In a recent article published in the journal Nutrition, researchers in Australia summarized how diet could help decrease low-density lipoprotein cholesterol (LDLc) or triglyceride concentrations in polygenic hypercholesterolemia.
Study: A Review of Low-Density Lipoprotein-Lowering Diets in the Age of Anti-Sense Technology. Image Credit: Ralwell / Shutterstock
Elevated LDLc or dyslipidemia, including high levels of total cholesterol, increases the risk of cardiometabolic disorders and cardiovascular diseases (CVDs), especially ischemic heart disease (IHD), if not managed in time. Pharmacological treatment is sometimes a prerequisite for cases with complex dyslipidemia with a genetic component. Subsequently, pharmacological research yielded several highly effective drugs based on monoclonal antibody (mAb) therapy, some of which researchers even reviewed in this paper.
Drugs based on novel pharmacological approaches, however, would become more accessible as demand increases, their costs decline, and, more importantly, their methods of administration become as convenient as popping pills daily.
Two cost-effective LDLc-lowering drugs, statins, and ezetimibe, are also available for clinical use. They are a strong competitor or alternative to strict dieting because they lower LDLc by ~20%. Another treatment option is proprotein convertase subtilisin kexin type 9 (PCSK9)-inhibiting mAbs. Clinical studies have shown these mAbs lower LDLc by up to 60%, thereby reducing cardiovascular risk in a dose-dependent manner. Biochemical and genomic studies have shown that PCSK9 is crucial during LDL and lipid metabolism.
Perhaps this is why researchers are clinically evaluating approaches inhibiting PCSK9 via small interfering ribonucleic acid (siRNA) interference. Unfortunately, though attractive, these therapies are expensive and inapt for moderate hypercholesterolemia, triggered in most cases by wrong eating patterns.
In the current narrative review, researchers extensively searched published literature in English up to February 2023 on topics related to LDLc and treatment options to lower it in humans. Multiple genetic studies have confirmed that it is the cause of atherosclerotic CVD.
Studies evaluating the effect of diet on LDLc
Ancel Keys and Mark Hegsted, in the 1950s and 1960s, quantified changes in total cholesterol levels in response to dietary changes. Their equations demonstrated that saturated fats increase total and LDLc twice as much as polyunsaturated fats lower them. They also determined that monounsaturated fatty acids (MUFA) have a no-to-minimal effect on serum cholesterol in humans. Nearly seven years later, the Prospective Urban Rural Epidemiology (PURE) study confirmed that if saturated fat intake is low, it is difficult to quantify its effect on mortality or CVD outcomes. This study also showed that the high-saturated fat diet increased LDLc the most, while MUFA and polyunsaturated fatty acids (PUFA) barely increased it. Later, another study showed that high MUFA or high carbohydrate diets also lowered LDLc.
However, whether dairy intake increases serum lipids and cardiovascular risk remains controversial. Thus, it is still debatable whether milk fat, rich in saturated fatty acids, including myristic acid, lowers LDLc concentrations or not. On the other hand, it is well-recognized that the elimination of trans fatty acids makes a diet healthier.
Further, the researchers pointed out how the LDL particle size indicates CVD risk. Paradoxically, diets rich in saturated fatty acids with larger circulating LDL particles lower CVD risk. Though partially, genetics also determines how an individual responds to dietary fat manipulation.
Regarding reducing dietary cholesterol intake, the researchers found that reductions in LDLc were moderate when people reduced dietary intake of its identifiable sources, such as eggs. Yet, it did not work as much as substituting saturated fatty acids with PUFA. Accordingly, randomized controlled trials (RCTs) applying nonlinear models have shown that lowering cholesterol by 100 mg lowers LDLc by 4.5 mg/dL.
Next, the researchers pointed out that besides dietary fats and oils, other foods, such as oats, barley, and nuts, lower LDLc. However, these plant-based foods should have saturates along with phytosterols. Intriguingly, they found that indigestible fiber and carbohydrates also lower LDLc. Finally, the researchers emphasized adopting a whole-diet approach alongside optimizing body mass, eating more fish and plant-based foods; while reducing meat, alcohol, and salt intake, and, importantly, altering the nature of dairy product consumption to manage LDLc levels.
To summarize, the best approach should be to diversify dietary intake. For instance, substituting saturated fatty acids with PUFA could lower LDLc by >10%. Eating a plant-based diet could also reduce LDLc by ~20% if taken in the right proportions. Reducing dietary cholesterol consumption and supplementing the diet with plant sterols and other nutrients might also prove beneficial.
With support from health professionals and before LDLc-lowering pharmacological products substitute the dietary options, it is best to adopt a whole-diet nutritional approach to mitigate the CVD risks arising from elevated LDLc levels. Nonetheless, future research should focus on devising a whole-diet approach that reduces total LDLc by 20%, at par with drugs like statins or ezetimibe.
This strategy could successfully work for people with mild-to-moderate hypercholesterolemia and be more desirable, for it intervenes through diet, not drugs. Foods fortified to lower LDLc should be cost-effective too. Nevertheless, PCSK9-inhibiting mAbs that lowers LDLc by more than 25% might compete with diet once they become affordable for the masses.