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Published: Nature Metabolism, June 8, 2021
Where: University of Sydney
👍 The Takeaway:
Not all carbohydrates are inherently bad for metabolic health. For example, resistant starch, which you can get from cooking and cooling foods like potatoes and rice, can be beneficial to glucose processing. However, the ones common to the processed and sugary foods found in Western diets—particularly high fructose corn syrup—can do a lot of damage, even in small amounts. Our extrapolation from this study? Avoid high fructose corn syrup at all costs. Fructose disproportionately contributes to poor metabolic outcomes, and it sneaks into a considerable proportion of processed and packaged foods.
🔬What It Looked At:
This study sought to unpack the effects of different types of carbohydrates on health outcomes as part of a low-protein-high-carbohydrate (LPHC) diet in mice, as well as the impact of varying protein-to-carbohydrate ratios. The authors aimed to build on previous research showing that mice that ate LPHC diets containing complex carbohydrates had better mid-life metabolic health and longer lifespan compared to those who ate high protein-low carb diets, which could come as a surprise to people who are advocates of low-carb diets.
In this study, the authors hypothesized that LPHC diets with relatively complex carbohydrates, like starch and resistant starch, would lead to better metabolic health than those involving fructose-containing carbohydrates (such as sucrose and high fructose corn syrup, both of which contain fructose and glucose), which lead to higher blood sugar spikes as well as other physical damage. The authors note that many nutrition studies examine macronutrients in isolation, but that’s not how we actually eat. So they wanted to find out in this study how carbohydrates and proteins interact with each other and lead to different outcomes.
Carbohydrates, also known as saccharides, can be divided into three types that differ in their chemical complexity. Monosaccharides, such as glucose and fructose, are the smallest and simplest type and can’t be broken down into smaller carbs. As such, they’re the body’s most basic energy source. Disaccharides are made up of two monosaccharides joined together; one example is sucrose, or table sugar, which is made up of glucose and fructose that are chemically linked. And polysaccharides, such as starch, are complex molecules made up of many monosaccharides. Through digestion in the small intestine, complex saccharides get broken down into their smallest units, such as glucose. An exception is resistant starch, which is fermented in the colon instead, making it similar to fiber.
In this study, the authors used 700 male mice to compare the metabolic health outcomes of 33 unique diets with different ratios of protein and carbohydrates as well as varying types of carbohydrates: 50:50 mixtures of the monosaccharides fructose and glucose (as a proxy for HFCS), sucrose, readily digestible starch, and resistant starch. All diets were isocaloric, meaning they had the same number of calories, and fat content was fixed at 20 percent.
📈 What It Found:
In diets containing the highest amount of carbohydrates (10:70 protein to carbohydrates), metabolic outcomes varied considerably based on the type of carbohydrate consumed. Compared to mice that ate similar amounts of normal starch, mice that ate resistant starch had healthier metabolic outcomes, such as lower adiposity—fat buildup—and lower fasting blood insulin levels. But mice that were fed mostly an HFCS-like mix of 50:50 glucose and fructose gained the most weight compared to those that ate glucose and fructose in different ratios (primarily due to fat, not lean mass), ate more, and had lower insulin sensitivity and glucose tolerance. Surprisingly, mice that ate that 50:50 fructose:glucose mix fared worse than mice that ate sucrose, even though sucrose molecules are made of fructose and glucose linked together. Something seems to be worse about having monosaccharide forms of glucose and fructose mixed (i.e., HFCS) compared to chemically linking them into a disaccharide (i.e., sucrose).
Also, eating normal starch—or “readily digestible starch”—produced about the same outcomes as eating sucrose in LPHC diets. Substituting resistant starch, however, resulted in significant metabolic improvement.
Why HFCS is Worse than Sucrose
First, the mice that ate the 50:50 mix (simulating HFCS and the highest fructose ratio tested) also ate the most calories.
One hypothesis the authors offer for the higher calorie intake is that fructose stimulates appetite—a study in humans found that a 50:50 mixture led to greater appetite than lower-fructose ratios. In the current study, because sucrose was provided as a solid while the fructose/glucose mixture was liquid, the fructose in the sucrose may have been released more slowly and converted into glucose before absorption, leading to an effectively lower fructose dose. The authors also noted that the HFCS-like mixture impacted the mice’s microbiome differently from sucrose and could partially explain the change in appetite. The HFCS-like mixture promoted Lactobacillus, which was positively impacted correlated with insulin resistance.
However, it’s not just eating more calories: mice on the HFCS-like mixture diet also showed the most significant increase in adiposity, particularly fat buildup in the liver thought to be caused by de novo lipogenesis (DNL), which is a driver of non-alcoholic fatty liver disease and other negative metabolic consequences. And while too much fructose in any capacity can drive DNL, there’s evidence that the glucose and fructose mixture found in HFCS can be more detrimental than fructose alone, potentially in part because “co-ingesting fructose and glucose reduces the satiety value of these monosaccharides, leading to greater calorie intake.”
Related article: Why fructose is bad for metabolic health
Why Mice That Ate Resistant Starch Had Better Metabolic Outcomes
Starches are just chains of glucose molecules. Normal starches—like those found in potatoes or rice—are quickly broken down into glucose in our gut, leading to a rapid rise in blood sugar. Resistant starch, however, has a unique molecular makeup that prevents it from being digested in the small intestine. Instead, it passes through unchanged, then ferments in the colon with the help of friendly bacteria that live in the gut. This means that resistant starch doesn’t immediately release glucose into the bloodstream, which is why eating foods containing resistant starch doesn’t cause a spike in blood sugar.
Building on their previous research, the authors also propose that eating resistant starch causes changes in protein metabolism and insulin sensitivity that ultimately lead to higher energy expenditure and fat-burning, resulting in less adiposity.
What About the Protein-to-Carb Ratios?
In all diets, the lower the amount of protein, the more the mice ate. This illustrates the “protein leverage” hypothesis, which posits that people instinctively prioritize getting enough protein, regardless of the caloric content. So if we ate only meat, the theory goes, we’d consume less because we’d hit our protein requirements without needing to eat a lot of food. But if we restrict protein intake, the tendency is to eat more to meet those requirements.
🤔 Why It Matters:
“The results of our study could provide an explanation for contradictory findings of human trials on protein and carbohydrate restriction,” write the study authors. Where high- and low-carb studies sometimes both show beneficial outcomes, it turns out the type of carbohydrate makes a big difference. Easy-to-digest carbohydrates found in the Western diet, made up of processed foods and beverages sweetened with HFCS, lead to poor metabolic health. In contrast, the traditional diet of people from Okinawa, some of the longest-lived humans on Earth, is a high-carbohydrate diet where the majority of calories come from sweet potatoes, which can be high in resistant starch.
The takeaway, says lead author Dr. Jibran Wali, a biomedical fellow at the University of Sydney’s Charles Perkins Center, is to avoid taking a blanket approach to all carbs. “Not all carbs are bad,” he says. Limit the bad carbs, absolutely, “but then you should not be avoiding the good carbohydrates”—the resistant starches found in many plant foods that can help improve insulin sensitivity and may not even be digested and bring glucose into the bloodstream.