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      The Role of n-3 Long Chain Polyunsaturated Fatty Acids in Cardiovascular Disease Prevention, and Interactions with Statins

      review-article
      1 , * , 2 , 3 , 1
      Nutrients
      MDPI
      omega-3, cardiovascular disease, statins

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          Abstract

          Decreases in global cardiovascular disease (CVD) mortality and morbidity in recent decades can be partly attributed to cholesterol reduction through statin use. n-3 long chain polyunsaturated fatty acids are recommended by some authorities for primary and secondary CVD prevention, and for triglyceride reduction. The residual risk of CVD that remains after statin therapy may potentially be reduced by n-3 long chain polyunsaturated fatty acids. However, the effects of concomitant use of statins and n-3 long chain polyunsaturated fatty acids are not well understood. Pleiotropic effects of statins and n-3 long chain polyunsaturated fatty acids overlap. For example, cytochrome P450 enzymes that metabolize statins may affect n-3 long chain polyunsaturated fatty acid metabolism and vice versa. Clinical and mechanistic study results show both synergistic and antagonistic effects of statins and n-3 long chain polyunsaturated fatty acids when used in combination.

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          Most cited references67

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          Distribution, interconversion, and dose response of n−3 fatty acids in humans

          n-3 Fatty acids have important visual, mental, and cardiovascular health benefits throughout the life cycle. Biodistribution, interconversion, and dose response data are reviewed herein to provide a basis for more rational n-3 dose selections. Docosahexaenoic acid (DHA) is the principal n-3 fatty acid in tissues and is particularly abundant in neural and retinal tissue. Limited storage of the n-3 fatty acids in adipose tissue suggests that a continued dietary supply is needed. A large proportion of dietary alpha-linolenic acid (ALA) is oxidized, and because of limited interconversion of n-3 fatty acids in humans, ALA supplementation does not result in appreciable accumulation of long-chain n-3 fatty acids in plasma. Eicosapentaenoic acid (EPA) but not DHA concentrations in plasma increase in response to dietary EPA. Dietary DHA results in a dose-dependent, saturable increase in plasma DHA concentrations and modest increases in EPA concentrations. Plasma DHA concentrations equilibrate in approximately 1 mo and then remain at steady state throughout supplementation. DHA doses of approximately 2 g/d result in a near maximal plasma response. Both dietary DHA and EPA reduce plasma arachidonic acid concentrations. Tissue contents of DHA and EPA also increase in response to supplementation with these fatty acids. Human milk contents of DHA are dependent on diet, and infant DHA concentrations are determined by their dietary intake of this fatty acid. We conclude that the most predictable way to increase a specific long-chain n-3 fatty acid in plasma, tissues, or human milk is to supplement with the fatty acid of interest.
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            Why US adults use dietary supplements.

            Dietary supplements are used by more than half of adults, although to our knowledge, the reasons motivating use have not been previously examined in US adults using nationally representative data. The purpose of this analysis was to examine motivations for dietary supplement use, characterize the types of products used for the most commonly reported motivations, and to examine the role of physicians and health care practitioners in guiding choices about dietary supplements. Data from adults (≥20 years; n = 11 956) were examined in the 2007-2010 National Health and Nutrition Examination Survey, a nationally representative, cross-sectional, population-based survey. The most commonly reported reasons for using supplements were to "improve" (45%) or "maintain" (33%) overall health. Women used calcium products for "bone health" (36%), whereas men were more likely to report supplement use for "heart health or to lower cholesterol" (18%). Older adults (≥60 years) were more likely than younger individuals to report motivations related to site-specific reasons like heart, bone and joint, and eye health. Only 23% of products were used based on recommendations of a health care provider. Multivitamin-mineral products were the most frequently reported type of supplement taken, followed by calcium and ω-3 or fish oil supplements. Supplement users are more likely to report very good or excellent health, have health insurance, use alcohol moderately, eschew cigarette smoking, and exercise more frequently than nonusers. Supplement users reported motivations related to overall health more commonly than for supplementing nutrients from food intakes. Use of supplements was related to more favorable health and lifestyle choices. Less than a quarter of supplements used by adults were recommended by a physician or health care provider.
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              alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans.

              Blood levels of polyunsaturated fatty acids (PUFA) are considered biomarkers of status. Alpha-linolenic acid, ALA, the plant omega-3, is the dietary precursor for the long-chain omega-3 PUFA eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Studies in normal healthy adults consuming western diets, which are rich in linoleic acid (LA), show that supplemental ALA raises EPA and DPA status in the blood and in breast milk. However, ALA or EPA dietary supplements have little effect on blood or breast milk DHA levels, whereas consumption of preformed DHA is effective in raising blood DHA levels. Addition of ALA to the diets of formula-fed infants does raise DHA, but no level of ALA tested raises DHA to levels achievable with preformed DHA at intakes similar to typical human milk DHA supply. The DHA status of infants and adults consuming preformed DHA in their diets is, on average, greater than that of people who do not consume DHA. With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                15 June 2018
                June 2018
                : 10
                : 6
                : 775
                Affiliations
                [1 ]DSM Nutritional Products, 4303 Kaiseraugst, Switzerland; manfred.eggersdorfer@ 123456dsm.com
                [2 ]Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; pcc@ 123456soton.ac.uk
                [3 ]NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO16 6YD, UK
                Author notes
                [* ]Correspondence: julia.bird@ 123456dsm.com ; Tel.: +31-15-279-3998
                Author information
                https://orcid.org/0000-0001-6015-3576
                Article
                nutrients-10-00775
                10.3390/nu10060775
                6024670
                29914111
                7a101b9d-742a-49e6-bd24-b3939b516f23
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 25 May 2018
                : 13 June 2018
                Categories
                Review

                Nutrition & Dietetics
                omega-3,cardiovascular disease,statins
                Nutrition & Dietetics
                omega-3, cardiovascular disease, statins

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