Ginkgo biloba and Dementia

By Maria Cayelli, MD. Dr. Cayelli is Family Medicine Specialist, Anderson, SC; she reports no financial relationship relevant to this field of study.

The term "dementia" refers to central nervous system (CNS) pathology that makes it hard for a person to remember, learn, and communicate. It may also involve perception, emotional behavior, and cognitive skills. Usually, dementia presents as forgetfulness, but may eventually lead to disruptive behavior.

Dementia is classically described as a progressive syndrome characterized as a general persistent decline from a previously attained level in mental ability. Causes of dementia may include genetic predisposition, primary brain diseases such as Parkinson's disease, exogenous intoxication, infection, and metabolic conditions. The onset is primarily insidious.

Although there are pharmaceutical treatments approved for dementia, their efficacy is inconsistent. One of the most popular remedies touted for the prevention and treatment of dementia is over-the-counter Ginkgo biloba. It is marketed as an aid to improve memory and enhance cognitive skills. Since Ginkgo biloba is a top selling herbal for dementia, it is surprising that there is a lack of conclusive data supporting this indication.

Traditional Use and Pharmacology

Ginkgo has been used for centuries in traditional Chinese medicine and is currently supported by the German Commission E for use with dementia syndromes, such as Alzheimer's, vascular, and mixed dementia. In China, the nuts are consumed but not the fruits. Because of the rancid butter odor of the Ginkgo fruits, it was mainly cultivated for landscaping. It is from these fruits or nuts that the extract (EGb 761) is derived.

Ginkgo biloba is typically available as a plant extract containing several compounds that may have positive effects on cells within the brain and the body. These potent substances include flavonoids and terpenoids (ginkgolides) that suppress platelet-activating factor and reduce oxidative stress in the brain. Ginkgo biloba is thought to have both antioxidant and anti-inflammatory properties that may protect cell membranes and help regulate neurotransmitter function.

Ginkgo and Quality of Life in the Elderly

Cieza et al conducted a randomized, double-blind, placebo-controlled, 4-week trial in 66 healthy volunteers ages 50-65 years using a standardized extract of ginkgo.1 At trial's end, the volunteers self-judged themselves by way of mental and general health and quality of life, and found positive effects with treatment.

Clinical Effect of Ginkgo in Adults in Dementia

Elsbagh et al randomized postmenopausal women to receive either a standardized extract of ginkgo or placebo for 6 weeks. The findings were that ginkgo only showed benefit on mental flexibility, and then only in people who were previously poor performers in this regard.2 In 2000, LeBars et al retrospectively studied a group with mild-to-severe dementia for 52 weeks, and found slight improvements in cognition, activities of daily living, and social behavior.3,4 In 2002, LeBars did a similar study in which ginkgo had positive effects on cognition and social functioning in the mildly cognitively impaired group. While there was not an improvement in the severely affected group treated with EG 761, a greater deterioration was seen in the placebo group.5

Clinical Effect of Ginkgo in Healthy Adults

Ginkgo's effect of cognition in healthy older adults is slight and may depend on baseline performance. Hartley and colleagues did a 7-day treatment study with menopausal women and found no effects on menopausal symptoms, sleepiness, bodily symptoms, or aggression with 120 mg/day of ginkgo.6 However, it did help in attention, memory, and mental flexibility. Mix and colleagues found that ginkgo improved delayed-free recall and recognition tasks, as well as improved speed of processing abilities and speed of response.7,8 Healthy adult participants felt their memory was improved with treatment. On the other hand, Solomon and colleagues did not find ginkgo to be beneficial to memory function in healthy adults.9 Carlson and colleagues studied 90 cognitively intact men and women ages 65-85-years-old for 4 months taking 180 mg/day of Ginkgo biloba, and found no improvement in cognitive function or quality of life. Nathan and colleagues also studied ginkgo in healthy older subjects, and found no effects at the 120 mg dose.10 Burns and colleagues used a longer duration of treatment, and found intermediate term storage and retrieval was improved.11 Again, the improvements were most notable in older (55-79-years-old) adults and not the younger (18-43-years-old).

Proposed Mechanism of Action

There has been great speculation on the mechanisms by which Ginkgo biloba might improve or even prevent dementia states. It is believed that the herb improves microcirculation, suppresses platelet-activating factor, improves hypoxic tolerance, and eliminates harmful free radicals. In addition, it may have neuroprotective effects and is an antioxidant. Synergistic actions of several of these factors may help enhance memory.

Dosage

For dementia, the typical dose is 120-240 mg/day, in divided doses, using a standardized extract of Ginkgo biloba, standardized to 22%-27% flavone glycosides (quercetin, kaempferol, isorhamnetin) and 5%-7% terpene lactones (2%-3% ginkgolides A, B, and C; 2%-3% bilobalide).

Adverse Effects

The standard leaf extract appears to be quite safe, although adverse reactions include mild gastrointestinal symptoms, headache, dizziness, palpitations, constipation, and skin reactions. There have been case reports of bleeding with Ginkgo biloba in light of reported effects on platelets, but it is not clear if the patients were at higher risk for bleeding complications due to clinical status or if ginkgo contributed to the adverse events.

Conclusion and Recommendation

Despite the lack of conclusive, definitive studies supporting the use of Ginkgo biloba to prevent or treat memory loss, it continues to be one of the top selling herbal products. It appears to be safe to use with rare adverse effects, although concerns about bleeding persist. Thus use of Ginkgo in patients at risk of bleeding, especially those on warfarin and aspirin, needs to be avoided or very carefully monitored. Dosing of ginkgo should start at 120 mg/day of ginkgo leaf extract in divided doses. The exact dosing depends on the specific formulation used. Ginkgo biloba works best long term in older adults with dementia. Ginkgo does seem to help the younger population with respect to both attention and memory, There is presently an ongoing, large clinical trial of Ginkgo biloba to determine if the herb prevents the onset of dementia, slows cognitive decline and functional disability, reduces the incidence of cardiovascular disease, and decreases the rate of premature death.12

References

1. Cieza A, et al. Effects of Ginkgo biloba on mental function in healthy volunteers. Arch Med Res. 2003;34:373-381.

2. Elsabagh S, et al. Limited cognitive benefits in Stage +2 postmenopausal women after 6 weeks of treatment with Ginkgo biloba. J Psychopharmacol. 2005;19:173-181.

3. LeBars PL, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. JAMA. 1997;278:1327-1332.

4. LeBars PL, et al. A 26-week analysis of a double-blind, placebo-controlled trial of the Ginkgo biloba extract EGb 761 in dementia. Dement Geriatr Cogn Disord. 2000;11:230-237.

5. Le Bars PL, et al. Influence of the severity of cognitive impairment on the effect of the Ginkgo biloba extract EGb 761 in Alzheimer's disease. Neuropsychobiology. 2002;45:19-26.

6. Hartley DE, et al. Effects on cognition and mood in postmenopausal women of 1-week treatment with Ginkgo biloba. Pharmacol Biochem Behav. 2003;75:711-720.

7. Mix JA, Crews WD Jr. An examination of the efficacy of Ginkgo biloba extract EGb761 on the neuropsychologic functioning of cognitively intact older adults. J Altern Complement Med. 2000;6:219-229.

8. Mix JA, Crews WD Jr. A double blind, placebo-controlled, randomized trial of Ginkgo biloba extract EGb761 in a sample of cognitively intact older adults: Neuropsychological findings. Hum Psychopharmacol. 2002;17:267-277.

9. Solomon PR, et al. Ginkgo for memory enhancement: A randomized controlled trial. JAMA. 2002;288:835-840.

10. Nathan PJ, et al. The acute nootropic effects of Ginkgo biloba in healthy older human subjects: A preliminary investigation. Hum Psychopharmacol. 2002;17:45-49.

11. Burns NR, et al. Ginkgo biloba: No robust effect on cognitive abilities or mood in healthy young or older adults. Hum Psychopharmacol. 2006;21:27-37.

12. DeKosky ST, et al. The Ginkgo Evaluation of Memory (GEM) study: Design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia. Contemp Clin Trials. 2006;27:238-253.