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Vitamin B12: Oral Supplements More Effective Than Injections?

Vitamin B12: Oral Supplements More Effective Than Injections?

Vitamin B12 is an unusual nutrient. It is needed in much smaller amounts than most other known vitamins, and is the only vitamin that can’t be reliably supplied by a varied wholefood plant-based diet and regular exposure to the sun.

Here we take a closer look at this elusive nutrient; where it comes from and why you need it. We also delve deeper into the reasons why so many people aren’t getting enough, the warning signs that you might be running low and the best way to correct a deficiency.

What Does Vitamin B12 Do?
Vitamin B12 (cobalamin) is needed for well over 100 crucial daily functions, including:
• Helps the blood carry oxygen
• Formation of normal red blood cells
• Helps your body to make use of protein and fats
• Energy production
• DNA synthesis
• Methylation co-factor
• Homocysteine metabolism
• Essential for healthy nerves
• Helps your body to deal with toxins
• Foetal development during pregnancy

Where Does Vitamin B12 Come From?
Just like all the other B vitamins, B12 is water-soluble and needs to be regularly supplied by your diet. Unlike the other B vitamins though, B12 is found in rich supply in animal products such as grass-fed beef, dairy products, eggs and fish. This is why vegetarians and strict vegans in particular, are at high risk of deficiency.

How is Vitamin B12 Absorbed?
1. Vitamin B12 enters the body attached to amino acids in protein foods.
2. When it comes into contact with stomach acid, this bond is broken, and B12 can then be absorbed into the system with the help of intrinsic factor.
3. Intrinsic factor is a protein secreted by the cells of the stomach lining. It attaches to unbound B12 and takes it to the intestines to be absorbed.

To Achieve Optimal B12 You Need:
• Dietary sources (animal foods, fortified foods or supplements)
• Stomach acid
• Intrinsic factor

Best Food Sources of B12
• Grass-fed beef
• Lamb
• Dairy products
• Eggs
• Oysters
• Sardines
• Tuna
• Turkey
• Chicken

Who’s Most at Risk of Deficiency?
• Vegans / Vegetarians
• Anyone regularly taking stomach-acid reducing medications (antacids, H2 receptor antagonists, proton pump inhibitors)
• Anyone with low stomach acid
• Frequent antibiotic use
• Anyone taking metformin (oral diabetes medicine that helps to control blood sugar levels)
• Elderly people (stomach acid production tends to reduce with age)
• Smokers (nicotine can block absorption)
• Alcoholics
• 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
• Atrophic gastritis – thinning of stomach lining affects intrinsic factor production
• Pernicious anaemia – autoimmune condition affecting intrinsic factor production
• Overgrowth of intestinal bacteria
• Parasites

Symptoms of B12 Deficiency
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, it’s worth a quick trip to your GP for further investigation, especially if you’re at higher risk because of your age 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 range1. The good news is that it’s relatively easy to correct once it has been identified.

How To Correct B12 Deficiency – Supplements or Injections?
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, there is a common misconception that intramuscular injections which bypass the need for both of these, are 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:
1. Pain - Intramuscular injections can cause significant pain (especially in people who are very slim) and oral supplements are pain-free.
2. Adverse reactions - Whilst serious adverse reactions are rare, injections can be dangerous in those taking blood thinners (anti-coagulants). No adverse reactions of oral B12 supplementation have been reported.
3. 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.
4. Compliance – For most people, oral supplementation is an easier and more attractive prospect than regular intramuscular injections and this may increase compliance.

Research now shows that high doses of oral vitamin B12 (eg. 1000mcg daily) can be just as effective at treating deficiency, even in the absence of intrinsic factor, and may be a suitable alternative to intramuscular injections for many people.

What’s The Evidence?
• 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.2,3
• Several case control and case series studies have suggested that oral vitamin B12 has equal efficacy and safety as intramuscular vitamin B12.4-7
• 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.8
• 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.9,10
• 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.11 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.12 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.13
• 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.14

What’s The Best Form To Take?
Vitamin B12 is best supplemented in the form of methylcobalamin as this is a superior, activated, body-ready form of vitamin B12.

Choose High Dose Oral Supplementation to increase Vitamin B12
Evidence suggests that high dose oral supplementation at 1000mcg is an effective strategy to increase vitamin B12 in those with deficiency. In addition, oral supplementation is associated with significant cost saving, no side effects and increased compliance, compared to intramuscular injections.

References:
1. Vashi P, Edwin P et al. Methylmalonic acid and homocysteine as indicators of vitamin B12 deficiency in cancer. PLOS One January 25, 2016. https://doi.org/10.1371/journal.pone.0147843
2. 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.
3. 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.
4. Andres E, Fothergill H,MeciliM. Efficacy of oral cobalamin (vitamin B12) therapy. Expert Opinion on Pharmacotherapy 2010;11(2):249–56.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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,
10. Andrès E, Loukili EH, Noel E et al. Vitamin B12 (cobalamin) deficiency in elderly patients CMAJ 2004;171(3):251-9
11. Nyholm E, Turpin P, Swain D, et al Oral vitamin B12 can change our practice. Postgraduate Medical Journal 2003;79:218-219.
12. 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-
13. 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
14. 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