Methodology for altering omega-3 EPA+DHA and omega-6 linoleic acid as controlled variables in a dietary trial

MacIntosh, Beth; Ramsden, Christopher E.; Honvoh, Gilson; Faurot, Keturah R.; Palsson, Olafur S.; Johnston, Angela; Lynch, Chanee; Anderson, Paula; Igudesman, Daria; Zamora, Daisy; Horowitz, Mark S.; Gaylord, Susan; Mann, J. Douglas

doi:10.1016/j.clnu.2021.04.050

Cited by 11 publications

(10 citation statements)

References 42 publications

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“…The three diets were high n-3 (H3 diet), high n-3+low n-6 (H3-L6 diet), and average US n-3 and n-6 intake (control diet) 4546. The H3 diet was designed to increase EPA+DHA to 1.5 g/day while maintaining average US intakes of linoleic acid (7.2% of energy).…”

Section: Methodsmentioning

confidence: 99%

“…To maximize credibility, all study oils contained 25% extra virgin olive oil, which provided an equivalent green hue; the control group received substantial amounts of fish and shellfish products that were low in EPA+DHA, including a low EPA+DHA tuna fish; all three diet groups received identical amounts of packaged foods (eg, frozen fruits and vegetables, whole wheat bread, low fat cheese) and frozen proteins (eg, fish and lean poultry); and all three groups had access to equally intensive, intervention specific web materials designed to complement food provision and diet advice. Nutrient intakes were assessed using two unannounced, telephone administered, 24 hour recalls (one weekday, one weekend day) during each phase (preintervention and intervention), as previously described 4546…”

Section: Methodsmentioning

confidence: 99%

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Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial

Ramsden

Zamora

Faurot

et al. 2021

BMJ

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ObjectiveTo determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine.DesignThree arm, parallel group, randomized, modified double blind, controlled trial.SettingAmbulatory, academic medical center in the United States over 16 weeks.Participants182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine).InterventionsThree diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: H3 diet (n=61)—increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n=61)—increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n=60)—maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of energy. All participants received foods accounting for two thirds of daily food energy and continued usual care.Main outcome measuresThe primary endpoints (week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six item questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary.ResultsIn intention-to-treat analyses (n=182), the H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (−1.6, −4.2 to 1.0, and −1.5, −4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (−1.7, −2.5 to −0.9, and −1.3, −2.1 to −0.5, respectively), moderate to severe headache hours per day (−0.8, −1.2 to −0.4, and −0.7, −1.1 to −0.3, respectively), and headache days per month (−4.0, −5.2 to −2.7, and −2.0, −3.3 to −0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (−2.0, −3.2 to −0.8), suggesting additional benefit from lowering dietary linoleic acid. The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2.ConclusionsThe H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life.Trial registrationClinicalTrials.gov NCT02012790

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial

Ramsden

Zamora

Faurot

et al. 2021

BMJ

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“…Previous studies have shown that decreasing LA and/or increasing EPA and DHA in the diet changes the proportions of these fatty acids in the blood (MacIntosh et al, 2013, 2021; Ramsden et al, 2013; Taha et al, 2014; Wood et al, 2014) and alters the ECB profile (Ramsden et al, 2015). In a controlled feeding study in men, the levels of plasma EPA and DHA were higher when competing LA was 4% of energy (en%) rather than 10 en% (Liou et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Reducing LA from 8 en% to 1 en% in mice decreased erythrocyte phospholipid ARA and decreased 2‐AG and AEA levels threefold (Alvheim et al, 2012), indicating that regulation of the ARA in the phospholipid pool is a critical determinant for ECB production. Furthermore, in a cohort of adults with chronic headaches, reduction of dietary LA with increased EPA and DHA (MacIntosh et al, 2021) resulted in lower plasma ARA and subsequent decreases in 2‐AG (−25%) but not AEA (−3%) (Ramsden et al, 2013, 2015). However, it is not yet known whether these ECB lowering effects of dietary manipulation are due to decreasing dietary LA, increasing dietary EPA and DHA, or a combination of both.…”

Section: Introductionmentioning

confidence: 99%

Dietary linoleic acid lowering alone does not lower arachidonic acid or endocannabinoids among women with overweight and obesity: A randomized, controlled trial

Courville,

Majchrzak‐Hong,

Yang

et al. 2023

Lipids

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The linoleic acid (LA)‐arachidonic acid (ARA)‐inflammatory axis suggests dietary LA lowering benefits health because it lowers ARA and ARA‐derived endocannabinoids (ECB). Dietary LA reduction increases concentrations of omega‐3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DHA derived ECB. The aim of this study was to examine targeted reduction of dietary LA, with and without EPA and DHA, on plasma EPA and DHA and ECB (2‐arachidonoyl glycerol [2‐AG], anandamide [AEA], and docosahexaenoyl ethanolamide [DHA‐EA]). Healthy, pre‐menopausal women (n = 62, BMI 30 ± 3 kg/m2, age 35 ± 7 years; mean ± SD) were randomized to three 12‐week controlled diets: (1) high LA, low omega‐3 EPA and DHA (H6L3); (2) low LA, low omega‐3 EPA and DHA (L6L3); or (3) low LA, high omega‐3 EPA and DHA (L6H3). Baseline plasma fatty acids and ECB were similar between diets. Starting at 4 weeks, L6L3 and L6H3 lowered plasma LA compared to H6L3 (p < 0.001). While plasma ARA changed from baseline by 8% in L6L3 and −8% in L6H3, there were no group differences. After 4 weeks, plasma EPA and DHA increased from baseline in women on the L6H3 diet (ps < 0.001) and were different than the H6L3 and L6L3 diets. No differences were found between diets for AEA or 2‐AG, however, in L6L3 and L6H3, AEA increased by 14% (ps < 0.02). L6H3 resulted in 35% higher DHA‐EA (p = 0.013) whereas no changes were seen with the other diets. Lowering dietary LA did not result in the expected changes in fatty acids associated with the LA‐ARA inflammatory axis in women with overweight and obesity.

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“…Inflammatory diseases with high C-reactive protein levels benefit from omega-3/omega-6 supplementation, with EPA proving more effective than DHA [41][42]. The therapeutic utility of omega-3/omega-6 use has also been demonstrated in the improvement of algic symptoms of a muscular-tensive, neuropathic [43][44] or autoimmune nature from rheumatoid arthritis [16], as well as in cystic fibrosis [45], periodontitis [46], sperm motility [47], male hypotestosteronism in overweight or obese individuals (but only when supplementing with DHA) [48], and Concerning cognitive performance and psychological stability, there are encouraging results in the literature with regard to cognitive function [54] (although it appears that DHA supplementation has efficacy on attention in ADHD [55][56]77], EPA supplementation has efficacy on long-term memory, working memory, and problem solving function [57,78], and DHA+EPA has efficacy on executive functions in Alzheimer'type dementia [58]), particularly if DHA/EPA supplementation is used).…”

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confidence: 99%

The effects of omega-3 and omega-6 fatty acids on the mental and physical health of children, adolescents, and adults

Norooziseyedhosseini¹,

Imani²,

Sumra³

et al. 2023

Preprint

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Background: Omega-3 and omega-6 fatty acids are commonly used in pregnancy, lactation, and malnutrition. Paediatrics has been investigating whether omega-3/omega-6 supplementation affects human growth and neurodevelopment in recent decades.Aims: To assess the current state of knowledge regarding the use of omega-3/omega-6 type fatty acids in the diet in adolescent and adult populations.Materials and Methods: Through September 2022, Pubmed has chosen 72 original articles on the topic of human growth and nutrition in paediatrics.Results: According to the literature, the use of omega-3/omega-6 fatty acids, with a higher prevalence in the former group than the latter, appears to be most effective in hypertension, dyslipidemia, and high C-reactive protein values, cardiovascular risk, and neuropatic pain, while having less impact on neurodegenerative (except in multiple sclerosis) and mental disorders (except in depression). Combining omega-3 and omega-6 fatty acids with spirulina algae, chitosan, probiotics, vitamin D, fibre, and plant extracts yields intriguing results.Conclusions: Although significant evidence emerges on the importance of omega-3 and omega-6 fatty acid supplementation, significant structural flaws in research designs continue to emerge from published studies; additionally, many studies assume that fatty acid supplementation can have a curative effect on already active diseases, when in fact such prescriptions should be considered as adjuvant therapies to prevent or promote symptomatic regression, precisely because of their fatty acid content. Future research that can address the critical issues raised is hoped to promote a more comprehensive approach to the topic of omega-3/omega-6 supplementation in human health.

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Methodology for altering omega-3 EPA+DHA and omega-6 linoleic acid as controlled variables in a dietary trial

Cited by 11 publications

References 42 publications

Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial

Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial

Dietary linoleic acid lowering alone does not lower arachidonic acid or endocannabinoids among women with overweight and obesity: A randomized, controlled trial

The effects of omega-3 and omega-6 fatty acids on the mental and physical health of children, adolescents, and adults

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