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Effect of Flaxseed (Linum usitatissimum L.) Supplementation on Vascular Endothelial Cell Morphology and Function in Patients with Dyslipidaemia-A Preliminary Observation.
Kanikowska, D, Malińska, A, Mickiewicz, A, Zawada, A, Rutkowski, R, Pawlaczyk, K, Sato, M, Bręborowicz, A, Witowski, J, Korybalska, K
Nutrients. 2022;14(14)
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Flaxseed appears to be a valuable source of polyunsaturated fatty acids, phytosterols and fibre, which lower lipids and have anti-atherogenic activity. The aim of this study was to determine the effects of 10 weeks of supplementation with the flaxseed (28g/day) on endothelial cells function, serum lipids and proinflammatory mediators in patients with mild and severe dyslipidaemia. This study is a prospective study of two groups of patients. The first group (n=14) was composed of lean (n=6), and obese (n=8) outpatients receiving therapy of lipoprotein apheresis (once every two weeks) for severe hyperlipidaemia. The second group was composed of 11 obese outpatients with dyslipidaemia receiving a diet at home. In both groups, flaxseed was given blindly. Results show that patients diagnosed with dyslipidaemia who took 28g daily of flaxseed showed a significant reduction in serum lipids but exhibited a slight beneficial effect on endothelial cells. However, it only shows that flaxseed might have the potential ability to improve endothelial function but, in obese patients, it does not have the potency to reverse endothelial ultrastructural changes observed in electron microscopy. Authors conclude that flaxseed supplementation produced consistent lipid-lowering effects and can modulate VEGF (endothelial cell marker) concentration depending on the severity of dyslipidaemia.
Abstract
CONTEXT Flaxseed has a characteristic fatty acids composition and unique phytonutrient profile that may have health-promoting properties. OBJECTIVE This study aimed to determine the effects of 10 weeks of supplementation with the flaxseed (28 g/day) on endothelial cells (EC) function, serum lipids and proinflammatory mediators in patients with mild and severe dyslipidaemia. MATERIALS AND METHODS Eleven lean patients with severe dyslipidaemia treated with apheresis (group 1; 10 weeks treated in four phases: (i) ordinary diet, (ii) ordinary diet + flaxseed, (iii) ordinary diet (wash out), (iv) ordinary diet + placebo) and eleven obese patients with mild dyslipidaemia-not treated with apheresis (group 2; 10 weeks treated in two phases: (i) ordinary diet, (ii) low fat diet + flaxseed). Flaxseed was given blindly. Serum was collected at the end of each phase of the study. ECs were exposed in vitro to the medium supplemented with pooled serum taken from patients from both groups to detect their morphological changes using light and electron microscopy. ECs proliferation was also measured at the end of each study phase. RESULTS Serum vascular endothelial growth factor was decreased after flaxseed supplementation but only in group 1. ECs proliferation was increased after flaxseed supplementation only in obese patients. ECs exposed to medium supplemented with obese patients' serum revealed the following cellular abnormalities: accumulation of lipid droplets, changes of rough endoplasmic reticulum and mitochondria, and flaxseed did not reverse observed changes. At the same time, flaxseed supplementation decreases total cholesterol in both tested groups, low-density lipoprotein cholesterol in group 1 and triglycerides in group 2. CONCLUSIONS Our findings support the potential role of flaxseed in treating dyslipidaemia but indicate only a slight impact on endothelial cell function.
2.
Linoleic Acid-Rich Oil Alters Circulating Cardiolipin Species and Fatty Acid Composition in Adults: A Randomized Controlled Trial.
Cole, RM, Angelotti, A, Sparagna, GC, Ni, A, Belury, MA
Molecular nutrition & food research. 2022;66(15):e2101132
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Dietary polyunsaturated fatty acid intake is associated with reduced cardiometabolic disease risk. In addition, higher linoleic acid (LA) biomarkers have been associated with a reduced risk for cardiometabolic diseases and conditions. The main aim of this study was to determine whether a modest addition of an oil rich in LA could change the LA content in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMCs). The secondary aim was to determine if the LA-rich oil could alter cardiolipin species in PBMCs. This study is a randomised double-masked placebo-controlled study of 84 participants who were randomly assigned to one of the two groups: either the high-oleate-cookie (n = 42) or LA-cookie groups (n = 42). Results show that dietary supplementation with less than one serving of LA-rich oil per day increases LA in PBMC cardiolipin as well as LA levels. Authors conclude that patients with obesity, cardiometabolic disease, and other conditions related to mitochondrial dysfunction could be a future cohort that should be studied.
Abstract
SCOPE Higher circulating linoleic acid (LA) and muscle-derived tetralinoleoyl-cardiolipin (LA4 CL) are each associated with decreased cardiometabolic disease risk. Mitochondrial dysfunction occurs with low LA4 CL. Whether LA-rich oil fortification can increase LA4 CL in humans is unknown. The aims of this study are to determine whether dietary fortification with LA-rich oil for 2 weeks increases: 1) LA in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC); and 2) LA4 CL in PBMC in adults. METHODS AND RESULTS In this randomized controlled trial, adults are instructed to consume one cookie per day delivering 10 g grapeseed (LA-cookie, N = 42) or high oleate (OA) safflower (OA-cookie, N = 42) oil. In the LA-cookie group, LA increases in plasma, erythrocyte, and PBMC by 6%, 7%, and 10% respectively. PBMC and erythrocyte OA increase by 7% and 4% in the OA-cookie group but is unchanged in the plasma. PBMC LA4 CL increases (5%) while LA3 OA1 CL decreases (7%) in the LA-cookie group but are unaltered in the OA-cookie group. CONCLUSIONS LA-rich oil fortification increases while OA-oil has no effect on LA4 CL in adults. Because LA-rich oil fortification reduces cardiometabolic disease risk and increases LA4 CL, determining whether mitochondrial dysfunction is repaired through dietary fortification is warranted.
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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, CE, Zamora, D, Faurot, KR, MacIntosh, B, Horowitz, M, Keyes, GS, Yuan, ZX, Miller, V, Lynch, C, Honvoh, G, et al
BMJ (Clinical research ed.). 2021;374:n1448
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This study could be of interest to practitioners who are interested in dietary interventions that may decrease the incidence or severity of headaches in women. Omega 3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are believed to be precursors for molecules that may have pain reducing properties. Whereas omega 6 fatty acids such as linoleic acid are believed to be precursors for molecules that may have pain promoting effects. The objective of this 3 armed randomised, double blinded controlled trial was to determine whether increasing dietary intake of omega 3 EPA and DHA, whilst either maintaining or decreasing omega 6 linoleic acid, may lead to a decrease in headache frequency and severity. 182 participants were assigned into one of 3 treatment groups, the first, H3 diet, increasing EPA and DHA to 1.5g/day and maintaining linoleic acid, the second, H3-L6 diet, increasing EPA and DHA to 1.5g/day whilst decreasing linoleic acid and the control group maintaining EPA, DHA and linoleic acid. Both the H3 and H3-L6 diets increased the levels of the molecule believed to be involved in reducing pain to a statistically significant level. This was found to be consistent with the results reported by the patients both in headache hours per day and days with headache in the month. The authors conclude that increasing levels of omega 3 fatty acids in the diet whilst decreasing levels of omega 6 fatty acids in the diet may decrease the frequency and severity of headaches. This study was for 16 weeks and predominantly women with a mean age of 38, further studies for longer and on other populations such as men, children and older populations, would be required to see if the same results could be obtained.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Important from a public health perspective
- Increasing n-3 levels and decreasing n-6 levels could be modified by dietary change and appear to reduce the frequency and duration of headaches in migraine sufferers
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Circulating lipid mediators have been implicated in headache pathogenesis.
Objective
To 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.
Study Design
Three arm, parallel group, randomized, modified double blind, controlled trial.
Participants
182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine).
Interventions
Three 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 total energy intake
- H3-L6 diet (n=61)—increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of total energy intake
- Control diet (n=60)—maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of total energy intake
All participants received foods accounting for two thirds of daily food energy and 1/3rd from foods not provided by the Research Kitchen. For these foods participants rely on their training by the dietitian and website diet guides for shopping and choosing foods in restaurants. Participants were encouraged to continue seeing their headache physician and continue usual care.
Results
In intention-to-treat analyses (n=182) at 16 weeks
- The H3-L6 and H3 diets increased circulating 17-HDHA 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 (quality of life) 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, suggesting additional benefit from lowering dietary linoleic acid (−2.0, −3.2 to −0.8).
- 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.
Conclusions
The 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.
Clinical practice applications:
These findings might be useful for Nutritional Therapists and Clinical Practitioners:
- To inform practitioners of the benefits of assessing n-3 and n-6 fatty acids in migraine patients.
- Inform practitioners of the potential benefits to reducing n-6 as well as increasing n-3 levels in migraine patients
- Inform practitioners of the potential lack of correlation between headache duration and frequency and quality of life measures
Considerations for future research:
- Trialing larger doses of n-3
- Longer term follow up whilst maintaining these diets
- Attempting to validate an optimal serum level of 17-HDHA for these patients that could be used in clinical practice
Abstract
OBJECTIVE To 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. DESIGN Three arm, parallel group, randomized, modified double blind, controlled trial. SETTING Ambulatory, academic medical center in the United States over 16 weeks. PARTICIPANTS 182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine). INTERVENTIONS Three 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 MEASURES The 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. RESULTS In 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. CONCLUSIONS The 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 REGISTRATION ClinicalTrials.gov NCT02012790.
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Alpha-Linolenic and Linoleic Fatty Acids in the Vegan Diet: Do They Require Dietary Reference Intake/Adequate Intake Special Consideration?
Burns-Whitmore, B, Froyen, E, Heskey, C, Parker, T, San Pablo, G
Nutrients. 2019;11(10)
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Fish and seafood are good sources of long-chain omega-3 fatty acids, like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A vegan diet does not include animal-sourced foods and is therefore void of EPA and DHA, unless algae-derived omega-3 supplements are consumed. Thus, vegans rely on the body's own production of long-chain fatty acids from plant-derived alpha-linolenic acid (ALA). However, adequate conversion can have several limitations. Vegan diets are generally rich in linoleic acid (LA), an omega-6 fatty acid, which in high levels can impede the conversion of ALA to EPA and DHA. Furthermore, the efficiency of conversion is influenced by gender, age or health conditions like obesity. This review sought to discuss whether vegans require special dietary recommendations for fatty acids and what these suggestions could be. Most studies assessing biological indicators of fatty acid status showed that vegans had lower levels of EPA and DHA compared to omnivores. Thus, the authors concluded that special consideration should be given to ALA and LA intake in vegan diets. In the absence of a set recommendation for a fatty acid ratio, a ratio of 4:1 (omega-6:omega-3) was proposed for vegans and omnivores. A reduction in LA and an increased intake of ALA of 2.2–4.4 g/day (or 1.1 g/day/1000 Kcals) was suggested to achieve such. This article is a useful guide when considering adequate fatty acid balance and omega-3 conversion for individuals following a vegan diet.
Abstract
Good sources of the long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) include cold-water fish and seafood; however, vegan diets (VGNs) do not include animal-origin foods. Typically, US omnivores obtain enough dietary EPA and DHA, but unless VGNs consume algal n-3 supplements, they rely on endogenous production of long-chain fatty acids. VGN diets have several possible concerns: (1) VGNs have high intakes of linoleic acid (LA) as compared to omnivore/non-vegetarian diets. (2) High intakes of LA competitively interfere with the endogenous conversion of alpha-linolenic acid (ALA) to EPA and DHA. (3) High somatic levels of LA/low ALA indicate a decreased ALA conversion to EPA and DHA. (4) Some, not all VGNs meet the Dietary Reference Intake Adequate Intake (DRI-AI) for dietary ALA and (5) VGN diets are high in fiber, which possibly interferes with fat absorption. Consequently, health professionals and Registered Dietitians/Registered Dietitian Nutritionists working with VGNs need specific essential fatty acid diet guidelines. The purpose of this review was: (1) to suggest that VGNs have a DRI-AI Special Consideration requirement for ALA and LA based on VGN dietary and biochemical indicators of status and (2) to provide suggestions to ensure that VGNs receive adequate intakes of LA and ALA.
5.
Omega-3 polyunsaturated fatty acids and vegetarian diets.
Saunders, AV, Davis, BC, Garg, ML
The Medical journal of Australia. 2013;199(S4):S22-6
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Even though vegetarians may have a lower overall risk of common chronic disease, they may still be at a disadvantage where essential fatty acids (EFAs) intake is concerned. The main aim of this study was to review EFA intake and status of vegetarians in order to assess whether current intakes in this population are sufficient to achieve and maintain optimal health. A secondary aim is to explore the potential benefits of adding supplemental sources of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). This review shows that: - although vegetarians consume minimal EPA and DHA, their plasma levels of omega-3 polyunsaturated fatty acids are typically low but stable. - there are no official separate recommendations for intake of fatty acids by vegetarians. - improving EFA status in individuals who are vegetarians might offer further protection. - there may be advantages to adding DHA and possibly EPA supplements derived from microalgae, particularly for people with increased needs (e.g., pregnant and lactating women) or reduced conversion ability (e.g., people with diabetes, metabolic syndrome or hypertension, and older people). Authors conclude that there is no convincing evidence that vegetarians or vegans experience adverse effects as a result of a low dietary intake of EPA and DHA.
Abstract
While intakes of the omega-3 fatty acid α-linolenic acid (ALA) are similar in vegetarians and non-vegetarians, intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low in vegetarians and virtually absent in vegans. Plasma, blood and tissue levels of EPA and DHA are lower in vegetarians than in non-vegetarians, although the clinical significance of this is unknown. Vegetarians do not exhibit clinical signs of DHA deficiency, but further research is required to ascertain whether levels observed in vegetarians are sufficient to support optimal health. ALA is endogenously converted to EPA and DHA, but the process is slow and inefficient and is affected by genetics, sex, age and dietary composition. Vegetarians can take practical steps to optimise conversion of ALA to EPA and DHA, including reducing intake of linoleic acid. There are no official separate recommendations for intake of fatty acids by vegetarians. However, we suggest that vegetarians double the current adequate intake of ALA if no direct sources of EPA and DHA are consumed. Vegetarians with increased needs or reduced conversion ability may receive some advantage from DHA and EPA supplements derived from microalgae. A supplement of 200-300 mg/day of DHA and EPA is suggested for those with increased needs, such as pregnant and lactating women, and those with reduced conversion ability, such as older people or those who have chronic disease (eg, diabetes).
6.
Separation of cinchona alkaloids, opium alkaloids, heroin, and related narcotics by dynamic-coating high-speed liquid chromaotgraphy.
Wu, CY, Siggia, S, Robinson, T, Waskiewicz, RD
Analytica chimica acta. 1973;63(2):393-402
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It has already been shown that replacing saturated fatty acids (SFA) with omega 6 (n-6) linoleic acid (LA) can reduce low density lipoproteins (LDL) which is hypothesised to reduce the risk of cardiovascular disease. However, this study looked at the prevention of secondary heart disease and mortality in recovered data from a single-blinded, parallel group, randomised controlled trial carried out between 1966-1973 which replaced dietary SFAs with n-6 polyunsaturated fatty acids (PUFAs) derived from safflower oil. This study also used this recovered data to update their meta-analysis published in 2010. The study was of 458 men who had suffered a recent coronary event and measured mortality over the 7 year period. Results showed a significant reduction in total cholesterol in the intervention group, however, it showed an increase in mortality. The study concluded that the mechanism of cardiovascular disease is independent of cholesterol levels which contradicts traditional understanding and worldwide dietary advice. The updated meta-analysis showed no benefit in replacing SFAs for n-6 or PUFAs for cardiovascular health.