In this closing perspective, the author exposes why targeting a single nutrient like sugar is in his opinion unlikely to be efficient in preventing obesity and metabolic diseases. He defends the proposal that the concept of fructose toxicity is based on major misconceptions of nutritional physiology. He specifically proposes that (1) sugar being a non-essential nutrient does not obligatorily imply that it has no beneficial effect; (2) alterations of blood triglyceride concentration and hepatic glucose production within the normal range may merely reflect adaptations to a fructose-rich diet rather than early markers of diseases; (3) overfeeding is a normal physiological response to exposure to an energy-dense, palatable nutrient rather than the consequence of ‘leptin resistance’; (4) we may presently overemphasize the role of biological regulations and of gene-related heredity when assessing the effects of fructose in particular, and the determinants of obesity in general.
Obesity prevalence has increased continuously over the past 50 years, and has now reached epidemic proportions in several countries of the world. This rise occurred over a too-short period to be associated with important changes in the human genome, and is therefore related to recent changes in lifestyle. It has been successively blamed on dietary carbohydrates, saturated fat, and more recently on fructose and added sugars. Many intervention studies aimed at reducing the dietary content of these nutrients have been performed, and have sometimes resulted in short-term weight loss. They however failed to remain efficient in the long term.
An increase in sugar consumption is obviously one of several recent changes in our diet. This, and the observation that excess sugar consumption can cause the development of obesity and of most of its co-morbidities in animal models and humans, has led to the proposal that sugar intake may play a causal role in increasing body fat mass. It is increasingly argued that sugar is obesogenic due to its high fructose content, which impairs the normal regulation of food intake in the brain and/or increases body fat mass independently of energy intake by stimulating de novo lipogenesis. However, many arguments supporting a ‘toxic’ effect of sugars,1 and recommendations to drastically reduce sugar consumption in the general population may be based on misconceptions of normal nutritional physiology.
First, sugar is increasingly presented as a non-essential nutrient, which was absent from our diet until recently, and which can be deleted without harm. Sucrose, as an end product of photosynthesis, is present very early in the food chain. It was likely the major carbohydrate for hunter-gatherers until it was replaced by cereals’ starch with the development of agriculture. The presence of specific fructose-metabolizing enzymes in most animals, including carnivores, attests that fructose was indeed a highly valuable source of energy. Furthermore, a nutrient being dispensable does not necessarily imply that it does not exert beneficial effects. You can certainly have a healthy diet without eating tomatoes, but that does not means that tomatoes have no beneficial effects whatsoever! Ethanol is certainly not an essential nutrient, and exert undisputable toxic effects on the liver, yet it may have some benefical effects on health when consumed in moderate amounts.2 Given the effect of chronic psycho-social stress on many chronic diseases, the recent observation that sugar may alleviate neuro-endocrine stress responses may possibly be such a beneficial effect.3
Second, fructose induces a modest increase in hepatic glucose output and increases blood triglycerides, which are considered as ‘adverse metabolic effects’. A gross increase in hepatic glucose output and frank hypertriglyceridemia are certainly markers of risk for vascular diseases in subjects with insulin resistance and diabetes. However, it may be exaggerated to conclude that an increased blood triglyceride concentration within the physiological range, or an impaired suppression of hepatic glucose without hyperglycemia, is synonymous with increased risk for health. It may merely reflect physiological adaptations to a nutrient that needs first to be converted into glucose and fat in splanchnic tissue before being used in other parts of the body.4 By analogy, hyperketonemia is clearly a hallmark of diabetic ketoacidosis, yet a physiological increase in blood ketones during short-term starvation is not a risk factor for diabetes!
Third, many scientists propose that obesity results from a failure of normal weight-regulating mechanisms. Food intake and energy expenditure are indeed regulated by hypothalamic centers responsive to blood glucose and insulin as markers of immediate nutritional status, and to blood leptin as a marker of body fat stores. This ‘homeostatic’ food control system is highly efficient in stimulating food-seeking behavior when energy-depleted, and is responsible for physiological adaptations to starvation, such as inhibition of reproduction. In contrast, it appears highly inefficient in preventing excess energy intake when palatable foods are available. In parallel with this homeostatic system, food intake is also regulated by neocortical centers that link food consumption to activation of brain ‘reward pathways’,5 and elicit feelings such as ‘liking’ or ‘wanting’ specific foods. This ‘hedonic’ food control system is modulated by activation of taste receptors,6 and can stimulate food intake even in well-fed individuals.7 Viewed in an evolutionary perspective, this system triggers a physiological overfeeding response, which allowed our hunter-gatherer ancestors to eat as much as possible and store energy when discovering a place where fruits or berries were in abundance.
Finally, we may tend to overemphasize the potential role of biological dysfunctions and of genes in obesity. Human genes have not changed drastically since the appearance of Homo sapiens on earth, yet humans have developed very efficient means for transgenerational transmission of information (language, books, electronic records, and so on). This ‘non-genetic hereditary material’ was at the origin of a continuous development of technical skills, including cooking and gastronomy, which somehow led to our present food intake habits and to the development of food industry.
I would therefore propose that non-genetic evolution of humans resulted in the large availability of convenient, highly processed food and that obesity is the consequence of normal, genetically controlled overfeeding when exposed to an ample food supply. I would further propose that eradication of obesity will require profound mutations in our ‘non-genetic hereditary material’, until the production of cheap, convenient, and palatable energy-dense food is no longer favored. One may remain optimistic, because evolution of concepts and ideas occurs much faster than genetic mutations!
Meanwhile, we should keep in mind that sugar is not more obesogenic than any other energy-dense palatable food. Our concern regarding obesity in affluent countries should also not overshadow the fact that malnutrition remains a major issue in large portions of the world, and that producing sufficient food in a sustainable way to feed an ever-increasing world population will soon become our main nutritional challenge. In this context, it appears premature to recommend a drastic reduction of sugar consumption in the general population when sugar presently contributes a substantial portion of world’s food energy production.
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The author’s work in this area has been supported by grants 320030–135782, 320030–138428, 32003B-156167 and IZ73Z0–152331 from the Swiss National Science Foundation, 11-06 from the Bundes Amt fur Sport BASPO and from Nestle SA, Switzerland and Ajinomoto Inc, Japan. The editorial Aisstance of Mrs E. Tappy is warmly acknowledged. This article is based on a symposium entitled ‘Sweeteners and Health: Findings from Recent Research and their Impact on Obesity and Related Metabolic Conditions’ presented at the 22nd European Congress on Obesity, Prague, on 7 May 2015 with sponsorship from Rippe Lifestyle Institute.
LT has received lecture fees from Rippe Lifestyle Institute, Nestlé SA and Soremartec. LT has also received grant support from the Swiss National Foundation for Science and Federal Office for Sport BASPO, Switzerland, and serves as an expert witness for the French food security agency ANSES.
This article is based on a symposium entitled ‘Sweeteners and Health: Findings from Recent Research and their Impact on Obesity and Related Metabolic Conditions’ presented at the European Congress on Obesity on May 7, 2015 with sponsorship from Rippe Lifestyle Institute.
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Tappy, L. What nutritional physiology tells us about diet, sugar and obesity. Int J Obes 40, S28–S29 (2016). https://doi.org/10.1038/ijo.2016.11