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e-MonitorA Research Review from MediHerb’s Experts

This US e-Monitor is for educational purposes only. MediHerb and Standard Process do not recommend or suggest that any herb discussed is for use in the diagnosis, cure, mitigation or treatment of any disease or disease-related condition. MediHerb and Standard Process are not responsible for any recommendations or suggestions health care professionals make for any medical uses. Health care professionals should refer to the Contraindications & Cautions CD for MediHerb botanicals before recommending any products to patients.

Ginkgo and Novel Cardiovascular Risk Factors

A study assessing the clinical impact of Ginkgo on a number of novel

cardiovascular (CV) risk factors, especially nanoplaque formation and

lipoprotein (a), was reviewed in a previous edition of the Clinical

Monitor (see e-Monitor No. 19, July 2008). Now the authors have

revisited blood samples taken from the trial participants and subjected

them to further analysis.1 As well as nanoplaque formation being

reduced by 14.3% and nanoplaque size by 23.4%, oxidised LDL was

reduced by 21%, lipoprotein (a) by 26.3%, interleukin-6 by 12.9%,

matrix metalloproteinase 9 (MMP-9) by 32.9%, white blood cell (WBC)

count by 7.5% (mainly from monocytes and eosinophils) and highly-

sensitive C-reactive protein (hs-CRP) by 39.3%.

References1 Siegel G, Ermilov E. Atherosclerosis 2011; 218(1): 250-2522 Niccoli G, Sgueglia GA, Conte M et al. Atherosclerosis 2011; 215(1): 166-169

Clinical Monitor by Kerry Bone

No. 46 April 2014

Comment

MMP-9 is a relatively new marker to assess plaque stability.

Unstable plaque is the most significant factor leading to

major adverse cardiac events such as heart attacks.

CRP is usually measured to less than 5 mg/L. When it was

realised that values less than 5 mg/L might also contribute

to CV risk, a more sensitive technique was developed to

measure these low numbers (hs-CRP). Interestingly, the

Ginkgo reduced CRP regardless of the starting value. Hence,

one patient with a relatively low value of 1.60 exhibited

a reduction to 0.64, while in another a reading of 46.6

(indicating a high degree of inflammation) dropped to 29.3.

The latter observation suggests Ginkgo might be a significant

anti-inflammatory treatment in its own right.

WBC count is emerging as a significant CV risk factor in

patients with pre-existing arterial disease. In particular,

eosinophil activation has been linked to major adverse events

in several clinical trials, especially in patients with stents.2

Ginkgo biloba

e-Monitor No. 46 April 2014



Intriguing Clinical Versatility of Green Tea

Recently published trials and systematic reviews point to the clinical

versatility of green tea. Of particular interest is the double blind,

randomised, controlled trial in women with symptomatic uterine

fibroids (UF).1 A total of 39 reproductive-age women (age 18 to 50

years, day 3 serum follicle-stimulating hormone <10 mIU/mL) with

symptomatic UF were recruited for this study. All participants had at

least one fibroid lesion 2 cm3 or larger, as confirmed by transvaginal

ultrasonography. They were randomised to oral daily treatment with

either 800 mg of green tea extract (45% EGCG) or placebo (800 mg

of brown rice) for 4 months, and fibroid volumes were measured at

the end, also by transvaginal ultrasonography. The fibroid-specific

symptom severity and health-related quality of life (HRQL) of

these patients were scored at each monthly visit. Of the final 39

women recruited for the study, 33 were compliant and completed

all five visits of the study. In the placebo group (n=11), fibroid

volume increased (24.3%) over the study period. However, patients

randomised to green tea extract (n=22), showed a significant

reduction (32.6%, p = 0.0001) in total volume. In addition, green

tea treatment significantly reduced fibroid-specific symptom severity

(32.4%, p = 0.0001) and induced a significant improvement in

HRQL (18.53%, p = 0.01), compared to the placebo group. Anaemia

also significantly improved by 0.7 g/dL (p = 0.02) in the treatment

group, while average blood loss significantly decreased from

71 mL/month to 45 mL/month (p = 0.001). No adverse effects,

endometrial hyperplasia and other endometrial pathology were

observed in either group.

Type 2 diabetes is a huge challenge for modern communities.

Hence, any natural treatments with high level evidence of efficacy

are of immense relevance. Clinical trials of green tea products

in this context have yielded inconsistent results. Consequently,

a team of Chinese scientists undertook a meta-analysis of trials

investigating the impact of green tea (as extract or beverage) on

glucose control and insulin sensitivity. The meta-analysis included

a variety of participants, including those with type 2 diabetes and

insulin resistance, or of normal health.2 Seventeen relevant trials

(n=1133) were located and included in the meta-analysis. Green tea

consumption significantly reduced fasting glucose and haemoglobin

A1c (HbA

1c) concentrations by 0.09 mmol/L (p < 0.01) and 0.3%

(p < 0.01), respectively. Further analysis from high quality studies

found green tea significantly reduced fasting insulin by 1.16 μIU/mL

(p = 0.03). No significant publication bias (omission from publication

of negative studies) was detected. Subgroup analyses revealed that

green tea lowered fasting blood glucose in those at risk of metabolic

syndrome, but had no such effect in healthy participants. In addition,

green tea significantly lowered fasting glucose in subgroups with

higher catechin intakes, but no effect found in the subgroup with the

lowest catechin intake. Catechin (polyphenol) doses ranged from

208 to 1207 mg/day (median 457 mg/day).

Min Zhang (in collaboration), currently based at the University of

Western Australia, combined the results of 6 investigations conducted

in China over the past decade with co-workers into the role of

green tea in cancer prevention.3 One epidemiological investigation

was a prospective cohort study (n=254) and the other five were

observational case-control studies. Higher green tea consumption

was consistently observed as being associated with a lower risk of

mortality due to ovarian cancer, and a decreased risk of ovarian,

breast, and colorectal cancers, and adult leukaemia occurrences in

the observational studies. The adjusted hazards ratio (HR) and 95%

confidence interval (CI) for case mortality from ovarian cancer was

0.40 (0.18 to 0.90) in the patients who consumed green tea at the

highest level, compared with non-tea drinkers. Compared with never

or seldom tea drinkers, the adjusted odds ratio (OR) ranged from

0.07 to 0.61 for ovarian, breast, and colorectal cancers and adult

leukaemia in those who consumed green tea at the highest level.

Significant inverse dose-response relationships were also observed

for quantity, duration and frequency of green tea consumed. The

authors concluded that regular consumption of green tea enhanced

survival of ovarian cancer and decreased risks of ovarian, breast, and

colorectal cancers and adult leukaemia.Camellia sinensis




References 1 Roshdy E, Rajaratnam V, Maitra S et al. Int J Womens Health 2013; 5: 477-4862 Liu K, Zhou R, Wang B. Am J Clin Nutr 2013; 98(2): 340-3483 Zhang M, Li L, Liu P et al. Funct Food Health Dis 2012; 2(10): 339-3504 Misaka S, Yatabe J, Müller F et al. Clin Pharmacol Ther 2014 Jan 13.

[Epub ahead of print]

Broad-Spectrum Anti-inflammatory Activity of Boswellia

Recently published pilot clinical trials have highlighted the clinical

versatility of Boswellia (Boswellia serrata) as an anti-inflammatory

agent. In particular, its combination with turmeric seems to be

particularly powerful. In one trial reported at a neurology conference,

42 patients with multiple sclerosis receiving interferon therapy also

took a placebo or 900 mg/day of Boswellia (presumably as the

powdered resin).1 After one month there was a significant reduction

in fatigue only in the Boswellia group (p = 0.013), which the authors

attributed to the anti-inflammatory effects of the herb.

A combination of turmeric (Curcuma longa) and Boswellia was

investigated in 16 patients with chronic kidney disease, a disorder

characterised by increased inflammation.2 In a small placebo-

controlled trial, the patients were randomised to receive either

the herbal combination (Boswellia extract 516 mg/day (10%

3-acetyl-11-keto-β-boswellic acid, AKBA) and turmeric extract

824 mg/day (95% curcuminoids)) or a placebo (roasted rice

powder) for 8 weeks. Baseline levels of key plasma markers

(interleukin-6 (IL-6), tumour necrosis factor- (TNF- ) and serum

C-reactive protein (CRP)) indicated elevated inflammation and low

antioxidant protection. A significant time effect (p = 0.03) and time

x compliance interaction effect were observed for IL 6 reduction

in the herbal group, indicating an anti-inflammatory effect. No

significant differences were observed for the other markers, which

the authors mainly attributed to the small sample size and/or other

drug medication.

A similar Boswellia and turmeric combination was assessed in a

12-week trial involving 30 patients with osteoarthritis (OA) of the

knee.3 Patients were randomly assigned to take either 700 mg/day

of turmeric extract (90.5% curcuminoids and 7.5% essential oil) with

300 mg/day Boswellia extract (75% boswellic acids, 10% AKBA) or

200 mg/day of the drug celecoxib. At the completion of the trial,

64% of the patients in the herbal group were no longer classified as

moderate to severe, versus only 39% in the drug group. Otherwise,

there was no overall difference in pain severity, walking distance and

joint tenderness between the two groups. The authors concluded that

the efficacy and tolerability of the herbal combination was superior to

celecoxib for the treatment of active OA.

Finally, a fascinating pilot trial investigated the value of Boswellia in

patients with diffuse axonal injury (DAI), a common consequence of

Boswellia serrata

Comment

For the uterine fibroid study, the authors had previously

demonstrated the ability of EGCG from green tea to inhibit

proliferation and induce apoptosis in human leiomyoma

cells in animal and in vitro models. These preclinical data

encouraged them to initiate a clinical trial, using a relatively

high dose of the herb. Their finding that green tea can shrink

a benign tumour in the human body is a groundbreaking

discovery that could well have implications for other benign

tumours, such as parathyroid and pituitary adenomas, benign

sinonasal tumours (including nasal polyps) and perhaps even

benign prostatic hyperplasia.

When using high doses of green tea it should be kept in

mind that it may interact with pharmaceutical drugs. Tables

reviewing such research are available, but a recent clinical

finding is that 700 mL/day of green tea beverage for 14 days

markedly reduced the plasma concentration and activity of

the beta-blocker nadolol in healthy volunteers.4




moderate to severe head injury.4 In total, 38 patients with pure DAI

were enrolled in this 12-week, double blind, randomised, cross-

over study. The patients were randomly assigned to receive either

capsules of placebo (n=20) or Boswellia resin at 1080 mg/day

(n=18) for 6 weeks, and then switched to the other intervention for

another 6 weeks. The disability rating scale (DRS) was used to assess

the outcome at 2-, 6- and 12-weeks post-trauma. A non-significant

trend for improvement of DRS total scores was observed after the

use of Boswellia. Regarding the DRS sub-scores, however, there was

significant improvement in ‘cognitive ability to self-care’ during the

second 6 weeks for the group receiving Boswellia. Moreover, both

groups experienced a close-to-significant increase in the cognitive

function-related items of the DRS during the periods they were on

Boswellia. The reported adverse events were all of a mild quality and

had similar frequency between the groups. The authors concluded that

Boswellia resin does not significantly affect general outcome, but may

enhance the cognitive outcome of patients with DAI.

References1 Majfinasab N, Siahpush A.Mohammadianinejad SE et al. Ir J Neurol 2013;

12(Suppl 1): 102 Moreillon JJ, Bowden RG, Deike E et al. J Complement Integr Med 2013; 10(1): 1-103 Kizhakkedath R. Mol Med Rep 2013; 8(5): 1542-15484 Moein P, Abbasi Fard S, Asnaashari A. Brain Inj 2013; 27(12): 1454-1460

Promising Evidence for Herbs in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a group of inflammatory

conditions of the digestive tract, with the two major autoimmune

diseases Crohn’s disease (CD) and uncreative colitis (UC) comprising

the majority of cases. A group of researchers used a database search

to locate seven placebo-controlled clinical trials where herbs were

evaluated for the treatment of IBD.1 They then included the results of

these trials into a meta-analysis comprising 474 patients. Comparison

of herbal treatment with placebo yielded a significant relative risk

or risk ratio (RR) of 2.07 (p = 0.0002) for clinical remission and a

significant RR of 2.59 (p = 0.01) for clinical response. There was also a

non-significant RR of 0.89 for any adverse event, and a non-significant

RR of 0.97 for serious adverse events. The seven trials located

(several of which have been reviewed in past issues of the e-Monitor)

were Andrographis in IBD, Boswellia in CD, Aloe vera in UC, two for

wormwood (Artemisia absinthium) in CD, Boswellia in collagenous

colitis and wheat grass juice (Triticum aestivum) in UC.

Aloe vera

Comment

The results of these trials will need to be further explored

in larger studies, although the value of Boswellia in OA has

already been confirmed several times. An intriguing finding

is that the addition of turmeric to Boswellia seems to confer

a clinical efficacy in OA that is superior to the normal dose of

the drug celecoxib.




References 1 Rahimi R, Nikfar S, Abdollahi M. World J Gastroenterol 2013; 19(34): 5738-57492 Kanazawa A, Sako M, Takazoe M. Surg Today 2013 Oct 17. [Epub ahead of print]3 Langhorst J, Varnhagen I, Schneider SB et al. Aliment Pharmacol Ther 2013; 38(5):490-500

Comment

The validity of performing a meta-analysis of trials involving

different treatments and across different diseases (even though

they all fell under the banner of IBD) can be questioned. They

authors did attempt to address this as follows:

“The present meta-analysis may have been limited by small

sample sizes of studies and heterogeneity. Since the included

trials involved herbal medicines containing different plants

administered to patients with various subtypes of IBD, the

trials were disaggregated. Thus, sub-analyses based on type

of IBD and plant type was performed. The results of sub-

analysis based on IBD type showed that herbal medicines

significantly induce clinical remission in patients with CD and

clinical response in patients with UC; however the induction

of clinical remission in patients with UC and induction of

clinical response in patients with CD by herbal medicines

were not significant. The results of sub-analyses based on

plant type demonstrated that induction of clinical remission

was obtained only by Artemisia absinthium and Boswellia

serrata and induction of clinical response was gained by only

Aloe vera and Triticum aestivum. None of the plants caused

induction of endoscopic or histological efficacy.”

However, such a disaggregation undermines the rationale for

conducting a meta-analysis.

On the positive side, the study does highlight the accumulating

evidence of the value of herbs in IBD. This is not just confined to

the seven trials mentioned. One large and recent study from Japan

followed 258 patients for 3 years who had undergone surgery

for CD.2 Patients were stratified to receive either 5 aminosalicylic

acid (2250 to 3000 mg/day), azathioprine (50 to 100 mg/day)

or the traditional herbal formula daikenchuto (7.5 to 15 g/day,

comprising processed ginger 50%, Panax ginseng 30% and

Japanese or Szechuan pepper 20% (Zanthoxylum species)).

These therapies were initiated within one month of surgery and

continued for at least a year. Of the 258 patients, 44 needed

reoperation with intestinal resection within 3 years due to disease

recurrence. However, the rate was significantly lower in the herbal

group than in the pooled non-herbal group (11.3% versus 24.5%,

p = 0.01).

A herbal tablet comprising myrrh 100 mg, chamomile extract

70 mg and coffee charcoal 50 mg (4 tablets per day) was

investigated for maintaining remission in UC, compared to the

drug 5 aminosalicylic acid (mesalazine), 500 mg/day.3 Using a

randomised, double blind, double-dummy study over a 12-month

period in patients with UC, the primary endpoint was non-

inferiority of the herbal preparation, as defined by the Clinical

Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints

were relapse rates, safety profile, relapse-free times, endoscopic

activity and faecal biomarkers. A total of 96 patients (51 female)

with inactive UC were included. Mean CAI demonstrated no

significant difference between the two treatment groups in

the intention-to-treat (p = 0.121) or per-protocol (p = 0.251)

analysis. Relapse rates in total were 22/49 patients (45%) in the

drug treatment group and 25/47 patients (53%) in the herbal

treatment group (p = 0.540). Safety profile and tolerability were

good and no significant differences were shown in relapse-free

time, endoscopy and faecal biomarkers. The authors concluded

the herbal preparation of myrrh, chamomile extract and coffee

charcoal is well tolerated and shows a good safety profile. They

claimed first evidence for its potential efficacy comparable to the

gold standard therapy mesalazine, which merits further study.

e-MonitorA Research Review from MediHerb’s Experts



Clinical Studies Evaluating Herbs

Effects of ginger (Zingiber officinale) on plasma glucose level,

HbA1c and insulin sensitivity in type 2 diabetic patients.

Mahluji S, Attari VE, Mobasseri M et al. Int J Food Sci Nutr 2013; 64(6): 682-686

A randomised, double-blind, placebo-controlled trial conducted in Iran

investigated the effect of ginger rhizome (Zingiber officinale) in

64 patients with type 2 diabetes. Ginger powder was provided

as tablets and prescribed at 2 g/day. Placebo tablets, of similar

colour, consisted of corn starch with a very small amount of ginger

powder added to provide a ginger odour. The participants in the two

groups were matched for hypoglycaemic and hypolipidaemic drug

consumption and duration of disease. Tablets were taken for 8 weeks.

There were no significant differences regarding energy or nutrient

intakes at baseline or during the trial. Treatment with ginger was

found to improve insulin sensitivity and some blood lipid parameters.

� Blood levels of insulin, triglycerides and LDL-cholesterol decreased

significantly from baseline for the ginger group. Total cholesterol

and HDL-cholesterol were unchanged.

� Significant improvements were also found for insulin resistance

(homeostasis model assessment, HOMA) and insulin sensitivity

(quantitative insulin-sensitivity check index, QUICKI), but

there were no statistically significant differences in glycated

haemoglobin (HbA1c) and fasting plasma glucose.

� Significant changes were not observed for the placebo group

throughout the study.

BaselineAfter Ginger Treatment

Insulin (μU/mL) 12.7 11.0

HOMA 4.4 3.9

QUICKI 0.309 0.313

triglycerides (mg/dL) 152.3 127.7

LDL-cholesterol (mg/dL) 79.6 67.8

Note: Differences from baseline for ginger treatment were significant (p < 0.05), and the results were significantly better than the results in the placebo group – the results (from baseline) for insulin, HOMA and QUICKI in the placebo group worsened (although not reaching significance).

Key Finding

Treatment with relatively high doses of ginger powder

improved some parameters in diabetic patients.

Clinical Research Review by Michelle Morgan

No. 46 April 2014

Zingiber officinale




A randomized controlled pilot trial: the effects of

EGb 761 on information processing and executive

function in multiple sclerosis.

Diamond BJ, Johnson SK, Kaufman M et al. Explore 2013; 9(2): 106-107

The effect of Ginkgo in patients with multiple sclerosis has been

investigated in several clinical studies, including a pilot randomised

controlled trial (Explore 2006; 2(1): 19-24) that showed modest

benefits on fatigue and symptom severity. Twenty-one patients

completed that trial: 12 received standardised Ginkgo extract (EGb 761,

240 mg/day) and 9 received placebo for 4 weeks. The daily dosage of

Ginkgo corresponded to 12 g of dried leaf, providing 57.6 mg of ginkgo

flavone glycosides and 14.4 mg of terpenoids. New data derived from

the trial, relating to cognitive function, has been published.

� There were no significant differences between Ginkgo and

placebo on visual-spatial memory or attention/concentration.

� Those treated with Ginkgo showed enhanced processing speed

on the Visual Threshold Serial Addition test, unlike those in the

placebo group, for whom processing speed slowed. The difference

between the change from baseline between Ginkgo and placebo

was significant (p = 0.05).

� The Ginkgo-treated group also emitted fewer verbal intrusions

on the California Verbal Learning test than the placebo group

(p = 0.03). (An intrusion is a type of error.)

� Reduced fatigue (which was reported in the previous publication)

accounted for some of the improvement in processing speed.

Key Finding

Preliminary results show that standardised Ginkgo extract

improved information processing in patients with multiple

sclerosis.

Evaluation of contextual and demographic factors

on licorice effects on reducing hot flashes in

postmenopause women.

Menati L, Khaleghinezhad K, Tadayon M et al. Health Care Women Int 2014; 35(1): 87-99

A randomised, double-blind trial conducted in Iran compared treatment

with licorice to hormone replacement therapy in menopausal women.

Only women with blood pressure within the normal range were

enrolled. Fifty-two women completed the trial. They received licorice

extract (1140 mg/day, providing 34 mg/day of glycyrrhizin)* or HRT

(conjugated oestrogen 0.312 mg/day and medroxyprogesterone

2.5 mg/day) for 90 days.

� There was a significant reduction in the duration of hot flashes

in both the licorice and HRT groups, from baseline. Although the

duration of hot flashes had a greater reduction in the licorice

group, the difference between the groups was not

statistically significant.

� The number of hot flashes decreased in both groups (significantly

in the case of HRT), although there was no significant difference

between the groups.

� HRT reduced the severity of hot flashes significantly more

than licorice.

� Few side effects were reported: two cases of nausea in the

licorice group, one case of headache and another of breast pain

in the HRT group.

Reviewer’s Note

*Information obtained using the brand name indicates the 650-mg tablet

to contain 380 mg of standardised extract of Glycyrrhiza glabra, as well

as calcium carbonate. Three tablets were taken each day (1140 mg/day

of extract). Dried herb equivalent is unknown.

Key Finding

Preliminary results suggest licorice significantly reduced the

duration of hot flashes in normotensive menopausal women.

Hormone replacement therapy had a greater effect on the

number and severity of hot flashes.




Beneficial effect of Astragalus membranaceus on

estimated glomerular filtration rate in patients with

progressive chronic kidney disease.

Okuda M, Horikoshi S, Matsumoto M et al. Hong Kong J Nephrol 2012; 14(1): 17-23

A clinical study conducted in Japan treated patients with progressive

chronic kidney disease (CKD) with Astragalus for more than 3 months.

Thirty-five patients, with an average age of 64.1 years, completed

the study. Patients had CKD stage 4 or 5 with estimated glomerular

filtration rate (eGFR) decreasing in the 3 months prior to the study,

despite the use of conventional treatment. Participants were treated

with 5 g/day of Astragalus* and they continued to take their

conventional treatments.

� The mean eGFR of 15 patients with CKD stage 4 had

decreased in the 3 months prior to baseline (from 20.8 to

16.7 mL/min/1.73 m2), but increased after the initial period of

3 months of treatment with Astragalus to 18.6 (p < 0.05) and

remained similar to baseline at 6 months (17.8) and 12 months

(16.3). (Normal results range from 90–120 mL/min/1.73 m2.

Older people have lower normal GFR levels.)

� In 20 patients with CKD stage 5, the beneficial effect of

Astragalus was limited to the first 3 months only (3 months

prior: 10.5 mL/min/1.73 m2; baseline: 8.0; 3 months: 8.4;

6 months: 6.8). (This suggests that residual nephrons are

required for Astragalus to exert an effect.)

� Astragalus had no significant effect on other laboratory

parameters, including blood urea nitrogen, uric acid, serum

creatinine, urinary protein excretion. In a subset of patients,

Astragalus treatment improved creatinine clearance in the same

way as eGFR (improving at 3 months, stabilising at 6 months).

� Thirteen patients with CKD stage 4 who continued Astragalus

treatment for more than 24 months, showed eGFR at 24 months

of 13.3 mL/min/1.73 m2 and thus did not require dialysis.

� Of the 35 patients, 7 (one in stage 4, 6 in stage 5) required

dialysis within 12 months of Astragalus treatment. Their mean

eGFR at baseline was relatively low at 7.4 mL/min/1.73 m2.

Reviewer’s Note

*The trial authors clarified in a personal email, 8th October 2013, that

dried root powder was administered, with most patients taking the

powder after first stirring it into water.

Key Finding

Treatment with Astragalus root powder maintained the

estimated glomerular filtration rate in patients with chronic

kidney disease stage 4. This beneficial effect allowed a delay

in the initiation of dialysis.

Safety, Adverse Reactions, Herb-Drug Interactions

Ethanol in herbal medicinal products for children: Study

data from 50,425 children and pharmacovigilance data

support safety.

Steinhoff B, Kelber O, Nauert C et al. Forsch Komplementmed 2013; 20(Supp 3): 20, Abstract OP200

A systematic evaluation of prospective and retrospective studies that

used herbal products and a survey of market and pharmacovigilance

data from Germany was conducted.

� Seventeen studies involving 50,425 children aged 0–12 years

were evaluated. None of the 15 adverse events reported were

related to the ethanol content of the products.

� During the past few years more than 764 million daily doses were

sold. From 2005 to 2009, 10.8 million packages were prescribed

to children. No adverse effects attributable to the ethanol content

were reported in the pharmacovigilance system.Astragalus membranaceus




Reviewer’s Notes

An earlier publication (Pharm Ind 2008; 70(9): 1124-1127) investigated

this issue, and provided some quantitative examples.

� Characteristic doses for children of one year of age e.g. 0.5 mL of

a 12% ethanolic solution results in blood ethanol concentration of

0.0003–0.0008%. This amount of ethanol is completely eliminated

from the blood within 1–2 minutes. (Blood ethanol content was

calculated using worst-case assumptions.)

� With a dose of 0.3 mL (6 drops) of a 30% ethanolic solution, as used

in children up to 3 months of age, 70 mcg of ethanol are ingested,

which is eliminated within 6–7 minutes. This dose achieves a

maximum blood ethanol concentration of up to 0.003%. The human

body produces physiological blood levels of ethanol of up to 0.003%.

� A valerian tincture with 66% ethanol is recommended in a single

dose of 2.5 mL for patients aged 12 years or above. At this dose,

1.4 g of ethanol is ingested, an ethanol quantity which corresponds

to 350 mL of fruit juice, for which there are no (ethanol-related)

health concerns advised.

Key Finding

Herbal medicines professionally prescribed to children are

unlikely to pose a safety hazard on the basis of ethanol.

Diet & Lifestyle

Garlic intake is an independent predictor of endothelial

function in patients with ischemic stroke.

Lau KK, Chan YH, Wong YK et al. J Nutr Health Aging 2013; 17(7): 600-604

A cross-sectional study investigated the effects of garlic on endothelial

function in patients with ischaemic stroke (ISS). Consecutive Chinese

patients with a history of atherothrombotic ISS were recruited from

outpatient clinics from July 2005 to December 2006. The condition had

been confirmed by cranial computed axial tomography or magnetic

resonance imaging. Daily Allium vegetable intake (including garlic,

onions, Chinese chives and shallots) was ascertained by means of

a validated food frequency questionnaire, and brachial artery flow-

mediated dilatation (FMD) was measured using high-resolution

ultrasound in all patients. The mean age of the study population was

65.9 years and 69% were males.

� Mean Allium vegetable intake and garlic intake of the study

population was 7.5 g/day and 2.9 g/day respectively. Mean FMD

was 2.6%.

� Daily intake of Allium vegetables and garlic significantly correlated

with FMD (p < 0.01).

� Patients with a low Allium intake (less than 3.37 g/day) had a

lower FMD compared to those with an Allium intake greater than

3.37 g/day (2.1% vs 3.0%, p < 0.05).

� After adjusting for confounding factors, analysis identified that

daily Allium vegetable and garlic intake (p < 0.01), but not

onions, Chinese chives and shallots were independent predictors

for changes in FMD in patients with ISS.

à An increase of 0.07% in FMD for every one gram increase in

daily garlic intake was noted (p < 0.01).

� There was also a trend that hypertension was an independent

predictor of FMD.

Allium sativum




Flaxseed-derived enterolactone is inversely associated

with tumor cell proliferation in men with localized

prostate cancer.

Azrad M, Vollmer RT, Madden J et al. J Med Food 2013; 16(4): 357-360

Studies have shown the enterolignans derived from linseed (also

known as flaxseed) have potential anticancer activities. For example,

linseed (30 g/day) taken for about 30 days prior to surgery

significantly reduced tumour proliferation rates among men who

elected to have prostatectomy for localised prostate cancer

(Cancer Epidemiol Biomarkers Prev 2008; 17(12): 3577-3587).

The data from this randomised trial was utilised to investigate the

associations between urinary levels of the enterolignans enterolactone

and enterodiol with prostatic tumour expression of nuclear factor

kappa B (NF-kappaB), vascular endothelial growth factor (VEGF)

and Ki67. (The lignans secoisolariciresinol and matairesinol are

present in several foods including linseed. They are converted to the

enterolignans, enterolactone and enterodiol, by aerobic intestinal

microflora. NF-kappaB is a transcription factor that controls cell growth,

angiogenesis and inflammatory response. VEGF is a proangiogenic

protein. Ki67 is a marker of cell proliferation.)

� Significant correlations were found between intakes of linseed

lignans and urinary concentrations of total enterolignans,

enterolactone and enterodiol (p < 0.0001 for each).

� Urinary concentrations of total enterolignan and enterolactone

were significantly and inversely correlated with Ki67 in the tumour

tissue (p = 0.011, and p = 0.007, respectively). A near-significant

inverse association was observed for enterodiol (p = 0.064).

� Prostatic tissue expression of VEGF was lower in patients with

higher enterolactone, although this did not reach statistical

significance.

� No association was found between enterolignans and NF-kappaB.

Key Finding

Dietary intake of linseed inhibits cancer cell growth and may

reduce tumour angiogenesis in patients with prostate cancer.

High dietary intake of saturated fat is associated with

reduced semen quality among 701 young Danish men

from the general population.

Jensen TK, Heitmann BL, Jensen MB et al. Am J Clin Nutr 2013; 97(2): 411-418

There is evidence that diet affects semen quality. Studies conducted

with men attending infertility clinics have found an association

between saturated fat intake and a lower sperm concentration. A

cross-sectional study investigated the association between dietary

fat intake and semen quality among 701 young Danish men from

the general population. Men were divided into quartiles according to

percentage intake of total energy from total fat and from saturated fat,

polyunsaturated fat and monounsaturated fat. In addition, quartiles of

total daily omega-3 and omega-6 fatty acid intake were calculated.

Data was adjusted for a range of variables, such as body mass index,

alcohol consumption, smoking, aspects of diet, cryptorchidism.

� A lower sperm concentration and total sperm count was found in

men with a high intake of saturated fat.

� A significant dose-response association was found, and men

in the highest quartile of saturated fat intake had a 38% lower

sperm concentration (p < 0.04 for trend) and a 41% lower total

sperm count than did men in the lowest quartile (p < 0.02 for

trend). (In the highest quartile, more than 15.19% of energy was

derived from saturated fat, in the lowest it was less than 11.20%

of energy.)

� No association between semen quality and intake of other types

of fat was found.Flaxseed




An after-school snack of raisins lowers cumulative food

intake in young children.

Patel BP, Bellissimo N, Luhovyy B et al. J Food Sci 2013; 78(Suppl 1): A5-A10

A Canadian study investigated the effect of ad libitum consumption

of raisins, grapes, potato chips and chocolate chip cookies on appetite

and energy intake in 8- to 11-year-old children. On four separate

weekdays, one week apart, 26, normal-weight children were given

a standardised breakfast, morning snack (apple) and a standardised

lunch. After school, they randomly received one of the four snacks and

were instructed to eat until “comfortably full”. Appetite was measured

before and 15, 30 and 45 minutes after snack consumption, using a

subjective score composed of aspects such as desire to eat, hunger

and fullness.

� Children consumed the least calories from raisins and grapes

and the most from cookies (p < 0.001). (However, the weight

of raisins consumed was similar to potato chips and lower than

grapes and cookies (p < 0.009).

� Raisins and grapes led to lower cumulative food intake

(breakfast + morning snack + lunch + after-school snack)

(p < 0.001), while the cookies increased cumulative food

intake (p < 0.001) compared to the other snacks.

� Grapes lowered appetite compared to all other snacks

(p < 0.001) when expressed as a change in appetite per

kilocalorie of the snack.

Grapes RaisinsPotato Chips Cookies

Energy consumed (kcal) 177 228 413 505

Weight consumed (g) 254 75 74 108

Cumulative food intake (kcal) 1049 1099 1284 1376

Factors associated with low water intake among US high

school students - National Youth Physical Activity and

Nutrition Study, 2010.

Park S, Blanck HM, Sherry B et al. J Acad Nutr Diet 2012; 112(9): 1421-1427

A cross-sectional study investigated plain water intake among high

school students (grades 9 through 12) in the United States. Data from

11,049 students was used, although complete information on all

variables for the adjusted odds ratio analysis was only available for

9,077 students. Low water intake was defined as drinking a bottle or

glass of water less than 3 times a day during the past 7 days.

� Nationwide, 54% of high school students reported having low

water intake.

� Variables significantly associated with a greater odds for low

water intake were:

à age 15 years or less (odds ratio (OR) 1.1),

à consuming less than 2 glasses of milk per day (OR 1.5),

à consuming non-diet soda once or more per day (OR 1.6),

à consuming other sugar-sweetened beverages once or more

per day (OR 1.4),

à consuming fruit and 100% fruit juice less than 2 times per day

(OR 1.7),

à consuming vegetables less than 3 times per day (OR 2.3),

à eating at fast-food restaurants 1 to 2 days per week and 3 or

more days per week (OR 1.3 and OR 1.4, respectively),

à being physically active 60 minutes or more per day on less

than 5 days per week (OR 1.6)

� Being obese was significantly associated with reduced odds for

low water intake (OR 0.7).

Raisins




Prospective study of breakfast eating and incident

coronary heart disease in a cohort of male US health

professionals.

Cahill LE, Chiuve SE, Mekary RA et al. Circulation 2013; 128(4): 337-343

Eating habits were assessed in 1992 in 26,902 American male health

professionals aged 45 to 82 years who were free of cardiovascular

disease and cancer. During 16 years of follow-up, 1527 cases of

incident coronary heart disease (CHD) were diagnosed. The data was

analysed and adjusted for a range of factors including demographic,

diet, lifestyle and other CHD risk factors.

� Men who skipped breakfast had a 27% higher risk of CHD

compared with men who did not (relative risk: 1.27; p = 0.01).

� Compared with men who did not eat late at night, those who

ate late at night had a 55% higher CHD risk (relative risk: 1.55;

p = 0.03).

� The associations for risk (for both breakfast and late-night eating)

were attenuated when further adjusted for body mass index,

hypercholesterolaemia, hypertension and diabetes. This suggests

that eating habits may affect risk via these traditional factors.

� No association was observed between eating frequency (times

per day) and risk of CHD.

Eating attentively: a systematic review and meta-analysis of

the effect of food intake memory and awareness on eating.

Robinson E, Aveyard P, Daley A et al. Am J Clin Nutr 2013; 97(4): 728-742

A systematic review investigated the results of studies that examined

the effect that manipulating memory, distraction, awareness or

attention has on food intake in adults. Five study types were identified,

which were: distraction on immediate intake, distraction on later

intake, memory enhancement on later intake, reduced awareness

on immediate intake and increased awareness on immediate intake.

Twenty-four studies were included in the analysis.

� High quality evidence suggests that attentive eating influences

food intake.

� Eating when distracted produced a moderate increase in

immediate intake but increased later intake to a greater extent.

� The effect of distraction on immediate intake appeared to be

independent of dietary restraint. (The results were similar

for participants with high or low restraint. Restraint refers to

deliberate dietary restriction, typically to avoid weight gain or

with a view to eating healthily. Therefore, using attentive eating

techniques such as mindfulness, slow eating and/or reducing

habituation (repeating what you eat), may help people limit their

food intake without having to restrain their intake.)

� Enhancing memory of food consumed reduced later intake,

but this effect may depend on the degree of the participants’

tendencies toward disinhibited eating. (Disinhibition refers to

a tendency to overeat as a consequence of external cues or

emotion. Highly disinhibited eaters were less likely than were

participants with low disinhibition to decrease their food intake

as a result of memory enhancement. This may be because such

individuals have poorer retention or retrieval of food memory.)

� Removing visual information about the amount of food eaten

during a meal increased immediate intake.

� Enhancing awareness of food being eaten may not affect immediate

intake. (This may be because participants in the control condition had

little else to do and so were already attending closely to their food. In

addition, this finding was based on a very small number of studies.)

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