Fat Research During the MadMen Era

My friends keep obsessing over the new season of MadMen, so lets take a look at some of the landmarks of obesity related topics in this era. This era is well known for establishing Ancel Key’s Lipid hypothesis which states saturated fat increases cholesterol and increased cholesterol is a risk for heart disease therefore reduction of cholesterol and saturated fat reduced heart disease. This hypothesis is still widely accepted today. However, contradictory evidence was emerging around the same time. Two notable scientists providing an alternate hypothesis to heart disease at this time were Peter Ahrens and John Gofman.

John Gofman is famous for pioneering cholesterol research. While everyone was focusing on cholesterol as the circulating fat during the 50s, Gofman pointed out that the body circulated more lipid like substances than just cholesterol such as triglycerides. Additionally, there was also the lipoproteins that were involved in these lipids. This discovery naturally lead to the question: is there more to this story than just cholesterol? However, due to the technology at the time, it was only feasible to measure cholesterol (total).

With time, scientists eventually discovered three important Lipoproteins involved with cholesterol: HDL (the so called good one), LDL (what we commonly think of as the bad one) and VLDL (which carries most of the triglycerides). While everyone else was concerned about total cholesterol, Gofman realized that LDL seemed to be in larger amounts in patients with atherosclerosis independent of their total cholesterol. Therefore, Gofman pointed out that measuring total cholesterol was useless. However, even more compelling, was Gofman’s research on VLDL.

Gofman discovered that eating saturated fats could raise LDL which would fall in line with our current way of thinking. However, he also discovered that eating more carbohydrates would raise VLDL levels! The implications of this finding showed the potential dangers of using a low fat – high carbohydrate diet. For example, Gofman pointed out that the substitution of saturated fats for carbohydrates (the “carbohydrate factor” as he put it) could potentially cause more harm for individuals if it elevated their VLDL levels too high. This was of particular concern since cholesterol levels during this era was measured as total cholesterol and not into more specific subsets.

John W. Gofman

“If LDL was abnormally elevated, then this low-fat diet might help, but what Gofman called the ‘carbohydrate factor’ in these low-fat diets might raise VLDL so much that the diet would do more harm than good.”

– Gary Taubes, Good Calories Bad Calories

Another prominent scientist at this time was Peter Ahrens who is associated with terming the phenomenon of carbohydrate-induced lipemia. Simply put, this is circulation of fatty triglycerides in the blood (carried by VLDLs as shown from Gofman’s research) which is a risk for heart disease. The question is: was a person more likely to have this circulating systemically on a high carb or a high fat diet?

Since VLDLs were more likely to increase under carbohydrates consumption, you would be right if you said a diet focused more on carbohydrates. Ahrens demonstrated this by showing blood serum from the same patient following a high fat or high carbohydrate meal. The test tube was cloudy with triglycerides if they had eaten the carbohydrate diet but clear if they had eaten the high fat diet. However, during this period, having a high triglyceride level was still being questioned whether or not to play a role in heart disease. Ahrens warned the lipid hypothesis needed more questioning before low-fat diets (which would mean an increase of calories from carbohydrates) should be recommended since they did not know whether carbohydrates, fats or some other factor played a role in heart disease.
***Of note, Ahrens showed that a high carbohydrate diet would have less triglyceride levels if the total caloric intake was very low. A point he used to argue certain Asian countries having lower heart disease despite having a high carbohydrate diet at the time.

Margaret Albrink, at the metabolic division of Yale Medical School would provide some observations on the importance of triglycerides. Her findings showed high triglycerides were more common than elevation of cholesterol in patients with cerebral, coronary and aortic atherosclerosis. And that potential accumulation of triglycerides may be the most common lipid derangement in coronary artery disease.

Albrink presented her results to the association of the American Physicians but was met with anger and disbelief. This occurred only recently after the American Heart Association decided to accept and endorse Ancel Key’s idea of saturated fat and cholesterol (Lipid hypothesis) being the culprit. Albrink would continually be attacked by proponent’s of the lipid hypothesis. However, she would receive more support from other scientists later such as Nobel laureate Joseph Goldstein who found elevated triglyerides just as common if not more so than cholesterol in over 500 patients with heart disease. Even more interesting was a study done by Peter Kuo which showed:

More than 90% of the 286 patients were found to have hyperglyceridemia derived from increased endogenous lipogenesis from carbohydrate. This abnormal carbohydrate sensitivity was revealed with an ad libitum carbohydrate (35% to 40%) diet. Since lipoproteins synthesized from carbohydrates were shown to be rich in both triglyceride and cholesterol, carbohydrate-sensitive hyperglyceridemia was frequently found in association with hypercholesteremia. The abnormal metabolism was controlled by a sugar-free diet, with a carbohydrate allowance of 125 to 150 gm supplied as starches.

So 90% of the subjects had elevated triglycerides related to carbohydrate consumption. Additionally, since VLDLs carry triglycerides and cholesterol (majority triglycerides), that could potentially mean increases in cholesterol levels could be related to carbohydrate consumption as well. Interestingly enough, the elevated triglycerides and cholesterol were controlled when patients were put on limited carbohydrates…

Even more interesting was an editorial put out by the Journal of the American Medical Association about these new discoveries:

“Research,like therapeutics, experiences cyclic fads. These are characterized by a rush of investigators towards an avenue of research initiated by publication of a few promising studies. For nearly fifteen years, an almost embarrassingly high number of researchers boarded the “cholesterol bandwagon” in pursuit of understanding of atherosclerosis. This fervent embrace of cholesterol to the exclusion of other biochemical alterations resulted in a narrow scope of study of a disease which is probably multifaceted in causation. Fortunately, other fruitful approaches have been made possible in the past few years by identification of the fundamental role of such factors as triglycerides and carbohydrate metabolism in atherogenesis.”

Somehow tho, saturated fats and cholesterol being the culprit behind heart disease has still become unquestionable medical facts to many practitioners and thus society. Just how sure are we of this?

Peter Ahrens

“Some thought him to be obtuse or stubborn, as he refused to endorse claims that changing our diets by lowering cholesterol intake would be the sole and most effective weapon to win the battle against heart disease. He was indefatigable in pointing out the necessity of additional clinical research in human subjects to delineate individual differences in response to diet. Unpopular as these views may have been, time has revealed the correctness of his views.
http://www.jlr.org/content/42/6/891.full

Serum Lipids and Cerebral Vascular Disease
ROBERT G. FELDMAN, MD; NEW HAVEN; MARGARET J. ALBRINK, MD
Arch Neurol. 1964;10(1):91-100.

Hyperlipidemia in Coronary Heart Disease I. Lipid levels in 500 survivors of  Myocardial InfarctionJOSEPHL.GOLDSTEIN,WILLIAMR.HAzzmm, HELMUTG.ScinoTT, EDWINL.BIERMAN,andARNoG.MOTULSKYwiththeassistanceof MARYJoLEVINSKIandELLEND.CAMPBELL

Hyperglyceridemia in Coronary Artery Disease and Its Management
Peter T. Kuo, MD JAMA.1967;201(2):87-94. doi: 10.1001/jama.1967.03130020033007

CORONARY HEART DISEASE AND CARBOHYDRATE METABOLISM JAMA.1967;201(13):1040-1041. doi:10.1001/jama.1967.03130130066017CORONARY HEART DISEASE AND CARBOHYDRATE METABOLISM JAMA.1967;201(13):1040-1041. doi:10.1001/jama.1967.03130130066017

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