Brain boosting bioactives, Part 2: From citicoline and curcumin to resveratrol

In part 1 we looked at omega-3s, the B vitamins, vitamin E, magnesium, lutein, and phosphatidylserine​, and we continue now with citicoline, curcumin, and more.

[Editor’s note: The list is not intended to be exhaustive but a "30,000 foot" review of the key ingredients]

Citicoline​

One of the leading consumer brands in the cognitive health sector is Nawgan, a brain health product formulated by Rob Paul, PhD, and available in numerous retail outlets. The product’s main ingredient is Kyowa Hakko’s Cognizin-branded citicoline ingredient.

A recent study using Cognizin found that daily supplements may improve attention in adolescent males, and boost motor speed and decreased impulsivity (Journal of Attention Disorders​​, doi: 10.1177/1087054715593633)

Scientists from the University of Utah and Kyowa Hakko reported that 28 days of supplementation with either 250 mg or 500 mg Cognizin per day produced significant improvements in motor speed, attention and impulsivity, compared with the placebo.

Danielle Citrolo, registered pharmacist and manager of technical services for Kyowa Hakko USA, said that the study’s findings are consistent with prior research using the ingredient that were conducted with healthy adult women.

“To see strong results, with minimal side effects, in an adolescent population opens the door for additional, ground-breaking research on brain health,”​ said Citrolo.

Curcumin ​

Curcumin – the natural pigment that gives the spice turmeric its yellow color – has been gaining attention for its potential brain health benefits.

Curcuminoids, the naturally occurring compounds in the rhizomes of turmeric or Curcuma longa, have been intensely studied for their biological activities including antioxidant, liver protective, healing, anti-inflammatory activity and more. While inflammation has been established as a root cause of most of chronic diseases its role in neuro conditions like Alzheimer’s has only been recently understood.

Ingredients from suppliers such as Sabinsa and Verdure Sciences have been used in studies, with impressive results. In very early studies using Sabinsa’s Curcumin C3 Complex, for example, researchers were able to demonstrate in in-vivo​ models that low dosage of Curcumin effectively disaggregates the amyloid as well as prevents fibrils and oligomer formation (Yang F et al., 2005, J.Biol.Chem​​. Vol. 280, pp. 5892-5901).

Clinical data from Alzheimer disease patients have also indicated that Curcumin C3 Complex supplementation was well tolerated in geriatric subjects which was very encouraging for future longer trials on Alzheimer’s subjects. (Ringman et al. Alzheimer’s Res​. 2012, Vol 4. No. 5).

A 2014 study using Verdure’s Longvida ingredient found that curcumin may boost working memory and mood in healthy older adults (Journal of Psychopharmacology​​, Vol. 29 pp. 642-651). In addition, a study of the acute (single dose) effects of the supplement indicated that curcumin was associated with significantly improved measures of sustained attention, wrote researchers from Swinburne University of Technology in Melbourne.

L-theanine​

Unilever has been leading research into this compound in tea. L-theanine, an amino acid found in tea leaves, is thought to help reduce stress, promote relaxation and improve the quality of sleep.

A 2013 review by Suzanne Einother and Vanessa Martens from Unilever Research and Development, Vlaardingen in the Netherlands concluded that the evidence from randomized control trials supports a role for L-theanine and caffeine to benefit mood and performance.

Writing in the American Journal of Clinical Nutrition​​ Einother and Martens said that the performance benefits of tea are supported by a number of studies, “with particularly consistent evidence for improved attention”​.

 Furthermore, the beverage “consistently improved self-reported alertness and arousal”​.

“These studies showed the validity of laboratory findings by supporting the idea that tea consumption has acute benefits on both mood and performance in real-life situations.”​

However, the European Food Safety Authority (EFSA) has rejected both article 13.1 and 13.5 (submitted by Unilever) health claims petitions linking black tea consumption and improved mental focus.

There is also some data for other tea compounds, with results of a pilot study from Japan indicating that extracts from green tea may boost a range of cognitive functions, with particular benefits observed for short term memory (Nutrients​​, 2014, Volume 6, Number 10, Pages 4032-4042).

“These results support the findings of previous epidemiological studies, and additionally demonstrate that green tea improves cognitive function or reduces the progression of cognitive dysfunction even at the relatively low catechin and theanine concentrations that can be obtained from ordinary levels of daily green tea intake,”​ wrote scientists from the University of Shizuoka and Ito En Ltd.

“The green tea powder used as a daily dose in this study contained as its main bioactive components 227 mg of catechins and 42 mg of theanine, concentrations that are approximately equal to two to four cups of bottled or home-brewed green tea.”​

Resveratrol​

Resveratrol, a powerful polyphenol and anti-fungal chemical, is often touted as the bioactive compound in grapes and red wine, and has particularly been associated with the so-called 'French Paradox'.

While many research dollars have been spent exploring the potential cardiovascular benefits of the polyphenol, some evidence supports a potential role for the ingredient in brain health.

A 2010 paper published in the American Journal of Clinical Nutrition​​ (doi:10.3945/ajcn.2009.28641) from UK-based scientists reported that a single dose of 250 or 500 milligrams of resveratrol may boost blood flow in the brain but did not affect cognitive performance.

“The results of the current study provide the first indication in humans that resveratrol may be able to modulate cerebral blood flow variables,” ​wrote the researchers, led by David Kennedy from the Brain, Performance and Nutrition Research Centre at Northumbria University.

“Thus, it seems reasonable to suggest that the potential effects of this molecule on brain function deserve a great deal more research attention with a clear focus on both healthy humans and pathologic groups,” ​they added.

A study by scientists from the Max Planck Institute for Human Cognitive and Brain Sciences​ in Germany reported that 26 weeks of resveratrol supplements at a dose of 200 mg per day was associated with improved memory performance and glucose metabolism in older adults (J Neurosci​. 2014, Vol. 34, pp. 7862-70).

“Our findings offer the basis for novel strategies to maintain brain health during aging,” ​they concluded.

Blueberry anthocyanins​

Media coverage of the potential brain benefits of blueberries have been cited by some as leading a boom in blueberry sales in various markets. The beneficial effects of the blueberries are thought to be linked to their flavonoid content - in particular anthocyanins and flavanols. The exact way in which flavonoids affect the brain are unknown, but they have previously been shown to cross the blood brain barrier after dietary intake.

It is believed that they may exert their effects on learning and memory by enhancing existing neuronal connections, improving cellular communications and stimulating neuronal regeneration.

A 2010 study led by Robert Krikorian from the University of Cincinnati Academic Health Center​ found that a daily drink of about 500 mL of blueberry juice was associated with improved learning and word list recall, as well as a suggestion of reduced depressive symptoms in older people with early memory problems (Journal of Agricultural and Food Chemistry​, doi: 10.1021/jf9029332).

“These preliminary memory findings are encouraging and suggest that consistent supplementation with blueberries may offer an approach to forestall or mitigate neurodegeneration,”​ they wrote.

“Interpretation of our findings should be tempered because of the relatively small sample size and the absence of a blueberry-specific control, although comparison with the analogous placebo beverage data provides some assurance that the observed changes in memory performance were not attributable to practice effects,”​ they added.

Herbs and botanicals​

Numerous herbs and botanicals have been linked to cognitive function and brain health, from bacopa to ginkgo, and from Ashwagandha to ginseng.

Ginkgo biloba is one of the herbal industry’s big players, with data from the ABC Herb Market Report for 2011 (using SPINS data for the sale of single ingredient Ginkgo extracts) putting the US Ginkgo market at an estimated $18.4 million ($4.1 million in the natural health foods channel, and $14.3 million in the food drug and mass market channel). The global market is reported to be worth $1 billion.

A new systematic review and meta-analysis of randomized controlled trials by scientists at the Beijing University of Chinese Medicine concluded that, “Ginkgo biloba is potentially beneficial for the improvement of cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer’s disease. ​

“However, due to limited sample size, inconsistent findings and methodological quality of included trials, more research are warranted to confirm the effectiveness and safety of ginkgo biloba in treating mild cognitive impairment and Alzheimer’s disease.”​ (Current Topics in Medicinal Chemistry​, ​15​: 1-9).

Other herbs with potential in the cognitive health sector in clude Schisandra, Ashwagandha, Vinpocetine, Ginseng, Rhodiola, and Bacopa.

Please click here to read our recent article, Botanical ingredients step up to battle cognitive decline​​