Reply to MA Belury et al. and J Moore

Dear Editor:

The aim of my recent Perspective (1) was to point out that changes in the amount of SFAs consumed will have little impact on SFA concentrations in the body, and that humans can produce SFAs from other nutrients, including excess PUFAs and carbohydrates. The paper emphasizes that replacing dietary SFAs with PUFAs lowers serum cholesterol because the body's mechanisms respond to increases in dietary PUFAs rather than decreases in dietary SFAs. These mechanisms are reasonably well understood and we should integrate this information into our understanding of the impact of dietary constituents on human physiology. Both letters dismiss the fact that the death rate for people with very low cholesterol is greater than for people with normal or moderately high cholesterol and both cite references that do not discuss the consequences of very low cholesterol.

Authors frequently “select” literature that supports their respective arguments. The literature regarding diet, serum cholesterol, lipoprotein subfractions, cardiovascular disease (CVD), and other health effects can be overwhelming, and data as well as conclusions are often inconsistent. There is often little attention to subtle changes in the amounts of PUFAs when substitutions are made. The meta-analysis by Mensink (2) included 84 studies with multiple variations in diets. To draw clear conclusions just regarding the impact of some specific changes in fatty acids is challenging, as indicated by the author in the statement of limitations: “Inclusion of only those studies with strictly controlled diets greatly reduced the chance that dietary factors other than those being studied contributed to the changes observed in serum lipids and lipoproteins. This approach, while valuable … does not provide a clear picture of what might happen in real world settings in which modification of SFA intake might be accompanied by other changes in diet.”

Krauss and Kris-Etherton (3) addressed the shortcomings of low-saturated-fat recommendations, citing studies that resulted in substantial LDL-cholesterol reduction but no CVD benefit and studies that had no significant reduction in LDL cholesterol but substantial CVD benefits. The impact of changes in dietary fats and carbohydrates on CVD risk is complicated by lipoprotein subfractions that are more reliable indicators of CVD risk than LDL cholesterol alone (4). One meta-analysis (5) found that replacing SFAs and trans-fatty acids with predominantly ω-6 PUFAs produced a 13% nonsignificant increase in fatal and nonfatal coronary artery disease (CAD; RR: 1.13; 95% CI: 0.84, 1.53; P = 0.43), whereas replacement with a mixture of ω-6 and ω-3 PUFAs resulted in a 22% significant decrease in fatal and nonfatal CAD (RR: 0.78; 95% CI: 0.65, 0.93; P = 0.005). This reference is “selected” to illustrate the complexities of PUFA substitutions.

The recommendations to lower saturated fat consumption can be confusing to the general populace. Guidelines for parents to give children low-fat milk and dairy products resulted in a large decrease in milk consumption by children and a large increase in sweetened beverage consumption (6). The Perspective emphasizes that full-fat milk consumption is associated with less obesity and cardiometabolic risk in children and adolescents. This is an example of harmful outcomes to young children that can result from following the recommendations to reduce SFAs in dairy products—outcomes that can persist with that population throughout life.

The Perspective errs in the statement that replacing dietary SFAs with carbohydrates does not change serum cholesterol. Replacing SFAs with carbohydrate in the cited reference did not significantly change the ratio of total cholesterol to HDL cholesterol for common SFAs, and in fact increased this ratio when lauric acid was replaced by carbohydrate (7). The ratio of total cholesterol to HDL cholesterol is a more reliable indicator of CVD risk than total cholesterol or LDL cholesterol alone (7). One meta-analysis found that a 5% replacement of dietary SFAs with carbohydrate produced a significant increase in CAD events, although no change in CAD deaths (8).

The section on PUFA oxidation is oversimplified because the aim of that section is to point out that PUFAs are precursors for powerful mediators of the immune response, and it indicates that both proinflammatory and proresolving mediators are formed from both ω-3 and ω-6 PUFAs. It is important to recognize that peroxidation of PUFAs in LDL is a major cause of atherosclerosis (9). There is no convincing evidence, from a mechanistic standpoint, that SFAs per se are responsible for harmful outcomes regarding atherosclerosis, type 2 diabetes, metabolic syndrome, inflammation, and cancer. The consequences of dietary fat substitutions in free-living humans are complex and there is too much inconsistency in the outcomes with regard to various diseases and overall health and longevity to draw firm conclusions. It is best to glean as much information as possible from a variety of scientific studies to develop a more complete picture.

I agree with Moore that refined carbohydrates and sugars are not the proposed alternative for SFAs and there was no intention to imply that. The Perspective attempts to give a balanced presentation with regard to the influence of dietary PUFAs on inflammation and oxidative stress, and animal models and mechanistic studies that show those influences should not be rejected out of hand. This information was presented to make nutrition counselors aware of the potential of PUFAs to augment inflammation and oxidative stress (9). Health care providers should make recommendations on a case by case basis.

The reference Moore cites regarding replacement of SFAs with PUFAs decreasing atherosclerosis does not measure atherosclerosis; it only measured total cholesterol and LDL cholesterol (10). A recent review of atherogenesis (9) describes the role of oxidized lipids and inflammation on the development of atherosclerosis. Space limitations preclude addressing all of Moore's criticisms, but blaming SFAs on increased serum triglycerides or insulin resistance ignores the fact that SFAs were replaced with PUFAs and mechanistic studies have shown how PUFAs and not dietary SFAs influence those physiological effects. Many of the facts presented to support his arguments distort the information with regard to diets and participants involved in the studies. It is my opinion that giving a fair assessment of the literature cited is more important than selecting fragments of data from a wide range of studies and not giving the complete picture regarding those citations.

Notes

The sole author is responsible for all content in this Letter to the Editor. There are no sources of support, other than employment at Long Island University. The author has published 2 books, The Fats of Life: Essential Fatty Acids in Health and Disease (Rutgers University Press, Piscataway, NJ, 2010, 2013) and The Low-Fat Lie: Rise of Obesity, Diabetes and Inflammation (Universal Publishers, Irvine, CA, 2019). Some readers consider these scholarly works a conflict of interest.