Vitamin B12 is a class of chemically related compounds, also called cobalamins that contain cobalt. It is considered the most important factor in the maintenance of nerves and also has a number of other important functions within the body, however deficiency and depletion of B12 are prevalent around the world.
VItamin B12 deficiency can affect many bodily systems including neurologic, hematologic, immunologic, vascular, gastrointestinal, musculoskeletal and genitourinary. Symptoms include extreme tiredness / lack of energy, pins and needles, a sore and red tongue, muscle weakness, difficulty walking (eg balance problems), depression, problems with memory, understanding and judgement, paranoia or hallucinations and many more.
In this week’s blog we interview NHS GP Dr Ayan Panja who gives us his insight on the widespread issue of vitamin B12 deficiency, the testing that is currently available in this area and the complications that can potentially arise if deficient in this nutrient.
Dr Panja will be joining Dr Rangan Chatterjee as a panel member at our Cytoplan Practitioner Education Event on July 1st, you can find out more about this event via this link.
Dr Panja, to start things off we wanted to ask what you think the prevalence of B12 deficiency is, and why are there different opinions on prevalence?
The prevalence varies across the globe for obvious dietary reasons. In the UK it is deemed to be between 1-6% and as high as 80% in parts of Asia and Africa. It is more common over the age of 60. The difficulty arises in how we actually define B12 deficiency. Pernicious anaemia is an autoimmune condition and some clinicians only consider that as true deficiency.
On a practical level many GPs and gastroenterologists look at normal ranges from blood tests. It’s more important to think about whether a person’s B12 is functioning properly, even if it is in the ’normal range’. This is where much of the discourse around prevalence arises.
Why are the daily recommended intakes in the UK, US and elsewhere different?
Intake guidelines on B12 (aka cobalamin) differ because there is no one area that is more contentious in medical circles across the globe than that around diet, supplements or vitamins. It is difficult, even in retrospect, to conduct robust studies that could identify how much of a particular vitamin is enough for a population with different ages, genes, ethnicities and lifestyle habits. This makes public health messaging really difficult. The World Health Organisation conducted a technical consultation on folate and B12 deficiencies in 2008 and “recognised the lack of universally accepted cut offs to define deficiency of either vitamin…”. One of the reasons for this is testing methods and their reliability. There are exceptions. Vitamin D testing is a far simpler affair for instance.
In what circumstances are B12 deficiency tests carried out, and what are those tests?
There can be many reasons to check a person’s B12 levels. They include:
- persistent tiredness
- unexplained aches and pain
- neurological symptoms
- food intolerances
- coeliac disease
- memory loss symptoms
- family history of pernicious anaemia
- those on the drug metformin or on potassium supplements
- people who are heavy drinkers of alcohol
- a person with unexplained anaemia.
The standard test to measure B12 levels will be a blood test which measures serum B12 levels – that is the amount of B12 that is floating around in the blood, not the amount within the blood cells themselves.
What are the issues and complications around B12 deficiency testing?
It can be hard to get a measure of someone’s level of ‘functioning’ B12. There are other tests which serve as indirect measures of B12 status including methylmalonic acid (MMA) and homocysteine. MMA levels increase when B12 levels drop. Homocysteine is an amino acid which is also raised with low B12 as part of an elegant and critical cellular process which is important for many functions called the methylation cycle. There is much disagreement around the validity of these tests amongst groups of professionals. High homocysteine levels are linked to an increased risk of heart disease, stroke and dementia. My personal view is that sub optimal B12 is under-diagnosed and I have a very low threshold for testing B12 levels.
What is the generally accepted normal B12 range?
In the NHS it is usually 150-900 ng/L but I have seen patients with symptoms of B12 deficiency with levels within these ranges.
Do you think that most GPs understand B12 deficiency properly?
There is still no real consensus on testing. Deficiency can cause so many symptoms from depression, infertility, digestive issues, poor hair and nails, joint pains, cramps – the list goes on. In Cambridgeshire, a NHS neurology team has started giving high doses of intramuscular B12 to those with chronic fatigue as it seems to help. Many of these patients probably have a methylation issue by virtue of their genes. There is a gene mutation affecting MTHFR (an enzyme that converts dietary folate [vitamin B9] into an active form) which can alter how someone processes other B vitamins including B12. Methylation occurs over a billion times a second. I doubt that most GPs would be aware of this gene mutation. I certainly wasn’t until about 3 years ago but it can be a useful test in the right context.
In which circumstances are tablets or injections prescribed?
Tablets are generally not recommended very commonly, as B12 is poorly absorbed from the stomach, especially if the patient has poor absorption. Injections or sublingual sprays or lozenges (under the tongue) work far better.
If someone does not have a B12 deficiency, can they gain an energy boost from a B12 injection?
Yes possibly as it will help the conversion of carbohydrates into glucose that the body can use. It also helps muscle contraction.
Can it help with weight loss, as sometimes claimed?
It is not something that I have come across but possibly because it helps convert carbohydrates into glucose and helps in the breakdown of fats and proteins.
Do you agree with campaigners who are pushing for B12 injections to be made available over-the-counter, and doctors to prescribe more frequent treatment? If so, why?
I think there are too many people out there who have been misdiagnosed and so I totally understand the push for more OTC B12 preparations like injections. There would need to be some governance around training and safety for injectables. There are already sublingual supplements available OTC which is great. I don’t think it’s a bad thing. People can already freely buy drugs like ibuprofen, codeine and paracetamol – which are fatal in overdose. I think if people feel unwell on supplementary B12 then they should seek advice from their GP. I personally would want to know more about their methylation and the form of B12 supplement is key.
What do you think is behind the recent increase in availability of B12 injections in private “clinics”/salons, such as at Harvey Nichols?
For many years, in the USA particularly, intravenous vitamin therapy has been available street corners at “IV Lounges”. They tend to be frequented by anyone from City workers with hangovers to people with chronic fatigue and cancer. It dates back to the era of the Myers cocktail formulated in the 1960s by Dr John Myers from Baltimore who wanted to improve nutrient intake in his patients with poor health. It taps into the modern concept of wellbeing on a number of levels. People are busier than ever with little time to focus on their health. Many want a quick fix of something whilst continuing to carry on with their not so healthy habits.
There’s nothing more ‘medical yet natural’ in people’s minds than an IV vitamin drip. Others who have them may feel let down by conventional medicine or feel that they are not nutrient replete, so find that an IV drip keeps them feeling well whilst dealing with a chronic illness. The absorption of intravenous nutrients is obviously superior compared to oral vitamins. The MHRA will have the final say on how the actual contents of the drips are regulated, as historically many of the products have come in to the UK from outside the EU.
Cytoplan Editor’s notes
With many thanks to Dr Ayan Panja for providing us with his thoughts on the global problem of vitamin B12 deficiency. It is indeed an issue of widespread concern and is one of the most documented and researched nutrient deficiencies in medical science.
If looking to supplement with vitamin B12 then understanding the different forms is particularly important.
Forms of B12
The most commonly found ‘forms’ of B12 used in supplements are cyanocobalamin, methylcobalamin, hydroxycobalamin and adenosylcobalamin. In supplements cyanocobalamin is the most commonly used form despite methylcobalamin and hydroxycobalamin being better absorbed, retained and used by the body.
The inactive cyanocobalamin and hydroxycobalamin forms can be converted to the active cofactor forms – methylcobalamin in the cytoplasm of cells and adenosylcobalamin in the mitochondria.
Cyanocobalamin is an inactive form of B12 and exists only via chemical supplementation. It is not present in nature meaning the body does not metabolically recognise it and absorption is much less efficient.
Hydroxycobalamin is a natural inactive form of vitamin B12 attached to a hydroxyl group. This form can be converted into active methylcobalamin and adenosylcobalamin in the body. For some people this form may be indicated rather than the active methylcobalamin. Hydroxycobalamin has a high affinity to plasma proteins. This property helps to retain the hydroxyl protein complex in the blood stream for a much longer period of time, compared to cyanocobalamin. Hydroxycobalamin may be indicated where high nitric oxide levels are suspected as it is an effective nitric oxide scavenger. Too much nitric oxide can contribute to oxidative stress. Hydroxycobalamin may also be recommended for people who do not tolerate methyl groups.
Methylcobalamin is an active form of B12 where the cyanide group is replaced with a methyl group. It occurs in the cytoplasm of cells and can be synthesised from hydroxycobalamin by the addition of a methyl group. It is needed for vital cellular processes including methylation and DNA synthesis. Thus methylcobalamin is a cofactor in the methionine cycle (methylation cycle). The purpose of this cycle is to regenerate SAM (s-adenosyl methionine) the universal methyl donor.
In the process homocysteine is converted to methionine. Methylcobalamin is the only form able to cross the blood brain barrier without further metabolism, other forms need to be reduced. This form of B12 may be recommended to provide ‘methyl’ groups or for people with specific genetic polymorphisms that can result in less effective recycling of B12. It would also be indicated where an active form is required, for example if it is suspected that there are conversion issues from the inactive hydroxycobalamin form.
Adenosylcobalamin is the mitochondrial form of B12 which acts as a co-factor for a metabolic enzyme involved in energy production. It can be synthesised from hydroxycobalamin or methylcobalamin. People with certain genetic polymorphisms may have a reduced capacity to synthesise adenosylcobalamin. This can result in elevated levels of methylmalonic acid which can be measured in blood or urine and which provides an indirect measure of B12 status.
As well as MTHFR mutations, other methylation cycle genes such as MTR and MTRR may affect how B12 is used and recycled; plus TCN mutations can affect B12 transport proteins. Mutations in all these genes can increase the need for B12.
Factors that can contribute to low levels of B12 and deficiency
Vegan or vegetarian diets, damage to parietal cells in the stomach (eg due to gastritis), low stomach acid (eg due to antacid medication), nitrous oxide (used in some surgical operations), genetics, malabsorption (eg Crohns), surgery to stomach/small intestine, some prescription drugs (eg metformin and others).
Dr Ayan Panja
MRCGP, MBBS, DRCOG, DFFP
Dr Ayan Panja has been a doctor for 18 years having qualified from the Imperial College School of Medicine. He works as a GP Partner in St Albans, Hertfordshire and has a keen interest in preventive medicine.
With many thanks to Dr Panja for taking part in this Q &A session on the topic of vitamin B12 deficiency. If you have any questions regarding the health topics that have been raised, or any other health matters please do contact me (Clare) by phone or email at any time.
Clare@cytoplan.co.uk, 01684 310099
A Cytoplan Practitioner Education Day
Join Dr Rangan Chatterjee and a panel of experienced clinicians to discuss the evolution of lifestyle medicine, and be part of creating the fabric of future primary care in the 21st century. The panel will include this week’s blog interviewee Dr Ayan Panja, Technical Director of Cytoplan Amanda Williams and nutrition practitioner Miguel Toribio-Mateas.
To find out more information, and to book your place, please follow this link.
5 BANT & RCGP CPD hours.
£65 (early bird tickets – £60 until 17th April)
£55 for students
A healthy lunch and refreshments will be provided throughout the day