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Treatment of rheumatic diseases with borage

as well as with dietary supplements or medications containing borage-derived ingredients

1. Possible mechanism of action, active substances, available preparations

Borage (Borago officinalis), also known as starflower, belongs to the borage family (Boraginaceae). Originally known in the Orient and the Mediterranean region, it has been cultivated in Germany since the Middle Ages as a spice and medicinal plant (hence the suffix “officinalis”) and is now also found growing wild. 

Borage is an annual herb growing 50–75 cm tall, with hairy stems and elongated leaves growing directly from the stem. The blue flowers and later fruit clusters are grouped at the top of the plant. The flowering period is from May to August. It is related to comfrey, which looks similar but forms rhizomes and also belongs to the Boraginaceae family.

As medicinal plants, the flowers in particular were used for a wide variety of indications (Boraginis flos, Flores boraginis); “inflammation,” “rheumatism,” and “blood purification” are also historically cited, while the leaves, due to their cucumber-like taste, are used more in the kitchen and specifically in Frankfurt green sauce. 

Borage seeds consist of 1/3 oil (Boraginis officinalis oleum raffinatum, Boraginis oleum, DAC). This oil contains a significant amount of gamma-linolenic acid (GLA) as well as a range of other fatty acids (35–38% linoleic acid, 16–20% oleic acid, 10–11% palmitic acid, 3.5–5.5% gadoleic acid (11Z-eicosenoic acid), 3.5–4.5% stearic acid, 1.5–3.5% erucic acid, approximately 1.5% nervonic acid, and less than 1% each of arachidic acid, behenic acid, palmitoleic acid, vaccenic acid, myristic acid, eicosadienoic acid, and alpha-linolenic acid)[6].

Borage seed oil is sold as an over-the-counter dietary supplement in pharmacies in strengths of 500, 750, and 1000 mg of oil with a stated GLA content of approximately 20%, as well as in 240 mg GLA capsules. Online, 250-ml bottles are also available for culinary use. It has little to no taste of its own. Some preparations contain additional fatty acids or vitamin E. The indicated use is “as a substitute for unsaturated fatty acids.” Borage seed oil is also marketed as a skin care product.

2. Overview of the scientific evidence in the literature regarding the clinical efficacy of borage for rheumatic diseases 

Use of borage for rheumatoid arthritis (RA)

Results of a PubMed search ((Borago[Title]) OR (Borago[Text Word]) OR (Borage[Title]) OR (Borage[Text Word])) AND (Arthritis[text word]) yielded 19 results, of which 11 qualified for a full-text analysis. The search ((Borago[Title]) OR (Borago[Text Word]) OR (Borage[Title]) OR (Borage[Text Word])) AND (Rheum [text word]) yielded no further results.

In a study by the University of Shiraz (Iran), 51.4% of 500 surveyed patients with RA reported using herbs in general, and 36.8% reported using borage; however, the rate of borage use was not significantly higher than that of controls without RA [2].

No studies on the use of the whole plant, leaves, or flowers were found. The published studies are limited to the oil extracted from borage seeds.

The high content of gamma-linolenic acid (GLA) in the seeds is considered a potential active ingredient in borage seed oil. In an 18-month randomized study, fish oil and borage seed oil—alone and in combination (but not a placebo)—were compared as add-ons to standard RA therapy; 150 patients with RA were randomized. Approximately half of the patients could be evaluated. A moderate improvement in DAS and CDAI was observed, with no difference between the groups [3]. Olendzkie et al. reported from the same study a significant improvement in LDL and HDL levels in the overall cohort over time. They found no differences between the arms. No relevant changes in erythrocyte sedimentation rate or C-reactive protein were documented [4].

Leventhal et al. observed a 36% reduction in the number of painful joints and a 28% reduction in the number of swollen joints in a small (37 patients) 24-week randomized, placebo-controlled study of RA patients treated with borage seed oil [5]. Zurier et al. describe a randomized, placebo-controlled study involving 56 patients, 41 of whom were evaluable after 6 months. Among those receiving the active treatment, 14 out of 22 achieved at least a 25% improvement in joint symptoms, compared to 4 out of 19 in the placebo group [6]. Macfarlane et al. view these two studies as evidence of a probable effect; further studies on the substance are not mentioned in their review [7].

In a three-arm randomized study, Belch et al. treated 16 patients with RA with GLA from evening primrose, 15 with a GLA-fish oil combination, and 18 with placebo. They documented a reduction in NSAID requirements after 12 months [8]. In a review, the author also attributes this effect to borage seed oil due to its comparable composition [9].

Cameron et al. conducted reviews in 2009 and 2011 on studies involving GLA for RA, summarizing 7 studies each on evening primrose oil, black currant oil, and borage oil. The data indicate a required dose of at least 1400 mg GLA/day, while 500 mg GLA/day was not effective. The data show a reduction in pain intensity (mean difference (MD) of -32.83 points, 95% confidence interval (CI) -56.25 to -9.42 on a 100-point pain scale) and a reduction in functional impairment (MD -15.75%, 95% CI -27.06 to -4.44%) [10, 11].

In an animal model using rats, GLA was associated with less inflammation than placebo in cases of acute crystal-induced arthritis and immunologically triggered arthritis induced by Freud’s adjuvant; a 5-fold higher ratio of GLA to arachidonic acid under GLA therapy was cited as an explanation [12].

Other Indications

Literature searches for the indications “lupus,” “spondylitis,” and “fibromyalgia” yielded no results in each case.

The search query ((Borago[Title]) OR (Borago[Text Word]) OR (Borage[Title]) OR (Borage[Text Word])) AND (Pain[text word]) yielded 7 results, 6 of which are already listed under the “Arthritis” indication. An additional review recommends 1–3 g of GLA (from the three sources mentioned: borage, black currant, and evening primrose) for pain management without providing its own study data [13].

3. Possible side effects and limitations

The plant contains pyrrolizidine alkaloids (amabiline, intermedine, lycopsamine, supinine, thesin). These are classified as genotoxic , carcinogenic, and hepatotoxic , and their consumption should be avoided [14]. There are further statements to this effect [15-17], and in the European Union, maximum levels for pyrrolizidine alkaloids have been established effective 07/2022 (Regulation (EU) 2020/2040). Due to its high pyrrolizidine content, Borago should also no longer be used for pharmaceutical purposes [18].

The Cochrane review of 7 studies on GLA in RA documented an increase in adverse events in the active treatment group (20% versus 3% in the placebo group) (relative risk 4.24, 95% CI 0.78 to 22.99) [11]. A study by Kast identifies a potential theoretical risk associated with borage seed oil due to reported prostaglandin E antagonism and possible teratogenic effects, without providing concrete evidence for this [19].

4. Final Recommendation of the Commission

The scientific evidence is sufficient to warn against the regular use of borage leaves and flowers. The pyrrolizidine alkaloids contained in borage are potentially teratogenic, carcinogenic, and hepatotoxic. 

GLA, a component of borage seed oil, has demonstrated a limited anti-inflammatory effect and a slight improvement in the lipid profile in animal studies of crystal-induced arthritis and Freund’s adjuvant-induced arthritis in rats, as well as in small controlled studies involving patients with rheumatoid arthritis. The effect requires a daily dose of at least 1500 mg of GLA and is comparable to the effect of fish oil. A combination of plant-based and animal-based unsaturated fatty acids is no more effective than the individual substance. Although some of the studies were systematic, controlled, and conducted with validated outcome measures, they involved very small patient cohorts, high dropout rates, and were calculated without a selection strategy for dropouts; one study lacked a placebo arm. Due to this insufficient data, therapeutic use is not recommended. 

GLA derived from borage seed oil from certified manufacturers or from other plant sources can be used as an alternative to other oils, vegetables, nuts, algae, or fish containing omega-3 fatty acids as part of a health-oriented diet in accordance with the Commission’s recommendation [20], if the latter cannot be used, for example, in cases of allergies. 

From a rheumatological perspective, the published data and regulatory status do not justify the use of borage seed oil preparations as an adjunctive treatment for rheumatic diseases. 


Bibliography and References

  1. Asadi-Samani M, Bahmani M, Rafieian-Kopaei M. The chemical composition, botanical characteristics, and biological activities of Borago officinalis: a review. Asian Pacific Journal of Tropical Medicine 2014; 7(S1), S22-S28, ISSN 1995-7645, doi.org/10.1016/S1995-7645(14)60199-1
  2. Rambod M, Nazarinia M, Raieskarimian F. The prevalence and predictors of herbal medicine use among adult rheumatoid arthritis patients: A case-control study. Complementary Therapies in Medicine 2018; 41,220-224, ISSN 0965-2299, doi.org/10.1016/j.ctim.2018.10.004
  3. Reed GW, Leung K, Rossetti RG, Vanbuskirk S, Sharp JT, Zurier RB. Treatment of rheumatoid arthritis with marine and botanical oils: an 18-month, randomized, and double-blind trial. Evid Based Complement Alternat Med. 2014;2014:857456. doi: 10.1155/2014/857456. Epub 2014 Mar 19. PMID: 24803948; PMCID: PMC3977504
  4. Olendzki BC, Leung K, Van Buskirk S, Reed G, Zurier RB. Treatment of rheumatoid arthritis with marine and botanical oils: influence on serum lipids. Evid Based Complement Alternat Med. 2011;2011:827286. doi: 10.1155/2011/827286. Epub 2011 Oct 9. PMID: 22007257; PMCID: PMC3189621
  5. Leventhal LJ, Boyce EG, Zurier RB. Treatment of rheumatoid arthritis with gamma-linolenic acid. Ann Intern Med. 1993 Nov 1;119(9):867-73. doi: 10.7326/0003-4819-119-9-199311010-00001. PMID: 8214997
  6. Zurier RB, Rossetti RG, Jacobson EW, DeMarco DM, Liu NY, Temming JE, White BM, Laposata M. Gamma-linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum. 1996 Nov;39(11):1808-17. doi: 10.1002/art.1780391106. PMID: 8912502
  7. Macfarlane GJ, El-Metwally A, De Silva V, Ernst E, Dowds GL, Moots RJ; Arthritis Research UK Working Group on Complementary and Alternative Medicines. Evidence for the efficacy of complementary and alternative medicines in the management of rheumatoid arthritis: a systematic review. Rheumatology (Oxford). September 2011;50(9):1672-83. doi: 10.1093/rheumatology/ker119. Epub 2011 Jun 6. PMID: 21652584
  8. Belch JJ, Ansell D, Madhok R, O'Dowd A, Sturrock RD. Effects of altering dietary essential fatty acids on requirements for nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double-blind placebo-controlled study. Ann Rheum Dis. 1988 Feb;47(2):96-104. doi: 10.1136/ard.47.2.96. PMID: 2833184; PMCID: PMC1003460
  9. Belch JJ, Hill A. Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr. 2000 Jan;71(1 Suppl):352S-6S. doi: 10.1093/ajcn/71.1.352s. PMID: 10617996
  10. Cameron M, Gagnier JJ, Little CV, Parsons TJ, Blümle A, Chrubasik S. Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part 2: Rheumatoid arthritis. Phytother Res. 2009 Dec;23(12):1647-62. doi: 10.1002/ptr.3006. PMID: 19941324.
  11. Cameron M, Gagnier JJ, Chrubasik S. Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD002948. doi: 10.1002/14651858.CD002948.pub2. PMID: 21328257
  12. Tate G, Mandell BF, Laposata M, Ohliger D, Baker DG, Schumacher HR, Zurier RB. Suppression of acute and chronic inflammation by dietary gamma-linolenic acid. J Rheumatol. 1989 Jun;16(6):729-34 PMID: 2550629
  13. Chrubasik S, Pollak S. Pain management with herbal antirheumatic drugs. Wien Med Wochenschr. 2002;152(7-8):198-203. German. doi: 10.1046/j.1563-258x.2002.11115.x. PMID: 12017748
  14. Federal Institute for Risk Assessment Opinion No. 038/2011 dated August 11, 2011 www.bfr.bund.de/cm/343/analytik-und-toxizitaet-von-pyrrolizidinalkaloiden.pdf
  15. BfR Opinion No. 030/2016 dated September 28, 2016. Pyrrolizidine alkaloids: Levels in food should continue to be reduced as much as possible. www.bfr.bund.de/cm/343/pyrrolizidinalkaloide-gehalte-in-lebensmitteln-sollennach-wievor-so-weit-wie-moeglich-gesenkt-werden.pdf
  16. Press Release 18/2013, dated July 15, 2013. Levels of pyrrolizidine alkaloids in herbal teas and teas are too high. www.bfr.bund.de/de/presseinformation/2013/18/gehalte_an_pyrrolizidinalkaloiden_in_kraeutertees_und_tees_sind_zu_hoch-187296.html
  17. Updated FAQ from the BfR dated December 16, 2022 www.bfr.bund.de/cm/343/fragen-und-antworten-zu-pyrrolizidinalkaloiden-in-lebensmitteln.pdf
  18. BfArM Commission E ASK-NR Monograph -49052 Federal Gazette No. 127 of July 12, 1991
  19. Kast RE. Borage oil may reduce rheumatoid arthritis activity by increasing cAMP, which suppresses tumor necrosis factor-alpha. Int Immunopharmacol. 2001 Nov;1(12):2197-9. doi: 10.1016/s1567-5769(01)00146-1. PMID: 11710548
  20. Keyßer, G., Michalsen, A., Reuß-Borst, M. et al. Recommendations of the Commission on Complementary Therapies and Nutrition regarding Ayurvedic medicine, homeopathy, nutrition, and the Mediterranean diet. Z Rheumatol (2023). doi.org/10.1007/s00393-023-01356-z

 

Borago officinalis Leventhal LJ, et al., 1993 [5] Randomisierte, doppel blinde, Placebo kontrollierte Studie, 24 Wochen. 37 Patienten eingeschlossen Einnahme von 1,4 g GLA (Gammalinolensäure) pro Tag, als Borretsch-samenöl. Placebo-kapseln enthielten Baumwoll-samenöl. Nach 6 Monaten zeigten sich bei RA-Patienten, die mit Borretschsamenöl behandelt wurden im Vergleich zur Placebogruppe signifikante Verbesserungen bei der Anzahl und den Werten schmerzhafter Gelenke, den Werten für Gelenkschwellungen, der ärztlichen Gesamtbeurteilung und den Schmerzen. Bei keinem Patienten in der Behandlungsgruppe kam es zu einer Remission. 7 Pat. (36,8 %) hatten eine deutliche Verbesserung und 7 Pat. (36,8 %) hatten keine Verbesserung. In der Placebogruppe kam es bei 1 (5,6 %) zu einer Verbesserung und bei 12 (63,2 %) nicht.
  Zurier RB, et al. 1996 [6] Randomisierte, doppel blinde, Placebo kontrollierte Studie, 6 Monate mit initial 56 RA-Patienten. Nach 6 Monaten erhielten beide gruppen GLA Ausgewertet nach 6 Monaten 22 Verum 19 Placebo Nach weiteren 6 Monaten Verum 21, Placebo-Verum 14 Patienten erhielten entweder 2,8 g/Tag GLA aus Borretsch-samenöl oder Placebo (Sonnenblumenkernöl). mit Borretschsamenöl behandelten Patienten zeigten im Vergleich zu den Placebo-Patienten eine signifikante Verbesserung: - bei der Anzahl der schmerzempfindlichen Gelenke - der Anzahl der geschwollenen Gelenke - der Punktzahl der schmerzempfindlichen Gelenke - den auf einer visuellen Analogskala (VAS) gemessenen Schmerzen - der Punktzahl im Fragebogen zur Gesundheitsbewertung - Insgesamt zeigte nach 6 Monaten ein größerer Prozentsatz der Behandlungsgruppe (64 %) im Vergleich zur Placebogruppe (21 %) eine signifikante Verbesserung, die als Verbesserung von mindestens 25 % bei mindestens vier Messgrößen definiert wurde. (6,5x höhere Wahrscheinlichkeit einer bedeutsamen Verbesserung als Placebo) - In den zweiten 6 Monaten nach Umstellung von Placebo auf GLA Besserung auch bei den verbleibenden 14 Patienten, bei Beibehaltung von GLA Konsolidierung
  Olendzki BC, et al., 2011 [4] Reed GW et al., 2014 [3] Randomisierte, doppel blinde, 3-armige Studie, 18 Monate mit initial 156 RA-Patienten (53 Borretsch-Öl 1,8g/Tag, 56 Fischöl 3,5g/Tag, 47 beides). Nach 9 Monaten wurden insgesamt 83 Patienten, nach 18 Monaten 69 Patienten erfasst. Kein Einfluss auf Gewicht, CRP, BSG Reduktion von Cholesterin, LDL und Triglyceriden, Steigerung von HDL Reduktion des DAS um 1,33 (9 Monate und 1,53 (18 Monate) (Borretschöl); 1,18 und 1,28 (Kombination) und 1,56 und 1,45 (Fischöl) Anstieg des Sharp Score um 0,69 (Borretschöl), 1,07 (Kombination) und 2,26 (Fischöl)

Last updated: September 28, 2024

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