Sweet-heart trouble

Monday 15 September 2014

Evidence implicating sugar in heart disease builds up

imageAs a young man, Pradeep Yadav saw his father suffer a heart attack, so he was careful. A teetotaller, he would not drink or smoke, and he exercised regularly. Like a true believer in the diet-heart hypothesis—that cholesterol and saturated fat in food raise the cholesterol level in blood, which in turn raises the risk of heart disease—he would even throw away the cholesterol-rich egg yolk. Then, many years later, one day he felt pain in his chest while jogging. He went for a medical check-up.

His blood report showed abnormal cholesterol levels and slightly high sugar, though not diabetes. The electrical activity of his heart showed disturbing signs. At first glance, Yadav had not come across as a candidate for heart disease to his doctor. He does not even have high blood pressure or obesity, which are associated with the disease. And he is just 40.

Only things not-so-healthy in his lifestyle are that his job at the Indira Gandhi International Airport requires him to do frequent night shifts and he has a sweet tooth. He would frequently have sweet beverages, biscuits and other snacks. Two teaspoons of honey in the morning and a glass of Glucon D after jogging were recent habits. On occasions he overindulged in sweets too. He thought he had earned it because he was keeping his weight in check.

After seeing his health report, Yadav eliminated sugar and snacks from his diet. Within a month not only his sugar level decreased, but also his cholesterol levels went back to normal. He was yet to begin medication. Further tests confirmed blockages in the arteries carrying blood to the heart, hence the pain.

Although one cannot put a finger on one thing and say this caused heart disease in a particular person, lots of studies show overindulging in sugar is linked to heart disease. Some also try to prove the link through experiments on people. Conventionally, sugar is viewed as empty calories, providing only energy and no nutrients, which can make one fat. And obesity, in turn, predisposes a person to metabolic diseases like diabetes and heart disease. But more recent research hints that sugar may predispose a person to metabolic diseases even without causing obesity.

One study published in the journal of American Medical Association, JAMA Internal Medicine, in April showed a significant association between having sugar other than what’s naturally present in fruit and vegetables and the increased risk of death from disorders of the heart and blood vessels, clubbed under the common term cardiovascular diseases (CVDs), in the US. Even one sugar-sweetened drink a day increased the risk.

The study, led by Quanhe Yang, senior scientist with US public health institute Centers for Disease Control and Prevention, analysed the national health and nutrition survey data of 31,000 people between 1988 and 2010. It then calculated the risk of dying using national death data. “Our analysis suggests that participants who consumed greater than or equal to 10% but less than 25% of calories from added sugar … had a 30% higher risk of CVD mortality; for those who consumed 25% or more of calories from added sugar, the relative risk was nearly tripled,” the authors wrote.

WHO recommends not exceeding 10 per cent of calories from added sugar. To put it in perspective, a 600 ml bottle of soda a day will provide an average person of 2,000-calorie diet 12 per cent of his/her energy requirement. Add two scoops of ice cream and the risk will rise exponentially.

imageThe association was independent of body weight, cholesterol level, physical activity, blood pressure, smoking and alcohol consumption—all factors to watch out for avoiding heart disease. Overall quality of diet also failed to explain the link. This hints that there is something specific about sugar.

This is the largest study of its kind that compared diverse lifestyles of adults aged 20 years and more. “This is an important study and the National Health and Nutrition Examination Survey data they have used is pretty solid,” says AmbrishMithal, who heads the endocrinology and diabetes division of Medanta hospital in Gurgaon, a satellite city of Delhi.

Association, however, is not the same as cause. It only helps in forming hypotheses. To prove a causal relationship one needs direct experiments or trials where all variables are controlled and the results have to be consistent and repeatable. A study, published in American Journal of Clinical Nutrition in May, analysed several such experiments on people. It found sugar influenced risk factors for heart disease independent of weight gain.

Fat and cholesterol in blood occur in the form of triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), together called lipids. High levels of triglycerides and LDL and low levels of HDL—as was the case with Yadav—are bad signs for cardiovascular health.

Researchers at the university of Otago in New Zealand, led by Lisa TeMorenga, selected 40 randomised controlled trials that examined the effects of modifying sugars on lipids and blood pressure, and put them through rigorous statistical analysis. Higher intake of sugar, which is a refined carbohydrate, was found to raise concentrations of triglycerides, LDL, total cholesterol and blood pressure. This was true even when the total amount of carbohydrate and energy remained the same. “This suggests that our bodies handle sugar differently to other types of carbohydrates,” says Te Morenga.

What this analysis does is consolidate the evidence. As Te Morenga puts it, until now the evidence relating to CVD risk factors from sugar in human studies, and involving relatively normal diets, was hard to make sense of.

These studies do not fit within the old framework of debate that sugars are markers of poor diet and obesity. “We are in the midst of a paradigm shift in research on the health effects of sugar,” wrote Laura A Schmidt, professor of health policy in the School of Medicine at the University of California, San Francisco, US, in JAMA Internal Medicine in February. “Too much sugar does not just make us fat; it can make us sick.”

Although such studies are rare in India, doctors Down To Earth spoke to agreed sugary drinks and other junk food play a role in the increasing cases of chronic diseases in the country. “Of course, they play a role. But no one has woken up to them,” says O P Yadava, senior cardiac surgeon and chief executive officer of the National Heart Institute in Delhi. “If you have to choose one thing, it is sugar rather than fat one has to cut down in diet.”

So how does sugar raise the risk?

Sugar is one part fructose and one part glucose. Most carbohydrates we eat, such as rice and bread, break down into glucose in the gut. Biochemical and dietary intervention studies in the past few years suggest it is the fructose component that does the most damage because it is metabolised differently than glucose. Unlike glucose, which can be used in every part of the body, fructose is metabolised mostly in the liver and is not regulated by the body’s energy requirement. It, therefore, puts a burden on the liver when taken in excessive amounts and the liver converts part of it into fat, explains Luc Tappy, a researcher at the University of Lausanne in Switzerland who is considered an authority on sugar metabolism.

This manifests in increased concentrations of circulating triglycerides and the risky kind of cholesterol, reduced insulin sensitivity and increased deposition of fat at the wrong places: in the liver and abdominal cavity—all bad signs for cardiovascular health. Some studies even suggest that high sugar intake may enhance genetic susceptibility to heart disease, writes Yang’s team.

“My data shows clearly sugar is a bigger problem compared to white bread, pasta and rice,” says Kimber Stanhope, nutritional biologist at the University of California, Davis, US, who has compared the effects of fructose against those of glucose (see interview). Some other studies also show adverse effects of fructose.

These effects are, however, inconsistent. Some studies do not show such results. Stanhope points out that several such studies are either not carefully conducted or are funded by the sugar industry. When New Zealand researchers excluded the studies funded by the food industry—14 of the 37—from their meta-analysis, the effect of sugar on lipids strengthened.

In public perception, however, sugar is just calorie-dense food that can make one fat if overindulged in. “We discourage added sugar but behavioural changes are not easy,” says Mithal of Medanta. Yadava says the message about the harmful effects of sugar has to go through the media. “We doctors do not have mass reach.”

While the evidence is not enough to nail sugar as a cause of metabolic diseases, it certainly prises open the debate from the straightjacket of empty calorie. Excessive sugar probably does more than displace nutrients from one’s diet.

`We've strong evidence that eating sugar contributes to heart disease'
 
Kimber Stanhope Kimber Stanhope, nutritional biologist at the University of California, Davis, US, is studying the health effects of fructose, a component of sugar. She has carried out carefully planned experiments feeding comparable groups of people fructose, glucose and high fructose corn syrup—which, like sugar, is part fructose and part glucose—and then comparing their effects on risk factors for metabolic disease. In an interview to Archana Yadav she shares her findings.

Your study clearly shows fructose has unique effects on the body. Are these effects significant enough to cause metabolic disease in the long-term?
That is very difficult to prove. That’s why all the nutrition research is based on population association studies; studies that show increased sugar consumption is associated with increased incidence of a particular disease. There are many, many studies that show that. But to prove that’s a cause-and-effect relationship, meaning sugar is causing that disease, we have to rely on diet intervention studies. But when you do a diet intervention study the best you can look at is a risk factor and that is because nobody ethically can do a study in which the intention is to cause human subjects to develop a disease.

Our earlier study, which was published in 2009, suggests compared to glucose, fructose causes increased lipid levels, increased fat-making in the liver—meaning the fructose is converted into fat in the liver—and it reduces insulin sensitivity. It also appears to have a unique effect by which the excess fat that is gained during the consumption of fructose-sweetened beverage gets deposited in visceral adipose. Now visceral adipose is the fat that is contained within the abdominal cavity and that fat is more associated with metabolic disease risk factors than the fat that’s deposited subcutaneously, that means under the skin. Those were the four major facts we reported in our 2009 study. Now 2009 was five years ago. What have we shown since? Well, we have shown when younger, healthier subjects consume high levels of fructose or high fructose corn syrup, we can see these increases in lipid within two weeks.

Other researchers have also conducted some very important work. There was a research study conducted in Denmark where they fed sucrose-sweetened cola, one litre a day, to humans for six months. Those research subjects also showed increased visceral fat, increased lipid and increased liver fat—which is something our study did not measure—compared to the control group who were consuming either water or aspartame-sweetened beverages or milk. That was a very important study that confirmed our results. There was also a study in Switzerland, in which young, healthy subjects consumed one-half the amount of fructose compared to our subjects in 2009. And those subjects also showed increased lipid levels and decreased insulin sensitivity in the liver within three weeks compared to subjects consuming the same amount of glucose.

Are these results consistent and repeatable?
There are studies that did not show the same differences between glucose and fructose that we saw. In some cases it might be because the studies were not as carefully conducted as our studies. Our studies were very carefully conducted. One of the reasons is, for example, in the 2009 study, our subjects lived at our clinical research centre, which is part of a hospital, for two weeks at the beginning of the study and two weeks at the end of the 12-week study. When you have your subjects at the clinical research centre you are minimising problems due to variables; subjects have different activity levels and different diets at home. The other problem is that some of the research that does not show fructose consumption or sugar consumption increasing risk factors has been funded by industry, for example the corn refiners. That is what makes it difficult for a person to look at all the research studies and say it is absolutely clear that sugar increases risk factors for metabolic disease. There are studies that do not show this but many of these studies are supported by the industry.

The most money that has been provided to answer that question about sugar consumption was $10 million but that was provided by the Corn Refiners Association to a scientist who serves as a consultant for the industry. And he has spent $10 million to do lots and lots of sugar diet-intervention studies, and all his data shows sugar is no problem. It is a very big problem. Right now I feel very frustrated.

How much of fructose is high enough to cause adverse effects?
We still need to do a very carefully controlled study to determine safe levels or prudent levels of fructose consumption. I have two problems answering that question. One, I have data I can’t talk about because it has not been published yet. The second problem is nobody as of yet has conducted a study where they have provided controlled diet throughout the entire intervention study.

I have written an NIH [National Institutes of Health] grant. In that study I have proposed my research group will make all meals for the subjects for eight weeks. And the meals will contain either zero per cent or five per cent, 10 per cent, 15 per cent or 20 per cent of energy as added sugar. This study did not get funded, but I will keep trying obtain funding because this is the kind of study that needs to be done before I can accurately answer how little fructose is safe and what constitutes overload. In most of the studies that have been conducted recently we provide the sugar-sweetened beverages to subjects that they consume at home along with their normal diet. And those normal diets aren’t controlled, so there is varying amount of sugar consumption going on.

The current debate on sugar gives an impression that it is okay to have any amount of carbohydrate as long as one does not touch sugar. But high levels of glucose and insulin in blood have also been shown to be linked to heart disease.
That is difficult to know for sure because at this point many of the studies that suggest carbohydrate consumption is related to metabolic disease did not separate the effects of sugar versus the effects of bread, rice, pasta and grain. We need more studies that will look at that. We need to look more carefully at the high complex carbohydrate diet that does not contain sugar. Does that diet promote metabolic disease? I don’t think we have done enough studies that we can say yes.

In my control diet the subjects consume white bread, white rice, white pasta, not whole grain. When I take away those carbohydrates and instead add the sugar I see raised risk factors. My data shows very clearly sugar is a bigger problem compared to white bread, pasta and rice. We need to do a study where we provide the number of calories people eat in order they do not lose weight. I have actually written an NIH grant to answer that question, too. It is very, very difficult to get grants for such studies. Conducting well-controlled diet intervention studies in humans are very expensive. 

Do we have enough evidence to say that sugar is an independent risk factor for heart disease?
If you put together the population studies that show associations between sugar consumptions and cardiovascular disease, and you look at the diet intervention studies that show increased risk factors when we replace food that people eat with sugar, I would say we have a very strong body of evidence that sugar consumption contributes to heart disease, and some of that data suggests it is independent of weight gain. But I would very much like to do the study where subjects are getting exactly their energy requirement, therefore, none of the subjects would gain weight, and that would be the definitive evidence that is necessary to prove that weight gain is not a factor; that it is only the sugar. My data in which I separate the subjects who did not gain weight and the subjects who did gain weight certainly suggests that I’m going to have increases in risk factors, that there is increase in risk factors even when subjects do not gain weight. When they do gain weight eating sugar the increases in risk factors are even higher. We need a longer term study like that in which the amount of sugar is controlled throughout the entire study. We are very hopeful that we will soon obtain NIH funding to conduct a study like this.

How long have you been studying fructose? How did you get interested in it?
I work with Dr Peter Havel and we were investigating leptin in 1996. Leptin had just been discovered two years earlier and everybody was very excited about leptin because it was looking to be a possible solution to obesity. Leptin is the hormone that is secreted by our fat cells all over the body, travels through the blood, goes to the brain and tells the brain to quit eating so much and to burn more calories. When there isn’t any leptin around, the brain says, “I need to eat more. I need to decrease my calorie-burning because there is not enough energy.” So we get very hungry when leptin levels are low.

It had been discovered that mice that did not have leptin were obese, but if they were provided leptin they got thin. So everybody was very excited about leptin. Was it possible we could provide leptin to obese people and they would get thin? It turned out that no you couldn’t. Obese people already have high levels of leptin because there are lots of fat cells making it but their brain was not responding to the leptin message.

But in 1996 everybody was still hopeful this would be the case. In our lab, we cultured fat cells in a petri dish and we found that the more glucose those fat cells took in and metabolised the more leptin they made. That led to a very interesting question: what happens when we eat fructose? When people eat fructose the fat cells do not get exposed to glucose. So does fructose consumption decrease leptin level? We conducted one-day studies that showed it did. So next, in 2007, we attempted to find out whether subjects consuming fructose with their normal diets would gain more weight than the subjects consuming glucose. We found they gained exactly the same amount of weight, so we didn’t prove our hypothesis. Initially, I was very disappointed. But the minute I saw our early results of what fructose was doing to the lipid levels in our older subjects compared to glucose I knew I’d be studying sugar and the effects of sugar on metabolic disease for the rest of my career.

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