Also known as: linolenic acid, linolenate, alpha-Linolenate, 9,12,15-Octadecatrienoic acid, 463-40-1, alpha-Lnn
Properties
A fatty acid that is found in plants and involved in the formation of prostaglandins. Alpha-linolenic acid has formula of C18H30O2, with molecular weight of 278.43. Alpha-linolenic acid is NOT the same as alpha-lipoic acid.
Source: flaxseed (Linum usitatissimum). Flaxseed is one of the richest dietary sources of alpha-linolenic acid and is also a good source of soluble fibre mucilage.
Potential Health Benefits
Neuroprotection
Nerve agents cause toxicity to peripheral and central sites through the irreversible inhibition of acetylcholinesterase, the enzyme that metabolizes acetylcholine. Excessive acetylcholine accumulation in synapses results in status epilepticus in the central nervous system. Prolonged status epilepticus leads to brain damage, neurological dysfunction and poor outcome. Anticonvulsants are effective but must be given rapidly following exposure. Previous findings suggested that α-Linolenic acid is neuroprotective against kainic acid-induced brain damage, acid it also exerts anti-depressant and anti-inflammatory activities and enhances synaptic plasticity in vivo. (1)
Recently, Xin Zeng and his colleagues have assessed the neuroprotective effect of α-linolenic acid in mice and its potential molecular mechanisms exposed to pentylenetetrazol. In the study, the mice were injected with pentetrazol 37 mg/kg, and alpha-linolenic acid was intra-gastrically administered for 40 days. The treatment with alpha-linolenic acid significantly reduced the overall frequency of epileptic seizures and improved the behavior impairment and cognitive disorder caused by pentetrazol toxicity. (2)
Reduced Risk of Allergic Diseases
Fatty acids (FA) are known to have a number of immunological effects and, accordingly, may play a role in the development of allergic diseases. Researchers from University of Tampere, Finland, investigated the effect of maternal intake of FA during pregnancy on the risk of allergic rhinitis, wheeze and atopic eczema in children aged 5 years. After adjusting for potential confounding variables, high maternal consumption of butter and butter spreads and higher ratio of n-6:n-3 FA during pregnancy were associated with an increased risk of allergic rhinitis in the offspring by 5 years of age. High maternal intakes of total PUFA and α-linolenic FA were associated with a decreased risk of allergic rhinitis. (3)
In a recent study, Kaori Yokoi and colleagues conducted a randomized, double-blinded, placebo-controlled trial on suppplementation of dihomo-γ-linolenic acid for pollen-induced allergic symptoms in healthy subjects. Each subject received four 250 mg capsules providing 314 mg dihomo-γ-linolenic acid/day (dihomo-γ-linolenic acid group, n = 18) or olive oil (placebo group, n = 15) for 15 weeks. In the dihomo-γ-linolenic acid group group, the cedar pollen associated symptoms of sneezing and a blocked nose in the "severity of allergic rhinitis symptoms" were significantly lower than those in the placebo group. (4).
Reduced Risk of Heart Failure (?)
According to The University of Maryland, Medical Reference (June 2013), there is some evidence that eating foods high in alpha-linolenic acid may benefit people at risk of heart diseases. The article cites a study that women who ate high levels of alpha-linolenic acid (1.5 g per day) had a 46% lower risk of sudden cardiac death than those who ate less amount of alpha-linolenic acid. However, researchers from University of Washington used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged ≥65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). They investigated the association of alpha-linolenic acid (ALA) with incident CHF. They found dietary alpha- linolenic acid (ALA) not associated with incident CHF. (5)
A study was done to examine the relation between omega-3 fatty acids in plasma phospholipid levels and cardiovascular disease risk factors in Canada. The researchers at Laval University Medical Center found significantly higher levels of alpha-linolenic acid (ALA) and docosapentaenoic acid in obese subjects, whereas significantly higher levels of docosahexaenoic acid (DHA) were observed in nonobese subjects. For cardiovascular disease risk factors, ALA levels were positively correlated with plasma triglyceride concentrations and negatively associated with diastolic blood pressure. (6)
In a report of 2022, Jiandi Wu and other researchers conducted a meta-analysis if there is a link of α-linolenic acid and the risk of heart failure. They found no association between α-linolenic acid and the risk of incident heart failure, suggesting that ALA might not be effective in the prevention of heart failure. (7)
Reduced Risk of High Cholesterol
Fukumitsu S and co-workers at Nippon Flour Mills Co., Ltd reported that eight lipid metabolism-related genes involved in cholesterol and triacylglycerol biosynthesis pathway and lipid transport were significantly down-regulated by α-Linolenic acid (ALA) treatment in their in vitro study. They further concluded that ALA is likely to inhibit cholesterol and fatty acid biosynthesis pathway by suppressing the expression of transcriptional factor sterol regulatory element binding protein SREBPs. and ALA promotes fatty acid oxidation in 3T3-L1 adipocytes. (8) On the other hand, eating food high in alpha-linolenic acid, such as walnut, has been shown to lower cholesterol and triglycerides in people with high cholesterol. (9) But, it is unclear if alpha-linolenic acid supplements would have similar benefits as foods rich in alpha-linolenic acid.
Reduced Risk of High Blood Pressure (Metabolic Syndrome)
Studies also suggest foods high in omega-3 fatty acids lower blood pressure slightly in people suffered from hypertension. But, it is also unclear if alpha-linolenic acid supplements also work in the same way. (10)
Neural Diseases
A major neuroprotective effect of α-linolenic acid was observed in in vivo models of both global ischemia and kainate-induced epilepsy; however, if sourced from flax seed oil, residues may have side effect due to its content of neurotoxic cyanogen glycosides and immunosuppressive cyclic nonapeptides. (11)
Lower concentrations of n-3 PUFAs have been reported to be associated with cognitive impairment and dementia, but also with depression-itself a potential risk factor for cognitive decline. Researchers from Taipei City Hospital found total erythrocyte n-3 PUFA concentrations are positively associated with cognitive function, particularly immediate recall, in older people with previous depression. Lower concentrations of n-3 PUFAs or ALA in erythrocyte membranes may be good predictors for cognitive impairment in older people with previous recurrent depression. (12)
In patients who have experienced a myocardial infarction (MI), n-3 (omega-3) PUFA status is low, whereas the risk of depression is increased. However, researchers from Leiden University Medical Center, Netherlands, found low- dose EPA-DHA supplementation, ALA supplementation, or a combination of both did not affect depressive symptoms and dispositional optimism in patients who had experienced an myocardial infarction. (13)
REFERENCE
1. Pan H. et al, Neurotoxicology. 2012 Oct;33(5):1219-29.
2. Xin Zeng et al, α-linolenic acid ameliorates pentylenetetrazol-induced neuron apoptosis and neurological impairment in mice with seizures via down-regulating JAK2/STAT3 pathway, Br J Nutr. 2024 May 22:1-34.
3. Nwaru BI et al, Br J Nutr. 2012 Aug;108(4):720-32.
4. Kaori Yokoi et al, Supplementation of Dihomo-γ-Linolenic Acid for Pollen-Induced Allergic Symptoms in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Trial, Nutrients. 2023 Aug 5;15(15):3465.
5. Lemailtre RN. et al, Am J Clin Nutr. 2012 Aug;96(2):269-74.
6. Gameau V. et al, Appl Physiol Nutr Metab. 2013 Mar;38(3):243-8.
7. Jiandi Wu et al, α-Linolenic Acid and Risk of Heart Failure: A Meta-Analysis,Front Cardiovasc Med. 2022 Jan 4:8:788452.
8. Cytotechnology. 2012 Nov 9.
9. Isabel Antonia Martínez-Ortega et al, Can different types of tree nuts and peanuts induce varied effects on specific blood lipid parameters? A systematic review and network meta-analysis, Crit Rev Food Sci Nutr. 2023 Dec 28:1-15.
10. Melika Same et al, Can daily consumption of enriched fatty acids diet be effective in improving metabolic syndrome? An attractive paradox for walnut kernel, Food Sci Nutr. 2024 Jan 28;12(4):2311-2333.
11. Wikipedia June 2013
12. Am J Clin Nutr. 2012 Feb;95(2):420-7
13. Am J Clin Nutr. 2011 Dec;94(6):1442-50