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PubMed Kang YA et al

Jeff Cohen, co-founder of the American Peptide Association, which provides clinical guidance for doctors and organizations, says that the FDA system of evaluating and approving drugs based on expensive, large-scale clinical trials is unrealistic for this industry

Certain digestive disorders, including Crohns disease and coeliac disease, can interfere with absorption, as can surgery involving the stomach or small intestine

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So, where do researchers go

It is important to keep an open mind though and there have been a couple of posts here recently where people have reported thinking some symptoms were B12 deficiency related and they turned out to be caused by something else