Reviewed: George A, Suzuki N, Abas AB, et al. Immunomodulation in middle-aged humans via the ingestion of Physta® standardized root water extract of Eurycoma longifolia Jack — a randomized, double-blind, placebo-controlled, parallel study [published online January 27, 2016]. Phytother Res. doi: 10.1002/ptr.5571.
Editor’s note: Two authors (A. George and A.B. Abas) are employed by Biotropics Malaysia Berhad, a sponsor of the study.
Tongkat ali (Eurycoma longifolia, Simaroubaceae) is a plant native to Southeast Asia. The roots have been used historically as a tonic, energy enhancer, and aphrodisiac. In Malaysia, it is sometimes inappropriately called “Malaysian ginseng” due to its tonic properties known in local folk medicine, but it is not related to “true ginseng” (i.e., Asian ginseng [Panax ginseng, Araliaceae]). In vitro studies indicate that the root extract has cancer suppression and antioxidant effects, suggesting that it may enhance immune function. Hence, the purpose of this randomized, double-blind, placebo-controlled, parallel-design study was to evaluate the ability of a proprietary water extract of tongkat ali root to enhance immune function in healthy, middle-aged adults.
Healthy subjects (N = 83, aged 40-59 years) participated in this study conducted in Tokyo, Japan. Excluded subjects had a history of heart failure, heart attack, atrial fibrillation, cardiac arrhythmia, hepatic disorder, renal disorder, cerebrovascular disorder, rheumatism, dyslipidemia, hypertension, or other chronic disease; used conventional pharmaceutical medicines, herbal medicines, or dietary supplements within 30 days of providing informed consent; had any allergies; were pregnant, lactating, or had plans to become pregnant during the study; had pollinosis (hay fever); or were currently tobacco (Nicotiana tabacum, Solanaceae) smokers.
Subjects were randomly assigned to receive either a rice (Oryza spp., Poaceae)-powder placebo or 200 mg tongkat ali standardized water-soluble root extract (Physta, known as LJ100 in the United States; supplied by Biotropics Malaysia Berhad; Shah Alam, Selangor, Malaysia) each day for four weeks. Each Physta hard gelatin capsule contained 30 mg fatty acid sucrose esters and 200 mg extract standardized to contain 0.8-1.5% eurycomanone, > 40% glycosaponin, > 30% polysaccharide, and > 22% protein.
At baseline and study end, subjects had blood drawn for the immune evaluation. The following primary endpoints were measured: number of neutrophils, lymphocytes, total T cells, CD4+ T cells, CD8+ T cells, CD8+CD28+ T cells, naïve T cells, memory T cells, B cells, and natural killer cells; ratios of CD4+/CD8+ T cells and naïve/memory T cells; T cell proliferative activity, T cell proliferative index (TCPI), immunological age, T lymphocyte age, and immunological grade.
The researchers also used Scoring of Immunological Vigor (SIV) as a primary endpoint. SIV is a patented evaluation method designed to assess “immunity with eight immune parameters [that] are easily affected by aging, stress and illness. SIV is the sum of eight immunological functional scores with three-point grades.” The total scores correlate to five immunological zones: sufficiently high, safety, observation, warning, and critical.
Secondary endpoints were change in mood as evaluated by the Profile of Mood States (POMS, Japanese brief version) and laboratory safety parameters. Subjects were instructed to maintain their regular dietary and exercise habits.
At baseline, there were no significant differences between the groups in terms of gender ratio, age, SIV, immunological age, immunological grade, and T lymphocyte age. Eighty-three subjects completed the trial, but two subjects were excluded from the final analyses due to a cold and low compliance, respectively. All 81 subjects included in the analysis took 90% or more of the capsules.
At week 4, there were significant differences in SIV and immunological grades between the two groups (P < 0.05 for both). SIV and immunological grade increased significantly in the tongkat ali group compared to baseline (P < 0.01 for both), but they did not change in the placebo group. Immunological age decreased significantly by 3.7 years in the tongkat ali group compared to baseline (P < 0.05), but it did not significantly decrease in the placebo group (P < 0.1).
Between-group comparisons showed significant increases in lymphocytes (P < 0.05), total T cells (P < 0.05), CD4+ T cells (P < 0.01), and naïve T cells (P < 0.05) in the tongkat ali group. However, there were no significant between-group differences in naïve/memory T cells or TCPI. The authors suggest that the lack of significant change in these two parameters may be due to the homeostatic balance in the body, short study duration, or small sample size.
Immunological grade improved from “warning” to “observation zone” in the tongkat ali group and was maintained at “warning” in the placebo group. There were no significant differences in immunological age or T lymphocyte age between groups. The POMS score did not differ between groups, although the improvement in the anxiety/tension domain approached significance (P < 0.054) in the tongkat ali group.
There were no significant changes from baseline in blood and biochemical analyses, urinalysis, somatometry (measurements of the dimensions of the body), or blood pressure. All adverse events (AEs) were considered mild and unrelated to treatment. There was no significant difference in the incidences of AEs between groups, and there were no clinically meaningful changes in safety parameters.
Immune system efficiency declines with age; specifically, there is a reduction in the number of naïve T cells. Tongkat ali increased the number of lymphocytes, total T cells, and naïve T cells, and reduced immunological age of the subjects in this study. Based on the data, the authors conclude that the tongkat ali formulation improved cell-mediated immunity in this population.
Acknowledged limitations were that only cell-mediated immunity was evaluated, the study population included only middle-aged subjects, and the relatively small sample size and short study duration. This study had excellent reporting; all of the Consolidated Standards of Reporting Trials (CONSORT) of herbal interventions criteria were fulfilled.
Overall, the authors conclude that immunity was improved in healthy, middle-aged men and women with comparatively lower levels of immunity (i.e., baseline immunological grades of “warning”) who took 200 mg per day of a tongkat ali product for four weeks. Recommendations for future research include longer-duration trials, and the inclusion of participants in other age groups, those with allergies, and those who have altered immune systems. The study was funded by a grant from the Ministry of Agriculture and Agro-Based Industry Malaysia.
—Heather S. Oliff, PhD