Brainy Botanicals

Several key herbs have been shown to benefit brain health in a number of ways.

Ginkgo biloba has long been used as a mental booster, but in the past four years, three major studies have been published that questioned its effectiveness. Most recently in September 2012, a randomized placebo-controlled trial from France said long-term use of standardized Ginkgo biloba extract did not reduce the risk of Alzheimer's disease progression compared with placebo.¹ The randomized, parallel-group, double blind, placebo-controlled GuidAge clinical trial, included 2,854 adults aged 70 years or older who reported memory complaints to their primary-care physician. After five years, 61 participants in the two 120-mg/d doses of EGb761 Ginkgo (from Schwabe) group had been diagnosed with probable Alzheimer's disease (1.2 cases per 100 person-years) compared with 73 participants in the placebo group (1.4 cases per 100 person-years). However, in a subgroup analysis, researchers found a group that took ginkgo regularly for four years (not accounting for dropouts) experienced significant positive results. The incidence of Alzheimer's was reduced by 47 percent compared to placebo.

The 2012 study was in line with other recent studies that question the herb's effectiveness in treating or preventing Alzheimer's disease. In 2009, a JAMA study found older adults who used Ginkgo biloba for several years did not see a reduction in cognitive decline compared to adults who received placebo.² And in 2008, another JAMA study concluded the use of Ginkgo biloba was not effective in reducing the rate of dementia or Alzheimers disease among more than 1,500 elderly study participants after several years of use.³

However, the supplement industry questioned the conclusions of all three studies. For the 2012 study, both the American Botanical Council (ABC) and the Council for Responsible Nutrition (CRN) said ginkgo is not a drug designed to prevent diseases, such as Alzheimer's. The 2006 JAMA study was limited in that the data was drawn from a previous clinical trial, and about 40 percent of the subjects dropped out, according to ABC. And the Natural Products Association (NPA) said the 2008 JAMA study looked exclusively at people almost 80 years old, who are far more likely to have Alzheimers, while ignoring those in middle ages, and it did not factor the genetic role of Alzheimers disease.

In contrast, in a 2006 study, EGb 761 suppressed amyloid-beta pathological behaviors.⁴ Amyloid-beta is a peptide that forms plaque in the brains of patients with Alzheimer's disease. In this study EGb 761 also protected against toxicity, preventing synaptic loss and neural degeneration seen in Alzheimers disease. And in 2008, researchers at Johns Hopkins showed daily doses of EGb 761 prevented or reduced brain damage after an induced stroke.⁵

Healthy university students taking French maritime pine bark (as Pycnogenol®, from Horphag Research) improved their mental performance in a September 2011 eight-week study.⁶ Fifty-three university students (aged 18 to 27) were given 100 mg/d of Pycnogenol, and an equivalent number of students were given a control protocol. Pycnogenol significantly improved sustained attention, memory, executive functions and mood ratings. Students taking Pycnogenol had higher test scores on university exams than the control group. The specific results showed control group students failed nine tests out a total of 84 (10.71 percent), while the students in the Pycnogenol group failed seven tests out of 112 (6.25 percent). The average test score was 23.81 in controls versus 26.1 in the Pycnogenol group. In addition to the performance results, researchers noted alertness and contentedness improved significantly within the Pycnogenol group, which also saw levels of anxiety decrease by 17 percent. Several mechanisms may have contributed to the improved cognitive results, according to researchers, including antioxidant activities and blood circulation improvement.

Fisetin, a flavonol found in strawberries, apples, grapes and onions, produced an increase in serotonin and demonstrated other anti-depressive effects in mouse models, according to a March 2012 study from China.⁷ In a 2006 study conducted at The Salk Institute for Biological Studies, La Jolla, CA, a rat model showed it may facilitate long-term memory, and therefore may be useful for treating patients with memory disorders.⁸ And an in vitro study reported fisetin, along with the flavonoids luteolin, quercetin and myricetin, inhibited beta amyloid protein formation.⁹

The principal alkaloid of the lesser periwinkle plant (Vinca minor L.), vinpocetine, exhibited cerebral blood-flow enhancing and neuroprotective effects, according to a 2011 review.¹⁰ Vinpocetine improved the cerebrovascular reserve capacity in patients with ischemic stroke and mild cognitive impairment in a Hungarian study from 2007.¹¹ Vinpocetine also favorably influenced the cognitive status and general condition of patients with chronic decreased blood flow to the brain. The study authors recommended vinpocetine for the treatment of patients with mild cognitive impairment.

Curcumin, the principal curcuminoid of the Indian spice turmeric, is a strong antioxidant known to fight inflammation, but other research has centered on its ability to fight mental decline. Curcumin can help reduce amyloid-beta levels. A study from 2001 reported a low (160 ppm) and a high dose (5,000 ppm) of dietary curcumin lowered oxidized proteins and interleukin-1beta, a proinflammatory cytokine elevated in the brains of mice who had Alzheimer's-like symptoms.¹² Interestingly, the low-dose, but not high-dose curcumin, reduced glial fibrillary acidic protein (GFAP), a marker of neurologic damage in adults who suffer strokes and traumatic brain injuries, and beta-amyloid.

Researchers led by Robert A. DiSilvestro from the Ohio State University, Columbus, found a low dose (80 mg/d) of a curcumin-lipid preparation (as Longvida Optimized Curcumin, from Verdure Sciences) reduced plasma contents of beta amyloid protein by 8 percent in healthy middle aged people (aged 40 to 60 years).¹³ The subjects were given either curcumin (n=19) or placebo (n=19) for four weeks. Curcumin supplementation also helped reduce other indicators of heart disease and inflammation.

In 2006, University of California, Berkley, researchers found curcumin (as Curcumin C3 Complex from Sabinsa) helped the immune system clear the brain of amyloid-beta.¹⁴ Using blood samples from six Alzheimer's disease patients and three healthy control patients, the researchers isolated cells called macrophages, which remove waste products such as amyloid beta. The team treated the macrophages with curcumin for 24 hours in a cell culture and then introduced amyloid beta. Treated macrophages from three out of six Alzheimer's disease patients showed improved uptake or ingestion of amyloid beta compared to the patients' macrophages not treated with curcumin.

A 2011 Indian study found curcumin also has mood benefits.¹⁵ Curcumin (as BCM-95®, distributed by Europharma) helped alleviate depression comparably to a couple of well-known antidepressant drugs in an animal study. Researchers compared BCM-95 to fluoxetine (active ingredient in Prozac®) and imipramine (active ingredient in Tofranil®) in an animal scientific model of depression. They found the effect of the 100 mg/kg of curcumin was similar to that of the two drugs. The researchers concluded curcumin's antidepressant-like activity could be due to an increase in brain levels of neurotransmitters including serotonin, norepinephrine and dopamine.

Bacopa monnieri , a perennial herb that grows well in marshy areas, significantly improved memory acquisition and retention in healthy older Australians in a 2010 study.¹⁶ The randomized, double blind, placebo-controlled trial included 81 healthy participants older than 55 years of age who received either an extract of Bacopa monnieri (as BacoMind from Natural Remedies Pvt. Ltd.), 300 mg/d, or an identical placebo. Bacopa significantly improved verbal learning, memory acquisition, and delayed recall as measured by the Rey Auditory Verbal Learning Test (AVLT).

Bacopa also improved higher order cognitive processes such as learning and memory in a 2001 study from different Australian researchers.¹⁷ The double blind, placebo-controlled study randomly allocated subjects to treatment with bacopa (300 mg) or placebo. Bacopa significantly improved speed of visual information processing measured by the IT task, learning rate and memory consolidation measured by the AVLT, and state anxiety compared to placebo, with maximal effects evident after 12 weeks.

Another study found bacopa helped adults, aged 40 to 65 years, decrease the rate of forgetting newly acquired information.¹⁸ Data from a 2007 mouse study suggested bacopa works by reducing brain beta-amyloid levels in an Alzheimer's disease model.¹⁹

Bacopa is also known as brahmi, but brahmi can also refer to gotu kola (Centella asiatica), an herb that has been used for centuries in Ayurvedic and traditional Chinese medicine to alleviate symptoms of depression and anxiety. In 2011, a review of both bacopa and gotu kola reported research indicates both plants possess neuroprotective properties and can help patients with memory loss.²⁰ The researchers noted "exciting patent activity" has recently focused on improving extraction methods, enriching and purifying novel compounds from the plants, and providing novel synergistic formulations. On its own, gotu kola at 12 g/d reduced anxiety in human subjects.²¹

Find more information on brain health in INSIDER's Cognitive Content Library.

References listed on the next page.

References:

1.       Vellas B et al. "Long-term use of standardised ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial." Lancet Neurol. 2012 Sep 5.

2.       Snitz BE et al. "Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial." JAMA. 2009 Dec 23;302(24):2663-70.

3.       DeKosky ST et al. " Ginkgo biloba for prevention of dementia: a randomized controlled trial." JAMA. 2008 Nov 19;300(19):2253-62.

4.       Wu Y et al. " Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans." J Neurosci. 2006 Dec 13;26(50):13102-13.

5.       Saleem S et al. " Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury." Stroke. 2008 Dec;39(12):3389-96.

6.       Luzzi R et al. "Pycnogenol® supplementation improves cognitive function, attention and mental performance in students." Panminerva Med. 2011 Sep;53(3 Suppl 1):75-82.

7.       Zhen L et al. " The antidepressant-like effect of fisetin involves the serotonergic and noradrenergic system." Behav Brain Res. 2012 Mar 17;228(2):359-66.

8.       Maher P, Akaishi T, Abe K. "Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory."' Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16568-73.

9.       Akaishi T et al. "Structural requirements for the flavonoid fisetin in inhibiting fibril formation of amyloid beta protein." Neurosci Lett. 2008 Oct 31;444(3):280-5.

10.   Patyar S et al. "Role of vinpocetine in cerebrovascular diseases." Pharmacol Rep. 2011;63(3):618-28.

11.   Valikovics A. "[Investigation of the effect of vinpocetine on cerebral blood flow and cognitive functions].  [Article in Hungarian]" Ideggyogy Sz. 2007 Jul 30;60(7-8):301-10.

12.   Lim GP et al. "The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse." J Neurosci. 2001 Nov 1;21(21):8370-7.

13.   DiSilvestro, R et al "Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people." Nut J 2012 Sept 26;11:79 DOI:10.1186/1475-2891-11-79

14.   Zhang L et al. " Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients." J Alzheimers Dis. 2006 Sep;10(1):1-7.

15.   Sanmukhani J, Anovadiya A, Tripathi CB. "Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study." Acta Pol Pharm. 2011 Sep-Oct;68(5):769-75.

16.   Morgan A, Stevens J. "Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial." J Altern Complement Med. 2010 Jul;16(7):753-9.

17.   Stough C et al.  "The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects." Psychopharmacology (Berl). 2001 Aug;156(4):481-4.

18.   Roodenrys S et al. " Chronic effects of Brahmi (Bacopa monnieri) on human memory." Neuropsychopharmacology. 2002 Aug;27(2):279-81.

19.   Dhanasekaran M et al. " Neuroprotective mechanisms of ayurvedic antidementia botanical Bacopa monniera." Phytother Res. 2007 Oct;21(10):965-9.

20.   Shinomol GK, Muralidhara, Bharath MM. "Exploring the role of "Brahmi" (Bocopa monnieri and Centella asiatica) in brain function and therapy." Recent Pat Endocr Metab Immune Drug Discov. 2011 Jan;5(1):33-49.

21.   Bradwejn J et al. " A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects." J Clin Psychopharmacol. 2000 Dec;20(6):680-4.