Elsevier

Nutrition

Volume 60, April 2019, Pages 74-79
Nutrition

Basic nutritional investigation
Aldehydes identified in commercially available ω-3 supplements via 1 H NMR spectroscopy

https://doi.org/10.1016/j.nut.2018.10.004Get rights and content

Highlights

  • Supplementation with ω-3 is helpful in achieving cardiovascular protective effects.

  • Epidemiologic data does not universally support such effects.

  • Many commercially available ω-3 supplements are oxidized at time of consumption.

  • This study identified aldehydes in 8 of 12 products, at concentrations between 1 and 7 mMol/L.

  • Aldehydes pose potentially serious health risks, even at very low intake volumes.

Abstract

Objectives

Cardiovascular disease (CVD) is the leading cause of mortality globally. Studies have suggested that supplementary ω-3 oils may provide cardiovascular protection, although the literature is equivocal. Recently, it has been established that many commercially available ω-3 supplements are unacceptably oxidized, leading to myriad potential health risks. One oxidation product of concern is aldehydes, which have been shown to have mutagenic, cytotoxic, and inflammatory properties that may contribute to many different disease processes, including CVD. The aim of this study was to assess the prevalence of aldehyde contamination in commercially available ω-3 supplements.

Methods

We tested 12 different ω-3 oils (6 fish, 4 krill, 2 algae), using 1 H-nuclear magnetic resonance scanning. This work is of a pilot nature, as such we randomly selected and purchased 12 different oils over the counter from various local retailers according to the sales representatives’ recommendations.

Results

The four krill products contained aldehydes at concentrations between 5.652 (±0.496) and 6.779 (±1.817) mMol/L. Both algae samples contained aldehydes: 1.235 (±0.111) and 1.565 (±0.618) mMol/L. Two of the six fish oils contained aldehydes 1.568 (±0.291) and 4.319 (±2.361) mMol/L. There is currently no standard for aldehyde content nor for labeling of ω-3 supplements. Two-thirds (8 of 12) of the ω-3 supplements tested in this study contained aldehydes. Aldehydes have the potential to precipitate serious health problems even at very low absolute intake volumes. These findings may provide reason for sober reflection.

Introduction

Cardiovascular disease (CVD) is the leading cause of mortality globally [1]. CVD is demonstrably causally related to chronic inflammation [2], [3], [4], among other factors. Studies have suggested that ω-3 fatty acids (FAs) have anti-inflammatory and therefore cardioprotective effects [5], [6], [7], [8], [9]. The long-chain polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the main ω-3 FAs that have been attributed to cardioprotective effects [8]. Because the Western diet is usually low in ω-3 FAs, supplementation is generally recommended [10], [11]. Worldwide, ω-3 FAs are one of the most commonly consumed supplements [12].

Despite the popularity of supplementation with ω-3 oils, benefits for cardiovascular health are unclear [5], [10], [12], [13]. Supplementation with ω-3 may not actually be associated with a lower risk for mortality ascribable to cardiac death, sudden death, myocardial infarction, or stroke [10], [13], [14]. One possible explanation for this equivocality may be in the propensity for PUFAs, of which ω-3 is a form, to oxidize. PUFAs tend to oxidize because of their large numbers of carbon–carbon double bonds and owing to the position of these bonds [15]. Aldehydes are a potential oxidation product. Aldehydes have been shown to have mutagenic, cytotoxic, immune system aggravating, and inflammatory properties in addition to direct injurious effects on endothelial cells that may contribute to many different disease processes [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37]. Therefore, it is important to determine whether oxidation is a common problem in commercially available ω-3 FA supplements.

Several existing studies have concluded that lipid peroxidation is indeed a common problem in ω-3 FA supplements [15], [20], [38], [39]. The oxidative state of oils has been commonly determined by measurement of the peroxide and anisidine values. Although these methods can determine the total amount of primary and secondary oxidation products, the composition of these lipid peroxides (LOPs) in terms of groupings of types of LOPs is undetermined by these methods. Because different aldehydes have distinct modes of action and various grades of reactivity, it is important to determine the type(s) of aldehydes present. Nuclear magnetic resonance (NMR) spectroscopy often is used to study chemical structures. 1 H NMR can be used to identify the carbon-hydrogen structures present in organic compounds, and thus the group of any aldehydes present [40]. As NMR is a very sensitive detection method, it is possible to detect very small concentrations that may not be detectable using other methods. Because even small amounts of aldehydes may be harmful [26], this study is of great importance. Therefore, we investigated the hypothesis that aldehydes are indeed present in many commercially available ω-3 FA supplements. The focus of this study was exclusively on commercially available EPA- and DHA-rich encapsulated ω-3 FA supplements because these are the most common mediums for their consumption. Because of resource constraints, it was not the purpose of this study to identify the exact molecular species present. That task falls to future studies. This work is of a pilot nature, thus we randomly selected and purchased 12 different oils over the counter from various local retailers according to the sales representatives’ recommendations. Further study is required to assess the prevalence of aldehyde contamination in commercially available ω-3 supplements more widely.

Section snippets

Materials

All reagents were purchased from Sigma-Aldrich (U.K.), unless otherwise stated. Twelve different commercially available encapsulated ω-3 FA supplements were analyzed in this study. All ω-3 supplements were within their use-by dates. The samples were fish, krill, or algae oils. The use of the NMR machine was negotiated with a local university professor.

Sample preparation

Oil capsules were incised at one end and the oil collected in a clean glass tube. We immediately transferred 200 µL of each oil to another clean

Results

A typical 1 H NMR spectrum of krill oil with magnifications of its 0.80 to 1.02 and 9.75 to 9.83 ppm regions is shown in Figure 1. ω-3 FAs give rise to a signal at 0.97 ppm, ω-6 FAs at 0.89 ppm, ω-9 and saturated fatty acids (SFAs) both appear at 0.88 ppm (Table 1 provides further details). The difference between these signals is due to the carbon–carbon double bond at the ω-3 position in the ω-3 FAs compared with the position of double bonds in other unsaturated FAs. Quantification of ω-3 as a

Disclaimers

The present study did not make any inferences with respect to purified EPA or DHA oil products because the samples were not purified (i.e., fish, krill, or algae extracts). The study did not make inferences with respect to products containing antioxidants, as none of the samples tested contained these. This study was of a pilot nature; as such, more data is needed to determine the prevalence of oxidation in commercially available ω-3 supplements more widely.

Krill oils

Three different groups of aldehydes

Conclusion

Of the 12 ω-3 supplements tested in this study, 75% two-thirds, (8/12) contained aldehydes. Aldehydes are potentially problematic owing to the risks for multiple types of adduct formation with biological molecules, leading potentially to inflammation, dysfunction, CVD, DNA damage, cancers, and a myriad of other health concerns. Krill oils tested in this study invariably contained aldehydes, and at relatively very high concentrations. Fish and algae oils contained aldehydes in four of the eight

Acknowledgment

The authors acknowledge Martin Grootveld for allowing access to the NMR spectrometer, his advice on data collection and interpretation, and access to comparative spectra.

References (65)

  • L. Guo et al.

    Phosphatidylethanolamines modified by γ-ketoaldehyde (γKA) induce endoplasmic reticulum stress and endothelial activation

    J Biol Chem

    (2011)
  • S.J. Chapple et al.

    Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox signalling and function in health and disease

    Redox Biol

    (2013)
  • C. Cerletti et al.

    Platelet-leukocyte interactions in thrombosis

    Thromb Res

    (2012)
  • R. Kiwamoto et al.

    An integrated QSAR-PBK/D modelling approach for predicting detoxification and DNA adduct formation of 18 acyclic food-borne α,β-unsaturated aldehydes

    Toxicol Appl Pharmacol

    (2015)
  • N. Siddiqui et al.

    Multicomponent analysis of encapsulated marine oil supplements using high-resolution 1 H and 13 C NMR techniques

    J Lipid Res

    (2003)
  • A.N. Onyango et al.

    The rapid oxidative degradation of a phosphatidylcholine bearing an oxidatively modified acyl chain with a 2,4-dienal terminal

    Chem Phys Lipids

    (2004)
  • F.L. Chung et al.

    Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation

    Mutat Res

    (2003)
  • C.M. Spickett

    The lipid peroxidation product 4-hydroxy-2-nonenal: advances in chemistry and analysis

    Redox Biology

    (2013)
  • J. Kanner et al.

    The stomach as a bioreactor: dietary lipid peroxidation in the gastric fluid and the effects of plant-derived antioxidants

    Free Radic Biol Med

    (2001)
  • R. Maestre et al.

    Alterations in the intestinal assimilation of oxidized PUFAs are ameliorated by a polyphenol-rich grape seed extract in an in vitro model and Caco-2 cells

    J Nutr

    (2013)
  • F. Visioli

    Rusting the pipes: ingestion of oxidized lipids and vascular disease

    Vasc Pharmacol

    (2014)
  • K. Kanazawa et al.

    Dietary hydroperoxides of linoleic acid decompose to aldehydes in stomach before being absorbed into the body

    Biochim Biophys Acta

    (1998)
  • World Health Organization. Media centre cardiovascular diseases (CVDs). Fact sheet No. 317....
  • H.K. Maehre et al.

    ω-3 Fatty acids and cardiovascular diseases: effects, mechanisms and dietary relevance

    Int J Mol Sci

    (2015)
  • M.C. De Oliveira Otto et al.

    Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the multi-ethnic study of atherosclerosis

    J Am Heart Assoc

    (2013)
  • T.A.B. Sanders

    Conference on “PUFA mediators: implications for human health” Symposium 1: PUFA: health effects and health claims protective effects of dietary PUFA against chronic disease: evidence from epidemiological studies and intervention trials

    Proc Nutr Soc

    (2014)
  • M. Oliver

    Erythrocyte omega-3 polyunsaturated fatty acid levels are associated with biomarkers of inflammation in older Australians

    J Nutr Intermed Metab

    (2016)
  • A. Mohebi-Nejad et al.

    Omega-3 supplements and cardiovascular diseases

    Tanaffos

    (2014)
  • A. Abdelhamid et al.

    Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease

    Cochrane Database Syst Rev

    (2018)
  • E. Rizos et al.

    Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis

    JAMA

    (2012)
  • B.L. Halvorsen et al.

    Determination of lipid oxidation products in vegetable oils and marine omega-3 supplements

    Food Nutr Res

    (2011)
  • A. Ayala et al.

    Lipid peroxidation: production, metabolism, and signalling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal

    Oxid Med Cell Longev

    (2014)
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