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Antioxidant and Associated Capacities of Camu Camu ( Myrciaria dubia ): A Systematic Review

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Abstract An aging population in the United States presents important challenges for patients and physicians. The presence of inflammation can contribute to an accelerated aging process, the increasing presence of comorbidities, oxidative stress, and an increased prevalence of chronic pain. As patient-centered care is embracing a multimodal, integrative approach to the management of disease, patients and physicians are increasingly looking to the potential contribution of natural products. Camu camu, a well-researched and innovative natural product, has the potential to contribute, possibly substantially, to this management paradigm. The key issue is to raise camu camu's visibility through increased emphasis on its robust evidentiary base and its various formulations, as well as making consumers, patients, and physicians more aware of its potential. A program to increase the visibility of camu camu can contribute substantially not only to the management of inflammatory conditions and its positive contribution to overall good health but also to its potential role in many disease states.
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Antioxidant and Associated Capacities
of Camu Camu (Myrciaria dubia):
A Systematic Review
Paul C. Langley, PhD,
Joseph V. Pergolizzi Jr., MD,
Robert Taylor Jr., PhD,
and Caroline Ridgway, JD
An aging population in the United States presents important challenges for patients and physicians. The presence
of inflammation can contribute to an accelerated aging process, the increasing presence of comorbidities,
oxidative stress, and an increased prevalence of chronic pain. As patient-centered care is embracing a multi-
modal, integrative approach to the management of disease, patients and physicians are increasingly looking to
the potential contribution of natural products. Camu camu, a well-researched and innovative natural product, has
the potential to contribute, possibly substantially, to this management paradigm. The key issue is to raise camu
camu’s visibility through increased emphasis on its robust evidentiary base and its various formulations, as well
as making consumers, patients, and physicians more aware of its potential. A program to increase the visibility of
camu camu can contribute substantially not only to the management of inflammatory conditions and its positive
contribution to overall good health but also to its potential role in many disease states.
An aging population in the United States presents
important challenges for patients and physicians. The pres-
ence of inflammation can contribute to an accelerated aging
process, the increasing presence of comorbidities, oxidative
stress, and an increased prevalence of chronic pain. As patient-
centered care is embracing a multimodal, integrative approach to
the management of disease, patients and physicians are increas-
ingly looking to the potential contribution of natural products.
The contribution of chronic systemic inflammation to the
initiation and mediation of chronic diseases has been recog-
nized for many years (Fig. 1). Chronic inflammation can arise
from viral or microbial infections, antigens in the environ-
ment, autoimmune reactions, or the continual activation of
inflammatory molecules. The inflammatory process involves
cascades of molecular and cellular signals in the transition
from acute to chronic inflammation. Of particular interest is
the role of interleukin-6, which exhibits an anti-inflammatory
profile in acute inflammation yet is proinflammatory in dis-
eases such as collagen-induced arthritis.
Inflammation has
been linked to several disease states. Apart from diseases that
are inflammatory in nature, such as Crohn’s disease, celiac
disease, inflammatory bowel disease, and rheumatoid arthri-
tis, other diseases have inflammatory elements, such as obe-
sity, type 2 diabetes, some cancers, and Alzheimer’s disease;
chronic inflammation is also seen as a potential risk factor
for cardiovascular disease. More recently, the presence of
chronic inflammation has been shown to decrease pain
Large-scale observational studies have linked
chronic inflammation to unhealthy aging phenotypes,
cardiac death,
and the association of depressive symptoms
and pulmonary function.
All too often inflammation is considered something to get
rid of and is generally treated with medication to alleviate
pain, swelling, or stiffness. Primary treatment options, such
as nonsteroidal anti-inflammatories, are used to relieve the
discomfort but these are not without adverse effects. Well
known for their gastrointestinal adverse effects, use of non-
steroidal anti-inflammatory drugs must be closely moni-
tored, especially in select populations such as the elderly. In
addition, anti-inflammatory agents also disable the body’s
natural ability to detoxify, repair, and protect itself. Because
of this, some patients and physicians are beginning to move
Maimon Research LLC, Tucson, AZ.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Anesthesiology, Georgetown University School of Medicine, Washington, DC.
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA.
NEMA Research Inc., Naples, FL.
Amazon Origins, LLC, Naples, FL.
ªP.C. Langley et al. 2015; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative
Commons License Attribution-Non-Commercial Share Alike (
Volume 21, Number 1, 2015, pp. 8–14
DOI: 10.1089/acm.2014.0130
toward natural approaches, such as lifestyle and dietary
modifications, to improve overall health, immune function,
and the normal inflammatory response and strip themselves
of pharmaceutical medications.
A perennial question is how systemic chronic disease
markers might be modified by lifestyle and dietary modifi-
cations. A few observations are important in this regard:
The last 20 years has seen an increasing emphasis on
the antioxidant capacity of diet, the effect on antioxi-
dant status, and ultimately the effect of diet on health
outcomes through reducing oxidative damage and its
potential corresponding impact on disease status.
As far as lifestyle and dietary studies are concerned the
evidence base, although limited, would suggest that
‘‘Western’’ diets tend to be associated with biomarkers
for inflammation, typically C-reactive protein, while
‘‘Mediterranean’’ diets are inversely associated.
More substantive conclusions are limited by the dearth
of long-term cohort studies to evaluate the association
between absolute food intakes, dietary patterns, and
changes in inflammatory markers.
Regarding dietary supplements, attention has also been
given to claims that natural products containing par-
ticular minerals, vitamins, and phytochemicals may
have an anti-inflammatory effect in humans.
These claims include those for tropical fruits with
demonstrated claims for substantive antioxidant activ-
ity in vitro and that these have the potential to translate
to in vivo claims; even so, care must be taken to avoid
unsubstantiated medical claims.
Camu camu (Myrciaria dubia H.B.K. [McVaugh]) is a
particularly versatile berry, with its pulp, seeds, and skin all
presenting antioxidant potential in differing degrees once
processed. The plant is present in many environments, which
variously affect its biochemical profile and properties. Camu
camu is a low-growing shrub, populating swampy or flooded
areas. The shrub grows to a height of 1 to 3 m, with globular
fruits with a diameter of 1.0–3.2 cm. It has a thin, shiny skin
with a juicy (and extremely acidic) pink pulp surrounding
one to four seeds. The fruit is not consumed in its natural
state, except by the indigenous peoples who inhabit the
fruit’s natural territories, because of its very high acidity;
rather, it is generally consumed in the form of juices, purees,
and pulp, the last to support beverage production and pow-
der as a food additive.
The purpose of the present review is to report on the ev-
idence base for camu camu and to consider options for
product development. It is not the intention here to support or
otherwise report on potential medical claims. While there ap-
pears, on the basis of the evidence to date, to be a prospective
role for camu camu as a mediator for inflammation and
antioxidant stress, this should be seen in the context of its
unique vitamin C content compared with other tropical fruits,
together with its content of flavonoids and anthocyanins.
FIG. 1. Initiation of
and mediation of chronic
diseases associated with
PubMed was searched ( January 10, 2014) by using the
following keywords: (camu-camu OR myrciaria dubia)
AND (phenolic compounds OR ascorbic acid OR antioxi-
dant OR rats OR mice OR fruit). A total of 16 references
were found, 4 of which were not related to the fruit’s anti-
oxidant properties. Further literature searches were con-
ducted with Google Advanced Scholar, supplemented by
references cited in papers and references provided by the
manufacturers. All references have appeared, as far as can
be ascertained, in peer-reviewed journals.
Nutritional Composition and Antioxidant Activity
The nutritional content of camu camu fruit has been sum-
marized most recently by Akter et al. (2011).
The fruits are
a substantive source of minerals, such as sodium, potassium,
calcium, zinc, magnesium, manganese, and copper. They
contain small amounts of pectin and starch. The major
sugars are glucose and fructose. The fruits also contain a
range of amino acids, organic acids (such as citric acid,
isocitric acid, and malic acid), and fatty acids (predomi-
nantly stearic, linoleic, and oleic acid). There are 21 volatile
compounds. Camu camu fruits are a major source of a range
of bioactive compounds. These include many polyphenols
(flavonoids, phenolic acids, tannins, stilbenes, and lignans).
The compounds depend on state of maturity of the plant and
extraction method used. Total phenolic content is higher
than that in a range of other tropical fruits, with a higher
content in seeds and peel. Evidence for the anthocyanin
content of camu camu is mixed.
Antioxidant capacity
Zanatta et al. (2005) reported for the first time on the
anthocyanin profile of camu camu in fruits from two re-
gions of Sao Paulo, Brazil.
The major anthocyanins were
cyaniding-3-glucoside, which was the major pigment, fol-
lowed by delphinidin-3-glucoside. In addition to their light
attenuating role, anthocyanins act as powerful antioxidants.
More recently, the antioxidant capacity of camu camu was
reported to be the highest among the Brazilian fruits evalu-
ated by Goncalves et al. (2010).
These results confirmed
those of an earlier study by Rodrigues et al. (2006), which
examined fruit from two different sources.
In that study,
both samples exhibited significant and almost identical anti-
oxidant properties through use of the total oxidant scavenging
capacity assay against peroxyl radicals and peroxynitrite,
although the effects of the two samples on hydroxyl radicals
were substantially different.
Genovese et al. (2007) reported on a comprehensive as-
sessment of the bioactive compounds contents and antioxi-
dant activity of five exotic fruits and seven commercial frozen
pulps from Brazil.
The assessment considered vitamin C
and total phenolics content, together with antioxidant capacity
(b-carotene/linoleic bleaching method and 1,1-diphenyl-2-
picrylhydrazyl [DPPH] radical scavenging activity), flavo-
noids, chlorogenic acid content, and ellagic acid content.
Among the fruits, camu camu demonstrated the highest vi-
tamin C and total phenolics content and the highest DPPH
scavenging activity. The main flavonoids present were quer-
cetin and kaempferol derivatives. Cyaniding derivatives were
found only in camu camu. Camu camu and araca demon-
strated the highest total ellagic acid contents. In particular,
commercial frozen pulps had lower antioxidant capacity and
bioactive compound content than the respective fruits. In
addition, Chirinos et al. (2010) reported on the antioxidant
compounds and capacity of Peruvian camu camu at differ-
ent ripening or maturity stages.
The screening found that
ascorbic acid decreased while anthocyanin, flavonol and fla-
vonol contents, and DPPH antioxidant capacity increased
during ripening. Fractionating camu camu found that an ascor-
bic acid–rich fraction was the major contributor to antioxidant
capacity (67.5%–79.3%) while a phenolics-rich fraction had
only a minor role (20.7%–32.5%).
Stability of vitamin C content
The stability of camu camu pulp vitamin C has been eval-
uated by Justi et al. (2000).
When pulp was stored at -18C,
vitamin C concentration decreased considerably, a loss of 23%
(from 1.57 to 1.21 b/100 g) to day 28. This remained approx-
imately the same until the end of the observation period. After
335 days of storage, the content was 1.16 g/100 g of pulp. The
ascorbic acid loss was 26%.
Camu camu juice by-products
Myoda et al. (2010) reported on the total phenolic con-
tents and antioxidant and antimicrobial activities of residual
by-products of camu camu fruit production.
They found
that the seeds and fruit contained significantly more phenols
than did other tropical fruits—notably in the seed. Fractio-
nated seed and peel extracts showed potential antioxidant
activity, with antimicrobial activity to Staphylococcus au-
reus, due to lipophilic constituents.
The polyphenol and vitamin C content, together with the
antioxidant capacity of camu camu pulp powder and the
dried flour from the skin and seeds residue from pulp prep-
aration of camu camu, was reported in a recent paper by
Fracassetti et al. (2013).
The phenolic content of camu
camu flour was higher than that of pulp powder. In both
products, flavonol myricetin and conjugates, ellagic acid and
conjugates, and ellagitannins were detected. Cyanidin 3-
glucoside and quercetin (and its glucosoids) were found only
in the pulp powder, while proanthocyanidins were found
only in the flour. The vitamin C content was lower in the
pulp powder with a higher radical-scavenging capacity.
Animal Studies
Overall, six animal studies of camu camu juice have been
reported. These have assessed the antioxidant, genotoxic,
and antigenotoxic potential of camu camu juice in mice,
the effect of camu camu pulp on obesity in rats,
the he-
patoprotective effect of camu camu juice in rats, the anti-
inflammatory effects of camu camu,
the mutagenic effect
of camu camu juice on mouse bone marrow,
and sper-
matogenic effect in rats.
Anti-inflammatory effects of camu camu
Two studies have reported on the anti-inflammatory effect
of camu camu juice and seed extract on inflammatory ac-
tivity. The study by Yazawa et al. (2011) considered camu
camu seeds, while that by da Silva et al. (2012) addressed
the contribution of camu camu juice.
Both are high-
quality studies.
The potential role of camu camu seeds in anti-inflamma-
tory activity was reported by Yazawa et al. (2011).
that the seeds of many fruits contain ingredients with bio-
logical activity, the authors screened the methanolic extract
from camu camu seeds for anti-inflammatory activity fol-
lowing carrageenan-induced paw edema in mice that was
induced by injection. The mouse paws became edematous
after the injection, with edema reaching its peak at 4 hours in
the control group. While the increase in paw edema was
suppressed to less than 0.1% by oral treatment of dexa-
methasone (1.0 mg/kg), pretreatment of the mice with extract
of camu camu seeds (2000 mg/kg) significantly reduced
edema formation with respect to both size and volume at 2
and 4 hours after carrageenan treatment. The inhibitory ef-
fects of camu camu seeds were shown independently in four
experiments. The average inhibitory ratio was calculated as
35.7% 6.7% at 2000 mg/kg, 63.8% 7.3% at 1000 mg/kg,
and 85.1% 10.3% at 500 mg/kg at control paw thickness
at 2 hours. Results assessed both in vivo and in vitro sug-
gested that the extract suppresses the formation of paw
edema by inhibiting localized nitric oxide production from
macrophage-derived RAW 264.7 cells in vitro. The active
compound in the extract was identified as a potent anti-
inflammatory triterpenoid known as betulinic acid.
The antioxidant, genotoxic, and antigenotoxic potential of
camu camu juice on the blood cells of mice were reported
by da Silva et al. (2012).
The blood cells of mice after
acute, subacute, and chronic treatments were evaluated for
flavonoids and vitamin C, with in vitro antioxidant activity
evaluated by DPPH assay. Blood samples were collected for
analysis after treatment, and the alkaline comet assay was
used to analyze the genotoxic and antigenotoxic activity.
The amount of vitamin C per 100 mL of camu camu was
52.5 mg. DPPH assay showed an antioxidant potential of the
fruit. No camu camu concentration tested exerted any gen-
otoxic effect on mice blood cells. In the ex vivo test, the
juice demonstrated antigenotoxic effect, and acute treatment
produced the most significant results. After the treatments,
there was no evidence of toxicity or death.
Camu camu and rat obesity
Nascimento et al. (2013) reported on the antiobesity ac-
tion of camu camu pulp in a rat model of diet-induced
Obesity in the rats was induced by subcutaneous
injection of monosodium glutamate receiving diet ad libi-
tum. The rats were divided into two groups: an experimental
group that ingested 25 ml of camu camu pulp per day and a
nontreated control group. After 12 weeks, blood, liver, heart,
and white adipose tissue were collected and weighed together
with inflammatory and biochemical profiles. The camu camu
group reduced their weights of the fat in white adipose
tissues, glucose, total cholesterol, triglycerides, low-density
lipoprotein cholesterol, and insulin blood levels. High-density
lipoprotein cholesterol levels increased. Inflammatory mark-
ers and liver enzymes did not change.
Camu camu and liver protection in rats
The potential hepatoprotective effect of camu camu was
reported by Akachi et al. (2010).
Previous studies had dem-
onstrated the suppressive effects of fruits on D-galactosamine
(GalN)–induced liver injury in rats.
(2010) study, 12 kinds of lyophilized fruit juices were fed to
rats for 7 days, with liver injury induced by GalN injection.
The study found that certain fruit juices possessed or tended
to possess suppressive effects on GalN-induced increases in
plasma alanine aminotransferase and aspartate aminotransfer-
ase activities. These decreased to near-normal levels. The most
potent suppressive effect on GalN-induced liver injury was
associated with 1-methylmalate isolated from camu camu juice.
This was potentially attributed to the inhibition of the synthesis
of RNA and proteins through a decrease in the hepatic uridine
triphosphate concentration. This produced a necrosis of liver
cells, but the actual mechanism was unclear.
Mutagenetic effects on bone marrow
In a safety study, Castro et al. (2011) reported on the
potential mutagenic effect of a range of camu camu juice
concentrations on bone marrow cells of male and female
Through use of the micronucleus test, the authors
found the juice could not induce chromosomal mutations.
Spermatogenic cycle in male rats
The effect of camu camu in association with an extract of
black maca (Lepidium meyenii) on spermatogenesis was
reported by Gonzales et al. (2013).
The combination of
these two fruits—one with the highest content of ascorbic
acid and the other an extract of black maca—was evaluated
for their effect on the seminiferous tubule stages scored by
transillumination on intact tubules in adult male rats. Over 7
days the rats were assessed for daily sperm production, stage
of spermatogenic cycle, antioxidant activity, and flavonoid
and polyphenol levels. Camu camu increased the stages of
mitosis and meiosis, and a mixture of both increased sper-
miation as well. All treatments increased daily sperm pro-
duction and epididymal sperm count.
Human Trials
Inoue et al. (2008) reported on the first in vivo study in
humans of the antioxidative and anti-inflammatory properties
of camu camu.
The study population consisted of 20 ha-
bitual male smokers who were considered to have an accel-
erated oxidative stress state. These volunteers were randomly
assigned to take daily 1050mg of vitamin C tablets or 70 mL
of 100% camu camu juice containing 1050mg of vitamin C
as a dietary supplement for 7 days. Baseline characteristics,
including cigarette consumption, tar and nicotine intake, and
blood pressure, were similar in the two groups. In the camu
camu group, at 7 days, oxidative stress markers urinary 8-
OHdG levels and serum total reactive oxygen species levels
significantly decreased, as did the levels of the inflammatory
markers high-sensitivity C-reactive protein, interleukin-6, and
interleukin-8. No corresponding changes were observed in the
vitamin C group. These markers were restored in the washout
stage of 1 month after cessationofcamucamuuse.The
authors concluded that camu camu has more powerful an-
tioxidative and anti-inflammatory activities than daily intake
of 1500 mg of vitamin C, although the contents of vitamin C
are equivalent. They also concluded, given the equivalent
vitamin C contents, that camu camu possibly contains other
antioxidative substances, including and in addition to the
known presence of carotenoids and anthocyanins. A further
possibility was that camu camu had substances, such as
potassium, that increase the in vivo availability of vitamin C
by absorption or excretion.
A more recent study by Ellinger et al. (2012) reported on
the effects of a bolus consumption of a blended juice of ac¸ai,
Andean blackberries, and camu camu on the concentrations
of plasma antioxidants, plasma antioxidant capacity, and
markers for oxidative stress.
In this randomized controlled
crossover study, 12 healthy participants consumed 400 mL of
blended juice or a control sugar solution. The primary end-
point of the study was the total antioxidative capacity in blood;
multiple assays with different radicals and mechanisms (hy-
drogen or electron transfer) were used: Trolox Equivalent
Antioxidant Capacity (TEAC) and Folin-Ciocalteau (FCR).
The results indicated that TWEAC and FCR as parameters of
plasma antioxidative capacity were not affected by beverage,
time, or interactions between beverage and time, despite an
obvious increase in ascorbic acid and other substances with
reducing capacity in plasma. Bolus ingestion of the blended
juice only increased the concentration of plasma ascorbic acid
and several unknown substances with reducing properties. It
did not reduce markers of oxidative stress.
Safety in humans
The only published report of adverse events in humans
probably associated with ingestion of a preparation con-
taining camu camu was reported by Bertoli et al. (2013).
45-year-old man was admitted with a 2-week history of
pruritus, scleral icterus, and dark urine and with fever and
vomiting. Tests for hepatitis A, B, C and E viruses; Epstein-
Barr virus; and cytomegalovirus ruled out viral hepatitis
and metabolic or autoimmune cases of liver injury. Mag-
netic resonance cholangiography showed no abnormalities.
A liver biopsy demonstrated centrilobular hepatocellular
damage. There was no evidence of cholestasis. No necrotic
hepatocytes, eosinophilia, or epithelioid granulomas were
present. There was no identifiable fibrosis. Histologic find-
ings were compatible with drug toxicity of not very recent
origin. Application of the Naranjo et al. (1981) adverse-
reaction probability scale suggested camu camu as the most
likely cause of the acute hepatitis.
Signs of liver injury
gradually improved, and the patient was discharged.
With an aging U.S. population and a widespread recog-
nition of the part inflammation can play in the aging process,
the negative contribution of comorbidities and the high
prevalence of chronic pain in older populations, there is in-
creasing recognition and acceptance that in patient-centered
medicine integrative, multimodal approaches to disease man-
agement are central to achieving wellness and quality-of-life
targets. Driven in part by the recognition that, particularly
among older populations, multiple comorbidities are present,
physicians are becoming more focused on disease manage-
ment that not only crosses traditional specialist boundaries
but embraces nontraditional players, to include the pro-
spective positive role of natural products in treatment. At
the same time, the potential for polypharmacy-associated
adverse events has also raised awareness that if natural
products and possible dietary supplements are to be em-
braced as part of management protocols, there needs to be a
robust evidence base to address issues of dosing and drug
interactions. Once that evidence base is in place, medical
claims can be made. As an important intermediary step, it is
important that consumers, including patients and physicians,
are made more aware of the potential contribution of natural
products to overall health care.
Camu camu could potentially play a role in multimodal,
integrative approaches to health management. At this stage,
however, specific medical claims are not justified, despite
long-standing claims for vitamin C products. This does not
mean that communications to broaden disease awareness are
unimportant. Recommendations for screening and counsel-
ing to a physician audience as well as to patients to increase
their disease awareness, particularly if there are public
health implications, have a role to play.
At the same time, recognition of the contribution of
chronic systemic inflammation in the initiation and media-
tion of chronic disease has opened the way for a more
considered view of the role of diet and dietary supplements
in the management of disease. Communications to physi-
cians and patients of the need to reduce systemic inflam-
mation, to help restore normal inflammatory function, and to
help restore normal immune function not only meet a public
health need but also raise the issue of the prospective role of
such products as camu camu. Although patients seem in-
creasingly interested in dietary supplements as alternative
self-medication in disease states, all too often, unfortu-
nately, claims for anti-inflammatory status and the role of
the product in specific disease states do not rest on a sub-
stantive evidentiary base. The number of studies is limited,
but the evidence base for camu camu is more substantive
than that for competing products.
First, the antioxidant potential of camu camu has been
well established through several biochemical studies. These
studies have established the nutritional composition of camu
camu and the potential role of phytochemicals in disease
prevention and health promotion. As a case in point, the
presence of anthocyanins has been investigated in a number
of animal models and randomized clinical trials in their
association with blood pressure, endothelial function, and
cardioactive protection.
Second, a feature that stands out is the versatility of the
camu camu fruit. It is not just the fruit pulp but the skin and
seed products that show anti-inflammatory potential. Anti-
oxidant capacity is higher from flour produced from the skin
and seed residue than from the pulp or pulp powder.
Third, animal studies involving camu camu juice, while
in their early stages, are providing information on antioxi-
dant and antigenotoxic effects as well as protective effects
in many common conditions and disease states. Although
only suggestive, apart from the evidence for anti-inflam-
matory action, several avenues for further research in hu-
mans may merit attention to support evidence-based claims
for camu camu. These include the following:
1. Potential antiobesity action suggested by the Wistar
rat model for camu camu supplementation. A study
demonstrated a decrease in fat-storing tissue associated
with improvements in fat secretion, insulin levels, a
reduction in VLDL (very-low-density lipoprotein), and
an increase in high-density lipoprotein.
Because the
authors attributed these results to the high level of di-
etary fiber and the phenolic compounds found in camu
camu, there is the potential for antiobesity with camu
camu as a dietary supplement in human trials. Even so,
it should be noted that although obesity has been linked
to chronic systemic inflammation, no change was re-
ported for inflammatory markers.
2. Potential protective effect in liver injury suggested by
the rat model of GalN-induced injury
and the role
of 1-methylmalate presence in camu camu on other
types of liver injury and the potential for liver pro-
tection associated with, for example, alcohol abuse
and hepatitis.
3. Potential for the prevention of immune-related disease
in a study that suggested the seed extract is a source of
betulinic acid.
Finally, the two human studies of camu camu are highly
suggestive. While these studies differ in their design and
implementation, together they point to the potential contri-
bution of camu camu as a dietary supplement. The trial by
Inoue et al. (2008) evaluated the effect of camu camu in
persons who were smokers and were considered to have an
accelerated oxidative stress state;
Ellinger and colleagues’
study (2012), which combined camu camu in a fruit juice
cocktail, considered healthy nonsmokers.
While the juice
blend in the latter study did not reduce markers of oxida-
tive stress, the findings do not preclude beneficial effects
in situations with increased oxidative challenge, such as
smoking, physical activity, and after consumption of food.
To this extent, the Ellinger et al. (2012) results are not in-
consistent with those reported by Inoue et al. (2008).
The evidence to date suggests that camu camu could be a
viable option for maintaining a balanced immune response
and viable antioxidant mediating anti-inflammatory pro-
cesses. Although limited, the evidence indicates that the role
of camu camu in disease management may be driven by its
unique formulation as a natural way of increasing vitamin C.
At the same time, when patients are faced with the some-
times daunting requirements of disease management, camu
camu could be readily accommodated as a supplement in
daily treatment regimens as well as an alternative non-
pharmaceutical option.
Even so, it is important to establish clearly camu camu’s
place, not only as a supplement but as having a possibly
more central role in disease interventions. Further studies
should be considered. The objectives here should be to
support labeling and dosing for camu camu as an antioxidant
and as a dietary supplement to mediate inflammation and to
restore normal inflammatory and immune function. It is
important to recognize the role regulatory agencies, such as
the U.S. Food and Drug Administration, play and to ensure
that claims made are consistent with the evidence base for
the product. In this regard camu camu is well placed to build
on its evidence base with its recognized biochemical prop-
erties and vitamin C profile. More studies are definitely
needed to reinforce the existing evidence base, notably in
target small-scale human studies, and to give more confi-
dence to patients and physicians who are looking to alter-
native medicines. A possibility here is to undertake well-
designed, small-scale human studies directed to specific
disease states and stages of disease where there is a prior
expectation of an important role for camu camu in reducing
inflammation and oxidative stress.
The evidence base for camu camu rests on well-conducted
animal and human studies. The results of these studies point to
a potentially substantial role for camu camu in multimodal,
integrative disease and wellness management, notably with
regard to inflammatory conditions. As a supplement, the fruit
itself offers many avenues for processing and presentation. As
with all alternative medicine products, including dietary sup-
plements, the more substantive the evidence base, the greater
the confidence in the product. At the same time, if specific
medicinal claims can be supported, to include dosing and the
potential for adverse events, the more confidence consumers
will have in the product. In the case of camu camu, clearly
many options could be explored, notably in human trials, to
further evaluate its demonstrated anti-inflammatory and oxi-
dative capability, mechanism of action and its prospective
positive contribution to several disease states. At the same
time there is a pressing need to increase the visibility of nat-
ural products such as camu camu to point to their potential
benefits in populations that are not only aging but also ex-
periencing the negative effect of inflammatory and oxidative
NEMA Research received funding for the preparation of
this manuscript by Amazon Origins.
Author Disclosure Statement
Dr. Langley is a consultant for NEMA Research. Dr.
Pergolizzi is chief operating officer of NEMA Research. Dr.
Taylor is an employee of NEMA Research. Caroline
Ridgway is a consultant for Amazon Origins.
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Address correspondence to:
Caroline Ridgway, JD
Amazon Origins, LLC
P.O. Box 1766
Naples, FL 34106
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... Recently, Langley et al. (2015) cited Brazilian fruit pulps their analysis, among the fruits camu-camu showed a high content of chlorogenic acid, ellagic acid, quercetin and kaempferol. The authors highlight camu-camu as having the highest content of vitamin C, and total phenolics were responsible for the highest DPPH sequestering activity. ...
... In the separation of the active components of camu camu, Langley et al. (2015) and Myoda et al. (2010) noted that the proportion of ascorbic acid (67.5% -79.3%) and the quota of (20.7% -32.5%) of the phenolic compounds present in the peel and seed, which are mainly myricetin, ellagic acid and ellagitanins, cyanidine 3-glycoside, quercetin and proanthocyanidins, have values that are higher than the sum of the skin and the seed of acerola. The authors concluded that the fractional extracts of seeds and peel of camu-camu have a high total phenolic content when compared to other tropical fruits, thus highlighting their antioxidant activities. ...
... In addition to the evidence of antioxidant anti-inflammatory actions of the fruit and its residues, trials and many other supplementary studies have been applied including the use of obese individuals and their comorbidities (Kaneshima et al., 2013;Langley et al., 2015;Arellano-Acuña et al., 2016;Fidelis et al., 2019;Kerimi et al., 2019). This should deserve attention, since many of these diseases reveal a high oxidizing and inflammatory process. ...
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The Amazon Rainforest is rich in a diversity of species with various bioactive properties that have been widely used to treat a variety of inflammatory diseases. During the infection process, an oxidative stress environment is created that leads to cellular damage mediated by the transcription factor NF-kB, and triggers the production of pro-inflammatory chemical mediators, such as tumor necrosis factor-α [TNF-α] and interleukins IL-1β, IL-6, which causes a decline in the immune system. In this sense, the camu-camu fruit, which is native to the Amazon region, has in its nutritional composition several bioactive compounds and the highest level of vitamin C among Brazilian tropical fruits. It is also noted for its antioxidant and anti-inflammatory properties. Therefore, the objective of this review is to analyze the evidence collected in the literature regarding camu-camu as a functional food for the immune system in oxidative and inflammatory events.
... Myrciaria dubia (camu-camu) belongs to the Myrtaceae family, mostly distributed in the Amazon rainforests of Peru, Brazil, Venezuela, and Colombia [15]. In recent years, camucamu has become an economically important fruit species in the Amazon region. ...
... Due to the rich vitamin C content, camu-camu fruit is consumed globally in beverages, functional foods, and cosmetics in different forms of frozen pulp, juice, and extract [16]. Along with anti-oxidant activities, camu-camu has shown pharmacological effects, including those that are anti-inflammatory, anti-microbial, anti-hypertensive, and anti-obesity [15][16][17][18]. In a previous study, we reported the anti-inflammatory activities of camu-camu fruit extract by modulating MAPK and NFAT signaling pathways in keratinocytes [19]. ...
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Although Myrciaria dubia (camu-camu) has been shown to exert anti-oxidant and anti-inflammatory effects in both in vitro and in vivo studies, its use in allergic responses has not been elucidated. In the present study, the anti-allergic effect of 70% ethanol camu-camu fruit extract was tested on calcium ionophore (A23187)-induced allergies in RBL-2H3 cells. The RBL-2H3 cells were induced with 100 nM A23187 for 6 h, followed by a 1 h camu-camu fruit extract treatment. A23187 sanitization exacerbated mast cell degranulation; however, camu-camu fruit extract decreased the release of histamine and β-hexosaminidase, which are considered as key biomarkers in cell degranulation. Camu-camu fruit extract inhibited cell exocytosis by regulating the calcium/nuclear factor of activated T cell (NFAT) signaling. By downregulating the activation of mitogen-activated protein kinase (MAPK) signaling, camu-camu fruit extract hindered the activation of both histamine H1 and H4 receptors and inhibited histidine decarboxylase (HDC) expression by mediating its transcription factors KLF4/SP1 and GATA2/MITF. In A23187-induced ROS overproduction, camu-camu fruit extract activated nuclear factor erythroid-2-related factor 2 (Nrf2) to protect mast cells against A23187-induced oxidative stress. These findings indicate that camu-camu fruit extract can be developed to act as a mast cell stabilizer and an anti-histamine. This work also “opens the door” to new investigations using natural products to achieve breakthroughs in allergic disorder treatment.
... The trees produce rounded fruits with an average mass ranging from 2.2 to 13.5 g, flat and shiny exterior, diameter ranging from 1.0 to 3.8 cm, and containing three to four seeds per fruit unit. When in the ripening state, its color varies from dark red to purple, fruiting between November to March (Chagas et al., 2012;Langley et al., 2015;Neves et al., 2017). ...
... The fruit is not consumed because of the high acidity in its natural form, except for the indigenous people. This happens due to the high content of L-ascorbic acid and phenolic acid, which affect its palatability (Langley et al., 2015). Although there is evidence of its beneficial effect on health, fruit juice still has high sensory rejection rates (Vidigal et al., 2011). ...
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Brazil is one of the countries that share a part of the Amazon region that has been called Legal Amazon. Amazon forest offers the most extraordinary biodiversity of flora and fauna on the planet and, on its surface, can cohabit 50% of the total existing living species. According to some botanists, it would contain about 16-20% of the species that exist today. This region has native fruits with antioxidants and antiproliferative activities already reported by some authors. Consumption of these fruits would be an alternative because they are good sources of nutritional constituents, such as minerals, fibre, vitamins, water, and caloric content. However, the number of scientific studies related to their health benefits is still low. Eugenia stipitata, Myrciaria dubia H. B. K. (Mcvough), Endopleura uchi (Huber) Cuatrecasas, Eugenia punicifolia (Kunth) D.C and Garcinia madruno. Among the main compounds reported are the most interesting groups: phenolic compounds, unsaturated fatty acids, carotenoids, phytosterols, and tocopherols, flavonoids, vitamin B, vitamin A, and vitamin C, and carotenoids. The main beneficial effect of the Amazon fruits is the antioxidant effect; other functional properties as medicinal, antimicrobial, antimutagenic, antigenotoxic, antigenotoxic, and anti-inflammatory, antinociceptive, antidiabetic, and gastroprotective, are also reported. Therefore, these fruits can be considered a valuable source of functional foods due to their phytochemical compositions and their corresponding antioxidant activities.
... CC products have been used as a nutritional supplement that is well tolerated in humans. 44 CC is a fruit rich in polyphenols and has been shown in mouse model of inflammation-related diseases to reduce inflammation and improve gut microbiota with increased A. muciniphila and other beneficial bacteria. [32][33][34][35] However, no studies have been performed to test CC in PLWH. ...
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Introduction Despite the success of antiretroviral therapy (ART) in transforming HIV disease into a chronic infection, people living with HIV (PLWH) remain at risk for various non-AIDS inflammatory comorbidities. Risk of non-AIDS comorbidities is associated with gut dysbiosis, epithelial gut damage and subsequent microbial translocation, and increased activation of both circulating CD4+ and CD8+ T-cells. Therefore, in addition to ART, novel gut microbiota-modulating therapies could aid in reducing inflammation and immune activation, gut damage, and microbial translocation. Among various gut-modulation strategies under investigation, the Amazonian fruit Camu Camu (CC) presents itself as a prebiotic candidate based on its anti-inflammatory and antioxidant properties in animal models and tobacco smokers. Method and analysis A total of 22 PLWH on ART for more than 2 years, with a viral load <50 copies/mL, a CD4 +count >200 and a CD4+/CD8 +ratio <1 (suggesting increased inflammation and risk for non-AIDS comorbidities), will be recruited in a single arm, non-randomised, interventional pilot trial. We will assess tolerance and effect of supplementation with CC in ART-treated PLWH on reducing gut damage, microbial translocation, inflammation and HIV latent reservoir by various assays. Ethics and dissemination The Canadian Institutes of Health Research (CIHR)/Canadian HIV Trials Network (CTN) pilot trial protocol CTNPT032 was approved by the Natural and Non-prescription Health Products Directorate of Health Canada and the research ethics board of the McGill university Health Centre committee (number 2020-5903). Results will be made available as free access through publications in peer-reviewed journals and through the CIHR/CTN website. Trial registration number NCT04058392 .
... precatoria Mart.), and guarana (Paullinia cupana) have aroused interest due to their high content of bioactive compounds and antioxidants. These fruits also provide nutrients that are essential for proper organic functioning, since they have bioactive compounds such as ascorbic acid, phenolic compounds and methylxanthines, all of which have protective effects on the development and progression of dislipidemia [10][11][12][13][14]. ...
Aims: By using histological analysis, the study aims to evaluate the effect of a nutraceutical based on the Amazonian fruits of camu-camu (Myrciaria dubia (Kunth) Mc Vaugh), acai (Euterpe precatoria Mart.) and guarana (Paullinia cupana) on the brain tissue (hippocampus) of dyslipidemic rats. Methodology: Preclinical trials were conducted using male and female rats (n=30) of the Wistar strain (Rattus norvegicus) that were randomly divided into five groups (G) (n=6). G1 was control, G2 was induced to obesity with consumption of experimental feed (hypercaloric and hyperlipidic), G3 was induced to obesity with consumption of experimental feed and treated with simvastatin (50 mg/kg/day), and G4 and G5, which were induced to obesity with the consumption of experimental feed and supplemented with 100 mg/kg/day and 200 mg/kg/day of the formulation, respectively. The study period was 72 days, and, for 37 days, induction to obesity was performed with the experimental feed (hypercaloric and hyperlipidic). During the following weeks, for 35 days, after division of the groups, certain groups received, in parallel, treatment with simvastatin (G3) or supplementation with the nutraceutical (G4 and G5). Subsequently, histological slides of the brain tissue stained with violet cresyl were elaborated, photographed and analyzed. Results: No significant differences were observed between the mean of intact neurons among the experimental groups induced to obesity. The neurotoxic effect, evidenced by the significant difference between the mean of intact neurons between the control group and obesity-induced groups, corroborates the findings of neuronal damage and degenerative processes reported in the literature. Conclusion: The nutraceutical based on Amazonian fruits was not able to prevent the neurotoxic effect arising from the hyperlipidic and hypercaloric diet, and therefore did not present a neuroprotective effect in Wistar rats under the conditions established in the experiment.
... Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the Myrtaceae family that is native to the Amazon rainforest. Its fruit is well-studied for its antioxidative activities both in vitro and in vivo through the decrease of reactive oxygen species (ROS) production [1][2][3]. Camu-camu exhibits pharmacological effects on neuroprotection, antihypertension, antimicrobial, anti-proliferation, and anti-genotoxicity activities [4][5][6][7]. These activities are due to the effects of the vitamin C content, promising polyphenols such as gallic acid, quercetin, and ellagic acid, and proanthocyanins such as cyanidin-3-glycoside. ...
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Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.
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Overweight, obesity, and their comorbidities are currently considered a major public health concern. Today considerable efforts are still needed to develop efficient strategies able to attenuate the burden of these diseases. Nutritional interventions, some with plant extracts, present promising health benefits. In this study, we evaluated the action of Camu-Camu (Myrciaria dubia), an Amazonian fruit rich in polyphenols and vitamin C, on the prevention of obesity and associated disorders in mice and the abundance of Akkermansia muciniphila in both cecum and feces. Methods: We investigated the dose-response effects of Camu-Camu extract (CCE) in the context of high-fat-diet (HFD)-induced obesity. After 5 weeks of supplementation, we demonstrated that the two doses of CCE differently improved glucose and lipid homeostasis. The lowest CCE dose (62.5 mg/kg) preferentially decreased non-HDL cholesterol and free fatty acids (FFA) and increased the abundance of A. muciniphila without affecting liver metabolism, while only the highest dose of CCE (200 mg/kg) prevented excessive body weight gain, fat mass gain, and hepatic steatosis. Both doses decreased fasting hyperglycemia induced by HFD. In conclusion, the use of plant extracts, and particularly CCE, may represent an additional option in the support of weight management strategies and glucose homeostasis alteration by mechanisms likely independent from the modulation of A. muciniphila abundance.
Objetivos. Evaluar el efecto de la harina de Myrciaria dubia (camu camu) sobre el tejido hepático inducido a toxicidad por acetaminofén en ratones. Métodos. Diseño experimental. Se preparó una suspensión de harina de camu camu (HCC) con almidón al 1,6%. Se emplearon 40 ratones machos de la cepa BALB/c, con un peso promedio de 30,8 g y de dos meses de edad, los cuales fueron divididos en cinco grupos, recibiendo el siguiente tratamiento, vía orogástrica, por un período de 10 días, grupos I y II: almidón 1,6% 10 mL/kg; grupo III: HCC 200 mg/kg, grupo IV: HCC 500 mg/kg y grupo V: HCC 800 mg/kg. Al 6to día de tratamiento se le administró acetaminofén (300 mg/kg) a los grupos II-V hasta el 10mo día. Terminada la intervención los animales fueron puestos en ayunas de 12 horas, para luego ser sacrificados previa anestesia con pentobarbital sódico. Se extrajo el hígado, se identificó y seccionó el lóbulo mayor para el estudio bioquímico e histológico. Resultados. La harina de camu camu redujo los niveles del índice hepático, y presentó un mejor perfil del sistema glutatión, comparado con el grupo II; sin embargo, las cifras de lipoperoxidación no mostraron diferencia significativa. A nivel histológico, en los grupos que recibieron HCC se observaron hepatocitos binucleados, así como un mayor mantenimiento de la polaridad; sin embargo, algunas muestras evidenciaron microvacuolas y leve fragmentación de la cromatina. Conclusión. La harina de camu camu evidenció efecto hepatoprotector frente a la toxicidad por acetaminofén en ratones.
The cultivation of a very limited number of crops does not fulfil the nutritional requirements of the growing population. For this, underutilized crops can play a vital role to meet food and nutrition security globally. They are of significant importance in localized areas, as they are highly adapted to marginal lands, do not require high inputs and is resilient to climate variability. The underutilized crops include food crops, such as cereals, vegetables, legumes, oil seeds, root, and tubers, mainly produced as a source of income for livehood of poor farmers in developing countries. Limited germplasm resource availability, lack of information on production, nutritional quality of many of the underutilized plant products, and the lack of improved quality material are the main constraints impacting the availability and productivity of these crops. Plant germplasm resources are the materials required for initiating any crop improvement programme with the help of advances in genomic techniques and various programmes for the improvement of major underutilized crops. At national and international level, genebanks are concerned with the collection, maintenance, ex situ conservation, regional and global germplasm exchange. The chapter highlights the potential of underutilized crops in context to nutrition, food security, and germplasm resources of major underutilized crops for further crop improvement studies.
Nutraceuticals have been the focus of numerous research in recent years and accumulating data support their use for promoting some health benefits. Several nutraceuticals have been widely studied as supplements due to their functional properties ameliorating symptoms associated with neurological disorders, such as oxidative stress and chronic inflammatory states. This seems to be the case of some fruits and seeds from the Amazon Biome consumed since the Pre-Columbian period that could have potential beneficial impact on the human nervous system. The beneficial activities of these food sources are possibly related to a large number of bioactive molecules including polyphenols, carotenoids, unsaturated fatty acids, vitamins, and trace elements. In this context, this review compiled the research on six Amazonian fruits and seeds species and some of the major nutraceuticals found in their composition presenting brief mechanisms related to their protagonist action in improving inflammatory responses and neuroinflammation.
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The term “superfruit” has gained increasing usage and attention recently with the marketing strategy to promote the extraordinary health benefits of some exotic fruits, which may not have worldwide popularity. This has led to many studies with the identification and quantification of various groups of phytochemicals. This contribution discusses phytochemical compositions, antioxidant efficacies, and potential health benefits of the main superfruits such as açai, acerola, camu-camu, goji berry, jaboticaba, jambolão, maqui, noni, and pitanga. Novel product formulations, safety aspects, and future perspectives of these superfruits have also been covered. Research findings from the existing literature published within the last 10 years have been compiled and summarized. These superfruits having numerous phytochemicals (phenolic acids, flavonoids, proanthocyanidins, iridoids, coumarins, hydrolysable tannins, carotenoids, and anthocyanins) together with their corresponding antioxidant activities, have increasingly been utilized. Hence, these superfruits can be considered as a valuable source of functional foods due to the phytochemical compositions and their corresponding antioxidant activities. The phytochemicals from superfruits are bioaccessible and bioavailable in humans with promising health benefits. More well-designed human explorative studies are needed to validate the health benefits of these superfruits.
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Total phenolic contents, antioxidant- and antimicrobial-activities of residual by-products of camu-camu fruit juice production were investigated in order to clarify the potential as functional resources for food industry. The seed and peel of camu-camu juice residue contain significantly more abundant phenols, than other tropical fruits do. The phenol content was higher in the seed extracts than in those of the peel. The radical scavenging activity, reducing power and antimicrobial activity were assayed to investigate its functional properties. The fractionated seed and peel extracts, which contained high total phenolic contents, showed potent antioxidant activity. Especially, those of 25-75% MeOH fractions of the seed exerted stronger antioxidant activity than ascorbic acid. Moreover, the extracts of the seed and peel showed antimicrobial activity to S. aureus, which revealed that the lipophilic constituents were responsible for antimicrobial activities. From these results, the seed and peel of camu-camu juice residue are shown to be promising multi-functional resources.
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Hyperalgesia is a well recognized hallmark of disease. Pro-inflammatory cytokines have been suggested to be mainly responsible, but human data are scarce. Changes in pain threshold during systemic inflammation evoked by human endotoxemia, were evaluated with three quantitative sensory testing methods. Pressure pain thresholds, electrical pain thresholds and tolerance to the cold pressor test were measured before and 2 hours after the intravenous administration of 2 ng/kg purified E. coli endotoxin in 27 healthy volunteers. Another 20 subjects not exposed to endotoxemia served as controls. Endotoxemia led to a rise in body temperature and inflammatory symptom scores and a rise in plasma TNF-α, IL-6, IL-10 and IL-1RA. During endotoxemia, pressure pain thresholds and electrical pain thresholds were reduced with 20±4 % and 13±3 %, respectively. In controls only a minor decrease in pressure pain thresholds (7±3 %) and no change in electrical pain thresholds occurred. Endotoxin-treated subjects experienced more pain during the cold pressor test, and fewer subjects were able to complete the cold pressor test measurement, while in controls the cold pressor test results were not altered. Peak levels and area under curves of each individual cytokine did not correlate to a change in pain threshold measured by one of the applied quantitative sensory testing techniques. In conclusion, this study shows that systemic inflammation elicited by the administration of endotoxin to humans, results in lowering of the pain threshold measured by 3 quantitative sensory testing techniques. The current work provides additional evidence that systemic inflammation is accompanied by changes in pain perception.
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Atherosclerosis is one of the most important contributors to the global burden of cardiovascular diseases. With the recognition of atherosclerosis as an inflammatory disease, nutrition research interest has expanded towards the role of dietary patterns in the prevention of atherosclerosis primarily focused on associations with early inflammatory markers. This review summarizes the latest evidence from January 2010 until January 2013 of eight observational studies on the associations between empirically-derived dietary patterns and diet quality scores with markers of inflammation and endothelial function. Overall, results of recently published cohort studies support those of previously published cross-sectional studies suggesting that consuming a healthy type of diet characteristically abundant in fruits and vegetables is associated with lower concentrations of C-reactive protein and other inflammatory markers. Unfavourable associations were found between eating a Western dietary pattern high in meat and inflammatory markers. Different statistical approaches of deriving dietary patterns were applied in these studies and most of them lacked in reporting absolute intakes of foods and/or food groups. Future prospective cohort studies are needed to evaluate long-term associations between dietary patterns and changes in inflammatory markers by comparing various approaches of dietary pattern derivation within a population. Reporting absolute intakes of foods and/or food groups may also facilitate the identification of a typical dietary pattern that may beneficially influence inflammation.
Background: The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in a large population of men and women. Methods: We obtained data for 3044 middle-aged adults (28.2% women) who were participating in the Whitehall II study and had no history of stroke, myocardial infarction or cancer at our study's baseline (1997-1999). Interleukin-6 was measured at baseline and 5 years earlier. Cause-specific mortality, chronic disease and functioning were ascertained from hospital data, register linkage and clinical examinations. We used these data to create 4 aging phenotypes at the 10-year follow-up (2007-2009): successful aging (free of major chronic disease and with optimal physical, mental and cognitive functioning), incident fatal or nonfatal cardiovascular disease, death from noncardiovascular causes and normal aging (all other participants). Results: Of the 3044 participants, 721 (23.7%) met the criteria for successful aging at the 10-year follow-up, 321 (10.6%) had cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and the remaining 1855 (60.9%) were included in the normal aging phenotype. After adjustment for potential confounders, having a high interleukin-6 level (> 2.0 ng/L) twice over the 5-year exposure period nearly halved the odds of successful aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38-0.74) and increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15-2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58-3.80). Interpretation: Chronic inflammation, as ascertained by repeat measurements, was associated with a range of unhealthy aging phenotypes and a decreased likelihood of successful aging. Our results suggest that assessing long-term chronic inflammation by repeat measurement of interleukin-6 has the potential to guide clinical practice.
To study the association between inflammation and sudden cardiac death (SCD) in a community-based population of older adults. Inflammation is linked to adverse cardiovascular events but its association with SCD has been controversial. Older subjects, who are at particular risk for SCD, were underrepresented in previous studies addressing this issue. In the Cardiovascular Health Study, 5806 and 5382 participants had measurements of C-reactive protein (CRP) and Interleukin-6 (IL6), respectively; and were followed for up to 17 years. SCD risk as a function of baseline IL-6 and CRP was assessed in the overall population and a group of participants without known prevalent cardiac disease. In univariate analyses, both IL-6 [Hazard ratio (HR) 1.79 for 1+ log IL-6, 95% confidence interval (CI) 1.50-2.13; 5(th) vs. 1(st) quintile HR 3.36, 95%CI 2.24-5.05] and CRP (HR 1.31 for 1+ log CRP, 95%CI 1.18-1.45; 5(th) vs. 1(st) quintile HR 2.00, 95%CI 1.40-2.87) were associated with SCD risk. In covariate-adjusted analyses, accounting for baseline risk factors, incident myocardial infarction and heart failure, the association with SCD risk persisted for IL-6 (HR 1.26 for 1+ log IL-6, 95%CI 1.02-1.56, 5(th) vs. 1(st) quintile HR 1.63, 95%CI 1.03-2.56), but was significantly attenuated for CRP (HR 1.13 for 1+ log CRP, 95%CI 1.00-1.28, 5(th) vs. 1(st) quintile HR 1.34, 95%CI 0.88-2.05). Similar findings were observed in participants without prevalent cardiac disease. Greater burden of inflammation, assessed by IL-6 levels, is associated with SCD risk beyond traditional risk factors, incident myocardial infarction and heart failure.
The purpose of the present literature review was to investigate and summarize the current evidence on associations between dietary patterns and biomarkers of inflammation, as derived from epidemiological studies. A systematic literature search was conducted using PubMed, Web of Science, and EMBASE, and a total of 46 studies were included in the review. These studies predominantly applied principal component analysis, factor analysis, reduced rank regression analysis, the Healthy Eating Index, or the Mediterranean Diet Score. No prospective observational study was found. Patterns identified by reduced rank regression as being statistically significantly associated with biomarkers of inflammation were almost all meat-based or "Western" patterns. Studies using principal component analysis or a priori-defined diet scores found that meat-based or "Western-like" patterns tended to be positively associated with biomarkers of inflammation, predominantly C-reactive protein, while vegetable- and fruit-based or "healthy" patterns tended to be inversely associated. While results of the studies were inconsistent, interventions with presumed healthy diets resulted in reductions of almost all investigated inflammatory biomarkers. In conclusion, prospective studies are warranted to confirm the reported findings and further analyze associations, particularly by investigating dietary patterns as risk factors for changes in inflammatory markers over time.