This can be a reality sheet meant for well being professionals. For a reader-friendly overview of Vitamin B12, see our shopper reality sheet on Vitamin B12.
COVID-19
Introduction
Vitamin B12 is a water-soluble vitamin that’s naturally current in some meals, added to others, and out there as a dietary complement and a prescription treatment. As a result of vitamin B12 accommodates the mineral cobalt, compounds with vitamin B12 exercise are collectively referred to as “cobalamins” [1]. Methylcobalamin and 5-deoxyadenosylcobalamin are the metabolically energetic types of vitamin B12. Nonetheless, two others kinds, hydroxycobalamin and cyanocobalamin, change into biologically energetic after they’re transformed to methylcobalamin or 5-deoxyadenosylcobalamin [1-3].
Vitamin B12 is required for the event, myelination, and performance of the central nervous system; wholesome crimson blood cell formation; and DNA synthesis [1,4,5]. Vitamin B12 capabilities as a cofactor for 2 enzymes, methionine synthase and L-methylmalonyl-CoA mutase [1-3,5]. Methionine synthase catalyzes the conversion of homocysteine to the important amino acid methionine [1,2]. Methionine is required for the formation of S-adenosylmethionine, a common methyl donor for nearly 100 totally different substrates, together with DNA, RNA, proteins, and lipids [3,5]. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA within the metabolism of propionate, a short-chain fatty acid [2].
Vitamin B12 is certain to protein in meals and have to be launched earlier than it’s absorbed [5]. The method begins within the mouth when meals is combined with saliva. The freed vitamin B12 then binds with haptocorrin, a cobalamin-binding protein within the saliva. Extra vitamin B12 is launched from its meals matrix by the exercise of hydrochloric acid and gastric protease within the abdomen, the place it then binds to haptocorrin [1]. Within the duodenum, digestive enzymes free the vitamin B12 from haptocorrin, and this freed vitamin B12 combines with intrinsic issue, a transport and supply binding protein secreted by the abdomen’s parietal cells. The ensuing complicated is absorbed within the distal ileum by receptor-mediated endocytosis [1,5]. If vitamin B12 is added to fortified meals and dietary dietary supplements, it’s already in free kind and subsequently doesn’t require the separation step.
Vitamin B12 standing is usually assessed by measurements of serum or plasma vitamin B12 ranges. The cutoff between regular vitamin B12 ranges and deficiency varies by technique and laboratory, however most laboratories outline subnormal serum or plasma values as these decrease than 200 or 250 pg/mL (148 or 185 pmol/L) [2]. Ranges of serum methylmalonic acid (MMA), a vitamin B12-associated metabolite, are probably the most delicate markers of vitamin B12 standing, and an MMA stage better than 0.271 micromol/L suggests vitamin B12 deficiency [6-8]. Nonetheless, MMA ranges additionally rise with renal insufficiency and are typically increased in older adults [6,9,10]. One other marker is complete plasma homocysteine ranges, which rise shortly as vitamin B12 standing declines; a serum homocysteine stage increased than 15 micromol/L, for instance, suggests vitamin B12 deficiency [11]. Nonetheless, this indicator has poor specificity as a result of it’s influenced by different components, similar to low folate ranges and, particularly, by declines in kidney operate [6]. Specialists counsel that if a affected person’s serum vitamin B12 stage is lower than 150 pg/ml (111 pmol/L), the affected person’s serum MMA ranges must be checked to substantiate a analysis of vitamin B12 deficiency [7,9].
Really useful Intakes
Consumption suggestions for vitamin B12 and different vitamins are offered within the Dietary Reference Intakes (DRIs) developed by the Meals and Vitamin Board (FNB) on the Nationwide Academies of Sciences, Engineering, and Medication [1]. DRI is the overall time period for a set of reference values used for planning and assessing nutrient intakes of wholesome folks. These values, which fluctuate by age and intercourse, embrace:
Desk 1 lists the present RDAs for vitamin B12 [1]. For adults, the primary criterion that the FNB used to determine the RDAs was the quantity wanted to keep up a wholesome hematological standing and serum vitamin B12 ranges. For infants aged 0 to 12 months, the FNB established an AI that’s equal to the imply consumption of vitamin B12 in wholesome, breastfed infants.
* Ample Consumption (AI)
Sources of Vitamin B12 – “b vitamin absorption”
Meals
Vitamin B12 is of course current in meals of animal origin, together with fish, meat, poultry, eggs, and dairy merchandise [5]. As well as, fortified breakfast cereals and fortified dietary yeasts are available sources of vitamin B12 which have excessive bioavailability [12,13].
The common vitamin B12 stage within the breast milk of ladies with vitamin B12 intakes above the RDA is 0.44 mcg/L [14]. The U.S. Meals and Drug Administration specifies that toddler formulation offered in america should present at the least 0.15 mcg vitamin B12 per 100 kcal [15].
The estimated bioavailability of vitamin B12 from meals varies by vitamin B12 dose as a result of absorption decreases drastically when the capability of intrinsic issue is exceeded (at 1–2 mcg of vitamin B12) [16]. Bioavailability additionally varies by kind of meals supply. For instance, the bioavailability of vitamin B12 seems to be about thrice increased in dairy merchandise than in meat, fish, and poultry, and the bioavailability of vitamin B12 from dietary dietary supplements is about 50% increased than that from meals sources [17-19].
A wide range of meals and their vitamin B12 ranges per serving are listed in Desk 2.
*DV = Each day Worth. The U.S. Meals and Drug Administration (FDA) developed DVs to assist shoppers evaluate the nutrient contents of meals and dietary dietary supplements inside the context of a complete food regimen. The DV for vitamin B12 is 2.4 mcg for adults and kids aged 4 years and older [21]. FDA doesn’t require meals labels to record vitamin B12 content material except vitamin B12 has been added to the meals. Meals offering 20% or extra of the DV are thought of to be excessive sources of a nutrient, however meals offering decrease percentages of the DV additionally contribute to a healthful food regimen.
The U.S. Division of Agriculture’s FoodData Central [20] lists the nutrient content material of many meals and supplies a complete record of meals containing vitamin B12 organized by nutrient content material and by meals identify.
Dietary dietary supplements
Vitamin B12 is obtainable in multivitamin/mineral dietary supplements, in dietary supplements containing different B-complex nutritional vitamins, and in dietary supplements containing solely vitamin B12. Multivitamin/mineral dietary supplements sometimes include vitamin B12 at doses starting from 5 to 25 mcg [22]. Vitamin B12 ranges are increased, usually 50–500 mcg, in dietary supplements containing vitamin B12 with different B-complex nutritional vitamins and even increased, sometimes 500–1,000 mcg, in dietary supplements containing solely vitamin B12.
The commonest type of vitamin B12 in dietary dietary supplements is cyanocobalamin [1,3,22,23]. Different types of vitamin B12 in dietary supplements are adenosylcobalamin, methylcobalamin, and hydroxycobalamin [22].
No proof signifies that absorption charges of vitamin B12 in dietary supplements fluctuate by type of the vitamin. These charges are about 50% at doses (lower than 1–2 mcg) that don’t exceed the cobalamin-binding capability of intrinsic issue and are considerably decrease at doses nicely above 1–2 mcg [23,24]. For instance, absorption is barely about 2% at doses of 500 mcg and 1.3% at doses of 1,000 mcg [24].
Along with oral dietary dietary supplements, vitamin B12 is obtainable in sublingual preparations as tablets or lozenges [22]. Proof suggests no distinction in efficacy between oral and sublingual kinds [25,26].
Prescription medicines
Vitamin B12, within the types of cyanocobalamin and hydroxycobalamin, could be administered parenterally as a prescription treatment, normally by intramuscular injection [2]. Parenteral administration is usually used to deal with vitamin B12 deficiency attributable to pernicious anemia in addition to different circumstances (e.g., tropical sprue, pancreatic insufficiency) that end in vitamin B12 malabsorption and extreme vitamin B12 deficiency [5].
Vitamin B12 can also be out there as a prescription nasal gel spray. This formulation seems to be efficient in elevating vitamin B12 blood ranges in adults and kids [27,28]. A small scientific examine with 10 contributors (imply age 81 years) discovered that the bioavailability of a 1,000 mcg cobalamin dose was 2% with intranasal administration, which has similarities to the bioavailability of an oral dose [29].
Vitamin B12 Intakes and Standing
Most individuals in america eat enough quantities of vitamin B12. Knowledge from the 2013–2016 Nationwide Well being and Vitamin Examination Survey (NHANES) present that solely 3% of U.S. males had intakes from meals and drinks beneath the EAR for vitamin B12 of two mcg, and the speed for ladies was 8% [30].
Common day by day intakes of vitamin B12 from meals are 5.94 mcg for males aged 20 and older and three.78 mcg for ladies [31]. For youngsters aged 2–19, imply day by day intakes of vitamin B12 from meals vary from 3.76 mcg to 4.55 mcg [31].
In response to an evaluation of NHANES information from 2015–2016, folks of low socioeconomic standing, ladies, and non-Hispanic Blacks are most definitely to have low vitamin B12 intakes [32]. In america and the UK, roughly 6% of adults youthful than 60 years have vitamin B12 deficiency, however the fee is nearer to twenty% in these older than 60 [33]. As well as, serum vitamin B12 ranges are likely to drop, generally to subnormal ranges, throughout being pregnant, however they normally return to regular after supply [34].
Roughly 24% of males and 29% of ladies reported utilizing a dietary complement containing vitamin B12 in NHANES 2017–2018 [31]. The proportion in kids ranged from 30% of these aged 2–5 years to 10% of adolescents aged 12–19. Imply vitamin B12 intakes amongst complement customers from each meals and dietary supplements have been 290.3 mcg for males aged 20 and older, 402.5 mcg for ladies, and from 26.6 to 36.0 mcg for youngsters.
Vitamin B12 Deficiency
Causes of vitamin B12 deficiency embrace issue absorbing vitamin B12 from meals, lack of intrinsic issue (e.g., due to pernicious anemia), surgical procedure within the gastrointestinal tract, extended use of sure medicines (e.g., metformin or proton pump inhibitors, mentioned in additional element beneath within the part on interactions with medicines), and dietary deficiency [5,7]. As a result of individuals who have issue absorbing vitamin B12 from meals take up free vitamin B12 usually, their vitamin B12 deficiency tends to be much less extreme than that of people with pernicious anemia, who can not take up both food-bound or free vitamin B12. Sure congenital circumstances, similar to hereditary intrinsic issue defects and congenital vitamin B12 malabsorption (Imerslund-Gräsbeck illness), may also trigger extreme vitamin B12 deficiency [5].
The consequences of vitamin B12 deficiency can embrace the hallmark megaloblastic anemia (characterised by massive, abnormally nucleated crimson blood cells) in addition to low counts of white and crimson blood cells, platelets, or a mix; glossitis of the tongue; fatigue; palpitations; pale pores and skin; dementia; weight reduction; and infertility [2,5,7]. Neurological adjustments, similar to numbness and tingling within the arms and toes, may also happen [7]. These neurological signs can happen with out anemia, so early analysis and intervention is essential to keep away from irreversible harm [35]. In pregnant and breastfeeding ladies, vitamin B12 deficiency may trigger neural tube defects, developmental delays, failure to thrive, and anemia in offspring [7].
As a result of the physique shops about 1 to five mg vitamin B12 (or about 1,000 to 2,000 instances as a lot as the quantity sometimes consumed in a day), the signs of vitamin B12 deficiency can take a number of years to seem [7,33].
Vitamin B12 deficiency with the traditional hematologic and neurologic indicators and signs is rare [11]. Nonetheless, low or marginal vitamin B12 standing (200–300 pg/mL [148–221 pmol/L]) with out these signs is far more widespread, at as much as 40% in Western populations, particularly in these with low intakes of vitamin B12-rich meals [9,11]. The prevalence of vitamin B12 deficiency varies by cutoff stage and biomarker used. For instance, amongst adults aged 19 and older who participated in NHANES between 1999 and 2004, the speed of low vitamin B12 ranges in serum was 3% with a cutoff of lower than 200 pg/mL (148 pmol/L) and 26% with a cutoff of lower than 350 pg/mL (258 pmol/L) [36]. Roughly 21% of adults older than 60 had irregular ranges of at the least one vitamin B12 biomarker [36].
Sometimes, vitamin B12 deficiency is handled with vitamin B12 injections, as a result of this technique bypasses any limitations to absorption. Nonetheless, excessive doses of oral vitamin B12 may additionally be efficient. A 2018 Cochrane evaluation included three randomized managed trials (RCTs) that in contrast very excessive doses (1,000–2,000 mcg) of oral with intramuscular vitamin B12 for vitamin B12 deficiency in a complete of 153 contributors [37]. The proof from these research, though of low high quality, confirmed that the power of excessive oral doses of vitamin B12 dietary supplements to normalize serum vitamin B12 was just like that of intramuscular vitamin B12.