Vitamin B12 in Foods, Food Supplements, and Medicines—A Review of Its Role and Properties with a Focus on Its Stability

Abstract

Vitamin B12, also known as the anti-pernicious anemia factor, is an essential micronutrient totally dependent on dietary sources that is commonly integrated with food supplements. Four vitamin B12 forms—cyanocobalamin, hydroxocobalamin, 5′-deoxyadenosylcobalamin, and methylcobalamin—are currently used for supplementation and, here, we provide an overview of their biochemical role, bioavailability, and efficacy in different dosage forms. Since the effective quantity of vitamin B12 depends on the stability of the different forms, we further provide a review of their main reactivity and stability under exposure to various environmental factors (e.g., temperature, pH, light) and the presence of some typical interacting compounds (oxidants, reductants, and other water-soluble vitamins). Further, we explore how the manufacturing process and storage affect B12 stability in foods, food supplements, and medicines and provide a summary of the data published to date on the content-related quality of vitamin B12 products on the market. We also provide an overview of the approaches toward their stabilization, including minimization of the destabilizing factors, addition of proper stabilizers, or application of some (innovative) technological processes that could be implemented and contribute to the production of high-quality vitamin B12 products.

Determinants of vitamin B12 deficiency in patients with type-2 diabetes mellitus — A primary-care retrospective cohort study

“…There are however concerns with the healthfulness [ 70 – 74 ] of hawker foods; many are high in fat, sodium and carbohydrates, while being low in dietary fibre [ 75 – 77 ]. Hawker food preparation—often involving high heat, gravy or soups— could lead to B12-folate thermal degradation, or these water-soluble vitamins’ leaching into the cooking water respectively [ 78 , 79 ]. Nevertheless, these concerns are often outweighed by hawker foods’ convenience and affordability [ 71 ].…”

Effects of redox active agents on cyanocobalamin stability in heated milk

“…In fact, thiol/Cbl interactions have been researched and described to the extent that a possible pathway of CN‐B12 decomposition in the heated non‐fat milk may be outlined as follows: (a) the heat‐induced exposure of cysteine thiol groups (by protein unfolding and by cystine disulphide cleavage) enables thiolate complexation with CN‐B12(III) [where the complex is CysCN‐B12(III)], (b) hydrolysis of CysCN‐B12(III) yields CN‐B12(II) and cystine disulphide (Dereven'kov et al ., 2016), (c) CN‐B12(II) is oxidized (by O 2 in aerobic media) to OH‐B12(III) (Ansari et al ., 2004; Schnellbaecher et al ., 2019) and (d) OH‐B12(III) is irreversibly oxidized by H 2 O 2 (and/or other ROS) to biologically inactive oxidation products (Ahmad & Hussain, 1993; Ansari et al ., 2004; Monajjemzadeh et al ., 2014; Schnellbaecher et al ., 2019; Rakusa et al ., 2023), which include stable yellow corrinoids (“SYCs”, hydroxylated, chromophore‐altered derivatives of B12) (Salnikov et al ., 2021). The participants in this hypothesized pathway are CN‐B12, (heat‐exposed) cysteine, O 2 and transition metal‐generated H 2 O 2 , such that the pathway may be expected to proceed in B12‐fortified foods that contain cysteine (free or protein‐bound) and transition metals, when heated in the presence of O 2 at neutral or alkaline pH (foods that include the non‐fat milk evaluated in the present study).…”

“…CN‐B12 loss in fortified, extruded rice was found to increase linearly ( R 2 = 0.975) from 23% to 64% over the temperature range 126–180 °C, and extensive losses of B12 (30%–100%) have been reported for milk sterilized at 110–115 °C for 20–40 min, for baked bread, for cooked beef and herring, for UHT milk stored for 20 weeks at 24 °C, for wheat flour stored in paper bags at 25 °C and 65% relative humidity for 1.5 M, and for multivitamin (with B1 = B6 >> B12) parenteral solutions stored at 25–28 °C for 12 M and at 40 °C for 9 weeks. By contrast, no significant B12 loss occurred in pasteurized milk, in cooked vacuum‐packed herring, or in wheat flour packaged in moisture/oxygen impermeable multilayer PET/aluminium bags, only minor losses of CN‐B12 losses were reported for extrusion at 91–95 °C (3%) and for boiled (100 °C) CN‐B12 fortified rice (11%), and CN‐B12 recoveries were ≥95% in single vitamin (B12 only) parenteral solutions stored at 25–28 °C for 12 M and at 40 °C for 9 weeks (Rolls & Porter, 1973; Bennink & Ono, 1982; Oamen et al ., 1989; Andersson & Oeste, 1992; Ahmad & Hussain, 1993; Watanabe et al ., 1998; Czernichow et al ., 2003; Riaz et al ., 2009; Nishioka et al ., 2011; Monajjemzadeh et al ., 2014; Wieringa et al ., 2014; Gille & Schmid, 2015; Edelmann et al ., 2016; Bajaj & Singhal, 2019; Hemery et al ., 2020; Rakusa et al ., 2023). The results of these and related studies have implicated temperature, time, oxygen, redox active agents (including ascorbic acid, thiols, polyphenols, bisulphite, ferrous salts and hydrogen peroxide), other vitamins (B1, B2, B3 and B6), pH and light as potentially significant contributors to B12 decomposition (Schnellbaecher et al ., 2019; Rakusa et al ., 2023).…”

“…Among the twenty‐eight nutrients assigned U.S. Food and Drug Administration (USFDA) Reference Daily Intake (RDI) values, vitamin B12 (B12) has the lowest quantities, ranging from 0.5 μg for infants to 2.8 μg for pregnant and lactating women (USFDA, 2016). Despite these low amounts (0.4–2.1 nanomoles/day), it has been estimated that 6% of humans are B12 deficient and therefore vulnerable to consequent haematological, neurological, cognitive, immunological and inflammatory disorders (Allen et al ., 2010; Azzini et al ., 2021; Vincenti et al ., 2021; Rakusa et al ., 2023). Regarded as the highest risk for B12 deficiency are the elderly (decreased digestibility), breastfed infants of B12‐deficient mothers, individuals with gastrointestinal problems resulting in B12 malabsorption and vegans (since B12 occurs naturally only in animal‐derived foods, most notably meat, fish, eggs and milk) (Lamers, 2022; Rakusa et al ., 2023).…”

Nutritional Assessment of the Symptomatic Patient on a Plant-Based Diet: Seven Key Questions

“…Cyanide-stabilized cobalamin, cyanocobalamin, is the most common B12 supplement [ 50 , 57 , 58 , 59 ]. Cyanocobalamin releases a cyanide group for every molecule of B12 that is used.…”