Research Review By Novella Martinello©

Date Posted:

July 2010

Study Title:

Nuts and oxidation: a systematic review


López-Uriarte P, Bulló M, Casas-Agustench P, Babio N, & Salas-Salvadó J.

Author's Affiliations:

Human Nutrition Unit, Hospital Universitari Sant Joan de Reus, IISPV, Universitat Rovira i Virgili, Reus, Spain & CIBER 06/03, Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.

Publication Information:

Nutrition Reviews 2009; 67(9): 497-508.

Background Information:

Various epidemiological studies and clinical trials have already associated frequent nut consumption with a plethora of cardiovascular benefits such as reduced risk of coronary heart disease (CHD), type 2 diabetes, or death by all-causes, as well as benefits on plasma lipids and lipoproteins (1). Oxidative stress plays a key role in atherosclerosis and coronary heart disease.

Polyunsaturated fatty acids (PUFA) are the most susceptible to oxidation and the PUFA content of nuts (principally walnuts) may lead to an increase in LDL oxidation. However, some bioactive compounds in nuts may counteract the pro-oxidant effect of PUFA on LDL. This is important because nuts are a rich source of many antioxidants that may protect PUFA in vivo against oxidative modification.

Several methods have been used to assess the total antioxidant capacity (TAC) of nuts. However, the impossibility of comparing results obtained with different methodologies has seriously limited understanding of the role of TAC in disease prevention. Different nuts have different types of antioxidants such as catechins, flavonols, flavonoids, polyphenols, and tocopherols. The phytochemicals contained in nuts could work in synergy with other important nut constituents to promote antioxidant activities.

The article presents a systematic review of human and animals trials and studies conducted using in vitro assays to evaluate the effect of nuts on oxidative stress parameters, as past results related to the possible effect of nuts on oxidative stress is ambiguous.


Effects of tree nut extracts on oxidative stress in in vitro studies:

All of the six studies using in vitro assays that were analyzed in this review showed an improvement in most of the oxidative stress biomarkers assessed with several types of tree nut extracts on human plasma or LDL particles, bovine liver microsomal membranes, or plasmid DNA. Four studies found greater inhibition of lipid peroxidation in LDL (2). Using almonds or hazelnuts, two studies found decreased lipid peroxidation.

One study using pistachio extract found a significant decrease in TBARS formation in bovine liver microsomes and two studies showed that almonds and hazelnuts have a greater protective effect against strand breaking in supercoiled DNA than incubation with the control compounds quercetin or catechin. These studies demonstrate tree-nut extracts as a major source of antioxidants, with the potential capacity for modulating oxidative stress.

Effect of nuts on oxidation in animal studies:

An increase in dietary walnuts has been shown to be associated with a significant inverse effect in the aortic endothelin (ET-1) levels and it may be that the beneficial effects on CVD risk were not due to changes in oxidative stress but were partly due to ET-1–related effects on the endothelial processes. Another study evaluated the effect of pistachio consumption on serum paraoxonase-1 (PON1) and arylesterase activities and exhibited a significant increase in PON1 and arylesterase activities compared to controls.

A study involving rabbits showed nut consumption to significantly decrease plasma, liver, and aorta lipid peroxidation. It has been suggested that hazelnut oil may have antiatherogenic potential, which could be related to its reducing effect on oxidative stress biomarkers and, especially, on LDL oxidation. Both acute studies showed improved oxidative stress biomarkers after rodents consumed walnuts or flavonoid extracts from almond skin (3).

These results suggest that this flavonoid extract is bioavailable and acts in synergy with vitamins C and E to protect LDL against oxidation. This beneficial effect was related to the increased levels of blood melatonin secondary to the ingestion of walnuts.

The effect of nuts on biomarkers of oxidative stress in controlled feeding trials of humans:

Almost all the 20 studies analyzed were carried out in small, heterogeneous population samples, with a total of 656 individuals (400 men and 256 women). Most of the studies were crossover clinical trials (n = 15), but five used a parallel design. Nuts were administered in different types, doses, and presentations. The nuts evaluated were walnuts, peanuts, almonds, pistachios, cashews, pecans, and Brazil nuts. Comparisons were made with control diets or meals in which the individuals were asked not to consume nuts, nut butter, or nut oil of any kind.

The results from studies evaluating the effect of nuts on antioxidant capacity are mixed. One study revealed pistachios to significantly increase plasma antioxidant potential, measured as the capacity to inhibit TBARS production (4), while one study found no significant effects on the plasma antioxidant capacity after the whole-walnut or cashew diet interventions in subjects with metabolic syndrome (5). No significant differences were found among participants with type 2 diabetes patients using a walnut intervention. A study using raw, unblanched almonds added to meals found that the postprandial antioxidant capacity of serum was not significantly influenced.

All of the studies evaluating lipid peroxidation by measuring the oxidized LDL in serum observed that nut consumption induced no significant changes. Lipid peroxidation decreased in almost all the studies that evaluated the effect of dietary nut consumption. This effect was shown in subjects with metabolic stress and in healthy individuals. One study examining the effect of almond consumption among smokers found a significant decrease in plasma MDA concentrations and a better response in other oxidation parameters.

The effect of nuts (almonds) was also analyzed in hypercholesterolemic patients and in subjects at high risk of CHD. In both studies, erythrocyte MDA concentrations decreased significantly during the walnut-enriched-meat-diet period compared to the period without walnuts.

Only two of the 20 studies evaluated lipid peroxidation by measuring the 24-h urine isoprostane concentration – one trial found it to be significantly lower when patients received an almond supplement in the context of a low-fat diet compared to when they did not receive it and one trial found postprandial total 8-isoprostane-F2a plasma concentrations were not significantly influenced by the consumption of almond test muffins baked with either almond oil, seeds, or flour.

Eight of the 20 studies measured the effect of nut consumption on lipid peroxidation in LDL particles - some found an improvement in CD formation, whereas others did not find any significant effects. Four chronic clinical trials studied the effect of walnut consumption on CD formation using a crossover design. In all of these studies, response tended to be worse during the walnut consumption period. Mixed results were also observed when the effect of almond consumption on healthy and hypercholesterolemic patients was analyzed.

The effect of nut consumption on antioxidant non-enzymatic or enzymatic activity was measured in five studies. Positive effects were observed in three of them (using almond powder (6), walnut-enriched meat, and Brazil nuts) and no statistically significant effect in two (walnuts and cashews). Oxidative DNA damage was analyzed in only two studies, which were conducted in healthy male smokers after they had consumed a supplement of whole-almond powder, and results suggested that almonds can help decrease the oxidative stress mediated by tobacco.

Clinical Application & Conclusions:

Some whole nuts – almonds, pistachios, Brazil nuts, and peanuts - demonstrate beneficial effects for cardiovascular health. The potential antioxidant activity of the polyphenols, phytosterols, and other antioxidants contained in nuts, particularly in the skin, may counteract the pro-oxidant effects of fat, thus preventing potentially adverse effects on oxidation. This finding is not consistent among walnut trials.

Study Methods:

Articles were identified through the PubMed and Web of Science databases and from reference lists of other relevant publications selected for review. 20 clinical trials met inclusion criteria. Of these, five evaluated antioxidant capacity, 16 evaluated parameters related to lipid peroxidation, five evaluated antioxidant enzymatic and non-enzymatic activities, and two evaluated markers related to DNA damage.

Search Terms:
  • MeSH terms (PubMed): “nuts” [Mesh] AND“humans” [Mesh] in “All Fields” as tag terms
  • Web of Science: (oxidat*) AND (almond* OR cashew* OR hazelnut* OR macadamia* OR peanut* OR pistachio* OR walnut* OR chestnut* OR pecan* OR pine nut OR Brazil nut OR filbert* OR hickory*).
Inclusion Criteria:
  • randomized, controlled, clinical feeding trials
  • the intervention diet had to be supplemented with at least one of the following types of nut: almond, cashew, hazelnut, macadamia, peanut, pistachio, walnut, chestnut, pecan, pine nut, and Brazil nut
  • published in a scientific journal between January 1990 and January 2009
  • they had to be original
  • they had to evaluate the effects of nuts on at least one of the following oxidative stress biomarkers: in vivo antioxidant capacity, oxidized LDL, MDA concentrations, plasma or urine isoprostane concentrations, CD formation, antioxidant non-enzymatic and enzymatic activities or DNA damage were the primary or secondary objectives.

Additional References:

  1. Kelly JH Jr, Sabate J. Nuts and coronary heart disease: an epidemiological perspective. Br J Nutr 2006; 96(Suppl2): S61–S67.
  2. Gentile C, Tesoriere L, Butera D, et al. Antioxidant activity of sicilian pistachio (Pistacia vera L. var. bronte) nut extract and its bioactive components. J Agric Food Chem 2007; 55: 643–648.
  3. Chen CY,Milbury PE, Lapsley K, Blumberg JB. Flavonoids from almond skins are bioavailable and act synergistically with vitamins C and E to enhance hamster and human LDL resistance to oxidation. J Nutr 2005; 135: 1366–1373.
  4. Kocyigit A, Koylu AA, Keles H. Effects of pistachio nuts consumption on plasma lipid profile and oxidative status in healthy volunteers. Nutr Metab Cardiovasc Dis 2006; 16: 202– 209.
  5. Davis L, Stonehouse W, Loots du T, et al. The effects of high walnut and cashew nut diets on the antioxidant status of subjects with metabolic syndrome. Eur J Nutr 2007; 46:155– 164.
  6. Li N, Jia X, Chen CY, et al. Almond consumption reduces oxidative DNA damage and lipid peroxidation in male smokers. J Nutr 2007; 137: 2717–2722.