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Igwe 2016

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maymaycute1510
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PHYTOTHERAPY RESEARCH

Phytother. Res. 30: 701–731 (2016)


Published online 16 March 2016 in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/ptr.5581

REVIEW
A Systematic Review on the Health Effects of
Plums (Prunus domestica and Prunus salicina)

Ezinne O. Igwe* and Karen E. Charlton


School of Medicine, University of Wollongong, Northfields Avenue, Wollongong, New South Wales 2522, Australia

In recent times, plums have been described as foods with health-promoting properties. Research on the health
effects of plum continue to show promising results on its antiinflammatory, antioxidant and memory-
improving characteristics. The increased interest in plum research has been attributed to its high phenolic
content, mostly the anthocyanins, which are known to be natural antioxidants.
A systematic review of literature was carried out to summarize the available evidence on the impact of plums
(Prunus species; domestica and salicina) on disease risk factors and health outcomes.
A number of databases were searched according to the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses guidelines for relevant studies on plum health effects in vitro, animal studies and clinical trials.
A total of 73 relevant peer-reviewed journal articles were included in this review. The level of evidence re-
mains low. Of the 25 human studies, 6 were confirmatory studies of moderate quality, while 19 were exploratory.
Plums have been shown to possess antioxidant and antiallergic properties, and consumption is associated with
improved cognitive function, bone health parameters and cardiovascular risk factors. Most of the human trials
used the dried version of plums rather than fresh fruit, thus limiting translation to dietary messages of the
positioning of plums in a healthy diet.
Evidence on the health effect of plums has not been extensively studied, and the available evidence needs
further confirmation. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: plums; Prunus domestica; Prunus salcina; health effects; systematic review.

Prunes are the dried version of plums and are known


INTRODUCTION
for their laxative effect, which is commonly attributed to
its high fibre content (Tinker et al., 1991). Earlier studies
The plum is a drupe fruit which belongs to the subgenus attributed the laxative effect of prunes to the presence
Prunus (Family Rosaceae). The subgenus can be differ- of phenolics (chlorogenic acid) (Chok and Lang, 1961)
entiated from other subgenera (peaches, cherries, etc.) and sorbitol (Reele and Chodos, 1985) that are in the
as the shoots have a terminal bud and unclustered single fruit, together with its high fibre content (Stacewicz-
side buds, the flowers combine in groups of one to five Sapuntzakis et al., 2001). In the USA, prunes are re-
on short stems, and the fruit have a crease running down ferred to as dried plums. This name change was effected
one side and a smooth seed. Between 19 and 40 differ- in a bid to promote prunes as a health food instead of
ent species of plum exist. Of these, only 2, the hexaploid being associated with old age (Zasky, 2008). Prunes
European plum (Prunus domestica) and the diploid are produced industrially by drying plums at 85–90°C
Japanese plum (Prunus salicina and hybrids), are of for 18 h. This process is believed to have originated
commercial significance across the globe (Topp et al., thousands of years ago also near the Caspian Sea, the
2012). The nutritional composition of the two species same region where the European plums were discov-
is considered similar (Table 1). ered. With migration and civilization, prunes spread
The European plum is believed to have been discov- throughout Europe. Today, California, USA is the
ered about 2000 years ago, with its origin somewhere leading producer of prunes (dried plums) worldwide
near the Caspian Sea. The fruit was introduced into (Norton, 2009).
the USA in the 17th century by pilgrims, while the In classifying whole and natural foods based on their
Japanese plum has its origin in China but derived its unique nutritional composition, flavonoid content is
name from the country where it was mostly cultivated one of the most important methods of classification
and developed, Japan. The Japanese plum was intro- (Stadlmayr et al., 2011). The high levels of phenolic com-
duced into the USA in the late 19th century. Today, pounds, including flavonoids and particularly the sub-
the main producers of commercially grown plums are class of anthocyanins observed in the plum, have
the United States, Serbia, China and Romania. (UN resulted in a dramatically increased interest in plum-
Food and Agriculture Organization, 2011). based research since the 1990s (Nakatani et al., 2000;
Walle et al., 2003). A number of health benefits have
* Correspondence to: Ezinne Oyidia Igwe, School of Medicine, Univer-
sity of Wollongong, Northfields Avenue, Wollongong, New South Wales
been associated to the plum fruit and these include im-
2522, Australia. proved bone health, cognition and memory, antioxidant
E-mail: [email protected] anti-inflammatory effects and easement of constipation.
Received 23 July 2015
Revised 30 November 2015
Copyright © 2016 John Wiley & Sons, Ltd. Accepted 09 January 2016
702 E. O. IGWE AND K. CHARLTON

Table 1. Major nutritional composition of European (Prunus the high phenolic content (Yu et al., 2009a; Noratto
domestica) and Japanese (Prunus salicina) plums, per 100 g et al., 2009; Franklin et al., 2006; Pawlowski et al., 2014;
weight (data from (USDA, 2014); data are a mix of Japanese Shukitt-Hale et al., 2009).
and European plums) These observed health effects have been reported
from studies that have used different research designs
European plum (P. domestica) and (in vitro, animal studies and clinical studies) and have in-
Japanese plums (P. salicina) vestigated both plums, and related products and extracts
(Stacewicz-Sapuntzakis, 2013).
Fresh Dried Plum
The aim of this systematic literature review is to de-
Component plums prunes juice
termine the level of current evidence on the beneficial
Water/moisture (g) 87.23 30.92 84.02 health effects of plum and its associated products.
Energy (kj) 192 1006 243
Carbohydrate (g) 11.42 63.88 15.15
Protein (g) 0.70 2.18 0.51
Fat (g) 0.28 0.38 0.02
MATERIALS AND METHODS
Sugars, total 14.22
Glucose (g) 5.07 25.46 23.3a
Fructose (g) 3.07 12.45 11.8a A number of electronic databases were searched:
Sucrose (g) 1.57 0.15 3.7a Scopus, Web of Science, Cochrane library, CINAHL,
Total dietary fibre 1.4 7.1 0.9 MedLine and ScienceDirect up to June 2015 with a com-
bination of search terms, including plum or prunes or
Minerals Prunus domestica or Prunus salicina and health effects
Calcium (mg) 6 43 10 used as keywords (see Appendix 1 for Medline search
Iron (mg) 0.17 0.93 0.34 strategy).
Magnesium (mg) 7 41 8 Inclusion criteria for journal articles include
Phosphorus (mg) 16 69 15
1. Studies carried out in vitro, on animal and clinical
Potassium (mg) 157 732 154
studies.
Sodium (mg) 0 2 1
2. Studies that utilized the fresh, dried, juice version or
Zinc (mg) 0.10 0.44 0.11
extracts of the plum species P. domestica or P.
Copper (mg) 0.057 0.281 0.054
salicina.
Manganese (mg) 0.052 0.299 0.033
— 3. All studies assessing any health outcome associated
Fluoride (μg) 2.0 4.0
with plum consumption.
Vitamins 4. Studies reported in English. Only studies reported in
Ascorbic acid (C) (mg) 9.5 0.6 2.8 English were included due to language barrier, rea-
Thiamine (B1) (mg) 0.028 0.051 0.023 sons of time efficiency and cost of translation not be-
Riboflavin (B2) (mg) 0.026 0.186 0.059 ing feasible.
Niacin (B3) (mg) 0.417 1.882 0.473 Exclusion criteria for journal articles include
Pantothenic acid (B5) (mg) 0.135 0.422 0.072
Pyridoxine (B6) (mg) 0.029 0.205 0.027 1. Studies on the quantification of the nutritional com-
Total Folate (μg) 5 4 3 position and antioxidant properties of plums.
Vitamin A, RAE (μg) 17 39 50 2. Studies that utilize different species of plums, for
Vitamin E (mg) 0.26 0.43 0.18 example, the Japanese apricot, also known as
Vitamin K1 (μg) 6.4 59.5 4.3 Japanese plums in the Prunus mume specie.
3. Studies assessing properties related to plum cultiva-
Carotenoids
tion, harvest and the commercial aspects of the plum
Carotene, beta (μg) 190 394 554 fruit.
Carotene, alpha (μg) 0 57 0
Cryptoxanthin, beta (μg) 35 93 102 Articles were assessed for peer-reviewed status using
Lutein + zeaxanthin (μg) 73 148 49 Ulrich’s Web (available at: http://ulrichsweb.
serialssolutions.com.ezproxy.uow.edu.au/). A hand
Phenolic compoundsb
search yielded one additional article, which was relevant
Total (mg) 111 184 121c to this review.
Neochlorogenic acid (mg) 81 131 198.5a For the clinical trials, all the relevant studies retrieved
Chlorogenic acid (mg) 14.4 44 46.5a were classified as either confirmatory or exploratory

Anthocyanins (mg) 7.6 0.172c studies. They were rated for their quality using relevant

Catechins (mg) 5.4 criteria from the Delphi list, Cochrane Back Review
Group and the CONSORT Statement (Table 9), and
Table adapted from (Stacewicz-Sapuntzakis, 2013) and (Netzel
strength of evidence of study design assessed using the
et al., 2012)
a Australian National Health and Medical Research
(Stacewicz-Sapuntzakis, 2013) (plum juice concentrate)
b Council hierarchy levels of evidence with rankings from
(Mangels et al., 1993)
c level I–IV.
(Shukitt-Hale et al., 2009)
— The National Health and Medical Research Council ev-
No available data.
idence hierarchy has six levels according to type of
research question with systematic review of level II studies
These health-promoting properties have been attrib- classified as levels I, randomized controlled trials, classified
uted to the plum’s antioxidant capacity as a result of as level II. Studies ranging from a pseudorandomised
Copyright © 2016 John Wiley & Sons, Ltd. Phytother. Res. 30: 701–731 (2016)
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina) 703

controlled trial to a comparative study without concurrent studies, 5 animal studies and 4 clinical trials) while nine
controls classified as levels III-1 to III-3 and case series with studies investigated the effect of plums on different com-
either post-test or pre-test/post-test outcomes classified as ponents of the metabolic syndrome (cholesterol, high
level IV (NHMRC, 2000). blood pressure and anti-thrombosis; 3 animal studies
and 6 clinical trials). For its commonly known laxative ef-
fect and satiety, 8 clinical studies were carried out. Five
studies examined its anti-allergic, anti-microbial and
RESULTS immune-enhancing properties (2 in vitro studies and 3
animal studies), and 2 clinical studies examined its ef-
A total of 73 studies were eligible for inclusion in this fects on liver function and risk factors for kidney stone
review (Fig.1). Of these, 18 investigated bone health formation. Some of the findings reported from the
(2 in vitro, 12 animal studies and 4 clinical trials), and in vitro studies like improved bone health and anti-
20 investigated its anticancer and antiinflammatory inflammatory properties have also been confirmed in an-
properties (13 in vitro studies, 6 animal studies and 1 clin- imal and human studies. Tables 2–8 summarize the ex-
ical trial). Eleven studies reported on plums’ antioxidant perimental and clinical studies, and Table 9 summarizes
properties and their effect on cognition (2 in vitro the quality of the clinical studies included in this review.

Figure 1. PRISMA flow diagram for study selection process.

Copyright © 2016 John Wiley & Sons, Ltd. Phytother. Res. 30: 701–731 (2016)
704

Table 2. Evidence on the effect of plums and its associated products on bone health

Reference Location Plum product investigated Sample/method Level of evidence* Effects observed

In vitro studies
(Bu et al., 2008) USA Dried plum extract RAW 264.7 murine macrophage cells Inhibition of osteoclastogenesis under
(Prunus domestica) inflammatory and oxidative stress
conditions possibly by polyphenol content
(Bu et al., 2009) USA Polyphenols extracted from MC3T3-E1 cells pre-treated with dried plum Improvement of osteoblast activity and
dried plum (P. domestica) polyphenols (0, 2.5, 5, 10 and 20 μg/mL) and function by up-regulating Runx2, Osterix and
24 h later stimulated with TNF-α (0 or 1.0 ng/mL). IGF-I and increasing lysyl oxidase expression,
and reduction in osteoclastogenesis signalling

Copyright © 2016 John Wiley & Sons, Ltd.


Animal studies
(Smith et al., 2014a) USA Dried plum (P. domestica) Six weeks dietary supplementation of dried plum Restoration of bone mineral density by two
(5%, 15% or 25%) in adult, osteopenic higher doses and bone turnover suppression
ovariectomized rats
(Deyhim et al., 2005) USA Dried plum (P. domestica) Dietary supplementation of dried plum (5%, 15% Bone quality improvement (restoring bone
and 25%) in adult, osteopenic ovariectomized rats density) with all doses
for 40 days
(Franklin et al., 2006) USA Dried plum (P. domestica) Dietary supplementation of dried plum (5%, 15% Prevention of osteopenia in androgen deficient
and 25%) in orchidectomized rats for 90 days male rats
(Bu et al., 2007) USA Dried plum (P. domestica) Dietary supplementation of dried plum (25%) in Reversion of bone loss due to orchidectomy
osteopenic orchidectomized rats for 90 days
(Smith et al., 2014b) USA Dried plum (P. domestica) Dietary supplementation of dried plum (25%) in Improvement in bone mass and structure
adult mice for 4 or 12 weeks
(Rendina et al., 2013) USA Dried plum (P. domestica) Eight weeks dietary supplementation of dried plum Bone loss prevention with anabolic effect
(25%) in adult, osteopenic ovariectomized mice
(Halloran et al., 2010) USA Dried plum (P. domestica) Dietary supplementation of dried plum (15% or Restoration of lost bone and increase in bone
E. O. IGWE AND K. CHARLTON

25%) in adult and aged (old) male mice for 6 months volume
(Rendina et al., 2012) USA Dried plum (P. domestica) Dietary supplementation of dried plum (5%, 15% or Improvement of bone structure and
25%) in ovariectomized adult mice for 4 weeks biomechanical properties and suppression of
lymphocyte TNF-α production by higher doses
(Pawlowski et al., 2014) USA Dried plum powder extract Dietary supplementation of plum extract (9% or Improvement in bone calcium retention
(P. domestica) 20%) in ovariectomized rats for six intervention
(10 days) and washout (10 days) cycles
(Monsefi et al., 2013) Iran Plum extract (P. domestica) Oral administration of plum extract (1.6 g/kg) in Increased osteogenesis index in fetuses of
distilled water in pregnant mice for 30 days mice treated with plum extract
(Arjmandi et al., 2010) USA Dried plum (P. domestica) One hundred eighty 3-month-old female Diets supplemented with 5%
Sprague–Dawley rats assigned to 15 groups (n = 12) fructooligosaccharides and 7.5% dried plum
and either ovariectomized (14 groups) or was most effective in reversing both right
sham-operated (Sham, one group) then placed on femur and fourth lumbar bone mineral density
different dietary treatments including one and fourth lumbar calcium loss while significantly
supplemented with 5% fructooligosaccharides and decreasing trabecular separation.
7.5% dried plum for 60 days.

(Continues)

Phytother. Res. 30: 701–731 (2016)


Table 2. (Continued)

Reference Location Plum product investigated Sample/method Level of evidence* Effects observed

(Johnson et al., 2011) USA Dried plum Seventy two 3-month-old female Sprague–Dawley In combination with soy protein, dried plum and
(P. domestica) rats assigned to six groups (n = 12/group) and either fructooligosaccharides had the most pronounced
ovariectomized (five groups) or sham-operated effect in increasing lumbar bone mineral density.
(Sham, one group) then placed on a semi purified,
powdered casein-based diet for 45 days to induce
bone loss. Thereafter, the groups were placed on
different dietary treatments, including one
supplemented with 5% fructooligosaccharides and
7.5% dried plum for 60 days.

Copyright © 2016 John Wiley & Sons, Ltd.


Clinical trials
(Hooshmand et al., 2011) USA Dried plum Hypothesis: dried plums reverses bone loss in II Confirmatory Statistically significant increase in bone mineral
(P. domestica) osteopenic postmenopausal women. density of ulna and spine with decreased serum
n = 160 osteopenic postmenopausal women levels in bone turnover markers (bone-specific
Study design/methods: randomized controlled alkaline phosphatase and tartrate-resistant acid
trial. Postmenopausal women randomly assigned phosphatase-5b) observed
to treatment groups of dried plum (100 g/d) or
dried apple (75 g) daily for 1 year. Blood and urine
samples collected.
Sample size power: not stated
Dose: 100 g/day.
Duration: 1 year.
(Arjmandi et al., 2002) USA Dried plum Hypothesis: addition of dried plums to the diets II Exploratory Statistically significant increase in serum levels
(P. domestica) of postmenopausal women would positively of insulin-like growth factor-1 and bone-specific
influence markers of bone turnover. alkaline phosphatase associated with increased
n = 58 postmenopausal women rates of bone formation
Study design/methods: randomized controlled
trial. Postmenopausal women randomly assigned
to treatment groups of dried plum (100 g/d) or
dried apple (75 g) daily for 3 months. Blood and
urine samples collected.
Sample size power: not stated
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

Dose: 100 g/day.


Duration: 3 months.
(Hooshmand et al., 2014) USA Dried plum Hypothesis: dried plum has an effect on circulating II Exploratory Increase in bone mineral density of the ulna and
(P. domestica) levels of sclerostin and bone metabolism measured spine and also the receptor activator of NF-kB
in serum levels of receptor activator of NF-kB ligand ligand and osteopotegerin levels. A reduction in
and osteopotegerin. serum sclerostin was also observed.
n = 160 women with mild bone loss.
Study design/methods: randomised controlled trial.
Subjects randomly assigned to one of two groups
of dried plum or dried apple and provided with

Phytother. Res. 30: 701–731 (2016)


705

(Continues)
706

Table 2. (Continued)

Reference Location Plum product investigated Sample/method Level of evidence* Effects observed

500 mg Caplus 400 IU (10 μg) vitamin D.


Sample size power: not stated Dose: 100 g

Copyright © 2016 John Wiley & Sons, Ltd.


dried plum per day Duration: 1 year
(Simonavice et al., 2014) USA Dried plum Hypothesis: 6-month intervention with resistance II Exploratory No difference between groups or any
(P. domestica) training and a combination of resistance training group-by-time interaction observed for any of
and dried plum would improve total and regional the variables.
(lumbar spine, femur and forearm) BMD. Increase
lean body mass, skeletal muscular strength and
decrease fat body mass. Additionally, it was
hypothesized that the biochemical analyses for
both groups would reveal increased levels of bone
formation markers, decreased levels of bone
resorption markers, and decreased levels of
inflammation markers, with the RT + DP group
having the most improvements in these areas in
breast cancer survivors.
n = 23 female breast cancer survivors.
E. O. IGWE AND K. CHARLTON

Study design/methods: case–control. Subjects


stratified into 1(RT) or 2(RT + DP) treatment groups.
Sample size power: not stated
Dose: 90 g dried plum per day
Duration: 6 months

RT, resistance training; DP, dried plum.


*Clinical trials ranked using (NHMRC, 2000) Levels of Evidence Hierarchy where I is a systematic review (highest rating) and IV is a case series or cross-sectional study (lowest rating) and also classified
as exploratory or confirmatory studies.

Phytother. Res. 30: 701–731 (2016)


Table 3. Evidence on the anti-cancerous and antiinflammatory properties of plums and its associated products

Level of
Reference Location Plum product investigated Sample/method evidence* Effects observed

In vitro studies
(Yu et al., 2009a) Korea Immature plum extract Human hepatocellular carcinoma HepG2 cells, Cell growth inhibition by IPE, that is, induction of
(IPE) Kato III gastric cancer cells, HeLa human cancerous cell apoptosis
(Prunus salicina) cervical carcinoma cells, U937 leukaemia
cells and MCF 7 hormone-dependent breast
cancer cells
(Noratto et al., 2009) USA Mature red-fleshed plum MCF-7; the oestrogen-positive human breast Inhibition of breast cancer cell proliferation and

Copyright © 2016 John Wiley & Sons, Ltd.


extract cancer cell line, MDA-MB-453; the oestrogen significantly reduced toxicity on the normal cells
(Prunus domestica) negative human breast cancer cell line, and
MCF-10A; the breast epithelial cells
(Lee et al., 2009) USA Plum extract Chicken spleen, RP9 tumour cells and HD11 Stimulation of spleen lymphocyte proliferation
(P. salicina) macrophages and NO production by cultured macrophages and
inhibition of tumour cell growth
(Fujii et al., 2006) Japan Prune extract Caco-2 human colon carcinoma cell line, Induction of cell apoptosis of cancer cells but not
(P. domestica) KATO III human stomach carcinoma cell line normal cells
and CCD-18Co normal human colon fibroblast
cell line
(Lea et al., 2008) USA Plum extract SW1116, HT29, Caco-2 human colon cancer Growth inhibition and induction of differentiation
(P. domestica) cells and NCM460 human colon cells. on colon cancer cells
(Hooshmand et al., 2015) USA Dried plum polyphenol Stimulation of macrophage RAW 264.7 cells Reduction in Nitric oxide and malondialdehyde
1
extract with either 1 μg mL (for measurement of NO production with highest dose treatment
1 1
(P. domestica) production) or 1 ng mL (for measurement of (1000 μg mL ). Reduction in lipopolysaccharide-
COX-2 expression) of lipopolysaccharide to induced expression of COX-2 by the 100 and
1
induce inflammation and treated with different 1000 μg mL dose.
doses of dried plum polyphenols.
(Kim et al., 2003) USA Plum polyphenol extract Treatment of two cancer cell lines (HepG2 Antiproliferative activities on both cancer cell
(P. domestica) human liver cancer cells and DLD1 human lines in a dose dependent manner.
colon cancer cells) with polyphenol extract
of plum.
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

(Nishida et al., 2014) Japan Plum pectin extract Incubation of heparan sulfate in differentiated There was an obvious change in the sulphated
(P. domestica) Caco-2 cells with pectin extracted from plums. structures of HS following pectin
administration. Also, pectin upregulated human
HS 6-O-endosulfatase-2 (HSulf-2) expression
and inhibited HSulf-1 expression.
(Nishida et al., 2015) Japan Plum pectin extract Incubation of differentiated Caco-2 cells Pectin-treated differentiated Caco-2 cells
(P. domestica) (cultured in 6-well plates at a cell density of promoted growth of IEC-6 cells and also an
5
1.0 × 10 cells/well), with pectin, extracted upregulation of relative mRNA and protein
from plums. expression levels of Wnt3a protein.

(Continues)

Phytother. Res. 30: 701–731 (2016)


707
Table 3. (Continued)
708

Level of
Reference Location Plum product investigated Sample/method evidence* Effects observed

(Popov et al., 2014) Russia Plum pectic polysaccharide 0.05 mL of plum pectic polysaccharide added Reduction in the adhesion of peritoneal
extract to peritoneal cell suspension and incubated in leukocytes. Inhibition of the production of
(P. domestica) a 96-well superoxide anion radicals by reducing xanthine
flat-bottom tissue culture plate in the absence oxidase activity.
or presence of phorbol-12-myristate-13-acetate
at 37°C for 15 mins.
(Vizzotto et al., 2014) USA Plum polyphenol extract Oestrogen independent MDA-MB-435, Dose-dependent cytotoxic effect against MDA-
(P. domestica) oestrogen dependent MCF-7 breast cancer MB-435, weak activity against MCF-7 and small

Copyright © 2016 John Wiley & Sons, Ltd.


cell lines and one non-cancerous breast line or no activity against MCF-10A observed.
MCF-10A exposed to varying concentrations
of plum extracts for 24 h.
(Yu et al., 2007) Korea Immature, mid-mature and Six human cell cancer lines (Hep G2 human Cytotoxic effects observed and apoptosis
mature plum extract hepatocellular carcinoma cells and Kato 111 observed in MDA-MB-231 cells mediated by the
(P. salicina) human gastric carcinoma cells, Hela human immature plum extract.
cervical carcinoma cells, U937 human
leukaemia cells, MCF 7 hormone-dependent
human breast cancer cells, and MDA-MB-231
hormone-independent human breast cancer
cells) incubated with varying concentration of
plum extract.
(Yu et al., 2009b) Korea Immature plum extract Incubation of PMA-induced HepG2 human Antimigrative property in (phorbol 12-myristate
(P. salicina) hepatocellular carcinoma cells with Immature 13-acetate) PMA-induced HepG2 cells observed.
plum extract. A strong inhibitory effect on the PMA-induced
MMP-9 secretion through suppression of the
E. O. IGWE AND K. CHARLTON

transcriptional activity of the MMP-9 gene


independently of the TIMP gene in HepG2 cells
was also observed.
Animal studies
(Kim et al., 2008) Korea Immature plum extract IPE Intraperitoneal injection of IPE (2.5 or 5 g/kg Chemopreventive efficacy by inhibiting the
(P. salicina) bw/day) dissolved in phosphate buffered induction of CYP1A1 expression and reducing
saline for 5 days in male mice with the activity of glutathione peroxidase, superoxide
benzo(α)pyrene induced liver toxicity dismutase and catalase
(Cantu-Jungles et al., 2014) Brazil Polysaccharides from prunes Inducement of acute gastric ulcer in rats using Reduction and inhibition of gastric lesion area
(P. domestica) intragastric administration of ethanol P.A. after by prune polysaccharides fractions.
four different oral treatments including
polysaccharides from prunes fraction (3 and
10 mg/kg).
(Noratto et al., 2015) USA Plum juice Administration of plum juice in drinking water Antiadipogenic and anti-inflammatory effects.
(P. salicina) to obese Zucker rats ad libitum for 11 weeks Reduction in blood glucose, triglycerides and HDL
cholesterol levels

Phytother. Res. 30: 701–731 (2016)


(Continues)
Table 3. (Continued)

Level of
Reference Location Plum product investigated Sample/method evidence* Effects observed

(Mishra et al., 2012) India Plum extract Inducement of peptic ulcer by pyloric ligation Antioxidant and anti-ulcerogenic activity
(P. domestica) in Wistar albino rats after administration of
1
plum extract (100, 150 or 200 mg kg ) for
7 days

Copyright © 2016 John Wiley & Sons, Ltd.


(Yang and Gallaher, 2005) USA Dried plum Dietary supplementation of dried plum (4.75 or Inhibition of risk factors associated with colon
(P. domestica) 9.5%) in male Wistar rats for 10 days followed carcinogenesis (reduction in faecal total and
by administration of two doses (1 week apart) secondary bile acids concentration, reduction in
of azoxymethane and dietary supplementation colonic β-glucuronidase and 7α-dehydroxylase
for 9 more weeks activities and increased antioxidant activity)
(Gallaher and Gallaher, 2009) USA Dried plum Dietary supplementation of dried plum (4.75 or Development of atherosclerosis Impeded
(P. domestica) 9.5%) and cholesterol in apolipoprotein
E-deficient mice for 5 months.
Clinical trial
(Kasim-Karakas et al., 2002) USA Dried plum Hypothesis: prune intake may alter the III-2 Exploratory Decrease in the independent excretion of 2OHE1
(P. domestica) metabolism of estrogens because prunes are a and 16αOHE1 observed but no statistically
rich source of both soluble and insoluble fibre significant change in the 2OHE1 - 16αOHE1
and cinnamates and decrease intestinal transit ratio following prune supplementation
time.
n = 19 healthy premenopausal women
Study design/methods: crossover study.
After consuming habitual diets for three
menstrual cycles (control
run-in period), participants replaced dietary
simple sugars with prunes for another three
menstrual cycles (intervention period).
Sample size power: not stated
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

Dose: 100 g dried plum per day


Duration: 6 months.

*Clinical trials ranked using (NHMRC, 2000) Levels of Evidence Hierarchy where I is a systematic review (highest rating) and IV is a case series or cross-sectional study (lowest rating) and also classified
as exploratory or confirmatory studies.

Phytother. Res. 30: 701–731 (2016)


709
710

Table 4. Evidence on the antioxidant property and effect on cognition of plums and its associated products

Plum product Level of


Reference Location investigated Sample/method evidence Effects observed

In vitro studies
(Bouayed et al., 2009) France Phenolics from Polyphenolics extracted from seven varieties of Antioxidant activity and protection of blood
plums plum and quantified. Their antiradical activities granulocytes from H2O2-induced oxidative
(P. domestica) and protection against oxidative stress stress by preventing granulocytes from
evaluated in peripheral blood granulocytes. intracellular ROS accumulation.
(Donovan et al., 1998) USA Prune/prune Human LDL from plasma prepared from blood Inhibition of LDL oxidation.
juice extract collected from healthy volunteers.

Copyright © 2016 John Wiley & Sons, Ltd.


(P domestica)
Animal studies
(Shukitt-Hale et al., USA Plum juice/dried Two groups of aged rats with either Improved cognitive function assessed by
2009) plum powder consumption of a mixture of water and plum Morris Water Maze
(P. domestica) juice (100%) (Group 1) or dietary
supplementation with dried plum powder (2%)
(group 2) for 8 weeks
(Shahidi et al., 2013) Iran Plum extract Plum extracts (75, 100, 150 mg/kg) Improvement in learning and memory in
(P. domestica) administration by oral gavage to male mice mice assessed by the passive avoidance
once a day for 7 days test
(Kao-Ting et al., 2013) Taiwan Dried plum Dietary supplementation of dried plum powder Improvement in cognitive performance,
powder (Prunus (2%) in nicotinamide/streptozotocin-induced antioxidant activity and improvement in
salicina) diabetic rats for 2 months insulin sensitivity
(Sharma and Sisodia, India Plum extract Administration of optimum dose of plum Antioxidant capabilities and improved
2013) (P. domestica) extract in distilled water to mice for 15 days spatial learning
pre/post whole body exposure to 10 Gy
E. O. IGWE AND K. CHARLTON

gamma-radiations
(Bouayed et al., 2007) France Chlorogenic Administration of chlorogenic acid (20 mg/kg) Decrease in anxiety related behaviours
acid from P. to mice and antioxidant effect on peripheral (anxiolytic-like effect) and protection of
domestica blood granulocytes. granulocytes from oxidative stress by
chlorogenic acid in vitro.
Clinical trials
(Prior et al., 2007) USA Dried plum/ Hypothesis: changes in antioxidant capacity II Exploratory No effect on plasma hydrophilic (H-) or
dried plum following consumption of plum juice may be lipophilic (L-) antioxidant capacity measured
juice used to assess its potential to alter in vivo as Oxygen Radical Absorbance Capacity
(P. domestica) antioxidant status and provide estimates of (ORACFL)
dietary antioxidants necessary to prevent
postprandial oxidative stress.
n = 6 healthy volunteers.
Study design/methods: randomized cross-over
study. Fasting blood sample collected and
participants fed test juices and blood samples

(Continues)

Phytother. Res. 30: 701–731 (2016)


Table 4. (Continued)

Plum product Level of


Reference Location investigated Sample/method evidence Effects observed

collected at 1, 2 and 4 h post juice


consumption.
Sample size power: not stated
Dose: 315 mL of dried plum juice; or dried
plums (131 g blended in 315 mL water
Duration: 2 weeks (with 2 weeks washout

Copyright © 2016 John Wiley & Sons, Ltd.


period)
(Ko et al., 2005) Korea Plum juice Hypothesis: Consumption of fruit juices IV Exploratory Improved antioxidant activity in human
(P. salicina) could scavenge ROS generated in plasma measured by dichlorofluorescein
human plasma. fluorescence
n = 10 healthy men.
Study design/methods: cross-over study.
Consumption of single dose of 150 mL of
plum juice. Blood samples collected at 0,
30, 60, 90 and 120 min after consumption
Sample size power: not stated
Dose: a single dose of 150 mL
Duration: 1 day (with 1 day washout period)
(González-Flores et al., Spain Plum Hypothesis: there is a possible antioxidant IV Exploratory Statistically significant increase in
2011) (P. salicina) effect associated with diets enriched with antioxidant capacity and urinary
Japanese plums (P. salicina Lindl. cv. 6-sulfatoxymelatonin (aMT6-s)
Crimson Globe) in young, middle-aged and
elderly individuals.
n = 18 (6 per young, middle aged and older
group).
Study design/methods: Consumption of 390 g
plums without seeds per day divided into two
portions: 195 g as the lunch dessert and
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

195 g as the dinner dessert for 5 days. First-


void morning urines were collected before
treatment (basal values), the immediate day
after the last ingestion of plums (assay) and
1 day afterwards (post-assay).
Sample size power: not stated
Dose: 2 portions 390 g (195 g each) daily.
Duration: 5 days.

(Continues)

Phytother. Res. 30: 701–731 (2016)


711
712

Table 4. (Continued)

Plum product Level of

Copyright © 2016 John Wiley & Sons, Ltd.


Reference Location investigated Sample/method evidence Effects observed

(Netzel et al., 2012) Australia Plum juice Hypothesis: there is a possible antioxidant IV Exploratory Increase in urinary antioxidant capacity
(P. salicina) effect associated with Queen Garnet Plum and decrease in malondialdehyde
Juice ingestion on the urinary antioxidant excretion (biomarker for oxidative
capacity and the concentration of stress)
malondialdehyde, a biomarker for oxidative
stress.
n = 2 healthy male subjects
Study design/methods: crossover study.
Consumption of 400 mL of Queen Garnet
Plum Juice or 400 mL of water as an
antioxidant-free control beverage separated
by a 1-week washout phase.
Sample size power: not stated
Dose: single dose of 400 mL.
E. O. IGWE AND K. CHARLTON

LDL, low-density lipoprotein; ROS, reactive oxygen species.

Phytother. Res. 30: 701–731 (2016)


Table 5. Evidence on the effect of plums and its associated products on the different components of metabolic syndrome

Level of
Reference Location Plum product investigated Sample/method evidence* Effects observed/conclusion

Animal studies
(Negishi et al., 2007) Japan Prune extract Dietary supplementation of prune extract Suppression of high (systolic) blood pressure
(Prunus domestica) (25%) in stroke-prone spontaneously
hypertensive rats for 5 weeks
(Kuo et al., 2015) Taiwan Plum powder Dietary supplementation of plum powder Amelioration of some symptoms of neurodegenerative
(Prunus salicina) (2% or 5%) in high cholesterol diet in mice conditions like increased cholesterol and β-amyloid
for 5 months (Aβ) concentration in the brain by both doses
(Lucas et al., 2000) USA Dried plums Dietary supplementation (5% or 25% dried With elevated serum total cholesterol brought about by

Copyright © 2016 John Wiley & Sons, Ltd.


(P. domestica) plum) with dried plum in 48 ovariectomized ovariectomy, 25% prune diet prevented this increase
(ovx) 90-day old female Sprague–Dawley without affecting HDL cholesterol concentration and also
rats for 45 days. reduction in liver total lipids was observed.
Clinical trials
(Tinker et al., 1991) USA Dried plums Hypothesis: (a) prunes as a source of fibre can II Confirmatory Plasma LDL cholesterol was statistically significantly
(P. domestica) lower plasma cholesterol in men with mild to reduced after the prune period than the control, faecal
moderate hypercholesterolemia (5.2–7.5 mmol bile acid conc. of lithocholic acid was also statistically
cholesterol/L). (b) faecal bile acid excretion is significantly lower with prune consumption and both
increased in response to the ingestion of prunes faecal wet and dry weights were statistically
as a source of fibre, which may help explain the significantly higher with prune consumption.
cholesterol lowering effect of fibre.
n = 41 free living men with mild
hypercholesterolemia.
Study design/methods: crossover study. 8 weeks
period split into two experimental diet periods,
each lasting 4 weeks. Subjects randomly
assigned a diet sequence, starting with either
consumption of a grape juice-control
supplement (GJ control) or a prune supplement.
Sample size power: not stated
Dose: 12 prunes (~100 g/d)
Duration: 8 weeks.
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

(Chai et al., 2012) USA Dried plums Hypothesis: regular intake of apple favourably II Exploratory No statistically significant difference between treatment
(P. domestica) improves lipid profiles, reduces atherogenic groups in altering serum levels of atherogenic cholesterols
risk ratios, lowers C-reactive protein levels, observed. For the dried apple group, total cholesterol was
and decreases levels of oxidative stress statistically significantly reduced at 6 months.
marker in postmenopausal women
n = 160 postmenopausal women
Study design/methods: case–control study.
Subjects randomly assigned to treatment
groups of dried apple (75 g) or dried plum
(100 g/d)

Phytother. Res. 30: 701–731 (2016)


713

(Continues)
Table 5. (Continued)
714

Level of
Reference Location Plum product investigated Sample/method evidence* Effects observed/conclusion

Sample size power: 95%


Dose: 100 g/day
Duration: 1 year.
(Afaghi et al., 2009) Iran Prunes Hypothesis: 8 fruits (Golab apples, green II Exploratory Serving size of prunes was low glycemic load fruit. Prunes
apples, fresh apricots, prunes, cherries, among other tested fruits were low glycemic index and can
blueberries, golden no-seed grapes, and red be recommended for diabetics and weight loss management.
sultanas) are low glycemic index and
recommendable for diabetics and weight loss.

Copyright © 2016 John Wiley & Sons, Ltd.


n=8
Study design/methods: crossover study. Eight
subjects (healthy, young men aged 20–28,
normal weight with body mass index: 20–25
2
kg/m ) randomly assigned to one of eight
fruits and blood glucose measured at 0, 15,
30, 45,60, 90 and 120 mins after consumption.
Sample size power: 95%
Dose: 143 g
Duration: not stated — different occasions
after overnight fasting.
(Ahmed et al., 2010a) Pakistan Prunes Hypothesis: use of prunes is useful in II Confirmatory Reduction of blood pressure by single dose of prunes daily
(P. domestica) cardiovascular disorders to bring about changes group and the controls with the double dose of prunes
in blood pressure or prevention of atherosclerosis. showing a reduction in just systolic blood pressure. There was
n = 259 pre-hypertensive patients (systolic an increase in serum HDL of the control group whereas test
BP = 120–139 mmHg, diastolic BP = 80–89 mmHg) groups had significantly reduced serum cholesterol and LDL.
E. O. IGWE AND K. CHARLTON

Study design/methods: randomised controlled trial. The data predicts cardiovascular protective effects of prunes.
Patients randomly assigned to three groups of
A-single dose, B-double dose or C-control group.
Blood pressure was recorded fortnightly, and
blood samples were taken at 0 and 8 weeks.
Sample size power: not stated.
Dose: group A-11.5 gm. Group B-23 gm.
Control-glass of water.
Duration: 8 weeks.
(Santhakumar et al., Australia Plum juice Hypothesis: anthocyanin-rich Queen Garnet II Exploratory Queen Garnet Plum Juice supplementation inhibited platelet
2015a) (P. salicina) Plum Juice may ameliorate platelet activation- aggregation induced by adenosine diphosphate, collagen and
related thrombogenesis and maintain arachidonic acid. There was reduction in platelet activation-
haemostatic function by (1) reducing platelet dependent surface-marker P-selectin expression
aggregation and activation through blocking/ of activated de-granulated platelets. Increase in activated
inhibiting various platelet activation pathways; partial thromboplastin clotting time and reduction in plasma-
(2) prolonging clotting time and reducing

Phytother. Res. 30: 701–731 (2016)


(Continues)
Table 5. (Continued)

Level of
Reference Location Plum product investigated Sample/method evidence* Effects observed/conclusion

fibrinogen concentration; and (3) exhibiting fibrinogen and malondialdehyde levels, a plasma biomarker
favourable effects on lipid profile and of oxidative stress.
inflammation.
n = 21
Study design/methods: randomized, double
blind, placebo crossover trial. Healthy
volunteers randomly assigned to three
supplement groups of A-Queen Garnet

Copyright © 2016 John Wiley & Sons, Ltd.


plum juice, B-prune juice or C-colour
matched placebo. Blood samples were
collected at least 8 h pre-prandial and mid-
stream fasting urine samples collected.
Sample size power: not stated.
Dose: 200 mL/day of each juice.
Duration: 28 days with 2 weeks washout
period.
(Santhakumar et al., Australia Plum juice Hypothesis: anthocyanin-rich Queen Garnet II Exploratory Inhibition of adenosine diphosphate-induced platelet
2015b) (P. salicina) Plum Juice may impart anti-thrombotic aggregation both without and under exercise induced
effects via (a) inhibition of platelet oxidative stress, inhibition of arachidonic acid-induced
aggregation by simultaneously targeting aggregation under oxidative stress. Also, there was
different platelet activation pathways reduced platelet activation-dependant
(adenosine diphosphate: ADP-P2Y12/ P-selectin expression both without and under
P2Y1; collagen: GPVI/α2β1 and arachidonic oxidative stress. Favourable effects on
acid: cyclooxygenase-1–COX-1), (b) coagulation parameters both with and without
reducing platelet hyper-activation and de- oxidative stress were also observed.
granulation by blocking surface receptors
responsible for activation, and (c) favourably
altering coagulation parameters and lipid profile.
n = 13
Study design/methods: randomized, double
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

blind, placebo crossover trial. Healthy


volunteers randomly assigned to two
supplement groups of A-Queen Garnet
plum juice or B-a flavoured and coloured
formulated cordial placebo. Oxidative
stress was induced by constant load
exercise bout for 1 h at 70% of their
VO2PEAK Blood samples were collected at
fasting state and at least 8–12 h pre-
prandial on day 1 and day 29.

Phytother. Res. 30: 701–731 (2016)


715

(Continues)
716 E. O. IGWE AND K. CHARLTON

*Clinical trials ranked using (NHMRC, 2000) Levels of Evidence Hierarchy where I is a systematic review (highest rating) and IV is a case series or cross-sectional study (lowest rating) and also classified
The quality of the clinical studies included is, at best,
of moderate quality. There were 6 confirmatory studies
of moderate quality (1 on bone health, 2 on different
components of metabolic syndrome, and 3 on satiety
and laxative effect) and 19 exploratory studies. Evi-
dence on the health effect of plums has not been exten-
Effects observed/conclusion

sively studied, and the available evidence needs further


confirmation.

BONE HEALTH

Based on results from 18 studies (2 in vitro, 12 animal


studies and 4 clinical trials) reported in this review,
promising evidence exists on the effect of plum on bone
health. This body of evidence has mostly been in agree-
ment and also confirmed in human trials. Bu et al. (2008)
in their in vitro study involving two groups investigated
the effect of dried plum polyphenols on osteoclastogen-
esis in which one group was stimulated with lipopolysac-
charide (LPS) to induce inflammation and the other
evidence*

group stimulated with hydrogen peroxide (H2O2) to


Level of

induce lipid peroxidation. It was observed that the


LPS-stimulated sample produced NO (nitric oxide)
detectable at 8 h, which further increased at 16 h, while
the H2O2 stimulated cells did not produce NO. This in-
crease in NO associated with LPS was downregulated
by different doses (10, 20, 30 μg/mL) of plum polyphe-
nol at both 8 h and 16 h. The authors concluded
that dried plum polyphenols directly inhibit osteoclasto-
Duration: 28 days with 2 weeks washout

genesis, which leads to reduced osteoclast activity by


downregulation of Nuclear factor of activated T-cells,
Sample/method

cytoplasmic 1 (NFATc1) and inflammatory mediators.


Dose: 200 mL/day of each juice.
Sample size power: not stated.

The results from this in vitro experiment by Bu et al.


(2008) has also been confirmed in animal studies
(Deyhim et al., 2005; Franklin et al., 2006; Bu et al.,
2007; Smith et al., 2014a). Among these, the study by
Smith et al. (2014a) is slightly different in that unlike
the other studies that studied longer term effects of
dried plum on systemic biochemical markers of bone
metabolism and alteration in gene expression as the
period.

main outcome measure, their main objective was to un-


derstand the mechanism of action by which dried plum
altered bone metabolism. Regulators of osteoblast and
Plum product investigated

osteoclast differentiation and osteoblast activity were


LDL, low-density lipoprotein; HDL, high-density lipoprotein.

studied over a period of 6 weeks. Compared with the an-


abolic therapy using parathyroid hormone that signifi-
cantly increased systemic and local indicators of bone
formation with no effect on systemic marker of bone re-
sorption, dried plum supplementation suppressed bone
turnover with no effect on the indices of bone formation
at the endocortical surface. In another study by the
as exploratory or confirmatory studies.

same research team, dried plum supplementation ini-


Location

tially suppressed cancellous bone turnover but demon-


strated a biphasic response over time, exerting positive
effects on bone mass and bone structure (Smith et al.,
2014b). Plum extract has also been shown to be effective
Table 5. (Continued)

in increasing bone calcium retention by 20%


(Pawlowski et al., 2014).
Rendina et al. (2013) compared the dried plum with
other dried fruits (apple, apricot, grape and mango)
and observed that only the dried plum had an anabolic
Reference

effect on trabecular bone in the vertebra and prevented


bone loss in the tibia. This demonstrates a potentially
unique effect of plum that was absent in the other fruits
Copyright © 2016 John Wiley & Sons, Ltd. Phytother. Res. 30: 701–731 (2016)
Table 6. Evidence on the satiety and laxative effect of plums and its associated products

Plum product Level of


Reference Location investigated Sample/method evidence* Effects observed

Clinical trials
(Piirainen et al., Finland Prune juice (prepared from Hypothesis: prune juice alone may have a IV Confirmatory Laxative effect with increased flatulence.
2007) plum juice concentrate, laxative effect on the bowel function of those
prune puree, water and adults with certain gastrointestinal symptoms
7% fructose) but are otherwise healthy.
(Prunus domestica) n = 54 volunteers with mild GIT symptoms.
Study design/methods: 1 week baseline

Copyright © 2016 John Wiley & Sons, Ltd.


period, 2 week prune juice (consumption)
period followed by 1 week follow-up period
with daily record of bowel habit
Sample size power: not stated.
Dose: 125 mL twice a day.
Duration: 4 weeks.
(Cheskin et al., USA Plum juice Hypothesis: plum juice supplementation diet II Confirmatory Constipation relief and stool softening
2009) (P. domestica) would induce significant improvements in evident with consumption of plum juice.
bowel frequency, and consistency, and
possibly decrease appetite compared with
baseline as well as placebo and psyllium
treatments.
n = 36 adults with chronic constipation
symptoms.
Study design/methods: randomized
controlled crossover trial. Consumption of a
daily portion of plum juice in comparison with
psyllium and apple juice in adults with chronic
constipation symptoms.
Sample size power: not stated.
Dose: 8 oz (237 mL) per day.
Duration: 14 days.
(Attaluri et al., USA Dried plum Hypothesis: dried plums are as effective as II Confirmatory Effective treatment with dried plum on
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

2011) (P. domestica) psyllium in the treatment of adults with mild to moderate constipation observed.
chronic constipation.
n = 40 patients with chronic constipation.
Study design/methods: single blind,
randomized cross-over study. Consumption of
a daily portion of dried plums or psyllium for a
treatment period of 3 weeks after which
participants continued on their usual remedies
for constipation for another 6 weeks. For the

(Continues)

Phytother. Res. 30: 701–731 (2016)


717
Table 6. (Continued)
718

Plum product Level of


Reference Location investigated Sample/method evidence* Effects observed

duration of the study, subjects maintained


daily symptom and stool diaries.
Sample size power: 80%.
Dose: 50 g twice a day with meals.
Duration: 14 weeks (with 1 week washout
period between treatments).
(Farajian et al., Greece Prunes Hypothesis: a preload including dried prunes II Exploratory Reduced consumption of dessert with
2010) (P. domestica) consumed as a snack before a meal, lower energy intake observed. An increased

Copyright © 2016 John Wiley & Sons, Ltd.


compared with an isoenergetic bread product satiety at all time points between snack and
preload, would reduce (a) meal time energy intake, meal was also observed.
(b) appetite for dessert offered after lunch and,
(c) energy intake for the next 24 h.
n = 45 normal weight subjects.
Study design/methods: randomized cross-
over study. Fasting participants offered a
standardized breakfast followed by a preload
of either dried prunes or bread product after
2 h. Three hours after the preload, a
standardized lunch and desert was provided.
Subjects also rated their hunger, thirst, desire
to eat, motivation to eat and satiety on 100 mm
line visual analogue scales just before and right
after the preload consumption, every 45 min up
till the 180th minute On completion of the test
E. O. IGWE AND K. CHARLTON

day, detailed record of all foods and beverages


intake for the next 24 h was collected.
Sample size power: not stated.
Dose: five prunes (40 g) before meals on each
testing day.
Duration: 2 days (with 1 week washout period).
(Furchner-Evanson USA Dried plum Hypothesis: snack choices similar in fat, II Exploratory Satiety index area under the curve greater
et al., 2010) (P. domestica) protein, carbohydrate and sugar contents for dried plum trial. Consumption of the dried
while differing in fibre content have an effect plum elicited lower plasma glucose and insulin
on satiety, subsequent food intake and plasma area under the curve and tended to promote
glucose, insulin and ghrelin responses. a greater plasma ghrelin antioxidant capacity.
n = 19 healthy female subjects
Study design/methods: randomized crossover
study with at least 1 day washout. Subjects
randomly assigned to receive four different test
foods including dried plums. Blood samples

Phytother. Res. 30: 701–731 (2016)


(Continues)
Table 6. (Continued)

Plum product Level of


Reference Location investigated Sample/method evidence* Effects observed

collected at baseline and every 15 mins in 1 h


then 90 and 120 mins.
Sample size power: not stated.
Dose: served in a 238 kcal (1000 kj) portion.
Duration: not stated.
(Howarth et al., USA Dried plum Hypothesis: snack selection (dried plums vs II Exploratory No change observed with energy intake or
2010) (P. domestica) common carbohydrate-rich low-fat cookies) weight. In comparison with cookie, dried
influences daily energy consumption, nutrient plum promoted greater intake of fibre,

Copyright © 2016 John Wiley & Sons, Ltd.


intake and metabolic responses. potassium, riboflavin, niacin and calcium.
n = 26 healthy female subjects There was an observed reduction in total fat
Study design/methods: randomized crossover as well as cholesterol intake with dried plum
study with 2 weeks washout. Subjects snacks. Dried plum did not alter plasma
randomly assigned to receive either dried triglyceride concentration but softer stool
plums or low-fat cookies for two separate consistency was observed with dried plum
2-week feeding. A 7 day bowel habit consumption.
questionnaire was completed.
Sample size power: 80%
Dose: served in a 100 kcal portion
twice a day.
Duration: 4 weeks.
(Lucas et al., 2004) USA Dried plum Hypothesis: dradual incorporation of 100 g of II Exploratory With both dried plum and apples, there was no
(P. domestica) dried plum into the daily diet of healthy statistically significant differences observed
postmenopausal women would not cause for any of the parameters used to assess
significant changes in self-reported bowel bowel function.
habits including frequency of defecation, This indicates the absence of any negative side
faecal bulk and stool consistency. effects associated with prune consumption.
n = 58
Study design/methods: randomized
controlled trial. Postmenopausal women
randomly assigned to treatment groups of
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

dried plum (100 g/d) or dried apple (75 g)


daily for 3 months. A 7 day bowel habit
questionnaire was completed.
Sample size power: not stated
Dose: 100 g/day.
Duration: 3 months.
(Pasalar et al., Iran Prunes Hypothesis: prunes and flixweed are effective II Exploratory Using Rome III criteria to define constipation
2013) (P. Domestica) in the prevention of constipation among (less than three times of defecation/week,
Iranian pilgrims who attended the Hajj with straining, difficulty in defecation,
ceremony in 2010 in the kingdom of Saudi Arabia. unproductive urges, feeling

Phytother. Res. 30: 701–731 (2016)


719

(Continues)
720

Copyright © 2016 John Wiley & Sons, Ltd.


Table 6. (Continued)

Plum product Level of


Reference Location investigated Sample/method evidence* Effects observed

Study design/methods: randomised controlled of anorectal obstruction, hand manoeuver to


trial. 170 Iranian Hajj pilgrims randomly assigned facilitate stool extraction and feeling of
to two groups of case and control. Case group incomplete evacuation), a statistically
received measured doses of prunes and flixweed significant difference was observed
daily before lunch and dinner and control group between the groups with the case group
had their meals with no intervention. less constipated.
Sample size power: not stated
Dose: 40–50 g/day with 10–15 g of flixweed.
Duration: 3 weeks.

*Clinical trials ranked using (NHMRC, 2000) Levels of Evidence Hierarchy where I is a systematic review (highest rating) and IV is a case series or cross-sectional study (lowest rating) and also classified
E. O. IGWE AND K. CHARLTON

as exploratory or confirmatory studies.

Phytother. Res. 30: 701–731 (2016)


Table 7. Evidence on the anti-allergic, anti-microbial and immune-enhancing property of plums and its associated products

Plum product Level of


Reference Location investigated Sample/method evidence* Effects observed

In vitro studies
(Cevallos-Casals et al., USA Plum extract Plum extract placed in a well with diluted Inhibitory effects against Escherichia coli

Copyright © 2016 John Wiley & Sons, Ltd.


2006) (Prunus salicina) bacteria inoculum. 0157:H7 and Samonella enteritidis.
(Yaqeen et al., 2013) Pakistan Prune extract Ethanol extracts of prunes tested against nine Antibacterial activity observed.
(Prunus domestica) bacteria; five gram-positive bacteria
(Staphylococcus aureus, Streptococcuc
intermedias, Bacillus cereus, and Bacillus pumilus)
and four gram-negative bacteria (Eschrichia coli,
Proteus mirabilis, Shigella flexneri, Salmonella
typhi and Klebsiela pneumoniae).
Animal studies
(Karasawa et al., 2012) Japan Prune extract Dietary supplementation with 25% ovalbumin Reduction in allergic response in comparison
(P. salicina) and 1% prune extract over 6 weeks in rats with control group
injected 20 L of distilled water containing 20 g
of mite allergen between the 3rd to 6th week
(Lee et al., 2008) USA Plum powder Dietary supplementation with 0.5% or 1.0% Increase in body weight gain, levels of
(P. salicina) plum in 1-day old chickens and oral MRNAs for interferon-ϒ and interleukin-15.
inoculation with 5000 sporulated oocysts of There was a reduction in faecal oocyst
Eimeria acervulina at day 12 post-hatch. shedding and chickens fed the plum
supplemented diets exhibited greater spleen
cell proliferation
(Noratto et al., 2014) USA Plum juice Administration of plum juice in obese Zucker Several bacteria groups (e.g. Lactobacillus
(P. domestica) rats for 11 weeks. Body weight recorded once and members of Ruminococcacea) were
a week. found to be more abundant in the plum
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

group. There was also a distinct contrast


between the microbiota of control and
treatment groups.

*Clinical trials ranked using (NHMRC, 2000) Levels of Evidence Hierarchy where I is a systematic review (highest rating) and IV is a case series or cross-sectional study (lowest rating) and also classified
as exploratory or confirmatory studies.

Phytother. Res. 30: 701–731 (2016)


721
722

Table 8. Evidence on the effect of plum and its associated products on liver function and kidney stone risk factors

Plum product
Reference Location investigated Sample/method Level of evidence* Effects observed

Clinical trials
(Ahmed et al., 2010b) Pakistan Prune juice Hypothesis: prune juice does not alter liver function. II Exploratory Liver function test showed significant

Copyright © 2016 John Wiley & Sons, Ltd.


(Prunus domestica) n = 107 healthy volunteers reduction of serum alanine transaminase
Study design/methods: case–control study. and serum alkaline phosphatase but no
Participants randomly assigned to three different effect on serum aspartate transaminase
groups of A (single dose of 1 pack of prunes = and bilirubin
11.43 kg, i.e. three prunes), B (control; a glass of
water) and C (double dose of group A) consumed
daily. Blood samples were taken on week zero and
week 8 for liver function tests, that is, serum
alkaline phosphatase, bilirubin, aspartate
transaminase and alanine transaminase.
Sample size power: not stated
Dose: three prunes (~11.43 g) or a double dose
of six prunes (~22.86 g) per day.
Duration: 8 weeks.
(Keßler et al., 2002) Germany Plum juice Hypothesis: plum, cranberry- and blackcurrant II Exploratory No significant effect on urinary biochemical
(P. domestica) juice may have an influence on the urinary or physiochemical parameters
E. O. IGWE AND K. CHARLTON

composition and therefore on multiple risk


factors of kidney stone formation.
n = 12 healthy male subjects.
Study design/methods: Participants control-
fed a standardized diet daily with plum juice.
Twenty four-hour urine sample collected.
Sample size power: not stated
Dose: 330 mL of plum juice.
Duration: 5 days

*Clinical trials ranked using (NHMRC, 2000) Levels of Evidence Hierarchy where I is a systematic review (highest rating) and IV is a case series or cross-sectional study (lowest rating) and also classified
as exploratory or confirmatory studies.

Phytother. Res. 30: 701–731 (2016)


Table 9. Quality rating of included clinical studies using relevant criteria from the Delphi List, Cochrane Back Review Group and the CONSORT Statement (Verhagen et al., 1998; Van Tulder et al.,
2003; Schulz et al., 2010)

J Wom Health Appl Physiol Nutr Am J Clin Nutr J Am Coll Nutr J Food Nutr Res
J Nutr (2011) 106: Gend-B (2002) 11: Br J Nutr (2014) Metab (2014) 39: (2002) 76: (2007) 26: J Med Food (2005) (2011) 50:
923–930 61–68 112: 55–60 730–739 1422–1427. 170–181. 8(1): 41–46. 229–236.

n = 160 dried plum n = 58 dried plum n = 160 dried plum n = 23 dried plum n = 19 dried plum n = 6 dried n = 10 plum juice n = 18 dried plum
(Prunus domestica) (P. domestica) (P. domestica) (P. domestica) (P. domestica) plum/dried plum (P. salicina) Single (P. salicina)
100 g/day versus 100 g/day versus 100 g/day versus 90 g/day + resistance 100 g/day versus juice (P. domestica) dose of 150 mL 2 × 195 g/day Case
dried apple Parallel dried apple Parallel dried apple Parallel training versus habitual dietary 131 g versus versus selected series 5 days
12 months 3 months 1 year resistance training simple sugars selected fruits fruit juices Cross-over
case–control 6 months Cross-over 6 months Cross-over 2 weeks 18 days

Copyright © 2016 John Wiley & Sons, Ltd.


A Postmenopausal Postmenopausal Women with Female breast cancer Postmenopausal Healthy volunteers Healthy volunteers Healthy volunteers
women (Osteopenic) women mild bone loss survivors women (Healthy)
B Yes Yes Yes Yes No Yes No Not applicable
C No (not feasible) No (not feasible) No (not feasible) No (not feasible) No (not feasible) No No Not applicable
D Yes Yes Yes Yes Yes Yes Yes Yes
E Yes Yes Yes Yes Yes Yes Yes Yes
F Yes Yes Yes Yes Do not know Yes Yes Not applicable
G Yes Yes Yes Yes Yes Yes Yes Yes
H Yes Yes Yes Yes Yes Yes Yes Yes
I Yes Yes Yes Yes Yes Probably no Probably no Probably no
J No No No No No No No No
K Yes Yes Yes Yes Yes Yes Yes Yes
L Yes Yes Yes Yes Yes Yes Yes Yes
TS 10 10 10 9 8 9 8 7

J Food Biochem Am J Clin Nutr J Acad Nutr Diet Curr Top Nutraceut J Ayub Med Coll J Funct Foods J Funct Foods Nutr Res Internet J Nutr
(2012) 36: 159–170. (1991) 53 (5): (2012) 112: R (2009) 7: Abbottabad (2010a) (2015a) 12: (2015b) 14: (2007) 27: Wellness (2009)
1259–1265 1158–1168. 157–160 22(1): 38–31 11–22 747–757 511–513. 7: 1-1

n = 2 plum juice n = 41 prunes n = 160 dried plum n = 8 prunes n = 259 prunes n = 21 plum juice n = 13 plum juice n = 54 prune juice n = 36 Plum juice
(Prunus. salicina) (P. domestica) (P. domestica) 143 g/day versus (P. domestica) (P. salicina) (P. salicina) (P. domestica) (p. dometica)
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina)

Single dose of 100 g/day versus 100 g/day versus eight different fruits 11.5 g or 23 g/day 200 mL/day versus 200 mL/day versus 2 × 125mL/day 8 ounces/day vs
400 mL versus 360 mL grape juice dried apple Parallel Cross-over versus water Parallel prune juice/placebo placebo Cross-over Case-series 4 weeks psyllium and apple
400 mL water Cross-over 8 weeks 12 months 8 weeks Cross-over 28 days 28 days juice Cross-over
Cross-over 1 week 6 weeks
A Healthy volunteers Free living men Postmenopausal Healthy young men Pre-hypertensive Healthy volunteers Healthy volunteers Adults with mild Adults with chronic
with mild women patients GIT symptoms constipation
hypercholesterlemia symptoms
B No Not stated Not stated No Not stated Yes Yes Not applicable Yes
C No (not feasible) No (not feasible) No (not feasible) No (not feasible) No (not feasible) Yes Yes Not applicable no (not feasible)
D Yes Yes Yes Yes Yes Yes Yes Yes Yes

Phytother. Res. 30: 701–731 (2016)


723

(Continues)
724

Table 9. (Continued)

E Yes Yes Yes Yes Yes Yes Yes Yes Yes


F Yes Yes Yes Yes Yes Yes Yes Not applicable Yes
G Yes Yes Yes Yes Yes Yes Yes Yes Yes
H Probably no Probably no Yes Yes Yes No No Yes Yes
I Yes Yes Yes Yes Yes Yes No Probably no Yes
J No No No No No No No No No
K Yes Yes Yes Yes Yes Yes Yes Yes Yes
L Yes Yes Yes Yes Yes Yes Yes Yes Yes

Copyright © 2016 John Wiley & Sons, Ltd.


TS 8 8 9 8 8 9 8 7 10

Aliment Pharm Ther Eat Behav (2010) Appetite (2010) J Am Diet Assoc J Appl Res Res J Pharm Biol J Pharm Sci
(2011) 33: 822–828 11(3): 201–203 3: 564–569 (2010) 9: (2004) 4: 37–43 Chem Sci (2013) (2010b) 23:
1322–1327 2: 1195–1204 463–466.

n = 40 dried plum n = 45 prunes n = 19 dried plum n = 26 Dried plum n = 58 dried plum n = 170 dried n = 107 prunes
(P. domestica) (P. domestica) 40 g (P. domestica) (P. domestica) (P. domestica) plum and flixweed (P. domestica) three
2 × 50 g/day versus prune pre-load 238 kcal portion 100 kcal portion 100 g/day versus (P. domestica) groups of either
psyllium Cross-over versus bread versus baked foods versus low fat dried apple Parallel 40–50 g/day Parallel single dose, double
14 weeks product Cross-over and water Cross-over cookies Cross-over 3 months 3 weeks dose or control
over 1 week 4 weeks case–control 8 weeks
A Patients with Normal weight Healthy female Healthy female Postmenopausal Iranian Hajj pilgrims Healthy volunteers
chronic constipation individuals subjects subjects women
B yes Yes Yes Yes Yes Yes Yes
E. O. IGWE AND K. CHARLTON

C No (not feasible) No (not feasible) No (not feasible) No (not feasible) No (not feasible) No (not feasible) No (not feasible)
D Yes Yes Yes Yes Yes Yes Yes
E Yes Yes Yes Yes Yes Yes Yes
F Yes Yes Yes Yes Yes No Yes
G Yes Yes Yes Yes Yes Yes Yes
H Yes Yes No No Yes Yes Yes
I Probably no Probably no Yes Yes Yes Yes Yes
J no No No Yes No No No
K yes Yes Yes Yes Yes Yes Yes
L yes Yes Yes Yes Yes Yes Yes
TS 9 9 8 9 9 8 10

An eligibility criteria specified, B randomization appropriate, C treatment allocation concealed, D similarity at baseline, E outcome measures and control intervention explicitly described, F co-intervention
comparable, G outcome measures relevant, H adverse events and I drop-outs fully described, J sample size based on a priori power calculation, K point estimates and measures of variability presented for
the primary outcome measure, L appropriate timing giving a total score (TS) of 12.

Phytother. Res. 30: 701–731 (2016)


HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina) 725

studied. This anabolic effect of dried plum supplementa- and MCF 7 hormone-dependent breast cancer cells),
tion has also been observed by others (Halloran et al., this inhibitory effect was not observed in the hormone-
2010) in animal models. Prevention of age-associated dependent breast cancer cells, and as the fruit ripened,
bone loss was evident because of this anabolic effect, there was a reduction in its inhibitory effect. In a similar
while bone volume increased and already lost bone study, Noratto et al. (2009) aimed to identify the pheno-
was restored. lic fraction responsible for the potential chemopreven-
Investigating further, Monsefi et al. (2013) observed tive and/or chemotherapeutic action in plum. They
the effect of plum extract on bone parameters in the off- observed that all extract fractions were effective in
spring of pregnant mice as well as in non-pregnant mice. exerting antioxidant effect on studied cancer cell lines
Plum extract was orally administered to the sample pop- with the flavonols and procyanidins more effective than
ulation, and results showed that in the non-pregnant the phenolic acids and anthocyanins. This result was
mice, there was an increase in the femoral and tibial also confirmed by Lea et al. (2008) who, in addition,
lengths and serum calcium content, while the foetuses observed that the synergic effect of the total phenolic
and new-borns of the pregnant mice had higher osteo- content of the plum extract significantly increased its an-
genesis index, which was calculated by dividing the ossi- tioxidant activity.
fied length by the total length of each bone. Investigating this antioxidant effect on human colon
Ovarian hormone deficiency, which is evident in post- cancer cells, Fujii et al. (2006) and Lea et al. (2008), in
menopausal women, is a known major risk factor for os- similar studies with prune and plum extract, respec-
teoporosis (Baron, 1993). For this reason, effect of plum tively, observed that the extracts did not reduce the via-
consumption on bone health in human trials has been ble cell number of the human normal colon fibroblast
carried out mostly on postmenopausal women. A die- cells while inducing apoptosis of cancer cells. Noratto
tary supplementation trial compared the effects of con- et al. (2009), among other studies, also observed similar
sumption of dried plum (100 g) with dried apple (75 g) results in their study with breast cancer cell lines.
for 3 months on markers of bone turnover in postmeno- These results have also been confirmed in animal
pausal women (Arjmandi et al., 2002). The difference in studies. Kim et al. (2008) observed that IPE inhibited
the amount of dried plum and dried apple compared the growth of hepatoma HepG2 cells and had a protec-
was related to comparable quantities of energy, carbo- tive effect against benzo(α)pyrene induced liver toxicity
hydrates, fat and fibre, obtainable from 100 g of dried by decreasing serum aminotransferase and hepatic con-
plum. Baseline and post-treatment values of serum and tents of lipid peroxide. In addition to studying the anti-
urinary biochemical markers of bone status showed that oxidant capabilities in animal studies, Mishra et al.
only dried plums significantly increased serum levels of (2012) also observed an anti-ulcer effect after feeding
insulin-like growth factor-1 and bone-specific alkaline Wistar albino rats for 7 days with 100, 150 or 200 mg
phosphatase activity. kg 1 of plum extract and inducing peptic ulcer by pylo-
A similar longer-term randomized controlled study ric ligation. Gastric ulcerative index was estimated,
compared the effects of dried plum and dried apple which showed that the group pre-treated with plum
on osteopenic postmenopausal women for 1 year extract had a significantly reduced gastric volume and
(Hooshmand et al., 2011). In addition to similar results a significantly lower ulcerative index. This anti-ulcer
of Arjmandi et al. (2002), the authors observed that effect was also observed by (Cantu-Jungles et al., 2014)
dried plum significantly increased bone mineral density in which acute gastric ulcer was induced by administra-
of the ulna and spine. tion of ethanol P.A. after different oral treatments,
In a slightly different study, Simonavice et al. (2014) including prune polysaccharides, which showed a reduc-
examined the effects of resistance training and dried tion and inhibition of the gastric lesion area. Yang and
plum consumption on strength, body composition, Gallaher (2005) further investigated the effect of plum
blood markers of bone and inflammation in breast can- on colon cancer risk factors whereby they observed that
cer survivors. They observed that even though the even though dietary supplementation with dried plum
breast cancer survivors increased upper and lower body showed no inhibitory effect on aberrant crypt foci for-
strength, no improvements were observed in their body mation at the initiation stage of cancer and early pro-
composition and bone mineral density. gression, it was able to inhibit several risk factors
associated with colon carcinogenesis. These include
reduction in faecal total and secondary bile acid
concentration, decrease in colonic β-glucuronidase and
7α-dehydroxylase activities and increased antioxidant
ANTIOXIDANT AND ANTIINFLAMMATORY activities.
ACTIVITY Contrary to observing similar results with in vitro and
animal studies, results from human trials have not been
The antioxidant property of plums has mostly been at- in agreement. A study that investigated the plasma anti-
tributed to its high phenolic content (Ko et al., 2005; oxidant capacity changes after a meal observed that con-
Lea et al., 2008). Research on this health effect has sumption of a meal containing dried plum or dried plum
mostly been carried out with the ripe plum fruit or its juice did not alter plasma antioxidant capacity (hydro-
products. Yu et al. (2009a) on the other hand studied philic and lipophilic ORACFL) (Prior et al., 2007). This
the antioxidant effect of immature plum extract (IPE) result was contradicted by the findings of Ko et al.
on selected cancer cells in vitro. The authors observed (2005) that demonstrated that nine different fruit juices,
that even though the IPE was effective in inhibiting including plum juice, exhibited significant antioxidant
growth of the cancer cells (human hepatocellular carci- effects in human plasma within 30 mins of consumption
noma HepG2 cells, Kato III gastric cancer cells, HeLa by suppressing reactive oxygen species generation. Sim-
human cervical carcinoma cells, U937 leukaemia cells ilarly, González-Flores et al. (2011) confirmed the
Copyright © 2016 John Wiley & Sons, Ltd. Phytother. Res. 30: 701–731 (2016)
726 E. O. IGWE AND K. CHARLTON

antioxidant capability of plums in young, middle-aged neurodegeneration-related protein in streptozotocin-


and elderly adults. After consumption of 195 g of plum induced diabetic rats. Cognitive performance, assessed
twice a day for 5 days, there was a significant increase using the Morris water maze, showed that the plum sup-
from baseline in urinary 6-sulfatoxymelatonin (an anti- plemented diet had a significant beneficial effect on spa-
oxidant) and total antioxidant capacity levels measured tial memory and learning. There was also a significant
by colorimetric assay. Similarly, Netzel et al. (2012) ob- reduction in expression of cerebral beta-amyloid, which
served that following consumption of the Queen Garnet is evident in Alzheimer’s disease. Significant decreases
plum juice, there was a threefold increase in hippuric in hyperglycaemia, insulin resistance and oxidative
acid excretion (a potential biomarker for total polyphe- stress in the sample of rats were also observed.
nols intake and metabolite), an increase in urinary anti-
oxidant capacity and a reduction in malondialdehyde
excretion, which is a biomarker for oxidative stress.
CARDIOVASCULAR DISEASE RISK FACTORS

Insulin resistance, a major risk factor for metabolic syn-


COGNITIVE IMPROVEMENT drome and selected cancers, presents a major public
health concern (Tsugane and Inoue, 2010). Studying
Cognitive improvement associated with consumption of the beneficial health effects of plums on cardiovascular
plum has not been extensively studied in humans. Most disease risk factors, Noratto et al. (2015) compared the
of the available evidence is from animal studies. This effect of plum juice with peach juice and a placebo
effect on cognition has mainly been attributed to the an- group, which received the same amount of sugar in
tioxidant property of plums as a result its high polyphe- either peach or plum juice in obese Zucker rats. Their
nolic content. In a study in which four groups of mice results showed that the plum juice group had the lowest
were fed a high-cholesterol diet, with either 2% or 5% weight gain and also that plum polyphenols exerted the
plum powder supplementation, a significant difference highest anti-adipogenic and antiinflammatory effects in
was observed in the time taken to complete the Morris fat tissues. This provides evidence of the reduction of
water maze task between the group fed just the high- mRNA levels of peroxisome proliferator-activated
cholesterol diet and the control group, as well as the receptor associated with plum intake.
5% and 2% plum powder supplementation group Negishi et al. (2007) studied the effect of prune extract
(Kuo et al., 2015). In a similar study but slightly contra- on blood pressure elevation in stroke-prone spontane-
dictory results, Shukitt-Hale et al. (2009) compared the ously hypertensive rats for 5 weeks. They observed that
effects of 100% plum juice and 2% dried plum powder prune extract supplementation in diet suppressed the el-
supplementation to modify age-related deficits in cogni- evation of systolic blood pressure but not diastolic blood
tive function in aged rats. It was observed that there was pressure. A study by Gallaher and Gallaher (2009) on
an improvement in cognition with the plum juice, but apoE-deficient mice, known to be susceptible to rapid
not with the dried plum powder. development of atherosclerotic lesions when fed choles-
Using plum extract, Shahidi et al. (2013) supple- terol, investigated the ability of dried plum supplemen-
mented the diets of three groups of mice with different tation to reduce atherosclerosis. The percentage
doses (75, 100, 150 mg/kg). There was a statistically sig- arterial tree atherosclerotic lesion area was significantly
nificant difference in the number of trials to acquisition lower in groups fed the dried plum supplemented diet
in the passive avoidance test that evaluates learning (4.75%), either with or without cholesterol, compared
and memory between the control group and the plum with the group fed cholesterol without dried plum
extract treated groups. The retention test also showed supplementation.
that the treated groups had increased step through In human trials, results have been inconclusive. Chai
latency in the retention in comparison with the control et al. (2012) studied the effect of daily dried plum con-
group. These results are in line with similar studies sumption in comparison with dried apple on cardiovas-
(Sharma and Sisodia, 2013; Kao-Ting et al., 2013) that cular disease risk factors in postmenopausal women
demonstrate a beneficial health effect of plum on over a 1-year period. Results showed that serum total
cognition. cholesterol levels were significantly lower in the dried
Bouayed et al. (2007) examined the effect of apple group in comparison with the dried plum group
chlorogenic acid from plums on anxiety-related behav- only at 6 months. There was also a cholesterol-lowering
iours in mice using the light/dark test, the elevated plus effect for serum total and low-density lipoprotein cho-
maze and the free exploratory test. Results showed a lesterol at 12 months, but this was not significant.
decrease in anxiety-related behaviours (anxiolytic-like ef- Neither dried apple nor dried plum had a significant
fect) and protection of granulocytes from oxidative stress. effect on the serum levels of atherogenic cholesterol.
Plum consumption protected against oxidative stress Contrary to this observation, Tinker et al. (1991) ob-
induced by radiation with special attention to spatial served that in adult men with mild hypercholesterol-
learning. Sharma and Sisodia (2013) observed that plum emia, supplementation with prunes significantly
possesses prophylactic ability against radiation-induced lowered plasma low-density lipoprotein cholesterol
metabolic disorders and also improved spatial learning. compared with a grape juice control group. A signifi-
Exposed mice that had received plum performed better cantly lower faecal bile acid concentration of lithocholic
by taking less time to reach the coloured platform in the acid was also reported.
circular water tank apparatus (proxy for spatial learning Regarding the effect of prunes on high blood pres-
and memory). Similarly, Kao-Ting et al. (2013) studied sure, Ahmed et al. (2010a) conducted a study with three
the effect of plum consumption for 2 months on groups of pre-hypertensive patients who were random-
cognitive performance and expression of cerebral ized to receive on a daily basis, either a single dose of
Copyright © 2016 John Wiley & Sons, Ltd. Phytother. Res. 30: 701–731 (2016)
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina) 727

prunes (11.5 g), a double dose (23 g) or a glass of water Keßler et al. (2002) studied the effect of plum juice on
(control) for 8 weeks. Participants who received either urinary stone risk factors and observed that plum juice
the single dose or a glass of water on empty stomach had no significant effect on urinary composition. How-
in the morning showed significant reduction in both sys- ever, a study that utilized the Australian Queen Garnet
tolic and diastolic blood pressure, while the double dose plum reported an increase in urinary antioxidant capac-
was associated with only a reduction in systolic blood ity (Netzel et al., 2012).
pressure. The control (water) group also had significant Farajian et al. (2010) studied the short-term effect of
increase in serum high-density lipoprotein that was not prunes included as snacks prior to a meal on energy in-
seen by prune-treated groups take and satiety in normal-weight individuals. This
Plum juice supplementation with the novel-bred Queen study demonstrated that a preload of prunes in com-
Garnet plum that has higher anthocyanin concentrations parison with a bread product before a meal resulted
than the usual variant (Santhakumar et al., 2015a) ob- in lower energy intake at later meals, including lunch
served an inhibition of platelet aggregation induced by and the desert (910 Kcal ± 233 on prunes day vs
adenosine diphosphate, collagen and arachidonic acid. 971 Kcal ± 249 on bread product day. P value 0.010)
as well as increased satiety at all time points tested
between the snack and meal. Similar studies have also
observed similar results (Furchner-Evanson et al., 2010;
LAXATIVE EFFECT Howarth et al., 2010)

Studies have also been carried out on the commonly


known laxative effect of prunes, which has been attrib-
DISCUSSION
uted to its high fibre content. Piirainen et al. (2007)
studied the effect of prunes on individuals with mild gas-
trointestinal symptoms. This study observed that con- This systematic literature review identified 73 peer-
sumption of prune juice reduced the occurrence of reviewed journal articles on the health effects of plum
difficulty in defecation. Similarly, consumption of a daily and its associated products. Despite an increase in
portion of plum juice before a meal in adults with chronic plum-based research that has emerged over the past de-
constipation softened the stool, provided immediate re- cade, the level of evidence remains low. Of 25 clinical
lief and participants showed more preference to prune studies, nine studies included randomization to a plum
juice than apple juice (Cheskin et al., 2009). Similar re- supplementation group, but only one of these studies
sults were also observed with dried plum in patients with adequately described the method of randomization
mild to moderate constipation by Attaluri et al. (2011) in and blinding. Nonetheless, results from some of the
which the effect was attributed to a synergistic effect pro- study outcomes are consistent. Considering bone health
vided by sorbitol, dietary fibre and polyphenols. as the main study outcome, the polyphenols present in
the plum appear to be responsible for the benefits.
However, Hooshmand and Arjmandi (2009) suggested
that even though dried plum polyphenols have some
ANTI-ALLERGY AND ANTIMICROBIAL bone modulating properties, the synergistic effect of
these polyphenols, together with potassium and vitamin
PROPERTY
K, is required to produce potent effects on bone mass
and microarchitecture and to reverse ovariectomy-
On the anti-allergy capability of plum, Karasawa et al. induced bone loss in mature animals. Regardless,
(2012) carried out a study with prune extract diet sup- compared with other dried fruits (apple, apricot, grape
plementation and injection of mite allergen for 3 weeks. and mango), only the dried plum exhibited an anabolic
It was observed that with the prune extract supplemen- effect on trabecular bone in the vertebra and prevented
tation, number of sneezing events, total and mite bone loss (Rendina et al., 2013).
allergen-specific immunoglobulin E levels were signifi- Some of the findings from the in vitro studies have
cantly lower even though they were unable to identify been confirmed in animal studies but remain to be
any anti-allergic components in the prune extract. confirmed in human clinical trials. Most of the available
Studying the antibacterial property of plums, Yaqeen human trials used the dried version of plums rather than
et al. (2013) observed that when tested on five different fresh fruit, thus limiting translation to dietary messages
gram-positive bacteria, ethanol extracts of prunes exhib- of the positioning of plums in a healthy diet. The drying
ited an antibacterial property. This antibacterial prop- process significantly decreases anthocyanin and flavonol
erty was also observed by (Cevallos-Casals et al., 2006) content of plums (Piga et al., 2003). The effect of other
processing methods on the antioxidant properties of
plums has been studied by Valero et al. (2012).
Blanching decreased the tannins and antiradical effi-
OTHER EFFECTS ciency of the fruits but increased the total polyphenol
content, while osmotic dehydration had no effect on
Other reported beneficial health effects of plum include the total polyphenol and ferric reducing power. Fresh
its effect on liver function in healthy individuals. In a plums also have a higher free radical scavenging capac-
clinical trial, Ahmed et al. (2010b) observed a significant ity (superoxide and peroxy radicals) and antioxidant ac-
reduction in serum alanine transaminase and serum al- tivity than dried plums (Morabbi Najafabad and Jamei,
kaline phosphatase (clinical biomarkers of liver health) 2014). Regardless, prunes are known to contain higher
with no changes observed in serum aspartate transami- levels of phenolic compounds than most fruits and also
nase and bilirubin. possess higher radical scavenging activity, even possibly
Copyright © 2016 John Wiley & Sons, Ltd. Phytother. Res. 30: 701–731 (2016)
728 E. O. IGWE AND K. CHARLTON

the highest in dried fruit and vegetable products present dietary importance and are ubiquitously distributed
in human diet (Shahidi, 2012). Further studies are re- (Jaganath and Crozier, 2010). The major anthocyanins
quired to compare the health effects of fresh plum, plum found in the plum are cyanidin (3-rutinoside,
juice and dried plum in human trials. 3-glucoside and 3-xyloside) and peonidin (3-rutinoside
Extraction methodology is also an important factor in and 3-glucoside) (Usenik et al., 2009). Anthocyanins
plum-based research as different solvents have shown are absorbed in the small intestine and colon and
some disparity in extracts. Estimating the antioxidant transported in human serum and urine, mainly as me-
capacity of the whole plum fruit, Dhingra et al. (2014) tabolites to reach target cells (Talavéra et al., 2004;
observed that in extracting the bioactive compound in Kay, 2006). Anthocyanins are known to be natural anti-
plum, the ethyl acetate and butanol fraction showed oxidants and have generated a great amount of interest
the most antioxidant potential in comparison with the among researchers in the last decade. This trend has
hexane and aqueous fraction. also been observed among plum breeders as different
Evidence included in this systematic review was gath- varieties of plum are cultivated through hybridization.
ered from studies that differed in a number of ways, in- One of these hybrids is the Australian Queen Garnet
cluding population studied, study design, outcome plum, a hybrid of the Japanese plum developed through
measures and methods of randomization. This limits a breeding programme funded by the Queensland Gov-
comparison between studies. Limitations related to dif- ernment in Australia. This novel-bred Queen Garnet
ferent study designs are particularly evident in the plum is known for its exceptionally high anthocyanin
animal studies that show inconsistent results. For exam- levels, reaching up to 277 mg per 100 g fruit (Fanning
ple, Kuo et al. (2015) observed significant outcomes on et al., 2013). Even though levels of anthocyanin content
cognition using the Morris water maze task on mice in fruits progressively increase during fruit development
fed a high-cholesterol diet with 2% dried plum supple- and ripening, this is more than two times higher than the
mentation. Conversely, Shukitt-Hale et al. (2009) total anthocyanin content of regular plums that has been
showed that plum juice, but not a dried plum powder reported to range from 5 to 173 mg per 100 g across
(2% concentration), was effective in alleviating cogni- harvest years (Miletic et al., 2012). The beneficial health
tive deficits in aged rats. This may possibly be explained effects of these levels of anthocyanin found in the Queen
by a difference in the dosage of nutrients provided in Garnet plum are currently being researched. Preliminary
the two studies, or the food matrix, or both studies using this variant of plum have demonstrated anti-
(Wesche-Ebeling et al., 1996) but remains to be thrombotic activity in humans (Santhakumar et al., 2015a)
elucidated in dose-response studies. and a beneficial effect on metabolic syndrome in rat
There have been no reports on the side effects associ- models, in vivo and in vitro bioactivity (Bhaswant et al.,
ated with daily consumption of plum and its associated 2015). It is important that similar studies be performed with
products. Studies have shown that consumption of dried different hybrids of plum to confirm their beneficial health
plum over a long period has no significant effect on the effects in the fight against chronic diseases.
levels of insulin and glucose or bowel function Other parts of the plum fruit that are usually
(Hooshmand et al., 2013; Lucas et al., 2004). Regardless, discarded or used in animal feed may also provide food
plums are known to contain considerable levels of oxa- components that confer health benefits. The plum
lates, which occur naturally and may increase the risk pomace, a by-product (pulpy residue) from plum juice
of kidney stone formation (Ruan et al., 2013). High levels has been reported to contain 38-49% dietary fibre and
of oxalate in the body inhibit the absorption of calcium, have antioxidant and anti-inflammatory properties that
thereby resulting in precipitation of calcium, which can have been demonstrated in vitro (Milala et al., 2013).
result in stone formation in the kidney and bladder
(Massey, 2003; Weaver et al., 1987). Keßler et al. (2002)
observed that plum consumption had no significant ef-
fect on the risk factors associated with kidney stone de- CONCLUSION
velopment. These potential side effects have not been
reported with usual plum consumption; however, it is im- In conclusion, this systematic review has identified an
portant to identify the upper level of safe intake. emerging body of evidence that demonstrates the bene-
The increased interest in plum-based research has ficial health effects of plum consumption. The largest
been attributed to the fruit’s high levels of polyphenols amount of evidence to date relates to prevention and
and more recently its anthocyanin (a sub-class of flavo- management of osteoporosis, which shows promising
noids) content. Anthocyanins are water-soluble plant evidence as an adjunctive therapy. However, many of
pigments that are particularly conspicuous in fruits and the study designs were of low quality; therefore, it is im-
flower tissues where they are responsible for the diverse portant that well designed human trials are conducted to
range of red, blue and purple colours. Anthocyanins confirm these observed effects. Consideration of the nu-
are one of the most versatile subclasses of flavonoids tritional composition of plums and prunes and the ef-
that are known to protect chloroplasts from fects of processing on their bioactivity is also important
photodegradation by absorbing high-energy quanta, for future research. Elucidation of the mechanism of ac-
while scavenging free radicals and reactive oxygen spe- tion of plum polyphenols, identification of potential ad-
cies. The key characteristic that differentiates anthocya- verse effects and the effects of dosage on outcomes is
nin glycosides from other subclasses of flavonoid necessary to inform dietary guidelines for chronic dis-
glycosides is their ability to be absorbed after oral inges- ease prevention and management.
tion, although to a limited extent. In nature, about 17
different anthocyanins have been discovered, but only Conflict of Interest
six (cyanidin, delphinidin, petunidin, peonidin,
pelargonidin and malvidin) have been shown to be of The authors of this manuscript have no conflict of interest to declare.

Copyright © 2016 John Wiley & Sons, Ltd. Phytother. Res. 30: 701–731 (2016)
HEALTH EFFECTS OF PLUMS (Prunus domestica AND Prunus salicina) 729

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