Alpha-Linolenic Acid (ALA)

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    Last Updated: November 16, 2023

    Alpha-linolenic acid (ALA) is an essential omega-3 fatty acid found primarily in plants, including walnuts, chia seeds, flaxseed, hemp seeds, canola, and their respective oils. ALA has primarily been studied for its potential benefits for cardiovascular health and the prevention of cardiovascular disease, but the effects seem to be marginal at best.

    Alpha-Linolenic Acid (ALA) is most often used for .

    What is alpha-linolenic acid?

    Alpha-linolenic acid (ALA) is a short-chain omega-3 fatty acid found primarily in plants. ALA is an essential fatty acid (EFA), meaning the body cannot synthesize it and it must be consumed in the diet. Foods high in ALA include various nuts/seeds and their oils, such as walnuts, flaxseed, hemp seeds, chia seeds, and canola oil.[3] Smaller amounts can be found in kiwi fruit, spinach, watercress, and grass-fed beef.[4][5] ALA consists of an 18-carbon chain with three double bonds, making it a polyunsaturated fatty acid. Within the body, ALA can have many functions. It can be broken down for energy via the β-oxidation metabolic pathway; be incorporated into cell membranes, affecting their fluidity and cell signaling; influence gene expression; and be metabolized into other bioactive compounds, such as oxylipins (chemical messengers) or other omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), although this occurs at a low rate.[6] While both DHA and EPA (primarily found in fish oil) have many reported health benefits, the effects of ALA are less clear.

    What are alpha-linolenic acid’s main benefits?

    ALA may have small cardiovascular benefits, but the research is fairly mixed. In short-term trials (2–3 months), ALA seems to minorly reduce triglyercides (although less efficiently than fish oil), LDL-cholesterol, and total cholesterol.[7][8] However, these effects are not observed in longer trials.[9][7] ALA may reduce the risk of heart arrhythmias, but has not been found to reduce blood pressure or the risk of cardiovascular events (e.g., heart attack, stroke).[9] Additionally, ALA may reduce markers of inflammation including C-reactive protein and TNF-alpha; however, these effects are inconsistent and are mostly observed in people with higher baseline levels of these biomarkers.[10][11] Some observational studies have suggested that higher reported intakes of ALA are associated with reduced all-cause and cardiovascular disease mortality,[12][13] but this has not been found in randomized controlled trials (RCTs).[9]

    What are alpha-linolenic acid’s main drawbacks?

    ALA is generally considered to be safe and well-tolerated; however, there is a lack of research reporting on adverse effects.

    There are some important limitations to ALA research. Most trials provide ALA as foods or oils (e.g., flaxseed, walnut, canola, ALA-enriched-margarine), which means there are other bioactive compounds present, such as different fatty acids, fiber, vitamins and minerals, and polyphenols).[7] These compounds could influence the observed effects and make it challenging to disentangle the effects of ALA from the food as a whole. Additionally, ALA is ubiquitous in the diet, and many clinical trials do not account for baseline intakes of ALA which could impact the observed effects (or lack thereof).

    How does alpha-linolenic acid work?

    Animal models suggest that ALA might modulate blood lipid levels by reducing lipid synthesis while also stimulating lipid metabolism,[3] and may reduce inflammation by reducing the production of inflammatory mediators through inhibition of nuclear factor kappa B (NF-kB). In theory, reductions in inflammation and blood lipids could be protective against cardiovascular disease, but a protective effect hasn’t been consistently found with ALA supplementation. ALA can also be metabolized into other bioactive compounds, such as oxylipins (e.g., eicosanoids), which are a diverse group of lipid mediators that have immune-modulating effects.[14][15]

    What are other names for Alpha-Linolenic Acid (ALA)

    Note that Alpha-Linolenic Acid (ALA) is also known as:
    • α-linolenic acid
    • 18:3n-3
    • Omega-3 fatty acid
    Alpha-Linolenic Acid (ALA) should not be confused with:
    • Alpha-lipoic acid (an antioxidant)
    • Gamma (γ)-linolenic acid(an omega-6 fatty acid)
    • Linoleic acid (an omega-6 fatty acid)

    Dosage information

    As part of the regular diet, the Institute of Medicine has established an adequate intake (AI) level for ALA of 1.6 grams for men and 1.1 grams for women. This represents the daily amount that is thought to be nutritionally adequate.[1] ALA is highly bioavailable in foods and oils, but flax and chia seeds should be ground before consumption to ensure the ALA is available for absorption.[2]

    The optimal dosage for ALA as a supplement is not well established and is likely influenced by baseline levels of intake. For reducing triglycerides or LDL-cholesterol, a 2021 meta-analysis of RCTs found that ALA dosages of 3–8 grams daily were the most effective; however, the benefit on lipid levels was not observed beyond 3 months. Further complicating the issue is the form in which ALA is provided. In clinical trials, ALA is provided in a variety of ways, including as ALA-enriched margarine, in walnuts, in ground flax or chia seeds, or in their oils. Due to the heterogeneous nature of these dosage forms and the presence of other bioactive compounds, the consumption of, for example, 3 grams of ALA in walnuts may not produce the same effects as consuming 3 grams of ALA in flaxseed oil.

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    Frequently asked questions

    What is alpha-linolenic acid?

    Alpha-linolenic acid (ALA) is a short-chain omega-3 fatty acid found primarily in plants. ALA is an essential fatty acid (EFA), meaning the body cannot synthesize it and it must be consumed in the diet. Foods high in ALA include various nuts/seeds and their oils, such as walnuts, flaxseed, hemp seeds, chia seeds, and canola oil.[3] Smaller amounts can be found in kiwi fruit, spinach, watercress, and grass-fed beef.[4][5] ALA consists of an 18-carbon chain with three double bonds, making it a polyunsaturated fatty acid. Within the body, ALA can have many functions. It can be broken down for energy via the β-oxidation metabolic pathway; be incorporated into cell membranes, affecting their fluidity and cell signaling; influence gene expression; and be metabolized into other bioactive compounds, such as oxylipins (chemical messengers) or other omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), although this occurs at a low rate.[6] While both DHA and EPA (primarily found in fish oil) have many reported health benefits, the effects of ALA are less clear.

    What impacts the conversion of alpha-linolenic acid to DHA and EPA?

    In the body, ALA can function as a precursor for the production of the long-chain omega-3 fatty acids EPA and DHA. However, these conversions are limited; they have been estimated to occur at rates of <8% and <4% for EPA and DHA, respectively.[3] There are many factors that can impact the efficiency of this conversion, such as sex, genetic polymorphisms, disease states, and habitual fatty acid consumption.[19][3]

    For example, premenopausal women can convert ALA to EPA and DHA at a significantly greater rate due to higher levels of estrogen, which can upregulate the expression of the enzymes required for the conversion.[3][20] This likely relates to the importance of DHA during fetal development and lactation. Another contributing factor may be the level of omega-6 fatty acids consumed.

    Both ALA and linoleic acid (LA) — an essential omega-6 fatty acid — compete for the same enzymes that convert them into longer chain fatty acids. Restricting LA while increasing ALA intake has been shown to increase levels of EPA and sometimes DHA in clinical trials, although the effect is small.[21]

    Lastly, the dose of ALA is important. For example, a clinical trial found that 30 grams daily of ground flaxseed was sufficient to raise levels of EPA in the blood, but 10 grams daily was not.[22]

    What are the signs and symptoms of alpha-linolenic acid deficiency?

    ALA is an essential fatty acid that must be consumed in adequate amounts to prevent deficiency. In the United States, the majority of adults meet or exceed the recommended adequate intake of ALA, and deficiency is uncommon.[23][1] When deficiency does occur, it may lead to dry, scaly skin, vision problems, and neuropathy.[24][25] In rodent models of ALA deficiency, impaired learning abilities have been observed, but this hasn’t been found in humans.[26]

    What are alpha-linolenic acid’s main benefits?

    ALA may have small cardiovascular benefits, but the research is fairly mixed. In short-term trials (2–3 months), ALA seems to minorly reduce triglyercides (although less efficiently than fish oil), LDL-cholesterol, and total cholesterol.[7][8] However, these effects are not observed in longer trials.[9][7] ALA may reduce the risk of heart arrhythmias, but has not been found to reduce blood pressure or the risk of cardiovascular events (e.g., heart attack, stroke).[9] Additionally, ALA may reduce markers of inflammation including C-reactive protein and TNF-alpha; however, these effects are inconsistent and are mostly observed in people with higher baseline levels of these biomarkers.[10][11] Some observational studies have suggested that higher reported intakes of ALA are associated with reduced all-cause and cardiovascular disease mortality,[12][13] but this has not been found in randomized controlled trials (RCTs).[9]

    Does ALA impact glycemic control or the risk of type 2 diabetes?

    In animal and in vitro studies, ALA has demonstrated anti-diabetic effects in a number of ways, including modulating insulin signaling, modulating glucose metabolism, and improving insulin resistance by reducing triglycerides in the liver and lowering systemic inflammation.[3][16] However, human clinical trials have not shown much promise, and ALA does not seem to have an impact on the risk of type 2 diabetes or glycemic control in general.

    A 2022 meta-analysis of RCTs found that higher intakes of ALA had no effect on the incidence of diagnoses of type 2 diabetes (for those healthy at baseline), or on markers of insulin resistance (HOMA-IR) or glycemic control (fasting glucose, HbA1c, fasting insulin).[17] Similarly, when just looking at people with type 2 diabetes, a 2017 meta-analysis of RCTs found that ALA had a neutral effect on glycemic control.[18]

    What are alpha-linolenic acid’s main drawbacks?

    ALA is generally considered to be safe and well-tolerated; however, there is a lack of research reporting on adverse effects.

    There are some important limitations to ALA research. Most trials provide ALA as foods or oils (e.g., flaxseed, walnut, canola, ALA-enriched-margarine), which means there are other bioactive compounds present, such as different fatty acids, fiber, vitamins and minerals, and polyphenols).[7] These compounds could influence the observed effects and make it challenging to disentangle the effects of ALA from the food as a whole. Additionally, ALA is ubiquitous in the diet, and many clinical trials do not account for baseline intakes of ALA which could impact the observed effects (or lack thereof).

    How does alpha-linolenic acid work?

    Animal models suggest that ALA might modulate blood lipid levels by reducing lipid synthesis while also stimulating lipid metabolism,[3] and may reduce inflammation by reducing the production of inflammatory mediators through inhibition of nuclear factor kappa B (NF-kB). In theory, reductions in inflammation and blood lipids could be protective against cardiovascular disease, but a protective effect hasn’t been consistently found with ALA supplementation. ALA can also be metabolized into other bioactive compounds, such as oxylipins (e.g., eicosanoids), which are a diverse group of lipid mediators that have immune-modulating effects.[14][15]

    Update History

    Correction

    correction

    In the FAQ "What impacts the conversion of alpha-linolenic acid to DHA and EPA" we accidentally called the omega-6 fatty acid linoleic acid, alpha-linoleic acid. We corrected the spelling to linoleic acid (LA) throughout.

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    References

    1. ^Trumbo P, Schlicker S, Yates AA, Poos M, Food and Nutrition Board of the Institute of Medicine, The National AcademiesDietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acidsJ Am Diet Assoc.(2002 Nov)
    2. ^Austria JA, Richard MN, Chahine MN, Edel AL, Malcolmson LJ, Dupasquier CM, Pierce GNBioavailability of alpha-linolenic acid in subjects after ingestion of three different forms of flaxseed.J Am Coll Nutr.(2008-Apr)
    3. ^Yuan Q, Xie F, Huang W, Hu M, Yan Q, Chen Z, Zheng Y, Liu LThe review of alpha-linolenic acid: Sources, metabolism, and pharmacology.Phytother Res.(2022-Jan)
    4. ^Mary E Van Elswyk, Shalene H McNeillImpact of grass/forage feeding versus grain finishing on beef nutrients and sensory quality: the U.S. experienceMeat Sci.(2014 Jan)
    5. ^Pereira C, Li D, Sinclair AJThe alpha-linolenic acid content of green vegetables commonly available in Australia.Int J Vitam Nutr Res.(2001-Jul)
    6. ^Sala-Vila A, Fleming J, Kris-Etherton P, Ros EImpact of α-Linolenic Acid, the Vegetable ω-3 Fatty Acid, on Cardiovascular Disease and Cognition.Adv Nutr.(2022-Oct-02)
    7. ^Hao Yue, Bin Qiu, Min Jia, Wei Liu, Xiao-Fei Guo, Na Li, Zhi-Xiang Xu, Fang-Ling Du, Tongcheng Xu, Duo LiEffects of α-linolenic acid intake on blood lipid profiles:a systematic review and meta-analysis of randomized controlled trialsCrit Rev Food Sci Nutr.(2021)
    8. ^Chen H, Deng G, Zhou Q, Chu X, Su M, Wei Y, Li L, Zhang ZEffects of eicosapentaenoic acid and docosahexaenoic acid versus α-linolenic acid supplementation on cardiometabolic risk factors: a meta-analysis of randomized controlled trials.Food Funct.(2020-Mar-26)
    9. ^Asmaa S Abdelhamid, Tracey J Brown, Julii S Brainard, Priti Biswas, Gabrielle C Thorpe, Helen J Moore, Katherine Ho Deane, Carolyn D Summerbell, Helen V Worthington, Fujian Song, Lee HooperOmega-3 fatty acids for the primary and secondary prevention of cardiovascular diseaseCochrane Database Syst Rev.(2020 Feb 29)
    10. ^Yin S, Xu H, Xia J, Lu Y, Xu D, Sun J, Wang Y, Liao W, Sun GEffect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Adv Nutr.(2023-Sep-29)
    11. ^Su H, Liu R, Chang M, Huang J, Jin Q, Wang XEffect of dietary alpha-linolenic acid on blood inflammatory markers: a systematic review and meta-analysis of randomized controlled trials.Eur J Nutr.(2018-Apr)
    12. ^Sina Naghshi, Dagfinn Aune, Joseph Beyene, Sara Mobarak, Masoomeh Asadi, Omid SadeghiDietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studiesBMJ.(2021 Oct 13)
    13. ^Chen LH, Hu Q, Li G, Zhang L, Qin LQ, Zuo H, Xu GDietary Intake and Biomarkers of α-Linolenic Acid and Mortality: A Meta-Analysis of Prospective Cohort Studies.Front Nutr.(2021)
    14. ^Cambiaggi L, Chakravarty A, Noureddine N, Hersberger MThe Role of α-Linolenic Acid and Its Oxylipins in Human Cardiovascular Diseases.Int J Mol Sci.(2023-Mar-24)
    15. ^Bertoni C, Abodi M, D'Oria V, Milani GP, Agostoni C, Mazzocchi AAlpha-Linolenic Acid and Cardiovascular Events: A Narrative Review.Int J Mol Sci.(2023-Sep-20)
    16. ^Wang Q, Wang XThe Effect of Plant-Derived Low-Ratio Linoleic Acid/α-Linolenic Acid on Markers of Glucose Controls: A Systematic Review and Meta-Analysis.Int J Mol Sci.(2023-Sep-21)
    17. ^Brown TJ, Brainard J, Song F, Wang X, Abdelhamid A, Hooper L,Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials.BMJ.(2019-Aug-21)
    18. ^Jovanovski E, Li D, Thanh Ho HV, Djedovic V, Ruiz Marques AC, Shishtar E, Mejia SB, Sievenpiper JL, de Souza RJ, Duvnjak L, Vuksan VThe effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials.Medicine (Baltimore).(2017-May)
    19. ^Adam Ameur, Stefan Enroth, Asa Johansson, Ghazal Zaboli, Wilmar Igl, Anna C V Johansson, Manuel A Rivas, Mark J Daly, Gerd Schmitz, Andrew A Hicks, Thomas Meitinger, Lars Feuk, Cornelia van Duijn, Ben Oostra, Peter P Pramstaller, Igor Rudan, Alan F Wright, James F Wilson, Harry Campbell, Ulf GyllenstenGenetic adaptation of fatty-acid metabolism: a human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acidsAm J Hum Genet.(2012 May 4)
    20. ^Graham C Burdge, Stephen A WoottonConversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young womenBr J Nutr.(2002 Oct)
    21. ^Wood KE, Mantzioris E, Gibson RA, Ramsden CE, Muhlhausler BSThe effect of modifying dietary LA and ALA intakes on omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) status in human adults: a systematic review and commentary.Prostaglandins Leukot Essent Fatty Acids.(2015-Apr)
    22. ^Edel AL, Patenaude AF, Richard MN, Dibrov E, Austria JA, Aukema HM, Pierce GN, Aliani MThe effect of flaxseed dose on circulating concentrations of alpha-linolenic acid and secoisolariciresinol diglucoside derived enterolignans in young, healthy adults.Eur J Nutr.(2016-Mar)
    23. ^Papanikolaou Y, Brooks J, Reider C, Fulgoni VLU.S. adults are not meeting recommended levels for fish and omega-3 fatty acid intake: results of an analysis using observational data from NHANES 2003-2008.Nutr J.(2014-Apr-02)
    24. ^P B Jeppesen, C E Høy, P B MortensenEssential fatty acid deficiency in patients receiving home parenteral nutritionAm J Clin Nutr.(1998 Jul)
    25. ^Holman RT, Johnson SB, Hatch TFA case of human linolenic acid deficiency involving neurological abnormalities.Am J Clin Nutr.(1982-Mar)
    26. ^Yamamoto N, Saitoh M, Moriuchi A, Nomura M, Okuyama HEffect of dietary alpha-linolenate/linoleate balance on brain lipid compositions and learning ability of rats.J Lipid Res.(1987-Feb)

    Examine Database References

    1. Triglycerides - Hao Yue, Bin Qiu, Min Jia, Wei Liu, Xiao-Fei Guo, Na Li, Zhi-Xiang Xu, Fang-Ling Du, Tongcheng Xu, Duo LiEffects of α-linolenic acid intake on blood lipid profiles:a systematic review and meta-analysis of randomized controlled trialsCrit Rev Food Sci Nutr.(2021)
    2. Triglycerides - Asmaa S Abdelhamid, Tracey J Brown, Julii S Brainard, Priti Biswas, Gabrielle C Thorpe, Helen J Moore, Katherine Ho Deane, Carolyn D Summerbell, Helen V Worthington, Fujian Song, Lee HooperOmega-3 fatty acids for the primary and secondary prevention of cardiovascular diseaseCochrane Database Syst Rev.(2020 Feb 29)
    3. HbA1c - Brown TJ, Brainard J, Song F, Wang X, Abdelhamid A, Hooper L, Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials.BMJ.(2019-Aug-21)
    4. TNF-Alpha - Yin S, Xu H, Xia J, Lu Y, Xu D, Sun J, Wang Y, Liao W, Sun GEffect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Adv Nutr.(2023-Sep-29)