Glycaemic response or fructose?

One view is that the key driver of carbohydrate-related risk is glycaemic response i.e. the degree to which carbohydrates raise blood glucose and insulin levels. If glycaemic response is the critical factor then the dietary measure of interest would be glycaemic load, which takes into consideration both the amount of carbohydrate consumed and its potential to raise blood glucose.

An alternative view is that fructose drives the chronic disease risk associated with dietary carbohydrate. If so, we should expect fructose or perhaps sucrose (the major dietary source of fructose) to be associated with risk for chronic disease in large population studies. And, importantly, glycaemic load would not be linked with risk.

Let’s look at the epidemiology and see if it supports one argument or the other.

Glycaemic load and coronary heart disease risk

Four meta-analyses of prospective cohort studies of glycaemic load and risk for coronary heart disease have been published in the last couple of years (Dong 2012, Fan 2012, Ma 2012, Mirrahimi 2012). The findings are essentially the same – glycaemic load is associated with heart disease in women but not men. In two of the meta-analyses the links between glycaemic load and heart disease were stronger in overweight subjects. Fan (2012) also found an association with stroke incidence, as did Sieri (2013) in a recent cohort study. In all four meta-analyses the relative risks for heart disease in men were positive – they just failed to reach statistical significance, perhaps due to smaller numbers.

A study in a Chinese cohort published last year found glycaemic load was associated with coronary heart disease risk in both genders (Yu 2013). Compared to studies in western populations carbohydrate intake was high (68% of calories) but sugar intake was relatively low. Most of the carbohydrate was starch, 87% of which came from white rice and refined wheat products.

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Fructose or sucrose and coronary heart disease risk

There are virtually no prospective cohort studies that find a significant association between fructose intake and risk for coronary disease. The few studies that have looked at total sugars and heart disease risk generally find no association (Beulens 2007, Sieri 2013). A recent exception found an association between ‘added sugars’ and cardiovascular disease in a study in the United States (Yang 2014).

There are few data about the consumption of sugar-sweetened beverages and risk for coronary heart disease. And the findings are mixed – Fung (2009) found a positive association but this was not confirmed by Eshak (2012). Eshak (2012) and Larsson (2014) found links with stroke, albeit inconsistent between genders.

Glycaemic load and risk for type 2 diabetes

In the last three years at least four meta-analyses of cohort studies have considered whether glycaemic load affects the risk for type 2 diabetes, the latest published this year by the Harvard team (Bhupathiraju 2014). All four meta-analyses found that high glycaemic load increases risk for type 2 diabetes.

A recent meta-analysis found that consumption of white rice, a high GI food, was associated with increased risk for type 2 diabetes in Asian populations where it is by far the major contributor to glycaemic load (Hu 2012). The association was also positive in western populations but failed to reach significance.

Fructose or sucrose and risk for type 2 diabetes

No meta-analysis of studies into whether fructose or sucrose affects risk for type 2 diabetes has been published and there are just a few cohort studies to go on. The findings are mixed. In a small cohort Montonen (2007) found intake of glucose and fructose combined, but not sucrose, was associated with increased risk of type 2 diabetes whereas in the large EPIC cohort sucrose, glucose and fructose were not associated with diabetes risk in men or women.

A couple of months ago a meta-analysis of studies into sugar-sweetened beverages and risk for type 2 diabetes and found a positive association (Greenwood 2014). Interestingly, the same study also found a positive association between non-sugar beverage consumption and diabetes. This raises questions about whether these links are causal or alternatively whether soft drink consumption is a marker for other lifestyle behaviours that are associated with risk.

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Glycaemic load or fructose?

Given the public debate about fructose and sucrose the paucity of data linking these sugars with risk for type 2 diabetes and coronary heart disease risk comes as a surprise. It is clear that glycaemic load is a more consistent predictor of risk for these conditions than fructose or any individual sugar or total sugars or added sugars. This doesn’t let sugars off the hook but rather suggests that the risk for chronic disease posed by sugars should be seen in the context of their contribution to glycaemic load.

The significant contribution of sugar-sweetened beverages to glycaemic load in western diets has an interesting parallel in Asian diets – white rice, a high GI, starch-rich food. Both are also nutrient-poor. Some dietary recommendations in Australia still encourage the replacement of sugars with starch but the rationale for this is lacking if limiting glycaemic load is the most effective means of lowering carbohydrate-related risk.

Poor quality carbohydrate is not a narrow concept. It’s broad and includes some traditional foods currently recommended for healthy eating.

Those who have been following the carbohydrate quality debate will enjoy a recent feisty review by Professor Tom Wolever from the University of Toronto published in the European Journal of Clinical Nutrition. Wolever is the co-inventor of the glycaemic index concept and is obviously a little peeved that other measures of carbohydrate quality such as wholegrain have gained acceptance in dietary guidelines whereas GI has not.

Wholegrains versus GI

Here is how Wolever weighs up the relative merits of wholegrains and GI as measures of carbohydrate quality (minimally edited).

The evidence for the health benefits of wholegrains comes from epidemiological studies showing strong associations between high intake of wholegrains and reduced risk for cardiovascular disease, diabetes and obesity. Recent large clinical trials in subjects without diabetes showed that increased wholegrain consumption reduced systolic blood pressure, but none showed any significant effect of wholegrains on blood glucose, insulin sensitivity and/or insulin secretion, inflammatory markers or body weight (Tighe 2010, Brownlee 2010, Kristensen 2012). One study found that wholegrains reduced LDL-cholesterol, but another found the opposite.

On the other hand, trials of low-GI diets of similar magnitude in subjects without diabetes showed significant beneficial effects of a low-GI diet on blood lipids,(Jebb 2010, McMillan-Price 2006) inflammatory markers (Gogebakan 2011) body weight (Larsen 2010) and possibly insulin sensitivity. When the results of the four low-GI studies are combined, there is a significant reduction in LDL-cholesterol and C-reactive protein and a strong trend towards weight reduction.

Low-GI diets have at least as many, if not more, statistically significant effects than wholegrain-enriched diets; this does not support the hypothesis that wholegrain is a better marker of carbohydrate quality than GI.

I confess I have struggled to understand how wholegrains could lower risk for diabetes and coronary heart disease for the reasons that Wolever summarises. A small effect on systolic blood pressure really isn’t good enough. There is always the possibility that wholegrains may be operating via a yet-to-be-discovered mechanism, but this appears unlikely. Wholegrains have no effect on the inflammatory marker CRP suggesting no effect on underlying disease processes.

So how can one explain nutritionists’ recent embrace of wholegrains as a measure of carbohydrate quality? Perhaps the decision makers like the message – simple and easy to understand. But then again, if the message has shortcomings should we be broadcasting it? ‘Eat less fat’ was a simplification of ‘eat less saturated fat’ and look where that took us.

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Alternatively, perhaps there is a philosophical dimension to it. Nutritionists like the idea of wholegrains because it fits nicely with our philosophy about nutritional health being a natural consequence of eating simple, whole foods. But we are not philosophers; nutritionists are meant to be scientists and to make recommendations based on the facts.

The facts about GI?

The experts are yet to agree on what the facts relating to GI actually are. If you want to understand the GI debate and the case for and against, Wolever’s review is for you. He lists the criticisms of GI made by its detractors, such as imprecise measurement, lack of reproducibility, inaccurate tables and the notion that GI does not apply to mixed meals. He then addresses the issues one by one and challenges his critics to prove him wrong.

And the politics

As you may have guessed, there is a little politics involved here. In North America several influential nutritionists took a stand against GI early on and have defended their position ever since. They now concede that glycaemic ‘response’ is relevant to health but have reservations about the relevance of the GIs of individual foods. Wolever won’t have an easy task convincing them. Sometimes the acceptance of new approaches in science proceeds slowly, funeral by funeral.

In Europe leading nutritionists have been more accepting of the GI concept, especially following the results of the Diogenes study, which showed beneficial effects on weight management. The European Union is now funding a large new trial, with an Australian arm, into whether a high protein, low GI diet is superior to a conventional healthy diet for the prevention of type 2 diabetes.

It is noteworthy that Wolever doesn’t see GI as an alternative to wholegrains but as a complement to it. They are both measures of carbohydrate quality. I would add the caveat that some wholegrain foods and some low GI foods are nutrient-poor, again highlighting that carbohydrate quality is a complex, multi-faceted concept.

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