An important question is whether alterations in diet—whether in regard to carbohydrate, fat, or saturated fat content—have predictable effects on lipoprotein profiles and, specifically, atherogenic dyslipidemia. This has implications for nutritional counseling for patients at risk for CVD: which diets are likely to induce or worsen atherogenic dyslipidemia and thereby increase CVD risk, and thus should be avoided, and which diets may reverse the dyslipidemia and should be recommended. A related question is whether particular diets are of greater or less benefit in individuals with atherogenic dyslipidemia compared to those without it.
In one study, 105 healthy middle-age men were placed on high-fat (46% of calories from fat), low-carbohydrate and low-fat (24% of calories from fat), high-carbohydrate diets in a crossover design in which they experienced 6 weeks on each diet [37
]. To simplify the interpretation of the study results, the proportions of types of fat (unsaturated vs. saturated, 1:1 ratio) and types of carbohydrates (simple vs. complex, 1:1) remained fixed in these diets. Across all subjects, there were significantly higher levels of triglycerides and the LDL3/LDL4 subfractions (small and very small LDL particle concentrations), as well as lower HDL-C levels, while on the low-fat diet compared to the high-fat diet. Thirty-six subjects who were pattern A or intermediate (as judged by LDL peak particle diameter) when on the high-fat diet converted to pattern B on the low-fat diet; all of the individuals who were pattern B on the high-fat diet remained pattern B on the low-fat diet. In a follow-up study, the individuals who had been pattern A on both the high-fat and low-fat diets were subjected to a very-low-fat diet (10% of calories from fat, with replacement by carbohydrates) [38
]. One-third of the subjects converted to pattern B on this diet. Thus, reduction of fat along with increased carbohydrate intake altered lipoprotein profiles towards atherogenic dyslipidemia.
Of interest, individuals who were pattern B on a high-fat diet, when compared to those who were pattern A on a high-fat diet, experienced a much larger reduction in LDL-C when on a low-fat diet [37
]. This was confirmed in both men and in pre-menopausal women, with a two- to threefold greater reduction in LDL-C observed [39
]. This phenomenon appeared to be the consequence of differential effects on lipoprotein profiles. Pattern A individuals experienced a larger decrease in LDL1 (large LDL particle concentrations) and an increase in LDL3 (small LDL particle concentrations) with little change in LDL2 (medium-large particle concentrations), whereas pattern B individuals displayed a decrease in LDL2 with a smaller decrease in LDL1 and no change in LDL3. Besides explaining the discrepancy in LDL-C alteration, these observations also explain why many pattern A individuals converted to pattern B (35%) but not vice versa (6%).
Extrapolating across all of these studies, the prevalence of pattern B increases with the amount of dietary carbohydrate and decreases with the amount of dietary fat. However, in these studies the changes in the proportions of calories derived from fat were largely balanced by reciprocal changes in calories from carbohydrates, making it difficult to determine whether dietary fat or carbohydrates are the major influence on atherogenic dyslipidemia. A study in 178 overweight men shed some light on this question. When compared on a higher-carbohydrate diet (54% of calories from carbohydrates, 1:1 simple:complex) versus a lower-carbohydrate diet (39% of calories from carbohydrates, 1:1 simple:complex), between which the difference was made up of protein calories (15 vs. 29%) rather than fat (minimal change), the subjects had a higher prevalence of pattern B when on the higher-carbohydrate diet [41
]. This observation suggests that dietary carbohydrates are the principal driver of atherogenic dyslipidemia.
A more complete analysis with the 178 overweight men was highly informative as to the effects of varying carbohydrates and saturated fat, as well as weight loss, on lipoprotein profiles [42
]. Four diets were compared: (1) 54% of calories from carbohydrates (1:1 simple:complex) with low saturated fat, (2) 39% of calories from carbohydrates (1:1 simple:complex) with low saturated fat, (3) 26% of calories from carbohydrates (1:1 simple:complex) with low saturated fat, and (4) 26% of calories from carbohydrates (1:1 simple:complex) with high saturated fat. Diets (1) and (2) had equal fat content, diets (3) and (4) had equal fat content that was higher than that of diets (1) and (2). The subjects underwent a weight-maintenance phase of 3 weeks on the assigned diets, followed by a weight-loss phase of 5 weeks (with a subsequent four-week weight stabilization period) on the same diets.
During the weight-maintenance phase, the subjects on the low-carbohydrate diets [(3) and (4)] experienced significant decreases in their triglyceride levels as well as their LDL3 and LDL4 levels (small and very small LDL particle concentrations); the individuals on the higher-carbohydrate diets displayed only modest changes. In contrast, during the weight-loss phase, the individuals on higher-carbohydrate diets experienced larger decreases in triglycerides and small LDL particle concentrations than did those on low-carbohydrate diets. Thus, by the end of the study, the higher-carbohydrate subjects had “caught up” with the low-carbohydrate subjects. The lower the dietary carbohydrate content, the lower the prevalence of pattern B, both after the weight-maintenance phase and after the weight-loss phase, although the differences in the prevalence of pattern B were smaller after weight loss, again pointing to a “catch-up” phenomenon.
Comparing the low-saturated-fat and high-saturated-fat low-carbohydrate diets [(3) vs. (4)], there were essentially no differences in changes in triglycerides, small LDL particle concentrations, or prevalence of pattern B, either in the weight-maintenance or weight-loss phases [42
]. This finding indicates that dietary saturated fat content has little influence on the components of the atherogenic lipoprotein phenotype. This agrees with the results of a study that compared the effects of four-week treatments with a high-saturated-fat diet (38% of calories from fat, with 20% of calories from saturated fat), a monounsaturated fatty acid (MUFA) olive oil-rich diet (38% of calories from fat, with 22% of calories from MUFA), and a high-carbohydrate diet (30% of calories from fat, with <10% of calories from saturated fat, and 55% of calories from carbohydrates) in 84 individuals [43
]. (In all diets, ~40% of the carbohydrate calories came from simple carbohydrates, the remainder from complex carbohydrates.) There were no differences in triglycerides, LDL size, or prevalence of pattern B between the high-saturated-fat and high-MUFA diets; in contrast, both high-fat diets yielded higher LDL sizes than the high-carbohydrate diet, with one-third of the subjects converting from pattern A to pattern B with the high-carbohydrate diet. The lack of difference in LDL size seen between the two high-fat diets is consistent with two earlier studies, one of which noted a minimal increase in LDL size with a high-MUFA diet compared to a high-saturated-fat diet [44
], the other of which reported no difference [45
Finally, analysis of a prospective cohort study (the Framingham Heart Study) confirmed that fat content in the diet, after multivariable adjustment for carbohydrate intake and a variety of other potential confounders, did not significantly affect LDL size or triglyceride levels in either men or women [46
]. This was true regardless of the quality of fat studied—total fat, saturated fat, MUFA, or polyunsaturated fatty acid (PUFA) content. Thus, it appears that both the quantity and quality of fat consumed (assuming no change in the number of calories obtained from carbohydrates) have minimal effects on the atherogenic lipoprotein phenotype.
Although it is possible that different types of carbohydrates may have different effects on lipoproteins, none of the discussed studies were able to shed light on this question, since in all cases the ratio of simple to complex carbohydrates was kept constant among the experimental diets. Given that carbohydrate intake appears to be the primary driver of atherogenic dyslipidemia, it would be desirable for future studies to directly compare diets in which the proportions of different types of carbohydrates are varied, with the overall number of calories coming from carbohydrates being held constant.
In conclusion, either lowering the dietary carbohydrate content or losing weight appears to attenuate atherogenic dyslipidemia (although there does not appear to be an additive effect of the two), whereas altering the total fat or saturated fat content has little influence. However, being placed on a lower-fat, higher-carbohydrate diet appears to result in lower LDL-C levels than a higher-fat, lower-carbohydrate diet, particularly for individuals starting with pattern B. Thus, it remains unclear whether having high or low dietary carbohydrate content is more beneficial for cardiovascular health. It should be noted that the intervention studies described above were all short-term (weeks) and so were not able to compare long-term CVD outcomes resulting from the various diets. Thus, we await long-term studies before these data can be used to help shape nutritional recommendations for patients at CVD risk.