A precision and personalized medicine approach to dyslipidemia and dyslipidemia- induced cardiovascular disease—including high LDL cholesterol, elevated triglycerides, low high-density lipoprotein (HDL) and HDL function, and other related cardiometabolic conditions such as insulin resistance and metabolic syndrome—is completely different from the conventional medicine approach. In this article, we will review the major paradigm shift that has emerged in the past 10 to 15 years regarding HDL, which is best known for its ability to carry cholesterol from the blood vessel to the liver for redistribution, metabolism, and elimination. Strong experimental evidence suggests that HDL facilitates other cardioprotective effects in the body through various anti-inflammatory, antioxidative, antiapoptotic, anti-immune and antithrombotic processes. On the other hand, emerging data demonstrates that total HDL cholesterol does not represent the full story, because randomized trials aimed at raising HDL do not show benefit. The latest understanding regarding the management of HDL is that in order for HDL to have cardioprotective benefits, it must be functional. Loss of HDL function may negatively impact cardiometabolic health. New guidelines suggest that tests of HDL function provide more value than traditional total lipid testing and even more than advanced lipid testing of HDL size. Nutrition and nutraceutical supplements may be the most effective way to prevent, repair, and reverse the loss of HDL function that occur in patients. The main takeaway concept is that the heterogeneity of HDL structure, composition, size, HDL particle number (HDL-P), and function is much more important and valuable than the measurement of HDL-C alone to provide comprehensive analysis of the protective qualities of HDL cardiovascular disease. Instead, advanced lipid biomarker testing should include HDL size, HDL particle number, total HDL content, and ultimately reverse cholesterol transport (RCT) and cholesterol efflux capacity (CEC), which are measures of measure of HDL functionality, once they become commercially available.

HDL: The paradigm shift about the role of HDL

In other words, if HDL is the garbage collector, there’s a range of options in the fleet. Some garbage trucks look good but don’t perform. Some have flat tires. But some of the garbage trucks are top of line, some have large carrying capacity and others have small carrying capacity, and others are highly dependable and perform beyond expectations. That’s the spectrum of HDL functionality.

We can no longer rely on high HDL for heart health protection, because experts are now questioning the composition and function of the various types of HDL.

HDL mapping of various subspecies of HDL

There are five different forms of HDL. The test used to measure these different forms is called “HDL mapping,” which includes α-1, α -2, α -3, α -4, and pre-β HDL. All of these forms are important; however, in the past the emphasis had been on the large HDL, which was α-1 in particular with a little bit of α-2. The concept has since changed. Some of the small particles, which are necessary to dock on the LDL tissue receptors and remove it, may be just as important in transforming to a larger HDL—which can handle more LDL, take it out, and deposit it in the liver. While the HDL size is important, it may be all types of HDL that play a role in this process.

But even size doesn’t matter without proper function. For example, a patient may have a normal level of all HDL sizes with the HDL mapping, but the HDL function may be abnormal. Think of it like a garbage truck with four flat tires. Although the garbage truck is large and potentially powerful, it won’t make it to its destination to complete its job (i.e., cleaning up LDL). That’s why functionality is the biggest key factor.

Testing 1, 2, 3

For any patient with a history of HDL-related problems, the first and most important step is to complete an advanced lipid profile, which will guide treatment options such as nutritional support, exercise, weight loss, and nutraceutical supplementation. This requires specialized labs—now available all over the United States—that determine all the previously mentioned parameters, including HDL size, HDL

Designing a nutritional medicine treatment protocol

Supplementation can play a key role in HDL management. Keep in mind, there are very few pharmaceutical agents that modify HDL. In fact, most won‘t affect the three parameters we’ve covered. However, various nutraceutical supplement and nutritional changes can modify at least one of these key factors.

Targeted nutritional therapy is associated with clinical benefit in various forms of dyslipidemia, including the use of red yeast rice, berberine, plant sterols or stanols (phytosterols), soluble fiber, citrus bergamot, flax seeds, and omega-3 fatty acids.

Key takeaways

A personalized, precision, and integrative cardiovascular medicine approach to dyslipidemia—including advanced lipid testing with LDL, HDL, and VLDL particle size and number and HDL function related to RCT and CEC are required to determine CHD risk and then provide targeted prevention and treatment strategies. This is completely different from the conventional medicine approach.

In this article, we explored the major paradigm shift that has emerged in the past 10 to 15 years regarding HDL, which is best known for its ability to carry cholesterol from the blood vessel to the liver for redistribution, metabolism, and elimination.

HDL facilitates other cardioprotective effects in the body through various anti-inflammatory, antioxidative, anti-immune, and antithrombotic activity.

Emerging data demonstrates that total HDL cholesterol does not represent the full story, because randomized trials aimed at raising HDL do not show benefit.