Whey, Tryptophan, & Serotonin

Also see –
Tryptophan, Fatigue, Training, and Performance
Carbohydrate Lowers Free Tryptophan
Gelatin > Whey
Thyroid peroxidase activity is inhibited by amino acids
Protective Glycine

“Whey, which is sold as a protein supplement, and egg whites contain too much tryptophan and can be antithyroid if used excessively.” -Ray Peat, PhD

“For example, whey protein contains much more tryptophan than whole milk or cheese does, and would tend to suppress the thyroid and activate the whole serotonin-stress system. Whey might be good for fattening pigs, but its acceptance in the health food industry as a powdered protein supplement is just another example of the harmful effects of serotonin mythology.” -Ray Peat, PhD

Am J Clin Nutr. 2000 Jun;71(6):1536-44.
The bovine protein alpha-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress.
Markus CR, Olivier B, Panhuysen GE, Van Der Gugten J, Alles MS, Tuiten A, Westenberg HG, Fekkes D, Koppeschaar HF, de Haan EE.
BACKGROUND:
Increased brain serotonin may improve the ability to cope with stress, whereas a decline in serotonin activity is involved in depressive mood. The uptake of the serotonin precursor, tryptophan, into the brain is dependent on nutrients that influence the cerebral availability of tryptophan via a change in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp-LNAA ratio). Therefore, a diet-induced increase in tryptophan availability may increase brain serotonin synthesis and improve coping and mood, particularly in stress-vulnerable subjects.
OBJECTIVE:
We tested whether alpha-lactalbumin, a whey protein with a high tryptophan content, may increase the plasma Trp-LNAA ratio and reduce depressive mood and cortisol concentrations in stress-vulnerable subjects under acute stress.
DESIGN:
Twenty-nine highly stress-vulnerable subjects and 29 relatively stress-invulnerable subjects participated in a double-blind, placebo-controlled study. Subjects were exposed to experimental stress after the intake of a diet enriched with either alpha-lactalbumin or sodium-caseinate. Diet-induced changes in the plasma Trp-LNAA ratio and prolactin were measured. Changes in mood, pulse rate, skin conductance, and cortisol concentrations were assessed before and after the stressor.
RESULTS:
The plasma Trp-LNAA ratio was 48% higher after the alpha-lactalbumin diet than after the casein diet (P = 0.0001). In stress-vulnerable subjects this was accompanied by higher prolactin concentrations (P = 0.001), a decrease in cortisol (P = 0.036), and reduced depressive feelings (P = 0.007) under stress.
CONCLUSIONS:
Consumption of a dietary protein enriched in tryptophan increased the plasma Trp-LNAA ratio and, in stress-vulnerable subjects, improved coping ability, probably through alterations in brain serotonin.

Physiol Behav. 2004 Jun;81(4):585-93.
Alpha-lactalbumin combined with a regular diet increases plasma Trp-LNAA ratio.
Beulens JW, Bindels JG, de Graaf C, Alles MS, Wouters-Wesseling W.
Brain serotonin influences food intake and mood. It is synthesised from tryptophan (Trp) of which uptake in the brain is dependent on plasma ratio of tryptophan to the sum of other large neutral amino acids (Trp-LNAA). A carbohydrate-rich diet increases this ratio, whereas a protein-rich diet decreases it. Yet, if the protein source is alpha-lactalbumin the ratio increases. It is, however, unknown whether this also happens in the context of a regular diet (15% protein). We studied the effect of an alpha-lactalbumin supplement combined with regular diet on plasma Trp-LNAA ratio, serum prolactin (marker of serotonin synthesis), food intake, appetite, macronutrient preference and mood. Eighteen healthy males participated in a double-blind, randomised, placebo-controlled, crossover study. One hour after breakfast they received a drink containing alpha-lactalbumin and carbohydrates (AS) or carbohydrates (PS) only. Plasma Trp-LNAA ratio, serum prolactin, food intake, appetite, macronutrient preference and mood were assessed before and 90 min after consumption of the supplement. Changes of plasma Trp-LNAA ratio differed (P<.001) between both supplements, increasing by 16% after AS and decreasing by 17% after PS. Decrease of serum prolactin was slightly smaller after AS than after PS (P=.083). Appetite, food intake, macronutrient preference or mood did not differ between supplements. We conclude that an alpha-lactalbumin-enriched supplement combined with a regular diet increases plasma Trp-LNAA ratio and may influence serum prolactin, but we could not demonstrate effects on appetite, food intake, macronutrient preference and mood.

Am J Clin Nutr. 2002 Jun;75(6):1051-6.
Whey protein rich in alpha-lactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subjects.
Markus CR, Olivier B, de Haan EH.
BACKGROUND:
Cognitive performance often declines under chronic stress exposure. The negative effect of chronic stress on performance may be mediated by reduced brain serotonin function. The uptake of the serotonin precursor tryptophan into the brain depends on nutrients that influence the availability of tryptophan by changing the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp-LNAA ratio). In addition, a diet-induced increase in tryptophan may increase brain serotonergic activity levels and improve cognitive performance, particularly in high stress-vulnerable subjects.
OBJECTIVE:
We tested whether alpha-lactalbumin, a whey protein with a high tryptophan content, would increase the plasma Trp-LNAA ratio and improve cognitive performance in high stress- vulnerable subjects.
DESIGN:
Twenty-three high stress-vulnerable subjects and 29 low stress-vulnerable subjects participated in a double-blind, placebo-controlled, crossover study. All subjects conducted a memory-scanning task after the intake of a diet enriched with either alpha-lactalbumin (alpha-lactalbumin diet) or sodium caseinate (control diet). Blood samples were taken to measure the effect of dietary manipulation on the plasma Trp-LNAA ratio.
RESULTS:
A significantly greater increase in the plasma Trp-LNAA ratio after consumption of the alpha-lactalbumin diet than after the control diet (P = 0.0001) was observed; memory scanning improved significantly only in the high stress-vulnerable subjects (P = 0.019).
CONCLUSION:
Because an increase in the plasma Trp-LNAA ratio is considered to be an indirect indication of increased brain serotonin function, the results suggest that dietary protein rich in alpha-lactalbumin improves cognitive performance in stress-vulnerable subjects via increased brain tryptophan and serotonin activities.

Am J Clin Nutr. 2005 May;81(5):1026-33.
Evening intake of alpha-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention.
Markus CR, Jonkman LM, Lammers JH, Deutz NE, Messer MH, Rigtering N.
BACKGROUND:
Brain serotonin function is thought to promote sleep regulation and cognitive processes, whereas sleep abnormalities and subsequent behavioral decline are often attributed to deficient brain serotonin activity. Brain uptake of the serotonin precursor tryptophan is dependent on nutrients that influence the availability of tryptophan via a change in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp:LNAA).
OBJECTIVE:
We tested whether evening consumption of alpha-lactalbumin protein with an enriched tryptophan content of 4.8 g/100 g increases plasma Trp:LNAA and improves alertness and performance on the morning after sleep, particularly in subjects with sleep complaints.
DESIGN:
Healthy subjects with (n = 14) or without (n = 14) mild sleep complaints participated in a double-blind, placebo-controlled study. The subjects slept at the laboratory for 2 separate nights so that morning performance could be evaluated after an evening diet containing either tryptophan-rich alpha-lactalbumin or tryptophan-low placebo protein. Evening dietary changes in plasma Trp:LNAA were measured. Behavioral (reaction time and errors) and brain measures of attention were recorded during a continuous performance task.
RESULTS:
Evening alpha-lactalbumin intake caused a 130% increase in Trp:LNAA before bedtime (P = 0.0001) and modestly but significantly reduced sleepiness (P = 0.013) and improved brain-sustained attention processes (P = 0.002) the following morning. Only in poor sleepers was this accompanied by improved behavioral performance (P = 0.05).
CONCLUSION:
Evening dietary increases in plasma tryptophan availability for uptake into the brain enhance sustained alertness early in the morning after an overnight sleep, most likely because of improved sleep.