Establishing Reference Values for Lipids in the Blood

Posted on June 04, 2019

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Markus Wenk and Andrej Shevchenko noticed a problem in lipidomic research—that despite the amount of research cropping up on the topic of blood plasma lipidomics, there were not published numbers for the absolute molar quantities for disease molecules or their healthy counterparts.

This means that researchers cannot compare data, which limits the widespread creation of new knowledge, when it could be right at our fingertips. This is not to say that the issue lies in quantifying more of the data—the data provided could be semiquantitative and still provide enough information to where it is replicable and can be compared against other related studies. As the field progresses, lipid researchers need to agree on a system of measurement and, ultimately, establish reference values for lipids in the blood.

The Advent of LIPID MAPS

When researching lipids in the blood, labs establish systems and standards for measurement using control samples with each assay as well as external certification.

Before lipidomics was even an area of research, Edward Dennis introduced the idea to the National Institutes of Health. When the NIH created a new grant specifically to support and launch new interdisciplinary scientific initiatives, the Lipid Metabolites and Pathways Strategy, or LIPID MAPS, was created.

The 12 principal investigators working on the LIPID MAPS project were determined to develop techniques for the budding field of lipidomics, from which emerged a standardized system of classifying lipid types, a website where researchers could access a bank of features in mass spectra, and more. The project propelled the field forward, but there are still areas that need improvement.

Continuing the Pursuit of Standardization

As an extension of the LIPID MAPS research, individuals set out to determine the quantity of as many lipid species as possible in human blood plasma. A plasma sample supplied by the National Institute of Standards and Technology (NIST), created from a pool of 100 volunteers whose age and ethnicity matched the average population of the United States, was used for this research. This sample contained certified measurements of cholesterol, triglycerides, free fatty acids, and several steroid hormones and lipid vitamins. Aside from knowing that the measurements were certified and matched the average population, the lipid content remained unknown.

When John Bowden became a researcher with NIST in 2011, he saw an opportunity for further standardization and harmonization. So in 2014, Bowden and his team took the same plasma sample mentioned above and used it in 30 labs across the U.S. to find out just how much variability existed in the field through different methodologies and philosophies for measuring lipids. Bowden and his team found significant variability, but the study received a mix of acceptance from the scientific community. However, for Bowden and his team, identifying a lack of consensus in the field was what they set out to do in the first place.

A Path Toward Reference Values

So the question now is: How does the field advance so that we achieve improved reference values for lipids in the blood?

For one, the improvement of technology, namely benchtop mass spectrometers, will allow scientists to more accurately distinguish lipid species. The technology allows scientists to distinguish between species that they couldn’t distinguish between before, but there still exists a challenge: a single feature in an MS spectrum could indicate more than one molecular species. So mass spectrometry alone will not suffice.

Another way to advance on this front is for researchers to indicate their degree of certainty when they publish data, which is an issue that Bowden and his team at NIST are proponents of. This small step will help avoid misidentification and will encourage everyone to make conscious strides toward eliminating false certainty.

Ultimately, it has been clear that the field needs to prioritize standardization and reproducibility, and that there has existed a gap between discovery lipidomics and clinical research involving lipids. One group has been working to revive LIPID MAPS to provide more resources for the field, another group has begun research on technological limits and possibilities for blood lipidomics, and the final group is working to improve reporting standards for lipid data.

Defining reference values for blood lipids is the only way for scientists in the field to operate under a unified understanding of analytes, how to accurately measure in a way that’s reproducible, and the techniques to do so.

According to Andrej Shevchenko’s mother, one of the first researchers to speak up on this issue, “Before you arrive at a reference value, what the normal parameter is, it’s all noise.” To stay up to date with the latest in lipid research, contact Avanti today.