Appraisal of the 2024 NICE guidelines

 

Understanding the 2024 NICE Guidelines on Vitamin B12 Deficiency and Pernicious Anaemia

In 2024, the UK’s National Institute for Health and Care Excellence (NICE) published its final set of guidelines regarding vitamin B12 deficiency. They are a significant step forward, as they have clearly outlined some crucial steps in diagnosis and treatment. However, they also raise concerns, especially around the diagnosis and treatment of a condition called pernicious anaemia (PA). PA is the most common non-dietary cause of B12 deficiency and is often poorly understood and wildly underdiagnosed. PA is a serious, lifelong condition requiring regular vitamin B12 injections. However, many patients report that current treatment guidelines (one injection every 2–3 months) are by far not enough to manage their symptoms effectively.

 

Controversial Renaming

The 2024 NICE guidelines suggest replacing the term “pernicious anaemia” with “autoimmune gastritis” (AIG). The authors of this article argue that this change is problematic. While AIG and PA are related—AIG can lead to PA over time—they are absolutely distinct entities. PA is a later, more specific stage of the disease, defined by a true inability to absorb B12 due to intrinsic factor deficiency. Renaming PA will create confusion, not only for patients but also for healthcare providers. It might also overlook the fact that PA can occur independently of full-blown AIG. Therefore, the authors advocate for keeping the name or at least adopting a clearer, more accurate term that reflects the autoimmune nature and B12-related consequences of the disease.

 

Challenges in Diagnosis

PA can be difficult to diagnose because its symptoms are vague and vary from person to person. Some people may not show typical digestive symptoms, which can mislead doctors. Current testing methods have also serious limitations. The testing of serum B12 may yield different results, depending on the specific assay used. Derived biomarkers, such as methylmalonic acid and homocysteine, are not very reliable markers. As an example, 30-50% of people with biochemically detected B12 deficiency were found to have normal serum MMA. Furthermore, the most commonly used test checks for antibodies against intrinsic factor, but this only detects PA in less than half of cases. Other tests, like stomach biopsies or checking gastrin levels are underused, despite being helpful. Undergoing a upper gastrointestinal endoscopy is a burdensome procedure for many. Surveys show that most PA patients in the UK are not given such a gastroscopy (an internal examination of the stomach), which -in contrast- is a standard diagnostic tool in other countries.

 

Positive Developments in the Guidelines

Despite the concerns, the new guidelines do include promising changes. They recognize the importance of tailoring treatment to the individual—a shift from the one-size-fits-all model. Many patients feel better with more frequent injections, and many are able to self-administer B12 at home, allowing optimal treatment while reducing the burden on healthcare providers. The guidelines also highlight the need for more research, including how to better support patients in managing their own care. This includes reviewing whether regular monitoring, such as for cancer risk, should be introduced for PA and AIG patients—something currently missing in UK practice but found in some European healthcare systems.

 

In short, the 2024 NICE guidelines represent progress but don’t fully address the complex reality of pernicious anaemia. Replacing its name may oversimplify a multifaceted condition and hinder proper diagnosis and care. The authors stress the importance of clearer diagnostic pathways, more personalized treatment, and ongoing medical education. They call for a more patient-centered approach that reflects both the science and the lived experiences of those with PA.

Find the full paper at: https://www.nature.com/articles/s41430-025-01583-4

 

Parkinson’s disease & vitamin B12

Parkinson’s disease (PD) is a complex neurodegenerative disorder that affects movement and a wide range of motor and non-motor functions. Among the various factors studied in relation to PD, vitamins—particularly vitamin B12—have garnered significant attention. Recent research suggests that vitamin B12 deficiency not only exacerbates the symptoms of PD but may also play a role in its progression. This article explores the intricate relationship between vitamin B12 and Parkinson’s disease, including its potential mechanisms, clinical manifestations, and therapeutic implications.

Given the strong association between B12 deficiency and PD symptoms, supplementation has been proposed as a potential therapeutic strategy. Studies suggest that vitamin B12 supplementation may:

1. Improve gait and balance in PD patients with neuropathy.

2. Reduce homocysteine levels, potentially slowing cognitive decline.

3. Support nerve regeneration and reduce the risk of neuropathy.

4. Enhance overall well-being and quality of life in PD patients.

However, it is important to note that while B12 supplementation can address deficiency-related symptoms, it is not yet proven to modify the course of PD itself. More research is needed to determine whether B12 therapy can alter disease progression in a meaningful way.

For PD patients, regular monitoring of vitamin B12 levels is recommended, especially for those undergoing long-term Levodopa therapy. If a deficiency is detected, supplementation should be considered to prevent further complications. Physicians may also recommend dietary adjustments to include more B12-rich foods or prescribe injectable forms of the vitamin for better absorption.

Link: https://link.springer.com/article/10.1007/s00702-024-02769-z

 

 

B12 & central nervous system

In this exciting new study, the authors (several of them being CluB-12 members) enrolled 231 healthy elderly volunteers (median age 71.2 years old) with a median B12 blood concentration of 414.8 pmol/L (as measured by automated chemiluminescence assay). They performed a variety of evaluations, including multifocal visual evoked potential testing, processing speed testing, and magnetic resonance imaging to assess neurological status. They also measured serum biomarkers of neuroaxonal injury, astrocyte involvement, and amyloid pathology.

Their main findings were:
Low B12, especially decreased holo-transcobalamin (sometimes called ‘active B12’, as this is the form of B12 that can be taken up into the brain), was associated with visual evoked potential latency delay, processing speed impairment (in an age-dependent manner), and larger volumes of white matter hyperintensities on MRI. High levels of holo-haptocorrin (the biologically inactive fraction of B12) correlated with serum levels of Tau, a biomarker of neurodegeneration.

In a press release, the authors wrote: “The current threshold to consider B12 deficiency as a diagnosis and to supplement with vitamin B12, is currently set at 148 pmol/L and is successful at treating most cases of B12-related anaemia. However, a significant amount of people with B12 levels above that threshold have complained of neurological symptoms which improved when getting B12 supplementation. We show that in an older population, lower B12 levels (but above the current threshold of 148 pmol/L) are associated with impaired myelination (slower mfVEPs), neurological function (slower processing speed) and structure (higher WMH lesions on MRI). However, serum biomarkers for neurodegeneration (Tau and UCHL-1) were elevated in people with higher inactive B12 levels.” Remember, dear readers, inactive B12 can not be taken up into the brain. It may be a mere marker, and not a cause of higher Tau levels.
 
The authors have drawn a number of important conclusions:
• The current threshold that defines B12 deficiency must be revisited.
• Clinicians should consider B12 supplementation in older patients with neurological complaints even if B12 levels are higher than 148 pmol/L. But, how do we select these individual;s, and what follow-up do we provide for them?
• Both low active B12 levels and high inactive B12 levels should be considered in future studies about the impact of B12 on neurological function;
• We must invest in more research about the underlying biology of B12 insufficiency since it may impact brain ageing and can be a preventable cause of cognitive decline.
 
Research grant providers should prioritize research in the aforementioned areas.

Link to the article: https://onlinelibrary.wiley.com/doi/10.1002/ana.27200

 

Semmelweis museum

In de hart van Boedapest, Hongarije, staat het kleine maar indrukwekkende Semmelweis museum, ter ere van een man die de medische wereld in de 19e eeuw heeft getransformeerd: Dr. Ignacz Semmelweis.

Het leven van Semmelweis leest als een tragedie van enerzijds wetenschappelijke frustratie maar anderzijds voldoening en en overwinning. Semmelweis leefde in een periode waarin de noodzaak van hygiënische maatregelen in de geneeskunde niet algemeen werd erkend. Aanvankelijk weigerden veel artsen zijn theorieën en inzichten te accepteren, wat zijn boodschap des te krachtiger maakte en ons nu, meer dan ooit, herinnert aan het belang van persoonlijke hygiëne.

 

Ignacz Semmelweis werd geboren op 1 juli 1818 in Buda, het huidige deel van Boedapest. Hij kwam uit een welgestelde familie en kreeg een uitstekende opleiding. Semmelweis studeerde geneeskunde aan de Universiteiten van Pest en van Wenen, waar hij in 1844 afstudeerde; vijf dagen nadat zijn moeder overleed. Na zijn geneeskunde studie bekwaamde hij zich verder in de chirurgie en de verloskunde, en in juli 1846 werd hij benoemd als medisch specialist in de verloskunde in de Vrouwenkliniek in Wenen, die onder leiding stond van professor Klein.

 

Hier werd hij geconfronteerd werd met de hoge sterftecijfers onder kraamvrouwen. In die tijd waren er twee afdelingen in de kliniek, één waar voornamelijk vroedvrouwen werkten, en één waar medische studenten de patiënten begeleidden. De sterfte aan kraamvrouwenkoorts was rond de 3% in de eerste afdeling, maar tot wel 18% in de tweede afdeling! Het viel op dat vrouwen die bevielen in de vroege ochtend, meestal meer kans hadden om te overlijden dan vrouwen die overdag bevielen. Dit wekte zijn nieuwsgierigheid en leidde tot een diepgaand onderzoek. In de vroege jaren 1800 was er nog weinig begrip van infectiepreventie, en artsen voerden vaak hun taken uit zonder enige vorm van hygiëne. Semmelweis begon op te merken dat de artsen en student-artsen die bevallingen hielpen, vaak ook overleden vrouwen onderzochten zonder hun handen goed te ontsmetten. Hij kwam op het idee dat een soort besmetting, veroorzaakt door deze “klinische infecties”, verantwoordelijk kon zijn voor de enorme sterfte onder kraamvrouwen. Eén belangrijke en dramatische gebeurtenis ondersteunde zijn conclusies: de 44-jarige hoogleraar Kolletschka overleed in 1947 aan een beeld dat erg op dat van kraamvrouwenkoorts leek, nadat hij tijdens een autopsie in zijn vinger was geprikt door een student met het mes, dat voor de autopsie werd gebruikt. Kolletschka overleed, zo werd beschreven, een aantal dagen later aan de gevolgen van een zeer ernstige infectie. In 1847 introduceerde Semmelweis daarom een procedure om de handen grondig te wassen met een chlooroplossing voordat studenten bevallingen bijwoonden en uitvoerden. Het resultaat was verbluffend; de sterftecijfers daalden van meer dan 18% naar minder dan 2%. Dit ontdekkingsproces was essentieel voor de verdere ontwikkeling van hygiënische praktijken in de geneeskunde.

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