Active-B12 measures Holotranscobalamin (HoloTC), the biologically active component of vitamin B12 (10-30%). It is the earliest marker of deficiency due to the shorter half life of active-B12. It reacts early in the process and is decreased before clinical signs, not just in deficiency, and it is now commonly used as a first line marker for early serum depletion. Risk populations include individuals with low vitamin B12 intake (e.g. vegetarians, vegans and macrobiotic diet), elderly people (e.g. pernicious anemia, achlorhydria, malabsorption caused by gastrointestinal disorders), neurodegenerative and neuropsychiatric disorders (e.g. dementia, Alzheimer's disease), macrocytic anaemia (e.g. low absorption of vitamin B12 or pernicious anemia), chronic alcoholism, some medications and other diseases.