Vitamin B12 deficiency causes reversible megaloblastic anemia, demyelinating disease, or both. Current assays have insufficient sensitivity and specificity; methylmalonic acid levels are useful to confirm diagnosis. Parenteral or high-dose oral vitamin B12 is effective therapy.

https://www.nejm.org/doi/pdf/10.1056/NEJMcp1113996

Vitamin B12 Deficiency

Background: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations. Methods: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years. Outcome: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions.

/pdf/facts-and-recommendations-about-total-homocysteine-23jbkelsns.pdf

Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

/pdf/biomarkers-of-nutrition-for-development-bond-iron-review-4ibc6okj7y.pdf

Biomarkers of Nutrition for Development (BOND)-Iron Review.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)60109-3.pdf

Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial.

Aims/hypothesis
Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years.

/pdf/vitamin-b12-and-folate-concentrations-during-pregnancy-and-2yjgmt92oq.pdf

Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study.

Background: There is a need for systematic evaluation of methods before their release to the market. We addressed this problem in novel homocysteine assays as part of an European Demonstration Project involving six centers in four countries.

Methods: Two immunological methods for measurement of plasma total homocysteine (P-tHcy), the fluorescence polarization immunoassay (FPIA) and the enzyme immunoassay (EIA), were compared with two comparison methods, HPLC and gas chromatography–mass spectrometry (GC-MS). All laboratories performed the following procedures: ( a ) familiarization; ( b ) determination of linearity and precision by analyzing five plasma samples with interrelated concentrations for 20 days; ( c ) correlation using patients’ samples; and ( d ) assessment of long-term performance.

Results: Both immunological methods were linear for P-tHcy between 5 and 45 μmol/L. The intralaboratory imprecision (CV) was <5% for FPIA and <9% for EIA used with a sample processor. The bias was −2% to 3% for FPIA and 2–4% for EIA used with a sample processor.

Conclusions: The immunological methods provide results with little bias compared with HPLC and GC-MS. The imprecision of the assays must be considered in the context of their intended use(s).

/pdf/evaluation-of-novel-assays-in-clinical-chemistry-gotwzg0gwc.pdf

Frode Engbaek

Papers

Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion

Evaluation of Novel Assays in Clinical Chemistry: Quantification of Plasma Total Homocysteine