Metabolic Disease: Is It the Fat, Sugar, or Processed Food?

Caroline M. Apovian, MD


June 18, 2020

The increasing rise in prevalence of obesity and metabolic disease over the past 50 years has spurred research on the macronutrient content of the food we eat, as well as on the calories we consume and the ingredients in the food we eat. Research and debates have been inconclusive so far.

The 80th Scientific Sessions of the American Diabetes Association offered yet another debate, among three researchers who have done much to transcend the original low-carbohydrate vs low-fat debates earlier in this century. Sarah Hallberg, DO, medical director at Virta Health, presented data that favor high saturated– and total-fat diets compared with low-fat, high-carbohydrate diets. Barbara Corkey, PhD, professor of medicine at Boston University, focused on the quality of carbohydrates and added ingredients in modern food. And Kevin Hall, PhD, a senior investigator at the National Institutes of Health, argued that it's a matter of the types of carbohydrates that people are consuming.

Are You Really What You Eat?

Hallberg started the session with a discussion on saturated fat content in the diet and lipid levels, presenting a study of the effects of stepwise increases in dietary carbohydrate on circulating fatty acids and palmitoleic acid in metabolic syndrome. The results of this study — which progressively increased dietary carbohydrate while concomitantly decreasing total saturated fat — indicated that dietary and plasma saturated fat are not related. In fact, it was found that increasing dietary carbohydrate promotes incremental increases in plasma palmitoleic acid, which is a biomarker consistently associated with adverse health outcomes. The corollary was also true, which is that palmitoleic acid decreased with increases in dietary saturated fat.

She presented other studies showing that a low-carbohydrate diet, despite being higher in saturated fat, decreases circulating saturated fatty acids, and that dietary carbohydrate restriction improved metabolic syndrome independent of weight loss.

The literature seems to suggest that palmitoleic acid is a marker of excessive carbohydrate consumption that can reflect shunting of carbohydrate and can predict future metabolic disease. In fact, increasing palmitoleic acid levels at age 50 has been associated with increased hs-C-reactive protein levels, a marker of inflammation, at age 70 years. Hallberg discussed how palmitoleic acid is an independent marker of triglyceridemia and abdominal adiposity, making a good case for this serum marker to be measured more frequently in clinical practice.

According to Hallberg, one can predict a metabolic health continuum depending on the dietary matrix of saturated fats and carbohydrates we consume. At one end of the spectrum is low consumption of dietary carbohydrates, resulting in increased saturated fat oxidation and decreased saturated fat synthesis, leading to decreased plasma saturated fat and palmitoleic acid, increased insulin sensitivity, and normolipidemia. At the other end is high dietary carbohydrate, predicting increased saturated fat storage and increased saturated fat synthesis, leading to increased plasma saturated fat and palmitoleic acid, increased insulin resistance, and dyslipidemia.

At the end of her talk, Hallberg presented a study that has been widely duplicated, where 2 weeks of a high-fat, carbohydrate-restricted diet resulted in increased insulin sensitivity, decreased triglycerides, and reduced hunger. She concluded that we do not know what causes insulin resistance and metabolic disease, that consumed saturated fat and serum or stored saturated fat are not the same thing in the context of carbohydrate restriction, and that increased palmitoleic acid may be an early warning sign of diabetes risk.

My summary: Low-carb, high-fat diets are healthy for the cardiovascular system and do not increase diabetes risk. Patients should be able to enjoy saturated fat in the diet as long as simple carbohydrate is minimized, and this should maintain good serum lipid levels.

'The Nature of Carbohydrates Has Changed'

Next was Dr Barbara Corkey, who began by reminding us that the sequence of appearance of obesity and hyperlipidemia, insulin resistance, and elevated basal insulin has not been established, but all three are correlative and all three can stress susceptible beta cells in the pancreas. Both obesity and hyperinsulinemia can be induced separately in vitro and can cause insulin resistance. She added that correlation is also strong with consumption of processed foods and extensive use of plastics, but we do not know what comes first.

Corkey noted that historically, our ancestors thrived on both high-fat and high-carb diets, depending on the environment, with warm environments lending toward high-carb diets and cold environments lending toward high-fat, meat-eating patterns. History makes it difficult for us to blame high-carb diets for our problems, but the nature of carbohydrates has changed since our ancestors roamed the planet, she said.

With a reminder that carbohydrates are now processed with preservatives and many other ingredients to make them shelf stable, and that insulin secretion is aberrant in metabolic disease, she posed the question: Could it be that some of these ingredients cause hyperinsulinemia? Before 1908, a generation of carbohydrate consumers did not develop metabolic disease, but now we do.

Corkey's lab found that many of these added ingredients do cause glucose-stimulated insulin secretion and an increase in basal glucose and insulin. She also found that basal insulin can be increased by excess nutrients or fuel, monoglycerides, and iron. Diazoxide and low-glycemic and ketogenic diets, on the other hand, have been shown to lower insulin levels. Hyperinsulinemia should be treated before obesity or hyperglycemia ensue; however, this is not the way metabolic disease is treated today.

Corkey concluded that although carbohydrates do not cause metabolic disease, they are essential for disease development. Carbohydrate removal from the diet can improve metabolic disease and type 2 diabetes. This will decrease hyperinsulinemia, fat storage, and non-food chemical consumption, and it causes no harm, as there are no essential carbohydrates.

My summary: Carbohydrates are not needed in the human diet. If you want to avoid diabetes risk, there is no real need for carbs; a ketogenic diet will reduce risk.

Ultraprocessed Foods Affect Calorie Intake

The last speaker was Dr Kevin Hall. He described how he tested the energy intake predictions of the carbohydrate-insulin model proposed by Ludwig and Ebbeling. He found very little difference in metabolic energy expenditure with low-fat vs low-carb diets in a study of monitored feeding in a crossover design trial.

However, in body composition studies, he did find more body fat loss on the low-fat diet, with no changes in total body weight. Meta-analyses corroborate very little differences in change in metabolic rates between isocaloric low-fat vs low carb-diets. This was also the case in body composition changes between isocaloric low-fat vs low-carb diets in the same meta-analysis.

He showed us how the composition of the US food supply has increased in both fat and carbohydrate content. Dietary quality has also changed dramatically, with the purchase of ultraprocessed foods in the United States going up from 24% to 55% between 1938 and 2001.

Hall then described his study that matched ultraprocessed and unprocessed diets for calories, carbs, fats, proteins, sugar, sodium, and fiber. The ultraprocessed diet caused the participants to eat 500 calories more per day than when they were on the unprocessed diet, and also caused body fat mass gain. Surprisingly, there were no differences in self-reported measures of appetite and pleasantness or familiarity of the foods.

My summary: It is not about the macronutrient content of the diet; it is about processed food. If you avoid processed food, you could maintain a normal body weight.

The Bottom Line

All three speakers gave presentations that, in the end, pointed a finger at carbohydrates, with the first speaker suggesting that consumption of carbohydrates increases lipids and consumption of saturated fat doesn't. The second speaker nuanced this by saying that it could be the type of carbohydrate that is the problem, and the third speaker directly confronted processed food as the culprit in fat gain, if not metabolic disease. Well, we can hardly call this a debate!

The bottom line, in my opinion, is that processed food — with all the sugar, salt, fat, and endocrine-disrupting chemicals — may have changed the body weight set point that we all defend and could be the cause of the increased prevalence of type 2 diabetes and obesity. Patients must be counseled to eat "clean," meaning healthy, fresh, unprocessed foods, for healthy living and avoidance of metabolic dysfunction.

Caroline Apovian, MD, is director of nutrition and weight management, and professor of medicine, at Boston University School of Medicine. She is an internationally recognized authority on nutrition and has authored hundreds of papers, reviews, and book chapters on obesity and nutrition.

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