Nathan J, Panjwani S, Mohan V, Joshi V, Thakurdesai PA. Efficacy and safety of standardized extract of Trigonella foenum-graecum L seeds as an adjuvant to L-Dopa in the management of patients with Parkinson’s disease. Phytother Res. 2014;28(2):172-178.
Parkinson’s disease (PD) is an incurable, progressive neurodegenerative disease affecting dopaminergic systems that results in impaired motor function. Current therapy is symptomatic and primarily consists of levodopa (L-Dopa; the direct precursor of dopamine), which can help patients initiate voluntary movement. However, long-term (more than five to six years) L-Dopa therapy almost invariably results in response fluctuations, dyskinesia (involuntary muscle movements), or dystonia (muscle contractions that cause abnormal postures).
There is increasing evidence that the pathogenesis of PD involves the impairment of mitochondrial function, oxidative damage, and inflammation. Fenugreek (Trigonella foenum-graecum, Fabaceae) seeds have the potential to counter all three of these factors; in vivo, fenugreek seed extracts have potent antioxidant and anti-inflammatory effects and the ability to maintain mitochondrial function. The purpose of this six-month, randomized, double-blind, placebo-controlled study was to evaluate the effect of a standardized hydroalcoholic extract of fenugreek seed (IBHB; Indus Biotech Private Limited; Pune, India) as an adjuvant to L-Dopa therapy in patients with PD.
Patients (n=50, aged 18-70 years) with PD and on a stable dose of L-Dopa with carbidopa (another levodopa-related drug compound) were included in this study conducted at the Movement Disorder Clinic at Shushrusha Hospital in Mumbai, India. The exclusion criteria were as follows: refusal or inability to provide informed consent; pregnant or lactating women; hypersensitivity to fenugreek or related products; history or presence of gastrointestinal, liver, kidney, or cardiac disease; maintenance therapy with any other drug; history of drug dependency or alcohol abuse; any serious neurological or psychological disease apart from PD; and participation in a clinical trial within the prior 30 days.
Patients were treated with placebo (dicalcium phosphate) or 300 mg IBHB, a hydroalcoholic extract of fenugreek seed standardized to trigonelline and hydroxyleucine, for six months. According to the authors, “[b]oth active and placebo [treatments] were analysed and complied with quality requirements related to microbial content and heavy metals.” The patients were instructed to consume two capsules daily with water, one taken an hour before breakfast and the other an hour before evening tea.
The primary outcome measure was change in the Unified Parkinson’s Disease Rating Scale (UPDRS) total score or any of its three subsections: (1) cognition, behavior, and mood; (2) activities of daily living; and (3) motor function. The secondary outcome measures were Hoehn and Yahr (H&Y) staging (a rating of PD symptom progression), safety assessment, and Patient’s and Investigator’s Global Assessment. All assessments were made at baseline and every month for six months. There were no significant differences between groups at baseline. Of the 50 enrolled patients, 42 (23 IBHB, 19 placebo) completed the study and were included in the per protocol analysis.
There were no statistically significant differences from baseline or between groups for total UPDRS. However, there were clinically important differences (CIDs) in the total UPDRS score (5.79) and UPDRS motor score (5.68) in the IBHB group.
A decrease in H&Y staging is thought to be of clinical significance. In the IBHB group, 21.7% of patients changed from a higher stage to a lower stage, compared to 5.3% of patients in the placebo group. The number of patients with no H&Y stage change was similar in both groups.
IBHB was well tolerated; six patients in the placebo group dropped out, while only two in the IBHB group withdrew. There were no serious adverse events, and all laboratory parameters remained within normal range.
The authors conclude that IBHB, a standardized fenugreek seed extract, slows the progression of PD when taken as an adjunct to L-Dopa therapy and has a good safety profile. This study is limited by the relatively small sample size; the authors acknowledge that IBHB should be evaluated in a larger population to confirm these findings.
—Heather S. Oliff, PhD