Vitamin B12: What You Need To Know

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Vitamin B12 is a vitally important water-soluble nutrient that needs to be consumed regularly in the diet. Vitamin B12 is found in animal foods so anyone following a vegan diet is at high risk of deficiency. Here we take a closer look at this essential nutrient; where it comes from and why you need it. We also delve deeper into the factors that increase risk of deficiency, signs that you might be running low and current research comparing the effectiveness of oral supplements and injections for correcting a deficiency.

What does vitamin B12 do?

Vitamin B12 has vital roles to play in many physiological functions that sit right at the very foundations of health. It is essential for supporting healthy blood and nerves, and for DNA synthesis too. Vitamin B12 is essential for:

• Helping the blood carry oxygen.
• Healthy red blood cell formation.
• Helping your body to make use of protein and fats.
• Cellular energy production.
• DNA synthesis.
• Methylation co-factor.
• Homocysteine metabolism.
• Healthy nerves.
• Foetal development during pregnancy.

Where does vitamin B12 come from?

Vitamin B12 is concentrated in animal tissues and is only found naturally in foods of animal origin. There are no naturally occurring bioactive sources of vitamin B12 from plant sources.¹ This is why those following a vegetarian or strict vegan diet in particular, are at high risk of deficiency. Foods that are naturally high in vitamin B12 include liver, beef, lamb, chicken, eggs, fish and dairy foods.

How is vitamin B12 absorbed?

1. Vitamin B12 enters the body attached to amino acids in protein foods such as beef and liver. However, it needs to be released before it can be absorbed.

2. The process of releasing B12 starts in the mouth when the protein foods are mixed with saliva. This process continues when they move into the stomach and come into contact with stomach acid. Vitamin B12 is finally freed following the action of digestive enzymes in the duodenum.

3. Only once the B12 is released can it then be absorbed into the system with the help of intrinsic factor. Intrinsic factor is a glycoprotein secreted by the cells of the stomach lining. It attaches to the unbound B12 and takes it to the intestines to be absorbed.

4. As you can see, vitamin B12 absorption is a complicated process and relies heavily on optimal digestive processes including saliva, stomach acid, digestive enzymes and intrinsic factor.

5. If vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and therefore does not require the separation step.

6. Vitamin B12 can also be absorbed by passive diffusion, however this process is known to be highly inefficient — estimates suggest that only around 1% to 2% of the oral vitamin B12 dose is absorbed passively.

Food sources of vitamin B12

• Beef.
• Lamb.
• Liver.
• Dairy products.
• Eggs.
• Seafood.
• Fish.
• Turkey.
• Chicken.

Vitamin B12 storage

Recommended needs of vitamin B12 for adults are around 1.5mcg per day. A typical Western diet containing animal foods is estimated to contain somewhere between 7-30 mcg / day of cobalamin, and it is likely that around 1-5 mcg of this will be absorbed and stored in the liver. Storage reserves of vitamin B12 are somewhere around 2-5 mg so symptoms of low B12 would not typically appear until 3-5 years after a pattern of low dietary intake (i.e. strict vegan diet without B12 supplementation) or poor absorption has been established.²

Factors that increase risk of B12 deficiency

• Vegan / Vegetarian diet.
• Stomach-acid reducing medications (antacids, H2 receptor antagonists, proton pump inhibitors).
• Low stomach acid.
• Frequent antibiotic use.
• Metformin (oral diabetes medicine that helps to control blood sugar levels).
• Ageing (stomach acid production tends to reduce with age).
• Smoking (nicotine can block absorption).
• Alcoholism.
• Digestive disorders such as Crohn’s or coeliac disease.
• Stomach ulcers.
• Weight loss surgery / any other operation where part of the stomach or small intestine is removed.
• Food-bound vitamin B12 malabsorption.
• Atrophic gastritis – thinning of stomach lining affects intrinsic factor production.
• Pernicious anaemia – autoimmune condition affecting intrinsic factor production.
• Bacterial overgrowth.
• Parasites.
• Helicobacter Pylori infection.
• And more.

Symptoms of B12 deficiency

Vitamin B12 deficiency is a common but serious condition. A mild deficiency may not cause any symptoms. Symptoms tend to develop slowly and may not be recognised immediately. Initial signs of low B12 may include slightly elevated homocysteine (HC) and methylmalonic acid (MMA) levels.

As the problem worsens, symptoms can include:

• Low energy.
• Chronic fatigue.
• Weakness.
• Lightheadedness.
• Heart palpitations and shortness of breath.
• Pale skin.
• Poor dental health including bleeding gums and mouth sores.
• Sore red tongue.
• Yellowing of the skin.
• Mouth ulcers.
• Constipation, diarrhoea, nausea, loss of appetite, or gas.
• Nerve problems like numbness or tingling, muscle weakness, and problems walking.
• Joint pain.
• Vision loss.
• Mental problems like depression, memory loss, or behavioural changes.
• Poor concentration.
• Severe vitamin B12 deficiency can cause serious clinical symptoms such as megaloblastic anaemia, paralysis, dementia, fatigue, and mood disturbance. If left untreated, serious neurological and neuropsychiatric complications can occur. Vitamin B12 deficiency has also been linked with an increased risk of myocardial infarction and stroke.

What to do if you suspect deficiency?

Signs of B12 deficiency, especially the more common ones such as low energy and constipation, can be symptomatic of so many different health problems that low B12 can often be difficult to spot. It is however, an incredibly important nutrient and crucial that you keep your levels within a healthy range. If you are even slightly concerned that you might be low, first port of call is a trip to your GP for further investigation, especially if you’re at higher risk because of your age, diet or other factors such as taking antacids or gastrointestinal problems that affect absorption. Vitamin B12 levels are usually tested with a simple blood test. Test results can be inaccurate however since large amounts of B12 are stored in the liver. Also, taking large amounts of folic acid can mask a B12 deficiency so this also needs to be taken into account. It has been suggested that 50% of patients with diseases related to B12 deficiency have normal B12 levels when tested.

If you suspect a deficiency, but tests have come back normal, secondary tests such as checking your homocysteine (HC) and / or methylmalonic acid (MMA) levels can be useful. A deficiency of B12 at the tissue level can lead to elevation of both MMA and HC even when serum vitamin B12 is found within the reference range.³ The good news is that it’s relatively easy to correct once it has been identified.

How to correct B12 deficiency

As you can see above, with the long list of factors which increase deficiency risk, there can be a wide variety of reasons underlying vitamin B12 deficiency. It is crucial therefore for a healthcare provider to determine the cause of deficiency as this will influence the most effective course of treatment and preventative action moving forward.

Prevalent causes of vitamin B12 deficiency are pernicious anaemia (autoimmune condition that affects intrinsic factor production) and food-bound vitamin B12 malabsorption; both of which are associated with atrophic gastritis (chronic inflammatory disease of the stomach).

Plant-based diets (without regular B12 supplementation) are a significant risk factor for vitamin B12 deficiency as is ageing – vitamin B12 malabsorption and vitamin B12 deficiency are more common in older adults. And in fact, it’s because of this increased risk that the Linus Pauling Institute now recommends that all adults older than 50 years take supplemental vitamin B12 daily.⁴

Vitamin B12 intramuscular injections or supplements?

Deficiency is treated either with intramuscular injections or oral supplements and with proper treatment, symptoms of B12 deficiency usually begin to improve in days.

Since vitamin B12 requires both stomach acid and intrinsic factor to be absorbed, intramuscular injections which bypass the need for both of these, were once considered to be the only way to treat deficiency, especially for people with autoimmune pernicious anaemia who don’t produce intrinsic factor.

There are however, several problems with intramuscular injections:

Pain

Intramuscular injections can cause significant pain (especially in people who are very slim). In contrast, oral supplements are pain-free.

Adverse reactions

Whilst serious adverse reactions are rare, injections can be dangerous in those taking blood thinners (anti-coagulants). Oral B12 supplements are not associated with these effects.

Cost

Intramuscular injections are a ‘considerable source of work’ for healthcare professionals, mainly GPs and community nurses. There is little difference in the cost of oral versus intramuscular therapy when the medication alone is considered. However, intramuscular administration often involves a special trip to a health facility or a home visit by a health professional to administer the injection. Oral treatment could therefore save considerable health service resources.

Compliance

For most people, oral supplementation is an easier and more attractive prospect than regular intramuscular injections and this may increase compliance.

In fact, research is now beginning to suggest that high doses of oral vitamin B12 (eg. 1000mcg daily) may be as effective at treating deficiency, even in the absence of intrinsic factor, and may be a suitable alternative to intramuscular injections for many people.

Supplement forms of vitamin B12

Vitamin B12 contains the mineral cobalt, so any compounds with B12 activity are collectively called cobalamins. Vitamin B12 can be supplemented in forms including cyanocobalamin, adenosylcobalamin, methylcobalamin and hydroxycobalamin. Vitamin B12 is also widely available in sublingual preparations as tablets or lozenges.

Vitamin B12 supplements & injections – what’s the latest research?

• A Cochrane Review published in 2005 and updated in 2018, comparing oral with intramuscular vitamin B12, suggested that high doses of oral vitamin B12 may be as effective as intramuscular administration in obtaining short-term haematological and neurological responses in vitamin B12-deficient people.^5,6

• Several case control and case series studies have suggested that oral vitamin B12 has equal efficacy and safety as intramuscular vitamin B12.^7-10

• Kuzminski et al. demonstrated that 2mg of orally administered cyanocobalamin daily was as effective as 1mg administered intramuscularly on a monthly basis and suggested it to possibly be superior.¹¹

• Two additional systematic reviews, have found oral (1,000-2000mcg) vitamin B12 to have similar effectiveness to intramuscular injections for treatment of vitamin B12 deficiency.^12,13

• A UK study investigated the effectiveness, safety and acceptability of oral vitamin B12 as a replacement therapy in patients with vitamin B12 deficiency in a city general practice population.¹⁴ Patients previously maintained on vitamin B12 injections were given 1000mcg of oral cobalamin daily for up to 12 months. All patients maintained satisfactory serum B12 levels and showed normal haematology and neurology. Compliance and acceptability was reported to be excellent.

• A Canadian qualitative and quantitative assessment of patient perspectives of oral vitamin B12 therapy in primary care concluded switching patients from injection to be both feasible and acceptable to patients.¹⁵ As a result of increased convenience, the authors recommended clinicians should offer oral B12 therapy to patients who are currently receiving injections, as well as newly diagnosed vitamin B12 deficient patients who can tolerate and are compliant with oral medications. Other authors similarly conclude supplementation is a route that best meets patient’s lifestyles which tends to make them more compliant.¹⁶

• These observations have resulted in a review of preventative strategies and key recommendations relating to vitamin B12 deficiency in patients undergoing bariatric surgery, which recommended that high dose oral cyanocobalamin should be given consideration especially where there are compliance concerns relating to intramuscular therapy or where compliance becomes a problem in asymptomatic patients with vitamin B12 deficiency.¹⁷

• In a 2020 randomised controlled trial published in BMJ Open researchers investigated the effects of oral versus intramuscular (IM) administration of vitamin B12 in 283 patients over 65 years old with vitamin B12 deficiency. Patients were followed up at 8, 26 and 52 weeks. At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm. Quality of life and adverse events were comparable across groups. 83.4% of patients preferred the oral route. The researchers concluded that “oral administration of vitamin B12 in patients older than 65 years is probably as effective as IM administration, and it also lacks adverse events and is preferred by patients”.¹⁸

• Whilst more research is needed to fully determine whether high dose supplementation is as effective as intramuscular injections, the research to date certainly looks promising.

References:
1. O’Leary F, Samman S. Vitamin B12 in Health and Disease. Nutrients 2010 Mar; 2(3): 299-316.
2. Hunt A, Harrington D, et al. Vitamin B12 deficiency. Clinical Review. BMJ 2014; 349: g5226.
3. Vashi P, Edwin P et al. Methylmalonic acid and homocysteine as indicators of vitamin B12 deficiency in cancer. PLOS One January 25, 2016.
4. https://lpi.oregonstate.edu/mic/vitamins/vitamin-B12
5. Vidal-Alaball J, Butler CC, Cannings-John R, Goringe A, Hood K, McCaddon A, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews 2005, Issue 3.DOI: 10.1002/14651858.CD004655.pub2Wang H, Li L, Qin LL, Song Y, Vidal-Alaball J, Liu TH.
6. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews 2018, Issue 3. Art. No.: CD004655. DOI: 10.1002/14651858.CD004655.pub3.
7. Andres E, Fothergill H,MeciliM. Efficacy of oral cobalamin (vitamin B12) therapy. Expert Opinion on Pharmacotherapy 2010;11(2):249–56.
8. Bahadir A, Reis PG, Erduran E. Oral vitamin B12 treatment is effective for children with nutritional vitamin B12 deficiency. Journal of Paediatrics and Child Health 2014;50 (9):721–5.
9. Bolaman Z, Kadikoylu G, Yukselen V, Yavasoglu I, Barutca S, Senturk T. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Clinical Therapeutics 2003; 25(12):3124–34.
10. Castelli MC, Friedman K, Sherry J, Brazzillo K, Genoble L, Bhargava P, et al. Comparing the efficacy and tolerability of a new daily oral vitamin B12 formulation and intermittent intramuscular vitamin B12 in normalizing low cobalamin levels: a randomized, open-label, parallel-group study. Clinical Therapeutics 2011; 33:358–71.
11. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood 1998;92(4):1191–8.
12. Butler CC, Vidal-Alaball J, Cannings-John R, et al; Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials, Family Practice, 2006; 23, 279–285.
13. Andrès E, Loukili EH, Noel E et al. Vitamin B12 (cobalamin) deficiency in elderly patients CMAJ 2004;171(3):251-9.
14. Nyholm E, Turpin P, Swain D, et al Oral vitamin B12 can change our practice. Postgraduate Medical Journal 2003;79:218-219.
15. Kwong JC, Carr D et al Oral vitamin B12 therapy in the primary care setting: a qualitative and quantitative study of patient perspectives BMC Family Practice 2005, 6:8 doi:10.1186/1471-2296-6.
16. Mozo C, Berry L, Webb S et al Patient selection of vitamin B12 (cyanocobalamin) administration route and how this affects outcomes and compliance. Surgery for Obesity and Related Diseases , 2006 Volume 2 , Issue 3 , 323 P41.
17. Majumder S, Soriano J, Cruz AL Vitamin B12 deficiency in patients undergoing bariatric surgery: Preventive strategies and key recommendations Surgery for Obesity and Related Diseases 2013;9; 1013-1019.

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