February 2016 Issue

Brain Health: Brain-Boosting Supplements — How Effective Are They?
By Densie Webb, PhD, RD
Today's Dietitian
Vol. 18 No. 2 P. 14

It's something everyone fears—the loss of cognitive function that can occur with age. Neurodegenerative disorders and diseases (NDDs) such as dementia and Alzheimer's disease are rapidly growing causes of disability and death among the older population.1 While there's no cure, there have been major advances in the understanding of NDDs and the mechanisms behind them. Armed with this knowledge, researchers have found that some natural compounds and supplements have potential therapeutic effects for NDDs and other brain disorders.

These polyphenol compounds are the chief components in turmeric, the bright yellow spice that stains your fingers and is a common ingredient in Indian foods. Studies in the lab and in mice suggest curcuminoids may work by breaking up the amyloid proteins in the brain that are the hallmark of Alzheimer's.2 A study of healthy older adults found that 400 mg of curcumin per day (approximately four teaspoons of turmeric)3 improved both immediate and longer term (four weeks) attention, memory, mood, and alertness.4 However, another study using a different supplemental form of curcumin found no beneficial effects among people with mild to moderate Alzheimer's disease.5 The researchers suggest this might have been due to limited bioavailability of the particular compound. Andrew Scholey, PhD, codirector of the Centre for Human Psychopharmacology at Swinburne University in Melbourne, Australia, who was involved in the four-week study, says, "At the moment, we don't have enough evidence. A couple of published trials found no effect, but they used low doses and not a particularly bioavailable form. Better trials are being conducted at the moment, so we will wait for their outcome."

Bottom line: It's too soon for dietitians to recommend curcumin supplements for NDDs, and it's impossible to consume the same amount of curcumin from foods as is found in supplements.

L-theanine is an amino acid found in tea leaves and is a major component of tea. It's promoted to help reduce stress, promote relaxation, and act as a sleep aid. Considerable research has been done on this compound, but most of it has been conducted in animals. In human studies, doses about 10 to 20 times what's found in a cup of tea (4.5 to 22.5 mg) have been used and some have suggested benefits.6 Several studies have been done in which test subjects were diagnosed with ADHD,7 schizophrenia, or schizoaffective disorder and were given 400 mg/day, which was found to alleviate anxiety and improve general functioning.

Bottom line: While researchers are hopeful that L-theanine will prove effective in alleviating stress and anxiety in people with various brain disorders, most say that further study is needed.

Resveratrol is a major polyphenol compound found in a variety of berries, peanuts, wine, and medicinal plants, but in the diet most of it comes from grapes and red wine.1 In the lab, resveratrol has been shown to protect neurons against β-amyloid induced toxicity and cell death.1 It has been shown to be safe at a wide range of doses (from 25 mg to 5 g per day).1 One study reported that 250 to 500 mg/day increased blood flow to the brain.8 Because blood flow to the brain is negatively affected in several neurological disorders, including Alzheimer's disease, researchers have suggested that this may be clinically beneficial. However, the amounts normally found in the diet are unlikely to have beneficial effects.9 One cup of red grapes contains an average of 0.24 to 1.25 mg of resveratrol; one liter of red wine contains an average of 1.9 mg.

Bottom line: Evidence suggests that much larger doses than what's found in the diet are both safe and effective, and several clinical trials are investigating its efficacy in treating age-related neurodegenerative diseases. Pharmaceutical analogs of resveratrol are under development.

Blueberry Anthocyanins
Blueberries are especially rich in anthocyanins, natural plant compounds that give all berries their deep, lush colors, which have been shown to have anti-inflammatory effects. Evidence has accumulated to suggest that consumption of blueberries may forestall or even reverse age-related neuronal deficits and foster healthful aging.10 A small study in which nine older adults with early memory impairment were given 15 to 22 oz of wild blueberry juice per day for 12 weeks found that they experienced cognitive benefits as assessed by memory tests.11 The anthocyanins in blueberries are thought to reduce inflammation in the brain, activate synaptic signaling, and improve blood flow to the brain. As part of the long-term Nurses' Health Study, Harvard researchers found an association between a high intake of flavonoids, particularly from berries, and reduced rates of cognitive decline in older adults.12 According to Robert Krikorian, PhD, from the department of psychiatry and behavioral neuroscience at the University of Cincinnati Academic Health Center, who conducted the original blueberry juice study and has since conducted similar studies with whole, freeze-dried blueberries and blueberry powder, "I think supplementation with blueberries for anthocyanins may include a 1/4 to 1/2 cup two to four times a week. Recent data on the circulation of anthocyanin metabolites indicates that they persist for several days and are widely distributed in the body."

Bottom line: There are a wealth of cellular studies and studies in animals on the neurological benefits of consuming blueberry polyphenols, as well as population studies showing an association between consumption and brain health. However, there's little clinical research, especially long-term studies in humans. Further studies are needed to confirm the cognitive benefits of blueberries, blueberry juice, or blueberry anthocyanin supplements.

Ginkgo Biloba
A specific extract of the Ginkgo plant, EGb 761, has been studied extensively for its neurological benefits for conditions such as dementia, Alzheimer's disease, and ischemic stroke. Although it hasn't gotten FDA approval in the United States, it's available by prescription in European countries.13 It has been shown to be safe and is unlikely to interfere with prescription medications. Its effectiveness is attributed to the combination of the individual components (ginkgolides, bilobalides, and flavonoids) it contains. It appears to improve memory and cognitive function at doses of 240 mg/day.14 In Europe, it's also used in combination with conventional drugs to treat symptoms of cognitive decline, such as forgetfulness.15

Bottom line: Of the supplements reviewed here, Gingko biloba appears to be the most promising in terms of alleviating the symptoms of dementia, which involve significant impairment of cognitive abilities, such as reasoning, judgment, memory, and focus, and sometimes can progress to Alzheimer's disease. There's little evidence, however, that it will improve mental acuity in young, healthy individuals.

Rhodiola Rosea
Also known as golden root or roseroot, Rhodiola root has a long tradition as a medicinal plant in Iceland, Sweden, France, Greece, and Russia.16 It's used to improve mental performance, memory, and concentration. One placebo-controlled, double-blind, cross-over study supplied a standardized Rhodiola SHR-5 extract (170 mg) to young, healthy physicians on night duty and found a significant improvement in cognitive functioning, including short-term memory and ability to calculate and concentrate.17 It has been suggested that Rhodiola increases serotonin levels in the brain and reduces the activation of the stress response system.16 Studies reporting a positive effect on physical performance used doses of 200 mg to 680 mg/day. Those reporting a positive effect on mental fatigue reported doses of 100 to 576 mg/day.

Bottom line: While several studies have found Rhodiola to benefit both mental and physical performance, they have varied in quality and size. Most researchers agree that larger, well-controlled clinical trials are needed.

— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Texas.

1. Bigford GE, Del Rossi G. Supplemental substances derived from foods as adjunctive therapeutic agents for treatment of neurodegenerative diseases and disorders. Adv Nutr. 2014;5(4):394-403.

2. Yang F, Lim GP, Begum AN, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005;280(7):5892-5901.

3. Tayyem RF, Heath DD, Al-Delaimy WK, Rock CL. Curcumin content of turmeric and curry powders. Nutr Cancer. 2006;55(2):126-131.

4. Cox KH, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol. 2015;29(5):642-651.

5. Ringman JM, Frautschy SA, Teng E, et al. Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther. 2012;4(5):43.

6. Einöther SJ, Martens VE. Acute effects of tea consumption on attention and mood. Am J Clin Nutr. 2013;98(6 Suppl):1700S-1708S.

7. Lyon MR, Kapoor MP, Juneja LR. The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Altern Med Rev. 2011;16(4):348-354.

8. Kennedy DO, Wightman EL, Reay JL, et al. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010;91(6):1590-1597.

9. Semba RD, Ferrucci L, Bartali B, et al. Resveratrol levels and all-cause mortality in older community-dwelling adults. JAMA Intern Med. 2014;174(7):1077-1084.

10. Shukitt-Hale B. Blueberries and neuronal aging. Gerontology. 2012;58(6):518-523.

11. Krikorian R, Shidler MD, Nash TA, et al. Blueberry supplementation improves memory in older adults. J Agric Food Chem. 2010;58(7):3996-4000.

12. Devore EE, Kang JH, Breteler MM, Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol. 2012;72(1):135-143.

13. Nash KM, Shah ZA. Current perspectives on the beneficial role of ginkgo biloba in neurological and cerebrovascular disorders. Integr Med Insights. 2015;10:1-9.

14. Gauthier S, Schlaefke S. Efficacy and tolerability of ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials. Clin Interv Aging. 2014;9:2065-2077.

15. Ihl R. Gingko biloba extract EGb 761®: clinical data in dementia. Int Psychogeriatr. 2012;(24 Suppl 1):S35-S40.

16. Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H. Rodiola rosea in stress induced fatigue — A double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000;7(5):365-371.

17. Brown RP, Gerbarg PL, Ramazanov Z. Rhodiola rosea: a phytomedicinal overview. HerbGram. 2002;56:40-52.