Hi Alcyone, A friend of mine had some skin cream of a chemo drug to get rid of some precancerous skin on her face. She had a terrible depressive crash and all sorts of symptoms of the type you might expect from a folate antagonist which many chemo drugs are. She went up from her usual 800mcg of Metafolin and intermittent MeCbl to 4000mcg of Metafolin and 4000mcg of MeCbl and the depression and other symptoms receded strongly over several days. For the second round of the drug she took the Metafolin and MeCbl starting a day ahead and throughout the 2 week cycle and had no side effects at all unlike the first cycle. Being cold all the time is an explicit B12 deficiency symptom.