Re: Lipoceutical glutathione and methylB

[Guest guest]

My son has been on MethylB injections for about a year and, overall, has

done very well on them. Aproximately 8 weeks ago, I introduced the

lipoceutical

glutathione and have seen great improvements. However, now when I give the

methylB injections, I am getting an increase in stimming and scritpting,

Infact, we lose him for a day and a half. I know he needs B12 so what do I

do?

Is he detoxing more quickly and effeciently so the injections are too much

with the LipoGSH or what???? I spoke to someone and Coastal and he was unsure

how to proceed. He thought we should maybe try loading for 2 weeks (like

some parents are doing when first starting the methylB injections). I'm just

not sure what to do. Any ideas?

[Guest guest]

I queried Dr. Neubrander and here is his reply:

Jaquelyn: Regarding the patient's question I must first respond by saying

that what

may be happening is that with the L-GSH one is going " overboard " on the

glutathione part of the methylation/transsulfuration pathways. Considering

Jill's work, the GSH levels returned to control levels with MB12. If this

child's " research lab " values [in contrast to commercial lab values e.g.

from Great Smokies] actually did return to normal, then more GSH precursors

that will become GSH is maybe too much and what this child really needs is

the methylation portion of the pathway to be enhanced greater than the

transsulfuration pathway.

The way I would treat this patient is to temporarily stop the L-GSH, return

to what was working with the MB12, and then slowly and progressively add the

L-GSH back into the regimen to establish " equiibrium " between the

methylation vs. transsulfuration pathways. Jim

Re: Lipoceutical glutathione and methylB

>

> My son has been on MethylB injections for about a year and, overall, has

> done very well on them. Aproximately 8 weeks ago, I introduced the

lipoceutical

> glutathione and have seen great improvements. However, now when I give

the

> methylB injections, I am getting an increase in stimming and scritpting,

> Infact, we lose him for a day and a half. I know he needs B12 so what

do I do?

> Is he detoxing more quickly and effeciently so the injections are too

much

> with the LipoGSH or what???? I spoke to someone and Coastal and he was

unsure

> how to proceed. He thought we should maybe try loading for 2 weeks (like

> some parents are doing when first starting the methylB injections). I'm

just

> not sure what to do. Any ideas?

>

>

>

[Guest guest]

,

One of our suspicions about why METHYL-B12 is needed, as opposed to

cyanocobalamin or hydroxycobalamin, is that to make methyl-B12 on your own,

you have to first make glutathionylcobalamin. If you have insufficient

glutathione, this could be a weak step. If you have been solving the

glutathione problem, it is possible your son doesn't need the methylB12

that helped him so much before. Why don't you ease off, and see if he does

better?

Something else that could be happening, is that if your son previously was

experiencing a big push towards the sulfur pathway because of low

glutathione (meaning homocysteine went the route to cysteine rather than

methionine), then when adequate gluathione eliminated the need for

methionine to be routed so much to the sulfur chemistry rather than

methylation, you might have seen stepped up cycling through methionine

synthase or TMG. The excess methyl-B12 may have been pushing this so hard

that your son might have begun to run out of other cofactors that are

needed there. On the other hand, he might have been getting too much

activity in some other not-yet-determined methyl-B12 dependent step.

On sulfurstories, we had a mom of a child with the MTHFR polymorphism that

makes you need a lot more riboflavin than ordinariily to accomodate

methionine synthase. When she started him on lipo GSH, he started to have

signs of B2 deficiency: cracked corners of the mouth. Taking huge amounts

of riboflavin made this symptom go away. It helped that we knew what

caused that symptom and that we knew about the polymorphism, too., because

now it all made sense. This mom actually figured this out, except I added

that getting the glutathione would start rerouting more homocysteine to

methionine synthase, burdening the methylation cycle more than in the

past. Curiously, I had the very same experience earlier of taking a sulfur

supplement, then taking more methyl-B12, and getting the cracked corners of

the mouth. Just as in this child, B2 solved that for me in short order.

But, what causes the stimming?

Offhand, my suspicions would be that the methyl-B12 is pushing something

that is using up tryptophan, because stimming tends to happen as a low

serotonin symptom. In support of that, I'll put below the abstract from

the study where someone took some adults with autism and restricted

tryptophan for one day, and they got " stimmish " symptoms as a result.

Have you seen any changes in sleep patterns? MethylB12 does seem to alter

the making of melatonin, which is made from serotonin.

Yet another possibility is that the methylB12 was enhancing a niacin

dependent pathway, and if your son had low tryptophan, his body would have

started to use tryptophan extravagantly to make niacin, thus shorting the

availability of tryptophan to make serotonin. If that is the case, taking

a form of niacin might help.

I don't know if you have done a fasting plasma amino acid profile, but I

wouldn't be surprised if it would show low tryptophan.

Arch Gen Psychiatry. 1996 Nov;53(11):993-1000. Related Articles, Links

Comment in:

* Arch Gen Psychiatry. 1996 Nov;53(11):980-3.

Effects of tryptophan depletion in drug-free adults with autistic

disorder.

McDougle CJ, Naylor ST, Cohen DJ, Aghajanian GK, Heninger GR, Price LH.

Clinical Neuroscience Research Unit, Abraham Ribicoff Research

Facilities, Connecticut Mental Health Center, New Haven, USA.

BACKGROUND: The primary objective of this study was to investigate the

behavioral and biochemical responses to acute tryptophan depletion in

drug-free adult patients with autistic disorder. METHODS: Twenty drug-free

adults with autistic disorder (16 men and 4 women) (mean [+/- SD] age, 30.5

+/- 8.5 years) underwent short-term tryptophan depletion in a double-blind,

placebo-controlled, randomized crossover design. Patients received a

24-hour, low-tryptophan diet followed the next morning by an amino acid

drink. Behavioral ratings were obtained on the morning of the amino acid

drink (baseline) and 180, 300, and 420 minutes after the drink. Plasma free

and total tryptophan levels were obtained at baseline and 5 hours after the

drink. The active and sham testing sessions were separated by 7 days.

RESULTS: Eleven (65%) of the 17 patients who completed both test days

showed a significant global worsening of behavioral symptoms with

short-term tryptophan depletion, but none of the 17 patients showed any

significant change in clinical status from baseline after sham depletion (P

= .001). Tryptophan depletion led to a significant increase in behaviors

such as whirling, flapping, pacing, banging and hitting self, rocking, and

toe walking (P < .05). In addition, patients were significantly less calm

and happy and more anxious. No significant change was observed in social

relatedness or repetitive thoughts and behavior. Plasma total and free

tryptophan levels were reduced 86% and 69%, respectively, 5 hours after the

tryptophan-deficient amino acid drink. Patients who had a significant

global exacerbation of symptoms had significantly higher baseline plasma

total tryptophan levels (P < .001) and Autism Behavior Checklist scores (P

= .005) than did patients who showed no significant change in symptoms

after tryptophan depletion. CONCLUSIONS: The results of this study are

consistent with previous research that has implicated a dysregulation in

serotonin function in some patients with autism. These data suggest that

the short-term reduction of serotonin precursor availability may exacerbate

some symptoms characteristic of autism in some patients. Continued

investigation into the role of serotonin in the pathogenesis and treatment

of autistic disorder is warranted.

Publication Types:

* Clinical Trial

* Randomized Controlled Trial

PMID: 8911222 [PubMed - indexed for MEDLINE]

Brain Res. 1998 Jun 8;795(1-2):98-104. Related Articles, Links

Methylcobalamin amplifies melatonin-induced circadian phase shifts by

facilitation of melatonin synthesis in the rat pineal gland.

Ikeda M, Asai M, Moriya T, Sagara M, Inoue S, Shibata S.

Advanced Research Center for Human Sciences, Waseda University,

Saitama, Japan. msikeda@...

Effects of methylcobalamin (methyl-B12), a putative drug for treating

human circadian rhythm disorders, on the melatonin-induced circadian phase

shifts were examined in the rat. An intraperitoneal injection of 1-100

microg/kg melatonin 2-h before the activity onset time (CT 10) induced

phase advances of free-running activity rhythms in a dose-dependent manner

(ED50=1.3 microg/kg). Injection of methyl-B12 (500 microg/kg) prior to

melatonin (1 microg/kg) injection induced larger phase advances than saline

preinjected controls, while the injection of methyl-B12 in combination with

saline did not induce a phase advance. These results indicate amplification

of melatonin-induced phase advances by methyl-B12. Pinealectomy abolished

the phase alternating effect of methyl-B12, suggesting a site of action

within the pineal gland. In fact, methyl-B12 significantly increased the

content of melatonin in the pineal collected 2-h after activity onset (CT

14). In contrast, no difference in melatonin content was found at CT 10,

indicating that the effect of methyl-B12 may be gated after the activity

onset time when endogenous melatonin synthesis is known to increase. These

results suggest that methyl-B12 amplifies melatonin-induced phase advances

via an increase in melatonin synthesis during the early subjective night at

a point downstream from the clock regulation. Copyright 1998 Elsevier

Science B.V. All rights reserved.

PMID: 9622603 [PubMed - indexed for MEDLINE]

Protein Expr Purif. 2004 Nov;38(1):84-98. Related Articles, Links

[Click here to read]

Purification of the recombinant human serotonin N-acetyltransferase

(EC 2.3.1.87): further characterization of and comparison with AANAT from

other species.

Ferry G, Ubeaud C, Dauly C, Mozo J, Guillard S, Berger S, Jimenez S,

Scoul C, Leclerc G, Yous S, Delagrange P, Boutin JA.

Pharmacologie Moleculaire et Cellulaire, Institut de Recherches

SERVIER, 125, chemin de Ronde 78290 Croissy-sur-Seine, France.

Melatonin is synthesized by a series of enzymes, the penultimate one,

serotonin N-acetyltransferase, catalyzing the limiting reaction. In the

present study, we compared the recombinant serotonin N-acetyltransferases

from rat, ovine, and human. The human protein is particularly difficult to

purify because it interacts strongly with a putative chaperone protein from

bacteria whereas the rat and sheep enzymes, which interact less strongly

with this protein, have been purified close to homogeneity. We identified

the contaminating protein as GroEL, the bacterial equivalent of Hsp60. We

present numerous catalytic activities (substrate and cosubstrate

specificities as well as inhibitor specificities) measured on the three

species enzymes from which we deduced that the presence of the chaperone

might partly explain the differences between the various species enzyme

characteristics, beside the inter-species ones resulting from sequence

differences. Despite several trials reported in the literature, a

purification to homogeneity of the human (recombinant) enzyme has never

been described. We present a new purification method, by using an original

denaturation/renaturation process in which the enzyme is immobilized on an

affinity chromatography column. The enzyme is then eluted in an active and

pure form (i.e., absence of chaperone). The up-scaled system permitted us

to perform the necessary experiments for the measurement of more accurate

affinities of human serotonin N-acetyltransferase towards its main natural

substrates, showing that only the activity of the enzyme towards

phenylethylamine was modified.

PMID: 15477086 [PubMed - in process]

Adv Exp Med Biol. 2003;527:435-41. Related Articles, Links

Increase in conversion of tryptophan to niacin in pregnant rats.

Shibata K, Fukuwatari T, Murakami M, Sasaki R.

Laboratories of Food Science and Nutrition, Department of Life Style

Studies, School of Human Cultures, The University of Shiga Prefecture,

Hikone, Shiga 522-8533, Japan.

There is the report that the deaths by pellagra in women is

approximately twofold excess that in men. In the present experiment, in

order to clarify a factor in the etiology of pellagra in female and to get

basic information how much niacin should be supplemented in pregnant state,

we investigated the effects of pregnant on the metabolism of tryptophan to

niacin in rats. The daily urine samples were collected from day -17 and day

+6 (the delivery day was designated as day 0) and the intermediates of

tryptophan to niacin were measured. The metabolites such as kynurenic acid,

xanthurenic acid, anthranilic acid, 3-hydroxyanthranilic acid, quinolinic

acid, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide,

N1-methyl-4-pyridone-3-carboxamide were increased with progress in pregnant

and returned to normal levels after the delivery. The catabolism of

tryptophan is accelerated during pregnancy, indicataing that pregnancy

would not be an etiology of pellagra and no niacin supplement needs but

tryptohan supplement would need.

PMID: 15206761 [PubMed - indexed for MEDLINE]

At 04:14 PM 12/14/2004 -0500, you wrote:

>My son has been on MethylB injections for about a year and, overall, has

>done very well on them. Aproximately 8 weeks ago, I introduced the

>lipoceutical

>glutathione and have seen great improvements. However, now when I give the

>methylB injections, I am getting an increase in stimming and scritpting,

>Infact, we lose him for a day and a half. I know he needs B12 so what

>do I do?

> Is he detoxing more quickly and effeciently so the injections are too much

>with the LipoGSH or what???? I spoke to someone and Coastal and he was

>unsure

>how to proceed. He thought we should maybe try loading for 2 weeks (like

>some parents are doing when first starting the methylB injections). I'm just

>not sure what to do. Any ideas?

>

>

>

[Guest guest]

I certainly don't put myself in the same league as Dr J or , but

fwiw, my daughter found that she was better off giving the LipoGSH in

the a.m. as she gives M-b-12 and TD-DMPS at night. (not same night)

This seemed to " straighten " things out. I just offer this as an

observation and what worked for us.

Ann