Gamma-Linolenic acid
Encyclopedia
γ-Linolenic acid is a fatty acid found primarily in vegetable oils. It is sold as a dietary supplement for treating problems with inflammation
and auto-immune diseases, although its efficacy is disputed.
(also called ω−6 or omega-6) fatty acid, meaning that the first double bond on the methyl end (designated with n or ω) is the sixth bond. In physiological literature, GLA is designated as 18:3 (n−6). GLA is a carboxylic acid
with an 18-carbon chain and three cis double bond
s. It is an isomer
of α-linolenic acid
, which is a polyunsaturated n−3 (omega-3) fatty acid, found in rapeseed (canola), soybeans, walnuts, flaxseed (linseed oil), perilla, chia, and hempseed.
. This herbal plant was grown by Native American
s to treat swelling in the body.
In the 17th century, it was introduced to Europe and became a popular folk remedy, earning the name king's cure-all.
in 1919, Heiduschka and Lüft extracted the oil from evening primrose seeds and described an unusual linolenic acid, which they name γ-.
Later, the exact chemical structure was characterized by Riley.
Although there are α- and γ-forms of linolenic acid, there is no β-form. One was once identified, but it turned out to be an artifact of the original analytical process.
) oil, blackcurrant
seed oil, borage
oil, and hemp seed oil
. GLA is also found in considerable quantities in edible hemp
seeds and from spirulina, a cyanobacterium. Each contains varying amounts of the fatty acid, with GLA safflower oil at 40% GLA being the most heavily concentrated form. In comparison, borage oil ranges from 15% to 20% GLA and evening primrose oil ranges from 8% to 10% GLA. All are widely available in pharmacies
, health food store
s, and online shop
s.
The human body produces GLA from linoleic acid
(LA). This reaction is catalyzed by Δ6-desaturase
(D6D), an enzyme that allows the creation of a double bond on the sixth carbon counting from the carboxyl terminus. LA is consumed sufficiently in most diets, from such abundant sources as cooking oil
s and meat
s. However, a lack of GLA can occur when there is a reduction of the efficiency of the D6D conversion (for instance, as people grow older or when there are specific dietary deficiencies) or in disease states wherein there is excessive consumption of GLA metabolites.
(DGLA). This is one of the body's three sources of eicosanoid
s (along with AA
and EPA
.) DGLA is the precursor of the prostaglandin
PGH1, which in turn forms PGE1 and the thromboxane
TXA1. PGE1 has a role in regulation of immune system
function and is used as the medicine alprostadil
. TXA1 modulates the pro-inflammatory properties of the thromboxane TXA2.
Unlike AA and EPA, DGLA cannot yield leukotrienes. However it can inhibit the formation of pro-inflammatory leukotrienes from AA.
Although GLA is an n−6 fatty acid, a type of acid that is, in general, pro-inflammatory, it has anti-inflammatory properties. (See discussion at Essential fatty acid interactions: The paradox of dietary GLA.)
properties lacking some of the common side-effects
of other anti-inflammatory drugs. Herbal medicine advocates recommend GLA for autoimmune disorders, arthritis
, eczema
, and PMS
, with noticeable results not expected for months. Research is ongoing, investigating GLA as a potential anticancer
agent. GLA is unique among the omega-6 polyunsaturated fatty acid
s (linoleic acid, GLA and arachidonic acid
) in its potential to suppress tumor growth and metastasis.
GLA can also form a lithium salt, increasing its solubility in water. The resulting compound is Li-GLA, also called lithium gammalinolenate. Li-GLA is currently in phase II clinical trials to determine whether it is useful in the treatment of HIV
infections, since it has the ability to destroy HIV-infected T cell
s in vitro
. It has a number of side-effects, including a reduction in hemoglobin
, hematuria
, gastrointestinal disturbance, fatigue, and headache.
. The UK's Medicines and Healthcare products Regulatory Agency
has withdrawn GLA's product licence for atopic eczema. Still, the US National Institute of Health's MedlinePlus states that there is 'B' grade evidence ('good scientific evidence') for the efficacy of evening primrose oil in the treatment of eczema
and skin irritation
. But it cautions that large well-designed studies are still needed. A controlled study of borage oil for eczema found no benefit to GLA; it underperformed placebo.
published much research on the use of GLA (as evening primrose oil) as a dietary supplement for treating atopic eczema.
He also founded Scotia Pharmaceuticals, which sold this oil as a pharmaceutical, which led to controversy even after his death.
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and auto-immune diseases, although its efficacy is disputed.
Chemistry
GLA is categorized as an n−6Omega-6 fatty acid
n−6 fatty acids are a family of unsaturated fatty acids that have in common a final carbon–carbon double bond in the n−6 position, that is, the sixth bond, counting from the methyl end.The biological effects of the n−6 fatty acids are largely mediated by their conversion to n-6 eicosanoids...
(also called ω−6 or omega-6) fatty acid, meaning that the first double bond on the methyl end (designated with n or ω) is the sixth bond. In physiological literature, GLA is designated as 18:3 (n−6). GLA is a carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
with an 18-carbon chain and three cis double bond
Double bond
A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...
s. It is an isomer
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...
of α-linolenic acid
Alpha-linolenic acid
α-Linolenic acid is an organic compound found in many common vegetable oils. In terms of its structure, it is named all-cis-9,12,15-octadecatrienoic acid. In physiological literature, it is given the name 18:3 ....
, which is a polyunsaturated n−3 (omega-3) fatty acid, found in rapeseed (canola), soybeans, walnuts, flaxseed (linseed oil), perilla, chia, and hempseed.
History
GLA was first isolated from the seed oil of evening primroseOenothera
Oenothera is a Genus of about 125 species of annual, biennial and perennial herbaceous flowering plants, native to North and South America. It is the type genus of the family Onagraceae, the Evening Primrose Family. Common names include evening-primrose, suncups, and sundrops.The species vary in...
. This herbal plant was grown by Native American
Indigenous peoples of the Americas
The indigenous peoples of the Americas are the pre-Columbian inhabitants of North and South America, their descendants and other ethnic groups who are identified with those peoples. Indigenous peoples are known in Canada as Aboriginal peoples, and in the United States as Native Americans...
s to treat swelling in the body.
In the 17th century, it was introduced to Europe and became a popular folk remedy, earning the name king's cure-all.
in 1919, Heiduschka and Lüft extracted the oil from evening primrose seeds and described an unusual linolenic acid, which they name γ-.
Later, the exact chemical structure was characterized by Riley.
Although there are α- and γ-forms of linolenic acid, there is no β-form. One was once identified, but it turned out to be an artifact of the original analytical process.
Dietary sources
GLA is obtained from vegetable oils such as: GLA safflower oil (Carthamus tinctorius), evening primrose (Oenothera biennisOenothera biennis
Oenothera biennis is a species of Oenothera native to eastern and central North America, from Newfoundland west to Alberta, southeast to Florida, and southwest to Texas, and widely naturalized elsewhere in temperate and subtropical regions.-Growth and flowering:Oenorthera biennis has a life span...
) oil, blackcurrant
Blackcurrant
Blackcurrant, Ribes nigrum, is a species of Ribes berry native to central and northern Europe and northern Asia, and is a perennial....
seed oil, borage
Borage
Borage, , also known as a starflower, is an annual herb originating in Syria, but naturalized throughout the Mediterranean region, as well as Asia Minor, Europe, North Africa, and South America. It grows to a height of , and is bristly or hairy all over the stems and leaves; the leaves are...
oil, and hemp seed oil
Hemp oil
Hempseed oil is pressed from the seed of the hemp plant irrespective of the strain of cannabis. Cold pressed, unrefined hemp oil is dark to clear light green in color, with a pleasant nutty flavor. The darker the color, the grassier the flavour....
. GLA is also found in considerable quantities in edible hemp
Hemp
Hemp is mostly used as a name for low tetrahydrocannabinol strains of the plant Cannabis sativa, of fiber and/or oilseed varieties. In modern times, hemp has been used for industrial purposes including paper, textiles, biodegradable plastics, construction, health food and fuel with modest...
seeds and from spirulina, a cyanobacterium. Each contains varying amounts of the fatty acid, with GLA safflower oil at 40% GLA being the most heavily concentrated form. In comparison, borage oil ranges from 15% to 20% GLA and evening primrose oil ranges from 8% to 10% GLA. All are widely available in pharmacies
Pharmacy
Pharmacy is the health profession that links the health sciences with the chemical sciences and it is charged with ensuring the safe and effective use of pharmaceutical drugs...
, health food store
Health food store
A health food store is a type of grocery store that primarily sells health food, organic foods, local produce, and often nutritional supplements...
s, and online shop
Online shop
Online shopping is the process whereby consumers directly buy goods or services from a seller in real-time, without an intermediary service, over the Internet. It is a form of electronic commerce...
s.
The human body produces GLA from linoleic acid
Linoleic acid
Linoleic acid is an unsaturated n-6 fatty acid. It is a colorless liquid at room temperature. In physiological literature, it has a lipid number of 18:2...
(LA). This reaction is catalyzed by Δ6-desaturase
Desaturase
A fatty acid desaturase is an enzyme that removes two hydrogen atoms from a fatty acid, creating a carbon/carbon double bond. These desaturases are classified as...
(D6D), an enzyme that allows the creation of a double bond on the sixth carbon counting from the carboxyl terminus. LA is consumed sufficiently in most diets, from such abundant sources as cooking oil
Cooking oil
Cooking oil is purified fat of plant origin, which is usually liquid at room temperature ....
s and meat
Meat
Meat is animal flesh that is used as food. Most often, this means the skeletal muscle and associated fat and other tissues, but it may also describe other edible tissues such as organs and offal...
s. However, a lack of GLA can occur when there is a reduction of the efficiency of the D6D conversion (for instance, as people grow older or when there are specific dietary deficiencies) or in disease states wherein there is excessive consumption of GLA metabolites.
Source of eicosanoids
From GLA, the body forms dihomo-γ-linolenic acidDihomo-gamma-linolenic acid
Dihomo-γ-linolenic acid is a 20-carbon ω−6 fatty acid. In physiological literature, it is given the name 20:3 . DGLA is a carboxylic acid with a 20-carbon chain and three cis double bonds; the first double bond is located at the sixth carbon from the omega end. DGLA is the elongation product...
(DGLA). This is one of the body's three sources of eicosanoid
Eicosanoid
In biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, ....
s (along with AA
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
and EPA
Eicosapentaenoic acid
Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...
.) DGLA is the precursor of the prostaglandin
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
PGH1, which in turn forms PGE1 and the thromboxane
Thromboxane
Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring....
TXA1. PGE1 has a role in regulation of immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
function and is used as the medicine alprostadil
Alprostadil
Prostaglandin E1 , known pharmaceutically as alprostadil, is a prostaglandin. It is a drug used in the treatment of erectile dysfunction and has vasodilatory properties.-Sexual dysfunction:...
. TXA1 modulates the pro-inflammatory properties of the thromboxane TXA2.
Unlike AA and EPA, DGLA cannot yield leukotrienes. However it can inhibit the formation of pro-inflammatory leukotrienes from AA.
Although GLA is an n−6 fatty acid, a type of acid that is, in general, pro-inflammatory, it has anti-inflammatory properties. (See discussion at Essential fatty acid interactions: The paradox of dietary GLA.)
Health and medicine
GLA is sometimes prescribed in the belief that it has anti-inflammatoryInflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
properties lacking some of the common side-effects
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
of other anti-inflammatory drugs. Herbal medicine advocates recommend GLA for autoimmune disorders, arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
, eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
, and PMS
Premenstrual stress syndrome
Premenstrual syndrome is a collection of physical and emotional symptoms related to a woman's menstrual cycle...
, with noticeable results not expected for months. Research is ongoing, investigating GLA as a potential anticancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
agent. GLA is unique among the omega-6 polyunsaturated fatty acid
Polyunsaturated fatty acid
Polyunsaturated fatty acids are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic property....
s (linoleic acid, GLA and arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
) in its potential to suppress tumor growth and metastasis.
GLA can also form a lithium salt, increasing its solubility in water. The resulting compound is Li-GLA, also called lithium gammalinolenate. Li-GLA is currently in phase II clinical trials to determine whether it is useful in the treatment of HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infections, since it has the ability to destroy HIV-infected T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
. It has a number of side-effects, including a reduction in hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
, hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
, gastrointestinal disturbance, fatigue, and headache.
Atopic eczema
Conflicting data are found for GLA in the treatment of eczemaEczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
. The UK's Medicines and Healthcare products Regulatory Agency
Medicines and Healthcare products Regulatory Agency
The Medicines and Healthcare products Regulatory Agency is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe....
has withdrawn GLA's product licence for atopic eczema. Still, the US National Institute of Health's MedlinePlus states that there is 'B' grade evidence ('good scientific evidence') for the efficacy of evening primrose oil in the treatment of eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
and skin irritation
Irritation
Irritation or exacerbation, in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-lining damage. A stimulus or agent which induces the state of irritation is an irritant...
. But it cautions that large well-designed studies are still needed. A controlled study of borage oil for eczema found no benefit to GLA; it underperformed placebo.
History
The medical use of GLA has been controversial. David HorrobinDavid Horrobin
David Frederick Horrobin was an entrepreneur, medical researcher, author and editor. He is best known as the founder of the biotechnology company Scotia Holdings and as a promoter of evening primrose oil as a medical treatment, Horrobin was founder and editor of the journals Medical Hypotheses and...
published much research on the use of GLA (as evening primrose oil) as a dietary supplement for treating atopic eczema.
He also founded Scotia Pharmaceuticals, which sold this oil as a pharmaceutical, which led to controversy even after his death.