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Study under review: Transient decrements in mood during energy deficit are independent of dietary protein-to-carbohydrate

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Weight loss is big business. Some authorities estimate that 45 million Americans are trying to lose weight each year and spend upwards of $33 billion annually to do so. It has been suggested[1] that overweight and obese people experience significant improvements on a range of subjective symptoms after weight loss, regardless of diet composition.

However, dieting is also common in healthy-weight people looking to improve body composition and/or athletic performance. Consuming high-protein diets has become a popular method to aid in weight loss, as research has shown high-protein diets suppress hunger and preserve lean body mass during energy restriction in sedentary[2] and athletic[3] populations. These benefits are important for dietary adherence and long-term success, but they are only a piece of the puzzle.

Dieting can be psychologically complex. The brain and nervous system communicate through small chemicals called neurotransmitters. Collectively, these neurotransmitters are what allow us to be aware, have emotion, remember things, move our body, regulate body temperature, sleep, and do or feel anything that our brain allows for. In fact, many diseases like Parkinson's, Alzheimer’s, depression, insomnia, ADHD, and anxiety have been linked to neurotransmitter imbalances.

Figure 1: Select roles of mood-related neurotransmitters

There are many ways to classify neurotransmitters, but for our purposes it’s especially important to understand the role that amino acids play in different neurotransmitters. Some amino acids, such as glycine, taurine, and glutamate, serve directly as neurotransmitters, whereas other amino acids like tyrosine and tryptophan serve as precursors for neurotransmitter synthesis. Tyrosine is the precursor for the synthesis of the catecholamines: dopamine, adrenaline (epinephrine), and noradrenaline (norepinephrine). These neurotransmitters play a central role in attention, learning, motivation, and alertness. Tryptophan serves as the precursor for serotonin, which can have an indirect effect on well-being and happiness, and plays a variety of other roles as well.

There is some controversy surrounding high-protein diets because the consumption of a lot of large neutral amino acids – tyrosine, tryptophan, and the branch-chained amino acids (BCAAs) – has been shown to alter brain neurochemistry[4] through basic competition. That is, these amino acids all share the same transporters that allow access into the brain, and thus they all compete for entry. Since the transporters are not specific to any one of the amino acids, the largest determinant of which enters the brain is their concentrations[5]. Thus, if the plasma level of the BCAAs increases, then brain concentrations of tryptophan, tyrosine, and their respective neurotransmitters is reduced. Theoretically, this may have negative consequences for mood, sleep, hunger, and overall liveliness.

On the other hand, carbohydrate intake has been observed to increase serotonin production[6] secondary to insulin promoting tryptophan uptake in the brain. Theoretically, this may benefit mood. > The study under review aimed to compare the effects of different dietary protein-to-carbohydrate ratios on cognitive performance, mood, and sleep quality during short-term energy restriction.

Who and what was studied?

The outcomes presented in this study were actually secondary outcomes that were collected in a previous controlled trial. That trial aimed to evaluate the effects of protein intake on body composition, protein balance[7], and calcium homeostasis during a short-term energy deficit. Thirty-nine volunteers (82% men) with an average age of 21 years and average BMI of 25 completed the study. Despite the technically “overweight” BMI, the inclusion criteria required study participants to be recreationally active (defined as three to four days a week of aerobic and/or resistance exercise) and physically fit (VO2peak of 40–60 mL/kg/min) - VO2peak being a measurable determinant of endurance capacity unique to each individual participant.

The volunteers spent 31 days in a metabolic ward under constant supervision to ensure compliance to the prescribed diets and physical activity. Using a randomized block design, they were divided into three groups differing in protein and carbohydrate content, but matched for total caloric intake and fat:

  • Low-protein (LP) group consuming 0.8 g/kg/day protein

  • Moderate-protein (MP) group consuming 1.6 g/kg/day

  • High-protein (HP) group consuming 2.4g/kg/day

The increase in protein was accommodated by an equal reduction in carbohydrates. Throughout the entire 31-day study period, protein was held constant at the assigned amount, fat was roughly 30% of total energy intake, and carbohydrates made up the remainder. Alcohol and smoking were forbidden, and all the subjects had “lights out” by 11:00 p.m. to ensure similar and adequate sleep between the groups. Nutritional supplements were also forbidden, with the exception of a daily multivitamin provided by the researchers.

The first ten days of the study served as the control period, with subjects practicing weight maintenance. Their energy expenditure was estimated from pre-study indirect calorimetry measurements and physical activity logs. During the subsequent 21 days, energy intake was reduced by 30% (through reductions in fat and carbohydrates) and physical activity energy expenditure was increased by 10%, for a total daily deficit of 40% compared to weight maintenance.

All diets were prepared by research dietitians and protein was provided as mixed, high-quality proteins (e.g. dairy, lean meats, and vegetable-based proteins). The subjects all performed regular physical activity. This included three days a week of low-volume resistance training, where the participants performed one single-joint movement per major muscle group (three sets of 15 repetitions) using workloads determined during the pre-study period, plus daily steady-state endurance activity at a low- to moderate-intensity (40–60% VO2peak) pace on a treadmill or stationary bicycle.

A battery of cognitive tests were administered on days 11, 20, and 30 in the afternoon, about four hours after lunch. These time points were selected to represent the beginning (day 11), the midpoint (day 20), and end (day 30) of the dieting period. During the control period, three practice sessions were allowed for familiarization and to help reduce the potential of a learning effect (performing better because of practice rather than the variable of interest). During the cognitive testing, self-reported mood state was also assessed, utilizing the Profile of Mood States questionnaire. This questionnaire asks the question, “how are you feeling right now?” and has the responder rate 65 mood-related adjectives on a zero to four point scale.

Self-reported sleep quality was assessed every morning upon waking using a questionnaire asking how long it took to fall asleep, alertness at bedtime and upon waking, number of awakenings during the night, restedness upon waking, and four questions used to calculate an overall index of sleep quality.

Finally, blood samples were collected following an overnight fast on days 10 and 31 to quantify plasma amino acid levels.

In this study, 39 people were kept under observation for a month while progressively consuming fewer calories and engaging in more physical activity as the study went on. Researchers administered cognitive tests and measured plasma amino acid levels.

What were the findings?

The original trial that provided data for this study assessed the impact of protein intake on body composition. All three groups lost weight during the energy deficit, but the total fat loss as a percentage of weight loss was greater and the total fat-free mass loss smaller in the moderate- and high-protein groups compared to the low-protein group. The diets during both the energy balance (first 10 days) and energy deficit phases can be seen in Figure 2.

Figure 2: Protein & carb intake by study period

Total mood disturbances, anger, and tension significantly increased in all groups from day 11 to day 20, but were not significantly different from day 11 to day 30, and were not significantly different between any of the groups, suggesting that diet composition had no effect on mood changes. Additionally, confusion and vigor tended to increase during the energy deficit with no difference between groups. Depression and fatigue were the only mood-states that did not differ throughout the intervention.

There was also a lack of differences between any groups on the cognitive tests throughout the intervention. Although there were nine cognitive tests administered, only one test (the Four-Choice Reaction Time test) differed in any of the group comparisons, with the high protein group performing better than the moderate protein group.

While all groups tended to improve on cognitive tests during the energy deficit period, the improvements were observed in tests that also happened to improve during every practice session within the energy balance phase. This suggests that the improvements through the energy deficit period were a result of a learning effect rather than being due to the energy deficit.

There were also no significant differences in sleep quality throughout the intervention in any group or between the groups, with the one exception being a significant reduction in alertness upon waking in the low-protein group from day 11 to day 20, which returned to normal at day 30.

Finally, plasma BCAA concentrations were significantly higher and tyrosine concentrations significantly lower in the moderate- and high-protein groups relative to the low-protein group on day 11, but the difference between the high- and moderate-protein groups was not significant. Moreover, upon entering an energy deficit (days 20 and 30), all groups showed significant elevations in plasma BCAA and reductions in tyrosine concentrations, with the between-group differences losing their significance. However there was a slight trend for the high- and moderate-protein groups to retain their difference relative to the low-protein group.

The biggest shift in mood happened after day 11. Study participants felt significantly more anger and tension, though depression and fatigue were not affected. Mood did not change much after day 20. The results were fairly consistent between groups eating different amounts of protein, though the high- and moderate-protein groups had higher BCAA concentrations and lower tyrosine levels than the low-protein group.

What does the study really tell us?

The purpose of this study was to examine how the dietary protein-to-carbohydrate ratio influenced cognitive performance, mood, and subjective sleep quality. The premise is that manipulating dietary protein and carbohydrate intake would modulate neurotransmitter synthesis (primarily serotonin and dopamine). It was indeed shown that plasma BCAA and tyrosine, but not tryptophan, concentrations were impacted by the dietary treatments in a relatively short period of time, as the differences were noticeable by the end of the ten-day control period. However, at this time there were no differences between the groups in cognition, mood, or sleep.

At the end of the dieting period, the differences in plasma BCAA and tyrosine concentrations became insignificant between groups. However, there was a trend towards significance, suggesting that a larger sample size or longer duration may have been needed to detect the differences. Regardless, mood changes were not different between the groups and were transient, returning to pre-dieting levels by the end of the intervention. This suggests that it may have been the caloric deficit, not the plasma amino acid concentrations, that increased anger, tension, and total mood disturbances.

Similar things can be said for cognition, with all but one change occurring without difference between the groups. Finally, subjective sleep was mostly unaffected during the entire study. The one exception was the low-protein group feeling less alert upon waking during the first ten days of the dieting period only. Seeing how dopamine and noradrenaline play a central role in alertness, this outcome could be the result of the reduction of plasma tyrosine concentrations when the dieting period began. However, this would not explain why the sleep effects were not seen in the other groups.

So overall, what does this study tell us? It shows that a 40% caloric deficit in lean and recreationally active young adults may have a transient effect on mood regardless of the protein-to-carbohydrate ratio. It also tells us that the dietary protein-to-carbohydrate ratio does impact plasma concentrations of BCAAs and tyrosine, but not tryptophan. This could be owed in part to the dietary supply of amino acids, with all groups consuming 16 times more BCAAs and seven times more tyrosine and phenylalanine than tryptophan. Nonetheless, this suggests that downstream effects of the dietary protein to carbohydrate ratio would be limited to the catecholamines and not serotonin.

However, tryptophan entry into the brain is facilitated by insulin[6], which acts to reduce plasma BCAA and tyrosine levels by shuttling them into skeletal muscle and organs, and consequently also reduces competition for entry into the brain. Blood amino acid measurements were done after an overnight fast, when insulin is minimal. Similarly, the cognitive tests and mood questionnaire were completed roughly four hours after lunch, when insulin levels would be expected to have returned to baseline. Thus, it is possible that different outcomes would have been seen if the tests were administered closer to lunch when the subjects were in the postprandial state.

Another limitation of the study is that it was originally powered to detect changes in muscle protein synthesis and body composition, not cognitive outcomes. Also, without an energy-balance control group for comparison, it is not possible to separate the effects of the energy deficit from the effects of learning or the environment.

When interpreting this study, it’s important to keep certain caveats in mind. This study does not tell us how the dietary protein-to-carbohydrate ratio would impact mood and cognition in obese people or in individuals who diet while already extremely lean. Nor does this study tell us how the ratio would impact performance in physique athletes such as bodybuilders or wrestlers. It also doesn’t tell us how the ratio interacts with the absolute caloric deficit, as both groups in the study had an identical 40% reduction in energy intake.

The results of this study suggest that mood is affected during caloric restriction, regardless of the specific macronutrient breakdown. However, since the participants of this study were slightly overweight young people, further research is needed to confirm whether this association holds true for other populations.

The big picture

This study is one of many that examine differences in cognition and mood between low- and high-carbohydrate weight-loss diets that use different durations, study populations, and magnitude of energy deficit.

For instance, in an eight week study of overweight or obese subjects, nearly all cognitive outcomes showed no difference between low or high carbohydrate groups. In a separate year-long study, obese subjects had similar mood improvements from both low-carb and low-fat diets in the first two months, but after a year the low-fat group had greater improvements. Cognitive outcomes weren’t different between groups.

For these types of studies, outcomes have to be taken with a grain of salt. Mood improvements may be due to weight loss rather than diet composition. Study results also differ depending on how mood was measured, and compliance with the diets as well as the type of nutritional counseling provided makes trials even harder to compare.

Energy deficits have also been explored in several studies. One found that two days of near 100% caloric deprivation had no effect on mood in healthy young men, and a study in physically active soldiers found a 30-day energy deficit[8] (40%) to not significantly affect mood-state in comparison with a calorie-adequate diet.

In overweight and obese men and women, a six month long 25% energy deficit[9] was shown to improve depression scores at three and six months, but participants who followed a 67% energy deficit for three months followed by a weight maintenance diet only showed improvement at the end of the intervention. In all three of these energy deficit studies, results also showed no significant changes in cognition as a result of dieting. Perhaps surprisingly, energy deficits have often been shown to not impact sleep. In the short-term near 100% caloric deprivation study mentioned earlier, sleep was also unchanged, and a previous study in overweight premenopausal women found that four weeks of an 800kcal/day diet (energy deficit of 1460 kcal/day) did not affect sleep quality.

Increasing the dietary protein-to-carbohydrate ratio has been shown to result in some cognitive improvements in other studies, but typically for only certain selected outcomes rather than cognition or mood as a whole. For example, one trial[10] compared the effects of a normal (1.5g/kg) or high (3g/kg) protein diet in healthy normal-weight young adults. For three weeks, all foods and beverages were provided by the research staff. Cognitive performance improved in both groups, but only the high protein group significantly reduced reaction time. The high-protein group ended up with significantly higher plasma concentrations of the BCAAs, which the authors suggest may have been the cause of the improved reaction time Collectively, the above suggests that changes in mood are reliant on a variety of factors, such as the length of the diet, magnitude of caloric restriction, and occasionally composition of the diet. Although the evidence is somewhat mixed, these studies also suggest that dieting may improve mood in overweight/obese people more so than in lean people.

Importantly, while these other studies had differing fat intakes, the current study controlled for fat intake so that the only dietary manipulation was the protein to carbohydrate ratio. It was also highly controlled, with subjects being housed in a metabolic ward and given all meals and beverages. Thus we’re able to derive a fairly specific conclusion: boosting protein probably won’t help you avoid the doldrums of starting a diet. The initial ten days of beginning a diet may be the most psychologically difficult, but that this will pass with time. Additionally, it appears that cognition and sleep is likely to remain relatively unchanged throughout a dieting period. It’s important to keep in mind that the results were in non-obese young people, so they can’t be generalized to athletes with much greater caloric demands or to people who are pushing the boundaries of leanness.

The results of this study support the idea that changes in mood may be influenced more by the duration and magnitude of a diet, rather than its macronutrient composition.

Frequently Asked Questions

Q. Would BCAA supplements impact these neurotransmitters?

Since BCAAs are the “problem” in regard to competition for entry of neutral amino acids into the brain, it stands to reason that supplementing high doses of BCAAs would have similar if not worse effects on brain chemistry.

A recent study[5] evaluated the administration of a BCAA, essential amino acids (EAA), or a milk EAA mixture on brain amino acid and neurotransmitter concentrations. It found that the BCAAs in an amount similar to many low dose BCAA supplements that are currently being marketed does indeed blunt increases in serotonin by competitively inhibiting the uptake of tryptophan from the bloodstream.

Q. Can I just take supplemental tryptophan to increase serotonin levels and improve my mood?

If only it were so easy. While serotonin levels are associated with mood, many other factors are involved. In studies where people are purposely deprived of tryptophan[11], some show a markedly worse mood. However, this is highly dependent on who the subject is, and those who have a history of depression are more likely to experience the effect.

Tryptophan supplements have been widely studied[12], and do improve mood (as well as sleep) in certain subjects. People often face choices between medicating for moderate depression with SSRIs, or taking a supplement such as tyrosine or 5-HTP (the precursor to serotonin). Mood is an incredibly complex phenomenon, and unfortunately studies rarely if ever compare medications to supplements. And lifestyle factors such as stress and sleep can be as or more important than what you’re putting in your mouth.

Bottom line: Mood and depression issues rarely have quick fixes in the form of pills. Supplements that can increase serotonin can also have side effects from too much serotonin being present throughout the body. It’s usually best to take a step back and consider a variety of angles rather than a singular amino acid or other supplement.

What should I know?

Jumping into a 40% energy deficit may result in mood disturbances for the first ten or so days, which return to pre-dieting levels by the third week, regardless of the protein-to-carbohydrate ratio. This matches up quite nicely with what many refer to as the “low-carb flu”. The lack of differences between the groups of the current study suggests that perhaps it should be called the “dieting flu,” as it appears that these effects are not isolated to low-carbohydrate diets. Similarly, cognition and subjective sleep quality showed minimal changes, some of which were transient.

When considered in conjunction with the benefits of higher protein diets during times of caloric restriction for muscle preservation and satiety, it seems prudent to not worry about the hypothetical problems that a high protein to carbohydrate ratio would have on brain chemistry and neurotransmitters, as these changes do not appear to significantly impact cognitive function. Any mood or cognitive disturbances that do occur appear to be transient and may be owed to the caloric deficit itself rather than the macronutrient ratios.

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See other articles with similar topics: Mood, Diet, Dieting, Macros, Tryptophan, BCAAs, Brain.

See other articles in Issue #04 (February 2015) of Study Deep Dives.

Other Articles in Issue #04 (February 2015)


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