The film seeks to refute both the documentary Super Size Me and the lipid hypothesis, a theory of nutrition started in the early 1950s in the United States by Ancel Keys and promoted in much of the Western world.

Naughton addresses Spurlock's argument that the current prevalence of obesity cannot have been caused by home cooking or by non-corporate, family-owned restaurants, since they have been around longer than corporate fast food chains.

Naughton and his interviewees say that anti-McDonald's sentiment is motivated by anticonsumerism, the desire by lawyers to sue rich corporations rather than family restaurants of comparatively modest means, and paternalism by advocacy groups like the Center for Science in the Public Interest.

Naughton challenges the notion that the United States is experiencing an obesity epidemic by pointing out that the Centers for Disease Control, which made that assertion in 2004, recanted it the following year.

The documentary also focuses on the science and politics behind the nutrition recommendations given by the U.S. government, largely based on the lipid hypothesis, which Fat Head claims is in error on all three of its main propositions.

According to the film, among other sources such as Mark Sisson, there has never been a single scientific study that has linked a high fat diet to increased rates of heart disease.

[4] William Lee of DVD Verdict similarly considered that, despite the middle part where experts are interviewed and concepts such as cholesterol are explained, the intention of debunking dietary myths "is lost in the ill-conceived, confrontational presentation of Fat Head".