorry, I'm not a biologist, but I do believe that the peer-reviewed studies trumps your personal experiences.

Actually it is part of the point. It isn't a usuable product for some unknow percentage of persons. With the folic acid if the folic acid, to the degree that it blocks metafolin, the amount excreted by the kidneys goes up very much, 2x or more. The same with glutathione. It increases the urine excretion several fold over metafolin without glutathione. ANd this has nothing to do with the blocking of methylfolate but a simple chemical reaction of making glutathionylcobalamin out of mb12 and adb12 and immediately excreting it, also a test you can easily duplicate.

I understand that. I guess I wasn't clear; my point was simply to give examples of liposomal encapsulated products already available, not to endorse them in any way.

 

[Freddd]

There is evidence from peer-reviewed studies of enhanced absorption through liposomal encapsulation. Here is one example showing a 29-fold increase in absorption of a liposomal encapsulated formula of curcumin:


J Nat Prod. 2011 Apr 25;74(4):664-9. Epub 2011 Mar 17.
Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation.
Cuomo J, Appendino G, Dern AS, Schneider E, McKinnon TP, Brown MJ, Togni S, Dixon BM.
Source

USANA Health Sciences, Inc., 3838 West Parkway Boulevard, Salt Lake City, Utah 84120, USA. john.cuomo@us.usana.com
Abstract

The relative absorption of a standardized curcuminoid mixture and its corresponding lecithin formulation (Meriva) was investigated in a randomized, double-blind, crossover human study. Clinically validated dosages were used for both products, and plasma levels of all three major curcuminoids [curcumin (1a), demethoxycurcumin (1b), and bisdemethoxycurcumin (1c)] were evaluated. Total curcuminoid absorption was about 29-fold higher for Meriva than for its corresponding unformulated curcuminoid mixture, but only phase-2 metabolites could be detected, and plasma concentrations were still significantly lower than those required for the inhibition of most anti-inflammatory targets of curcumin. Remarkably, phospholipid formulation increased the absorption of demethoxylated curcuminoids much more than that of curcumin (1a), with significant differences in plasma curcuminoid profile between Meriva and its corresponding unformulated curcuminoid mixture. Thus, the major plasma curcuminoid after administration of Meriva was not curcumin (1a), but demethoxycurcumin (1b), a more potent analogue in many in vitro anti-inflammatory assays. The improved absorption, and possibly also a better plasma curcuminoid profile, might underlie the clinical efficacy of Meriva at doses significantly lower than unformulated curcuminoid mixtures.

PMID:
21413691



Sorry, I'm not a biologist, but I do believe that the peer-reviewed studies trumps your personal experiences.



I understand that. I guess I wasn't clear; my point was simply to give examples of liposomal encapsulated products already available, not to endorse them in any way.

Hi Adreno,

Your quoting of the liposomal encapsulated curcuminoid mixture is interesting but may not have any bearing whatsoever on how it may affect adb12 and mb12. it also doesn't say, at least in what you included whether it went through digestion or was a skin absorbtion study.

Sorry, I'm not a biologist, but I do believe that the peer-reviewed studies trumps your personal experiences.

You are very mistaken. They are talking about pomegranates and I'm speaking of chateaubriand. They are toally different, not even apples to oranges (both fruit). If there were a peer reviewed study that did the study correctly, which is rare unfortunately, I could either agree with them or critque them or see what was different for different results. Don't you trust yourself to be able to so something so simple that a junior high school sicence fair might host such a study? I've spent lots of time reading peer reviewed studies and a lot of them are so badly witten up that the writeuyp wouldn't passs high school chemisty. Further a lot of qquestions asked are trying to get narrow answers that support the marketing, NOT the actual efectivness. There are not any studies I have seen on b12 for instance, that study the diffusion of mb12 and adb12 into the tissues directly healing things that don't heal based on any previous studies of inactive cobalamins. The Japanese studies with 50mg doses of methylb12 on neurological spinal cord and brain diseases are the ones I'm working off of. The established the effectiveness of mb12 at doses large enough to enter the CSF by diffusion. In another study with diabetic neuropathy with intrathecal injections of 2.5mg of mb12 established that the CSF effective serum levels varies from less than 3 months to more than 4 years. Then there are the studies that have measured the cobalamin levels in the cerebral spinal fluid of people with CFS, FMS, Parkinson's, ALS, Alzheimer's, Autism, SupraNuclearPalsy and fould that all those are low regardless of blood serum level regarding the difficulty in those with neurological diseases ahving enough b12 in theie=r CSF. Then there are the othger studies that build on the low CSF cobalamin and pinpointed with elevated MMA and/or Hcy. Then there are the studies of some of those diseases and that giving folks cyancbl/hycbl, folic acid and b6 did not affect the CSF HCY level and did not alter disease progression where as 2.5mg intrathecal mb12 injections do affect disease progression. However, nobody has done this kind of sublingual vs injection and a study on reducing homocycteine hasd no relevance at all. It's one of about 100 smilar studies with minor variations demonstrating that whatever they did do did mange to recduce homocysteine for some percentage of people and neither method done was terribly inferior or superior to the other. The outcome was a forgone conclusion based on hundreds of other similar studies with minor variations that have been done over the past 50+ years. Why don't you come up with some actually relevant peer reviewed studies. I would be interested in reading them.

I was a professional photographer and can cerrtainly do colorimetry to compare the color of urine using subtractive color printing filters. One can approximate very well with a naked eye within a few percent of meter. The only way for mb12 or any cobalamin into urine is the blood through the kidneys.

I'm trying to figure out how to make preventing and healing of all these diseases routine, not defending the kind of research that got us into this place intially. The same as Rich. He would look for perhaps somewhat different genetics, but you know, thye exact same genes may be causing any number of the various changes we are looking for. If everybody's genes were eactly one way and all in full agreement with how sicience to this point has defined, then none of us would be sick. If doctors knew how to treat us effectively we wouldn't be sick. So, the best that can said is that they are not trying to make us sick on purpose or withholding known effective treatments. My docs were all puzzled, it's only some who had to call me names and punish me for having "an imaginary woman's disease". The honest ones just said I would be better served finding somebody who understood it. How right they were.

In the thousands of papers I have read I have to admit that when they very deep in chemistry it goes way beyond anything I know. I do much better at picking out docs who commit fraud and docs with lots of poor outcomes, or good outcomes for that matter. But I do know slanted questions and answers when I see them on the subject of b12, time relase opioids and some other such things, scrambled data, graphs that don't match data tables and things like that. It's interesting that the same information theory that picks out fraudulent docs also picks out faulty research, none of it perfectly.

I've helped write and present papers at group medical insurance conferences. Of course they were more likely to be things like "Effects of reimbursement methods on outcomes." Or "Methods of selecting preferred physicians for 2nd opinion referrals". If I were offerring the advice I give on these things to a group health plan for data mining purposes to select people for nutritional interventions I would guarantee, with my payment level at risk, the minimum level of results with 100,000 people by secondary measures such as reduced pharamacy costs and reduced provider visists and so on thereby reducing costs and increasing patient satisfaction.

Now I am perfectly willing to give you exact written directions by which you, or anybody, can replicate my results on absorbtion, within reasonable statistical limits. That is precisely what the quoted studies you provided were doing. That is how the system works. The big difference is that since I don't have lots of expensive lab toys, I have to to things that can be seen with the naked eye, like outright healing and red tinted urine. Also, to save my life and that of my children and grandchildren I need faster results then 1 small step each 5 years. By healing myself I have demonstrated I know of what I speak. The question is opnly how these things apply to others and what the differences and percentages are, So here we are 50 years, maybe 100 years ahead of these kind of studies. So far nobody outside of Japan appears to be interested in how high dose methylb12 works and the diffusion associated with it. Of course Japan has an Alzheimer's rate 20% of ours. Their cobalamin low level alert is 550pg/ml instead of 160pg/ml as in USA and UK, and they are the only country of which I'm aware using methylb12 as their official form of b12 and doing research of it's effect on neurological diseases with low CSF cobalamin.

We are right here right now attempting to make it simpler to identify "paradoxical folate deficiency" and other "induced folate deficiency" and "induced potassium deficiency" for that matter. NONE of those things are defined or recognized except "paradoxical folate deficiency" was named in a case study of a horse. They affect the health of some unknown percentage of the people here somewhere between >20% and <100% in the aggragate of the several things. Have fun and be in good health.

 

[Freddd]

Hi, Freddd and Adreno.

Freddd, sorry I wasn't clear, I didn't mean to suggest a transdermally applied liposome, though that's what the abstract is about. I meant one taken orally. The key thing is the liposomal containment, which allows the substance to go right through lipid membranes. The liposomes are thought to pass through the wall of the stomach, into the blood stream. From there, they can enter peripheral cells or go through the blood-brain barrier, delivering their cargo. This is not the same as an ordinary oral supplement.

Adreno, thanks, I wasn't aware that these products are available. I think they might work for some PWMEs. I realize that folic acid is a problem for Freddd and some others, and for them it would be better just to have the B12 forms in the liposomes, I think.

I still think this is a viable concept, worth trying. Incidentally, Readisorb is Dr. Tim Guilford's company. He's the pioneer of putting glutathione into liposomal form. I met him several years ago. He will be speaking at the OHM meeting in San Francisco in late February, and I plan to attend. Maybe I'll have a chance to talk to him about this stuff.

Best regards,

Rich

HI Rich,

I missed your reply before I replied to some other things. So, we are then in position whereby it is feasable for those so inclined to test the absorbtion rate for this adb12 product. A person could take 10 and see if it produces the urine coloration equal to 51mg sublingually of the closest apples to apples test, Country life Dibencozide also with folic acid. Adreno, do I see your hand going up to volunteer to test the absorbtion rate of the two products to see what it takes with the lioposomal encapsulated adb12 vs an established and verified sublingual? It should preferably be somebody not troubled by folic acid or at least not known to be troubled by it.

According to what I have seen on absorbability of folic acid, it is absorbed at 70% or so normally, so there is little room for improvement there.

 

[maddietod]

Hmm, can't be me, because it looks like I have folic acid issues.

But I'm curious and confused about this visual urine test. What's the baseline? How do you calibrate gradations of color? I take my B-Complex and I pee yellow - that's all I can compare this to. [I know you're not talking about a multi-B, here.]

Madie

 

[richvank]

HI Rich,

I missed your reply before I replied to some other things. So, we are then in position whereby it is feasable for those so inclined to test the absorbtion rate for this adb12 product. A person could take 10 and see if it produces the urine coloration equal to 51mg sublingually of the closest apples to apples test, Country life Dibencozide also with folic acid. Adreno, do I see your hand going up to volunteer to test the absorbtion rate of the two products to see what it takes with the lioposomal encapsulated adb12 vs an established and verified sublingual? It should preferably be somebody not troubled by folic acid or at least not known to be troubled by it.

According to what I have seen on absorbability of folic acid, it is absorbed at 70% or so normally, so there is little room for improvement there.

Hi, Freddd.

I don't think a urine colorimetric comparison would be valid in comparing the absorption of a liposomal form to a "bare" adenosyl B12. That type of comparison would be valid for comparing two ways of putting "bare" adenosyl B12 into the bloodstream, as you have done with sublingual and injectable. But liposomal B12 will likely readily go on into the cells, so there won't be a lot of excess dumped into the urine. I think there would have to be another way of comparing how much actually gets into the cells, such as a urine methylmalonate test,

Best regards,

Rich

 

[Freddd]

Hi, Freddd.

I don't think a urine colorimetric comparison would be valid in comparing the absorption of a liposomal form to a "bare" adenosyl B12. That type of comparison would be valid for comparing two ways of putting "bare" adenosyl B12 into the bloodstream, as you have done with sublingual and injectable. But liposomal B12 will likely readily go on into the cells, so there won't be a lot of excess dumped into the urine. I think there would have to be another way of comparing how much actually gets into the cells, such as a urine methylmalonate test,

Best regards,

Rich

Hi Rich,

I think then that this is a MUST try to either demonstrate that it is excreted at the normal rate or not.

But liposomal B12 will likely readily go on into the cells, so there won't be a lot of excess dumped into the urine. I think there would have to be another way of comparing how much actually gets into the cells, such as a urine methylmalonate test,

I don't think that there will be that kind of difference. First of all adb12 in a 3mg sublingual dose, say 750mcg or so getting into serum, starts affecting the mitochondria in 5 minutes and it takes only 2 or 3 such doses to saturate the mitochondria to the end of any noticable difference. It's difficult to happen faster. The CNS is the much tougher play. A single dose of sublingual mb12 or adb12 will elliminate high MMA is most everybody. Even I had enough conversion for that though not enough to get to mito saturation. Only a tiny fraction of those with very specific adb12 response have elevated urine MMA and high CSF MMA doesn't typically show in the urine. MMA is useless for making fine distinctions in the way normally interpreted. The system is very broken by the time urine MMA shows up.

So your hypothesis is that regardless of absorbtion or amount taken, ie 7.5mg absorbed, that it will not be excreted rapidly in the urine thereby confirming absorbtion so it will look like it is not being absorbed.

So we need some adb12 virgins to do the test so they can tell by effectiveness if is being absorbed in saturation and even CNS amounts in a single dose? I hypothesize MMA won't do it and you hyphothesize that excretion won't do it How does it come out of the wrapper? How quickly does it exit the wrapper?. How does it get into the mitochondria? Wouldn't it have to exit the wrapper for that?

Anyway, very interesting. So we shall see. Thankyou Rich.

 

[Freddd]

Hmm, can't be me, because it looks like I have folic acid issues.

But I'm curious and confused about this visual urine test. What's the baseline? How do you calibrate gradations of color? I take my B-Complex and I pee yellow - that's all I can compare this to. [I know you're not talking about a multi-B, here.]

Madie

Hi Madie,

Just for a crude calibration, 5mg injection, 25mg sublingual can make a barely noticable naked eye difference. 10 mg injection, 50mg sublingual makes a much more dramatic difference. 20mg injection or 100mg sublingual makes a very dramatic difference.


Where urine would be yellow from b-complex, 5mg would darken the yellow a little towards orange or brown. 10mg would cause a much more blatent orange or brown coloration. 20mg would push that towards a muddy red.


Where urine would be clear without b-complex, 5mg would darken the urine a little towards pink. 10mg would cause a much stronger pink coloration. 20mg would push that towards magenta.

You have to be observing preferably under indirect daylight for a full spectrum light against a white background. The mini flourescents lack red generally making it invisible.

 

[richvank]

How does it come out of the wrapper? How quickly does it exit the wrapper?. How does it get into the mitochondria? Wouldn't it have to exit the wrapper for that?

Hi, Freddd. The "wrapper" is made of phosphatidylcholine. It merges with the phospholipid plasma membrane of the cell, and releases its contents inside the cell. To get it into the mitochondria, you use a Russian doll structure, with nested phospholipid membranes, so that one is sacrificed getting into the cell, and then the inner one is sacrificed getting into the mitochondrion. Actually, you need a third one to get through the wall of the stomach initially.

This is already done with NT Factor, which Garth Nicolson has shown to deliver phospholipids to the mitochondrial inner membrane.

Liposomal technology was pioneered with pharmaceuticals, but in recent years has been used for nutritional supplements, including vitamin C and glutathione, and according to what adreno has posted, also with forms of B12.

Best regards,

Rich

 

[Freddd]

Hi, Freddd. The "wrapper" is made of phosphatidylcholine. It merges with the phospholipid plasma membrane of the cell, and releases its contents inside the cell. To get it into the mitochondria, you use a Russian doll structure, with nested phospholipid membranes, so that one is sacrificed getting into the cell, and then the inner one is sacrificed getting into the mitochondrion. Actually, you need a third one to get through the wall of the stomach initially.

This is already done with NT Factor, which Garth Nicolson has shown to deliver phospholipids to the mitochondrial inner membrane.

Liposomal technology was pioneered with pharmaceuticals, but in recent years has been used for nutritional supplements, including vitamin C and glutathione, and according to what adreno has posted, also with forms of B12.

Best regards,

Rich

Hi Rich,

So this will take the folic acid right into where to could do the worst damage? So an otherwise possibly beneficial looking innovation could be a catastrophe waiting to happen for 20% or whatever of population unable to utilize folic acid at all? Adb12 doesn't have any problem getting into the cell or mitochondria as is easily demonstrable, entering in 5 minutes after it hits the tissue. And 15-25% absorbtion is no slouch compared to all sorts of things. 1% passive absorbtion is the pits. I'm not sure what problem this is supposed to solve. It only soves a problem compared to cyancbl or hydroxcbl or any form taken orally. Putting folic acid into my brain sounds like a terrible idea. Talk about a Trojen horse, this is it. Putting folic acid in it is a terrible choice. Now I am properly frightened of ever trying this item. Thank you for the information. If it induces severe folate deficiency in susceptable folks can they be sued do you think? Maybe you have never been hit with a slegehammer folate deficiency but I have.

 

[adreno]

Hi Adreno,

Your quoting of the liposomal encapsulated curcuminoid mixture is interesting but may not have any bearing whatsoever on how it may affect adb12 and mb12. it also doesn't say, at least in what you included whether it went through digestion or was a skin absorbtion study.

Sorry, I'm not a biologist, but I do believe that the peer-reviewed studies trumps your personal experiences.

You are very mistaken. They are talking about pomegranates and I'm speaking of chateaubriand. They are toally different, not even apples to oranges (both fruit). If there were a peer reviewed study that did the study correctly, which is rare unfortunately, I could either agree with them or critque them or see what was different for different results. Don't you trust yourself to be able to so something so simple that a junior high school sicence fair might host such a study? I've spent lots of time reading peer reviewed studies and a lot of them are so badly witten up that the writeuyp wouldn't passs high school chemisty. Further a lot of qquestions asked are trying to get narrow answers that support the marketing, NOT the actual efectivness. There are not any studies I have seen on b12 for instance, that study the diffusion of mb12 and adb12 into the tissues directly healing things that don't heal based on any previous studies of inactive cobalamins. The Japanese studies with 50mg doses of methylb12 on neurological spinal cord and brain diseases are the ones I'm working off of. The established the effectiveness of mb12 at doses large enough to enter the CSF by diffusion. In another study with diabetic neuropathy with intrathecal injections of 2.5mg of mb12 established that the CSF effective serum levels varies from less than 3 months to more than 4 years. Then there are the studies that have measured the cobalamin levels in the cerebral spinal fluid of people with CFS, FMS, Parkinson's, ALS, Alzheimer's, Autism, SupraNuclearPalsy and fould that all those are low regardless of blood serum level regarding the difficulty in those with neurological diseases ahving enough b12 in theie=r CSF. Then there are the othger studies that build on the low CSF cobalamin and pinpointed with elevated MMA and/or Hcy. Then there are the studies of some of those diseases and that giving folks cyancbl/hycbl, folic acid and b6 did not affect the CSF HCY level and did not alter disease progression where as 2.5mg intrathecal mb12 injections do affect disease progression. However, nobody has done this kind of sublingual vs injection and a study on reducing homocycteine hasd no relevance at all. It's one of about 100 smilar studies with minor variations demonstrating that whatever they did do did mange to recduce homocysteine for some percentage of people and neither method done was terribly inferior or superior to the other. The outcome was a forgone conclusion based on hundreds of other similar studies with minor variations that have been done over the past 50+ years. Why don't you come up with some actually relevant peer reviewed studies. I would be interested in reading them.

I was a professional photographer and can cerrtainly do colorimetry to compare the color of urine using subtractive color printing filters. One can approximate very well with a naked eye within a few percent of meter. The only way for mb12 or any cobalamin into urine is the blood through the kidneys.

I'm trying to figure out how to make preventing and healing of all these diseases routine, not defending the kind of research that got us into this place intially. The same as Rich. He would look for perhaps somewhat different genetics, but you know, thye exact same genes may be causing any number of the various changes we are looking for. If everybody's genes were eactly one way and all in full agreement with how sicience to this point has defined, then none of us would be sick. If doctors knew how to treat us effectively we wouldn't be sick. So, the best that can said is that they are not trying to make us sick on purpose or withholding known effective treatments. My docs were all puzzled, it's only some who had to call me names and punish me for having "an imaginary woman's disease". The honest ones just said I would be better served finding somebody who understood it. How right they were.

In the thousands of papers I have read I have to admit that when they very deep in chemistry it goes way beyond anything I know. I do much better at picking out docs who commit fraud and docs with lots of poor outcomes, or good outcomes for that matter. But I do know slanted questions and answers when I see them on the subject of b12, time relase opioids and some other such things, scrambled data, graphs that don't match data tables and things like that. It's interesting that the same information theory that picks out fraudulent docs also picks out faulty research, none of it perfectly.

I've helped write and present papers at group medical insurance conferences. Of course they were more likely to be things like "Effects of reimbursement methods on outcomes." Or "Methods of selecting preferred physicians for 2nd opinion referrals". If I were offerring the advice I give on these things to a group health plan for data mining purposes to select people for nutritional interventions I would guarantee, with my payment level at risk, the minimum level of results with 100,000 people by secondary measures such as reduced pharamacy costs and reduced provider visists and so on thereby reducing costs and increasing patient satisfaction.

Now I am perfectly willing to give you exact written directions by which you, or anybody, can replicate my results on absorbtion, within reasonable statistical limits. That is precisely what the quoted studies you provided were doing. That is how the system works. The big difference is that since I don't have lots of expensive lab toys, I have to to things that can be seen with the naked eye, like outright healing and red tinted urine. Also, to save my life and that of my children and grandchildren I need faster results then 1 small step each 5 years. By healing myself I have demonstrated I know of what I speak. The question is opnly how these things apply to others and what the differences and percentages are, So here we are 50 years, maybe 100 years ahead of these kind of studies. So far nobody outside of Japan appears to be interested in how high dose methylb12 works and the diffusion associated with it. Of course Japan has an Alzheimer's rate 20% of ours. Their cobalamin low level alert is 550pg/ml instead of 160pg/ml as in USA and UK, and they are the only country of which I'm aware using methylb12 as their official form of b12 and doing research of it's effect on neurological diseases with low CSF cobalamin.

We are right here right now attempting to make it simpler to identify "paradoxical folate deficiency" and other "induced folate deficiency" and "induced potassium deficiency" for that matter. NONE of those things are defined or recognized except "paradoxical folate deficiency" was named in a case study of a horse. They affect the health of some unknown percentage of the people here somewhere between >20% and <100% in the aggragate of the several things. Have fun and be in good health.

Meriva curcumin is oral (capsule) based. You can find it on iHerb.

I am unwilling to carry out your experiment because: 1) I have enough side effects from 5mg mb12 and 3mg adb12 already, and 2) I don't have the biochemical knowledge to evaluate whether such an experiment is valid. Is the color of urine a valid measure of how much nutrient has been delivered into cells? Is it independent of water intake, kidney function, or other variables?

I do know that liposomal encapsulation is a hot thing in pharmacology, and that research has shown it to be superior in delivering drugs/nutrients into cells. This is because, as Rich has explained, the liposomes allow the drug/nutrient to enter through the cell membrane.

My main point is, that I cannot accept your offhand dismissal of the superiority of liposomal delivery over sublingual route, without seeing any data on this. I have just not seen any evidence that sublingual absorption is significantly better than oral, for any drug/nutrient. If anyone knows of such research, I'd like to see it. And even if it is superior to oral, we still need comparisons with liposomal delivery, before we can make any conclusions.

I'm not interested in defending any research, product, or method of delivery. I'm interested in finding out which is the most effective.