Study: Green tea and L-theanine for mild cognitive impairment

reference

Park SK, Jung IC, Lee WK, et al. A combination of green tea extract and L-theanine improves memory and attention in individuals with mild cognitive impairment: a double-blind, placebo-controlled study.J Med Food.2011;14(4):334-343.

design

Randomized, placebo-controlled prospective study. Neuropsychological testing was performed at baseline and 8 and 16 weeks post-treatment.

These tests included the Rey Kim Memory Test and the Stroop Color Word Reading Test. Twenty-four subjects were randomly selected for EEG measurements.

Participant

91 participants (25 men) took part in this study. The age was between 40 and 75 years. 46 received treatment and 45 received placebo. All complained of poor memory, scored between 21 and 26 on the Mini Mental Scale Examination-K (MMSE-K), and were between the second and third levels of the Global Deterioration Scale (GDS).^1.2The MMSE-K is a Korean version of the MMSE and is used to quickly measure various cognitive functions with scores between 0 and 30, with a score of 30 being normal. The GDS is a test used to assess the clinical symptoms and severity of Alzheimer's disease. GDS scores range from “no cognitive decline” (GDS 1) to “very severe” (GDS 4–7). Study participants ranged from GDS 2 (normal with subjective memory impairment) to GDS 3 (mild dementia). Foods and drinks containing caffeine were restricted during the study period.

Study medications and dosage

Subjects were randomly assigned to either a treatment group or a placebo group. All took two 430 mg capsules twice daily, 30 minutes before meals, for 16 weeks. The treatment capsules consisted of 360 mg of green tea extract and 60 mg of L-theanine, which corresponds to a daily dose of 1,440 mg of green tea extract and 240 mg of L-theanine. The strength of the green tea extract is not specified in the study.

Target parameters

EEG was used to evaluate the short-term response to a daily dose of the drug taken at once. The Rey-Kim memory test was used to assess changes in verbal and visuospatial memory, and the Stroop color word reading test was used to assess attention.

Key findings

In the domain of verbal and visuospatial memory, subjects with an initial MMSE-K score of 21 to 23 showed a significant increase in memory quotient (MQ) after 16 weeks (P=0.0478). The treatment also improved immediate memory (P≤0.01) at 16 weeks compared to baseline. No improvement was seen in patients receiving placebo. The overall differences between the treatment and placebo groups did not reach significant levels. When measuring attention using the Stroop Color Word Reading Test, the subgroup of participants with an MMSE-K score of 21-23 again showed a significant increase over placebo after 8 weeks (P=0.0306) and 16 weeks (P=0.133). There was no significant effect in the placebo group. Theta brain wave activity began to increase an hour after taking the drug and continued for up to three hours with the eyes open. EEGs measured during reading showed increased theta waves after 2 and 3 hours. The combination of green tea and L-theanine tested in this study significantly improved cognitive function by increasing memory and attention in subjects with mild cognitive impairment whose MMSE-K score was between 21 and 23.

Effects on practice

There is no reason to question the need for additional non-toxic and inexpensive therapies that slow the development of Alzheimer's disease. We'll leave it to other reviews to summarize the high financial and emotional costs of this disease.

Green tea, and particularly L-theanine, should be added to a growing list of possible therapies to treat early Alzheimer's disease. Although the improvements measured in this study were modest, these data, when taken in conjunction with other studies, provide a compelling argument that L-theanine, along with green tea polyphenols and caffeine, provides clinical benefit.

Kakuda reported in 2002 that green tea had several neuroprotective effects. It protected neurons from the toxic effects caused by exposure to glutamic acid. Preadministration of L-theanine-protected hippocampal CA1 pyramidal neurons against transient forebrain ischemia in gerbils. L-theanine also protected neurons in the CA3 region of the hippocampus from injury caused by kainate exposure. L-Theanine also protected low-density lipoproteins (LDL) from oxidative changes that lead to atherosclerosis.³Egashira confirmed protection against ischemic damage in 2008.⁴

A paper by Nathan et al. from 2006 partially explains this protective effect: “L-theanine increases serotonin, dopamine and GABA levels in the brain and has micromolar affinities for AMPA, kainate and NMDA receptors.” Additionally, it may have been shown to exert neuroprotective effects in animal models. … Overall, L-theanine exhibits a neuropharmacology that suggests a possible neuroprotective and cognition-enhancing agent and requires further investigation in animals and humans.”⁵

The combination of caffeine with green tea epicatechin, epigallocatechin and epigallocatechin gallate induces enzyme activity.

Another possible explanation for green tea's benefit in Alzheimer's disease is its effect on the activity of enzymes called neutral endopeptidases. These enzymes break down amyloid beta peptide plaques in the brain. The combination of caffeine with green tea epicatechin, epigallocatechin and epigallocatechin gallate induces enzyme activity.⁶

Of particular interest is a 2009 study on mice. Pretreating the mice for five weeks with L-theanine in their drinking water protected them from brain damage when they were subsequently injected with beta-amyloid protein.⁷

Of equal interest is a paper published in April 2011. In it, Kakuda describes "a study of elderly subjects with normal or mild cognitive dysfunction, volunteers who consumed powdered green tea with a high concentration of theanine (equivalent to 47.5 mg/day (-1) of theanine)." They “showed significantly less decline in cognitive function compared to the placebo group.”⁸

There is another aspect to this research. Patients suffering from Alzheimer's disease, as well as their family members who act as caregivers, may suffer from anxiety.⁹Spouses who act as caregivers for people with Alzheimer's disease have an increased risk of developing the disease themselves - about six times the expected risk.¹⁰L-Theanine can be used to reduce anxiety.^11,12,13We might consider giving green tea and L-theanine not only to our Alzheimer's patients, but also to the family members who care for them.

Green tea and L-theanine should be included in the list of foods and nutrients we consider in the treatment of early Alzheimer's disease.