M Hari Krishna,

Prof Sudhakar's contact address is posted at the end of his comment.

Best regards,

John Stone, UK Editor

my 5 year is diagnosed with PDD. He's been on: Mb12, Phospholipids, Glutathione & Folic Acid (All injected IV)
The Results are nothing less than amazing.
He's been on this treatment for 7 months now and I could assure you that the GFCF diet it important too. If your child is not on this diet, I highly suggest getting him/her on the diet for faster results.

What is the difference biochemically between the three forms of Vit B12 - cyanocobalamin, methylcobalamin, & hydroxycobalamin?
Could this oxidative stress problem, and the inactivation of methionine synthase be a problem in persons with ADHD?associated with learning disorders? and emotional instability? My stepson deals with these issues since a very young age & was born via an emergency C Section for fetal distress (cord wrapped around neck several times & meconium aspiration on a ventilator for a day.) There is however ADHD in the family on the paternal side & possibly on the maternal. Has any link or similarity been drawn between these two groups of disorders which are epidemic at this time?
Thank you for addressing this in any form possible. Suzanne M. Picinich, DO

Can someone address B12 toxicity? Why do some kids develop seizures and get B12 toxic? Why does giving P5P or Methyl Folate help MB12 absorption?
The compounding pharmacist told me Hydroxy B12 was the more bio-available form of B12 and my son has responded well on it but he doesn't really have a problem with MB12 if it is given with P5P and Methyl Folate. Once we gave him a Revitapop (just B12) and he didn't sleep for almost 72 hrs so I learned that he cannot tolerate just B12.
It's unfortunate that for parents we have to do so much trial and error here. I agree with earlier posts that there clearly needs to be much more research in this area. HELP!

@Mattea. No our DAN doc did not try Hydroxyl B12 first. Our experience was five years ago, and I'm not sure if that nuance was understood back then or not. However, upon investigation of Yasko's Protocol and the understanding of the probability that my son has COMT, I tried an oral Hydroxyl B-12. Works beautifully for both of us (I have NVLD & Methyl B12 was a problem for me too).

I am certainly very familiar with the cobalt-containing corrin ring structure of vitamin B12. The cobalt is held within the ring by four bonds, very similar to the way iron is held within its heme ring in hemoglobin. This is how nature harnesses the intrinsic oxidative potential of these heavy metals and puts them to critical metabolic use.

In the case of B12, the tail portion of the molecule bends back to bond to the cobalt via the lower face of the corrin ring. When B12 is bound to the enzyme methionine synthase the tail is displaced and instead a portion of the enzyme reversibly binds to the cobalt from the underside. This on and off binding from below controls the tendency of the cobalt to either pick up a methyl group (from methylfolate) or donate a methyl group (to homocysteine) on the upper surface of the corrin ring. Its a very clever piece of biochemistry.

There is undoubtedly some breakdown of the corrin ring, just like there is breakdown of the heme ring, and it would be important to know how much of this occurs after methylB12 administration. However, I'm not aware that anyone has measured this, although the vast majority of the dose is undoubtedly excreted as unchanged B12. When the Geier's paper compared the toxicity of free cobalt with measurements of total plasma or urinary cobalt, which is likely to be vitamin B12, they ignored this obviously important issue. Methods exist for specifically measuring cobalamins, which should have been done to see what proportion of the cobalt was still B12.

As I pointed out, even if 100% of the cobalt was released from the B12, the concentration the Geiers found in plasma was 40,000-fold below the toxic level they reported. So if 1% of the B12 was broken down and released its cobalt, the difference would be more than a million-fold. Even though zero would be better, this is a very big margin of safety. However, there should be a direct measurement of the cobalt-containing species to see what proportion was free.

In any case methylB12 is obviously not for everyone, even though many do appear to benefit. Genetic testing may indeed be a useful predictor of who will benefit, and different dosage schedules and routes of administration may allow individualization of its use. Its unfortunate that methylB12 has not yet been studied in this manner, but hopefully this may occur in the future.

The Geiers study clearly shows that more work is needed in this area. After initially responding very well, my daughter crashed on MB12. There is a doctor in NJ that commented to me she has a large number of patients that have come to her because they crashed on MB12. Dr. Neubrander's email about 'organic' vs 'inorganic' cobalt should send up red flags. We've been haggling over this terminology about mercury for close to a decade.

This post is not meant to slam Dr. Neubrander or fall firmly on the side of the Geiers. This study raises a concern that should be investigated further. Just like everything else we try in autism - some things are miracles for our children and other things cause serious side effects or have no effect.

If some children can't handle MB12 shots, then its a great opportunity to find new insights into this disorder.

Sorry Jack, I would disagree with the opinion you have expressed above. With all due respect, in my view the Geiers work receives an unjustified recognition in an audience of non specialists. This is particularly relevent with regard to their work on testosterone and Lupron therapy. This is sad but a critical caution must be observed by all in order to make the best choices for their autistic loved ones. Until fair and informed guidelines on interventions are being produced, parents will remain vulnerable and highly influenced. I would suggest that it should be one of AoA’s priorities to continue to demand that suitable research in intervention is being conducted, not solely by Autism Speaks but also by the many practitioners involved in autism treatment.

Dr. Neubrander's email to patients

That this article and content was to be published was nothing new to me because it first came to my attention when the Geirs presented their theory at Cherry Hill a year ago. I lecture to physicians about the flaws in this study when doing training seminars. A full discussion would take an hour or more to write so I will only list a few key points here.

It is the cobalt inorganic salts that are toxic, not the organic form of cobalt that is bound on all four binding sites in the corrin ring. The more we take of B12 by any route of administration, the more that passes unchanged from the blood to the urine. If one did not find it to be high in the urine, then that would indicate a problem.

Laboratories do not differentiate between organic and inorganic amounts of cobalt but report the total amount of cobalt present along with a reference range that was created for the inorganic toxic form for miners and "old fashioned beers" (no longer used). An analogy would be to consider the total number of eggs one will be adding to a cake mix before and after it is baked and then try to compare the taste and texture of eggs to a cake. As an environmental physician, we see fairly rapid cause and effect for truly toxic agents, only one of which are heavy metals or metals in general. The effects of mercury or lead or arsenic are just as rapid and severe after exposure as are the effects from toxic amounts of poisonous chemicals. Therefore, common sense dictates that from the thousands of children I have treated, added to that the tens of thousands of children who have now been treated worldwide, if there really was a problem we would have seen it by now and that the effects would be pronounced. Exactly the opposite is what we as clinicians and parents see to be the case. Add to that incredible amount of clinical data that has and continues to be accumlated the fact that other published "clinical" studies (not quoted in the Geir article) support the fact that higher doses are safe and possibly more effective than lower doses.

All of that should be taken into account and weighed against the findings of the recent 2010 Okada rat study. In that study whereby rat's nerves were transected, they found that the methyl analog of the B12 family was significantly more biologically active than any other form of B12. They also documented that it is the shortest lived analog and therefore clinicians should consider giving it by injections instead of the usual routes of administration. In addition, they found the greatest benefits at high to very high doses. What occurred in the rat's nervous tissue under these conditions (organic cobalt plus the cobalamin molecule) was that it increased the length of axons, increased formation of neurites, increased resistance to apoptosis, was involved in kinase signaling pathways, and helped repair the transected nerves.

Therefore, what you do with "this study" is up to you but "published studies show" that mercury and vaccines are safe and not related to the autism epidemic. Many other "published studies" have proven many things we believe to not be true but are passed along as fact. Therefore, the final thing that any parent has to do, you just being one of them, is to decide for yourself what you choose to believe and after that follow your heart. I have no qualms with that. However, as for me, after observing thousands of my own patients do so well on injectable MB12, and where the majority of them do even better with daily shots than every two or three day shots, I can confidently say I've read the study and do not agree with its implications.

Sincerely,

Jim Neubrander, M.D.

This really is unbelievable. When Geier and Geier publish a retrospective study using the VAERs database that links thimerisol to autism, the medical establishment labels them as unqualified quacks, hired shills for the trial lawyers of desperate parents. When they publish a study that mistakenly associates methyl-B12 with heavy metal cobalt poisoning, they are now dedicated researchers exposing the snake oil methods of (other) quacks taking advantage of (again) desperate parents, who unwittingly poison their children.

MB12 (methylcobalamin) is one of a very small list of interventions that truly works, and importantly, we understand why it works. Thanks to the tireless work of Dr. Deth, Dr. Waly and Dr. Nuebrander, we understand that MB12 reactivates methionine synthase (MS) in the brain that was deactivated by oxidative stress. We understand that phospholipid methylation can resume thus allowing proper neuron membrane permeability/flexibility and neuronal signal synchronization. In any other disorder, these three men would be viewed with admiration; MB12 would be considered a godsend.

Unfortunately, all three men have publicly stated they think thimerisol plays a key role in the inactivation of MS in the first place. They have stated thimerisol depletes glutathione, this preventing reactivation of MS on its own. They must be destroyed.