Introduction 

Schilling test is a laboratory test which was used by medical practitioners in the past to correctly identify the cause of vitamin B12 deficiency. Although this test is only of historical importance now, it is still significant because it helped physicians understand how vitamin B12 is absorbed in the body and what problems can occur in the pathway of its proper utilisation.¹

In this article, you will understand what the schilling test is, the basis behind it, how it is done and its current significance. 

Why is vitamin B12 important?

Vitamin B12 is necessary for a process called myelination, which is basically the process of formation of a proteinaceous cover on the nerve fibre required for its proper functioning. Along with that, it is essential in synthesis of DNA, the molecule which contains all genetic information.^2,3,4

What happens when you develop a deficiency of vitamin B12?

An important feature of B12 deficiency is a type of anaemia called megaloblastic anaemia where mature red blood cells (RBCs) are abnormally large with a preserved nucleus. It is associated with low counts of other blood cells like the white blood cells (WBCs) and the platelets. When vitamin B12 levels are low in the blood proper DNA synthesis does not occur which is required for cell division and adequate red blood cell production

If you don’t get enough B12, or if your body can’t absorb it properly, you might experience symptoms due to inflammation of the tongue (glossitis) like redness, swelling, and pain of the tongue, symptoms of anemia like tiredness and palpitations, and infertility and memory loss.^4,5,6 Numbness and tingling sensation are also common complaints found in such patients.⁶

An important point to know here is that the occurrence of numbness is sometimes observed without the presence of anemia, thus necessitating early treatment to prevent irreversible nerve damage.⁷

Who is most at risk of developing a vitamin B12 deficiency?

1. Older adults- 3%–43% of older adults may have B12 deficiency⁸
2. Pernicious anaemia- This is the most common cause of serious B12 deficiency worldwide and is more common in women and those of European descent⁹
3. Gastrointestinal disorders- Conditions like celiac and crohn’s disease can block B12 absorption¹⁰
4. Gastrointestinal surgeries- Stomach surgeries (e.g., gastric bypass) reduce B12 absorption. Due to loss of cells that make stomach acid and intrinsic factor, important for the absorption process¹¹
5. Vegetarians and vegans - These individuals have a higher risk because B12 is naturally contained only in animal foods¹²
6. Infants of Vegan Mothers- Risk of early, severe B12 deficiency if exclusively breastfed¹³

How is vitamin B12 absorbed from the body?

Absorption of vitamin B12 from food is via a specific process which involves various organs of the gastrointestinal tract like the mouth, stomach and the small intestines. 

1. In the mouth, saliva helps release vitamin B12 from food
2. More vitamin B12 is freed from the food due to the action of acid in the stomach
3. Vitamin B12 molecules then gets attached to a protein called the “intrinsic factor” (IF), produced by parietal cells in the stomach
4. This vitamin B12 attached to the intrinsic factor (IF) travels to the small intestine, where absorption into the bloodstream takes place¹⁰

A problem at any steps mentioned above can cause a low level of B12 in your blood. 

What is pernicious anaemia? 

Pernicious anaemia is an autoimmune problem where your body mistakenly attacks and destroys parietal cells of the stomach which are responsible for the production of intrinsic factor. The resultant low levels of intrinsic factor leads to high amounts of free vitamin B12, which cannot be absorbed in the intestines.¹⁴

In such cases, the problem lies entirely in how the gastrointestinal system in your body absorbs this B12, not in how much B12 you are consuming. Since the absorption of B12 is a complex process, there needs to be a specific test to detect the problematic site so that appropriate treatment can be given. This is where the Schilling test comes in. 

What is the schilling test?

The schilling test, developed in the 1950s, was used to understand the reason for low B12 levels in the body. It involved administration of a small dose of radioactive vitamin B12 followed by urine collection for 24 to 48 hrs.¹⁵ This allowed physicians to track how much of the ingested B12 was absorbed into the body and later on passed in the urine. If the radioactive B12 appeared in the urine, this meant that the absorption process was working normally.

The schilling test can be described in 3 stages,

Stage 1 

1. You swallow a tiny amount of radioactive B12
2. Two hours later, you get a big shot of regular B12 in your muscle (flushing dose)
3. This “flushing” dose fills up your body’s B12 stores quickly
4. So any B12 you absorb from the swallowed dose has nowhere to go (as it can’t enter the stores) except out through your urine
5. If enough radioactive B12 shows up in your urine in the first 24, your body is absorbing it just fine

Stage 2

The test is repeated using intrinsic factor along with the radioactive B12.

1. If you absorb B12 now and excrete it in urine (after intrinsic factor is given from the outside): this means you were missing intrinsic factor before, a strong sign of pernicious anaemia
2. You still don’t absorb B12 and B12 is not present in urine: The problem isn’t with the intrinsic factor—it might be something else

Stage 3 

Other versions of the test sometimes involve extra steps like using antibiotics or digestive enzymes to check for other absorption issues in the intestine or pancreas.¹⁶

Why was the schilling test important?

Before modern laboratory testing methods were invented, this test was the only way doctors could identify the cause of B12 deficiency, thus enabling proper treatment which could be as follows:

• Patients diagnosed with pernicious anemia require administration of injectable B12 throughout their life
• If the problem is a dietary deficiency, oral B12 supplements can be given
• Other issues like bacterial overgrowth or a pancreatic issue need specific treatment like administration of antibiotics or extrinsic enzymes¹⁷

Why is the schilling test no longer used?

Even though it was once common, the Schilling test is now considered obsolete. Here’s why:

1. The patient should have a normal kidney function for this test to give reliable results¹⁵
2. Handling radioactive material is complicated, requiring a lot of technical knowhow
3. Urine collection is required for about 24 hours for one step which is cumbersome¹⁵
4. Intrinsic factor required for step 2 is difficult to purchase at economical rates for the test to be done on a large number of people
5. Newer blood tests can easily detect B12 and antibodies for intrinsic factor directly

What can we learn from the schilling test today?

From a historical standpoint, the schilling test holds a lot of significance. Apart from a glimpse into the diagnostic difficulties that physicians used to face, it shows us how innovations in science and cross integration of fields can aid diagnosis. 

FAQs

Can you get enough Vitamin B12 from a plant-based diet?

Not naturally. Vitamin B12 is mostly found in animal products. People following vegan or strict vegetarian diets should take B12 supplements or eat fortified foods to avoid deficiency.¹⁸

Can medications affect B12 absorption?

Yes. Drugs like proton pump inhibitors, metformin, and long-term antacids can reduce stomach acid or interfere with absorption. Ask your physician about any possible drug interactions.¹⁹

Can B12 deficiency happen even if your blood B12 levels are “normal”?

Yes. Blood levels may appear normal, but functional deficiency can exist. Elevated methylmalonic acid (MMA) and homocysteine are better indicators.²⁰

Summary

The Schilling test used to be the gold standard for diagnosing the reason behind vitamin B12 deficiency, in the olden days. 

Beyond identifying the mere presence of the deficiency, it specifically pinpoints the reason for it , allowing specific treatments in conditions like pernicious anemia. 

While modern medicine has moved on to more convenient and faster tests, this test still holds a valuable place in the understanding of B12 absorption. Furthermore, it is a testament to the strides that laboratory diagnostics have taken and how innovation can help medicine.