Whey Protein and Cortisol: Back to the Research

By Neel Duggal, December 9, 2014

In the first part of a three-part series on whey protein and cortisol, we examined a research study from theyear 2000 assessing the impact of whey-derived protein Alpha-lactalbumin on chronic stress. Ultimately, researchers unveiled that consumption of this protein can lead to quantifiable decreases in levels of cortisol and its stress-related symptoms while simultaneously increasing production of serotonin and its positive impact upon mood (Markus). However, as with most scientific research, new questions arose and researchers wanted to know more specifics about the relationship between whey and stress. In this final part of a three-part series on whey protein, we continue to examine more recent literature documenting the impact of the consumption of whey-derived Alpha-lactalbumin protein on the cortisol, serotonin, and chronic stress. Read below to see how InsideTracker’s monitoring capabilities coupled with a thorough examination of suitable interventions can help you optimize levels of 30 biomarkers.



When Whey Works

Summary: Consumption of whey-derived Alpha-lactalbumin immediately increases the plasma trp:LNAA ratio. However, this is not accompanies by increased production of serotonin production or reduction of cortisol levels. Thus, eating whey does not immediately reduce symptoms associated with chronic stress.

The Science: A follow-up study in 2005 sought to determine if Alpha-lactalbumin had an immediate impact on levels of cortisol and chronic stress. To assess this, researchers recruited a total of 43 subjects consisting of 20 healthy subjects and 23 subjects who had recovered from depression. Both groups received a meal high in Alpha-lactalbumin and another high in casein (which served as the placebo). On both occasions, subjects underwent a stress test -- an unsolvable, time-constrained mental arithmetic task with loud noise (65 dB-80dB) and their mood levels, salivary cortisol levels, and ratio of tryptophan to large neutral amino acids were subsequently monitored.

The researchers hypothesized that the depressed individuals would experience improved mood and brain cognition and decreased stress and cortisol levels after consuming the Alpha-lactalbumin proteins. This was again based on the principle that a diet rich in Alpha-lactalbumin would result in increased levels of tryptophan and subsequently a higher ratio of tryptophan to large neutral amino acids- ultimately stimulating the production of serotonin and decreasing cortisol production.

As hypothesized, the increase in dietary Alpha-lactalbumin led to rises in Trp and Trp:LNAA. However, only minimal effects were found on mood and cortisol response to stress, leading the authors to conclude that

“a 1 [day] diet enriched with Alpha-lactalbumin is not sufficient to prevent a stress-induced mood deterioration or a cortisol Response in unmedicated, recovered depressed subjects” (Merens, 415)

The researchers explained their findings by stating that the 1-day intervention with Alpha-Lactalbumin was simply not strong enough, going on to elaborate

“the intervention did not fail, but a 1 day Alpha-lactalbumin diet may be too weak also to affect mood and cortisol responses to stress in recovered patients” (Merens, 421).

Because the Trp:LNAA ratio was improved, a more logical interpretation of the investigator’s research is that a short, inconsistent dosage of Alpha-lactalbumin is insufficient to induce a measurable effect. Instead, a larger, more consistent dosage of Alpha-lactalbumin would need to be consumed to have any noticeable impact.

Whey and Your Brain Power

Summary: Consumption of whey-derived Alpha-lactalbumin increases the trp:LNAA ratio and ultimately stimulates the production of serotonin. As a result, stress-vulnerable subjects who consumed whey protein experience improve brain cognition and reduced anxiety. Because of this, whey might be useful in helping individuals experiencing symptoms of chronic stress.

The Science:A 2005 study aimed to investigate the effect of whey-derived Alpha-lactalbumin and its impact on brain cognition. This time, researchers looked more closely at Alpha-lacatalbumin’s effect on the production of the neurotransmitter serotonin. As previously stated, high levels are directly correlated to improved brain cognition and anti-depressive qualities. Serotonin is also thought to promote sleep regulation and cognitive processes, whereas sleep abnormalities and subsequent behavioral decline are often attributed to deficient brain serotonin activity.

To investigate this hypothesis, researchers used 14 healthy subjects with mild sleep complaints and 14 without mild sleep complaints in a placebo-controlled, double-blind study. The 28 subjects slept at the laboratory for 2 separate nights so that cognitive morning performance could be evaluated after an evening diet containing either tryptophan-rich Alpha-lactalbumin characteristic of whey, or tryptophan-low placebo protein. Evening dietary changes in the plasma Trp:LNAA ratio were measured. Behavioral measures, as quantified by reaction time and errors of attention, were recorded during a continuous performance task. The researchers hypothesized that increasing whey-derived Alpha-lactalbumin would improve brain functions and cognition. This was primarily based on the fact that Alpha-lactalbumin is abundant in the amino acid tryptophan, which is the structural precursor to serotonin.

The researchers concluded that evening Alpha-lactalbumin intake caused a 130% increase in Trp:LNAA before bedtime and modestly but significantly reduced sleepiness and improved brain-sustained attention processes the following morning (Markus, 2005, p. 1032). Furthermore, improved behavioral performance associated with Alpha-lactalbumin was only observed in poor sleepers. These findings collectively support the notion that evening consumption of tryptophan-rich Alpha-lactalbumin may improve early morning performance indirectly by enhancing available brain tryptophan and subsequent sleep improving serotonin production.

Other research the following year also supported the notion that Alpha-Lactalbumin had a positive impact upon Serotonin production. As previously stated, high levels of serotonin are directly correlated with improved brain cognition and anti-depressive qualities while low levels of brain serotonin are associated with reduced cognitive functions. Since cognitive dysfunctions sometimes persist after remission of depression, the researchers sought to investigate the effects of a diet enriched with alpha-lactalbumin on cognition in recovered depressed patients.

Twenty-three recovered depressed patients and 20 healthy matched controls without a history of depression consumed meals rich in alpha-lactalbumin or casein protein in a double-blind crossover design. Mood, cognitive function and plasma amino acids were assessed at both sessions before and after dietary intake. Through a variety of tests, researchers observed that

“Alpha-lactalbumin protein had no effect on mood, but improved abstract visual memory and impaired simple motor performance. These effects were independent of history of depression (Booji, 1).

These findings are in line with the previous studies and hypotheses of the researchers. However, they also support the notion that Alpha-lactalbumin may improve memory. Researchers explained the impaired motor performance by emphasizing

“Alpha-lactalbumin impaired cognitive performance when the task was relatively easy and monotonous, possibly due to its sleep-inducing properties” (Booji, 7).

Thus, it is important to emphasize that while high levels of serotonin can have therapeutic properties it can lead to sloppiness!


Whey, Cortisol, and Muscle-Building


Summary: Whey protein might reduce elevation of cortisol levels during muscle recovery. Because elevated cortisol levels work antagonistically to muscle-building efforts by the body, this might be another mechanism through which whey helps with athletic endeavors.

The Science: Whey is most commonly associated with building muscle while cortisol is catabolic and leads to diminishment of tissues including muscle tissues. Because of this and the negative association between whey protein and cortisol, a group of researchers in 2013 expanded upon the limited prior research examining its impact during resistance exercise. In this broad study, they also investigated the effects of soy and whey protein supplementation on testosterone and sex hormone binding globulin (SHBG) during resistance exercise.

In their inquiry, provided 10 young men with either a 20 g supplementation of soy protein and whey protein. Then, they followed each participant perform acute heavy resistance exercise test consisting of 6 sets of 10 repetitions in the squat at 80% of the subject’s one repetition maximum over 14 days. The researchers monitored serum cortisol levels and observed that, during recovery, the subjects who consumed whey protein had reduced cortisol levels. Ultimately, the researchers concluded that

 “…whey might influence the response of cortisol during an acute bout of resistance exercise by also blunting its normal increase” (Kraemer, 72).
How Long Whey Works 


Summary: Sustained consumption of whey-derived Alpha-lactalbumin is known to result in quantifiable reduction of cortisol and symptoms associated with chronic stress. However, its therapeutic effects upon the body are sustained after it is taken out of one’s diet. Thus, whey protein can have a long-term impact in treating chronic stress.

The Science: Instead of looking at whey protein’s short-term impact on either cortisol or serotonin levels, researchers investigated Alpha-lactalbumin’s direct, long-term impact upon depressive cognitive indicators and sociability. To do this, researchers looked at mouse models and compared the effects of a diet rich in whey proteins on individual behavior in mice. During a 30 day-long dietary intervention, male mice had unlimited access to an experimental diet containing 17 % weight by mass of one of three protein sources: Alpha-lactalbumin, native whey, or casein. Mice had voluntary access to a running wheel. Social behavior was tested at baseline and at the end of the intervention. Half of each dietary group was then withdrawn from the diet and running wheel for 7 days, and social activity and individual behavior tests – mazes in an open field, elevated-plus maze, light-dark box and a forced swimming- were performed to evaluate anxiety and depression-like status.

Based on prior studies, researchers hypothesized that mice who consumed higher amounts of Alpha-lactalbumin and the high-quality native whey would experience reduced anxiety and depression-like status. Though the researchers did not explicitly state why, this again is based upon prior research findings that unveiled that a higher trp:LNAA ratio results in higher serotonin and reduced cortisol production that leads to lower stress-associated symptoms. Unlike prior studies, though, the researchers sought to investigate the long-term effects of whey and whey-derived Alpha-lactalbumin.

Whey-fed mice changed their behavior more often, suggesting that they were more dynamic. Aggression Behavior was observed in 29 % of alpha-lactalbumin and whey-fed mice and in 58 % of casein-fed mice, suggesting a lower level of anxiety on the former group (Vekovischeva, 1340). There were no differences in aggressive behavior, though.  Additionally, a whey-protein diet also contributed to reduced anxiety to mice undergoing each of the anxiety tests in standard conditions.

These behavioral changes also remained visible for a full 7 days after the conclusion of the intervention, suggesting that whey proteins have a prolonged improvement on the mental capacities of mice. Because of these findings, the researchers concluded that their

“study shows that the long-term ingestion of whey proteins may modulate behavior when compared with casein. Diet enriched with [alpha]-lac exhibited anxiolytic and anti-depressive activities while the whey diet improved sociability” (Vekovischeva, 1336).

Thus, this research study supports the notion that whey may have a potentially long-term impact upon reducing stress and improving brain cognition in mice, a close mammalian ancestor to humans.

Limitations of Whey

Summary: Whey-derived Alpha-lactalbumin is known to have a long-term impact upon stress-vulnerable subjects. However, its impact on cortisol and serotonin and levels in mentally healthy adults may be limited. More research is needed to investigate its potential therapeutic effects on chronic stress in non-stress vulnerable subjects.

The Science: The bulk of research on the impact of whey and whey-derived Alpha-lactalbumin on cortisol, serotonin, and stress focused on designing interventions with stress-vulnerable subjects and examining the results. Little research has focused on seeing the impact whey has on improving stress levels in subjects that are neither under a lot of stress nor stress-vulnerable.

To investigate this more thoroughly, researchers designed an intervention where they assessed the biochemical and cognitive effects of ingesting 40 grams of Alpha-lactalbumin in 28 healthy female subjects in a parallel group, placebo-controlled design. The researchers then measured the salivary cortisol levels to see if there was a measurable increase.

Relative to a casein-derived control protein, Alpha-lactalbumin increased plasma TRP and the ratio of TRP to neutral amino acids. However, there was no effect on salivary cortisol secretion or tasks of emotional processing shown previously to be sensitive to pharmacological manipulation of 5-HT in healthy volunteers (Witbracht). The results suggest that Alpha-lactalbumin produces a relatively modest increase in TRP availability, which may not be sufficient to produce the changes in emotional processing seen with administration of pure TRP in healthy subjects.

Because of these findings, whey-derived alpha-Lactalbumin may be more effective in treating subjects more vulnerable to stress, anxiety, and depression.

No Whey: Key Takeaways


Abundant research illustrates that whey protein can do much more than make you buff. Its main bioactive component- Alpha-lactalbumin- can help lower elevated cortisol levels and treat symptoms associated with chronic stress, such as depression and anxiety, while simultaneously improving serotonin production, which is associated with improved brain function. While there are a variety of other research-substantiated lifestyle adjustments other than whey-derived Alpha-lactalbumin that can optimize levels of this peculiar double-edged “stress hormone” and its more angelic neurotransmitter counterpart serotonin, it is important to regularly monitor them, along with other crucial biomarkers. They tell all of us stories about our physical and mental well-being.

InsideTracker -an efficient and affordable audit of 30 well-researched biomarkers commonly found in the blood- provides an invaluable service for anybody interested in both maximizing health and wellness by monitoring these blood biomarkers and then providing research-proven interventions to help modify their levels if not already optimized.

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Part 1: Whey Protein's Impact on Mood & Stress

Part 3: My Four Way Solution to Reduce Stress: Combating High Cortisol

Some other blog posts we think you'll love:

Reduce Your Stress Now

List of References

Booij, L., Merens, W., Markus, C. R., & Van der Does, A. W. (2006). Diet rich in α-lactalbumin improves memory in unmedicated recovered depressed patients and matched controls. Journal of Psychopharmacology, 20(4), 526-535.

Kraemer, W. J., Solomon-Hill, G., Volk, B. M., Kupchak, B. R., Looney, D. P., Dunn-Lewis, C., ... & Volek, J. S. (2013). The Effects of Soy and Whey Protein Supplementation on Acute Hormonal Responses to Resistance Exercise in Men. Journal of the American College of Nutrition, 32(1), 66-74.

Markus, C. R., Jonkman, L. M., Lammers, J. H., Deutz, N. E., Messer, M. H., & Rigtering, N. (2005). Evening intake of α-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention. The American journal of clinical nutrition, 81(5), 1026-1033.

Markus CR, Olivier B, Panhuysen GE, et al. 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. Am J Clin Nutr. 2000;71:1536-1544.

Markus, C. R., Olivier, B., & de Haan, E. H. (2002). Whey protein rich in α-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. The American journal of clinical nutrition, 75(6), 1051-1056.

Merens, W., Booij, L., Markus, R., Zitman, F. G., Onkenhout, W., & Van der Does, A. J. (2005). The effects of a diet enriched with α-lactalbumin on mood and cortisol response in unmedicated recovered depressed subjects and controls. British Journal of Nutrition, 94(03), 415-422.

Scrutton, H., Carbonnier, A., Cowen, P. J., & Harmer, C. (2007). Effects of α-lactalbumin on emotional processing in healthy women. Journal of Psychopharmacology.

Vekovischeva, O. Y., Peuhkuri, K., Bäckström, P., Sihvola, N., Pilvi, T., & Korpela, R. (2013). The effects of native whey and α-lactalbumin on the social and individual behaviour of C57BL/6J mice. British Journal of Nutrition, 110(07), 1336-1346.

Witbracht, M. G., Van Loan, M., Adams, S. H., Keim, N. L., & Laugero, K. D. (2013). Dairy food consumption and meal-induced cortisol response interacted to influence weight loss in overweight women undergoing a 12-week, meal-controlled, weight loss intervention. The Journal of nutrition, 143(1), 46-52.


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