Supplementing the brain–body health relationship

Studies have shown that L-citrulline may help to reduce exercise-induced gastrointestinal injuries and that taking L-alanyl-L-glutamine after strenuous activity may increase cognitive function

In a round up of recent research, studies have shown that L-citrulline may help to reduce exercise-induced gastrointestinal injuries and that taking L-alanyl-L-glutamine after strenuous activity may increase cognitive function. Yet, with a national survey revealing that Americans fear mental decline more than physical debility, exercise alone may not be enough to guarantee long-term brain health.

According to a recently published study in the American College of Sports Medicine, L-citrulline might be a preferred pre-workout ingredient for endurance athletes. Oral supplementation with L-citrulline before exercise may help to reduce the gastrointestinal (GI) problems associated with physical strain during strenuous exercise.1

Participants in the double-blind, placebo-controlled study took 10g of L-citrulline orally before exercise. The results of subsequent tests showed increased levels of L-arginine, an amino acid involved in the production of nitric oxide (NO). Blood flow in the stomach and small intestine drops during exercise, which can lead to blood vessels and fragile internal linings becoming damaged, and may be responsible for unpleasant GI symptoms. Nitric oxide is known to support blood circulation, especially in the presence of L-arginine.1

'The results of this study may be useful for athletes with ischaemia-related abdominal symptoms during strenuous exercise,' said researcher Dr Kaatje Lenaerts, Maastricht University Medical Centre. 'The current study demonstrates that a single oral dose of L-citrulline before exercise reduces intestinal injury and can be taken without side-effects.'

According to Kyowa Hakko, who provided the L-citrulline used in the study, it’s a better precursor of arginine and NO than arginine itself. This is shown by acute oral administration of L-citrulline raising plasma arginine levels to about 227% with 3.8g/body surface area of L-citrulline (within 4 hours) compared with only 90% with the equivalent dose of arginine.2

Further, a related animal study published in Biochemical and Biophysical Research Communications showed that L-citrulline plus L-arginine supplementation caused a more rapid increase in plasma L-arginine levels and a marked enhancement of NO bioavailability, including plasma cGMP concentrations, than with dosage with the single amino acids. Blood flow in the central ear artery in rabbits was also significantly increased by L-citrulline plus L-arginine administration as compared with the control.3

Strenuous exercise and cognitive function

In further research, a study has shown that taking L-alanyl-L-glutamine after strenuous exercise may increase cognitive function. According to a study published in the European Journal of Sport Science, taking Sustamine after endurance exercise increases athletes’ reaction times and cognitive function when compared with no hydration.4

Twelve male athletes performed four endurance trials of various lengths. One trial allowed no hydration, with another consisting of consuming an energy drink. The other two trials included low and high doses of Sustamine in energy drinks. Participants were then given a reaction time test in which they had to press buttons as quickly as possible when lit up with either a hand or foot. With no hydration, researchers found that the athletes’ reaction times were negatively affected, whereas those taking Sustamine saw a noticeably higher number of correct hits.

For cognitive tests, participants were required to subtract the number 7 from a random four-digit number. The number of correct answers was recorded. Non-hydrated subjects had correct answers as high as 5.02; those who ingested Sustamine had correct answers as high as 5.96 to 7.3.

Sustamine is a dipeptide of glutamine that provides several substantial benefits such as enhanced recovery, immune system support and increased metabolic rate. On top of these benefits, research suggests that Sustamine is absorbed more than 240% better than standard L-glutamine, which means you get results while having to use less.5

Mental deterioration versus physical decline

The link between physical activity and cognition is well-founded. According to leading neuroscientist, Dr Deborah Yurgelun-Todd, diet and exercise are two of the best ways to care for the brain. 'Individuals should establish good brain health habits such as eating healthy foods with omega-3 fatty acids — monounsaturated fatty acids have been found to deliver nutrients to the brain — and staying active, exercising to reduce stress and tension,' she notes. And, although the exercise-induced reduction in cognitive ability described above may only be temporary, it does serve to highlight a more important issue.

To bring much-needed attention to Brain Health Awareness Week in March, national survey data was released that shed light on consumer concerns related to brain health and function. Among the notable results, the survey found that 57% of Americans fear reduction in brain function more than physical decline (43%).

Additionally, more than half (54%) of survey respondents admit to having trouble remembering names, whereas 30% admit to not remembering friends’ or family members’ birthdays. The survey also showed forgetfulness is prevalent in younger Americans. The majority of millennials (59%) report frequent forgetfulness during their morning routines, with most forgetting keys (32%), mobile phones (28%) and remembering to turn off appliances (21%).

In addition to studying healthy lifestyle habits that impact brain health, Dr Yurgelun-Todd is one of only five researchers in the US who has studied the brain nutrient citicoline. Her most recently published study found that by supplementing study participants with Cognizin citicoline for 6 weeks, they made 28% fewer commission errors during memory recall tests.6

In a separate study, she saw an increase in the formation of brain membranes by 35% and the restoration of brain energy by 13.6%.7 'This study shows the significant positive effects that Cognizin citicoline can bring to healthy individuals who decide to use citicoline as a daily supplement,' said Dr Yurgelun-Todd.

Citicoline is referred to by the scientific community as a 'brain nutrient' because it aids the production of a critical building block in brain cells. Although the brain produces its own levels of citicoline naturally — to protect its cell membranes’ integrity and help ward off disease — studies show that oral supplementation with citicoline allows for the improved transport of critical nutrients and signal-sending neurotransmitters in the brain.

Remarkably, consumer awareness of citicoline remains low, despite years of positive research, including a study published in the international, peer-reviewed journal, Methods and Findings in Experimental and Clinical Pharmacology, which found that citicoline improved memory deficits in the elderly. In the placebo-controlled study, a group of elderly subjects who exhibited memory deficits (without dementia) were observed after administration of 1000mg and 500mg of citicoline. After only a 4-week administration period, results indicated that citicoline improved memory in free recall tasks and resulted in significant improvement in word recall.8

In a separate study, also conducted by Dr Yurgelun-Todd, Cognizin citicoline, during a 28 day supplementation period, produced improved cognitive scores on attention and performance in the study participants. The randomised, double-blind, placebo-controlled study included 60 healthy adult women, aged 40 to 60, using a daily oral supplement of 250 or 500mg and was published in Food and Nutrition Sciences.7

Dr Yurgelun-Todd notes that citicoline supplementation is another way consumers can positively impact their overall brain health. 'Cognizin citicoline is a powerful, well-researched supplement that is already naturally produced in the brain,' she said. 'It plays a major role in healthy brain function — especially when it comes to boosting memory and concentration.'

Although the national survey results reveal Americans’ enduring fear of mental decline, consumers are empowered to support sustained mental effort and boost healthy brain functions such as memory, focus and concentration through daily supplementation with the powerful, naturally occurring 'brain nutrient' Cognizin citicoline. Exercise alone might not be enough!


1. K. van Wijck, et al., 'L-Citrulline Improves Splanchnic Perfusion and Reduces Gut Injury During Exercise,' Medicine and Science in Sports and Exercise 46(11), 2039–2046 (2014).

2. M. Masahiko, et al., 'Oral Supplementation with a Combination of L-Citrulline and L-Arginine Rapidly Increases Plasma L-Arginine Concentration and Enhances NO Bioavailability,' Biochemical and Biophysical Research Communications 454(1), 53–57 (2014).

3. K.P. Kuhn, et al., 'Oral Citrulline Effectively Elevates Plasma Arginine Levels for 24h in Normal Volunteers,' Circulation: AHA Scientific Sessions, abstract 1692, II–1339 (2006).

4. G.J. Pruna, et al., 'Effect of Acute L-Alanyl-L-Glutamine and Electrolyte Ingestion on Cognitive Function and Reaction Time Following Endurance Exercise,' Eur. J. Sport Sci. (Epub 16 October 2014): DOI:10.1080/17461391.2014.969325.

5. R.C. Harris, et al., 'L-Glutamine Absorption is Enhanced After Ingestion of L-Alanylglutamine Compared with the Free Amino Acid or Wheat Protein,' Nutr. Res. 32(4), 272-277 (2012).

6. M.M. Silveri, et al., 'Citicoline Enhances Frontal Lobe Bioenergetics as Measured by Phosphorus Magnetic Resonance Spectroscopy,' NMR Biomed. 21(10), 1066–1075 (2008).

7. E. McGlade, et al., 'Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women,' Food and Nutrition Sciences 3, 769–773 (2012).

8. X.A. Alvarez, et al., 'Citicoline Improves Memory Performance in Elderly Subjects,' Methods and Findings in Experimental and Clinical Pharmacology 19(3), 201–210 (1997).