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nutrients
Review
A Review of the Health Benefits of Cherries
Darshan S. Kelley 1, 2, *, Yuriko Adkins 1,2 and Kevin D. Laugero 1,2
1US Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center,
Davis, CA 95616, USA; yuriko.adkins@ars.usda.gov (Y.A.); kevin.laugero@ars.usda.gov (K.D.L.)
2Department of Nutrition, University of California, Davis, CV 95616, USA
*Correspondence: darshan.kelley@ars.usda.gov or darshan.kelley@gmail.com
Received: 16 February 2018; Accepted: 14 March 2018; Published: 17 March 2018
Abstract:
Increased oxidative stress contributes to development and progression of several human
chronic inflammatory diseases. Cherries are a rich source of polyphenols and vitamin C which
have anti-oxidant and anti-inflammatory properties. Our aim is to summarize results from human
studies regarding health benefits of both sweet and tart cherries, including products made from
them (juice, powder, concentrate, capsules); all referred to as cherries here. We found 29 (tart 20,
sweet 7, unspecified 2) published human studies which examined health benefits of consuming
cherries. Most of these studies were less than 2 weeks of duration (range 5 h to 3 months) and
served the equivalent of 45 to 270 cherries/day (anthocyanins 55–720 mg/day) in single or split
doses. Two-thirds of these studies were randomized and placebo controlled. Consumption of cherries
decreased markers for oxidative stress in 8/10 studies; inflammation in 11/16; exercise-induced
muscle soreness and loss of strength in 8/9; blood pressure in 5/7; arthritis in 5/5, and improved sleep
in 4/4. Cherries also decreased hemoglobin A1C (HbA1C), Very-low-density lipoprotein (VLDL)
and triglycerides/high-density lipoprotein (TG/HDL) in diabetic women, and VLDL and TG/HDL
in obese participants. These results suggest that consumption of sweet or tart cherries can promote
health by preventing or decreasing oxidative stress and inflammation.
Keywords: cherries; polyphenols; anthocyanins; inflammation; oxidative stress; chronic diseases
1. Introduction
Epidemiological studies indicate an inverse association among fruit and vegetable intake and the
risk for several chronic inflammatory diseases [
1
,
2
]. Consumption of fruits and vegetables has been
reported to reduce the risks of all-cause mortality, and morbidity and mortality from cardiovascular
disease (CVD), stroke, diabetes, and some cancers [
3
–
6
]. Besides providing essential vitamins, minerals,
carotenoids and dietary fiber, fruits contain polyphenols [
7
–
9
] which are believed to decrease risk for
metabolic syndrome, diabetes, nonalcoholic fatty liver disease (NAFLD) and CVD [10–17].
The cherry fruit is a nutrient dense food with relatively low caloric content and significant amounts
of important nutrients and bioactive food components including fiber, polyphenols, carotenoids,
vitamin C, and potassium [
18
]. In addition, cherries are also good source of tryptophan, serotonin, and
melatonin [
19
,
20
]. While there are more than a hundred cultivars of cherries, they are grouped into two
major types, the sweet (Prunus avium L.) and tart (Prunus cerasus L.) cherries [
21
]. The most commonly
grown cultivar of sweet cherries in the USA is Bing and for the tart is Montmorency. The majority of
sweet cherries are consumed fresh with the remaining 20–25% processed as brined, canned, frozen,
dried, or juiced. In contrast, 97% of tart cherries are processed primarily for cooking and baking [18].
Both sweet and tart cherries are rich in polyphenols [
18
,
21
,
22
]. Many factors including the cultivar,
stage of ripening, portion of fruit, storage, and others contribute to the polyphenolic concentration
and composition of cherries [
22
]. Cyanidin-3-glucoside and cyanidine-3-rutinoside are the major
anthocyanins in both Bing and Montmorency cherries. In addition to the anthocyanins, cherries are
Nutrients 2018,10, 368; doi:10.3390/nu10030368 www.mdpi.com/journal/nutrients
Nutrients 2018,10, 368 2 of 22
also rich in hydroxycinnamates and Flavin-3-ols. Hydroxycinnamates and Flavin-3-ols respectively
make up about 25% and 40% of the total phenolics in Montmorency cherries and 50% and 5% in Bing
cherries [
23
,
24
]. Other flavonoids make up the remainder of the phenolics in both sweet and tart
cherries [18].
Published literature suggested that tart cherries had higher concentrations of total phenolic
compounds while the sweet cherries contained more anthocyanins [
18
]. Thus, the total phenolics
for the flesh, pits, and skins of Bing cherries were 134, 92, 333 mg/100 g fresh weight, and the
corresponding values for Montmorency cherries were 301, 157, and 558 mg/100 g, respectively [
18
,
25
].
The total anthocyanin concentrations for Bing cherries were 26.0, 10.4, and 60.6 mg/100 g of flesh,
pits, and skins, while the corresponding values for the Montmorency cherries were 0.0, 0.8, and
36.5 mg/100 g, respectively [
18
,
26
]. Anthocyanin concentrations in 10 other cultivars of red sweet
cherries (Benton, Black Gold, Glacier, Hedelfingen, Kiona, Kordia, Kristin, Regina, Selah and Skeena)
ranged from 82–297 mg/100 g; yellow sweet cherries (Gold and Rainer) 2–41 mg/100 g, and for red
sour cherries (Montmorency and Balton) 27–76 mg/100 g [
27
]. Total anthocyanin in six other cultivars
of sweet cherries (Delta Marca, Celste, Bigarreau, Durone Nero, Lapins and Moretta) ranged from
2.1–344.9 mg/100 g fresh weight (approximately 0.6–22% of the total phenolics) [
28
]. Thus, there is
wide range in the concentration of anthocyanins in the different cultivars of cherries which may be due
to the factors listed above and the precision of the analytical methods used. Further analyses under
identical conditions are needed to compare the phenolic composition of specific cultivars of cherries.
Melatonin is another antioxidant which is linked to sleep regulation, and is found in both sweet and
tart cherries; its concentration ranged from 10–20 ng/g fresh weight in both Hongdeng and Rainier
ripe sweet cherries [
29
] and it was 2.1 ng/g and 13.5 ng/g, in Balton and Montmorency tart cherries,
respectively [30].
The antioxidant capacity of sweet and tart cherries varied when compared using different test
systems. Thus, in the oxygen radical absorbing capacity (ORAC) and ferric reducing ability of plasma
(FRAP) assays, the edible portion of the Montmorency cherries had greater antioxidant activity than
those in the sweet cherries [
18
], however, in a liposome-based system, the sweet cherries exhibited
the highest antioxidant activity [
27
]. Recent
in vitro
studies have shown that the antioxidant effect
between anthocyanins and quercetins/ascorbic acid was synergistic in the Sandra Tardiva cultivar of
sweet cherries [22].
Both anthocyanins and hydoxycinnamates are believed to be rapidly absorbed in humans reaching
maximum plasma concentrations in less than 2 h and are quickly eliminated [
31
,
32
]. Low plasma
concentrations may also result from the inability to measure some of their metabolites. Results of a
recent study in healthy men using
13
C labelled cyanidine-3-glucoside, reported that the serum peak
concentration reached at 10.2 h after the ingestion and metabolites of anthocyanin were present in
the serum for greater than 48 h. The amount of
13
C in urine, fecal and breath samples collected in
48 h accounted for 12.3% of the
13
C consumed [
33
]. These findings suggest that anthocyanins have a
minimum of 12.3% bioavailability and their metabolites remain in circulation longer than previously
believed. Further studies are needed to confirm the bioavailability of anthocyanins.
Given the high concentrations of bioactive compounds (e.g., anthocyanins, hydoxycinnamates,
Flavin-3-ols) in cherries, it is not surprising that cherry consumption promotes health. Results from
published animal and human studies suggest that consumption of cherries may reduce the risk of
several chronic inflammatory diseases including, arthritis, cardiovascular disease (CVD), diabetes, and
cancer. Furthermore, there is evidence that cherry consumption may improve sleep, cognitive function,
and recovery from pain after strenuous exercise. Some of these findings have been reviewed [
18
,
34
,
35
].
Since the last published review on the health benefits of cherries (Bell et al., 2014), another review
has been recently accepted for publication [
36
]. This recent review focuses on the anti-arthritic effects
of tart cherries and the fate of phytochemicals in the human gastrointestinal tract. Our review that
follows includes all published effects of both sweet and tart cherries on markers of oxidative stress,
inflammation, exercise-related muscle damage, arthritis, diabetes, cardiovascular disease, sleep, and
Nutrients 2018,10, 368 3 of 22
cognitive functions. Our objective is to summarize the results from human studies regarding the health
benefits of cherries or products (juice, powder, concentrate, capsules) made from sweet or tart cherries.
Results from animal and cell culture studies are also included to support the findings from human
studies or to highlight the potential mechanisms involved. We used PubMed and Google scholar to
find published human studies with cherries or cherry products. A total of 29 studies were found and
are discussed below.
2. Clinical Studies Involving Consumption of Cherries and Their Products
We found a total of 29 human studies that examined health promoting effects of cherries or
products derived from cherries. Twenty of these studies used tart cherries or products, 7 used sweet
cherries or products, and 2 used fresh and canned cherries but did not specify whether the products
were derived from tart or sweet cherries. Since cherries used as fresh are often sweet, it is likely that
these two studies used either sweet or both sweet and tart cherries. All published human studies
with cherries were grouped according to the clinical end points being investigated and are listed in
Table 1. Responses tested include oxidative stress (10 studies); markers of inflammation (16 studies);
exercise induced pain, muscle damage and recovery (9 studies); risk factors for diabetes and CVD
including hemoglobin A1C (HbA1C), blood pressure and lipids (9 studies); markers for arthritis
besides inflammation (5 studies); quality and quantity of sleep (4 studies); stress, anxiety, mood,
memory and cognitive functions (3 studies). Many of the studies tested more than one type of those
response variables.
Table 1.
List of Cherry studies investigating biological or clinical markers for pre-disease and
disease conditions.
Medical Condition Investigators Who Examined the Effect of Cherries or Cherry Products on Markers for
Listed Conditions
Oxidative stress
Total studies 10.
↓in 8 studies [37–45].
No change in 2 studies [46,47].
Inflammation
Total studies 16.
↓in 11 studies [37–41,44,46,48–52].
↑in 1 study [53].
No change in 4 studies [47,54–56].
Exercise induced pain, muscle damage,
and recovery
Total studies 9.
↓Pain, soreness, or muscle damage in 8 studies [37,39,41,44,46,49,57,58].
No change in 1 study [47].
Risk factors for diabetes and
cardiovascular disease
↓HbA1C in diabetic women [59]; no change in fasting glucose or insulin [23,45,51] in
healthy subjects;
↓
VLDL & TG/HDL ratio in obese [
52
] but no change in VLDL, LDL, HDL, TG, lipoprotein
particle size and number in healthy [23,42,45].
↓SBP [51,54,60,61];
↓both SBP and DBP [59,62];
No change in either SBP or DBP [42].
↓ENRAGE, EN-1, PAI-1 [51]
Arthritis and associated risk factors
↓gout attacks [63,64];
↓Osteoarthritis [55];
↓plasma uric acid [40,52,63]
Sleep Total 4 studies.
↑quantity and quality of sleep [38,39,53,65,66]
Stress, anxiety, mood, memory and
cognitive functions
↓Urinary cortisol, stress, anxiety, and improved memory, mood, and cognitive functions
[19,38].
NC in cognitive functions within 5 h of a TC concentrate [60]. Serum cortisol
↓[41,46] and NC [50].
VLDL, very low density lipoprotein; TG/HDL, triglycerides/high-density lipoprotein; HDL, high-density
lipoprotein; LDL, low-density lipoprotein; SBP, systolic blood pressure; DBP, diastolic blood pressure; ET-1,
endothelin-1; ENRAGE, extracellular newly identified ligand for the receptor for advanced glycation end products;
PAI-1, plasminogen activator inhibitor-1; NC, no change; TC, tart cherry.
Table 2lists characteristics of the study participants, study design and duration, treatment and
dose, and the major findings of the individual studies. Study participants included ranged from young
Nutrients 2018,10, 368 4 of 22
athletes to elderly with dementia, insomnia, arthritis, or other chronic conditions. Both male and
female subjects were included with a sample size ranging from 9 to 633. The daily dose of cherries
used ranged from 45 to 270 cherries (anthocyanins 55–720 mg/day), which were served as a single
dose or split into 2 or 3 doses. Nineteen of the studies used randomized, placebo-controlled design
with a cross-over or parallel format; there were 10 studies which did not include the control groups
and tested the responses before and after cherry consumption. Study duration ranged from 5 h to
3 months. Results from these studies are discussed below.
2.1. Effects of Cherries on Oxidative Status, Inflammatory Response, Exercise-Induced Pain, Muscle Damage,
and Recovery
Polyphenols, melatonin, carotenoids, and vitamins E and C all contribute to the antioxidant and
anti-inflammatory properties of cherries [
18
,
21
,
22
,
34
,
67
]. Markers of oxidative stress monitored in the
human studies with cherries included plasma/serum ORAC, FRAP, trolox equivalent antioxidant
capacity (TEAC), F-2 isoprostane, nitrotyrosine (NT), superoxide dismutase (SOD), lipid peroxidation
(LOOH), total serum antioxidant status (TAS), thiobarbituric acid (TBARS) and urinary isoprostanes;
ex vivo oxidation of 2,2-diphenyl-1-picrylhydrazyl (DPPH). Inflammation was assessed by examining
plasma concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), nitric oxide
(NO), cytokines (IL-1, IL-6, IL-8, TNF
α
, MCP-1, IL-1 receptor antagonist). We note that the biological
significance of the
in vitro
measures of oxidative stress (ORAC, FRAP, TAS) remains debatable. Muscle
damage was evaluated by determining serum concentrations of creatine kinase (CK) and lactate
dehydrogenase (LDH), recovery was estimated by the restoration of strength and decrease in muscle
soreness, and muscle pain levels were determined by the visual analog scale (VAS).
2.1.1. Antioxidant Effects of Consuming Cherries
Out of a total of 29 published human studies, 10 monitored the effects of cherries and cherry
products on markers of oxidative stress (Tables 1and 2). Oxidative stress was decreased (or antioxidant
capacity increased) in 8 studies [
37
–
43
,
48
], and it did not change in 2 studies [
46
,
47
]. Markers of
antioxidant capacity that were altered by cherry consumption included increased plasma ORAC [
40
],
FRAP [
42
], serum TAS [
37
,
39
,
41
], decreased plasma F2-isoprostane [
43
] and LOOH [
44
], and increased
urinary antioxidant capacity [
38
]. The lack of an effect of cherry juice on oxidative stress in the study
by [
47
] may have been due to the type of the exercise examined (water polo) which did not increase
oxidative stress. The nature of the supplements (tart cherry powder capsules) or the short-term
supplementation around a single bout of resistance training may be the reason for the lack of an effect
of tart cherry powder on oxidative stress in the study by [
46
] those studies showing antioxidant effects
included both sweet and sour cherries. Taken together, these findings from human studies suggest that
both sweet and tart cherries reduce oxidative stress. This inference is also supported by the results from
animal and cell culture studies in which cherry extracts increased the hepatic activity of antioxidant
enzymes in liver and decreased the iron or copper induced lipid peroxidation in vitro [21,36].
Nutrients 2018,10, 368 5 of 22
Table 2. Effects of cherries and products made from cherries on biological and clinical markers of human health.
Reference Study Subjects Study Design Treatment Major Findings Comments
Oxidative Stress
[37]10 well trained male athletes
(27.8 ±1.6 y., Mean ±SD)
CO, 7 d prior, 1 d of single leg
extensions and 2 d post
exercise; W/O 2 wk.
30 mL TCJ or placebo
(isoenergetic fruit concentrate)
b.i.d.
Recovery of maximum voluntary
contractions faster after TCJ than
placebo.
No effect of TCJ on serum CRP,
nitrotyrosine and CK.
[38,66]
Young, middle aged and
elderly (3 M + 3 F in each
group, 20–30, 45–55, 65–75 y.),
Before and after treatment,
3 d each.
3 d basal level and 3 d SC powder.
(141 g cherries/serving) b.i.d.
Total sleeping time, immobility,
and antioxidant capacity SC
powder > basal level. Sleep latency
SC < basal.
SC powder improved sleep and
antioxidant status in all age
groups.
[40] 10 healthy women, 22–40 y.
Blood and urine collected at 0,
1.5, 3 and 5 h after treatment.
Single bolus of Bing sweet
cherries (SC), (280 g).
↓in plasma ORAC and FRAP, and
↑in urinary UA at 1.5, 3 and 5 h;
↓in plasma UA at 5 h.
SC intake ↓plasma oxidative
stress and UA.
[41]
27 endurance trained runners
or triathletes (21.8 ±3.9 y,
Mean ±SD)
Parallel, PC, 10 d. Blood
samples taken pre, 60 min, 24
and 48 h post exercise.
Same supplements and protocol
as above. TC n= 11 and placebo
n= 18.
TC improved marathon time and ↓
markers of muscle catabolism
(creatinine, total protein and
cortisol) oxidative stress and
inflammation when compared with
placebo.
TC supplements may improve
recovery from exercise-induced
stress.
[42] 47 healthy adults (30–50 y.) Randomized, parallel, PC, 6
wk.
30 mL TC concentrate
(anthocyanins 270 mg/d) or
placebo.
↑FRAP, but no difference in SBP,
DBP, CRP, total- and HDL-C.
Lack of an effect on BP may be
due to low dose of
anthocyanins and healthy
participants.
[43] 6 M + 6 F (61–75 y.) Randomized, CO, PC, 2 wk.
each treatment, W/O 4 wk.
240 mL TCJ or placebo (Kool Aid)
b.i.d.
TCJ ↓plasma F2-isoprostane and
urinary 8-hydroxyguanosine,
placebo had no effect.
TCJ
↓
oxidative stress in elderly.
[46]23 resistance trained men
(20.9 ±2.6 y., Mean ±SD)
Randomized, parallel, PC, 10
d. Blood samples taken pre,
60 min., 24 and 48 h post
exercise.
TC (n= 11) or placebo (n= 12)
powder (480 mg/d) 7 d pre-, 2 d
post-and d of exercise. (TC
powder approx. equals 300 mL
TCJ).
TC
↓
post-exercise muscle soreness.
48 h post-exercise AST, ALT and
creatinine ↓by TC compared with
pre-. No change in serum markers
of oxidative stress and
inflammation.
TC improved recovery and
muscle soreness but not
markers of oxidative stress and
inflammation.
[47]
9 highly-trained male Water
polo players (18.6 ±1.4 y.,
Mean ±SD)
Randomized, CO, PC, each
period 7 d. W/O 5 wk. Blood
drawn d 1 before supplement,
d 6 pre- and post exercise; d 7
pre-exercise.
30 mL TCJ or placebo in a.m. and
60 mL p.m. after exercise on d 1–7
(total equivalent to 270 TC/d).
D 6 post exercise IL-6 TCJ >
placebo. CRP, UA, F2 isoprostane
on all test days and IL-6 on d 1 and
7 did not differ between TCJ and
placebo. No difference in measures
of performance and recovery.
Non-weight bearing sports may
not have caused substantial
oxidative stress and
inflammation to observe any
benefits of TCJ.
Nutrients 2018,10, 368 6 of 22
Table 2. Cont.
Reference Study Subjects Study Design Treatment Major Findings Comments
Oxidative Stress
[44]16 trained cyclists (30 ±8 y.,
Mean ±SD)
Randomized, CO, PC, TCJ or
placebo 8 d; W/O 14 d.
Stochastic cycling on d 5, 6, 7.
30 mL TCJ conc. or placebo (Kool
Aid) at 8 a.m. and 6 p.m. (approx.
200 TC/d).
Serum CRP, IL-6, and lipid
hydroperoxides TCJ < placebo in
blood samples taken on post-trial d
5, 6 and 7.
TCJ
↓
cycling induced CRP, IL-6
and lipid peroxidation.
[45] Same as in reference #19
FBG and urinary anti-oxidant
capacity measured, before,
5 d after, and 1 d post SC
supplement.
Same as in reference #19.
No difference in FBG, but urinary
antioxidant capacity ↑when
compared to placebo.
Since anthocyanins improve
insulin secretion, it is possible
that SC may
↓
FBG if monitored
within 2 h of their intake.
Inflammation
[48]Healthy 11 M + 1F (26 ±3 y.,
Mean ±SD,)
Randomized, CO, 2 doses.
Blood drawn at 0, 1, 2, 3, 5, 8,
24, 26, and 48 h after TCJ
intake. W/O 10 d.
30 or 60 mL TCJ (apporx.100 or
200 TC).
Serum CRP and UA
↓
within 3 h of
TCJ intake and remained low until
8 h; Urinary UA ↑within 3 h and
returned to basal level at 8 h
The dose of the TCJ had no
effect, suggesting 30 mL TCJ
was adequate to provide
maximum effect.
[37]10 well trained male athletes
(27.8 ±1.6 y., Mean ±SD)
CO, 7 d prior, 1 d of single leg
extensions and 2 d post
exercise; W/O 2 wk.
30 mL TCJ or placebo
(isoenergetic fruit concentrate)
b.i.d.
Recovery of maximum voluntary
contractions faster after TCJ than
placebo.
No effect of TCJ on serum CRP,
nitrotyrosine and CK.
[39]13 M + 7 F, (37 ±13 y., Mean
±SD,) marathon athletes
Parallel, PC; TCJ (7M + 3 F),
placebo (6 M + 4 F) 5 d before,
1 d during and 2 d post-race.
240 mL TCJ or placebo (Kool Aid)
b.i.d. (approx. 100 TC/d).
Exercise associated ↑in serumCRP,
IL-6, muscle damage and pain,
Placebo > TCJ. Total serum
antioxidant status TCJ > placebo.
TCJ ↓marathon induced
inflammation and pain.
[40] 10 healthy women, 22–40 y.
Blood and urine collected at 0,
1.5, 3 and 5 h after treatment.
Single bolus of Bing sweet
cherries (SC), (280 g).
↓in plasma ORAC and FRAP, and
↑in urinary UA at 1.5, 3 and 5 h;
↓in plasma UA at 5 h
SC intake ↓plasma oxidative
stress and UA.
[41]
27 endurance trained runners
or triathletes (21.8 ±3.9 y,
Mean ±SD)
Parallel, PC, 10 d. Blood
samples taken pre, 60 min., 24
and 48 h post exercise.
Same supplements and protocol
as above. TC n= 11 and placebo
n= 18.
TC improved marathon time and ↓
markers of muscle catabolism
(creatinine, total protein and
cortisol) oxidative stress and
inflammation when compared with
placebo.
TC supplements may improve
recovery from exercise-induced
stress.
[46]23 resistance trained men
(20.9 ±2.6 y., Mean ±SD)
Randomized, parallel, PC,
10 d. Blood samples taken pre,
60 min., 24 and 48 h post
exercise.
TC (n= 11) or placebo (n= 12)
powder (480 mg/d) 7 d pre-, 2 d
post-and d of exercise. (TC
powder approx. equals 300 mL
TCJ).
TC
↓
post-exercise muscle soreness.
48 h post-exercise AST, ALT and
creatinine ↓by TC compared with
pre-. No change in serum markers
of oxidative stress and
inflammation.
TC improved recovery and
muscle soreness but not
markers of oxidative stress and
inflammation.
Nutrients 2018,10, 368 7 of 22
Table 2. Cont.
Reference Study Subjects Study Design Treatment Major Findings Comments
Inflammation
[47]
9 highly-trained male Water
polo players (18.6 ±1.4 y.,
Mean ±SD)
Randomized, CO, PC, each
period 7 d. W/O 5 wk. Blood
drawn d 1 before supplement,
d 6 pre- and post exercise; d 7
pre-exercise.
30 mL TCJ or placebo in a.m. and
60 mL p.m. after exercise on d 1–7
(total equivalent to 270 TC/d).
D 6 post exercise IL-6 TCJ >
placebo. CRP, UA, F2 isoprostane
on all test days and IL-6 on d 1 and
7 did not differ between TCJ and
placebo. No difference in measures
of performance and recovery.
Non-weight bearing sports may
not have caused substantial
oxidative stress and
inflammation to observe any
benefits of TCJ.
[44]16 trained cyclists (30 ±8 y.,
Mean ±SD)
Randomized, CO, PC, TCJ or
placebo 8 d; W/O 14 d.
Stochastic cycling on d 5, 6, 7.
30 mL TCJ conc. or placebo (Kool
Aid) at 8 a.m. and 6 p.m. (approx.
200 TC/d).
Serum CRP, IL-6, and lipid
hydroperoxides TCJ < placebo in
blood samples taken on post-trial d
5, 6, and 7.
TCJ
↓
cycling induced CRP, IL-6
and lipid peroxidation.
[49]16 healthy male soccer
players
Randomized, CO, PC, TCJ or
placebo 8 d; baseline, 24, 48,
72 h post exercise.
30 mL TCJ conc. or placebo (Kool
Aid) twice a day.
TCJ improved performance,
recovery and muscle soreness, and
↓serum IL-6.
No effect of TCJ on LOOH and
CK, and CRP.
[50] 20 marathon runners
Randomized, TCJ (7 M + 3 F)
or placebo (6 M + 4 F) 5 d
before, 1 d during and 2 d
post-race.
TCJ or placebo as listed in 41.
Incidence and severity of URTS and
↑in plasma CRP at 24 and 48 post
race was greater in placebo than
TCJ.
TCJ ↓post-marathon
development of URTS.
[51]2 M + 16 F, 45–61 y., BMI
20–30 kg/m2, mild ↑in CRP
CO with blood drawn at −7,
0, 14 and 28 d of SC intake;
also 28 d after
discontinuation.
280 g depitted SC/d (45 SC)
replacing dietary carbohydrates.
SC ↓plasma conc. of CRP, IL-18,
ENRAGE, PAI-1, ET-1, TNF
α
, EGF,
ferritin, RANTES, NO and ↑
IL-1Ra.
SC intake ↓plasma markers of
CVD, arthritis, hypertension,
diabetes, cancer and
inflammation.
[52]
10 over weight and obese,
(38.1 ±12.5 y.,
BMI 32.2 ±4.6).
Randomized, CO, TCJ or
placebo beverage 4 wk.; W/O
2 wk.
240 mL TCJ or placebo
beverage/d.
TCJ ↓serum UA, TNF α, MCP-1,
ESR, TG, and VLDL compared with
placebo.
TCJ ↓inflammation and risk
factors for gout and CVD.
[54]49 subjs over the age of 70
with dementia
Randomized, parallel, PC, n=
24 in SC, and 25 in placebo
groups.
200 mL Bing SC or apple juice
once a day for 12 wk. Responses
tested at 6 and 12 wk.
SCJ improved verbal fluency, short
term memory and ↓SBP both at 6
and 12 weeks. No change in fasting
serum IL-6 and CRP.
200 mL of SCJ provided 138 mg
anthocyanins/d, which may
not be enough to ↓
inflammation.
[55]
44 M + 14 F (56.7 ±11.3 y.
non-diabetic grade 2–3 OA
patients
Randomized, CO, PC, TCJ or
placebo 6 wk.; W/O 1 wk.
240 mL TCJ or placebo (Kool Aid)
b.i.d.) (approx. 100 TC/d).
TCJ
↓
arthritis index, pain, stiffness
and function compared with
placebo.
No change in serum CRP.
Nutrients 2018,10, 368 8 of 22
Table 2. Cont.
Reference Study Subjects Study Design Treatment Major Findings Comments
Inflammation
[56]
Overweight and obese 37
men (61.4 ±7.7 y.,
BMI 31.7 ±4.3)
Before and after SC
consumption; no control
group.
142 g fresh SC 3 times a day, 4 wk.
Urinary PGEM, TBX2, serum CRP
and homocysteine did not change
with SC consumption.
Anthocyanin content of the
different batches of SC used
varied several folds.
[53] Same as in reference #19 Same as in reference #19. Same as in reference #19.
SC ↓sleep latency, number of
awakenings, ↑sleep time and
immobility.
↑IL-1 β, IL-8, TNF αin blood
drawn at 1 a.m.; perhaps
caused by 5-hydroxyindocle
acetic acid.
Exercised Induced Pain, Muscle Damage and Recovery
[37]10 well trained male athletes
(27.8 ±1.6 y., Mean ±SD)
CO, 7 d prior, 1 d of single leg
extensions and 2 d post
exercise; W/O 2 wk.
30 mL TCJ or placebo
(isoenergetic fruit concentrate)
b.i.d.
Recovery of maximum voluntary
contractions faster after TCJ than
placebo.
No effect of TCJ on serum CRP,
nitrotyrosine and CK.
[39]13 M + 7 F, (37 ±13 y., Mean
±SD,) marathon athletes
Parallel, PC; TCJ (7M + 3 F),
placebo (6 M + 4 F) 5 d before,
1 d during and 2 d post-race.
240 mL TCJ or placebo (Kool Aid)
b.i.d. (approx. 100 TC/d).
Exercise associated
↑
in serum CRP,
IL-6, muscle damage and pain,
Placebo > TCJ. Total serum
antioxidant status TCJ > placebo.
TCJ ↓marathon induced
inflammation and pain.
[41]
27 endurance trained runners
or triathletes (21.8 ±3.9 y.,
Mean ±SD)
Parallel, PC, 10 d. Blood
samples taken pre, 60 min., 24
and 48 h post exercise.
Same supplements and protocol
as above. TC n= 11 and placebo
n= 18
TC improved marathon time and ↓
markers of muscle catabolism
(creatinine, total protein and
cortisol) oxidative stress and
inflammation when compared with
placebo.
TC supplements may improve
recovery from exercise-induced
stress.
[46]23 resistance trained men
(20.9 ±2.6 y., Mean ±SD)
Randomized, parallel, PC, 10
d. Blood samples taken pre,
60 min., 24 and 48 h post
exercise.
TC (n= 11) or placebo (n= 12)
powder (480 mg/d) 7 d pre-, 2 d
post-and d of exercise. (TC
powder approx. equals 300 mL
TCJ).
TC
↓
post-exercise muscle soreness.
48 h post-exercise AST, ALT and
creatinine ↓by TC compared with
pre-. No change in serum markers
of oxidative stress and
inflammation.
TC improved recovery and
muscle soreness but not
markers of oxidative stress and
inflammation.
[47]
9 highly-trained male Water
polo players (18.6 ±1.4 y.,
Mean ±SD)
Randomized, CO, PC, each
period 7 d. W/O 5 wk. Blood
drawn d 1 before supplement,
d 6 pre- and post exercise; d 7
pre-exercise.
30 mL TCJ or placebo in a.m. and
60 mL p.m. after exercise on d 1–7
(total equivalent to 270 TC /d).
D 6 post exercise IL-6 TCJ >
placebo. CRP, UA, F2 isoprostane
on all test days and IL-6 on d 1 and
7 did not differ between TCJ and
placebo. No difference in measures
of performance and recovery.
Non-weight bearing sports may
not have caused substantial
oxidative stress and
inflammation to observe any
benefits of TCJ.
Nutrients 2018,10, 368 9 of 22
Table 2. Cont.
Reference Study Subjects Study Design Treatment Major Findings Comments
Exercised Induced Pain, Muscle Damage and Recovery
[49]16 healthy male soccer
players
Randomized, CO, PC, TCJ or
placebo 8 d; baseline, 24, 48,
72 h post exercise.
30 mL TCJ conc. or placebo (Kool
Aid) twice a day.
TCJ improved performance,
recovery and muscle soreness, and
↓serum IL-6.
No effect of TCJ on LOOH and
CK, and CRP.
[57] 14 male college students
Randomized, CO, PC 2 wk.
W/O; arm eccentric exercise
on d 4 of each period.
360 mL TCJ or placebo, b.i.d. for
4 d; each serving equals 50–60
TC.
Exercise associated loss of strength,
muscle damage and pain
TCJ < placebo.
Placebo used was Kraft Foods,
cherry flavored Kool Aid.
[58]36 M + 18 F (35.8 ±9.6 y.,
Mean ±SD), healthy runners
Randomized, parallel, PC; ran
26.3 ±2.5 km in 24 h TCJ or
placebo 7 d prior and on d of
race.
TCJ 355 mL b.i.d (19 M and 7F) or
placebo (15 M and 10F). About
200 TC/d.
Post run pain score, TCJ 12 ±18,
and placebo 37 ±20 mm.
TCJ prior to the race
↓
post-race
pain.
Diabetes and Cardiovascular Disease
[23]2 M + 16 F, 45–61 y., BMI
20–30 kg/m2, mild ↑in CRP
CO with blood drawn at −7,
0, 14 and 28 d of SC intake;
also 28 d after
discontinuation.
280 g depitted SC/d (45 SC)
replacing dietary carbohydrates.
SC ↓plasma conc. of CRP, IL-18,
ENRAGE, PAI-1, ET-1, TNF
α
, EGF,
ferritin, RANTES, NO and ↑
IL-1Ra.
SC intake ↓plasma markers of
CVD, arthritis, hypertension,
diabetes, cancer and
inflammation.
[42] 47 healthy adults (30–50 y.) Randomized, parallel, PC,
6 wk.
30 mL TC concentrate
(anthocyanins 270 mg/d) or
placebo.
↑FRAP, but no difference in SBP,
DBP, CRP, total- and HDL-C.
Lack of an effect on BP may be
due to low dose of
anthocyanins and healthy
participants.
[51]2 M + 16 F, 45–61 y., BMI
20–30 kg/m2, mild ↑in CRP
CO with blood drawn a
−
7, 0,
14 and 28 d of SC intake; also
28 d after discontinuation.
280 g depitted SC/d (45 SC)
replacing dietary carbohydrates.
SC ↓plasma conc. of CRP, IL-18,
ENRAGE, PAI-1, ET-1, TNF
α
, EGF,
ferritin, RANTES, NO and ↑
IL-1Ra.
SC intake ↓plasma markers of
CVD, arthritis, hypertension,
diabetes, cancer and
inflammation.
[52]10 over weight and obese,
(38.1
±
12.5 y., BMI 32.2
±
4.6)
Randomized, CO, TCJ or
placebo beverage 4 wk.; W/O
2 wk.
240 mL TCJ or placebo
beverage/d
TCJ ↓serum UA, TNF α, MCP-1,
ESR, TG, and VLDL compared with
placebo
TCJ ↓inflammation and risk
factors for gout and CVD
[54]49 subjs over the age of 70
with dementia
Randomized, parallel, PC,
n= 24 in SC, and 25 in
placebo groups.
200 mL Bing SC or apple juice
once a day for 12 wk. Responses
tested at 6 and 12 wk.
SCJ improved verbal fluency, short
term memory and ↓SBP both at 6
and 12 weeks. No change in fasting
serum IL-6 and CRP.
200 mL of SCJ provided 138 mg
anthocyanins/d, which may
not be enough to ↓
inflammation.
Nutrients 2018,10, 368 10 of 22
Table 2. Cont.
Reference Study Subjects Study Design Treatment Major Findings Comments
Diabetes and Cardiovascular Disease
[45] Same as in reference #19
FBG and urinary anti-oxidant
capacity measured, before, 5
d after, and 1 d post SC
supplement.
Same as in reference #19.
No difference in FBG, but urinary
antioxidant capacity ↑when
compared to placebo.
Since anthocyanins improve
insulin secretion, it is possible
that SC may
↓
FBG if monitored
within 2 h of their intake.
[59]19 diabetic women, BMI 29.6
±4.3
Before and after treatment, 6
wk.
40 g TC concentrate/d
(anthocyanins 720 mg/d).
↓HbA1C, SBP, DBP, total- and
LDL-C. No Control group.
[60]
15 M with early hypertension,
SBP > 130, DBP > 80
Randomized, CO, PC, W/O
14 d. Responses tested at 0, 1,
2, 3, 5, and 8 hr) after TC or
placebo intake.
60 mL TC concentrate (180 TC) or
placebo (fruit flavored cordial).
SBP, TCJ < placebo at 1, 2 and 3 h,
with peak reduction at 2 h.
↓in SBP associated with ↑in
circulating protocatechuic and
vanillic acids
[62]Pilot study with 6 young and
7 older adults
Before and after SCJ
consumption; no control
group
SCJ served either 300 mL at 0 h or
100 mL at 0, 1, and 2 h; BP
monitored at 0, 2 and 6 h
Both SBP and DBP significantly
↓
at
2 h with a single dose but not with
split dose; no effect at 6 h
Certain minimum blood
concentration of polyphenols is
needed to lower BP.
Arthritis and Associated Risk Factors
[40] 10 healthy women, 22–40 y.
Blood and urine collected at 0,
1.5, 3 and 5 h after treatment.
Single bolus of Bing sweet
cherries (SC), (280 g).
↓in plasma ORAC and FRAP, and
↑in urinary UA at 1.5, 3 and 5 h;
↓in plasma UA at 5 h
SC intake ↓plasma oxidative
stress and UA.
[52]10 over weight and obese,
(38.1
±
12.5 y., BMI 32.2
±
4.6)
Randomized, CO, TCJ or
placebo beverage 4 wk.; W/O
2 wk.
240 mL TCJ or placebo
beverage/d.
TCJ ↓serum UA, TNF α, MCP-1,
ESR, TG, and VLDL compared with
placebo.
TCJ ↓inflammation and risk
factors for gout and CVD.
[55]
44 M + 14 F (56.7 ±11.3 y.
non-diabetic grade 2–3 OA
patients
Randomized, CO, PC, TCJ or
placebo 6 wk.; W/O 1 wk.
240 mL TCJ or placebo (Kool Aid)
b.i.d.) (approx. 100 TC/d).
TCJ
↓
arthritis index, pain, stiffness
and function compared with
placebo.
No change in serum CRP.
[63] 12 gouty arthritis patients Before and after treatment, 3
d-3 month.
Fresh or canned tart cherries (TC)
227 g/d.
Blood UA normalized and no
attacks of arthritis in all subjs;
↑freedom of joint use in 4.
↓in Blood UA positively
associated with ↓in gout
attacks.
[64] 633 patients with gout
Case-CO, with or without
fresh cherries or extract for 2
d prior to gout attack.
Fresh cherries or extract, or
without both for 2 d prior to gout
attack.
Supplements
↓
gout attacks by 35%
compared to control, independent
of sex, obesity, alcohol, and drugs.
Attack risk ↓by 75% when
cherry intake was combined
with allopurinol use than
without either.
Nutrients 2018,10, 368 11 of 22
Table 2. Cont.
Reference Study Subjects Study Design Treatment Major Findings Comments
Sleep
[38,66]
Young, middle aged and
elderly (3 M + 3 F in each
group, 20–30 45–55, 65–75 y.),
Before and after treatment,
3 d each
3 d basal level and 3 d SC powder.
(141 g cherries/serving) b.i.d.
Total sleeping time, immobility,
and antioxidant capacity SC
powder > basal level. Sleep latency
SC < basal
SC powder improved sleep and
antioxidant status in all age
groups.
[39]13 M + 7 F, (37 ±13 y., Mean
±SD,) marathon athletes
Parallel, PC; TCJ (7M + 3 F),
placebo (6 M + 4 F) 5 d before,
1 d during and 2 d post-race
240 mL TCJ or placebo (Kool Aid)
b.i.d. (approx. 100 TC/d)
Exercise associated
↑
in serum CRP,
IL-6, muscle damage and pain,
Placebo > TCJ. Total serum
antioxidant status TCJ > placebo.
TCJ ↓marathon induced
inflammation and pain.
[53] Same as in reference #19 Same as in reference #19 Same as in reference #19
SC ↓sleep latency, number of
awakenings, ↑sleep time and
immobility.
↑IL-1 β, IL-8, TNF α, in blood
drawn at 1 a.m.; perhaps
caused by 5-hydroxyindocle
acetic acid.
[65]15 adults, 65 y. or older with
chronic insomnia
Randomized, CO, PC, 2 wk.
TCJ or placebo each, W/O
2 wk.
240 mL TCJ or placebo (Kool Aid)
b.i.d,
TCJ ↓insomnia severity, but not
sleep latency or sleep efficiency
Insomnia and the age of
subjects may have lessened the
effects of TCJ.
Stress, Anxiety, Mood, Memory, and Cognitive Function
[19]
Young, middle aged and
elderly, 5 M and 5 F in each
group.
Randomized, CO, PC, W/O 1
wk. Blood and urine collected
before, 5 d after and 1 d post
supplement.
5 d supplement with dried SC or
placebo powder with lunch and
dinner (280 fresh cherries SC/d).
SC improved mood, ↓anxiety and
urinary cortisol; ↑urinary
5-hydroxyindocle acetic acid
SC ↓stress and anxiety
[38]
Young, middle aged and
elderly (3 M + 3 F in each
group, 20–30 45–55, 65–75 y.),
Before and after treatment,
3 d each.
3 d basal level and 3 d SC powder.
(141 g cherries/serving) b.i.d.
Total sleeping time, immobility,
and antioxidant capacity SC
powder > basal level. Sleep latency
SC < basal.
SC powder improved sleep and
antioxidant status in all age
groups.
[41]
27 endurance trained runners
or triathletes (21.8 ±3.9 y.,
Mean ±SD)
Parallel, PC, 10 d. Blood
samples taken pre, 60 min.,
24 and 48 h post exercise
Same supplements and protocol
as above. TC n= 11 and placebo
n= 18
TC improved marathon time and ↓
markers of muscle catabolism
(creatinine, total protein and
cortisol) oxidative stress and
inflammation when compared with
placebo.
TC supplements may improve
recovery from exercise-induced
stress.
Nutrients 2018,10, 368 12 of 22
Table 2. Cont.
Reference Study Subjects Study Design Treatment Major Findings Comments
Stress, Anxiety, Mood, Memory, and Cognitive Function
[46]23 resistance trained men
(20.9 ±2.6 y., Mean ±SD)
Randomized, parallel, PC, 10
d. Blood samples taken pre,
60 min., 24 and 48 h post
exercise
TC (n= 11) or placebo (n= 12)
powder (480 mg/d) 7 d pre-, 2 d
post-and d of exercise. (TC
powder approx. equals 300 mL
TCJ).
TC
↓
post-exercise muscle soreness.
48 h post-exercise AST, ALT and
creatinine ↓by TC compared with
pre-. No change in serum markers
of oxidative stress and
inflammation.
TC improved recovery and
muscle soreness but not
markers of oxidative stress and
inflammation.
[50] 20 marathon runners
Randomized, TCJ (7M + 3 F)
or placebo (6 M + 4 F) 5 d
before, 1 d during and 2 d
post-race.
TCJ or placebo as listed in 41.
Incidence and severity of URTS and
↑in plasma CRP at 24 and 48 post
race was greater in placebo than
TCJ.
TCJ ↓post-marathon
development of URTS.
[60]
20 M + 10 F (45–60 y.) healthy
Randomized, CO, PC, W/O
14 d. Responses tested at 0, 1,
2, 3, and 5 h after TC or
placebo intake.
60 mL TC concentrate (180 TC) or
placebo (fruit flavored cordial).
SBP, TCJ < placebo at 1, 2 and 3 h,
with peak reduction at 1 h No effect
on cognitive functions or mood.
SBP but not DBP rapidly
responded to TC intake and the
↓was transient.
ALT, alanine aminotransferase; AST, aspartate amino transferase; b.i.d, two times a day; BMI, body mass index; CO, cross-over; CRP, C-reactive protein; d, day; CVD, cardiovascular
disease; CK, Creatinine; DBP, diastolic blood pressure; ET-1, endothelin-1; ENRAGE, extracellular newly identified ligand for the receptor for advanced glycation end products; ESR,
erythrocyte sedimentation rate; F, female; FBG, fasting blood glucose; FRAP, ferric reducing ability of plasma; h, hour; IL, interleukin; IL-1Ra, IL-1 receptor antagonist; M, male; min,
minute; mo, month; MCP-1, monocyte chemoattractant protein-1; NC, no change; NO, nitric oxide; OA, osteoarthritis; ORAC, oxygen radical absorbing capacity; PAI-1, plasminogen
activator inhibitor-1; PC, placebo controlled; PGEM, prostaglandin E2 metabolite; RANTES, regulated upon activation, normal T cell expressed and secreted; SBP, systolic blood pressure;
SC, sweet cherry; SCJ, sweet cherry juice; TC, tart cherry; TCJ, tart cherry juice; TBX2, thromboxane B2; TG, triglyceride; TNF
α
, tumor necrosis factor alpha; UA, uric acid; URTS, upper
respiratory tract symptoms; VLDL, very low density lipoprotein; W/O, wash out; wk., week; y., years; LDL, low-density lipoprotein; HDL, high-density lipoprotein.
Nutrients 2018,10, 368 13 of 22
2.1.2. Cherry Intake and Inflammation
Sixteen human studies investigated the effects of consuming cherries or cherry products on
markers of inflammation which were shown to be decreased in 11 studies [
23
,
37
,
39
–
41
,
44
,
46
,
48
–
52
] did
not change in 4 studies [
47
,
54
–
56
], and increased in 1 study [
53
] (Table 1). Markers of inflammation that
were decreased included ESR [
52
] plasma concentrations CRP [
23
,
39
,
44
,
48
,
50
,
55
], TNF
α
[
41
,
46
,
51
,
68
],
IL-6 [
39
,
41
,
44
,
46
,
49
], IL-8 [
39
,
41
,
44
,
46
,
49
], RANTES [
23
], NO [
23
], MCP-1 [
52
], and upper respiratory
tract symptoms [
50
]. Plasma CRP was also decreased by approximately 25% within 5 h of a bolus of
45 fresh Bing cherries compared with baseline values, although it did not attain significance [
40
]. In the
two studies by Levers et al. [
41
,
46
], the pre-exercise plasma levels of inflammatory cytokines (IL-6, IL-8,
and TNF
α
did not differ between the placebo and tart cherry groups, but their post exercise plasma
concentrations were significantly lower in the cherry group. In the study by Kelley et al. [
51
] plasma
concentrations of other inflammatory markers were also altered by consumption of sweet cherries,
including decreases in IL-18 and ferritin, and an increase in IL-1R antagonist.
In contrast, no change in serum CRP and IL-6 resulted from consumption of sweet cherry juice
for 6 and 12 weeks in elderly subjects with dementia (mean age 80 years), [
54
]. Besides the age of
the study participants, the low dose (138 mg/day) of anthocyanins used in this study may be the
reason for the lack of an effect of cherry juice on serum markers of inflammation. In the athletes
participating in a water polo game, consumption of tart cherry juice had no effect on plasma CRP
and IL-6, which may be because the non-weight bearing sport did not increase inflammation [
47
].
In another study, with obese subjects, consumption of fresh sweet cherries for 4 weeks did not alter
urinary prostaglandin E2 and Thromboxane B2, serum CRP, and homocysteine when compared
to the baseline [
56
]. The failure to detect changes in those markers, in this study, may be due to
the variations in the anthocyanin concentrations of different batches of fresh sweet cherries used,
which varied almost 20-fold during intervention. In another study, unexpectedly, the serum levels
of IL-1
β
, TNF
α
, and IL-8 were increased in the blood samples drawn at 1 a.m., following cherry
drinks with dinner [
53
]. Increase in these markers of inflammation in this study correlated with serum
concentrations of 5-hydroxyindole acetic acid, a metabolite of melatonin. Other studies have shown
that melatonin increased serum concentrations of IL-1
β
and TNF
α
, both of which induce sleep [
69
].
Despite some inconsistences, the findings discussed above support the anti-inflammatory effects of
cherries in humans. This conclusion is also supported by the inhibition of enzymes cyclooxygenase-1
and 2 by cherry extracts [
27
,
70
] and of nuclear factor-
κ
B in cultured human blood monocytes by
anthocyanins [71].
2.1.3. Effects of Consuming Cherries on Exercise Induced Muscle Damage and Recovery
Exercise-induced muscle pain, soreness and loss of strength were significantly reduced by cherry
consumption in 8 out of 9 studies [
37
,
39
,
41
,
44
,
46
,
49
,
57
,
58
], but were not different from the placebo
in one study that involved water polo athletes [
47
]. Post-exercise muscle damage as determined
by plasma concentration of CK and LDH when compared with placebo groups was reduced by
cherry products in one [
39
], but not in other studies [
37
,
44
,
49
]. The attenuation of exercise-induced
muscle damage by cherries seems to be related to the antioxidant and anti-inflammatory properties of
anthocyanins and other phenolic compounds found in cherries [
35
]. All the exercise related studies
were conducted with tart cherry products ranging from the equivalent of 50 to 270 cherries a day.
2.2. Effects of Consuming Cherries on Risk Factors for Diabetes and Cardiovascular Disease
2.2.1. Cherry Intake and Diabetes
Supplementation with cherries or cherry products did not alter fasting or randomly sampled
blood glucose and fasting insulin in healthy study participants [
23
,
45
]. In a study with diabetic women,
concentrated tart cherry juice at 40 mL/day (anthocyanins 720 mg/day) for 6 weeks significantly
decreased hemoglobin A1C (HbA1C) when compared with the levels before the supplementation;
Nutrients 2018,10, 368 14 of 22
fasting blood glucose (FBG) was also decreased by 8% but did not attain significance [
59
]. Although
this study did not include a control group, these findings are consistent with those found in animal and
in vitro
studies. Consumption of extracts from both sweet and tart cherries prevented alloxan-induced
diabetes in rats [
72
] and in mice [
73
]. Adding cherry extract or purified anthocyanins to the high fat
diets fed to mice and rats decreased circulating glucose, insulin and liver triglycerides when compared
with those groups fed the high fat diets without cherry products [
74
–
76
]. Sweet cherry fractions
rich in anthocyanins, hydroxycinnamic acid, or flavanols increased glucose consumption by cultured
HepG2 cells [
77
]. Aqueous extracts prepared from several cultivars of sweet cherries inhibited the
enzyme
α
glucosidase, which is involved in the intestinal absorption of carbohydrates [
78
]. Similarly,
tart cherry juice and one of its main polyphenols known as chlorogenic acid inhibited enzymes
α
glucosidase and dipeptidyl peptidase-4 which are involved in promoting diabetes [
79
,
80
]. Tart cherry
extract and select anthocyanins purified from it also inhibited the activity of human
α
amylase
in vitro
[
81
].
In vitro
addition of anthocyanins (delphindin-3-glucoside and cyandin-3-galactoside)
increased glucose-stimulated insulin secretion by cultured rodent pancreatic beta cells [
82
]. Results
from human, animal, and cell culture studies suggest that anthocyanins may decrease blood glucose
by slowing glucose production from complex carbohydrates, hepatic glucose output, decreasing the
production of glucagon by pancreatic
α
cells, and increasing hepatic glucose uptake and production
of insulin by pancreatic
β
cells [
80
]. Taken together, there exists evidence to suggest that cherry
consumption may promote healthy glucose regulation. Future studies are needed to confirm whether
these findings translate to reduced risk of diabetes.
2.2.2. Cherry Intake and Blood Lipids
Consumption of sweet cherries or tart cherry concentrate by healthy adults did not alter
concentrations of blood lipids, including triglycerides, low-density lipoprotein (LDL), very-low-density
lipoprotein (VLDL), high-density lipoprotein (HDL), total cholesterol, number of different lipoprotein
particles and their sizes in healthy adults [
23
,
42
]. In contrast to the studies with healthy participants,
another study with overweight and obese subjects who had elevated blood lipids reported a decrease
in VLDL and triglycerides/high-density lipoprotein (TG/HDL) ratio following consumption of tart
cherry juice for 4 weeks [
52
]. It seems the lipid profile of study participants prior to the supplementation
with tart cherries [
52
] versus sweet cherries [
23
] rather than the type of cherries may have contributed
to the different results between these two studies. As stated above, cherry extracts and purified
anthocyanins decreased liver triglycerides and cholesterol in mouse and rat models and prevented the
high fat diet induced development of NAFLD [74–76].
2.2.3. Cherry Intake and Blood Pressure
Effects of cherry consumption on blood pressure (BP) were examined in 7 studies; 3 of
these studies examined the acute effects [
60
–
62
], and 4 examined the chronic effects of cherry
consumption
[42,51,59,62]
. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP)
were significantly lowered within 2 h of a single dose of 300 mL of Bing cherry juice and returned
to the baseline levels at 6 h in the young and elderly adults [
62
]. However, if the juice was served in
3 doses of 100 mL each at 0, 1, and 2 h there was no decrease in either SBP or DBP at 2 or 6 h These
findings indicate that both the dose and time after ingestion are important in determining the BP
lowering effects of cherry juice. Time dependent effects of tart cherry concentrate were also observed
in two other studies where only the SBP was significantly decreased at 1 and 2 h after ingestion of
Montmorency cherry concentrate, but not at 4 and 5 h after the supplementation [
31
,
60
]. The acute
effects of cherry concentrate on BP were associated with increase in plasma concentrations of vanillic
and protocatechuic acids, which are metabolites of cyanindin-3-glucoside [60].
In a study with diabetic women, 6-week supplementation with 40 g/day of tart cherry concentrate
(anthocyanins 720 mg/day) significantly decreased both SBP and DBP when compared with the
pre-supplementation values [
59
]. In another placebo controlled parallel study of elderly subjects
Nutrients 2018,10, 368 15 of 22
200 mL/day of Bing cherry juice (anthocyanins 138 mg/day) significantly decreased SBP, but not DBP
at 6 and 12 weeks, when compared to the placebo group (Apple juice) [
54
]. Similarly, in another study
with healthy adults, Bing cherries consumed at 280 g/day (anthocyanins 100 mg/day) for 28 days
significantly decreased plasma concentration of endothelin-1 (ET-1) but the decrease in SBP did not
attain significance [
51
]. In contrast to the above studies, supplementing at 30 mL/day tart cherry
concentrate (anthocyanins 273 mg/day) for 6 weeks failed to decrease both SBP and DBP in healthy
adults with relatively low mean SBP of 110, and DBP of 70 mm Hg [
42
]. Normal blood pressures of
study participants, low dose of anthocyanins, and the time elapsed between consumption of cherry
juice and the monitoring of blood pressure may have contributed to the lack of a decrease in BP in
subjects consuming cherries. Further studies to determine the benefits of chronic consumption of
cherries need to be conducted in participants with border line blood pressure.
The decrease in blood pressure caused by the prolonged consumption of cherries may have
resulted from the decrease in endothelin-1 (ET-1) which is one of the most potent vasoconstrictors [
51
].
NO produced by endothelial NO synthase (eNOS) is an important vasodilator, and its expression was
increased by the addition of cyanidin-3-glucosdie to cultured human umbilical vein endothelial cells
and bovine vascular endothelial cells [
83
]. Hence, altered expression of both ET-1 and eNOS by cherry
consumption may have contributed to the decrease in blood pressure.
Extracellular newly identified ligand for the receptor for advanced glycation end products
(EN-RAGE) and plasminogen activator inhibitor-1 (PAI-1) are other risk factors for diabetes and CVD
whose plasma concentrations were significantly decreased following the consumption of sweet cherries
for 4 weeks by healthy study participants [
51
]. Plasma concentration of EN-RAGE was positively
associated with concentrations of CRP, hemoglobin A1C, and fasting blood glucose [
84
]. PAI-1 is the
major physiologic inhibitor of tissue-type plasminogen activator that prevents clot formation through
fibrinolysis. Plasma concentration of PAI-1 correlates with metabolic syndrome and may predict
future risk for type 2 diabetes mellitus (T2DM) and CVD [
85
]. Other
in vitro
studies demonstrated
that anthocyanins inhibited expression of NF-
κ
B, inflammatory cytokines, and adhesion molecules
which are involved in the initiation and progression of CVD [
86
]. Adding tart cherry extract to
the atherogenic diet fed to rabbits decreased plaque formation and improved cardiac functions [
87
].
Although further studies are needed, the available literature supports the conclusion that regular
consumption of cherries may reduce the incidence of T2DM and CVD.
2.3. Effects of Consuming Cherries on Arthritis and Associated Risk Factors
The earliest study regarding the health benefits of fresh and canned cherries was conducted in
1950 in patients with gout [
63
]. Results from this study demonstrated that consumption of fresh or
canned cherries prevented attacks of arthritis and restored the plasma uric acid (UA) concentrations to
normal levels in all 12 patients. Furthermore, 4 patients reported greater freedom of joint movements
in fingers and toes. These findings were published for more than 5 decades before the next human
study regarding cherries and health was conducted by [
40
]. The study by Jacob et al. investigated
the acute effects of ingesting a bolus of 45 sweet cherries in 10 young healthy women. They found
that cherry consumption decreased plasma markers of oxidative stress and inflammation. Plasma
UA concentration which is considered a marker for gout, was significantly reduced at 5 h after a
dietary bolus of sweet cherries, but not at 1.5 and 3 h when compared to pre-challenge values. Results
from recent studies regarding the effects of cherry consumption on plasma concentrations of UA
have been variable. In one study, with obese subjects, consumption of tart cherry juice for 4 weeks
significantly reduced plasma concentration of UA [
52
], while it was not altered by consumption of
tart cherry juice within 6 weeks in patients with osteoarthritis [
55
], or within 7 days in water polo
athletes [
47
]. Although the tart cherry juice did not decrease UA in patients with osteoarthritis,
it significantly decreased plasma CRP and the Western Ontario McMaster Osteoarthritis Index. In a
recent case-crossover study with 633 gout patients, consumption of fresh cherries or cherry extract
over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake of
Nutrients 2018,10, 368 16 of 22
cherries [
64
]. The effect of cherry intake persisted across subgroups stratified by sex, obesity status,
purine intake, alcohol, diuretic, and antigout medications use. When cherry intake was combined with
allopurinol use, the risk of gout attacks was 75% lower than during periods without either exposure.
Anthocyanins inhibited the activity of Xanthine oxidase, the enzyme involved in UA synthesis,
in vitro
and also decreased serum UA concentration in hyperuricemic mice [
88
]. Similarly, tart cherry juice
decreased the serum concentration of UA in hyperuricemic rats [
89
]. Although there are inconsistencies
in the results from different human studies, taken together, findings support the conclusion that
cherry consumption may reduce the incidence of arthritic attacks. These human findings regarding
the reduction in arthritis by cherry consumption are consistent with the reduction of adjuvant- or
collagen-induced arthritis in rat and mouse models by anthocyanins [
5
,
90
–
92
]. Suppression of the
expression of NF
κ
B, inflammatory cytokines, and inhibition of activities of enzymes cyclooxygenase-1
and -2 activities by purified anthocyanins and cherry extracts also supports the anti-arthritic properties
of cherries [
24
,
27
,
70
]. Further, long term, randomized, double blinded and placebo controlled human
trials are needed to confirm anti- arthritic effects of cherry products.
2.4. Effects of Consuming Cherries on Sleep, Mood, and Cognitive Functions
Both quality and quantity of sleep were improved by the consumption of sweet [
38
,
53
] as well
as tart cherries [
65
,
93
]. Effect on sleep could be detected within 3 days of consuming sweet cherries
(141 g or 25 cherries/day) and within 5 d of consuming tart cherries (240 mL of tart cherry juice;
approximately 100 cherries/day). The studies using sweet cherries also reported a decrease in urinary
cortisol and anxiety, and improved mood [
38
,
94
]. Those functions were not tested in the studies
using tart cherries [
65
,
93
]. However, mood and cognitive functions were not altered within 5 h of
supplementing with 60 mL (approximately 180 tart cherries) of tart cherry concentrate [
61
]. Similarly,
there was no significant difference in cognitive functions tested at 0 and 6 h after a single serving
of cherry juice (300 mL, anthocyanins 55 mg) to young and older adults [
95
]. Authors suggested
that the lack of an effect may be due to the low dose of anthocyanins served. While there are only
limited numbers of published studies testing the effects of cherries on cognitive functions, several
studies assessed the effects of other anthocyanin rich foods on cognitive functions. Thus, cognitive
functions were improved in 6 out of 7 human intervention studies using food-based anthocyanins [
62
].
Similarly, 17 out of 19 epidemiological studies reported significant benefits of fruit, vegetable, or juice
consumption on cognitive functions [96].
Serum cortisol levels did not differ between placebo and tart cherry groups (100–120 cherries/day,
5 days before and on the day of race) in marathon runners before and end of race; or 24 and 48 h after
the race [
50
]. In another study, which involved weight lifting the serum cortisol at 60 min post exercise
was significantly greater in the cherry consuming group compared with the placebo [
46
]. Yet, in another
marathon race study by the same authors, the serum cortisol at 60 min after the race was significantly
lower in the cherry group compared with that in the placebo group [
41
]. These differences in the
cortisol response may be related to the type of exercise, because supplementation with cherries did not
alter the serum markers of oxidative stress and inflammation in the study involving weight lifting,
while levels of these markers were decreased by consumption of cherries in the marathon runners.
Supplementing diets of aged rats with tart cherry powder improved working memory and
autophagy [
97
], and sweet cherry polyphenols protected cultured neuronal cells from damage
by increased oxidative stress [
98
]. Anthocyanins in animal models improved memory [
99
,
100
],
and prevented amyloid beta induced Alzheimer disease [
101
,
102
]. The results from these animal
and cell culture studies are suggestive of improved cognitive function in humans consuming cherries.
Overall, these reports support further examination of the possible cognitive enhancing effects of
cherry consumption.
Nutrients 2018,10, 368 17 of 22
3. Conclusions
Evidence from published reports is reasonably strong to indicate that consumption of cherries
decreased markers for oxidative stress, inflammation, exercise-induced muscle soreness and loss of
strength, and blood pressure acutely after ingesting cherries. Limited numbers of published reports
also indicate beneficial effects of consuming cherries on arthritis, diabetes, blood lipids, sleep, cognitive
functions, and possibly mood. It should be noted that many of these studies, which suggested health
benefits of cherry consumption, used amounts (45–270 cherries/day) that might be considered to
be a high dose. Because of the finite number of studies and some inconsistencies among the results,
additional studies are needed to support these claims. Several factors, including number of study
participants and their health status, composition of basal diet, duration of supplements, anthocyanin
concentration and composition, compliance, sensitivity, and precision of the analytical methods may
have contributed to the discrepancies among the published reports. Developments of stable and
standardized cherry products that retain nutrient composition of fresh cherries and of placebos devoid
of polyphenols are desperately needed to precisely assess the health promoting effects of cherry
consumption. It is important that all intervention studies report at least the daily total amounts
of phenolics and anthocyanins served to study participants. Additional studies are also needed to
understand the underlying mechanisms that may confer health benefits of cherry consumption.
Acknowledgments:
This work was supported by US Department of Agriculture’s Agricultural Research Service
intramural Project Number 2032-51530-024-00D and 2032-51530-022-00D. Cherry research conducted in the
laboratory of Darshan S. Kelley was partially funded by grants from the Washington State Fruit Commission
and the California State Advisory Board. Reference to a company or product name does not imply approval or
recommendation of the product by the U.S. Department of Agriculture to the exclusion of others that may be
suitable. USDA is an equal opportunity provider and employer.
Author Contributions:
Darshan S. Kelley wrote the original manuscript, with Darshan S. Kelley, Yuriko Adkins,
and Kevin D. Laugero providing editorial and conceptual input to the final version of the manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
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