Weighing Evidence of the Role of Saturated and Unsaturated Fats and Human Health

Dear Editor:

The article by Lawrence (1) asserts that there are many misconceptions in the extensive literature that have consistently established beneficial health effects of decreasing dietary SFAs and replacing them with unsaturated fatty acids, mainly omega-6 PUFAs and principally linoleic acid. The article by Lawrence has many inaccuracies and ignores the overwhelming literature that strongly demonstrates health benefits of replacing dietary SFAs with PUFAs. A repeated theme of Lawrence's article is the selection of individual papers with interpretations that are often misleading and, in some cases, inaccurate. In our letter, we discuss the scientific evidence that clearly refutes Lawrence's conclusions.

Relative to the associations of dietary SFAs and serum cholesterol and atherosclerosis, there is consistent evidence that reducing dietary SFAs, and specifically replacing them with unsaturated fatty acids, decreases LDL cholesterol and cardiovascular disease (CVD) risk (2–4). Importantly, elevated LDL cholesterol increases atherosclerosis and CVD risk and consequently is an established causal risk factor (5). There is also strong evidence that decreasing LDL cholesterol decreases fatal and nonfatal CVD and all-cause mortality, which is the basis for current cholesterol treatment guidelines (6). Lawrence states that flaws in the studies used to support the “diet–heart” hypothesis have been documented for years, to which we fervently disagree. The unintended consequence of the “diet–heart” hypothesis was published in the dietary guidelines of 1977, which recommended a reduction of total dietary fat, instead of SFAs. Lawrence misses the impact of the reduced fat intake recommendation that entailed a concomitant increase in carbohydrates, including sugars, and refined carbohydrates, which closely aligned with increased rates of obesity and type 2 diabetes (7).

We disagree with Lawrence's interpretation of the literature where he states that replacing dietary SFAs with carbohydrates does not change serum cholesterol. In fact, an extensive meta-analysis of controlled clinical studies by Mensink (8) showed that replacing SFA with dietary carbohydrate reduces total cholesterol and LDL cholesterol. In addition, claiming that all-cause mortality is higher in individuals with low total cholesterol compared with those with normal or moderately elevated cholesterol concentrations based on data from few select cohort studies ignores reverse causality, as well as the robust randomized controlled clinical trial evidence that demonstrates otherwise (6).

Lawrence's section on PUFA oxidation and inflammation is one-sided and oversimplifies an ever-expanding area of nutrition involving metabolomics, data analytics, physiology, endocrinology, and cell biology. Much of this literature is improving our understanding of the role of oxygenated metabolites derived from PUFAs in cellular processes involving gene expression, post-translational modification, and enzyme activity (9). Metabolites derived from PUFAs (e.g., prostaglandins, leukotrienes, and hydroxylated fatty acyl molecules) may induce acute inflammatory pathways but also exert potent anti-inflammatory and pro-resolving activities in tissues. Inflammation that is modulated by oxylipins is not determined simply by PUFAs, but rather a complex milieu of cellular processes including PUFA content of membranes, energy availability in cells, and the short half-life of most oxylipins.

In terms of saturated fats, there are numerous reports from preclinical and clinical studies showing that intake of SFAs not only promotes dyslipidemia and atherosclerosis (4–6) but is also associated with all-cause, cardiovascular, and cancer mortality (10). These topics are clearly relevant to how SFAs and PUFAs affect the pathogenesis of the metabolic syndrome, atherosclerosis, type 2 diabetes, and cancer, as well as premature mortality. Unfortunately, Lawrence failed to capture the state of the art of the consistent and evolving science showing the importance of PUFAs in maintaining and promoting health and the harmful outcomes of diets rich in SFAs.

As reputable researchers who appreciate and value scientific evidence, we can all agree that no good is served when strong and consistent evidence is ignored. The continuation of the message that dietary SFAs pose no health problem muddles public health messages; confuses many practitioners, scientists, and consumers; and erodes trust in sound science.

Notes

The authors’ responsibilities were as follows—All authors: wrote and read and approved the final manuscript.

Author disclosures: MAB discloses consultancy with Bath and Body Works, grant support from the United Soybean Board and service as an elected board member for the American Society for Nutrition. ER discloses consultancy with Amarin and consultancy, grant support, and personal fees with the California Walnut Commission. The other author reports no conflicts of interest.