Vitamin B12 Supplements

 

Vitamin B12 Supplements

Vitamin B12 supplements: which active ingredients are best? Dosages and forms. Vitamin B12 pills or injections? High dose B12 and the daily requirement.

Contents

  • What makes the ideal vitamin B12 supplement? Which factors should be carefully considered? 
  • Which vitamin B12 active ingredients are best?
  • What is the correct supplement dosage?
  • Which additives do vitamin B12 supplements contain? Are they vegan?
  • Vitamin B12 pills, drops or capsules – which form is superior?

Vitamin B12 Supplements: A Wide Selection

Whilst a balanced diet can ensure a good intake of vitamin B12, for those following a vegetarian/vegan diet or suffering from malabsorption, taking B12 supplements makes a lot of sense in order to avoid the consequences of vitamin B12 deficiency

However, with so many supplements on the market it is unsurprising that many consumers feel unclear about which is best. This page provides a comprehensive overview of B12 supplements to help you make the right choice.

Vitamin B12 Supplements: The Key Differences

In general, there are a multitude of benefits to ensuring a sufficient supply of vitamin B12 through supplements. Yet when it comes to actually selecting a product, there are many to choose from – each of which differ slightly and carry their own pros and cons. To make things simple, the B12 supplements currently available mainly differ in the following ways:

1. Active ingredient
Vitamin B12 exists in many forms: some are less and more effectively utilised in the body, and they each have particular advantages and disadvantages (see below). The most well known B12 forms are: methylcobalamin, hydroxocobalamin, adenosylcobalamin and cyanocobalamin.

Key point: where possible, look to purchase the natural B12 forms: hydroxocobalamin, adenosylcobalamin and methlycobalamin – ideally all 3 mixed together.

2. Dosage
Supplement dosages vary enormously, spanning from 10 µg until 5000 µg per dose – which are 3 x to 1600 x the recommended daily dosage, respectively. Both dosage levels are justified for different applications (see below).

Key point: neither very low, nor very high dosages are particularly useful. A good dosage for maintenance and preventing deficiency is 250-500 μg.

3. Type
Vitamin B12 comes in may forms e.g. capsules, pills, powder, lozenges, drops, oils, toothpaste and ampoules/injections. These vary only slightly in effect; the main differences are in application and composition.

Key point: capsules are the purest form. Injections are only required for those with severe deficiency.

4. Composition
Vitamin B12 can come as part of a B12 complex, multi-vitamin complex, or can be administered individually. Some supplements that only contain B12 can contain additives such as sweeteners, dyes and flavourings, which may have adverse health effects. We recommend pure supplements that contain no additives (see below).

Key point: where possible choose capsules, as almost no added ingredients are required. Always carefully check the ingredients of any supplements you consume. 

Summary: The Best Vitamin B12 Supplement

  • Active ingredient
    Oral: combination of all active forms 
    Injection: hydroxocobalamin
  • Dosage
    Oral (in regular cases): 250-500 µg/day
    Injection: 1000-1500 µg/week
  • Type
    Capsules, for those with difficulties swallowing: drops or spray
  • Composition
    As pure as possible, with natural ingredients

In the following we will illuminate all of these points in detail, giving tips for the application of B12 in different scenarios.

Vitamin B12 Active Ingredients

There are different forms of B12 (cobalamin) in supplements, each of which has a second chemical component bound to the actual B12 molecule. Which compound is used in the supplement, is acknowledged in the exact name of the active ingredient, which is always given on the packaging of good quality products. 

Particularly common is the synthetic B12 form – cyanocobalamin – as well as the natural forms hydroxocobalamin, adenosylcobalamin (5-deoxyadenosylcobalamin) and methylcobalamin.

Natural B12 food sources usually contain a mixture of the three natural forms, which are all needed by the body. Although the body can usually convert the different forms into each other – in our opinion, supplements which mix all three are ideal.

Here is a comparison of the 4 main active ingredients:

Cyanocobalamin
the “synthetic” B12

no

no

4

medium to poor

no own effect

Hydroxocobalamin
the “storable” B12

yes

no

3

very good

detoxifies cyanide and NO

Methylcobalamin
the “DNA and brain” B12

yes

yes

0

medium

DNA, brain, nerves, blood and detoxification

Adenosylcobalamin
the “energy and nerves” B12

yes

yes

0

medium

energy, nerves, muscles, brain and DNA

 Vitamin B12 Supplements and Active Ingredients

The main differences between the active ingredients found in supplements are clearly visible in the above table. To better understand these differences, let’s take a closer look at each of the forms. 

Cyanocobalamin

Cyanocobalamin is a synthetic substance that almost never naturally occurs. It consists of a combination of vitamin B12 and the toxin cyanide (hydrocyanic acid). Normally, cyanocobalamin is only found in cases of cyanide poisoning – the natural B12 binds to cyanide and is excreted as cyanocobalamin.

When large quantities of cyanocobalamin are artificially introduced into the body, one part is excreted and the other is broken down into B12 (cobalamin) and cyanide (hydrocyanic acid). Some people are severely allergic to cyanide, although the amount of cyanide ingested in supplements is extremely low. With well-functioning kidneys, the cyanide is for the most part excreted. On the other hand, people with kidney problems should generally avoid cyanocobalamin. Smokers should also choose a different active ingredient because they already have an increased cyanide intake (1).

Cyanocobalamin was created because it is very simple to synthetically produce and has good stability. In the USA, it was the most widely used agent in B12 supplements for a long time, and is still quite common today. Whilst high dosages of cyanocobalamin mostly produce good effects – it is increasingly replaced in supplements by other B12 forms, due to the above-named disadvantages. In the majority of guidelines for vitamin B12 treatment it is no longer used, as well as in the official recommendations of the World Health Organisation (WHO). Several researchers have even called for cyanocobalamin to be completely withdrawn from the market, as it is inferior in all respects to the other B12 forms (2, 3).

Hydroxocobalamin

Hydroxocobalamin is the form of B12 that is naturally produced by most bacteria. Whilst it has to be converted in the body into methylcobalamin and adenosylcobalamin; it has several advantages over cyanocobalamin in that it releases no toxins, is not excreted as quickly, is more readily available to the body, and is more storable – due to its improved ability to bind to protein. 

Today, hydroxocobalamin is the international standard of B12 supplements for injections and is also recommended by WHO as the ingredient of choice (4). In addition to B12 therapy after deficiency, high dose hydroxocobalamin is also used for detoxification because it binds to cyanide and nitride and transports them out of the body. The excretory product is cyanocobalamin.

Methylcobalamin and Adenosylcobalamin

These are the two biologically active forms of B12 that can be directly utilised by the body. Both cyanocobalamin and hydroxocobalamin need to be converted in the body into these coenzymes to be biologically available. Methylcobalamin is therefore often referred to as a “bio-identical” form of B12. In addition to their direct availability, methylcobalamin and adenosylcobalamin also have the advantage that they can be very well stored in the liver.

A Mix of all Natural Forms is Ideal 

The body needs both methyl- and adenosylcobalamin. The natural hydroxocobalamin also plays an important role in detoxification and provides a depot that lasts much longer in the blood than the more transient coenzyme forms.

In our opinion, the ideal active ingredient in B12 supplements is a mixture of the coenzyme forms, or even better of all three natural forms.

Vitamin B12 Supplement Dosage

The following table gives a breakdown of the dosage ranges used in the various applications of B12 supplements:

DosageApplicationRecommended for
Low dose 3-50 µgLow supplement in addition to the the dietary supply
Does not always cover daily requirement without other sources
 –
Medium dose 150-250 µgSupplements dietary supply
Covers daily requirement
Prevents deficiency

Vegans, vegetarians
Good absorption 
Good health 

Increased dose 300-500 µgCovers daily requirement
With increased need and absorption difficulties
In case of slight deficiency
Vegans, vegetarians
Unhealthy diets
Stress
Pregnant/breastfeeding mothers
Older people
Athletes and fitness enthusiasts 
Those who take medication 
Post-operation and disease
High dose 1000-3000 µgWith severe absorption disorders
Disease
Severe deficiency
Severe stomach symptoms
Chronic diseases
Anemia 
Megadose from 5000 µgFor high dose initial therapy  

For general use, the medium and high doses are the most appropriate options. In case of a severe deficiency, a high dose initial therapy is useful to refill the body’s stores. This can be done either through injections or very high dosage oral supplements (megadoses around 5000μg).

Absorption of Vitamin B12 in Supplements 

With a requirement of 2.4 μg, the dosage of many B12 supplements may seem overdosed at first. However, this impression is deceptive. Not all B12 contained in one dose is actually absorbed by the body.

When taken orally, the body can absorb a maximum of 1.5 μg per dose via intrinsic factor – no matter how high it is. Another 1% of the administered dose is taken via passive diffusion. To cover the requirement of 2.4 – 3 μg with a single dose, at least 100 – 150 μg must be taken. Alternatively, three smaller doses can be taken at long intervals throughout the day, to be absorbed via the intrinsic factor (3 x 5 μg would be appropriate). 

For people with suffering from malabsorption however, the intake of 1.5 μg of B12 through the intrinsic factor is often not possible. Plus, passive diffusion is often compromised in the body, due to a number of environmental/health factors. Here about 300 micrograms should be the absolute minimum maintenance dose – 500 micrograms is a sensible buffer to completely ensure that the daily requirement is met. 

High dose B12 of more than 1000 micrograms is a useful option if the body’s reserves are utterly depleted and if someone is experiencing severe deficiency symptoms. In such cases, not only the daily requirement needs to be covered, but also the body’s stores must be urgently refilled. 

Dosage of Vitamin B12 Pills and Capsules

As an overview once more, below are the rough quantities of B12 that are absorbed through oral supplements (pills, capsules) and other forms of one-off dosage. In this case only dosages above 100 μg can actually cover the daily requirement. For people with absorption disorders, the 1.5 μg of B12 absorbed with the intrinsic factor decreases and the values of passive diffusion apply.

10

1.5

0.1

1.6

30

1.5

0.3

1.8

50

1.5

0.5

2.0

100

1.5

1.0

2.5

500

1.5

5.0

6.5

1000

1.5

10.0

11.5

Supplements for Vitamin B12 Deficiency Treatment and Prevention 

Below is a description of the dosages applied in different instances of prevention and therapy.

1. Additional B12 intake to top up the dietary supply

If the diet contains sources of B12, which make a contribution yet are insufficient to meet the full daily requirements – e.g. vegetarian and vegan diets containing dairy and eggs/fortified foods – healthy individuals will need to take a small amount of B12 supplements. Under normal circumstances, such low doses of B12 may also be sufficient to prevent deficiency if health is absolutely optimal.

Oral supplements
(tablets, capsules)

low dose 3-50 µg/day
Injection

unnecessary 

2. Covering the daily requirement 

To cover the daily requirement (2.5 μg), it is worth taking oral supplements dosed significantly higher than the actual daily requirement – as described above. With three doses distributed throughout the day, intake via the intrinsic factor can however be optimised, so that a lower total intake is needed. 

If the daily requirement is to be covered through a single oral dose, the medium dose of B12 is 150-250 μg. This dose usually covers the needs of almost everyone. An increased dose of 300-500 μg is recommended if there is an increased need due to malabsorption, stress or illness.

Oral Supplements
(tablets, capsules)

3 x 3 – 5 µg/day or
1 x 150 – 250 µg/day (normal B12 need)
1 x 500 µg/day (increased B12 need)
Injection

Hydroxocobalamin: 1000 µg every 3-6 month
Cyanocobalamin: 100 µg every 2-3 weeks or 1000 µg/month

3. For diseases and malabsorption

In the case of absorption disorders, certain diseases and to refill the body B12 stores, high dose vitamin B12 is administered. 

If malabsorption is inhibiting the intake of B12 – fairly common due to mild inflammations of the gastrointestinal tract – high dosages of B12 must be taken (1000-2000 micrograms/day) as the body will only absorb a fraction of it. Simultaneously, an attempt should be made to find and eliminate the root cause of the disorder. 

With injections the same dosages apply as in the maintenance therapy, since through injection absorption disorders are bypassed.

For certain diseases, B12 therapy is used alongside other treatments. Here, too, high doses of the vitamin are usually administered. 

4. Initial therapy 

After discovering a serious deficiency, or after a long period of malnutrition, an initial therapy  with B12 is often undertaken to quickly replenish the body in a matter of days. Especially hydroxocobalamin has proven very successful here.

High dose B12 in initial therapy:

Oral supplements
(pills, capsules)

Hydroxocobalamin: 5000 µg /day for 4 weeks
Injections

Hydroxocobalamin: 4 weeks 1000 µg/week or 1-3 weeks 2 x 1000 µg/week
Cyanocobalamin: 5 -8 weeks 2 x 1000 µg/week

Further reading: Vitamin B12 Deficiency Treatment and Therapy

If you would like to check your vitamin B12 status, you can find more details on how to do so in our article: Vitamin B12 Deficiency Test

Vitamin B12 Forms

Vitamin B12 supplements exist in different forms. In addition to tablets, there are capsules, powders, nuggets, drops, syrup, toothpaste and ampoules/injection. 

Ultimately, fortified foods are to be regarded as a kind of supplement (details of which will not be discussed here). 

B12 in the form of oral supplements such as tablets and capsules are absorbed in the gut. They are the most common form of supplement for daily general use. Whilst absorption disorders located in the gut are often the cause of B12 deficiency; as described in more detail below – oral supplements are often just as effective here as injections, provided they are of a high enough dosage. 

Vitamin B12 Pills

B12 pills are undoubtedly the best-known form of supplement, although we also include dragées and similar forms in this category. One key difference is tablets for direct swallowing and those for sucking (lozenges), which we will address below. 

Tablets have a major disadvantage in that they often contain quite a few additives to ensure the desired shape, colour and taste. Some additives are believed to interfere with the breakdown of the tablet in the stomach or intestine; compromising the B12 intake.

Additionally, certain additives are under interrogation by consumer groups, suspected of having adverse health effects. 

Vitamin B12 Capsules

Capsules are much easier to make without additives – mostly only cellulose is needed – which is why they are often preferable to tablets. They are considered the purest and often most high quality form of supplement, especially popular with health-conscious consumers who want to avoid artificial additives.

People looking specifically for vegan vitamin B12 supplements should check the labels of both pills and capsules, as they may contain gelatine and/or lactose.

Sublingual Vitamin B12: Lozenges, Drops and Sprays

Due to our ability to absorb vitamin B12 sublingually via the oral mucosa – lozenges, drops and sprays make a lot of sense. Drops and sprays are more easily absorbed due to the fact that the B12 is already dissolved and they can be quickly swallowed. In contrast, lozenges have longer contact with the oral mucosa and release the vitamin slowly, which can also be quite beneficial. In the case of lozenges, however, the frequent use of additives such as sweeteners, colourants and flavours is a negative factor – drops and spray are often more natural.

It is difficult to compare sublingual and intestinal absorption as there is not yet enough data. What is certain however is that the sublingual route is at least as effective as the intestinal, making sublingual supplements a convenient alternative to tablets and capsules, especially for children and adults who have difficulty swallowing. 

Vitamin B12 Injections

For people with absorption disorders, B12 is traditionally administered via a weekly/monthly injection, using a dose of around 1000 µg. Mainly the active ingredients cyanocobalamin and hydroxycobalamin are available in injections, since adenosylcobalamin injections do not yet exist and methylcobalamin is rarely used. 

When does it make sense to undergo a B12 injection? The most obvious argument in favour of this form of intake is that, by bypassing the stomach and intestines, it is the surest way to absorb B12 in the instance of disorders. Even so, several studies have shown that high doses of orally administered B12 (~ 2000 μg/day) achieve the same effect, as 1% of the administered B12 is always absorbed via passive diffusion (5). Today, therapy with oral supplements is considered equivalent to injection (6). Although much higher amounts of B12 are used in the latter method, it eliminates the unpleasant experience of injection and possibly also the trip to the doctor.

On the other hand, because taking such high doses of oral supplements requires swallowing a lot of tablets or capsules, injections are still the best method for administering a B12 megadose to replenish the body’s store. Through a single injection with hydroxocobalamin about 700 micrograms are taken in, which circulates for quite a long time in the body. This could simply not be achieved through oral supplements. Plus, some individuals find injections at long intervals more practical – not to mention failsafe – than taking oral supplements every day. 

Vitamin B12 Toothpaste

One of the newest forms of supplement is B12-enriched toothpaste. In cooperation with the Vegetarian Federation (VEBU), Sante has developed a B12 toothpaste, which has proved its effectiveness in the first clinical trial at the University of Magdeburg. The active substance contained is cyanocobalamin. One gram of toothpaste contains about 100 micrograms of B12, so that when used twice a day, about 3.6 micrograms are absorbed – covering the daily requirement. This is a welcome addition to the supplement market, especially for vegans who want to cover their B12 intake through a combination of different sources. 

Vitamin B12 cream is also available. 

Vitamin B12 Supplement Composition

Ideally, vitamin B12 supplements should contain only the active ingredient/-s and, if required, a neutral carrier substance. Anything containing sweeteners (especially aspartame) are not recommended, as whilst they may make the intake more palatable; on the whole, they tend to carry more risks than benefits. Dyes are also completely unnecessary and should be avoided. What is more, a whole range of excipients are often used whose interactions with B12 are not yet sufficiently (if at all) researched. 

In our opinion, the purity of the supplement usually gives an indication of the general quality of the product; reputable suppliers tend to refrain from adding sweeteners and other meaningless ingredients. 

Vegans should always double-check that supplements do not contain animal ingredients such as lactose or gelatine.

Vitamin B Complex

All of the B vitamins are highly dependent on each other, when it comes to how they work in the body: they complement and strengthen each other, are involved in the production of different enzymes, and each provide a building block for a number of important and related metabolic processes. Every B vitamin should therefore be supplied in the sufficient quantity; an approximate balance should be maintained.

From this point of view, taking a vitamin B complex seems highly useful and effective. In particular, the combination of B12 and folic acid is very popular, given that these vitamins are so highly dependent on each other.

However, multivitamin supplements remain controversial. Some experts believe that the synthetically-produced vitamins do not work like their natural counterparts, in many cases (7). In such supplements, as described above in the case of B12, vitamins may be present in various forms that do not necessarily correspond to their natural form, having different effects on the body. In natural foods, vitamins are never found in a pure synthetic forms, but are incorporated into different molecules. They are also supplemented by a large number of other substances, such as minerals and trace elements. Many nutritionists thus believe that a vitamin intake through natural foods is preferential to an intake of synthetic substances. If vitamins are added artificially, care should be taken to ensure that they are in the most bio-identical form possible.

The other B group vitamins are much easier to obtain from foods than B12 – they are also abundant in plant-based produce. It can be argued, therefore, that it is much more useful to only take B12, obtaining the other B vitamins and folic acid through the diet. Many B vitamins are found in foods such as: wheat germ, yeast, nuts, rice, fruits, pulses and spinach.

Despite these considerations, there are some very good vitamin B complexes on the market.

Vitamin B12 Overdose

An overdose of B12 is almost impossible. If a very large amount is taken, most of it is simply excreted with the urine. No toxic effects have been documented, which is why no upper limit for dosage has been given. An intake of up to 5000 μg per day is considered safe in the eyes of conventional medicine.

However, a long-term intake of megadoses is suspected to potentially cause damage to the liver and kidneys, although specific cases have not been recorded. 

When starting a B12 therapy, it should be noted that the metabolism may change as a result – and certain substances should also be consumed more frequently. An inadequate intake of folic acid, for example, may cause tingling in the hands. Plus, need for iron may also increase significantly, as more blood cells are formed (the same applies for potassium). 

Overall, B12 is one of the most harmless vitamins. Commercially available supplements can be taken without hesitation in the above-mentioned doses. Even if you accidentally taking two or more daily doses, there is no risk of overdose. 

Supplementing Vitamin B12: Necessary Precautions 

Overall, vitamin B12 supplements are particularly user-friendly; there is nothing to worry about with this vitamin, other than obtaining a sufficient dosage. Supplements can be taken at any time of day, with or without food.

The absorption of vitamin B12, however, can be complicated or inhibited by the intake of various drugs and substances, examples of which are listed below: 

  • Alcohol

  • Nicotin

  • High doses of vitamin C

  • Aspirin

  • Acid inhibitors 

  • Antibiotics

  • Contraceptive medication 

  • Proton pump inhibitors 

  • Chemotherapy
  • Psychiatric drugs

  • Diabetes medication (metformin)

  • ACE inhibitors 

  • Medicines for heart palpitations 
    (beta blockers, nitrate sprays, nitroglycerin)

  • Cholesterol lowering drugs (statins)

  • Zidovudine

  • Colchicine

  • Nitrite

If you are taking one of the above-named substances, we advisable that you consult a doctor about how best to optimise your B12 intake. 

Sources:

1. Koyama K, Yoshida A, Takeda A, Morozumi K, Fujinami T, Tanaka N. Abnormal cyanide metabolism in uraemic patients. Nephrol Dial Transplant. 1997 Aug;12(8):1622-8.

2. Freeman AG. Cyanocobalamin—a case for withdrawal: discussion paper. J R Soc Med 1992; 85: 686-771. PubMed

3. Hans C. Andersson, Emmanuel Shapira, Biochemical and clinical response to hydroxocobalamin versus cyanocobalamin treatment in patients with methylmalonic acidemia and homocystinuria (cblC), The Journal of Pediatrics, Volume 132, Issue 1, January 1998, Pages 121-124, ISSN 0022-3476, http://dx.doi.org/10.1016/S0022-3476(98)70496-2.

4. WHO Model List of Essential Medicines, 18th list (April 2013) http://www.who.int/medicines/publications/essentialmedicines/en/

5. Lane LA, Rojas-Fernandez C. Ann Pharmacother Treatment of vitamin b(12)-deficiency anemia: oral versus parenteral therapy. . 2002 Jul-Aug; 36(7-8):1268-72.

6. Andrès E, Dali-Youcef N, Vogel T, Serraj K, Zimmer J. Oral cobalamin (vitamin B(12)) treatment. An update. Int J Lab Hematol. 2009 Feb; 31(1):1-8. Epub 2008 Nov 19.

7.  Thiel R.J., Natural Vitamins May Be Superior to Synthetic Ones. Medical Hypotheses, 2000; 55(6):461-469




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