Health benefits of nuts: potential role of antioxidants
Rune Blomhoff1*, Monica H. Carlsen1, Lene Frost Andersen1and David R. Jacobs Jr1,2
1Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
2Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis,
MN 55454-1015, USA
A diet rich in fruits, vegetables and minimally refined cereals is associated with lower risk for chronic degenerative diseases. Since oxidative stress
is common in chronic degenerative disease, it has been assumed that dietary antioxidants may explain this protective effect. Every dietary plant
contains numerous types of antioxidants with different properties. Many of these antioxidants cooperate in oxidative stress reduction in plants, and
we hypothesize that many different antioxidants may also be needed for the proper protection of animal cells. To test this hypothesis, it is useful to
identify dietary plants with high total antioxidant content. Several nuts are among the dietary plants with the highest content of total antioxidants.
Of the tree nuts, walnuts, pecans and chestnuts have the highest contents of antioxidants. Walnuts contain more than 20mmol antioxidants per
100g, mostly in the walnut pellicles. Peanuts (a legume) also contribute significantly to dietary intake of antioxidants. These data are in accordance
with our present extended analysis of an earlier report on nut intake and death attributed to various diseases in the Iowa Women’s Health Study.
We observed that the hazard ratio for total death rates showed a U-shaped association with nut/peanut butter consumption. Hazard ratio was 0·89
(CI ¼ 0·81–0·97) and 0·81 (CI ¼ 0·75–0·88) for nut/peanut butter intake once per week and 1–4 times per week, respectively. Death attributed
to cardiovascular and coronary heart diseases showed strong and consistent reductions with increasing nut/peanut butter consumption. Further
studies are needed to clarify whether antioxidants contribute to this apparent beneficial health effect of nuts.
Nuts: Antioxidants: LDL oxidation: Flavonoids: FRAP: Antioxidant defence: Oxidative damage
Nuts are not easily defined in a manner that would be both
compatible with popular usage and acceptable to botanists.
For example, the groundnut or peanut is a legume, and the
chufa nut, which is common in south Europe and Africa, is
a tuber. Some languages such as French, even lack an
umbrella word equivalent to nuts. ‘Noix’ in French looks
like one, but just means walnuts. In this text we will not
only include botanically defined nuts, but will also include
data on some foods which have traditionally been defined as
Nuts are highly nutritious and of prime importance for
people in several regions in Asia and Africa. Most nuts con-
tain a great deal of fat (e.g. pecan 70%, macadamia nut
66%, Brazil nut 65%, walnut 60%, almonds 55% and
peanut butter 55%). Most have a good protein content (in
the 10–30% range), and only a few have a very high starch
content (Davidson, 1999). Recently, many nuts have also
been identified as especially rich in antioxidants (Halvorsen
et al. 2002; Wu et al. 2004). Nuts therefore constitute one
of the most nutritionally concentrated kinds of food available.
Most nuts, left in their shell, have a remarkably long shelf-life
and can conveniently be stored for winter use.
The aim of this paper is first to present the importance of
antioxidants and oxidative stress for human disease, and
second to report new data on the antioxidant content of var-
ious nuts. We also extend the analysis of Ellsworth et al.
(2001) concerning the association between nut intake and
death attributed to various diseases in the Iowa Women’s
Health Study (IWHS).
Non-enzymatic oxidative damage and oxidative stress
Free radicals and other reactive oxygen and nitrogen species
(ROS and RNS) are formed as a result of normal cellular oxi-
dative metabolic reactions. Such molecules are also formed as
a consequence of diseases (e.g. inflammations) and from
tobacco smoke, environmental pollutants, natural food con-
stituents, drugs, ethanol and radiation. If not quenched by
antioxidants, these highly reactive compounds will react
non-enzymatically with, and potentially alter the structure
and function of, several cellular or extracellular components,
such as cell membranes, lipoproteins, proteins, carbohydrates,
RNA and DNA (Halliwell, 1996; Sies, 1997; Beckman &
Ames, 1998; Gutteridge & Halliwell, 2000; McCord, 2000).
When the critical balance between the generation of free
radicals and other ROS or RNS and the antioxidant defences
is unfavourable, oxidative damage can accumulate. Oxidative
stress is defined as ‘a condition that is characterized by
accumulation on non-enzymatic oxidative damage to mol-
ecules that threaten the normal function of the cell or the
organism’ (Blomhoff, 2005). Compelling evidence
emerged in the last two decades demonstrating that oxidative
stress is intimately involved in the pathophysiology of many
seemingly unrelated types of disease. Thus, oxidative stress
*Corresponding author: Rune Blomhoff, fax þ47 22 85 13 96, email email@example.com
British Journal of Nutrition (2006), 96, Suppl. 2, S52–S60
q The Authors 2006
is now thought to significantly contribute to all inflammatory
diseases (e.g. arthritis, vasculitis, glomerulonephritis, lupus
erythematosus, adult respiratory distress syndrome), ischemic
diseases (heart disease, stroke, intestinal ischemia), cancer,
(AIDS), emphysema, organ transplantation, gastric ulcers,
hypertension and preeclampsia, neurologic diseases (multiple
sclerosis, Alzheimer’s disease, Parkinson disease, amyotrophic
lateral sclerosis, muscular dystrophy), alcoholism, smoking-
related diseases and many others (see Halliwell, 1996; Sies,
1997; Beckman & Ames, 1998; Gutteridge & Halliwell,
2000; McCord, 2000;Blomhoff, 2005 for reviews).
The term ‘antioxidant’ cannot be defined purely chemically; it
is always related to the cellular or organismal context, and to
oxidative stress. Moreover, every molecule can be both an oxi-
dant and a reductant; this is determined by the reduction
potential of the molecule with which it reacts. An antioxidant
is therefore defined as ‘a redox active compound that limits
oxidative stress by reacting non-enzymatically with a reactive
oxidant’, while an antioxidant enzyme is ‘a protein that limits
oxidative stress by catalysing a redox reaction with a reactive
oxidant’ (Blomhoff, 2005).
A complex endogenous antioxidant defence system has
been developed to counteract oxidative damage and oxidative
stress. Such an antioxidant defence is essential for all aerobic
cells. The endogenous antioxidant defence has both enzymatic
and non-enzymatic components that prevent radical formation,
remove radicals before damage can occur, repair oxidative
damage and eliminate damaged molecules (Halliwell, 1996;
Gutteridge & Halliwell, 2000; Lindsay & Astley, 2002). The
endogenous antioxidant defence, which is produced by cells
themselves, consists of components such as glutathione, thior-
edoxin and various antioxidant enzymes. Mutations in genes
coding for these peptides or proteins often lead to increased
incidence of oxidative stress-related diseases as well as prema-
ture death (Dalton et al. 2004; Selverstone et al. 2005).
In addition to endogenous antioxidant defence, it has been
hypothesized that dietary components may also contribute to
antioxidant defence either by providing redox active com-
pounds that can directly scavenge or neutralize free radicals
or other ROS and RNS, or by providing compounds that can
induce the gene expression of the endogenous antioxidants
(Blomhoff, 2005; Moskaug et al. 2005).
Dietary compounds with the ability to induce the
production of endogenous antioxidants
An important antioxidant defence mechanism involves detox-
ification enzymes such as catalase, several types of glutathione
peroxidase and superoxide dismutase, the glutathione S-trans-
ferase family, g-glutamyl cysteine synthetase and NAD(P)H:
quinone reductase (quinone reductase) (Fahey et al. 1997;
Talalay, 2000; McEligot et al. 2005). Many of these enzymes
are generally referred to as phase two enzymes because they
catalyze the conversion of xenobiotics, mutagenic metabolites
or their precursors to compounds that are more readily
excreted. It is believed that if benign or non-damaging plant
compounds induce the phase two enzymes, cells are more
readily able to neutralize toxic agents such as free radicals
and other toxic electrophiles when they appear.
The major plant compounds believed to be able to support
the antioxidant defence via this mechanism include the gluco-
sinolates and several other sulphur-containing plant com-
pounds. Glucosinolates are widespread plant constituents,
and it is believed that glucosinolate breakdown products
(such as the isothiocyanate sulphoraphane) induce phase two
enzymes and are therefore responsible for the protective
effects shown by Brassica vegetables (Fahey et al. 1997;
Talalay, 2000; Lindsay & Astley, 2002). Allium vegetables
contain a number of other sulphur-containing compounds
that may also induce phase two enzymes. These compounds
include the cysteine sulphoxides and the dithiolthiones.
Like the glucosinolates, the active principles found in
allium vegetables result from enzymatic degradation of the
plant compounds (Fahey et al. 1997; Talalay, 2000; Lindsay
& Astley, 2002).
Dietary plants rich in compounds that induce phase two
detoxification enzymes include broccoli, Brussels sprouts,
cabbage, kale, cauliflower, carrots, onions, tomatoes, spinach
and garlic. The evidence for phase two enzyme inductions at
ordinary intake levels of plant foods in humans is, however,
limited, and the importance of this defence mechanism in
the overall protection against oxidative damage is still
Dietary compounds with the ability to directly scavenge or
neutralize reactive oxidants
In addition to the well-known antioxidants, vitamin C, vitamin
E and selenium, there are numerous other antioxidants in diet-
ary plants. Carotenoids are ubiquitous in the plant kingdom,
and as many as 1000 naturally occurring variants have been
identified. At least sixty carotenoids occur in the fruit and veg-
etables commonly consumed by humans (Lindsay & Astley,
2002). Besides the provitamin A carotenoids, a- and b-caro-
tene and b-cryptoxanthin, lycopene and the hydroxy-caroten-
oids (xanthophylls) lutein and zeaxanthin are the main
carotenoids present in diet. Their major role in plants is related
to light harvesting as auxiliary components and quenching of
excited molecules that may be formed during photosynthesis
(Halliwell, 1996; Gutteridge & Halliwell, 2000; Lindsay &
Phenolic compounds are also ubiquitous in dietary plants
(Lindsay & Astley, 2002). They are synthesized in large var-
ieties belonging to several molecular families, such as benzoic
acid derivatives, flavonoids, proanthocyanidins, stilbenes, cou-
marins, lignans and lignins. Over 8000 plant phenols have
been isolated. Plant phenols are antioxidants by virtue of the
groups (Lindsay & Astley, 2002).
Glutathione, thioredoxin and many antioxidant enzymes are
present in abundant amounts in the diet. However, they are not
absorbed as such from the diet but broken down into their con-
stituent amino acids by digestion. The dietary availability of
sulphur amino acids can, however, modulate the cellular glu-
tathione production (Halliwell, 1996; Gutteridge & Halliwell,
2000; Lindsay & Astley, 2002).
It was initially thought that supplementation of a single
antioxidant such as ascorbic acid, a-tocopherol or b-carotene
of the phenolichydroxyl
Health benefits of nuts: potential role of antioxidantsS53
would neutralize free radicals and other ROS or RNS and
thereby avoid any oxidative damage. The first strategy for test-
ing this hypothesis was, therefore, to study the ability of these
antioxidants to inhibit oxidative damage/stress in cell-free
experiments, cell cultures and experimental animals. Such
experiments generated many positive results (McCord, 2000;
Brigelius-Flohe et al. 2002; Cooper et al. 2004). Moreover,
observational epidemiological studies generally support the
hypothesis that the intake of foods rich in these antioxidants
is associated with reduced oxidative stress-related diseases
(Cooper et al. 2004; Stanner et al. 2004). However, large ran-
domized intervention trials that have been conducted to further
test the protective effect of individual antioxidant compounds
have not been supportive (Albanes et al. 1996; Omenn et al.
1996a, 1996b; Rapola et al. 1997). Several reviews and
meta-analyses have recently concluded that, for most forms
of oxidative-stress-related diseases tested so far, there is no
beneficial effect of supplemental a-tocopherol or, probably,
of supplemental b-carotene and ascorbic acid (Vivekananthan,
2003; Eidelman et al. 2004; Shekelle et al. 2004). The results
of intervention studies using supplements of selenium, which
is not an antioxidant itself but an essential building block of
the endogenous antioxidant defence, are more positive, how-
ever (Bjelakovic et al. 2004; Etminan et al. 2005).
The conclusion that antioxidant supplements do not contrib-
ute to the beneficial effects of fruits and vegetables is probably
premature. One explanation could be that the beneficial health
effect arises from the contribution made by other antioxidants
in fruits and vegetables. There are numerous antioxidants in
dietary plants, and only a small number of the antioxidants
in most dietary plants are contributed by a-tocopherol,
ascorbic acid and b-carotene. There is a distinct possibility
that some of these antioxidants, whose role in living plants
is pathogen protection and oxidative stress reduction, can do
better in randomized intervention trials than a-tocopherol,
ascorbic acid and b-carotene.
An alternative antioxidant hypothesis is built on the obser-
vation that antioxidants, which cooperate in an integrated
manner in plant cells, may also cooperate in animal cells.
A network of antioxidants with different chemical properties
may, therefore, be needed for proper protection against oxi-
dative stress (Jacobs & Steffen, 2003; Blomhoff, 2005).
The concerted action from a number of dietary antioxidants
should be expected from the complex physical structure that
constitutes a human being. The human body, its tissues and
organs, cells and macromolecules, consists of phases with a
range of physical variables, anatomical subdivisions, and
water- and lipid-soluble phases. Within these phases, and at
interfaces between phases, there are numerous chemical vari-
ables, such as pH, ionic strength, osmolality, electrical charge
and chemical concentration. These variables influence the
ability of the phases to act as solvents for lipid- and water-sol-
uble antioxidants. As some water-soluble antioxidants have
low partition coefficients into a lipid-soluble phase, their
entry or retention in a water-soluble phase will depend on
their pKa and the pH gradient across the membrane.
In addition, antioxidants with both hydrophobic and hydrophi-
lic characteristics may be distributed between water- and
lipid-soluble phases depending on the relative contribution
and stereochemistry of hydrophobic and hydrophilic substi-
tutions. Solubility is further modified when an antioxidant is
conjugated or bound into more complex substances such as
proteins. Although it would be much simpler to test the protec-
tive effect a of single or of a limited number of antioxidants,
we may never find such an association if it is actually true that
maybe hundreds of dietary antioxidants, such as carotenoids,
polyphenolic acids, sulfides, flavonoids and lignans, are bio-
active and work synergistically.
One theoretical, but likely, possibility is that antioxidants
with different partition coefficients recharge neighbouring
antioxidants in an integrated and complementary manner.
Such interactions have been proven in vitro for a-tocopherol,
a-tocotrienol, vitamin C, lipoic acid and thiols by Packer and
colleagues (Packer et al. 2001). Flavonoids from almonds
have also been shown to act in synergy with vitamin C and
vitamin E and other bioactive plant compounds to enhance
LDL resistance to oxidation (Chen et al. 2005).
A total antioxidant food table
A diet containing a high total content of antioxidants and a
variety of different antioxidants may therefore yield the best
protection against oxidative-stress-related diseases. A ranked
table with the total concentration of redox-active antioxidants
of various foods was, therefore, considered a useful tool for
testing alternative antioxidant hypotheses.
In previous studies, three methods were used to assess total
antioxidant capacity indietary
2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) equiv-
alent antioxidant capacity (TEAC) assay of Miller et al.
(1996), the ferric reducing ability of plasma (FRAP) assay
of Benzie & Strain (1996), and the oxygen radical absorbance
capacity (ORAC) assay of Glazer’s laboratory (DeLange et al.
1989) and others (Cao et al. 1993). The TEAC and the ORAC
assay are based on the antioxidant’s ability to react with or
neutralize free radicals generated in the assay systems, while
the FRAP assay measures the reduction of Fe3þ(ferric iron)
to Fe2þ(ferrous iron) in the presence of antioxidants. Since
the ferric-to-ferrous iron reduction occurs rapidly with all
reductants with half-reaction reduction potentials above that
of Fe3þ/Fe2þ, the values in the FRAP assay express the corre-
sponding concentration of electron-donating antioxidants.
For several reasons we selected the FRAP analysis, which
measures both water- and fat-soluble antioxidants (Halvorsen
et al. 2002; Dragland et al. 2003; Blomhoff, 2005). A major
advantage of the FRAP method is its ability to quantify the
amounts of total antioxidants or reductants in foods. Values
generated by the FRAP method can, therefore, be used to cal-
culate the total intake of antioxidants and the contributions by
various food groups to total dietary intake. The FRAP assay is
also the only one to directly measure antioxidants or reduc-
tants in a sample. The other assays are more indirect because
they measure the inhibition of reactive species (free radicals)
generated in the reaction mixture. These results also strongly
depend on the type of reactive species used. The FRAP
assay, in contrast, uses antioxidants as reductants in a redox-
linked colorimetric reaction. Moreover, the other assays (but
not FRAP) use a lag phase type of measurement. In previous
experiments this has been difficult to standardize and has
R. Blomhoff et al. S54
generated different results between different laboratories. In
the FRAP assay, pretreatment is not required, stoichiometric
factors are constant and linearity is maintained over a wide
range. One possible disadvantage of FRAP is the fact that it
does not react with thiols, because the reduction potential
for thiols is generally lower than that of the Fe3þ/Fe2þhalf-
reaction. However, since only limited amounts of plant gluta-
thione are absorbed by humans (Buettner, 1993), and almost
no other antioxidant thiols are present in dietary plants (one
exception is garlic), the FRAP method may be suitable for
assessing total antioxidants in plants. One disadvantage with
all of these assays is that they measure the total antioxidant
content of foods as eaten, but do not address bioavailability.
This problem exists for all nutrients, however, since food
tables list quantities of substances as eaten, not post-absorp-
Total amounts of antioxidants in nuts and other
We have systematically assessed total antioxidant content
(TAC) in a variety of dietary plants (Halvorsen et al. 2002;
Dragland et al. 2003; Blomhoff, 2005). Foods identified by
the FRAP assay as containing a high level of total antioxidants
include several berries, fruits, nuts, drinks and spices. Table 1
presents TAC values for several nuts while Table 2 contains
values for some other antioxidant-rich foods.
Our analyses demonstrate that walnuts contain massive
amounts of antioxidants, i.e. more than 20mmol antioxidants
per 100g. Pecans, chestnuts, peanuts and pistachios are also
very rich in total antioxidants with average values of 8·3,
4·7, 2·0 and 1·3mmol/100g, respectively. Hazelnuts, almonds,
Brazil nuts, macadamias, pine kernels and cashew nuts also
contained significant amounts of total antioxidants (i.e. 0·3–
0·7mmol/100g). Peanut butter, a common form of nut con-
sumption, contains only approximately a quarter of the total
antioxidants of peanuts. Though not in the top ranks of antiox-
idant containing foods, it is still an important contributor.
Remarkably, in walnuts, most of the antioxidants are
located in the pellicle and less than 10% is retained in the wal-
nuts when the skin is removed. In most other cases, nuts with-
out the pellicle contained less than 50% of the total
antioxidants compared to nuts with the pellicle. Also, Brazil
nuts and pistachios purchased without the outer shell con-
tained much fewer antioxidants than nuts purchased with the
shell. A significant portion of nut antioxidants is therefore
located in the pellicle, and nuts stored with the outer shell
tend to contain more antioxidants than nuts stored without
the shell. The TAC of most nuts are comparable with the
TAC of other antioxidant-rich foods (Table 2) and are much
higher than the TAC values of foods of animal origin such
as meat, cheese and milk, which contain 0·0–0·1mmol/100g
Based on their USDA-specified serving sizes, walnuts,
pecans, chestnuts, peanuts, and peanut butter contribute 6·5,
2·4, 1·3, 0·6 and 0·2mmol antioxidants per serving, respect-
ively. In comparison, other foods that are rich in antioxidants,
such as blueberries, cloves, coffee, dark chocolate and red
wine, contribute 11·9, 9·8, 6·7, 3·8 and 3·1mmol per serving,
respectively. The contribution of nut antioxidants to total diet-
ary intake of antioxidants may also be significant, since the
daily intake of total antioxidants in cereals, fruits and berries,
fruit juices, vegetables, tea and wine each contributes between
0·4–1·5mmol TAC (Svilaas et al. 2004).
The results shown in Table 1 are mean results based on the
analysis of several samples. The full list of results with all
individual items is shown in Table 3. As we can see from
this table, there are relatively large variations within each
nut product. For example, TAC in walnuts with pellicle
ranged from 10·8 to 33·3mmol per 100g. Hazelnuts and
almonds with pellicle ranged from 0·5 to 1·2mmol and 0·2
to 0·7 per 100g, respectively. These values suggest that
nut variety, cultivation conditions and/or storage conditions
Table 1. Total antioxidant content (TAC) in nuts and nut products
Products TAC (mmol/100g) Serving size (g) TAC (mmol/ serving size)
Almonds with pellicle
Almonds without pellicle
Brazil nuts with pellicle
Brazil nuts without pellicle
Brazil nuts with pellicle but purchased without outer shell
Cashews with pellicle
Chestnuts with pellicle
Chestnuts without pellicle
Hazelnuts with pellicle
Hazelnuts without pellicle
Macadamia nuts with pellicle
Peanuts with red pellicle
Peanuts without pellicle
Pecans with pellicle
Pistachios with pellicle
Pistachios with pellicles but purchased without outer shell
Walnuts with pellicle
Walnuts without pellicle
Mean values of items presented in Table 3 are given. Serving size as given by the USDA (U.S. Department of Agriculture, Agricultural Research
Service. 2004. USDA National Nutrient Database for Standard Reference, Release 17).
Health benefits of nuts: potential role of antioxidantsS55
markedly modify the content of total antioxidants. Nuts with
much higher antioxidant contents could reach the market
and be available for human consumption if these parameters
were systematically optimized.
Types of antioxidants found in nuts
Nuts contain numerous types of antioxidants. In almonds, for
example, there is a range of flavonoids, including catechins,
flavonols and flavonones in their aglycone and glycoside
forms (Sang et al. 2002; Frison-Norrie et al. 2002). Peanuts
and pistachios contain several flavonoids and are rich in
resveratrol (Lou et al. 2001), while walnuts contain a variety
of polyphenols and tocopherols. Polyphenols in walnuts are
typically non-flavonoid ellagitannins (Anderson et al. 2001).
Alkyl phenols are found in abundance in cashews (Trevisan
et al. 2005).
Protective effects of nut antioxidants on LDL oxidation in
in vitro experiments and animal models
Nuts probably have favourable effects on cardiovascular dis-
eases through several mechanisms. These effects may be
mediated by their fatty acid profiles, fibre or antioxidant con-
tents, or by a combination of these mechanism. Several recent
observations suggest that nut antioxidants have interesting bio-
logical effects that may be related to a favourable effect on
cardiovascular diseases (Mukuddem-Petersen et al. 2005).
Anderson et al. (2001) used polyphenol-rich extracts from
English walnuts and ellagic acid and studied both their ability
to inhibit LDL oxidation in vitro and their effects on LDL
alpha-tocopherol during oxidative stress: 2,2’-Azobis’(2-ami-
dino propane) hydrochloride-induced LDL oxidation was sig-
nificantly inhibited by 87 and 38% with the highest
concentration (1·0micromol/l) of ellagic acid and walnut
Table 2. Total antioxidant values in other antioxidant-rich foods
Product TAC (mmol/100g) Serving size (g) TAC (mmol/serving size)
Dark chocolate (70% cocoa)
Grape juice (blue)
Black coffee, filtered
140 (1 fruit)
103 (1 glass)
The serving size of each food is in accordance with the USDA National Nutrient Database for Standard
Reference (USDA, Agricultural Research Service. 2004. USDA National Nutrient Database for Standard Reference.
Table 3. Variations in antioxidant content of nuts (from different countries and geographic sources)
Productn Mean ^ SD Range Origin
Almonds with pellicle
Almonds without pellicle
Brazil nuts with pellicle
Brazil nuts without pellicle
Chestnuts with pellicle
Chestnuts without pellicle
Hazelnuts with pellicle
Hazelnuts without pellicle
Peanuts with red pellicle
Peanuts without pellicle
Pistachios bought without outer shell
Walnuts with pellicle
Walnuts without pellicle
0·41 ^ 0·16
0·11 ^ 0·02
0·15 ^ 0·09
0·19 ^ 0·05
0·39 ^ 0·18
0·70 ^ 0·28
0·42 ^ 0·12
0·57 ^ 0·16
0·84 ^ 0·43
8·33 ^ 1·50
0·37 ^ 0·29
1·27 ^ 0·16
0·89 ^ 0·11
23·07 ^ 7·19
1·13 ^ 0·64
USA, Spain, Norway, Australia,
USA, Unknown, Norway
USA, Norway, Unknown
USA, Norway, Australia
USA, Mali, China
USA, Norway, Mexico
USA, Netherlands, Norway
USA, Norway, France, Italy, Unknown
Italy and Unknown
R. Blomhoff et al.S56
extract, respectively. In addition, copper-mediated LDL oxi-
dation was inhibited by 14 and 84% in the presence of ellagic
acid and walnut extract, respectively. LC-ELSD/MS analysis
of the walnut extracts identified ellagic acid monomers, poly-
meric ellagitannins and other phenolics, mainly non-flavonoid
compounds. These results demonstrate that walnut polypheno-
lics are effective inhibitors of in vitro LDL oxidation.
More recently, Chen et al. (2005) demonstrated that
almond-pellicle flavonoids have a relatively high bioavailabil-
ity in hamsters and increase the resistance of copper-mediated
LDL in vitro and ex vivo. They also demonstrated that almond
pellicle flavonoids act in synergy with vitamins C and E.
Hatipoglu et al. (2004) investigated the effect of hazelnut
oil on prooxidant-antioxidant status in rabbits fed a high-
cholesterol diet. As expected, a high-cholesterol diet signifi-
cantly increased lipid and lipid peroxide levels in the
plasma, liver and aorta and led to histopathological athero-
sclerotic changes in the aorta. Hazelnut oil supplementation
reduced plasma, liver and aorta lipid peroxide levels and
aorta cholesterol levels and ameliorated atherosclerotic lesions
in the aortas of rabbits fed the high-cholesterol diet.
Nut antioxidants and human intervention studies
In a crossover trial with hypercholesterolemic patients,
Zambon et al. (2000) showed that the mean total cholesterol
level and the mean LDL cholesterol level decreased by 9·0
and 11·2%, respectively, when patients were submitted to
walnut dietary interventions. Moreover, the LDL particles
were enriched with polyunsaturated fatty acids from walnuts
but preserved their resistance to oxidation. Ros et al. (2004)
showed that, in moderately hypercholesterolemic patients,
walnuts significantly improved oxidative stress-related vascu-
lar endothelial function. In a study with a crossover design by
Iwamoto et al. (2002), forty healthy individuals were ran-
domly assigned to consume a walnut diet (44–58g/d) or a
control diet for 4 weeks. Although plasma lipid levels
improved significantly when subjects were fed the walnut
diet (i.e. total cholesterol and serum apolipoprotein B concen-
trations and the ratio of LDL cholesterol to HDL cholesterol
decreased significantly), LDL oxidizability was not influenced
by the diets in this study.
Hyson et al. (2002) compared the effects of whole-almond
versus almond-oil consumption on LDL oxidation in healthy
men and women. Using a randomized crossover trial design,
twenty-two normolipemic men and women replaced half of
their fat intake with either whole almonds or almond oil for
6-week periods. Both treatments improved lipid parameters
but neither treatment affected in vitro LDL oxidizability.
In a study by Durak et al. (1999), thirty healthy individuals
consumed hazelnuts (1g/d per kg body weight) in addition to
their normal daily diet for 30 days. These authors observed
that hazelnut supplementation improved both lipid biomarkers
and oxidative stress markers (i.e. malondialdehyde levels
decreased and antioxidant capacity increased).
Inflammation is often a cause or effect of oxidative stress.
A recent cross-sectional epidemiologic study of the consump-
tion of nuts and seeds (based on the sum of self-reported
frequency of ‘almonds, walnuts, pecans, other nuts’, ‘sun-
flower, pinyon, other seeds’, and ‘peanuts, peanut butter’)
found lower levels of the circulating inflammatory markers
C-reactive protein, interleukin-6, and fibrinogen with a
higher nut consumption (Jiang et al. 2006). Therefore, the
results of this study support the hypothesis that nut antioxi-
dants may reduce oxidative stress and, therefore, oxidative-
stress-related disease such as inflammation.
Nut/peanut butter consumption is associated with a
decreased incidence of cardiovascular diseases
We have extended the analysis of Ellsworth et al. (2001) on
the association between nut intake and death attributed to var-
ious diseases in the Iowa Women’s Health Study (IWHS). As
previously described (Ellsworth et al. 2001), this is a prospec-
tive cohort comprising 41 836 women aged 55–69 years
recruited via a baseline questionnaire (including a 127-item
food frequency questionnaire) mailed in 1986 and followed
through to 31 December 2001. Ellsworth et al. reported on
nut consumption (based on self-reported frequency of a
single item, ‘nuts’) in 34 111 postmenopausal women in the
first 12 years of follow-up, during which 3726 women died,
657 from coronary heart disease (CHD). After multiple adjust-
ment, they compared two or more 28·5g servings per week to
less than one serving per month and found a 19% lower risk
of death from CHD and a 12% lower risk of all-cause mor-
tality. In the present study, we excluded women who were
not postmenopausal and those with self-reported baseline
heart disease or diabetes. Our study consisted of a 15-year
follow-up of 31 778 women, comprising a total of 472 354
person years, with 5451 total deaths, including 1675 from car-
diovascular disease (CVD) and 948 from coronary heart dis-
ease. We studied whether the risk of death due to coronary
heart disease (CHD) or cardiovascular disease (CVD) is
associated with the sum of self-reported ‘nuts’ and ‘peanut
butter’ consumption in these women, who consume nuts as
part of their normal diet.
The mean (SD) consumption of nuts/peanut butter in the
IWHS was 2·37 servings/week (3·44), of which 0·75 (1·75)
and 1·62 (2·81) servings per week were nuts and peanut
butter, respectively. Median intakes of nuts plus peanut
butter and of each item separately are given in Table 4 for
four intake levels.
After adjustment for age and energy intake, the hazard ratio
for total death rates showed a U-shaped association with nut/
peanut butter consumption (Table 4). The hazard ratio was
0·89 (CI ¼ 0·81–0·97) and 0·81 (CI ¼ 0·75–0·88) for
nut/peanut butter intake once per week and 1–4 times per
week, respectively, but slightly higher for five or more times
per week (P ¼ 0·003 for quadratic trend). Death attributed
to CVD and CHD showed strong and consistent reductions
with increasing nut/peanut butter consumption, with hazard
ratios of 0·67 (CI ¼ 0·56–0·81) and 0·67 (CI ¼ 0·52–
0·86), respectively, for those reporting nut/peanut butter
intake five or more times per week. These findings were
slightly attenuated by additional adjustment. Most of the
association with deaths from cardiovascular and coronary
heart disease was attributable to peanut butter intake, which
constituted more than two-thirds of the total nut/peanut
butter intake in these data. Separate analyses confirmed that
the findings for the single ‘nuts’ item were similar to those
of Ellsworth et al. (2001) (data not shown). In particular,
fewer than 1000 women reported consumption of nuts five
Health benefits of nuts: potential role of antioxidantsS57
or more times per week, so there was very little power to study
daily consumption of nuts. No significant associations were
observed between nut consumption and death from cancer or
other diseases (data not shown).
The inverse association between nut intake and cardiovas-
cular and coronary heart diseases in epidemiological studies
may, or may not, be associated with antioxidants. Epidemiolo-
gic studies are not ideally suited for studying the role of
specific nuts or biological mechanism. These studies follow
disease rates according to broad consumption categories,
such as ‘nuts’ and ‘peanut butter’ in the case of the Iowa
Women’s Health Study. Nevertheless, the findings presented
here support the theory subscribed to in this paper, namely
that the complex and rich mix of nut constituents protects
against cardiovascular and perhaps other chronic diseases.
Whether this protection is due to the antioxidant content of
nuts cannot be ascertained from our data.
In conclusion, here we have identified several nuts as being
among the dietary plants with highest contents of total antiox-
idants. Of the tree nuts, walnuts, pecans and chestnuts have the
highest contents of antioxidants. In walnuts most of the anti-
oxidants are located in the walnut pellicle. These data are in
accordance with our present extended analysis of an earlier
report on the association between nut intake and death attrib-
uted to various diseases in the Iowa Women’s Health Study
(Ellsworth et al. 2001). Death attributed to cardiovascular
and coronary heart diseases showed strong and consistent
reductions with increasing nut/peanut butter consumption.
Interestingly, most of the association with deaths due to cardi-
ovascular and coronary heart disease was attributable to
peanut butter intake, which constituted more than two-thirds
of the total nut intake in these data. While these findings sup-
port the theory subscribed to in this paper, namely that the
complex and rich mix of nut constituents are protective
against cardiovascular and perhaps other chronic diseases,
they are not sufficiently specific to ascertain whether such pro-
tection is specific to the antioxidant content of nuts. The area
is ripe for intensive studies, including controlled intervention
studies, to clarify the extent to which the antioxidant content
and other biochemical features of nuts may contribute to
We thank Kari Holte for excellent technical assistance, and the
Research Council of Norway, the Throne Holst foundation and
the Norwegian Cancer Society for generous support to projects
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P value for trend‡
P value for quadratic trend
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‡Linear trend was tested in a separate model from the test of quadratic trend.
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