this question is for Rich.
I like to take methylb12 instead of the hydroxy because I have mutations in the MTRR enzyme which could limit the conversion of cobalamin to methylcobalamin.
Is there a danger in taking too much methylb12. I know about the issue with mercury but is there any other reason one couldn'ttake 2000 mcg of mb12 instead of hydroxyb12 if the MTRR mutations are present ?
Global Pilot
Hi, Global Pilot.
My concern about methylB12 is related only to its possible potential for methylating inorganic mercury that may be in the body, primarily from exposure to mercury vapor, as is released continuously from amalgam fillings in the teeth. Methyl mercury is readily able to cross the blood-brain barrier and enter the brain, where it apparently then reacts with enzymes containing selenium (and to a lesser extent, sulfur) and acts as a neurotoxin, with a residence time in the brain measured in years.
I do not have proof that this will actually occur in humans with the inventories of inorganic mercury that are actually present and the dosages of methyl B12 that are used in treating ME/CFS.
My concern comes from the fact that there are published papers indicating that methyl B12 is able to react and donate a methyl group to inorganic mercury, and in fact, it is one of the only substances in biological systems that is able to do this. The reason is that inorganic mercury exists as a doubly positive mercuric ion (Hg++). In order for a substance to donate a methyl group to it, the substance must be negatively charged. methyl B12 forms a carbanion, which is able to do this.
It is known that the way methylmercury enters fish is that bacteria in aquatic environments use methyl B12 and other similar substances to methylate mercury, and then are eaten and travel up the food chain to the larger fish. Apparently the bacteria methylate the mercury as a means of exporting it to their outer surfaces and so protecting themselves from its toxicity. It can have some toxic effects on fish (see first abstract below) and when people eat fish containing methylmercury, it can be toxic to them, especially if their bodies are low in selenium (see second abstract below). Methylmercury dumped as waste into the ocean in a fishing area was responsible for the Minimata disease disaster in Japan in the late 1950s, and methylmercury used to treat grain seed that was unfortunately later eaten by people caused a disaster in Iraq as well.
There have been experiments in guinea pigs in which it was found that methylation of mercury occurred in their bodies. It is not clear whether this methylation occurred within their own metabolism, or whether it was carried out by bacteria in their gut.
As far as I'm concerned, this is an issue that has not yet been resolved. I'm aware that people with certain polymorphisms will benefit more in terms of helping their methylation cycle by taking methyl B12 rather than hydroxo B12. I know that there are people who are taking dosages of methyl B12 of several milligrams per day, sublingually, and some are reporting benefits. I don't know what their body burdens of inorganic mercury might be. Unfortunately, there is no good way of evaluating it, short of doing autopsies, which isn't very helpful for people who want to keep living for a while!
It may be that supplementing with selenium will give sufficient protection from methylmercury toxicity. This approach is actually used by marine animals and birds, who eat seaweed, containing selenium, together with fish containing methylmercury. Some whales have been found to have large deposits of selenium-mercury compound in their livers. This is very chemically stable, and makes them both non-bioavailable. It should be noted, however, that selenium is toxic in large amounts as well, and the Institute of Medicine has placed a recommended upper limit on selenium supplementation of 400 micrograms per day. Some have argued that this limit is too conservative. The safe upper limit for an individual probably depends on a number of factors, the body burden of mercury being one of them, but it is difficult to determine what it should be on an individual basis. The Institute of Medicine attempts to set a limit with a safety factor that will apply to the general population.
I wish I could give you a more definitive answer to your question, but that's as much as I know. It's possible that I am being overly cautious in raising this issue, but I really do not want people to be harmed.
Best regards,
Rich
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009 Oct;27(4):212-25.
Reproductive, developmental, and neurobehavioral effects of methylmercury in fishes.
Weis JS.
Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA.
jweis@andromeda.rutgers.edu
Abstract
In the decades since the Minamata tragedy in Japan, there has been a considerable body of research performed on effects of methylmercury in fishes. The studies have revealed that some of the most sensitive responses seen in fishes are reminiscent of the symptoms experienced by the Minamata victims. This article reviews the literature, with a focus on mercury's effects on fish reproduction (hormone levels, gametogenesis, fertilization success), embryonic development (morphological abnormalities, rate), the development of behavior, and neurobehavioral effects in adults. Both experimental exposures and epidemiological approaches are included. There have been many studies demonstrating delayed effects of mercury exposure in that exposures during one life history stage can produce effects much later during different life history stages. For example, exposure of maturing gametes can result in abnormal embryos, even though the embryos were not themselves exposed to the toxicant. Exposures during sensitive embryonic periods can produce long-lasting effects that can be seen in adult stages. The existence of these manifold delayed effects renders the practice of short-term toxicity testing particularly unhelpful for understanding the effects of this (and other) toxicants.
PMID: 19953396 [PubMed - indexed for MEDLINE]
Toxicology. 2010 Nov 28;278(1):112-23. Epub 2010 Jun 16.
Dietary selenium's protective effects against methylmercury toxicity.
Ralston NV, Raymond LJ.
Energy & Environmental Research Center, University of North Dakota, 15 North 23rd Street, Grand Forks, ND 58202, USA.
nralston@undeerc.org
Abstract
Dietary selenium (Se) status is inversely related to vulnerability to methylmercury (MeHg) toxicity. Mercury exposures that are uniformly neurotoxic and lethal among animals fed low dietary Se are far less serious among those with normal Se intakes and are without observable consequences in those fed Se-enriched diets. Although these effects have been known since 1967, they have only lately become well understood. Recent studies have shown that Se-enriched diets not only prevent MeHg toxicity, but can also rapidly reverse some of its most severe symptoms. It is now understood that MeHg is a highly specific, irreversible inhibitor of Se-dependent enzymes (selenoenzymes). Selenoenzymes are required to prevent and reverse oxidative damage throughout the body, particularly in the brain and neuroendocrine tissues. Inhibition of selenoenzyme activities in these vulnerable tissues appears to be the proximal cause of the pathological effects known to accompany MeHg toxicity. Because Hg's binding affinities for Se are up to a million times higher than for sulfur, its second-best binding partner, MeHg inexorably sequesters Se, directly impairing selenoenzyme activities and their synthesis. This may explain why studies of maternal populations exposed to foods that contain Hg in molar excess of Se, such as shark or pilot whale meats, have found adverse child outcomes, but studies of populations exposed to MeHg by eating Se-rich ocean fish observe improved child IQs instead of harm. However, since the Se contents of freshwater fish are dependent on local soil Se status, fish with high MeHg from regions with poor Se availability may be cause for concern. Further studies of these relationships are needed to assist regulatory agencies in protecting and improving child health.
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
PMID: 20561558 [PubMed - indexed for MEDLINE]
