Sugar Addicted or Just Stressed Out? Study Investigates Modulatory Effects of Different Macronutrient Compositions on Serotonin in the Presence and Absence of Stress

Image 1: She has the reason she is so relaxed right in her hand... but does she know that sugar is no sustainable way of coping with stress unless you don't care that you thusly pave the way from from initial episodes of hypoglycemia over binges, to obesity and diabetes.

"Sugar addiction" is a recurring theme in the blogosphere and whether it exists or not and what potential causes and treatments might be is still a matter of a partly very emotional debate. If we go by the definition of "addiction", of which the venerable Oxford English Dictionary says that it was "a condition characterized by regular or poorly controlled use of a psychoactive substance despite adverse physical, psychological, or social consequences, often with the development of physiological tolerance and withdrawal symptoms", it would be, if we had prove that sugar is a "psychoactive" substance. After all, the "adverse physical, psychological, or social consequences", i.e. diabetes, obesity, eating disorders, isolation, depression etc., are too obvious to be argued away - and I don't have to tell you about the "withdrawal symptoms", do I? Or, could it be that this is all just in our brains? Well, according to a recently published study from the Neurochemistry and Biochemical Neuropharmacology Research Unit at the Department of Biochemistry of the University of Karachi in Pakistan (Moin. 2011), it actually is ;-)

A amino acidic tale of sugary binge eating and fat anorexia

In their study, which was unfortunately conducted on rodents, not humans (apparently decapitation of human subjects for research purposes is prohibited in Pakistan ;-), Samia Moin and his (or her?) colleagues tried to assess how different dietary macronutrient compositions effect the ability to cope with and the brain response to stress. To this ends the scientists fed 48 rodents with diets that contained either 1/3 sugar (sugar diet), 1/3 beef protein (protein diet) or 1/3 fat (fat diet) in addition to the standard rodent chow (normal diet). Unfortunately, they did not provide the specific macronutrient composition of the diets, so that I had to calculate the latter on my own. The results are depicted in figure 1 and are based on the assumption that the Pakistani "standard rodent chow" is identical to the one animals in US labs are fed ;-)

Figure 1: My calculation of the macronutrient composition of the experimental diets; the calculation is based on the "standard rodent diet" that is used in US labs, whether that was identical to the one the Pakistanis used, I cannot tell.

If you take a look at the macronutrient composition of the different diets, the inter-diet difference between the "normal" and the "sugar diet" ended up to be not so significant. I mean 58% vs. 72% of the calories from carbs? For me both would be high carb and thusly it should not really surprise you that of those 24 rats who had to endure 2h of immobilization stress the rats in the "normal" and "sugar" group showed a similar, yet for the "normal" diet 1-day postponed, stress response: They ate more!

Figure 2: Effect of repeated stress (2h immobilization) on food intake in the different groups (data calculated based on Moin. 2011)

If you look at the data in figure 2, it does yet become obvious that - at least within the study period - "more" has to be understood relative to an initial stress-induced decrease in food intake, which, and this is another interesting finding, was sustained at -44% (average over the 5-day period) in both the high fat and the high protein group.

The Pakistani perspective: "Carbohydrate help you cope with stress!"

From the perspective of the Pakistani scientists, this "restorative effect" of a high carbohydrate diet on stress-induced appetite may be a good thing, from the perspective of someone living in a society with an overabundance of both food and stress, it must however be consider a potential risk factor for obesity.

Figure 3: Changes in serotonin (5-HT), its metabolite 5-HIAA and its precursors in response to dietary intervention; the "normal" diet serves as a reference (data calculated based on Moin. 2011)

If we take a closer look at the diet induced changes in brain 5-HT (=serotonin), 5-HIAA (=main serotonin metabolite) and brain and serum tryptophan (=serotonin precursor) levels in figure 3, it becomes quite obvious that the changes in the macronutrient composition alone already "mess" with the serotonin metabolism. What stands out, here is that, contrary to the "sugar" and the "protein diet", the "fat diet" increases the amount of serotonin in the brains of the unstressed rats compared to the "normal" control by +20%.

Figure 4: Changes in serotonin (5-HT), its metabolite 5-HIAA and its precursors in response to stress in the different diet groups; data expressed relative to unstressed controls; only changes marked with an asterisk (*) are statistically significant, p < 0.05 (data calculated based on Moin. 2011)

A different picture emerges, though, when we take a look at the effects of combined macronutrient modulation and stress (cf. figure 4). Contrary to the changes in the "normal" and "sugar group" which (plasma tryptophan levels aside) lack statistical significance, we see a reduction serotonin metabolism (as indicated by reduced 5-HIAA levels) in both the "protein" and the "fat" diet and the serotonin level in the "protein" group was profoundly elevated in response to the 2h immobilization stress.

What implications do these 5HTs, 5-HIAAs and ABCDEFGs have?

From previous studies, we know for quite some time that high protein diets are associated with higher rates in stress-induced depression (Markus. 1998). Moreover a reduced 5-HIAA / 5-HT ratio in the brain has been identified as a characteristic feature of depression (Zangen. 1997). If we keep that in mind and take a final look at the data in figure 4 and figure 5, we would have to draw the following conclusions:

• a high sugar diet modulates the 5-HIAA / 5-HT in an "anti-depressive" way
   
• a high protein diet does not change the 5-HIAA / 5-HT ratio as long as there are no external stressors, when stress comes into play it is associated with a profound "pro-depressive" decrease in the 5-HIAA / 5-HT ratio
   
• a high fat diet induces a pro-depressive reduction in the 5-HIAA / 5-HT ratio in the absence of stress, but is associated with a less pronounced reduction in the 5-HIAA / 5-HT ratio in response to stress, when compared to a high protein diet

Now its up to you to tell me whether these neurotransmitter changes in a rodent study and the associated pro- and anti-depressive effects reflect the way you feel on different diets in the presence and absence of stress... and I suggest, whenever you feel good with the way you eat, discard all the information I have just given you and keep doing what works for you. Not just because you are no rat, but simply because we are all wired differently and this wiring may change overtime :-)