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Borage

Medically reviewed by Drugs.com. Last updated on Apr 1, 2019.

Scientific Name(s): Borago officinalis L.
Common Name(s): Bee fodder, Bee-bread, Borage, Burrage, Common bugloss, Cool tankard, Ox's tongue, Star flower

Clinical Overview

Use

Borage has been used in European herbal medicine since the Middle Ages, alone and in combination with fish oil for the treatment of rheumatoid arthritis, atopic eczema, and osteoporosis, although clinical evidence to support these uses is limited.

Dosing

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). The content of gamma-linolenic acid (GLA) is between 20% and 26% of the oil. A 2 g dose of dried herb brewed in 1 cup of boiling water taken 3 times daily has been suggested. 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.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Avoid use due to documented adverse effects (pyrrolizidine alkaloids).

Interactions

Because borage contains low concentrations of unsaturated pyrrolizidine alkaloids, which have been associated with hepatotoxic effects, it should not be used with hepatotoxic drugs such as anabolic steroids, phenothiazine, or ketoconazole. Borage may also lower the seizure threshold and should not be used with drugs that can lower the seizure threshold, such as tricyclic antidepressants and phenothiazines. Borage oil should also be used cautiously with any medication that may increase the risk of bleeding.

Adverse Reactions

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. Additionally, borage has been reported as the likely cause of several cases of methemoglobinemia in infants in Europe. In patients with rheumatoid arthritis (RA) taking borage, belching and soft stools occurred.

Toxicology

Because borage seeds contain small amounts of unsaturated pyrrolizidine alkaloids, including amabiline, a hepatotoxin, the German Federal Ministry of Health recommends no more than 10 mcg of unsaturated pyrrolizidine alkaloid consumption each day. Another source recommends no more than 1 mcg/day of unsaturated pyrrolizidine alkaloids. Internal use of whole borage leaf is not recommended.

Scientific Family

  • Boraginaceae (borage)

Botany

Borage is an annual plant that grows to about 0.6 m in height. The stem and leaves are covered with coarse, prickly hairs, and the flowers are large, star-shaped, and bright blue with contrasting black anthers. It is native to the Mediterranean region but has been widely naturalized in other areas. The fresh plant has a salty flavor and a cucumber-like odor.1

History

Borage leaves have been used as a potherb and in European herbal medicine since the Middle Ages, and were mentioned by Pliny (AD 61), Dioscorides (AD 40), and Galen (AD 129). Borage leaves and flowers were added to wine and lemon juice to make the popular English beverages claret cup and cool tankard. The leaves have been used to treat rheumatism, colds, and bronchitis, as well as to increase lactation in women. Infusions of the leaves have been used to induce sweating and diuresis.2

Chemistry

The leaves and flowers contain mucilage, tannin, and a small amount of essential oil. The seed yields a fixed oil with a high content (20% to 26%) of GLA, about twice the content of evening primrose oil, another commercial source.3 The triacylglycerol structure of borage oil has been compared with evening primrose oil and other GLA sources, with GLA attached at position sn-3 in evening primrose oil but at position sn-2 in borage seed oil.4, 5 This difference explains the apparently poorer bioavailability of GLA from borage seed oil compared with evening primrose oil.6 Results of numerous methods for analysis of GLA and other polyunsaturated fatty acids (PUFA) from borage seed oil and leaves have been published.4, 7, 8, 9

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.10 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.11, 12 More sensitive trace analyses are required to measure the safety of borage seed oils. Antioxidant activity of borage has been attributed to rosmarinic acid found in the plant leaves.13

Uses and Pharmacology

The 18-carbon fatty acid linoleic acid is considered essential in human nutrition because it must be obtained from the diet. It is converted by the enzyme delta-6-desaturase to GLA, which is thought to be rate-limiting in the pathway. GLA is further elaborated to the 20-carbon fatty acid dihomogammalinolenic acid (DGLA), a key metabolite for the synthesis of the anti-inflammatory prostaglandins of the 1-series (eg, PGE1) and 15-(S)-hydroxy-8,11,13-eicosatrienoic acid (15HETrE) by different types of cells.14 Theoretically, supplementation with GLA might bypass the rate-limiting step in biosynthesis, providing more of these anti-inflammatory modulators. In addition, pathophysiological conditions alter the ability to convert linoleic acid to GLA.14 Commercial sources of GLA include borage seed oil, evening primrose oil, and black currant seed oil, as well as the oil from the fungus Mucor javanicus.4 Cloning of delta-6-desaturase enzymes into plants that do not typically possess them has been proposed as a means to increase dietary GLA.15

Effects of gamma linolenic acid

Animal data

Extensive research has demonstrated that dietary supplementation with GLA can alter lipid fatty acid profiles in animal experiments. GLA itself is not always elevated; however, DGLA can be highly elevated by GLA supplementation. Macrophage phospholipids of mice fed borage seed oil showed altered ratios of 20-carbon PUFA.16 DGLA was selectively increased in the same system.17 The particular phospholipid classes altered by GLA supplementation were examined in mice.18 GLA and DGLA in cutaneous phospholipids were markedly increased in guinea pigs after an 8-week feeding experiment, along with the metabolites PGE1 and 15HETrE.19, 20, 21 Borage seed oil and evening primrose oil were equivalent sources of GLA in rats, despite the higher GLA content in borage oil.22 Upon stimulation with zymosan, isolated mouse peritoneal macrophages increased PGE1 synthesis when the mice had been maintained on high-GLA diets.23 Similar changes in hepatocyte PUFA were seen in Atlantic salmon smolts fed diets enriched with borage seed oil.24 Analysis of the interaction of cholesterol metabolism with PUFA metabolism in rats showed that GLA had a smaller hypercholesterolemic effect than alpha-linolenic acid.25 The effects of GLA supplementation in rats administered PUFA differed in immune tissues compared with other tissues.26 Other effects of GLA supplementation in animal models included an increase in Mn-superoxide dismutase in rats,27 decrease in rat liver fatty acid oxidation,28 changes in mouse macrophage–vascular smooth muscle cell interactions, and inhibition of serum cholesterol in aged rats on high-cholesterol diets.29 In a murine model of senile osteoporosis, mice supplemented with GLA-containing diets exhibited improved bone parameters, specifically suggesting a lower osteoclast activity level and, ultimately, a reduction in resorption rate and bone loss.30

Changes in these mediators of inflammation could possibly have an effect on a variety of diseases and conditions; some animal model experiments have been reported. Borage seed oil protected mice from experimental autoimmune encephalomyelitis, with improved clinical, biochemical, and histological parameters.31 Neovascularization of chemically burned rabbit corneas was favorably modulated by dietary GLA.32 The use of enteral and parenteral feeding formulations supplemented with GLA and fish oil was investigated with rat and pig models of acute endotoxin and burn injuries. Rats demonstrated increases in plasma GLA and DGLA,33 but lung microvascular permeability after endotoxin was not improved.34 Pulmonary eicosanoids were altered in endotoxic rats,35 but bacterial killing by macrophages was not changed.36 In pigs, pulmonary surfactant function was not altered despite changes in PUFA composition of the surfactant.37 GLA supplementation in aged rats provided protection against ventricular fibrillation.38 Thus, the link between dietary modulation of PUFA and functional changes remains tenuous in many cases.

Clinical data

Investigations in humans have followed a similar pattern. Borage seed oil increased plasma phospholipid GLA and DGLA levels while augmenting the arterial baroreflex control of vascular resistance in healthy humans, actions that may be useful in the treatment of hypertension.39 Proportions of different phospholipid types were unchanged, but DGLA was increased in platelets when borage seed oil was administered for 42 days.40 Neutrophils from participants whose diets were supplemented with GLA mobilized 3-fold more DGLA after ionophore stimulation compared with controls.41 In older participants, GLA had no effect on natural killer cell activity, while fish oil reduced it by 50%.42 In contrast, T-lymphocyte proliferation was decreased by GLA and fish oil in the same type of population.43 This effect on lymphocytes was reproduced by a second group for GLA in borage seed oil, where increases in plasma GLA and DGLA were observed.44 The release of proinflammatory leukotriene B4 from neutrophils with ionophore stimulation was reduced, while DGLA was elevated in healthy adults. The effects were greater at the higher of the 2 doses.45 In another study of healthy humans, administration of borage oil containing GLA 1.5 g/day for 3 weeks was found to decrease leukotriene synthesis as compared with baseline. After 2 weeks, activity returned to baseline.46 In a study of 50 formerly obese patients, supplementation with GLA (borage oil 5 g/day) was found to reduce weight regain, particularly when completing at least 50 weeks of treatment.47

Dermatological effects

Animal data

In a study of guinea pigs, borage oil given as part of a diet for 2 weeks reversed epidermal hyperproliferation.52

Clinical data

A randomized clinical trial conducted in adults and children favored placebo compared with borage oil for efficacy in atopic eczema.53 Other smaller trials noted a trend toward efficacy, but without reaching clinical importance.54, 55, 56, 57 In a trial designed to estimate the degree of prevention of atopic dermatitis in infants with a familial risk, borage oil supplementation had no effect on dermatitis incidence or serum immunoglobulin E and showed only a trend toward decreased severity of atopic dermatitis.58 In 2013, a Cochrane review identified 8 placebo-controlled randomized clinical trials conducted in adults and children that assessed borage oil for treatment of signs and symptoms of eczema. Meta-analyses could not be conducted on these studies because results were reported in different ways; however, assessments support previous reports of the lack of a significant effect of borage oil on global eczema symptoms. Atopic eczema/dermatitis syndrome has been recommended by an international task force to encompass all forms of eczema, including atopic dermatitis.94

In a study of 26 children ages 2 to 7 years, daily use of undershirts coated with borage oil (GLA 69.3 mg per 100 g of cotton) for 1 month slightly improved or improved erythema (61.6%), itch (65.3%), and dryness (57.7%). It was also shown to reduce transepidermal water loss, suggesting an improvement in the stratum corneum barrier.60 A review of the literature found varying results with the use of borage for atopic dermatitis, with a total of 12 studies of topical or oral borage oil identified. Of these studies, 5 found an effect, 5 found borage oil to be ineffective, and 2 found borage oil to be effective in some patients.61

In healthy female volunteers, a combination of GLA 150 mg in borage oil, catechin 47 mg, and vitamin E 2 mg mixed in a dairy matrix containing probiotics given twice daily was found to improve skin barrier function as early as 16 weeks, with the largest effects after 18 weeks.62 In another study, 45 healthy women were randomized to receive flaxseed 2.2 g/day, borage oil with tocopherol 10 mg/day, or placebo containing 2.2 g/day of medium-chain fatty acids for 12 weeks. Treatment with borage oil was found to exert anti-inflammatory activity as measured by chemically induced inflammation; it was also found to increase skin hydration and reduce transepidermal water loss.63 A small, open experiment in healthy elderly individuals reported improved cutaneous barrier function after 2 months of borage oil supplementation.59

Psychiatric disorders

Animal data

No animal data exist regarding the use of borage for psychiatric disorders.

Clinical data

In a 6-week, randomized, double-blind, parallel study, the effects of Echium amoenum (Boraginaceae) 500 mg compared with placebo were assessed in 44 patients with obsessive-compulsive disorder. By weeks 4 and 6, treatment with borage lowered obsessive, compulsive, and anxiety symptoms.68, 69

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults (2009) states that there is insufficient evidence for a recommendation of use.93

Respiratory distress syndrome

Animal data

In a study of rats, short-term (ie, 4 days) enteral feeding with a GLA and eicosapentaenoic acid (EPA) diet was found to form less inflammatory eicosanoids by alveolar macrophages.36

Clinical data

Compared with controls, 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.64 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 adult respiratory distress syndrome.65

In a study of 19 pediatric burn patients with acute respiratory distress syndrome, treatment with a specialized enteral product containing EPA, GLA, and antioxidants was found to improve oxygenation and pulmonary compliance compared with baseline after an average of 10.8 ± 0.9 days.66, 67

Rheumatoid arthritis

Animal data

No animal data exist regarding the use of borage for RA.

Clinical data

A 24-week randomized, double-blind, placebo-controlled trial of borage seed oil (GLA 1.4 g/day) in 37 individuals with RA found clinically important reduction in symptoms compared with a cotton seed oil placebo.48 A 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. Improvement was found in arthritis symptoms for both groups, with the cohort receiving 12 months of GLA supplementation improving throughout both phases.49 No adverse effects were detected in any of these regimens. In an 18-month, randomized, double-blind study, 146 patients with RA received either 3.5 g of omega-3 fatty acids, GLA 1.8 g/day, or combination therapy. No differences were found among treatment groups except for triglycerides. However, when the groups were combined, reductions in total and low-density lipoprotein (LDL) cholesterol and triglyceride levels, an increase in HDL cholesterol levels, and improvement in the atherogenic index were noted.50

A Cochrane review of trials from 1966 to 2000 suggests some benefit from GLA in RA, despite the relative poor quality of the individual studies. There was a trend toward reduction of morning stiffness, joint tenderness, and pain. Sufficient evidence was found to warrant further larger trials to provide optimal dosage, information regarding outcome, and duration of therapy.51

Other uses

Osteoporosis

A pilot study of fish oil plus borage seed oil in elderly, osteoporotic women found improved bone density in the treatment arm compared with placebo and improvement after crossover to all treatment in both groups.70

Diabetes

An in vivo experiment with borage oil failed to show an effect on insulin action and was associated with adversely affected lipid levels.71

Neurodevelopment

No differences in neurodevelopment were found in a randomized, controlled trial with infants fed supplemented formulas. However, in planned subgroup analysis, male participants fed the long-chain PUFA and borage oil–enriched formula scored higher on growth and neurodevelopment indicators.72

Asthma

No clinical effect could be demonstrated in a randomized, controlled trial of dietary supplementation versus placebo in asthma patients, despite measurable biochemical differences.5

Antimicrobial effects

In an in vitro study, borage was found to exert amoebicidal activity against Entamoeba histolytica.73 In another study, borage oil was found to exert bactericidal effects against Helicobacter pylori within 60 minutes of application.74

Hepatoprotective effects

Borage oil was found to exert hepatoprotective effects in rats with alcoholic steatohepatitis. Specifically, rats receiving the oil experienced an improvement in liver morphology, a reduction in triglyceride concentrations, and normalization of serum marker enzyme activities.75

Alcoholic hangover

One study found that GLA from borage significantly reduced the overall severity of alcoholic hangover, as well as headache, laziness, and fatigue, compared with placebo (P < 0.01).76

Transcutaneous delivery system

Borage oil has been used experimentally to deliver tamoxifen transcutaneously, with the aim of delivering tamoxifen and GLA through intact breast skin.77

Dosing

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).44, 53, 78 The content of GLA is 20% and 26% of the oil.48, 49

A 2 g dose of dried herb brewed in 1 cup of boiling water taken 3 times daily has been suggested.79

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.61

Pregnancy / Lactation

Avoid use due to documented adverse effects (pyrrolizidine alkaloids). Avoid use.11, 80, 81, 82, 83

Interactions

Because borage contains low concentrations of unsaturated pyrrolizidine alkaloids, which have been associated with hepatotoxic effects, it should not be used with hepatotoxic drugs, such as anabolic steroids, phenothiazine, or ketoconazole. Borage may lower the seizure threshold and should not be used with drugs that can lower the seizure threshold, such as tricyclic antidepressants and phenothiazines.84 Borage oil should also be used cautiously with coadministration of any medication that may increase the risk of bleeding.85

Adverse Reactions

Borage oil should be used cautiously in patients with epilepsy.86 A case report describes the development of temporal lobe and gelastic seizures ultimately progressing to status epilepticus occurring in a healthy 41-year-old woman who consumed borage oil 1,500 to 3,000 mg/day for 1 week.87 Additionally, borage has been reported as the likely cause of several cases of methemoglobinemia in infants in Europe.88 In patients with RA taking borage, belching and soft stools occurred.89

Toxicology

Because borage seeds contain small amounts of unsaturated pyrrolizidine alkaloids, including amabiline, a hepatotoxin, the German Federal Ministry of Health recommends no more than 10 mcg of unsaturated pyrrolizidine alkaloid consumption each day.10, 11, 12, 90, 91, 92 Another source recommends no more than 1 mcg/day of unsaturated pyrrolizidine alkaloid.79 Internal use of whole borage leaf is not recommended.

References

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