Dr. Ron’s Research Review – May 4, 2016

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This week’s research review focuses on celery.

Ischemic Stroke

A study enrolled 573 patients within 48 hours onset of ischemic stroke in China and examined the effects of Dl-3-n-butylphthalide (NBP), which was first isolated from the seeds of celery. Patients randomly received a 14-day infusion of NBP followed by an NBP capsule, a 14-day infusion of NBP followed by aspirin, or a 14-day infusion of ozagrel followed by aspirin. Ozagrel is a selective inhibitor of thromboxane A2 synthase and an inhibitor of platelet aggregation. 90-day treatment with NBP was associated with a significantly favorable outcome than 14-day treatment with ozagrel as measured by mRS (P < 0.001). (Cui et al., 2013)

Cognitive Impairment

A randomized, double-blind, placebo-controlled trial enrolled 281 patients aged 50-70 years who had a diagnosis of subcortical vascular cognitive impairment without dementia at 15 academic medical centers in China. Patients were randomly assigned to NBP (200 mg 3x/day) or placebo for 24 weeks. NBP showed greater effects than placebo on ADAS-cog (NBP change -2.46 vs. placebo -1.39; P = .03; ITT) and CIBIC-plus (80 [57.1%] vs. 59 [42.1%] patients improved; P = .01; ITT). Over the 6-month treatment period, NBP was effective for improving cognitive and global functioning in patients with subcortical vascular cognitive impairment without dementia and exhibited good safety. (Jia et al., 2015)

Blood Pressure

A study evaluated the efficacy of a standardized celery seed extract (150 mg/d, supplying 85% 3-n-butylphthalide) in 30 mild to moderate hypertensive patients. There was statistically significant decrease in both systolic blood pressure (8.2 mmHg, SD=3.6, P<0.005) and diastolic blood pressure (8.5 mmHG, SD=2.9, P<0.005) at week 3 and week 6 compared to baseline.

Dr. Ron

Articles

 

Ninety-day administration of dl-3-n-butylphthalide for acute ischemic stroke: a randomized, double-blind trial.
            (Cui et al., 2013) Download
BACKGROUND:  Dl-3-n-butylphthalide (NBP), first isolated from the seeds of celery, showed efficacy in animal models of stroke. This study was a clinical trial to assess the efficacy and safety of NBP with a continuous dose regimen among patients with acute ischemic stroke. METHODS:  A randomized, double-blind, double-dummy trial enrolled 573 patients within 48 hours of onset of ischemic stroke in China. Patients were randomly assigned to receive a 14-day infusion of NBP followed by an NBP capsule, a 14-day infusion of NBP followed by aspirin, or a 14-day infusion of ozagrel followed by aspirin. The efficacy measures were Barthel index score and the modified Rankin scale (mRS) at day 90. Differences among the three groups on mRS were compared using χ(2) test of proportions (with two-sided α = 0.05) and Logistic regression analysis was conducted to take the baseline National Institutes of Health Stroke Scale (NIHSS) score into consideration. RESULTS:  Among the 535 subjects included in the efficacy analysis, 90-day treatment with NBP was associated with a significantly favorable outcome than 14-day treatment with ozagrel as measured by mRS (P < 0.001). No significant difference was found among the three groups on Barthel index at day 90. The rate of adverse events was similar among the three groups. CONCLUSIONS:  The 90-day treatment with NBP could improve outcomes at the third month after stroke. The NBP treatment (both intravenous and oral) is safe (ChiCTR-TRC-09000483).

The effects of DL-3-n-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: A multicentre, randomized, double-blind, placebo-controlled trial.
            (Jia et al., 2015) Download
BACKGROUND:  Vascular cognitive impairment without dementia is very common among the aged and tends to progress to dementia, but there have been no proper large-scale intervention trials dedicated to it. Vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease (hereinafter, subcortical Vascular cognitive impairment without dementia) represents a relatively homogeneous disease process and is a suitable target for therapeutic trials investigating Vascular cognitive impairment without dementia. Preclinical trials showed that dl-3-n-butylphthalide (NBP) is effective for cognitive impairment of vascular origin. METHODS:  In this randomized, double-blind, placebo-controlled trial, we enrolled patients aged 50-70 years who had a diagnosis of subcortical Vascular cognitive impairment without dementia at 15 academic medical centers in China. Inclusion criteria included a clinical dementia rating ≥0.5 on at least one domain and global score ≤0.5; a mini-mental state examination score ≥20 (primary school) or ≥24 (junior school or above); and brain magnetic resonance imaging consistent with subcortical ischemic small vessel disease. Patients were randomly assigned to NBP 200 mg three times daily or matched placebo (1:1) for 24 weeks according to a computer-generated randomization protocol. All patients and study personnel were masked to treatment assignment. Primary outcome measures were the changes in Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and clinician's interview-based impression of change plus caregiver input (CIBIC-plus) after 24 weeks. All patients were monitored for adverse events (AEs). Outcome measures were analyzed for both the intention-to-treat (ITT) population and the per protocol population. RESULTS:  This study enrolled 281 patients. NBP showed greater effects than placebo on ADAS-cog (NBP change -2.46 vs. placebo -1.39; P = .03; ITT) and CIBIC-plus (80 [57.1%] vs. 59 [42.1%] patients improved; P = .01; ITT). NBP-related AE were uncommon and primarily consisted of mild gastrointestinal symptoms. CONCLUSIONS:  Over the 6-month treatment period, NBP was effective for improving cognitive and global functioning in patients with subcortical vascular cognitive impairment without dementia and exhibited good safety.

A Pilot Study to Evaluate the Antihypertensive Effect of a Celery Extract in Mild to Moderate Hypertensive Patients
(Madhavi et al., 2013) Download
Objective: To evaluate the efficacy of a standardized extract of celery seed, 150 mg/d, supplying 85% 3-n-butylphthalide (3nB) in mild to moderate hypertensive patients. Study Design: A single-arm study of 30 mild to moderate hypertensive patients given the test medication following a 7-day wash out period. The primary clinical assessment was the effect on blood pressure at week 3 and week 6. Secondary measures were fasting blood levels of total cholesterol, LDL cholesterol, HDL cholesterol, VLDL cholesterol, free fatty acids, and serum electrolytes (ie, sodium, potassium, calcium). Results: There was statistically significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at week 3 and week 6 compared to baseline. The change at week 6 for the SBP was 8.2 mmHg (SD=3.6, P<0.005) and for the DBP was 8.5 mmHG (SD=2.9, P<0.005). Conclusions: The results from this pilot study suggest that celery seed extract may have clinically relevant blood pressure–lowering effects, indicating that additional clinical research is warranted.

 

References

Cui, LY, et al. (2013), ‘Ninety-day administration of dl-3-n-butylphthalide for acute ischemic stroke: a randomized, double-blind trial.’, Chin Med J (Engl), 126 (18), 3405-10. PubMed: 24034079
Jia, J, et al. (2015), ‘The effects of DL-3-n-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: A multicentre, randomized, double-blind, placebo-controlled trial.’, Alzheimers Dement, PubMed: 26086183
Madhavi, D., et al. (2013), ‘A Pilot Study to Evaluate the Antihypertensive Effect of a Celery Extract in Mild to Moderate Hypertensive Patients’, Natural Medicine J, 5 (4), PubMed: