Dietary Villains in Cardiovascular Disease- Carbohydrate vs. Fat?

A Tale of Scientific Integrity and Conflicting Research

A recent special communication in the Journal of the American Medical Association (JAMA), entitled “Sugar Industry and Coronary Heart Disease Research: A Historical Analysis of Internal Industry Documents” (1), asserts that the sugar industry (now the Sugar Research Foundation, SRF) likely influenced research to stress the role of dietary fat, rather than sugar, on cardiovascular disease (CVD). For that report, Kearns et al.(1) obtained a myriad of SRF documents, from 1950 to the present, including annual reports, internal research, correspondences with academic researchers, and records of scientific debates.

In 1964, John Hickson, then SRF Director of Research, expressed his concern over reports that sugar increased blood cholesterol, and the risk of CVD. The SRF then formulated a strategy to counter such reports by replication and negation, concluding that sugar is causal for CVD (1). Ultimately, Hickson convinced the SRF to fund external research. In 1967, Hickson approached Dr. Fredrick Stares, Chair of the Harvard Nutrition Department, and two of his departmental peers, Robert McGandy and D. Mark Hegsted, to write a two-part review in the New England Journal of Medicine. In that two-part review, the authors(2,3)asserted that individual studies showing sucrose and starch as contributors to CVD were incorrectly interpreted or contained invalid data (2,3). The authors also discounted randomized clinical trials (RCTs) claiming that diets high in starch, or high in fat, contributed to CVD, while also asserting that population studies significantly showed sucrose to lower risk of CVD (2,3). The review concluded that there was “no doubt” that the only dietary risk for CHD was dietary cholesterol, which could be lessened by substituting polyunsaturated fat for saturated fat (2,3). In the end, the SRF would ultimate pay the authors $6500 ($45,600 in 2017 dollars). Stare was later bestowed with a position on the SRF’s Scientific Advisory Board; his financial ties to the SRF remained unknown until the mid-1970s (1).

The origin of this saga began with research into a troubling spike in CVD, in men, in the years following World War 2 (4,5); before 1900, such incidence had largely been unseen.(6)Intensive research sought to identify CVD risk factors, including dietary items, age, hypertension, smoking, diabetes, physical activity, and blood cholesterol levels.  This flurry of research eventually culminated into a debate whether CVD risk was due to dietary sugar vs. dietary fat. However, to examine causation, in humans, would require population-based nutrition studies over long time durations, while also being very difficult to carry out, due to lack of controlled conditions (7).

At the forefront of the anti-sugar camp was Dr. John Yudkin (Oxford University), beginning in 1957 (8). While his early research was quite diverse, Yudkin wrote various reviews, noting fallacies in prior and current populations studies linking dietary fat to CVD. In one publication, Yudkin asserted that trends in diet, as associated with mortality, in an population study in the United Kingdom, from 1928 to 1954, provided no evidence of a link between animal or hydrogenated fat and CVD, and that sugar was the dietary factor most signifi-cantly associated with CVD (8). Additionally, based on historical studies of numerous countries, Yudkin also asserted that gain of prosperity led to increases in both fat and sugar intake, with the latter associated with increased CVD risk (9). Moreover, in his assessment of the burgeoning incidence of CVD in the first half of the 20th century, he noted a considerable increase in cigarette smoking, and due to increased industrial machinery, a decline in physical activity. Regarding dietary factors, Yudkin noted that that humans evolved as carnivores, with sugar not significantly consumed until the 15th or 16th century (very short timespans in evolutionary). In 1700, sugar consumption was about 4 lbs/person, increasing to 18 lbs in 1800, and 60 lbs in 1900 (10). Yudkin further noted that, from 1920 – 1960, sugar intake increased over 2.5-fold(11), and today stands at 170 lbs/person/annum.
Dr. John Yudkin
Dr John Yudkin

The vilification of dietary fat actually dates back to 1913, when the Russian pathologist Nikolai Anitschkow fed purified cholesterol to rabbits, which elevated their serum cholesterol to over 1,000 mg/dl, concurrent with observation of “fatty streaks” in the animals’ arteries (12). While Anitschkow’s findings were largely ignored during his lifetime, they were later revisited by the brilliant and highly charismatic scientist, Dr. Ancel Keys (University of Minnesota), who in 1947, designed and led The Minnesota Prospective Study of Minneapolis businessmen, aged 45-55, following these men over many years, and post-CVD mortality, assessed a myriad of factors (13). Keys also well argued that war-induced dietary changes were brought about by Nazi occupation of several European countries, restricting the import of high-fat foods, livestock, eggs, etc., resulting in lower CVD incidence (14). Keys published that a controlled setting (a Minnesota insane asylum), over 6 years, showed that high-fat diets strongly correlated with elevated serum cholesterol[5], although later analyses of that data challenged such correlations (15,16). In another report, Keys argues that, like Yudkin, economically prosperous nations had higher incidences of CVD; Keys, however, argued that this increased risk was not due to the consumption of carbohydrates, but from saturated fats and cholesterol (17).

In 1956, Keys also initiated his “Seven Countries Study,” following the lifestyles and health of 40 – 59-year-old men, in the United States, Finland, the Netherlands, Italy, Yugoslavia, Greece, and Japan (18). This study was interpreted as revealing high blood pressure and cigarette smoking to significantly result in high serum cholesterol, stroke, and CVD, with minimal effect of physical activity (19), although later analyses disputed some of those associations (20). Based on this interpretation, and other seminal studies, Key formulated the Mediterranean diet, rich in fruits, whole grains, olive oil, and vegetables, but sparing in sweets and meat (21). In one recent meta-analysis, the Mediterranean diet demonstrated modest efficacy (22). and remains prevalent to this day.

However, the interpretation of the still-ongoing The Seven Countries study was, and remains, quite controversial. For example, some have claimed that from 22 countries with initially available data, Keys “cherry-picked” only those that supported his hypotheses, omitting others, such as West Germany and France, both known for high-fat diets but low CVD (6,23). Another criticism was that the study lacked information to correct for background incidence (24). Other objections were that the statistical analyses were not significant enough to draw conclusions, or that homogeneity of diets precluded its analysis for significance to CVD (25), a consideration foreshadowed by Yudkin (11). Another conclusion was that only age and hypertension could be linked to CVD risk (26). In parallel to The Seven Countries, one interpretation of the Nurses’ Health Study (during the timeframe of 1980-1994), using a complex data correction by assessing total energy intake, was that there was no association of dietary intake of saturated fat and cholesterol with CVD (27).

In 1946, another population study of similar nature, The Framingham Heart Study, (instituted by President Roosevelt in 1946 over his own heart disease), was interpreted to find no risk of dietary fat and CVD (28,29). While both studies showed overall serum cholesterol as a weak risk factor for CVD, it later became evident that the internal “packaging” of cholesterol, into high- or low-density particles, was more relevant than total cholesterol levels themselves (30).

Early on, Keys found a highly influential ally in Dr. Paul Dudley White, then-president of the American Association for Cardiology.  Following a heart attack, on September 25, 1955, President Eisenhower summoned White to his bedside, seeking the nature of his malady (6). White, already aligned with Keys, declared high-fat/high-cholesterol diets responsible for the burgeoning incidence of CVD. Subsequently, Keys and colleagues gained prominence in influential positions in the Eisenhower administration, American Heart Association, and the National Institutes of Health (6), with Keys being featured on the front page of Time magazine (31).

Dr. Ancel Keys
Dr. Ancel Keys, circa 1952
By this time, the anti-fat hypothesis had become deeply entrenched into American society, influencing food-makers to design low-fat dietary products, engendered a backlash against the dairy and meat industries, and spawning a spate of best-selling books of various low-fat diets. Food manufacturers raced to manufacture and market low-fat versions of numerous foods, vegetable oils to
usda food pyramid 1992
 replace animal fat oils, margarine to replace butter, and whole-wheat grains, rather than refined grains. In the 1970s, Dr. Richard Atkins, however, published his “Atkins diet,” consisting of high fat and protein, and very low levels of carbohydrates.(6) Atkins was mostly ridiculed, and his diet was soon discarded, although it has been revisited in recent times (see below).

In 1992, the Department of Agriculture’s proclaimed their dietary recommendations via a “food pyramid,” consisting of six horizontal sections, with carbohydrates at the bottom rung of the pyramid (thus the most important diet item), with fat and cholesterol atop the pyramid, suggesting only very sparing (< 5%) of consumption (32). The pyramid was revised in 2005 as “MyPyramid,” with the size of vertical colored sections indicating preferential food proportions. Those guidelines were again replaced in 2011, as “My Plate,” backed by First Lady Michelle Obama, showing food recommendations as sections of a plate, lacking portions for fat or meat altogether. 

Starting in the late 1970s, however, a new generation of researchers, unbeholden to previous dogma, began challenging the low-fat hypothesis. For example, in 1978, an American Heart Association study was interpreted to show no association between CVD and cholesterol-containing foods (33). 1980, Bond et al. noted the difficulty in measuring atherosclerosis (34), while another study demonstrated low- (LDL) and high-density (HDL) lipoproteins as more relevant to CVD than mere total cholesterol (35). Another study claimed that total fat intake (under constant total calories) did not alter serum cholesterol(15), with others reported a lack of correlation between obesity and total fat intake, rather total calories from any food type.(36) Indeed, over the past 40 years, dietary fat consumption has declined, while obesity, and carbohydrate intake, have soared (6,37). The well-established correlation between type 2 diabetes and CVD may further implicate sugar metabolism (38).

The Adkins diet (39), or various minor variants, has experienced a revival of sorts, demonstrating statistically significant weight loss, compared to other popular low-fat diets (Ornish, LEARN, and Zone) (40,41). In the short-term (one year), high-fat diet subjects underwent greater reduction in LDL, and greater increase in HDL, compared to those on a low-fat diet. However, after two years, the high- and low-diet groups yielded very similar outcomes (42). However, other reviews have acknowledged likely benefit from low carbohydrate/high fat diets (43-46).

The anti-fat movement also led to backlash again fast-food restaurants, although most complied with the sentiment by adding “healthy” foods such as salads and fruits to their menus. One pinnacle of the low-fat movement was Martin Sperlocks’s 2004 documentary, “Super Size Me,” following a claimed 30-day diet excluded to three meals/day from McDonalds, claiming an average of 5000 calories/day (recommended for me at 2500/day), increased cholesterol to 230 mg/dL (starting level undisclosed), a weight gain of 24 lbs, sexual dysfunction, and a body mass index rise of 13%. Criticism of the film noted that Sperlock did not detail his day-to-day foods eaten (nor the quantities), and many observed that 5000 daily calories (double the recommended number), from any food source, absent physical activity, would result in marked weight gain. Moreover, the filmmakers conceded that the 30-day diet actually resulted in over 30 lbs. over sugar, vs. 12 lbs. of fat. Ironically, others embarked on 30- to 180-day McDonalds-exclusive diets, claiming 40 mg/dL decreased cholesterol, and loss of 20- to 60-lbs, respectively.

So, what is the correct meaning of “healthy eating”? Could it be that >40 years of government-established guidelines, with implications to our own mortality, has been wrong? While it seems the vilification of high fat has been largely refuted, is sugar now public enemy #1? While various studies now support the effectiveness of high-fat/low-carbohydrate diet in weight loss, with no short-term detrimental effects (increased serum cholesterol, fatty deposits, etc.), the long-term safety of these diets remains unknown. Moreover, meta-analyses have also demonstrated effective weight loss by low-fat diets, including Keyes’s Mediterranean diet and the Ornish Diet. It is also clear that, in laboratory animals, high serum cholesterol can be achieved by the feeding of high-fat diets, although this may be species-specific.(47) Molecular mechanistic studies, of how sugar my affect LDL formation, or fatty, artery-blocking “plaques, remain largely unknown. Moreover, it seems that inflammatory responses play a role, and whether this is a cause or effect remains unanswered (48).

Thus, regardless of the outcome of the low carb vs. low fat debate, the “take-home” message from this tale is perhaps even more disturbing, i.e., that conflicted science, by a notable few, may have been integrated into the very fabric of our society. In this case, science was strongly subjective toward one narrative. Some steps have been taken to avoid these incidents in the future, including requirements to declare possible conflicts of interest, and minimizing industry-sponsored research funding to investigators. However, in this present-day hypercompetitive, unsustainable research environment (49,50), (likely to become even more exasperated by the current governmental administration) (51), desperate investigators may turn toward non-public sources of funding, even those again expecting specific outcomes.

Another deleterious outcome of such subjective science is its effect on public opinion. For example, given the corrupt studies of sugar and tobacco, why should the average person believe in climate change, the safety of vaccines, and the safety of genetically modified crops? It has recently been posited that public opinion of science is shaped by our own intuitive theories (52), such as our instictive understanding of geology and weather as static and undynamic, even while those notions oppose scientific findings that the climate is amenable to change, even by human activity. This hypothesis might suggest that many non-scientists are pre-existently anti-science, and debacles such as this will only deepen that sentiment.




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