aceite de borraja

Borage Oil (Borago officinalis)

1. Identity: Botanical Name, Source, and Preparations

Botanical name: Borago officinalis L. (family Boraginaceae). The plant is also known by the common names Borage, Starflower, and Bee Bread. Other historical names include Burrage and Bugloss. It is an annual herb belonging to the family Boraginaceae.

Borago officinalis is a native annual plant of the Mediterranean region that has been used since ancient times for both culinary and medicinal purposes. Borage is cultivated around the world but is native to Europe, North Africa, and Asia. It is a plant covered in rough hairs, with a thick stem growing to 60–100 cm, alternate and simple leaves that smell of cucumber, and pink, light blue, or less often white flowers.

Source of the oil: The herbal material of commercial relevance is the herb (Boraginis herba) and seeds (Boraginis semen), from which borage oil is obtained. Traditionally, borage was cultivated for culinary and medicinal uses, although today commercial cultivation is mainly as an oilseed.

Common forms and preparations: Borage is available as plant parts such as the leaf and flower, and as borage seed oil. Borage products, mainly seeds, oil, flowers, and leaves, are used for medicinal and culinary purposes. The seed oil is predominantly available as:

• Oral softgel capsules (the most common supplement form)
• Liquid seed oil for culinary or topical application
• Topically applied preparations, including borage oil–coated textiles studied in clinical settings
• Enteral nutrition formulas enriched with borage oil for hospital use
• A dried herb preparation of 2 g brewed in 1 cup of boiling water taken 3 times daily has also been described, though this is a traditional herbal-infusion use rather than a seed oil preparation.

The triglycerol stereospecificity of borage oil is distinct from that of other GLA-containing oils; GLA in borage oil is concentrated in the sn-2 position of the triglyceride, whereas in evening primrose oil it is concentrated in the sn-3 position.

2. Key Constituents and Chemical Composition

2.1 Fatty Acid Profile

Borage oil contains 20–26% gamma-linolenic acid (GLA), representing a unique omega-6 fatty acid with paradoxical anti-inflammatory properties. Borage oil has two to three times more GLA than evening primrose oil. By comparison, evening primrose oil contains 8–12% GLA, and blackcurrant oil contains 15–18% GLA.

In addition to GLA, the complete fatty acid profile of borage seed oil includes: not less than 22% C18:3 gamma-linolenic acid (GLA), between 9 and 12% C16:0 palmitic acid, between 3% and 5% C18:0 stearic acid, between 15% and 20% C18:1 oleic acid, between 35% and 42% C18:2 linoleic acid, between 3% and 5% C20:1 eicosenoic acid, between 1% and 4% C22:1 docosenoic acid, and up to 4% other fatty acids.

2.2 Minor Constituents

In addition to GLA, borage oil contains minor quantities of tocopherols, phytosterols, and squalene, and is thus used frequently in cosmetic products. Oils also contain mono- and diglycerides, free fatty acids, phospholipids, glycolipids, sterols, and other components including tocopherols, carotenoids, and phenolic compounds.

Phytochemical analyses indicate that borage herb contains carbohydrates, fatty acids, phytosteroids, polyphenols (including vanillic, p-coumaric, p-hydroxybenzoic, gentisic, caffeic, sinapic, rosmarinic, and chlorogenic acids, quercetin, isorhamnetin, and kaempferol), tannins, saponins, mucous compounds, organic acids (ascorbic, malic, citric, acetic, and lactic acid), tocopherols, allantoin, mineral salts, and vitamins, as well as volatile oil.

2.3 Pyrrolizidine Alkaloids

Because of the occurrence of toxic pyrrolizidine alkaloids in other members of the Boraginaceae family, borage leaves, seeds, and seed oil have been carefully investigated for their alkaloid content. The unsaturated, potentially toxic alkaloids lycopsamine and amabiline are found in borage leaves, stems, and roots in relatively low concentrations. The seeds and flowers contain the saturated pyrrolizidine alkaloid thesinine, along with traces of amabiline, supinine, and other alkaloids. Total alkaloid content of the plant is estimated at less than 0.001%, while mature seeds yield about 0.03% crude alkaloids.

3. Traditional and Historical Use

Borago officinalis, known as starflower, is a native annual plant of the Mediterranean region that has been used since ancient times for culinary and medicinal purposes, for the treatment of swelling and inflammation, respiratory complaints, and melancholy, as recalled in the old verse "Ego borago gaudia semper ago" ("I, Borage, bring always courage").

Pliny the Elder and Dioscorides said that borage was the nepenthe mentioned in Homer, which caused forgetfulness when mixed with wine. Across Western herbal traditions, borage has been revered for its ability to "restore courage," a theme reflected in the classical phrase Ego Borago gaudia semper ago — "I, Borage, always bring courage" — attributed to Pliny the Elder. Francis Bacon thought that borage had "an excellent spirit to repress the fuliginous vapour of dusky melancholie." John Gerard's Herball also mentions an old verse: "Ego Borago, Gaudia semper ago (I, Borage, bring always joys)."

Borage appears in several medieval treatises with new therapeutic indications. The 10th-century Old English Herbal is mostly a translation of the Latin Herbarium Apulei.

Traditionally, Borago officinalis has been used to treat hyperactive gastrointestinal, respiratory, and cardiovascular disorders, such as gastrointestinal complaints (colic, cramps, diarrhea), airways conditions (asthma, bronchitis), cardiovascular conditions (cardiotonic, antihypertensive, and blood purifier uses), and urinary complaints (diuretic and kidney/bladder disorders).

Additionally, health properties such as anti-obesity, diuretic, emollient, lenitive, laxative, anti-anemic, menstrual analgesic, and antipyretic properties are recorded in traditional use.

Borage plant parts have been used as a mild diuretic, expectorant, to induce sweating, and in proprietary mixtures promoted to increase milk supply; however, no scientifically valid clinical trials support this use.

Food and vegetable use of borage is common in Germany, in the Spanish regions of Aragón and Navarre, on the Greek island of Crete, and in the northern Italian region of Liguria. In Liguria, Italy, borage is commonly used as a filling for the traditional pasta ravioli and pansoti.

In the Unani system of medicine, Borago officinalis is known as starflower, borage, and gaozaban, and is an annual herb found in Syria, Europe, America, and Asia. It was popular for its mood-elevating properties from ancient times.

4. Mechanisms of Action

4.1 The GLA → DGLA Pathway

Gamma-linolenic acid (GLA, 18:3n-6) is an unusual omega-6 polyunsaturated fatty acid. Unlike other omega-6 fatty acids that are generally pro-inflammatory, GLA exhibits anti-inflammatory properties through its conversion to dihomo-gamma-linolenic acid (DGLA) and subsequent metabolites.

Linoleic acid is converted first to GLA then along the arachidonic acid pathway by an alternating sequence of delta-6-desaturation, chain elongation, and delta-5-desaturation. Dietary GLA supplementation bypasses the rate-limiting step of delta-6-desaturation and is quickly elongated to dihomo-gamma-linolenic acid (DGLA).

DGLA is metabolized via the cyclooxygenase (COX-1 and COX-2) pathway to 1-series prostaglandins, particularly PGE1, or converted via the 15-lipoxygenase pathway. GLA is converted to dihomo-γ-linolenic acid (DGLA), a precursor to a variety of 1-series prostaglandins and 3-series leukotrienes. It inhibits leukotriene synthesis to provide therapy in rheumatologic illness. Borage seed oil therefore may have anti-inflammatory and anti-thrombotic effects.

4.2 Prostaglandin and Eicosanoid Modulation

GLA is rapidly elongated to dihomo-gamma-linolenic acid (DGLA) by elongase enzymes, bypassing the rate-limiting delta-6 desaturase step. DGLA is then converted by cyclooxygenase (COX) enzymes to prostaglandin E1 (PGE1), which possesses anti-inflammatory properties. While fish oils enhance prostaglandin series 3 (PG3) production, GLA specifically promotes PGE1 synthesis, creating potential synergistic anti-inflammatory effects when the two are combined.

When borage seed oil (9 capsules/day) was administered for 12 weeks to both normal controls and patients with active rheumatoid arthritis, providing 1.1 g/day of GLA, GLA administration resulted in increased proportions of its first metabolite DGLA in circulating mononuclear cells. The ratios of DGLA to arachidonic acid and DGLA to stearic acid increased significantly. Significant reductions in prostaglandin E2, leukotriene B4, and leukotriene C4 produced by stimulated monocytes were seen after 12 weeks of GLA supplementation.

4.3 Tumor Necrosis Factor Suppression

Evidence from published research indicates that the gamma-linolenic acid component of borage oil increases prostaglandin E levels, which in turn increase cAMP levels, which suppress tumor necrosis factor-alpha (TNF-α) synthesis. Tumor necrosis factor-alpha has been shown to be a central mediator of inflammatory and joint destructive processes in rheumatoid arthritis. Double-blind studies have shown some benefit of borage oil in treatment of rheumatoid arthritis potentially through this mechanism.

4.4 Epidermal Barrier and Antiproliferative Effects

The accumulation of dihomo-gamma-linolenic acid (DGLA), an elongase product of GLA, into phospholipids and ceramides, along with 15-hydroxyeicosatrienoic acid (15-HETrE), the potent antiproliferative metabolite of DGLA, and of ceramides (the major lipid maintaining epidermal barrier), is greater in borage oil–fed animals than in those receiving lower doses of GLA. The antiproliferative efficacy of GLA in the epidermis is preferably exerted from the sn-2 stereospecificity of GLA in borage oil.

4.5 T Lymphocyte and Immune Modulation

DGLA is converted to 15-hydroxy DGLA, which has the virtue of suppressing 5-lipoxygenase activity. GLA and DGLA also modulate immune responses in an eicosanoid-independent manner by acting directly on T lymphocytes, and GLA suppresses acute and chronic inflammation, including arthritis, in animal models.

5. Scientific Evidence by Area of Use

5.1 Rheumatoid Arthritis

Rheumatoid arthritis (RA) is the most extensively studied therapeutic indication for borage oil.

A small, double-blind clinical trial from 1993 found that 24 weeks of borage seed oil supplementation significantly reduced RA symptoms in 37 people. Participants reported a 36% reduction in the number of tender joints and a 45% reduction in tenderness scores. By comparison, the participants taking a placebo saw no improvements.

In the same 1993 trial, the dose was GLA 1.4 g/day in 37 individuals with RA, with a cotton seed oil placebo. A further trial in 56 participants using a higher dose (GLA 2.8 g/day) included a 6-month double-blind phase and a second 6-month single-blind trial. Another small study from 1996 with 56 participants observed similar improvements with GLA; 64% of those who took GLA had a reduction in joint tenderness and morning stiffness, compared with around 20% who took a placebo.

For the treatment of rheumatoid arthritis, the amounts of GLA from borage used in successful double-blind trials were 1.4–2.8 grams daily for at least two months.

GLA and DGLA modulate immune responses by acting directly on T lymphocytes, and in several randomized, placebo-controlled trials in RA patients, GLA in borage or primrose seed oils reduced synovitis and the need for nonsteroidal anti-inflammatory agents.

Systematic review evidence: A Cochrane systematic review found evidence from seven studies indicating potential benefits of GLA from evening primrose oil, borage seed oil, or blackcurrant seed oil in terms of reduced pain intensity (mean difference –32.83 points on a 100-point pain scale, 95% CI –56.25 to –9.42), improved disability (MD –15.75%, 95% CI –27.06 to –4.44%), and an increase in adverse events. The review concluded there is moderate evidence that oils containing GLA (including borage seed oil) afford some benefit in relieving symptoms for RA.

The borage and blackcurrant seed oil trials were pooled in meta-analysis; the 3 trials together included 117 patients. The pooled effect size for swollen joint count was not statistically significant. There was moderate support for GLA having a medium to strong effect on reducing pain and tender joint count and a small effect on reducing stiffness in rheumatoid arthritis for those with active disease.

Evidence strength: Moderate. Multiple small randomized controlled trials (RCTs) and a Cochrane review support symptomatic benefit, but trials have small sample sizes and vary in design. The Cochrane review calls for further well-designed, fully powered confirmatory trials.

5.2 Atopic Dermatitis (Eczema)

The basis for using borage oil in atopic dermatitis is the GLA-deficit hypothesis. EFA deficiency replicates the symptoms of atopic dermatitis, and patients with the condition have been reported to have imbalances in EFA levels. Although direct proof is lacking, it has been hypothesized that patients with atopic dermatitis have impaired activity of the delta-6 desaturase enzyme, affecting metabolism of linoleic acid to GLA.

Borage oil is of particular interest because it contains two to three times more GLA than evening primrose oil. A review identified 12 clinical trials of oral or topical borage oil for treatment of atopic dermatitis and one preventive trial. All studies were controlled and most were randomized and double-blind, but many were small and had other methodological limitations. The results of studies of borage oil for atopic dermatitis were highly variable, with the effect reported to be significant in five studies, insignificant in five studies, and mixed in two studies.

Topical borage oil (coated textiles): The clinical effects of undershirts coated with borage oil rich in GLA on atopic dermatitis were evaluated in a double-blind placebo-controlled study. Thirty-two children aged 1–10 years were involved; 16 wore undershirts coated with borage oil every day for 2 weeks, and 16 wore non-coated undershirts as placebo. Those children who wore borage oil–coated shirts showed statistically significant improvements in erythema and itch. Transepidermal water loss from the back was decreased. In the placebo group, there were no statistically significant differences. The coated undershirts were found to be effective with no side effects in children with mild atopic dermatitis.

Oral borage oil — negative large trial: A randomized, double-blind, placebo-controlled parallel-group trial studying the efficacy and tolerability of borage oil (high GLA concentration) in children and adults with atopic eczema found that the mean SASSAD score fell from 30 to 27 in the borage oil group and from 28 to 23 in the placebo group. The difference between the mean improvements in the two groups was 1.4 points (95% CI –2.2 to 5.0) in favour of placebo (P = 0.45). No significant differences occurred between treatment groups in other assessments, and the treatments were well tolerated. The authors concluded that gamma-linolenic acid is not beneficial in atopic dermatitis in this study.

Cochrane review conclusion: Noting that the confidence intervals between active and placebo treatment are narrow, to exclude the possibility of any clinically useful difference, the Cochrane review concluded that further studies on evening primrose oil or borage oil for eczema would be hard to justify. The review does not provide information about long-term use of these products.

Borage oil given to at-risk neonates did not prevent development of atopic dermatitis. However, the majority of studies showed at least a small degree of efficacy or were not able to exclude the possibility that the oil produces a small benefit. Overall, the data suggest that nutritional supplementation with borage oil is unlikely to have a major clinical effect but may be useful in some individual patients with less severe atopic dermatitis.

Evidence strength: Weak to mixed for oral administration. The largest and most rigorous clinical trial and the Cochrane review found no statistically significant benefit for oral borage oil in eczema. Topical application (via coated textiles) showed some benefit in one small trial. Further research in this area has been deemed unlikely to change conclusions.

5.3 Acute Respiratory Distress Syndrome (ARDS) and Critical Illness

One of the most clinically significant areas of borage oil research involves its use in combination with fish oil (EPA/DHA) in specialized enteral nutrition formulas for critically ill patients.

Studies in animal models of sepsis-induced ARDS showed that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggested that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and improve clinical outcomes in patients with ARDS. A prospective, multicentred, double-blind, randomized controlled trial was subsequently undertaken.

A multicenter trial of fish oil and borage seed oil added to enteral feeding mixtures in patients with acute respiratory distress syndrome resulted in improvement in outcomes, with reduced major organ failures, shorter intensive care unit stays, and less ventilator support required. On the basis of this trial, Canadian practice guidelines for nutritional support in mechanically ventilated critically ill patients made the recommendation that the use of products with fish oils, borage oils, and antioxidants be considered in patients with ARDS.

A meta-analysis aggregating the results of three randomized clinical trials conducted in patients with ARDS found that an enteral formula enriched with fish oils appears to significantly reduce mortality by as much as 49%, ventilator days, and ICU length of stay by up to 6 days. More recent prospective, randomized trials of fish oils and borage oil in ARDS have shown no benefit, however.

In subsequent trials, an enteral formula enriched with borage oil (GLA) plus fish oil significantly reduced duration of mechanical ventilation and ICU stay; inflammatory cytokines were significantly lower in the treatment group.

Evidence strength: Mixed to moderate. The foundational multicenter RCT produced positive results; Canadian clinical practice guidelines once recommended this combination. However, more recent RCTs have not consistently replicated the benefit, and interpretive complications include variable feeding methods, patient populations, and co-administered treatments.

5.4 Anti-Inflammatory Effects: Cytokine Studies

Borage oil supplementation significantly reduced lipopolysaccharide (LPS)-stimulated IL-1β and PGE2 production in blood samples of healthy volunteers. TNF-α was modestly but significantly reduced. These results confirm systemic anti-inflammatory activity.

Dietary borage oil significantly raised DGLA in immune cell membranes and reduced leukotriene B4 and thromboxane production.

5.5 Other Areas with Limited or Preliminary Evidence

In herbal medicine, borage seed oil has also been used for seborrheic dermatitis, neurodermatitis, stress, premenstrual syndrome, diabetes, attention deficit-hyperactivity disorder (ADHD), alcoholism, pain and swelling (inflammation), and for preventing heart disease and stroke. There is insufficient scientific evidence to determine the effectiveness of borage for the majority of these uses.

Those with premenstrual syndrome, diabetes, scleroderma, Sjögren's syndrome, tardive dyskinesia, eczema, and other skin conditions may have a metabolic block that interferes with the body's ability to make GLA. However, most clinical trials supplementing GLA for these conditions have used evening primrose oil, and not borage oil specifically.

Cancer (preclinical only): Specific mechanisms inducing cytotoxicity have been observed for GLA in several preclinical studies: GLA induces apoptosis in cell lines checked by DNA fragmentation; GLA enhances the cytotoxicity of docetaxel in human breast cancer cells; human chronic myelogenous leukemia K562 cells are switched to the apoptotic pathway by activation of caspase-3 and release of cytochrome c; and GLA treatment in hepatocellular carcinoma cells upregulated genes encoding antioxidant proteins. These are in vitro and animal findings; no human clinical trials have established borage oil as a cancer treatment.

Antioxidant and phenolic activity: Borage seed extracts have demonstrated superior ferric-reducing antioxidant power (FRAP) compared to leaf extracts, owing to their richer content of tocopherols, polyphenols, and vitamin C. These findings affirm the potent antioxidant potential of Borago officinalis and support its therapeutic application in oxidative stress-related conditions. These findings are based primarily on in vitro and analytical studies.

6. Body Systems Associated with Borage Oil

• Musculoskeletal / Immune: Rheumatoid arthritis; reduction in joint tenderness, swelling, and morning stiffness; modulation of inflammatory eicosanoids
• Integumentary (skin): Atopic dermatitis, eczema, seborrheic dermatitis; epidermal barrier function and transepidermal water loss
• Respiratory / Critical care: Acute respiratory distress syndrome; lung inflammation and oxygenation in intensive care settings
• Cardiovascular: Historically used as antihypertensive and cardiotonic; studied for effects on prostaglandin E1 (anti-thrombotic potential), though human evidence is limited
• Gastrointestinal: Traditional use for colic, cramps, and diarrhea; GI adverse effects (soft stools, belching) also noted in clinical trials
• Hepatic: Importantly, the plant parts (but generally not the refined seed oil) contain pyrrolizidine alkaloids with hepatotoxic potential

7. Dosage Forms and Dosages Reported in Studies

Borage seed oil 1 to 3 g/day has been given in clinical trials; 1 g/day has been used in children, and up to 3 g/day has been used in adults.

Oral doses of 2,000 to 4,000 mg/day (GLA 400 to 1,000 mg) in adults and 1,000 to 2,000 mg/day (GLA 240 to 480 mg) in children with atopic dermatitis have been studied.

For rheumatoid arthritis, the amounts of GLA from borage used in successful double-blind trials were 1.4–2.8 grams of GLA daily for at least two months.

Studies using doses of 1.4 grams and 2.8 grams of GLA per day in RA patients both found statistically significant improvements. The higher dose corresponds to roughly 6 to 11 grams of borage oil daily, depending on GLA concentration.

In a study examining effects on platelet aggregation, male volunteers consumed on average 5.23 g of GLA (as borage oil) daily for 42 days followed by a 42-day washout period.

Topically, 0.5 ml of borage oil may be applied to areas of seborrhea daily for two weeks, and then three times a week until the condition is stable, based on one reported study.

8. Safety Considerations

8.1 Pyrrolizidine Alkaloids

Borage plant parts contain pyrrolizidine alkaloids that are toxic to the liver and lungs and possibly carcinogenic. These alkaloids might be excreted into breastmilk.

Borage oil may contain the pyrrolizidine alkaloid amabiline, which is hepatotoxic, leading to a risk of liver damage. Patients should use borage oil that is certified free of toxic unsaturated pyrrolizidine alkaloids (UPAs).

Consumption of 1–2 g of borage seed oil daily can result in an intake of toxic UPAs approaching 10 µg. The German Federal Health Agency specifies consumption to be limited to 1 µg of UPA daily.

Although the amount of PAs present in borage plant parts is considered to be low — less than 0.001% dry weight — borage leaf teas may contain very high, possibly unsafe levels of pyrrolizidine alkaloids. Based on this, the UK's Food Standards Agency recommends these be avoided.

Borage flower contains the pyrrolizidine alkaloid thesinine, which is considered to be nontoxic. Importantly, pyrrolizidine alkaloids in borage are not extracted with borage seed oil, and for this reason, products made from the oil would not be expected to contain PAs.

The German Commission E reports that borage contains hepatotoxic and carcinogenic pyrrolizidine alkaloids. In view of the known toxic pyrrolizidine alkaloid constituents, excessive or prolonged ingestion of borage should be avoided.

8.2 Hepatotoxicity — Clinical Case

A case report describes a patient who used borage oil and was admitted to the emergency room with jaundice, asthenia, decreased appetite, and right hypochondrial pain after use of the herbal medicine, being initially diagnosed with acute hepatitis induced by borage oil. Liver biopsy revealed intense lymphocyte inflammatory infiltrate in addition to plasma cells, neutrophils, and macrophages, with aggression to the limiting plaque and hepatocytes.

8.3 Neurological Effects — Seizures

Borage oil should be used cautiously in patients with epilepsy. A case report describes the development of temporal lobe and gelastic seizures ultimately progressing to status epilepticus in a healthy 41-year-old woman who consumed borage oil 1,500 to 3,000 mg/day for 1 week. There has been a single reported case of status epilepticus associated with borage oil ingestion.

8.4 Pregnancy

Borage oil may be unsafe during pregnancy because preliminary studies suggest borage oil has a teratogenic effect and that its prostaglandin E agonist action may cause premature labor.

8.5 Methemoglobinemia in Infants

Borage has been reported as the likely cause of several cases of methemoglobinemia in infants in Europe.

8.6 Common Gastrointestinal Effects

In patients with rheumatoid arthritis taking borage in clinical trials, belching and soft stools occurred. Borage seed oil is generally well tolerated in adults; however, only products certified as pyrrolizidine alkaloid free should be used.

8.7 Platelet Aggregation

When male volunteers consumed an average of 5.23 g of GLA (as borage oil) daily for 42 days, increased platelet aggregation was observed at days 22 and 43; this was not accompanied by a statistically significant rise in thromboxane A2, PGE1, or PGE2 formation. These observations suggest the enhanced platelet aggregation may be mediated by GLA, some other component of borage oil, or by a non-eicosanoid mechanism.

8.8 Regulatory and Quality Considerations

Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible for ensuring safety but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. In view of the known toxic pyrrolizidine alkaloid constituents, excessive or prolonged ingestion of borage should be avoided. Consumers should select seed oils that are specifically certified PA-free, as opposed to herbal preparations derived from leaves or other plant parts.

References

• Gadek JE et al. Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Crit Care Med. 1999. PubMed PMID: 10470743.
• GLA in borage oil reverses epidermal hyperproliferation in guinea pigs. PubMed PMID: 12368400.
• Takwale A et al. Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial. PubMed PMID: 14670885.
• Kanehara S et al. Clinical effects of undershirts coated with borage oil on children with atopic dermatitis: a double-blind, placebo-controlled clinical trial. J Dermatol. 2007. PubMed PMID: 18078406.
• Foster RH, Hardy G, Alany RG. Borage oil in the treatment of atopic dermatitis. Nutrition. 2010. PubMed PMID: 20579590.
• Cameron M, Gagnier JJ, Chrubasik S. Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2011. PubMed PMID: 21328257.
• Leventhal LJ. Borage oil reduction of rheumatoid arthritis activity may be mediated by increased cAMP that suppresses tumor necrosis factor-alpha. BMC Complement Altern Med. 2001. PubMed PMID: 11710548.
• Tate G et al. Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma-linolenic acid. Arthritis Rheum. 1989. PubMed PMID: 2171540.
• Bamford JT et al. Oral evening primrose oil and borage oil for eczema. Cochrane Database Syst Rev. 2013. PubMed PMID: 23633319.
• LactMed. Borage. National Library of Medicine, Drugs and Lactation Database. PubMed PMID: 30000849.
• Bamford JTM et al. Oral evening primrose oil and borage oil for eczema. PMC8105655.
• Cancer Prevention and Health Benefits of Traditionally Consumed Borago officinalis Plants. PMC4728661.
• Protective Effect of Borage Seed Oil and Gamma Linolenic Acid on DNA: In Vivo and In Vitro Studies. PMC3584109.
• Treatment of Rheumatoid Arthritis with Marine and Botanical Oils: An 18-Month, Randomized, and Double-Blind Trial. PMC3977504.
• Dihomo-γ-Linolenic Acid (20:3n-6) — Metabolism, Derivatives, and Potential Significance in Chronic Inflammation. PMC9916522.
• Health-Promoting Properties of Borage Seed Oil Fractionated by Supercritical Carbon Dioxide Extraction. PMC8535258.
• Michalak M, Zagórska-Dziok M. Phenolic Profile and Antioxidant, Anti-Ageing, Anti-Inflammatory, and Protective Activities of Borago officinalis Extracts on Skin Cells. PMC9865334.
• Borage. Drugs and Lactation Database (LactMed). NCBI Bookshelf NBK501790.
• Herbal medicines for the treatment of rheumatoid arthritis: a systematic review. Database of Abstracts of Reviews of Effects (DARE). NCBI Bookshelf NBK70088.
• Herbal therapy for rheumatoid arthritis. Cochrane Evidence Summary.
• Drugs.com Natural Products Database: Borage. (Cites primary clinical literature and pharmacopeial sources.)
• PeaceHealth Health Information Library: Borage Oil.
• Borage seed oil. Wikipedia (citing primary pharmacological sources).
• Medical News Today: Borage seed oil for rheumatoid arthritis: Does it help?
• Slama et al. Borago officinalis L.: A Review on Extraction, Phytochemical, and Pharmacological Activities. Chemistry & Biodiversity. 2024.
• Sufwan et al. Advances in Pharmacological Insights of Borago officinalis: A Comprehensive Review. Biological Diversity. 2025.
• American Herbal Products Association: Herbs in History — Borage.
• ConsumerLab: Pyrrolizidine Alkaloids in Supplements (including borage).
• Herbal hepatotoxicity: Difficulties in the diagnosis and treatment of liver lesions by borage oil. Research, Society and Development. 2025.
• The effect of borage oil supplementation on human platelet aggregation, thromboxane B2, prostaglandin E1 and E2 formation. ScienceDirect. 2006.
• Borage Oil — An Overview. ScienceDirect Topics.
• Borage Oil and Gamma-Linolenic Acid: A Comprehensive Monograph. Townsend Letter. January 2026.