Hi Globalpilot, Taking into account what Rich is saying here, I would like to add on to that. A little history might prove enlightening. The folate RDA is an extremely artificial amount having little bearing on what is actually needed. It was deliberately set too low to be fully effective. The fear was that a person would do serious damage to themselves by taking a lot of folate so as to correct macrocytic anemia (ie pernicious anemia) without preventing serious neurological damage from lack of b12. A reasonable less artificially lowered number for RDA might be closer to 3200mcg or so for a desirable dose. The prescription doses vary from about 5mg to 15mg. The standard inactive b12 therapy was established in the 1950s and early 60s. Remember that this was in a period when b12 was very expensive, maybe US$10 in 1960 dollars for 1mg. This works out to US$10,000 per gram in 1960 dollars. In 1960 a paperback book and a pack of cigarettes and a gallon of gasoline each cost about US$0.35. Now it's closer to US$4.00 each. That informal inflation rate puts b12 at about US$110,000.00 per gram in present value dollars. For that price you can now buy about 20 kilograms. The whole strategy was to use as little of a rare and expensive substance as possible. Further research put the amount needed extremely low, say 6mcg. At first there was not thought to be any dose proportionality in healing because with the inactive cobalamins, cyanocbl and hydroxcbl, the range is so narrow as to be almost imperceptible. The dose proportionality of cyanocbl and hydroxcbl has been measured to be in the 1-125mcg range, the maximum being the oral amount needed to saturate HTC2. No other form of delivery was researched as no others were considered possible and the active transport system is the only one that works with inactive cobalamins. So a 1mg injection seemed very generous and a single such injection per month could reverse pernicious anemia which, for a long time, was considered the only significant set of b12 deficiency symptoms. So now, methylb12 is known to have a much larger dose proportionate effectiveness range. Actually there are two ranges, the body and the central nervous system. The body range appears to be in the area of 1-5000mcg (injected SC, sublingual held 45-120 minutes is more in the area of 1-25,000mcg) daily. The CNS range, from a combination of Japanese research and my own private research with a number of participants indicates the range is from about 30mg (injected SC) to 180mg or more (injected SC) per day. The Japanese have lately been experimenting with IV infusion of 50+mg daily. At US$110/mg these larger doses are unaffordable, $20,000 daily, so your feet should fall off as your nervous system breaks down from the inside out. However, at today's prices it is feasible to self finance this kind of research. The "clinical data" of which Rich speaks is not available because the research has never been done because of the biases built into 60 years of research based on inactive cobalamins since, as "everybody knows" b12 has a very low top end of dose proportionality. So, with that history in place, and recognizing that what is important is the amount of b12 going into serum, not the nominal size of an oral or sublingual dose, I would say that a dose of about 1-5mg injected SC daily and the equivalent amount sublingual to serum, is fully sufficient for most anybody to heal their body. However, with the difficulty some groups (FMS, CFS, Parkinson's, Alzheimer's, ALS, MS and others) are known to have in getting cobalamin into the cerebral spinal fluid and CNS, a minimum dose of about 6-7.5mg injected SC is needed to penetrate the CSF/CNS. How much is needed for prevention is almost certainly a different story from stopping progressing damage and/or healing damage that is already done. "Large" doses are as much a matter of perception and purpose as anything else. 35 grams of b12 seems like a huge dose to me yet it is the standard size dose for saving the life of somebody poisoned with cyanide and is used over and over until all the cyanide is flushed from the body. Obviously this wasn't a dosage used in 1960. 5mg of mb12 can save the life of a bird, much smaller than a human, with avian botulism as it neutralizes the botulism toxin. So a several 5mg mb12 sublingual tablets daily can heal a body but leave the brain and cord to continue deteriorating. 30mg a day of mb12 SC can make a start at stopping the brain and cord deterioration and maybe healing it. 180mg a day does even better. What is large here?