Systematic Review of Ginkgo Finds Potential Treatment for Dementia

Dementia encompasses a wide range of symptoms associated with a decline in memory and loss of the ability to perform everyday activities in elderly populations. Alzheimer’s disease (AD) and vascular dementia (VD) make up the vast majority of dementia cases. Ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extract (GbE) has become one of the most widely used herbal remedies for dementia. Thus, many clinical trials have already examined the effects of GbE on dementia, and many systematic reviews (SRs) have analyzed these trials. This study sought to provide a comprehensive assessment of the effectiveness of GbE in the treatment of dementia based on the evidence provided in the SRs.

All SRs which evaluated the efficacy and effectiveness of GbE as treatment (not prevention) of patients with diagnosed dementia, AD and/or VD, or mild cognitive impairment (MCI) were included. SRs were eligible only if they included the use of statistical methods (i.e., meta-analysis) to analyze randomized controlled trial (RCT) data. SRs were included whether GbE was administered alone or in combination with drugs. There were no limitations on dosage, and GbE could be administered orally or intravenously. PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects (DARE), and Google Scholar were searched from inception to June 2016.

In total, 59 RCTs were reviewed, with patients ranging from those with any form of dementia, dementia with behavioral and psychological symptoms, cognitive impairment, or AD. Twelve SRs met the inclusion criteria; all included only RCTs (of which most were placebo-controlled trials). The included SRs were published between 2009 and 2016, and they were performed in China, Germany, Japan, and the United Kingdom. The standardized extract EGb 761® (Dr Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany) was used in many RCTs, with six SRs including only RCTs that used EGb 761. Intervention duration varied from two to 52 weeks, and dosing varied from 60 mg/day to 600 mg/day.

Outcomes of interest varied but included one or more of the following: cognitive performance, activities of daily living (ADLs), clinical global impression, quality of life (QOL), and safety. With the exception of three SRs1-3 all remaining SRs showed the statistically significant effectiveness of GbE on cognitive performance in people with dementia. Eight SRs evaluated the effect of GbE on ADLs, and, apart from one SR,3 seven SRs showed a statistically significant effect of GbE on ADLs in people with dementia. Five SRs evaluated the effect of GbE on clinical global impression of dementia, of which three showed a statistically significant effect of GbE. Of the five SRs that evaluated QOL, two concluded there was no significant difference in QOL, two did not pool the QOL data, and only one SR pooling data from two RCTs suggested a beneficial effect of GbE on QOL. Eight SRs evaluated the safety of GbE, and none found any significant difference in adverse events or side effects compared to placebo.

Seven SRs included RCTs in which GbE was administered for at least 22 weeks, and the data reported in these SRs consistently favored the beneficial effects of GbE. The five SRs in which GbE was administered for less than 22 weeks reported data that were “quite inconsistent.” This study found no particular evidence suggesting a beneficial effect of GbE on cognitive performance, ADLs, or clinical global impression when GbE was administered for less than 22 weeks. In addition, few SRs showed a beneficial effect of GbE at a dose less than 200 mg/day. In fact, four SRs consistently showed a beneficial effect of GbE on cognitive performance at a dose greater than 200 mg/day (usually 240 mg/day). Few SRs indicated a beneficial effect of GbE on ADLs and clinical global impression at a dose less than 200 mg/day.

The quality of SRs was evaluated using the AMSTAR (Assessment of Multiple Systematic Reviews) tool, and overall, the majority of reviews were found to be of good or acceptable quality. However, many of the reviewed RCTs in these SRs were of poor quality and had a high risk of bias, meaning the overall quality of evidence reviewed was low to moderate. That being said, based on the evidence gathered that met inclusion criteria, this overview found GbE to have beneficial effects over placebo on cognitive performance, ADLs, and clinical global impression when administered at a dose greater than 200 mg/day for 22 weeks or more. Globally, over 46 million people were living with dementia in 2015, and this number is expected to reach 131.5 million by 2050.4 With no cure or prevention yet found, future research is warranted. In order to better assess GbE efficacy as a treatment for dementia, future studies should take the beneficial dosing and intervention length found by this overview into account.


1Yang Z, Li W, Huang T, Chen J, Zhang X. Meta-analysis of Ginkgo biloba extract for the treatment of Alzheimer’s disease. Neural Regen Res. 2011;6(15):1125-1129.

2Wang BS, Wang H, Song YY, et al. Effectiveness of standardized Ginkgo biloba extract on cognitive symptoms of dementia with a six-month treatment: a bivariate random effects meta-analysis. Pharmacopsychiatry. 2010;43(3):86-91. doi: 10.1055/s-0029-1242817.

3Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. January 21, 2009;(1):CD003120. doi: 10.1002/14651858.CD003120.pub3.

4Dementia statistics. Alzheimer’s Disease International website. Available at: Accessed September 11, 2017.

Yuan Q, Wang CW, Shi J, Lin ZX. Effects of Ginkgo biloba on dementia: An overview of systematic reviews. J Ethnopharmacol. January 2017;195:1-9.


Review of Black Cumin for Metabolic Disorders

Black cumin (Nigella sativa, Ranunculaceae) seed is popular in the Middle East and Southeast Asia for treating diabetes, dyslipidemia, hypertension, and obesity. However, clinical evidence is inconclusive. The purpose of this systematic review was to evaluate the clinical and biochemical effects of black cumin on lipid profiles, glycemic factors, blood pressure, and anthropometric indices (weight, body mass index [BMI], and waist circumference), all of which are parameters of metabolic syndrome.

The following databases were searched from inception through June 2014: PubMed, Google Scholar, Thomson Reuters Web of Science, and Cochrane. The following medical subject headings (MeSH) and title/abstract (tiab) search terms were used: (“Nigella sativa” [MeSH] OR “black seed” [tiab] OR “black cumin” [tiab] OR “Kalonji” [tiab]) AND “Triglycerides” [MeSH] OR “Cholesterol” [MeSH] OR “Lipoproteins, LDL” [MeSH] OR “Lipoproteins, HDL” [MeSH] OR “Blood glucose” [MeSH] OR “Hemoglobin A, Glycosylated” [MeSH] OR “Blood pressure” [MeSH] OR “Body mass index” [MeSH] OR “Waist circumference” [MeSH]). The inclusion criteria were (1) published in English, (2) the effect of black cumin on clinical or biochemical parameters, and (3) clinical trial. The exclusion criteria were (1) animal studies, (2) review studies, (3) the effect of black cumin on unrelated blood or clinical parameters, (4) the effect of black cumin combined with other plants or exercise, and (5) duplicated studies.

A total of 515 articles were located, and 18 studies (with a total of 1531 subjects) met the inclusion/exclusion criteria. The studies were highly heterogeneous: five studies were randomized, double-blind, controlled studies; five studies had no control group, and eight studies were randomized controlled studies. Included patients were aged 18-65 years and had diabetes (n = 5 studies), metabolic syndrome (n = 7 studies), hyperlipidemia (n = 4 studies), hypertension/coronary disease (n = 2 studies), obesity (n = 1 study), or were healthy subjects (n = 4 studies). All treatments were oral and doses ranged from 200 mg/day to 5 g/day of seed extract (n = 2 studies), seed oil (n = 8 studies), or seed powder (n = 13 studies). Treatment duration ranged from two weeks to six months.

Table 1 summarizes the study findings. The authors note significant findings; however, they do not report whether the changes are compared with baseline or control. In Table 1, the column titled “overall effect” indicates which parameters had more evidence in favor of a significant improvement.

Table 1: Summary of Number of Studies with Significant Improvements in Measured Parameters

Number of Studies
Parameters Significant improvement No significant effect Overall effect (Yes/No)
Triglycerides 7 10 No
Total cholesterol 10 4 Yes
Low-density lipoprotein (LDL) cholesterol 11 3 Yes
High-density lipoprotein (HDL) cholesterol 6 10 No
Fasting blood sugar 13 3 Yes
Glycosylated hemoglobin 4 Yes
Blood pressure 4 5 No
Weight 2 6 No
BMI 2 6 No
Waist circumference 1 5 No

Based on the number of studies demonstrating a significant improvement, the evidence weighs more in favor of black cumin improving total cholesterol, LDL, fasting blood sugar, and glycosylated hemoglobin. Evidence does not support an effect of black cumin on blood pressure or anthropometric indices. A total of 10 studies evaluated safety. Two studies that treated subjects with 5 mL/day black cumin seed oil reported mild nausea that resolved after one week of treatment. Eight studies measured liver and kidney function and reported no adverse effects.

The authors conclude that black cumin should be “a complementary treatment protocol for many diseases, especially metabolic disorders.” However, even though the evidence leans more favorably in the direction of a benefit for some parameters, the heterogeneity of the studies must be taken into consideration. It would have been advantageous if the researchers conducted a meta-analysis to provide more scientific rigor to their analysis and conclusions. Recommendations for the effective dose or preparation cannot be gleaned from this analysis. More research is needed if black cumin is to be recommended as a treatment for patients with symptoms of metabolic syndrome.


Mohtashami A, Entezari MH. Effects of Nigella sativa supplementation on blood parameters and anthropometric indices in adults: A systematic review of clinical trials. J Res Med Sci. 2016;21:3. doi: 10.4103/1735-1995.175154.


Review on the Effectiveness of Aloe Vera for Oral Diseases

The succulent leaves of the aloe vera (Aloe vera, Xanthorrhoeaceae) plant have been used medicinally for hundreds of years. The clear gel, or mucilage, found inside the leaves, is well known for having wound-healing, anti-inflammatory, antioxidant, antitumor, and analgesic properties. These attributes could potentially help in treating oral ailments. The aim of this systematic review was to accumulate and assess clinical trials evaluating the effectiveness of aloe vera preparations in treating various oral diseases.

Studies on aloe vera were eligible if they were randomized, controlled, single- or double-blind, cross-sectional, or case-controlled trials published as full papers in English. PubMed (Medline), Scopus, Cochrane Database, Embase, and ScienceDirect were searched from July 1998 to December 2015. Search terms included “herbs,” “Ayurveda,” and “oral mucosa.” The Jadad scale (a scale ranging from 0 to 5, where the higher number indicates higher trial quality) was used to assess quality.

In total, 15 articles met the inclusion criteria. Only six trials achieved a Jadad score of 4/5; the rest scored between 0 and 3. Most studies were carried out in hospital clinics in countries such as Iran, Spain, India, the United States, and Saudi Arabia. Study populations ranged from 20 to 110 patients with clinically diagnosed oral mucosal lesions. Five of the 15 studies focused on patients with oral lichen planus (OLP). Two studies examined efficacy on oral submucous fibrosis (OSMF) in patients. The remaining studies investigated the effects of aloe vera on burning mouth syndrome, radiation-induced mucositis, Candida-associated denture stomatitis, xerostomia, and minor recurrent aphthous/stomatitis. All studies demonstrated a low risk of bias using the Cochrane Risk of Bias Tool. Blinding bias was low among all studies except one on Candida-associated denture stomatitis. Randomization sequence bias was high in seven studies.

Most studies showed statistically significant results for efficacy of aloe vera in treatment of oral lesions. There were no withdrawals due to adverse effects of aloe vera in any of the clinical trials. This review found aloe vera was most beneficial in patients with OLP. All five studies in patients with OLP demonstrated a low risk of bias and proved aloe vera effectively reduced lesion-associated pain and burning sensation, leading to partial or complete remission of symptoms. Studies conducted in patients with OSMF showed aloe vera to be effective in all stages of OSMF, particularly mild-stage OSMF clinically and early-stage OSMF histopathologically. Pain and burning sensations were significantly reduced in OSMF studies, and other outcome measures (mouth opening, cheek flexibility, tongue protrusion) were promising. The overall quality of OSMF studies was good with low risk of bias. Four trials in patients with aphthous stomatitis were reviewed, consisting of 319 patients. The overall quality of these studies was good. Lesion healing improved and there was significant remission of pain, erythema, and lesion size. Aloe vera was found to be less beneficial in patients with radiation-induced mucositis, as it was not effective in improving tolerance to head and neck radiotherapy, decreasing mucositis, or decreasing soreness; however, quality-of-life measures were improved in the patients receiving aloe vera. In the single Candida study reviewed, aloe vera had an anticandidal oral effect surpassed by that of Triphala, an Ayurvedic combination remedy.

Lack of randomization, lack of double-blinding, and a lack of description for withdrawals, dropouts, and methods to generate the sequence of randomization were all prevalent limitations that excluded trials from this review. The studies included demonstrated aloe vera has a wide spectrum of properties and uses and is a promising agent in treating oral lesions. However, based on this review, aloe vera may be better suited to OLP, OSMF, and aphthous stomatitis lesions versus those induced by radiation or Candida. For aloe vera to be more seriously considered for clinical treatment of oral lesions, future clinical trials should strive to meet more rigorous standards.


Nair GR, Naidu GS, Jain S, Nagi R, Makkad RS, Jha A. Clinical effectiveness of aloe vera in the management of oral mucosal diseases – A systematic review. J Clin Diagn Res. August 1, 2016;10(8): ZE01-ZE07. doi: 10.7860/JCDR/2016/18142.8222.