Refined Sugar Worsens Blood Lipid Markers of Cardiovascular Disease

Blood lipids such as LDL and HDL cholesterol are markers of the biological processes that impact cardiovascular disease, and they are commonly measured to assess cardiovascular risk.  When we think about the impact of food on blood lipids, dietary fat typically comes to mind.  Yet a new study shows that dietary carbohydrate, specifically high-fructose corn syrup, can have a large impact on blood lipid markers of cardiovascular disease risk.

Introduction

Dietary fats have well-established impacts on blood lipids.  For example, in short-term feeding trials, saturated fat tends to increase total cholesterol, increase LDL ("bad") cholesterol, and increase HDL ("good") cholesterol, while the omega-6 polyunsaturated fat linoleic acid decreases total cholesterol and decreases LDL cholesterol.  For this reason, dietary advice to reduce cardiovascular risk tends to focus on dietary fat.

The hypothesis that refined dietary sugar is harmful to the cardiovascular system isn't new.  In 1972, British physiologist and nutrition researcher John Yudkin published a classic book called Pure, White, and Deadly, which argued, among other things, that refined sugar is harmful to the cardiovascular system.  Yet at the time, the supporting data were weak, and the hypothesis was never taken very seriously by the scientific community.

Peter Havel and his group at UC Davis have begun to breathe new life into this hypothesis with their rigorous work on the cardiovascular effects of dietary sugars.

The study

Havel's team recruited 85 lean to obese volunteers that didn't have diabetes, kidney or liver disease, or high blood pressure (1).  They divided the volunteers into four groups, each of which received a different amount of high-fructose corn syrup (HFCS) beverage daily for two weeks:

1. 0 percent of calorie requirements as HFCS
2. 10 percent of calorie requirements as HFCS
3. 17.5 percent of calorie requirements as HFCS
4. 25 percent of calorie requirements as HFCS

A non-caloric sweetener (aspartame) was added to the 0 and 10 percent beverages so that they had a similar sweetness level as the 17.5 and 25 percent beverages.

After the two-week period, Havel's team measured the volunteers' body weight, blood lipids, and uric acid level (a marker of gout risk and also possibly metabolic health).

Results

After two weeks of drinking their assigned beverages daily, body weight increased with increasing HFCS dose.  This became non-significant after additional statistical adjustment (adjustment for multiple comparisons, which is rigorous), but the trend is still clear.  People in group 4 ended up gaining 1.8 lbs (0.8 kg), and the amount of weight gained was directly proportional to the dose of HFCS. 

Effect of HFCS dose on body weight.  Adapted from Stanhope et al., AJCN, 2015.

This is called a "dose-response relationship" because stepwise increases of the HFCS dose led to stepwise increasese of body weight.  A dose-response relationship provides very strong evidence that an effect is real.  

Havel's group also found dose-response relationships between HFCS dose and blood lipid levels.  The higher the HFCS dose, the higher the LDL climbed over the two-week period.  While LDL decreased slightly in group 1 receiving no HFCS, it increased by 18 percent in group 4.  ApoB concentration, a marker of LDL particle number, increased by 19 percent.

Effect of HFCS dose on fasting LDL cholesterol.  Adapted from Stanhope et al., AJCN, 2015. 

Uric acid levels also increased in a dose-response fashion with increasing HFCS.

Discussion

This new paper from Peter Havel's group suggests that supplementing the diet with HFCS leads to weight gain and detrimental changes in blood lipids.  The increases in LDL cholesterol and ApoB concentration they observed would be expected to lead to a significant increase in cardiovascular risk.  The higher the dose of HFCS, the worse the outcomes.

This study is certainly interesting, but it requires some interpretation.  The first thing to note is that calories weren't held constant, and volunteers were given calorie-rich beverages to drink in the context of their habitual eating patterns.  Usually in trials like this, when you ask people to add a calorie-rich food to their normal regimen, they don't fully compensate for the excess calories and end up overeating.  Judging by the increase in body weight, that appears to have happened here.  

Many studies have evaluated the impact of refined sugar on body weight, metabolism, and cardiovascular risk markers.  John Sievenpiper, a nutrition researcher at the University of Toronto, and his colleagues have conducted systematic meta-analyses of the studies on fructose-containing sugars, and their results show that there is a large difference between studies in which calories were held constant and those in which sugar-eating groups increased their calorie intake.  Basically, when calories are held constant, fructose has little unique impact on weight, metabolism, or cardiovascular risk factors (2, 3, 4, 5, 6).  When sugar intake and calorie intake rise in parallel, sugar increases body weight and begins to cause harmful metabolic and cardiovascular changes.  My interpretation of the evidence is that refined sugar exacerbates the harmful effects of overeating.  

So the increase in calorie intake that presumably occurred in Havel's study is highly relevant to the outcome he observed.  Yet, we need to remember that refined sugar tends to promote overeating, so in real life, it's very common for a high sugar intake and overeating to co-exist.  At the same time, when a person makes a major dietary change such as adding a large quantity of sweetened beverages to his diet all of a sudden, there is an adaptation period during which he gradually adjusts the rest of his diet to the change.  My suspicion is that the calorie intake of group 4 went way up at first, but that it would have gradually stabilized at a more normal (but perhaps still a bit too high) level as they began to compensate for the excess calories.  In other words, I would expect the long-term effects on weight and blood lipids to be somewhat attenuated relative to what was reported in this two-week trial.

Elevated uric acid is a marker of impaired metabolic function and increased gout risk.  The increased uric acid in the HFCS-consuming groups is not good, and probably reflects a combination of overeating and high fructose intake.  

Although Havel's team used HFCS for this study, the evidence overall suggests that HFCS is pretty much the same as sucrose (table sugar).  For me, the result is relevant to all forms of refined sugar that are about half fructose and half glucose.

In the end, I think this new study does raise serious questions about the health impacts of eating refined sugar-- particularly for cardiovascular health.  As we collectively recover from our 'sugar mania' phase, in which every ailment under the sun was blamed on sugar, I think we can settle into a more nuanced view of refined sugar as a dietary factor that interacts with excess calorie intake to adversely affect body weight, metabolic health, and the risk of cardiovascular disease.

And as a reminder, there is still no evidence whatsoever that sugar from fresh fruit is fattening or harmful to health.  The evidence currently suggests that fresh fruit, if anything, is slimming and promotes good health.  This is probably because fresh fruit doesn't favor overeating, and it also delivers an array of other beneficial substances such as polyphenols and fiber.