The choice of limiting or removing foods of animal origin from the diet is increasing in popularity due to ethical, environmental and health reasons, posing doubts over whether a number of these restrictions could be detrimental or useful [ 203 ]. The vegetarian diet can be sustainable at all stages of life and in all physiological conditions, including infancy, pregnancy, lactation, senescence and sports [ 13 ]. Compared to non-vegetarians, vegetarians have reduced body mass index (BMI), serum cholesterol, serum glucose and blood pressure with a lower mortality rate due to ischemic heart disease (IHD) [ 17 204 ]. However, underestimating the correct supplementation of cobalamin (Cbl) can nullify these benefits [ 103 ]. It is also necessary that the diet be balanced and nutritionally adequate to reduce the risks of other deficiencies which could indirectly affect the absorption of Cbl. Studies on the use of plant foods to increase the Cbl intake are promising, but still require more data. Some seaweed, mushrooms and fermented foods can be a useful source of Cbl, but the data are still insufficient and production is too heterogeneous. The standardization of Cbl-rich plant foods may be useful in preventing vitamin deficiency, overcoming the frequent ideological barriers on supplementation. The use of fortified toothpaste could be a promising alternative to the fortification of flour, resolving the possible reduction of vitamins during cooking [ 205 ]. Studies of efficacy in maintaining vitamin sufficiency with different Cbl forms are absent. More trials with vegetarian people using supplements or fortified foods are needed to better explain the efficacy of different strategies of cobalamin uptake, focusing on the best dosages, media or foods, if reliable. Future research on the half-life of Cbl in various human body districts after the intake of different vitamin B12 supplements (H-Cbl, Ado-Cbl, Me-Cbl, Cn-Cbl) would be very useful in helping us understand Cbl utilization and needs, especially in vegetarians. At present, there is no international consensus for supplementation in vegetarians. According to Carmel, a single oral dose of 50 μg, 500 μg or 1000 μg will be absorbed at an amount of 1.5 μg, 9.7 μg or 13 μg, respectively [ 151 ]. To meet the daily requirement of Cbl, one oral dose of 50–100 μg daily or 2000 μg weekly divided into two oral cyanocobalamin doses could be sufficient to meet the needs of 2.4 μg/day for healthy vegetarian adults, taking into account the efficiency of absorption and the passive route. In 1988, Herbert stated that vegetarians’ Cbl requirements could be satisfied by 1 μg tablet of vitamin B12 per day, based on human reabsorption through enterohepatic circulation [ 32 ]. This quantity is fairly low in respect to the proposed values for Cbl Dietary Reference Intake (DRI) in the general population [ 19 20 ]. Cyanocobalamin is the most economical—and historically the most used form—rendering it suitable for safe daily use [ 45 ]. There were no apparent substantial differences between the absorption of sublingual and oral forms [ 152 206 ]. However, oral dissolution could be critical in the secretion of the salivary R-binder and its subsequent bond. Since the Cbl would not be dissolved, about 88% could be not absorbed [ 54 ]. Since the development of a Cbl deficiency can also be observed among the LOV, the use of a supplement is necessary, regardless of the type of vegetarian diet [ 110 ]. In cases of malabsorption, such as hypochlorhydria or functional deficit, such amounts might be insufficient [ 151 207 ]. With senescence, the lowering of gastric secretion reduces the direct absorption capacities due to reduced release of IF and the impairment of active transport, but not of the passive transport. At the same time, the natural gastric barrier decreases with consequent risk of gastrointestinal bacterial overgrowth and competing for the use of ingested Cbl [ 69 ]. If rare genetic defects of cellular trafficking and processing proteins exist, the choice of alternative forms of Cbl, such as Me-Cbl or H-Cbl could improve the effectiveness of supplementation [ 154 210 ]. It was speculated that the use of Cn-Cbl is unsuitable for supplementation among smokers, because it represents a form preferentially excreted for the purpose of hydrocyanic acid removal [ 211 212 ]. In these cases, the use of H-Cbl may be desirable, although it is yet to be confirmed [ 213 214 ]. The data currently available do not permit an estimate of a maximum intake level for cobalamin. High levels of administration in particular lead to rare adverse events, mostly dermatological, such as pruritus, rash and skin eruptions [ 215 ]. The sufficiency of bodily stocks should not be a reason to delay supplementation, in light of the fact that the manifestation of the deficiency can occur through often irreversible neurological signs. The current data do not support the theory that vitamin deficiency needs 20–30 years to be manifested [ 125 ]. Nevertheless, future studies should take into account the possibility of supplementation even in a subclinical condition, as was already done for other deficiencies [ 216 217 ], which may become overt during the time-period [ 218 219 ]. The use of multiple diagnostic markers can facilitate the correct assessment of the status and allow a more sound decision in relation to the administration plan. The habit of using only one or a few of the multiple markers available implies that the deficiency status of Cbl among vegetarians, as among omnivores, may have sometimes been underestimated. Moreover, cobalamin displays other functions, not strictly metabolic, that could be lacking when deficient. A vitamin B12 deficiency could be related to oxidative stress markers like plasma glutathione, malondialdehyde and serum total antioxidant capacity, which could contribute to a neurophysiological disturbance [ 220 ]. Furthermore, Cbl, particularly H-Cbl, can act as a detoxifying agent, removing potentially dangerous cyanide molecules from the body [ 212 ].