Targeted alterations in dietary n-3 and n-6 fatty acids improve life functioning and reduce psychological distress among patients with chronic headache

Ramsden, Christopher E.; Faurot, Keturah R.; Zamora, Daisy; Palsson, Olafur S.; MacIntosh, Beth; Gaylord, Susan; Taha, Ameer Y.; Rapoport, Stanley I.; Hibbeln, Joseph R.; Davis, John M.; Mann, J. Douglas

doi:10.1097/01.j.pain.0000460348.84965.47

Cited by 59 publications

(56 citation statements)

References 54 publications

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“…Supporting this suggestion is evidence of reduced headache frequency in chronic migraine patients who reduced their LA intake from 7 to 2 % energy and increased EPA and DHA intake to 1.5 g/day for 12 weeks [64]. In these subjects, the frequency of headaches was positively associated with total LA concentration in plasma [65]. …”

Section: Discussionmentioning

confidence: 99%

Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism

et al. 2016

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Linoleic acid (LA, 18:2n-6) is a precursor to arachidonic acid (AA, 20:4n-6), which can be converted by brain lipoxygenase and cyclooxygenase (COX) enzymes into various lipid mediators involved in the regulation of brain immunity. Brain AA metabolism is activated in rodents by the bacterial endotoxin, lipopolysaccharide (LPS). This study tested the hypothesis that dietary LA lowering, which limits plasma supply of AA to the brain, reduces LPS-induced upregulation in brain AA metabolism. Male Fischer CDF344 rats fed an adequate LA (5.2 % energy (en)) or low LA (0.4 % en) diet for 15 weeks were infused with LPS (250 ng/h) or vehicle into the fourth ventricle for 2 days using a mini-osmotic pump. The incorporation rate of intravenously infused unesterified 14C-AA into brain lipids, eicosanoids, and activities of phospholipase A2 and COX-1 and 2 enzymes were measured. Dietary LA lowering reduced the LPS-induced increase in prostaglandin E2 concentration and COX-2 activity (P < 0.05 by two-way ANOVA) without altering phospholipase activity. The 14C-AA incorporation rate into brain lipids was decreased by dietary LA lowering (P < 0.05 by two-way ANOVA). The present findings suggest that dietary LA lowering reduced LPS-induced increase in brain markers of AA metabolism. The clinical utility of LA lowering in brain disorders should be explored in future studies.

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Section: Discussionmentioning

confidence: 99%

Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism

et al. 2016

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“…Plasma was collected at baseline and at the conclusion of the 12-week diet phase. We previously reported that the H3-L6 intervention produced marked reductions in headache frequency and severity and enhanced quality of life and function while reducing the use of acute pain medications (12, 13). Diet-induced changes in one or more families of n –6– or n –3–derived lipid autacoids likely contributed to these clinical benefits; however, the specific mechanisms responsible for these effects are unknown.…”

Section: Methodsmentioning

confidence: 99%

A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

et al. 2017

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Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy-or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivatives. All of these mediators were confirmed to be abundant in rat and human skin by mass spectrometry. However, only the two 11-hydroxy-epoxy-octadecenoates sensitized rat dorsal root ganglion neurons to release more calcitonin gene–related peptide (CGRP), which is involved in pain transmission, in response to low pH (which mimics an inflammatory state) or capsaicin (which activates ion channels involved in nociception). The two 11-hydroxy-epoxy-octadecenoates share a 3-hydroxy-Z-pentenyl-E-epoxide moiety, thus suggesting that this substructure could mediate nociceptor sensitization. In rats, intradermal hind paw injection of 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate elicited C-fiber–mediated sensitivity to thermal pain. In a randomized trial testing adjunctive strategies to manage refractory chronic headaches, reducing the dietary intake of linoleic acid was associated with decreases in plasma 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate, which correlated with clinical pain reduction. Human psoriatic skin had 30-fold higher 9-keto-12,13-trans-epoxy-(10E)-octadecenoate compared to control skin, and intradermal injection of this compound induced itch-related scratching behavior in mice. Collectively, these findings define a family of endogenous mediators with potential roles in pain and itch.

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“…We previously reported that the H3-L6 intervention produced marked reductions in headache frequency and severity 30 , reduced psychological distress 29 , and enhanced quality of life and function 29 compared to the L6 intervention, while reducing the use of acute pain medications 30 . Diet-induced changes in one or more families of n-3 or n-6 derived lipid autacoids likely contributed to these clinical benefits; however the specific lipid autacoids responsible for these effects are unknown.…”

Section: The Chronic Daily Headache (Cdh) Trialmentioning

confidence: 99%

Diet-Induced Changes in n-3- and n-6-Derived Endocannabinoids and Reductions in Headache Pain and Psychological Distress

Ramsden

Zamora

Makriyannis

et al. 2015

The Journal of Pain

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Omega-3 and omega-6 fatty acids are biosynthetic precursors to endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation—increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-L6 intervention)—reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators derived from omega-3 and omega-6 fatty acids. We therefore used data from this trial (n=55) to investigate (1) whether the H3-L6 intervention altered omega-3 and omega-6 derived endocannabinoids in plasma, and (2) whether diet-induced changes in these bioactive lipids were associated with clinical improvements. The H3-L6 intervention significantly increased the omega-3 docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, p<0.001) and docosahexaenoylethanolamine (+99%, p<0.001), and reduced the omega-6 arachidonic acid derivative 2-arachidonoylglycerol (-25%, p=0.001). Diet-induced changes in these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega-6 arachidonic acid, correlated with reductions in physical pain and psychological distress. These findings demonstrate that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids in humans, and suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have physical and/or psychological pain modulating properties. Trial Registration: ClinicalTrials.gov (NCT01157208) Perspective This article demonstrates that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids, and that these changes are related to reductions in headache pain and psychological distress. These findings suggest that dietary interventions could provide an effective, complementary approach for managing chronic pain and related conditions.

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Targeted alterations in dietary n-3 and n-6 fatty acids improve life functioning and reduce psychological distress among patients with chronic headache

Cited by 59 publications

References 54 publications

Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism

Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism

A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch

Diet-Induced Changes in n-3- and n-6-Derived Endocannabinoids and Reductions in Headache Pain and Psychological Distress

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