‘Neurotransmitter’ appears to be the buzz word of the moment; the belief being that nutrition can have a significant affect on the appearance of blood and brain neurotransmitters themselves, a substantial body of evidence supports this notion (Wurtman & Fernstrom, 1974; Growdon & Wurtman, 1977, 1980; Gelenberg, Wojcik & Growdon, 1980). Such evidence has given rise to a spate of theories, generally all of the ‘Broscience’ ilk, a number of which originate from Charles Poliquin’s ideologies. The Meat & Nut breakfast is his most infamous nutrition and neurotransmission tale. While I personally also see the benefits of the inclusion of meat and nuts at breakfast, Poliquin has vastly over exaggerated the impact this meal has on your brain neurotransmitters and thus the subsequent actions and emotions. Here we’ll critique the current evidence regarding nutrition and neurotransmission and hopefully dispel any of the Poliquin myths along the way.
Science talk, a neurotransmitter is a chemical signal which allows transmission of signals from one neuron to another, across a synapse; in English that basically means it’s a vehicle which allows messages to be transported from one nerve to another. Neurotransmissions allow, and control muscle fibre contraction, bodily actions, emotions and feelings. The most significant neurotransmitters in the human body are acetylcholine, norepinepherine, dopamine, GABA, glutamate, serotonin and endorphin.
Neurotransmitters and cognitive function
Serotonin is a known sleep inducing agent (Hartman & Spinweber, 1979), and human research has suggested serotonin reduces subjective alertness, objective performance, and increases feelings of relaxation and lethargy (Spring, 1984). Dopamine on the other hand is associated with pleasurable reward, behaviour, cognition, mood, memory, movement, attention and learning. Acetylcholine has a number of physiological functions, and is a widely distributed excitatory neurotransmitter that in the central nervous system is involved in wakefulness, attentiveness and memory. Interestingly, Alzheimers disease is characterised by a significant reduction in acetylcholine concentration and function (Francis, 2005), highlighting its importance in human performance.
Neurotransmitters and nutrition
The primary neurotransmitters are synthesized from the amino acids, tyrosine and tryptophan. The rates at which these neurotransmitters are synthesized depends upon the availability of the amino acid precursor; where tryptophan is the precursor of serotonin, and tyrosine is the precursor of dopamine and norepinepherine (Wurtman et al. 1980); this link was made in the 70’s and early 80’s when evidence from rat studies became available. The administration of a single dose of tryptophan elevated brain tryptophan levels, and thus the levels of serotonin and its major metabolite 5-hydroxyindole acetic acid (5-HTP). The administration of tyrosine similarly elevated brain tyrosine levels, and thus catecholamine synthesis increased in the central nervous system (CNS), while the consumption of lecithin or choline (found in fat) increases brain choline levels and neuronal acetylcholine synthesis (Wurtman & Fernstrom, 1975).
Most of these studies were on rats, using a single dose of the precursor, although similar effects have been seen following the consumption of dietary sources. The consumption of a single protein-free high-carbohydrate meal elevated brain tryptophan levels. Similarly the consumption of a single 40% protein meal accelerated brain catecholamine synthesis through increased availability of tyrosine (Wurtman & Fernstrom, 1975). A minimal change of delta 0.07 in the tryptophan to large neutral amino acid ratio is required to influence mood following protein consumption, so a considerable shift in the ratio is required to have an effect on subsequent cognition (Fernstrom, 1994).
These early observations clearly demonstrate that serotonin and catecholamine neurotransmitters are under specific dietary control, so in that regards Poliquin is correct. The acute effects of a high-carbohydrate protein-free meal, typical of most children’s and a vast majority of westerner societies breakfast (think cereals) do induce marked increases in serotonin synthesis, and thus may result in increased feelings of lethargy; however, is the absolute avoidance of carbohydrate justifiable based on the current evidence?
It appears not. Interestingly, the addition of protein to that otherwise protein-free high-carbohydrate meal suppressed the increases in brain tryptophan and serotonin (Wurtman & Fernstrom, 1975), because protein contributes to the blood plasma considerably larger amounts of the other neutral amino acids (e.g., BCAA’s, phenylalanine) than of tryptophan. Tryptophan and other large neutral amino acids, most notably the BCAA’s leucine, isoleucine and valine share and compete for uptake along the specific transport mechanism across the blood brain barrier (Maughan, 2000). Therefore brain 5-HTP synthesis will increase when there is an increase in the ratio of free tryptophan to BCAA’s in the blood (Chaouloff et al. 1986), thus explaining why the addition of protein to an otherwise protein-free high-carbohydrate meal can suppress serotonin synthesis.
Just to confirm, this theory has also been confirmed in humans. Using 20 men, Lieberman et al. (1985) administered single oral doses of tryptophan (50 mg/kg) and tyrosine (100 mg/kg) in a double-blind, crossover study. Tryptophan increased subjective fatigue and decreased self-ratings of vigour and alertness, but did not impair performance on any of the tests. Tyrosine produced no effects in our young population compared with placebo, but did decrease reaction time relative to tryptophan. The authors concluded that tryptophan has significant sedative-like properties, but unlike other sedatives may not impair performance in a series of cognitive tests. Now being critical, it’s extremely unlikely – probably impossible in fact – you’d ever consume 50 mg/kg tryptophan in a single dose from a dietary source, thus wouldn’t necessarily have to worry about the negative mental effects of tryptophan consumption.
So Poliquin, who strongly advocates the avoidance of carbohydrate at breakfast time has no science to back up such claims. The truth is the brain neurotransmitters are influenced by the ratio of free tryptophan to large neutral BCAA’s (Fischer et al. 2002), so a mixed meal that will maintain a balance in that ratio is adequate. Further an increase in the ratio of free tryptophan to large neutral amino acids following a high-carbohydrate meal is reversible through the addition of a protein to that meal.
An intricate study by Fischer et al. (2002) examined the cognitive effects of isoenergetic meals consisting of three carbohydrate ratios, a carbohydrate rich meal (4:1), a balanced meal (1:1), and a protein rich meal (1:4) in 15 healthy subjects. Not surprising, attention and decision times were improved in the first hour with the high carbohydrate meal, owing to the greater rise in glucose metabolism. But during the first hour it was both the balanced and higher protein meals that resulted in improved performance. Further, overall reaction times in a central task were fastest after the balanced or high protein meal, thus suggesting a high protein meal or a balanced meal seems to result in better overall cognitive performance. Although the results also revealed participants subjective measures of ‘tasty’ and ‘pleasant’ were greater in the balanced meal than in the high protein meal, which suggests this would be the most effective in a practical sense.
Now, from reading the above it may appear that carbohydrates contain significant amounts of tryptophan, thus increase free tryptophan concentrations after ingestion, thus increasing tryptophan uptake and stimulating serotonin synthesis. However, this is not the case. For the sake of dispelling Poliquins breakfast argument let’s take oats for example, the amino acid profile of 100g oats indicates a tryptophan concentration of 234 mg, compared to 694 mg isoleucine, 1284 mg leucine, and 937 mg valine, which collectively make up the BCAA’s. So a high carbohydrate breakfast doesn’t contain that much tryptophan and yet accelerates serotonin synthesis through an increase in tryptophan uptake by the brain, how does that work?
Although the carbohydrate meal itself doesn’t contain much tryptophan, the insulin that is secreted following the carbohydrate meal results in a decrease in plasma levels of the large neutral amino acids (tyrosine, phenylalanine, BCAA’s and methionine) that would ordinarily compete with tryptophan for uptake by the brain. Tryptophan then crosses the blood-brain barrier and is converted to serotonin (Spring, 1984).
So it’s not actually the carbohydrate that causes the problem, it’s the insulin response to that carbohydrate that is the issue.
The following is a novel thought that stemmed from logic and my intuition: looking at the insulin index created by Holt et al. (1997) beef, the food advocated by Poliquin in his infamous meat and nut breakfast comes in at an insulin area under the curve of 7910 ± 2193 pmol.min.L and grain bread, a food demonized by Poliquin in fear of it frying your brain cells comes in at 6659 ± 837 pmol.min.L. The insulin index clearly indicates beef is more insulinogenic than most forms of carbohydrate, therefore suggesting that the net effect in regards neurotransmitter synthesis of a high-protein carbohydrate-free meal may be similar to that of a mixed meal. The greater insulin response to beef consumption will lead to a reduction in the BCAA’s and other neutral amino acids, leaving free tryptophan to be taken up by the brain; interestingly 100g steak contains more tryptophan than the same portion of oats (288 mg).
Logic and intuition suggests this could be true, although a number of rat studies have disproved the hypothesis, where Rouch et al. (1998) revealed a high protein diet significantly reduced serotonin concentrations for 2-hours, Wurtman & Fernstrom (1975) reported similar findings. Interestingly, the reduction in serotonin following protein feeding is thought to be among the reasons why protein is more satiating that carbohydrate.
Finally, Poliquins suggestion that the first meal of the day dictates that whole days brain neurotransmitters. We’ll start with a rat study from 1995; Fernstrom & Fernstrom studied the brain tryptophan concentrations and serotonin synthesis rates of fasted rats fed a high-carbohydrate meal followed 2-hours later by a protein-containing meal. They demonstrated that when the high-carbohydrate meal was fed first, brain tryptophan concentrations increased as did serotonin synthesis, and these changes were reversed at 4-hours if the second meal contained protein. Interestingly they go on to conclude, and I quote: “brain tryptophan concentrations and serotonin synthesis are thus responsive to the sequential ingestion of protein and carbohydrate meals if there is a sufficient interval between meals”. Similarly, Rouch et al. (2003) reported the plasma ratio of free tryptophan to large neutral amino acids was increased by a carbohydrate meal, and remained high for 2-hours, a subsequent casein (protein) meal reversed this change. Interestingly, a first casein meal reduced the ratio, and was not increased again by a subsequent carbohydrate meal. These findings actually favour Poliquins suggestions, although the weight of the evidence doesn’t, again supporting my belief of a mixed meal consumption.
From a human perspective the reversible nature of neurotransmitter synthesis is supported by the central fatigue hypothesis, which predicts that the ingestion of BCAA’s during exercise will raise plasma BCAA concentration and hence reduce transport of free tryptophan into the brain; subsequently reducing the formation of serotonin and alleviating sensations of fatigue and therefore improve endurance performance (Gleeson et al. 2005). This hypothesis lacks support, although does highlight the obvious reversible nature of neurotransmitter synthesis.
Conclusion and recommendations
My recommendation based on this evidence is that a single macronutrient meal can have a significant impact on the brain neurotransmitters, where a protein-free high-carbohydrate meal can increase serotonin synthesis, and thus increase feelings of fatigue just as Poliquin suggests. Although alternatively, a high-protein high-fat carbohydrate-free meal can increase catecholamine synthesis. Granted you would favour catecholamine synthesis, but with your daily macronutrient requirements in mind, combined with the fact that eating single macronutrient meals would be extremely tasteless and boring it would be more appropriate to consume mixed meals than to focus on meals free from certain macronutrients in fear of a surge of sleep inducing neurotransmitters.
In conclusion the promotion of carbohydrate free, high-protein breakfasts is largely unsubstantiated. A mixed meal consisting of meat, carbohydrate (both starchy and fibrous) and fat (possibly nuts) is adequate, and in a practical sense is optimal.
Chaouloff et al. (1986) http://www.ncbi.nlm.nih.gov/pubmed/3083049
Fernstrom & Fernstrom (1995) http://ajcn.nutrition.org/content/61/2/312.short
Fernstrom et al. (1994) http://www.ncbi.nlm.nih.gov/pubmed/7903674
Fischer et al. (2002) http://www.ncbi.nlm.nih.gov/pubmed/11897269
Francis (2005) http://europepmc.org/abstract/MED/16273023
Gelenberg et al. (1980) http://www.ncbi.nlm.nih.gov/pubmed/6443584
Gleeson et al. (2005) http://jn.nutrition.org/content/135/6/1591S.abstract
Growdon & Wurtman (1977) http://www.ncbi.nlm.nih.gov/pubmed/14577
Hartman & Spinweber (1979) http://www.ncbi.nlm.nih.gov/pubmed/469515
Holt et al. (1997) http://ajcn.nutrition.org/content/66/5/1264.full.pdf
Lieberman et al. (1985) http://ajcn.nutrition.org/content/42/2/366.full.pdf
Rouch et al. (1998) http://www.sciencedirect.com/science/article/pii/S0031938498002042
Rouch et al. (2003) http://www.ncbi.nlm.nih.gov/pubmed/12722987
Spring et al. (1984) http://www.ncbi.nlm.nih.gov/pubmed/6400041
Wurtman, R., & Fernstrom, J. (1974). Nutrition and the Brain. Scientific American, 230, 84- 91.
Wurtman & Fernstrom (1975) http://ajcn.nutrition.org/content/28/6/638.abstract
Wurtman et al. (1980) http://www.ncbi.nlm.nih.gov/pubmed/6115400
Bio: Matt holds a BSc (Honours) degree in Sport & Exercise Science, an MSc in Nutrition Science. Through his own Performance Nutrition business, Nutrition Condition, he delivers frequent Health & Wellbeing Workshops to corporate and personal clients advising on how best to develop a sound, scientifically structured nutrition programme free from fads and marketing bias. Nutrition Condition also delivers Performance Nutrition services to professional athletes.
For regular updates follow Matt on Twitter @mattNCUK.