Attention deficit hyperactivity syndrome (ADHD) – bipolar disorder – aggressive behaviors may be linked with sugar intake

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New research suggests that conditions such as attention deficit hyperactivity syndrome (ADHD), bipolar disorder, and even aggressive behaviors may be linked with sugar intake, and that it may have an evolutionary basis.

The research, out today from the University of Colorado Anschutz Medical Campus and published in Evolution and Human Behavior, presents a hypothesis supporting a role for fructose, a component of sugar and high fructose corn syrup, and uric acid (a fructose metabolite), in increasing the risk for these behavioral disorders.

“We present evidence that fructose, by lowering energy in cells, triggers a foraging response similar to what occurs in starvation,” said lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine on the CU Anschutz Medical Campus.

Johnson outlines research that shows a foraging response stimulates risk taking, impulsivity, novelty seeking, rapid decision making, and aggressiveness to aid the securing of food as a survival response.

Overactivation of this process from excess sugar intake may cause impulsive behavior that could range from ADHD, to bipolar disorder or even aggression.

“While the fructose pathway was meant to aid survival, fructose intake has skyrocketed during the last century and may be in overdrive due to the high amounts of sugar that are in the current Western diet,” Johnson adds.

The paper looks at how excessive intake of fructose present in refined sugars and high fructose corn syrup may have a contributory role in the pathogenesis of behavioral disorders that are associated with obesity and Western diet.

Johnson notes, “We do not blame aggressive behavior on sugar, but rather note that it may be one contributor.”

Johnson recommends further studies to investigate the role of sugar and uric acid, especially with new inhibitors of fructose metabolism on the horizon.

“The identification of fructose as a risk factor does not negate the importance of genetic, familial, physical, emotional and environmental factors that shape mental health,” he adds.


Aggressive behavior is a major concern among adolescents and causes injury [1]. The prevalence of aggressive behavior varies between countries substantially [2,3]. Data from a study conducted in 79 countries suggest that the prevalence of frequent physical fighting (≥4 times during the past 12 months) was 10.4% in boys and 2.7% in girls [3].

Diet plays an important role in maintaining psychological wellbeing [4]. A Western dietary pattern is associated with increased mental health and behavioral problems. Soft drink consumption has been shown to be associated with mental health problems [5,6].

Some of the previous studies focused on the association between soft drink consumption and depression, suicidal ideation among adolescents [5,6,7].

Although the mechanisms are not fully understood, a positive association between soft drink consumption and these mental health problems has been reported in both developing and developed countries [5,6,7].

Most of the studies hypothesized that inflammation or oxidative stress caused by soft drink mediates the link between soft drink consumption and mental health problems.

Past studies on soft drink consumption and behavior have largely focused on internalizing behavior. A limited number of studies have examined the relationship between soft drink consumption and aggressive behavior among adolescents [8,9,10]. In the Youth Risk Behavior Survey in the USA, Solnick et al. found that soft drink consumption was positively associated with aggressive behavior [9].

In 26 industrialized countries, sugar consumption is positively associated with risk behavior, including physical fighting, mainly due to a sugary drink rather than sweets [10]. It is unknown whether this association exists in other countries with different culture and eating behaviors. Understanding the role of soft drink in the burden of injury and violence has its public health significance, as diet is a modifiable factor.

The aim of the study was to assess the association between soft drink consumption and aggression among school adolescents aged 12–15 years in 64 countries/regions participated in the global school-based student health survey (GSHS) between 2007 and 2016.

Discussion

In this cross-sectional study of a quarter million adolescents in 64 countries, soft drink consumption was positively associated with aggressive behavior in both genders. The association between soft drink consumption and aggressive behavior was stronger among non-smokers and those with sufficient physical activity. There are regional differences on the association between soft drink consumption and aggressive behavior. Substantial difference of soft drink consumption was observed in the study.

Comparison with Previous Studies

Although comparable results to our findings related to a positive association between soft drink consumption and aggressive behavior were reported in the USA among youth [9], Slovakia [8], and 26 industrialized countries [10], we for the first time categorized more studies from low and middle-income countries.

This allows us to limit some of the confounding effects common in high-income countries (e.g., stress and high-energy dense food). There seems to be no significant difference in the association between soft drink consumption and aggressive behavior by country level income. However, there was significant heterogeneity among countries.

The OR for aggressive behavior associated with soft drink consumption varied from 0.86 (95% CI 0.74–1.01) in Mozambique to 1.43 (95%CI 1.08–2.89) in Niue. The heterogeneity could not be explained by the country level soft drink consumption and prevalence of aggressive behavior (Figure 1).

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Figure 1
Forest plot of subgroup meta-analysis of the association between soft drink consumption and aggressive behavior. Abbreviation for regions: AR (African region), EMR (Eastern Mediterranean), RA (Region of Americas), SEAR (South East Asia Region), and WPR (Western Pacific Region). Values are odds ratio (OR) and 95% confidence interval (CI).

It is unknown whether different types of soft drink consumed in different countries may partly explain the difference. The use of types of sugar (e.g., high-fructose corn syrup (HFCS) vs. sucrose) to produce soft drink may contribute to the difference. Food culture difference may also explain the heterogeneity.

Genetic determinants play critical roles in modulating aggressive behavior [13,14,15]. Thus, the heterogeneity observed in our study could be partly due to the difference of genetic background in different countries. Existing evidence suggests there are interactions between genetics and sugar-sweetened beverage consumption on health outcomes (e.g., obesity) [16].

The weak positive association between fruit and vegetable intake with aggressive behavior is consistent with a study from the USA [9]. Further studies are needed to elucidate the association between overall dietary patterns and aggressive behavior. Unhealthy lifestyles often cluster and affect aggressive behavior [17].

It is worth noting that among those with a healthy lifestyle (e.g., non-smoking, no alcohol drinking, and sufficient physical activity) in our study, there was still a strong positive association between soft drink consumption and aggressive behavior. It is less likely that the link was confounded by these lifestyle factors. Similar to other studies [18,19], we found that obesity, smoking, and alcohol drinking was positively associated with aggressive behavior.

Potential Mechanisms

Although the exact mechanisms linking soft drink consumption and aggressive behavior remain to be studied, several hypotheses can be made. Firstly, high consumption of sugar can increase the level of oxidative stress and inflammation [20].

These changes have been shown to be associated with mental health problems [21]. In a study of Wistar rats, it has been shown that carbonated soft drinks can induce oxidative stress and alter the expression of certain genes that are associated with brain activity [22].

Secondly, soft drink is an important component of the western diet. It has been shown that the Western diet is related to mental health problems and externalizing behavior [4]. Gut microbiota is a mediator for the link between modern diet and many chronic diseases including mental health problems [23,24,25].

Several factors may mediate the association between soft drink consumption and aggressive behavior. Findings from the Health Behavior in School-Aged Children (HBSC) study suggest that daily nervousness and irritability mediated the association between soft drink consumption and aggressive behavior among adolescents in Slovakia [8].

Some soft drink contains caffeine and caffeine has been linked to insufficient sleep, nervousness, and impulsivity and risk taking in children and adolescents [26]. In the International Study of Childhood Obesity, Lifestyle, and the Environment (ISCOLE) [27] and other studies [28,29], soft drink consumption has been linked to shorter sleep duration.

Existing evidence suggests that poor sleep is a risk factor for aggressive behavior [30,31]. Thus, the link between soft drink consumption could be mediated by short sleep duration.

High consumption of HFCS in beverages may play a role in the epidemic of obesity [32]. One of the proposed mechanisms is based on the fact that fructose is metabolized differently than glucose in ways that favor de novo lipogenesis, which increase total body fat and do not stimulate insulin secretion or enhance the production of leptin, both afferent signals in the regulation of food intake and body weight [32].

In our data, soft drink consumption was positively associated with obesity. Although the previous study suggested that body size was associated with aggressive behavior, overweight/obesity is unlikely a strong confounding factor between soft drink consumption and aggressive behavior in the present study as the association between soft drink consumption and aggressive behavior was observed in all BMI categories. Furthermore, with the adjustment for BMI the effect estimates did not change.

Soft drink consumption clusters with other unhealthy lifestyles including smoking, alcohol drink, and sedentary activity [33]. In our study, the association between soft drink consumption and aggressive behavior was stronger among non-smokers and those with sufficient physical activity than their counterparts (Table 3).

It could be that the association between soft drink consumption and aggressive behavior was less confounded by other lifestyle factors among those with a relatively healthy lifestyle. Furthermore, it could also suggest that the adverse effects of soft drink consumption cannot simply be mitigated by other healthy lifestyles (e.g., fruit and vegetable consumption).

Strength and Limitation

The main strength of our study is the large number of participants (n = 263,890) and the comprehensive methods of collecting data through a well-designed survey aiming to pinpoint on the possible correlation between lifestyle factors and health conditions.

In addition, the study represents global dimension of behaviors, including 64 different countries with different food cultures, life style, and habits, encompassing five WHO regions (i.e., African region, Eastern Mediterranean, Region of Americas, South East Asia Region, and Western Pacific Region).

The consistent findings of the relationship between soft drink consumption and aggressive behavior in most of the countries is less likely due to chance or biased by unmeasured confounding factors. The main limitation of the study is its cross-sectional study design and a lack of quantitative measures of soft drink consumption other than the frequency of intake. Furthermore, unmeasured residual confounding variables, such as socioeconomic status and parenting style, could potentially contribute to the relationship between soft drink consumption and aggressive behavior.

Public Health Implications

Childhood aggressive behavior is a major predisposition to adolescent delinquency and later adult violence. Thus, understanding its risk factor may help diminish adult violence. Overall, population attributable risk of aggressive behavior due to soft drink consumption may vary substantially by countries.

In countries with high soft drink consumption, the benefit of reducing soft drink consumption might be substantial based on the study. Our findings may shed light on the practical implications from a public health perspective in increasing awareness on the harmful consequences of soft drink consumption on behavioral and mental health outcomes, such as aggressive behavior. This initial finding will serve as the first step in providing future interventions.

In conclusion, soft drink consumption was positively associated with aggressive behavior independent of sociodemographic and lifestyle factors. Strategies are needed to reduce the consumption of soft drink to prevent intentional injuries related to the aggressive behavior among adolescents. Further studies may provide further insight in the molecular mechanisms linking soft drink consumption and aggressive behavior.

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146469/


Aggressive behavior has been traditionally defined as an overt behavior with the intention of inflicting damage on another individual1.

The potential for aggressive behavior exists whenever the interests of two or more individuals conflict with broad similarities across species from mice to man1. Although aggression has advantages in competitive situations for obtaining food or defending territories and mates from competitors in the wild animal kingdom2, it is considered as one of the major social problems in human society.

The World Health Assembly officially declared violence as a major public health issue in 1996, and the World Health Organization (WHO) released the first World Report on Violence and Health in ref. 3. In addition, various forms of violence have incurred huge costs in treating victims and repairing infrastructure.

Therefore, it is important to identify relevant factors to promote or suppress aggressive behavior for effective interventions, thereby improving public health.

Intrinsic factors that modulate aggressive behaviors may include neuropeptides and neurotransmitters, which are small protein-like molecules, or chemical messengers regulating neuronal signaling. Vasopressin and oxytocin are frequently identified as neuropeptides related to aggressive behaviors. Several animal studies have demonstrated that oxytocin can reduce aggression4,5, albeit with other conflicting results6, while vasopressin is reported to increase male-male aggression in birds and mammals7,8.

In addition, a glucocorticoid hormone, cortisol in human and corticosterone in rodents, is widely studied as a stress hormone and a well-established target in the search for hormonal modulators of social aggression9,10. In addition to the roles of cortisol in temper and behaviors, it orchestrates a range of different metabolic processes.

Cortisol is known to promote catabolic changes in the body, therefore, reduction in body weight driven by heightened cortisol is often linked to aggressive behaviors in human and animal model studies11,12,13,14.

Lower levels of serotonin, a neurotransmitter related to mood, were reported to induce impulsivity and aggression15. Recently, transcript levels of genes such as Mecp2, Adrbk2, and Maoa and a few transcriptional signatures including NF-kB and MAPK signaling have been studied in relation to aggressive behavior16,17,18.

Furthermore, environmental factors including socioeconomic status and lifestyles have also been shown to affect aggressive behaviors11. Among such extrinsic factors, diet, one of the daily necessities of life, is believed to determine spirituality, mental well-being, intelligence, and temperament, including antisocial or aggressive behavior19.

For instances, administration of tyrosine, an amino acid serving as precursor of catecholamines and neurotransmitters, such as adrenaline and dopamine, was reported to lead to a significant increase in global mood scores in human20.

Tryptophan-rich diet was also reported to increase the level of serotonin and thereby elevate the mood in older women21.

With regard to cognitive behavior and mood, caffeine enhanced executive control and working memory with reduced feelings of fatigue22.

Similarly, sugar has recently drawn attention due to possible roles in modulating behavior and mood as well as health and disease.

Sugars are found in the diet either as a natural component of food or as an additive to foods and beverages. Although added sugar enhances food desirability by sweetening foods and beverages, it provides only empty calories with no nutrient value23.

Considering potential negative effects of excessive sugar intake, the WHO has recently suggested recommendations on the intake of free sugars in adults and children, with a particular focus on the prevention and control of unhealthy weight gain and dental caries24.

Increase in sugar intake could be attributable to rising consumption of sugar-sweetened beverages (SSBs)25,26. Numerous recent studies have reported that overconsumption of SSBs might be related to metabolic diseases such as obesity, type 2 diabetes and even cancers27,28,29,30,31,32.

While overconsumption of SSBs has been extensively studied for associations with physical health problems, its effects on behavioral changes have not been fully studied.

The association between aggressive behavior and sugar consumption remains controversial and inconsistent.

One study reported that a high level of sugar consumption was positively related with destructive-aggressive behaviors in hyperactive children33.

Others found that reduced sugar intake might be linked to a lower incidence of formal disciplinary actions in juvenile prison inmates34,35,36.

Furthermore, in adolescents, a relationship between levels of consumption of sugar-containing soft drinks and behavioral problems was found in a cross-sectional population-based survey37. In contrast, no such correlation was found in a study, in which oppositional or aggressive behaviors were assessed in the school-aged children provided with a sugar-sweetened diet38.

A lack of systematic animal studies to examine the causal relationship of sugar consumption with behavior problems is partly attributable to the as yet incomplete understanding of the effects of sugar intake on aggression.

In the present study, we aimed to investigate the effects of sugar on social aggression in an animal model. We assessed aggressive behaviors in mice that consumed a high sucrose solution from infancy to adulthood, with those given an artificial sweetener solution or plain water.

The levels of stress and aggression-related hormones were determined along with body weight changes. In addition, to elucidate the underlying molecular mechanisms of aggressive behaviors induced by sucrose consumption, we performed transcriptome analyses of brain tissues.

Findings from the transcriptome analysis prompted us to assess changes in numbers of inflammatory cells in peripheral blood using flow cytometry. The results show that continuous over-consumption of sucrose solution from infancy to adulthood leads to increased social aggression with pro-inflammatory responses in the brain. In addition, our findings provide insights into understanding the physiological and molecular mechanisms by which sugar plays roles in promoting aggressive behaviors.

reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385878/


Journal information: Evolution and Human Behavior

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