The association between lipid disorders and heart disease is well known. Medical checkups usually involve measurements of cholesterol and other lipid parameters, and most doctors advise their patients on how to improve their lipid pattern.
Dietary interventions to lower the risk of heart disease commonly aim at reducing blood levels of cholesterol, LDL cholesterol in particular. This is one of the main reasons why low-fat diets are usually recommended by public health authorities. Reducing the amount of saturated fat and cholesterol, in particular, is believed to be effective. However, in an era where metabolic abnormalities associated with obesity and insulin resistance are becoming increasingly common, other measures might be more effective.
Lately, low-carbohydrate diets have become popular for patients with obesity and metabolic syndrome. Metabolic syndrome is characterized by a large waistline, high blood pressure, glucose intolerance, low HDL cholesterol, and elevated triglycerides. It has been proposed that carbohydrate restriction may improve this lipid pattern as it raises HDL cholesterol and lowers triglycerides. However, some experts have concluded that carbohydrate restriction may be harmful because of the possible detrimental effects of increased LDL cholesterol (1).
Recently, it has become more common to assess the amount of circulating lipoprotein particles, rather than the amount of cholesterol itself. Such tests may be more accurate, particularly in people with metabolic syndrome. How these biomarkers are affected by dietary modification is an exciting and growing area of research. For the time being, we can call these lipid biomarkers nontraditional because their use is not widespread in the clinical setting.
Nontraditional Lipid Biomarkers
Scientific data suggest that the number of LDL particles is a stronger risk factor than LDL cholesterol (2). Furthermore, LDL particle size may be important as small particles are more strongly associated with the risk of heart disease than larger particles.
The triglyceride/HDL-cholesterol ratio appears to be a useful marker of the risk of coronary artery disease (3). A high ratio correlates with small LDL particle size and insulin resistance.
Apolipoprotein B (apoB) is a major component of atherogenic lipoprotein particles such as LDL, VLDL and Lp(a). Each of these particles contains a single apoB molecule. Hence, apoB measurements reflect the number of atherogenic particles, most of which are LDL particles.
Several studies suggest that apoB is a better predictor of heart disease risk than LDL cholesterol (4). Furthermore, it has been shown that apoB may be elevated despite normal or low concentrations of LDL cholesterol (5).
Apolipoprotein C-III (apo C-III) is found on the surface of triglyceride-rich lipoproteins (6). High levels of apo-C-III are associated with high triglyceride levels and increased risk of cardiovascular disease. Apo-C-III may contribute to the development of atherosclerosis by several mechanisms (7).
Apolipoprotein E (APOE) is a lipoprotein found primarily in chylomicrons and intermediate-density lipoprotein (IDL). APOE transports lipoproteins, fat-soluble vitamins, and cholesterol. The ApoE4 isoform is associated with lipid disorders, high blood cholesterol, and increased risk of coronary heart disease and stroke (8).
There are at least three slightly different alleles of the gene that codes for APOE. The major alleles are called e2, e3, and e4. The most common allele is e3, which is found in more than half of the general population. The e4 allele of APOE is associated with increased risk of cognitive decline and Alzheimer’s disease.
Lipid Biomarkers in the Metabolic Syndrome – The Role of Fructose
The metabolic syndrome is associated with increased risk of cardiovascular disease (9). It has been proposed that reducing the intake of added sugar may correct some of the metabolic abnormalities associated with this syndrome. The issue was recently addressed in a paper published by Robert Lustig and coworkers from the University of California (10).
Lustig studied 43 obese children (ages 8-19) with metabolic abnormalities typical of the metabolic syndrome. All were high consumers of added sugar in their diets (e.g. soft drinks, juices, pastries, breakfast cereals, salad dressings, etc.).
The children were fed the same calories and percent of each macronutrient as their home diet; but within the carbohydrate fraction, the added sugar was removed, and replaced with starch. For example, pastries were taken out, and bagels put in; yogurt was taken out, baked potato chips were put in; chicken teriyaki was taken out, turkey hot dogs were put in. Whole fruit was allowed.
After ten days, diastolic blood pressure fell, insulin resistance decreased, liver tests improved, and triglycerides, LDL cholesterol, and HDL cholesterol all improved.
Recently, more results from this study were published by Gugliucci and coworkers in the journal Atherosclerosis (11). The paper presents data on the effect of fructose restriction on the lipoprotein profile of these same children.
A total of 37 children participated in this part of the trial. They were given food and drinks totaling the same number of calories, fat, protein, and carbohydrates as their typical diets. The only change was their sugar intake. Dietary sugar decreased from 28 percent to 10 percent, and fructose from 12 percent to 4 percent of total calories.
After nine days, the researchers found a 33 percent drop in triglycerides, a 49 percent reduction in apoC-III and dramatic reductions in small, dense LDL particles. LDL size was significantly increased. Significant reductions were also found in apoB and apoE. The TG/HDL-C ratio decreased from 3.1 to 2.4. These changes in fasting lipid profiles correlated with changes in insulin sensitivity.
The Bottom Line
The above data suggest that the lipid abnormalities found in children with obesity and metabolic syndrome can be dramatically improved short-term by reducing the intake of added sugar, particularly fructose. This may implicate fructose consumption as a possible underlying cause of lipid abnormalities associated with the metabolic syndrome.
Interestingly, all of the lipid parameters tested were improved by fructose restriction. The effect on apoB and apo-CIII suggests that the availability of atherogenic LDL and triglyceride-rich lipoproteins was significantly reduced.
The main weakness of Lustig’s and Gugliucci’s studies is that there was no control group. It was not a controlled randomized trial. However, this does not mean that the results shouldn’t be taken seriously. But we will surely need a randomized study to confirm the findings
Recently, a meta-analysis of randomized controlled trials on the effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors was published in the British Journal of Nutrition (1). This meta-analysis demonstrated that compared with participants on low-fat diets, participants on low carbohydrate diets experienced a greater reduction in body weight and blood triglycerides and a greater increase in HDL cholesterol and LDL cholesterol. Despite the positive metabolic effects, the authors concluded that the beneficial changes of the low-carbohydrate diets must be weighed against the possible detrimental effects of increased LDL cholesterol.
Following this publication, I had the pleasure of co-authoring a letter to the editor of the journal which was published a few weeks later (12). In the letter we point out that although the exact mechanisms of low-carbohydrate diets are still debated (improved insulin dynamics, spontaneous reduction in energy intake, increased protein intake, etc), and they are by no means a panacea, the most robust effects of any single long-term dietary intervention in terms of improvements in parameters of insulin resistance, glucose metabolism, lipid biomarkers and cardiovascular disease risk, is the restriction of carbohydrate intake. Despite the author’s conclusions to the contrary, we believe that their meta-analysis supports this premise.
The recently published data by Gugliucci and coworkers clearly suggest that fructose restriction may be one of the magic bullets we need to correct the lipid abnormalities associated with obesity and the metabolic syndrome. If confirmed by randomized studies, this simple intervention may improve the health of millions of people worldwide.