What you will learn:
- What a neurotransmitter is
- The function of key neurotransmitters
- The relationship between food & neurotransmitters
- Optimising neurotransmitters with food
- My recommendations based on the existing research
Who this is applicable to:
- Especially nutrition nerds
Who should not read this:
- Charles Poliquin?
The suggestion made by Charles Poliquin within the articles and multimedia section of the Poliquin groups website reads as follows: ‘rotating meat and nuts breakfast… increased mental acuity and focused energy… allows for a slow and steady rise in blood sugar… to remain stable for an extended period of time… what you eat for breakfast sets up your entire neurotransmitter production for the day’.
All of these suggestions are made relative to popular breakfast choices that are generally higher in carbohydrate, including oats, cereal and bread.
Charles Poliquin for those who do not know is a well-respected highly successful strength and conditioning coach. I commend him for his achievements within the field of strength & conditioning, I actually own a number of his books, and his website www.strengthsensei.com is a fantastic resource.
It is not the aim of this article to openly criticise Poliquin’s practices or question his motives or intentions, nor will I launch an outright tirade on him. However I feel it is necessary to discuss the application of this much-famed breakfast. I have recently been vilified by a number of potential clients for advocating carbohydrate at breakfast. They citied Poliquin’s meat & nut breakfast and the research used within the meat & nut breakfast in their criticism of me. So I think it is only fair that I counter their suggestion and critique the breakfast in support of my stance in favour of a more flexible, practical approach to the first meal of the day.
As with all of my articles the extravagant claims will be examined meticulously and honestly with frequent reference to the existing evidence-base. Note the evidence-base, not cherry picking favourable research. Particularly pertaining to the claims of optimised neurotransmission and neurotransmitter production for the day.
A neurotransmitter is a chemical signal that allows for transmission of signals from one neuron to another, across a synapse. Neurotransmission allows for, and controls, muscle fibre contraction, bodily actions, emotions and feelings. The most significant neurotransmitters in the human body are acetylcholine, norepinephrine, dopamine, Gamma Amino Butyric Acid (GABA), glutamate, serotonin and endorphins. There is a substantial body of evidence to support the notion that nutrition has a significant influence on the appearance of blood and brain neurotransmitters (1, 2, 3).
Neurotransmitters and cognitive function
Research has demonstrated that serotonin is a known sleep-inducing agent (4), with human research indicating that serotonin reduces subjective alertness, objective performance and increases feelings of relaxation and lethargy (5). The neurotransmitter dopamine on the other hand is associated with pleasurable reward, behaviour, cognition, mood, memory, movement, attention and learning. Interestingly dopamine is critically involved in the drug addiction process by inducing pleasant states or by relieving distress (6). Acetylcholine has a number of physiological functions: it is a widely distributed excitatory neurotransmitter that interacts with the central nervous system and is involved in wakefulness, attentiveness and memory. Interestingly, Alzheimer’s disease is characterised by a significant reduction in acetylcholine concentration and function (7), highlighting its importance in human health performance.
Neurotransmitters and nutrition
Neurotransmitters are primarily synthesized from amino acids, particularly the branched chain amino acids (BCAAs) tyrosine and tryptophan. The rates at which neurotransmitters are synthesized depends upon the availability of the amino acid precursor. Research from rodent studies in the 70s and early 80s demonstrated that increased concentrations of tryptophan resulted in an elevation in serotonin synthesis, and increasing concentrations of tyrosine resulted in elevations in dopamine and certain catecholamines (8).
This was supported by earlier research indicating that 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, elevated brain tyrosine levels, and thus catecholamine increased in the central nervous system (CNS), while the consumption of lecithin or choline (found in fat) increased brain choline levels and neuronal acetylcholine synthesis (9). Ultimately concluding that tryptophan was the precursor for serotonin, tyrosine was the precursor for dopamine and choline the precursor for acetylcholine.
All of these early studies utilised both observational and knock-out rodent models, using a single dose of the precursor, although similar effects have been seen following the consumption of dietary sources (real food). Again using a rodent model Wurtman & Fernstrom (9) demonstrated that 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. Fernstrom (10) concluded that 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.
This data clearly demonstrates that the neurotransmitters serotonin, dopamine and the catecholamines are under specific dietary control. Essentially this is the data Poliquin has built his meat and nut breakfast on, and in that regard he is correct. The acute effects of a high-carbohydrate protein-free meal, atypical of a modern Western diet breakfast (think oatmeal and cereals) does 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? Is the process irreversible as Poliquin suggests, does breakfast dictate the neurotransmitters for the entire day?
If Poliquin had read a little further, instead of cherry picking the juiciest data he would have realised not.
Interestingly, in the same research by Wurtman & Fernstrom (9) found that the addition of protein to an otherwise protein-free high-carbohydrate meal suppressed the increases in brain tryptophan and serotonin synthesis, because protein contributes to the blood plasma considerably larger amounts of the other neutral amino acids (e.g. BCAAs, phenylalanine) than of tryptophan. Tryptophan and other large neutral amino acids, most notably the BCAAs leucine, isoleucine and valine, share the same specific transporter across the blood-brain barrier and thus compete for uptake (11). Therefore, brain 5-HTP synthesis will increase when there is an increase in the ratio of free tryptophan to BCAAs in the blood (12), thus explaining why the addition of protein to an otherwise protein-free high-carbohydrate meal can suppress serotonin synthesis.
This theory has also been confirmed in humans. Using 20 men, Lieberman et al. (13) 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. Compared to placebo there was no difference in performance with tyrosine, although tyrosine administration did reduce reaction time relative to tryptophan. Lieberman et al (13) concluded that tryptophan has significant sedative-like properties, but unlike other sedatives this may not impair performance in a series of cognitive tests. However it is extremely unlikely, probably impossible in fact, that a human would ever consume 50 mg/kg tryptophan in a single dose from a dietary source thus would not necessarily have to worry about the negative mental effects of lone tryptophan consumption.
Poliquin strongly advocates the avoidance of carbohydrate at breakfast, in fear of neurotransmitter malfunction, mental breakdown and impaired performance has only a handful of cherry picked studies to support him. The truth being that the brain neurotransmitters are influenced by the ratio of free tryptophan to large neutral BCAAs (14), so a mixed meal that is able to maintain a balance in that ratio is adequate to optimise neurotransmitter synthesis.
Furthermore, an increase in the ratio of free tryptophan to large neutral amino acids following a high-carbohydrate protein-free meal is reversible through the addition of protein to that meal, ultimately balancing the ratio again. This invalidates Poliquin’s suggestion that the first meal of the day dictates brain neurotransmitter production for that entire day.
Thanks must also go to my friend Alex Ritson for bringing to my attention the latest research out of John Fernstrom’s lab, that further supports this hypothesis (21).
Worth mentioning is this intricate study by Fischer et al. (14). They 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, in an attempt to elucidate which breakfast combination is most suitable in a school environment. Unsurprisingly, attention and decision times were improved in the first hour with the high carbohydrate meal, owing to the provision of and greater rise in glucose metabolism. However, during the first hour it was both the balanced and higher protein meals that resulted in improved performance. Furthermore, overall reaction times in a central task were fastest after both the balanced and high protein meal, thus suggesting a high protein meal or a balanced meal appear 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.
Having read the study by Fischer et al. (14) it would appear that carbohydrates contain significant amounts of tryptophan, thus increase free tryptophan concentrations after ingestion, elevating tryptophan uptake and stimulating serotonin synthesis. However, this is not the case. A bowl of oats for example, porridge or oatmeal depending which side of the pond you are, a common staple of many a Western breakfast and is vilified by Poliquin for the potential negative effects on neurotransmission and mental performance. Well, 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 BCAAs (15). So a high carbohydrate breakfast does not contain that much tryptophan although accelerates serotonin synthesis through an increase in tryptophan uptake by the brain, huh?
It would appear that although the carbohydrate meal alone does not contain much tryptophan, the insulin secreted following the carbohydrate meal results in a rapid removal and significant decrease in plasma levels of the large neutral amino acids (tyrosine, phenylalanine, BCAAs 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 (5).
It appears it is not actually the carbohydrate that causes the problem, it is in fact the insulin response to that carbohydrate that drives the large neutral amino acids out of the bloodstream, leaving tryptophan free to pass the blood brain barrier, with no competition.
The insulin index formulated by Holt et al. (16) clearly demonstrates that beef, the food favoured by Poliquin in his infamous meat and nut breakfast along with other more exotic meats elicits an insulin response of 7910 ± 2193 pmol/min/L and grain bread, a food demonized by Poliquin in fear of it frying all brain cells comes in at 6659 ± 837 pmol/min/L – insulin area under the curve. 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 BCAAs 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) (15).
Logic, intuition and a basic understanding of the insulin index suggests this could be true, although a number of rodent studies have disproved the hypothesis, where Rouch et al. (17) revealed a high-protein diet significantly reduced serotonin concentrations for 2-hours, Wurtman & Fernstrom (9) 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.
As discussed previously research has demonstrated that Poliquin’s suggestion that the first meal of the day dictates that whole days brain neurotransmitters is false, in that the process is reversible. Looking at some more of the evidence to disprove this claim a rodent study formulated to analyse the brain tryptophan concentrations and rates of serotonin synthesis in 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 the authors went on to conclude, 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. (18) 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. This finding actually favours Poliquin’s claims in that an initial high-protein carbohydrate-free meal is more favourable than a high-carbohydrate protein-free meal in regards neurotransmitter synthesis.
The reversible nature of neurotransmitter synthesis is supported by the central fatigue hypothesis in humans, which predicts that the ingestion of BCAAs 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 (19). To date this hypothesis still lacks support despite many years of research, although it 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 typical of the meals consumed at breakfast by many Westerners – think oatmeal et al – can increase serotonin synthesis, and thus increase feelings of fatigue as Poliquin claims. However, a high-protein high-fat carbohydrate-free meal can increase dopamine and catecholamine synthesis. Granted you would favour dopamine and 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 low-carbohydrate, high-protein, high-fat meat and nut breakfast is largely unsubstantiated, and supported by a few cherry picked studies. A mixed meal consisting of protein (possibly red meat if your finances allow), carbohydrate and fat (possibly nuts) is adequate, and in a practical sense is optimal.
Article by Matt Jones, MSc Nutrition