Medication Guide App

Borage

Scientific Name(s): Borago officinalis L. Family: Boraginaceae (borage family) 1

Common Name(s): Borage , burrage , common bugloss , bee-bread , bee fodder , star flower , ox's tongue , cool tankard

Uses

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

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 in adults). 2 , 3 , 4 The content of gamma-linolenic acid is between 20% and 26% of the oil. 5 , 6

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Documented adverse effects (pyrrolizidine alkaloids). Avoid use. 7 , 8 , 9 , 10 , 11

Interactions

None well documented.

Adverse Reactions

No adverse effects have been reported. Although no direct evidence is available, caution is advised in patients with epilepsy because of reports of lowered seizure threshold with evening primrose oil. 12

Toxicology

The presence of unsaturated pyrrolizidine alkaloids in leaves, flowers, and seeds of borage 13 , 14 suggests a potential for hepatotoxicity, although the total plant alkaloid content is low. 11 , 15 , 16

Botany

Borage is an annual 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 a native of Europe but has been widely naturalized in other areas. The fresh plant has a salty flavor and a cucumber-like odor.

History

Borage leaves have been used as a potherb and in European herbal medicine since the Middle Ages, and are 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 beverages of claret cup and cool tankard. Borage leaves have been used to treat rheumatism, colds, and bronchitis, and to increase lactation in women. Infusions of the leaves were used to induce sweating and diuresis. 17

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 gamma-linolenic acid (GLA), about twice the content of evening primrose oil, another commercial source. 18 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 sn-2 in borage seed oil. 19 , 20 This difference explains the apparently poorer bioavailability of GLA from borage seed oil compared with evening primrose oil. 21 Numerous methods for analysis of GLA and other polyunsaturated fatty acids (PUFA) from borage seed oil and leaves have been published. 19 , 22 , 23 , 24

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 concentration. 13 The seeds and flowers contain the saturated pyrrolizidine alkaloid thesinine, along with a trace of amabiline, supinine, and other alkaloids. Total alkaloid content of the plant is estimated as less than 0.001%, while mature seeds yield about 0.03% crude alkaloids. 11 , 14 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. 25

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 considered rate-limiting in the pathway. GLA is further elaborated to the 20-carbon fatty acid dihomogamma-linolenic 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. 26 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. 26 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 . 19 Cloning of delta-6-desaturase enzymes into plants that do not typically possess them has been proposed as a means to increase dietary GLA. 27

Animal data

Extensive research has demonstrated that dietary supplementation with GLA can alter lipid fatty acid profiles in experimental animals. GLA itself is not always elevated; however, DGLA can be highly elevated by GLA supplementation. Macrophage phospholipids of mice showed altered ratios of 20-carbon PUFA when they were fed borage seed oil. 28 DGLA was selectively increased in the same system. 29 The particular phospholipid classes altered by GLA supplementation were examined in mice. 30 GLA and DGLA in cutaneous phospholipids were markedly increased in guinea pigs after an 8-week feeding experiment, as well as the metabolites PGE 1 and 15HETrE. 31 , 32 , 33 Borage seed oil and evening primrose oil were equivalent sources of GLA in rats despite the higher GLA content in borage oil. 34 Upon stimulation with zymosan, isolated mouse peritoneal macrophages increased PGE1 synthesis when the mice had been maintained on high GLA diets. 35 Similar changes in hepatocyte PUFA were seen in Atlantic salmon smolts fed diets enriched with borage seed oil. 36 Analysis of the interaction of cholesterol metabolism with PUFA metabolism in rats showed that GLA had a smaller hypercholesterolemic effect than alpha-linolenic acid. 37 The effects of GLA supplementation in rats administered PUFA were different in immune tissues compared with other tissues. 38 Other effects of GLA supplementation in animal models include an increase in Mn-superoxide dismutase in rats, 39 decrease in rat liver fatty acid oxidation, 40 changes in mouse macrophage-vascular smooth muscle cell interactions, and inhibition of serum cholesterol in aged rats on high cholesterol diets. 41

Changes in these mediators of inflammation might be expected to have an impact on a variety of diseases and conditions. Animal model experiments have been reported for some of them. Borage seed oil protected mice from experimental autoimmune encephalomyelitis, with improved clinical, biochemical, and histological parameters. 42 Neovascularization of chemically burned rabbit corneas was favorably modulated by dietary GLA. 43 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 44 ; however, lung microvascular permeability after endotoxin was not improved. 45 Pulmonary eicosanoids were altered in endotoxic rats, 46 but bacterial killing by macrophages was not changed. 47 In pigs, pulmonary surfactant function was not altered despite changes in PUFA composition of the surfactant. 48 GLA supplementation in aged rats provided protection against ventricular fibrillation. 49 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. 50 Proportions of different phospholipid types were unchanged, but DGLA was increased in platelets when borage seed oil was administered for 42 days. 51 Neutrophils from subjects whose diets were supplemented with GLA mobilized 3-fold more DGLA after ionophore stimulation compared with controls. 52 In older subjects, GLA had no effect on natural killer cell activity, while fish oil reduced it by 50%. 53 In contrast, T-lymphocyte proliferation was decreased by GLA and fish oil in the same type of population. 54 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. 2 The release of pro-inflammatory 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. 55

Rheumatoid arthritis

Clinical trials have been performed with borage seed oil or purified GLA in several diseases. A 24-week randomized, double-blind, placebo-controlled trial of borage seed oil (GLA 1.4 g/day) in 37 individuals with rheumatoid arthritis found clinically important reduction in symptoms compared with a cotton seed oil placebo. 5 A trial in 56 subjects 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. 6 No adverse effects were detected in any of these regimens.

A Cochrane review of trials from 1966 to 2000 suggests some benefit from GLA in rheumatoid arthritis, 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. 56

Atopic eczema/dermatitis

A randomized clinical trial conducted in adults and children favored placebo compared with borage oil for efficacy in atopic eczema. 3 Other smaller trials noted a trend toward efficacy but without reaching clinical significance. 57 , 58 , 59 , 60 In a trial designed to estimate degree of prevention of atopic dermatitis in infants with a familial risk, borage oil supplementation had no effect on dermatitis incidence or serum IgE and showed only a trend toward decreased severity of atopic dermatitis. 61 A small, open experiment in healthy elderly individuals reported improved cutaneous barrier function after 2 months of borage oil supplementation. 62

Respiratory distress syndrome

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 noted improvement in outcomes, with reduced major organ failures, shorter intensive care unit stays, and less ventilator support required. 63 On the basis of this trial, Canadian practice guidelines for nutritional support in mechanically ventilated, critically ill patients, made the following recommendation: the use of products with fish oils, borage oils, and antioxidants should be considered in patients with adult respiratory distress syndrome. 64

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. 65

Diabetes

An in vivo experiment with borage oil failed to show an effect on insulin action and was associated with adversely affected lipid levels. 66

Neurodevelopment

No differences in neurodevelopment were found in a randomized, controlled trial with infants fed supplemented feeds. However, in planned subgroup analysis, boys fed the long-chain PUFA and borage oil-enriched formula scored higher on growth and neurodevelopment indicators. 67

Asthma

No clinical effect could be demonstrated in a randomized controlled trial of dietary supplementation versus placebo in asthma patients, despite measurable biochemical differences. 20

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. 68

Dosage

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 in adults). 2 , 3 , 4 The content of GLA is between 20% and 26% of the oil. 5 , 6

Pregnancy/Lactation

Documented adverse effects (pyrrolizidine alkaloids). Avoid use. 7 , 8 , 9 , 10 , 11

Interactions

None well documented.

Adverse Reactions

No adverse effects have been reported. Although no direct evidence is available, caution is advised in patients with epilepsy because of reports of lowered seizure threshold with evening primrose oil. 12

Toxicology

The presence of unsaturated pyrrolizidine alkaloids in leaves, flowers, and seeds of borage 13 , 14 suggests a potential for hepatotoxicity, although the total plant alkaloid content is low. 11 , 15 , 16

Bibliography

1. USDA, NRCS. 2004. The PLANTS Database, Version 3.5 ( http://plants.usda.gov ). National Plant Data Center; Baton Rouge, LA 70874-4490.
2. Rossetti RG, Seiler CM, DeLuca P, Laposata M, Zurier RB. Oral administration of unsaturated fatty acids: effects on human peripheral blood T lymphocyte proliferation. J Leukoc Biol . 1997;62:438-443.
3. Takwale A, Tan E, Agarwal S, et al. Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial. BMJ . 2003;327:1385.
4. Rosenstein ED, Kushner LJ, Kramer N, Kazandjian G. Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis. Prostaglandins Leukot Essent Fatty Acids . 2003;68:213-218.
5. Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with gammalinolenic acid. Ann Intern Med . 1993;119:867-873.
6. Zurier RB, Rossetti RG, Jacobson EW, et al. Gamma-linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum . 1996;39:1808-1817.
7. Rotblatt M, Ziment I. Evidence-Based Herbal Medicine . Philadelphia, PA: Hanley & Belfus; 2002.
8. Brinker FJ. Herb Contraindications and Drug Interactions . 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998.
9. Newall CA, Anderson LA, Phillipson JD, eds. Herbal Medicines: A Guide for Health-Care Professionals . London: Pharmaceutical Press; 1996.
10. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109:227-235.
11. Herrmann M, Joppe H, Schmaus G. Thesinine-4′-O-beta-D-glucoside the first glycosylated plant pyrrolizidine alkaloid from Borago officinalis . Phytochemistry . 2002;60:399-402.
12. Spinella M. Herbal Medicines and Epilepsy: The Potential for Benefit and Adverse Effects. Epilepsy Behav . 2001;2:524-532.
13. Larson KM, Roby MR, Stermitz FR. Unsaturated pyrrolizidines from borage ( Borago officinalis ), a common garden herb. J Nat Prod . 1984;47:747-748.
14. Dodson CD, Stermitz FR. Pyrrolizidine alkaloids from borage ( Borago officinalis ) seeds and flowers. J Nat Prod . 1986;49:727-728.
15. Langer T, Franz C. Determination of pyrrolizidine alkaloids in commercial samples of borage seed oil products by GC-MS. Sci Pharm . 1997;65:321-328.
16. Mierendorff HJ. Determination of pyrrolizidine alkaloids in the oil of seeds of Borago by thin-layer chromatography. Fett Wiss Technol . 1995;97:33-37.
17. Awang DVC. Herbal medicine borage. Can Pharm J . 1990;123:121-126.
18. Gibson RA, Lines DR, Neumann MA. Gamma linolenic acid (GLA) content of encapsulated evening primrose oil products. Lipids . 1992;27:82-84.
19. Lawson LD, Hughes BG. Triacylglycerol structure of plant and fungal oils containing gamma-linolenic acid. Lipids . 1988;23:313-317.
20. Ziboh VA, Naguwa S, Vang K, et al. Suppression of leukotriene B4 generation by ex-vivo neutrophils isolated from asthma patients on dietary supplementation with gammalinolenic acid-containing borage oil: possible implication in asthma. Clin Dev Immunol . 2004;11:13-21.
21. Fan YY, Chapkin RS, Ramos KS. Dietary lipid source alters murine macrophage/vascular smooth muscle cell interactions in vitro. J Nutr . 1996;126:2083-2088.
22. Wretensjö I, Svensson L. Gas chromatographic-mass spectrometric identification of the fatty acids in borage oil using the picolinyl ester derivatives. J Chromatogr . 1990;521:89-97.
23. Sewón P, Tyystjärvi E. Stearidonic and γ-linolenic acid contents of common borage leaves. Phytochemistry . 1993;33:1029-1032.
24. Laakso P, Voutilainen P. Analysis of triacylglycerols by silver-ion high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry. Lipids . 1996;31:1311-1322.
25. Bandoniene D, Murkovic M. The detection of radical scavenging compounds in crude extract of borage ( Borago officinalis L.) by using an on-line HPLC-DPPH method. J Biochem Biophys Methods . 2002;53:45-49.
26. Fan YY, Chapkin RS. Importance of dietary gamma-linolenic acid in human health and nutrition. J Nutr . 1998;128:1411-1414.
27. Palombo JD, DeMichele SJ, Liu JW, Bistrian BR, Huang YS. Comparison of growth and fatty acid metabolism in rats fed diets containing equal levels of gamma-linolenic acid from high gamma-linolenic acid canola oil or borage oil. Lipids . 2000;35:975-981.
28. Chapkin RS, Somers SD, Schumacher L, Erickson KL. Fatty acid composition of macrophage phospholipids in mice fed fish or borage oil. Lipids . 1988;23:380-383.
29. Chapkin RS, Somers SD, Erickson KL. Dietary manipulation of macrophage phospholipid classes: selective increase of dihomogammalinolenic acid. Lipids . 1988;23:766-770.
30. Chapkin RS, Carmichael SL. Effects of dietary n-3 and n-6 polyunsaturated fatty acids on macrophage phospholipid classes and subclasses. Lipids . 1990;25:827-834.
31. Miller CC, Ziboh VA. Gammalinolenic acid-enriched diet alters cutaneous eicosanoids. Biochem Biophys Res Commun . 1988;154:967-974.
32. Miller CC, Ziboh VA, Wong T, Fletcher MP. Dietary supplementation with oils rich in (n-3) and (n-6) fatty acids influences in vivo levels of epidermal lipoxygenase products in guinea pigs. J Nutr . 1990;120:36-44.
33. Miller CC, Tang W, Ziboh VA, Fletcher MP. Dietary supplementation with ethyl ester concentrates of fish oil (n-3) and borage oil (n-6) polyunsaturated fatty acids induces epidermal generation of local putative anti-inflammatory metabolites. J Invest Dermatol . 1991;96:98-103.
34. Raederstorff D, Moser U. Borage or primrose oil added to standardized diets are equivalent sources for gamma-linolenic acid in rats. Lipids . 1992;27:1018-1023.
35. Fan YY, Chapkin RS. Mouse peritoneal macrophage prostaglandin E1 synthesis is altered by dietary gamma-linolenic acid. J Nutr . 1992;122:1600-1606.
36. Tocher DR, Bell JG, Dick JR, Sargent JR. Fatty acyl desaturation in isolated hepatocytes from Atlantic salmon ( Salmo salar ): stimulation by dietary borage oil containing gamma-linolenic acid. Lipids . 1997;32:1237-1247.
37. Ihara-Watanabe M, Umekawa H, Takahashi T, Furuichi Y. Effects of dietary alpha- or gamma-linolenic acids on levels and fatty acid compositions of serum and hepatic lipids, and activity and mRNA abundance of 3-hydroxy-3-methylglutaryl CoA reductase in rats. Comp Biochem Physiol A Mol Integr Physiol . 1999;122:213-220.
38. Kaku S, Yunoki S, Ohkura K, et al. Interactions of dietary fats and proteins on fatty acid composition of immune cells and LTB4 production by peritoneal exudate cells of rats. Biosci Biotechnol Biochem . 2001;65:315-321.
39. Phylactos AC, Harbige LS, Crawford MA. Essential fatty acids alter the activity of manganese-superoxide dismutase in rat heart. Lipids . 1994;29:111-115.
40. Kumamoto T, Ide T. Comparative effects of alpha- and gamma-linolenic acids on rat liver fatty acid oxidation. Lipids . 1998;33:647-654.
41. Fukushima M, Ohhashi T, Ohno S, et al. Effects of diets enriched in n-6 or n-3 fatty acids on cholesterol metabolism in older rats chronically fed a cholesterol-enriched diet. Lipids . 2001;36:261-266.
42. Harbige LS, Layward L, Morris-Downes MM, Dumonde DC, Amor S. The protective effects of omega-6 fatty acids in experimental autoimmune encephalomyelitis (EAE) in relation to transforming growth factor-beta 1 (TGF-beta1) up-regulation and increased prostaglandin E2 (PGE2) production. Clin Exp Immunol . 2000;122:445-452.
43. Ormerod LD, Garsd A, Abelson MB, Kenyon KR. Effects of altering the eicosanoid precursor pool on neovascularization and inflammation in the alkali-burned rabbit cornea. Am J Pathol . 1990;137:1243-1252.
44. Karlstad MD, DeMichele SJ, Leathem WD, Peterson MB. Effect of intravenous lipid emulsions enriched with gamma-linolenic acid on plasma n-6 fatty acids and prostaglandin biosynthesis after burn and endotoxin injury in rats. Crit Care Med . 1993;21:1740-1749.
45. Mancuso P, Whelan J, DeMichele SJ, et al. Effects of eicosapentaenoic and gamma-linolenic acid on lung permeability and alveolar macrophage eicosanoid synthesis in endotoxic rats. Crit Care Med . 1997;25:523-532.
46. Mancuso P, Whelan J, DeMichele SJ, Snider CC, Guszcza JA, Karlstad MD. Dietary fish oil and fish and borage oil suppress intrapulmonary proinflammatory eicosanoid biosynthesis and attenuate pulmonary neutrophil accumulation in endotoxic rats. Crit Care Med . 1997;25:1198-1206.
47. Palombo JD, DeMichele SJ, Boyce PJ, et al. Effect of short-term enteral feeding with eicosapentaenoic and gamma-linolenic acids on alveolar macrophage eicosanoid synthesis and bactericidal function in rats. Crit Care Med . 1999;27:1908-1915.
48. Murray MJ, Kanazi G, Moukabary K, Tazelaar HD, DeMichele SJ. Effects of eicosapentaenoic and gamma-linolenic acids (dietary lipids) on pulmonary surfactant composition and function during porcine endotoxemia. Chest . 2000;117:1720-1727.
49. Charnock JS. Gamma-linolenic acid provides additional protection against ventricular fibrillation in aged rats fed linoleic acid rich diets. Prostaglandins Leukot Essent Fatty Acids . 2000;62:129-134.
50. Mills DE, Mah M, Ward RP, Morris BL, Floras JS. Alteration of baroreflex control of forearm vascular resistance by dietary fatty acids. Am J Physiol . 1990;259:R1164-R1171.
51. Barre DE, Holub BJ. The effect of borage oil consumption on the composition of individual phospholipids in human platelets. Lipids . 1992;27:315-320.
52. Chilton-Lopez, Surette ME, Swan DD, Fonteh AN, Johnson MM, Chilton FH. Metabolism of gammalinolenic acid in human neutrophils. J Immunol . 1996;156:2941-2947.
53. Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC. Dietary supplementation with eicosapentenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged > 55 y. Am J Clin Nutr . 2001;73:539-548.
54. Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC. Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. J Nutr . 2001;131:1918-1927.
55. Ziboh VA, Fletcher MP. Dose-response effects of dietary gamma-linolenic acid-enriched oils on human polymorphonuclear-neutrophil biosynthesis of leukotriene B4. Am J Clin Nutr . 1992;55:39-45.
56. Little C, Parsons T. Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev . 2001;(1):CD002948.
57. Henz BM, Jablonska S, Van de Kerkhof PC, et al. Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema. Br J Dermatol . 1999;140:685-688.
58. Kapoor R, Klimaszewski A. Efficacy of borage oil in patients with atopic eczema. Br J Dermatol . 2000;143:200-201.
59. Henz BM. Efficacy of borage oil in patients with atopic eczema. Br J Dermatol . 2000;143:201.
60. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic eczema. Health Technol Assess . 2000;4:1-191.
61. van Gool CJ, Thijs C, Henquet CJ, et al. Gamma-linolenic acid supplementation for prophylaxis of atopic dermatitis—a randomized controlled trial in infants at high familial risk. Am J Clin Nutr . 2003;77:943-951.
62. Brosche T, Platt D. Effect of borage oil consumption on fatty acid metabolism, transepidermal water loss and skin parameters in elderly people. Arch Gerontol Geriatr . 2000;30:139-150.
63. Gadek JE, DeMichele SJ, Karlstad MD, 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;27:1409-1420.
64. Heyland DK, Dhaliwal R, Drover JW, et al. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr . 2003;27:355-374.
65. Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH. Calcium, gamma-linolenic acid and eicosapentenoic acid supplementation in senile osteoporosis. Aging (Milano) . 1998;10:385-394.
66. Simoncikova P, Wein S, Gasperikova D, et al. Comparison of the extrapancreatic action of gamma-linolenic acid and n-3 PUFAs in the high fat diet-induced insulin resistance. Endocr Regul . 2002;36:143-149.
67. Fewtrell MS, Abbott RA, Kennedy K, et al. Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. J Pediatr . 2004;144:471-479.
68. Heard CM, Gallagher SJ, Congiatu C, et al. Preferential pi-pi complexation between tamoxifen and borage oil/gamma linolenic acid: transcutaneous delivery and NMR spectral modulation. Int J Pharm . 2005;302:47-55.

Copyright © 2009 Wolters Kluwer Health

Hide
(web5)