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Safflower

Scientific Name(s): Carthamus tinctorius L.
Common Name(s): American saffron, Bastard saffron, Dyer's saffron, False saffron, Gami-Honghwain, Hong hua, Safflower, Zafran

Clinical Overview

Use

Safflower has been used as a laxative and as a dietary supplement to modify lipid profiles and treat fever. However, there is no supporting evidence for these uses from clinical trials.

Dosing

Safflower oil 8 g/day has been associated with improvement in glycemic control.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Avoid use. Not recommended for use in pregnancy; abortifacient and emmenagogue effects have been suggested.

Interactions

None well documented.

Adverse Reactions

Allergy to the flowers has been reported. Safflower oil was generally well tolerated when used as a control in clinical trials.

Toxicology

Research reveals limited information regarding toxicity with the use of safflower oil.

Botany

Safflower is native to the Middle East and is widely cultivated throughout Europe, China, India, and the United States. A bushy annual that reaches approximately 1 m in height, it has shiny, oval, spiny-edged leaves that alternate around a single, smooth, upright stem. The plant produces profuse yellow to deep red flowers. Safflower produces a dry, one-seeded fruit known as an "achene" that is generally small and white and contains nuts with 1 seed. Seeds are produced in August and enclosed in a mass of down.1, 2, 3 Safflower roots extend 2 to 3 m into the soil, making them useful as rain-fed cropping systems.3

History

Although safflower is now recognized primarily as a source of healthy edible oil, traditional uses have not focused on the oil. Safflower was originally valued for the yellow and red dyes yielded by its flowers. These dyes have been used for centuries to color cosmetics and fabrics. The use of safflower extract to dye the wrappings of mummies has also been reported.5 Safflower had been used as a replacement for saffron but lost its popularity because of its lack of taste. Safflower tea has been used in traditional medicine to induce sweating and reduce fever. The oil has been employed as a laxative and has been used as a solvent in paints.4 A biblical reference is made to saffron in Song of Solomon 4:13-14.5

Chemistry

Safflower oil is characterized by the presence of a high proportion of n-6 polyunsaturated fatty acids, including linoleic (approximately 75%), oleic (13%), palmitic (6%), and stearic (3%), as well as other minor straight-chained fatty acids.6, 7, 8 Alpha- and gamma-tocopherol have also been described.9 Although safflower oil is a rich source of linoleic acid, the activity of delta 6-desaturase is required for its conversion to dihomogammalinolenic acid (DHGA) and arachidonic acid. In contrast, evening primrose oil appears to be a more bioavailable source of fatty acids for the production of DHGA.10

More than 200 compounds have been isolated from C. tinctorius, including flavonoids, phenylethanoid glucosides, coumarins, fatty acids, steroids, and polysaccharides.3

The seeds contain a lignan glycoside known as tracheloside11; serotonin derivatives and their glucosides have been found in the seed extract.11, 12

Uses and Pharmacology

Safflower oil has been used as a control or comparator agent in many clinical trials and experiments evaluating effects against conditions such as dyslipidemia, diabetes, cardiovascular conditions, and cancer.8, 13, 14, 15, 16, 17, 18, 19 Few quality clinical trials specifically investigating the effects of safflower have been published.

Cardiovascular

Animal/In vitro data

In a study of mice, injections of C. tinctorius (0.625 g/kg and 2.5 g/kg) given intraperitoneally each day for 5 days inhibited ST segment and T-wave elevation in isoproterenol-induced acute myocardial ischemia (P < 0.05) and also decreased levels of the inflammatory cytokines, interleukin-6, and tumor necrosis factor (TNF)-alpha (P < 0.05).20

Clinical data

Safflower showed no effect on blood pressure, heart rate, or brachial artery vascular conductance when used as placebo in clinical trials.14, 21

Safflower oil consumption has been reported to have variable effects on plasma lipids.10, 22, 23, 24, 25, 26, 27 Studies investigating the effects of phospholipids from safflower and soybean showed decreased hepatic lipid levels via decreased liver cholesterol and increased fecal neutral steroid.28

A decreased expression of adhesion molecules, induced by oxidized low-density lipoprotein (LDL), has been observed following consumption in meals rich in safflower. The clinical importance of this effect is unclear.9, 29, 30 Effects of safflower oil on platelet linoleic acid and thromboxane B2 levels were equivocal in small studies.31

Diabetes

Animal/In vitro data

In an in vitro study, N-p-coumaroyl serotonin and N-feruloyl serotonin isolated from safflower seed inhibited alpha-glucosidase, a well-known drug target in the management of diabetes.32 In a study of rabbits, C. tinctorius extract 200 mg/kg and 300 mg/kg administered for 30 days significantly increased insulin levels and caused a hypoglycemic effect.33 Daily intraperitoneal injections of C. tinctorius extract 200 mg/kg in rats increased insulin levels and decreased fasting blood glucose and cholesterol parameters.34

Clinical data

In a double-blind, crossover clinical trial (N = 35 evaluable) comparing conjugated linoleic acid (CLA) with safflower oil in menopausal women with type 2 diabetes mellitus, the 2 oils were administered in doses of 8 g/day for 16 weeks, with a 4-week washout period between treatments. CLA, but not safflower oil, decreased body mass index (BMI) and total adipose mass. Safflower oil, but not CLA, produced reductions in trunk adipose tissue and fasting blood glucose, and increased lean tissue and adiponectin levels.35 Benefits observed with safflower oil, and not CLA, included reduced hemoglobin A1c and C-reactive protein and increased high-density lipoprotein cholesterol.36

As a component of medical nutrition therapy for patients with type 1 or 2 diabetes, the American Diabetes Association Standards of Care (2014) recommend an increase in foods containing alpha-linolenic acid based on beneficial effects observed on lipoprotein profiles, heart disease prevention, and overall positive health in patients with diabetes (moderate-quality evidence). Likewise, as a component of medical nutrition therapy for patients with type 2 diabetes, the American Diabetes Association Standards of Care (2014) recommend higher-quality dietary fat intake as an alternative to decreased fat intake by replacing saturated and/or trans fats with mono- and polyunsaturated fatty acids in the diet. This Mediterranean-style approach to eating may improve glycemic control and cardiovascular disease risk factors (moderate-quality evidence).37

Obesity

Animal/In vitro data

There are no animal or in vitro data regarding the use of safflower for obesity.

Clinical data

Some studies in which saffron oil was used as a control have been published. One 8-week, randomized, double-blind clinical trial conducted in obese males compared the benefits of CLA, safflower oil, heated safflower oil, and olive oil for weight loss and vascular endothelial function. CLA was superior to safflower oil for reductions in body weight and BMI, but was inferior for postprandial vascular endothelial function improvement.38 A double-blind, randomized, crossover trial evaluated weight-loss and lipid-lowering effects of CLA compared with safflower oil. There were no changes in BMI or lipid levels compared with baseline following 8-week courses of CLA or safflower oil.27

CNS

Animal/In vitro data

Animal studies suggest that a moderate dietary intake of essential fatty acids may be required to maintain the integrity of CNS function.39

However, safflower oil–induced n-3 deficiency (high n-6 to n-3 ratio) had a deleterious effect on cognition in mice.40 In another experiment with mice, a safflower oil–rich diet (ie, depleted n-3 fatty acids) resulted in a decrease in insulin-degrading enzyme associated with an increase in beta-amyloid levels similar to those found in Alzheimer disease.41 Therefore, a low dietary intake of n-3 polyunsaturated fatty acids is considered a candidate risk factor for the development of Alzheimer disease, as well as for decreased cognition.40, 41

Clinical data

There are no clinical data regarding the use of safflower for its effects on the CNS.

Other uses

Antioxidant

Safflower’s antioxidant activity is responsible for inhibiting the production of oxidized LDL to ultimately reduce atherosclerosis.42 N-(p-coumaroyl) serotonin is a potent antioxidant compound present in safflower oil and has been shown to exert growth-promoting activity for mouse fibroblasts and human fibroblasts in vitro. Antioxidant activity and inhibitory effects on proinflammatory cytokine production from human monocytes were observed at similar doses.12

Estrogen-related osteoporosis

Linoleic acid, found in safflower seed oil, is believed to exert anti-inflammatory effects in bone. Specifically, it is believed to facilitate the formation of prostanoids, correct bone loss in women following ovariectomy, and increase the intestinal absorption of calcium.3 Safflower seed extract showed a protective effect in experiments.11

Pruritus in renal disease

Safflower oil supplementation resulted in clinically unimportant reductions in symptoms of pruritus.43

Human papillomavirus–induced laryngeal papillomatosis

A small, randomized, double-blind, crossover clinical trial in pediatric patients used safflower oil rich in oleic acid as the control arm versus CLA in patients requiring surgical intervention for human papillomavirus (HPV)–induced laryngeal papillomatosis. Patients received 2.5 g/day of each oil for 8 weeks, with a 6-week washout period between treatments. CLA produced greater improvement in HPV-induced laryngeal papillomatosis scores and required fewer surgical procedures compared with the control group.44

Hair growth

In a study including both in vivo and in vitro models, C. tinctorius increased the length of hair follicles in a manner similar to that of minoxidil. Mice treated with C. tinctorius had hair growth at day 15 similar to that observed in mice treated with minoxidil.45

Male infertility

In a study of rats with busulfan-induced infertility, C. tinctorius extract 10 mg/kg daily for 35 days significantly improved sperm morphology, motility, and count (P = 0.02, P = 0.03, and P = 0.00001, respectively). Higher doses of C. tinctorius (ie, 25 mg/kg and 50 mg/kg) generally did not improve these measures; the 25 mg/kg dose slightly but not significantly improved sperm count.46 In another murine model, C. tinctorius extract exerted toxic effects on testicular tissue.47

Lung dysfunction

In a study of rats, hydroxysafflor yellow A, a flavonoid component derived from C. tinctorius, attenuated gasoline engine exhaust–mediated lung damage. Specifically, the compound was found to improve measures of pulmonary function and increase adenosine 3′,5′-cyclic phosphate (cAMP) levels and protein kinase A activity while decreasing interleukin-6 and TNF-alpha levels.48

Tendon injury

The effect of safflower yellow on tendon injury was assessed in a study of chickens. Local application of safflower increased expression of basic fibroblast growth factor (bFGF) and collagen type I protein, improved tensile strength of the tendon, and increased adhesion.48

Dosing

In a study of women with diabetes, safflower oil 8 g/day was found to improve glycemic control.35

In a single-blind, placebo-controlled study, 9 capsules of safflower oil as placebo were used to provide 80 calories per day and contained alpha-linolenic acid 800 mg, oleic acid 160 mg, and palmitic acid 100 mg per capsule.14 Another trial used safflower oil 10 g/day as placebo.21 Studies in obese adults and adults with diabetes ranged from 3.5 to 8 g/day.27, 35, 38

Transcutaneous safflower oil 3 mL 4 times a day has been administered by massage to neonates. This method of administration resulted in absorption, as indicated by altered lipid profiles in the neonates.26

Pregnancy / Lactation

Avoid use. Information is limited. Abortifacient and emmenagogue effects have been suggested.49, 50 A study in mice demonstrated that C. tinctorius extract at doses of 1.4 mg/kg and 2.8 mg/kg caused toxic changes in the structure of the placenta. Neonate survival rates in mice receiving these doses (calculated at days 5, 15, 25, and 42 after birth) were decreased compared with controls.51

Another study in rats with maternal diabetes showed that diets supplemented with safflower oil and folic acid reduced malformation rates as well as decreased matrix metalloproteinase-2 and -9 activities.52

Interactions

None well documented.

Adverse Reactions

Case reports of immunoglobulin E–mediated allergy (eg, rhinitis, urticaria, asthma) to the flowers exist.53 A literature review of 14 case reports of allergic shock from the clinical use of safflower injection in China found that the majority of cases occurred less than 30 minutes after administration.54 Trials using safflower oil as a control report few adverse reactions.

Toxicology

Toxicologic information is limited. Foods are often cooked in safflower oil, and the oil is commonly used as a placebo in clinical trials. A study to determine the safety of safflower oil showed no adverse effects on liver enzymes and renal parameters (eg, uric acid, blood urea nitrogen, creatinine) at 10 g of oil per day.21 One study found that C. tinctorius extract at doses of 1.4 mg/kg and 2.8 mg/kg caused detrimental effects on the kidney tissue of mice.55

References

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3. Asgarpanah J, Kazemivash N. Phytochemistry, pharmacology, and medicinal properties of Carthamus tinctorius L. Chin J Integr Med. 2013;19(2):153-159.23371463
4. Dobelis, IN, ed. Magic and Medicine of Plants. Pleasantville, NY: Reader's Digest Association; 1986.
5. Duke JA, Duke PK, DuCellier JL, eds. Duke’s Handbook of Medicinal Plants of the Bible. Boca Raton, FL: CRC Press; 2008.
6. Kwon JS, Snook JT, Wardlaw GM, Hwang DH. Effects of diets high in saturated fatty acids, canola oil, or safflower oil on platelet function, thromboxane B2 formation, and fatty acid composition of platelet phospholipids. Am J Clin Nutr. 1991;54(2):351-358.1677525
7. Windolz M, ed. The Merck Index. 10th ed. Rahway, NJ: Merck & Co; 1983.
8. Paschos GK, Magkos F, Panagiotakos DB, Votteas V, Zampelas A. Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients. Eur J Clin Nutr. 2007;61(10):1201-1206.17268413
9. Masterjohn C. The anti-inflammatory properties of safflower oil and coconut oil may be mediated by their respective concentrations of vitamin E. J Am Coll Cardiol. 2007;49(17):1825-1826.17466237
10. Abraham RD, Riemersma RA, Elton RA, Macintyre C, Oliver MF. Effects of safflower oil and evening primrose oil in men with a low dihomo-gamma-linolenic level. Atherosclerosis. 1990;81(3):199-208.2112389
11. Kim KW, Suh SJ, Lee TK, et al. Effect of safflower seeds supplementation on stimulation of the proliferation, differentiation and mineralization of osteoblastic MC3T3-E1 cells. J Ethnopharmacol. 2008;115(1):42-49.17997241
12. Takii T, Hayashi M, Hiroma H, et al. Serotonin derivative, N-(p-Coumaroyl) serotonin, isolated from safflower (Carthamus tinctorius L.) oil cake augments the proliferation of normal human and mouse fibroblasts in synergy with basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF). J Biochem. 1999;125(5):910-915.10220583
13. Tsuzuki T, Igarashi M, Miyazawa T. Conjugated eicosapentaenoic acid (EPA) inhibits transplanted tumor growth via membrane lipid peroxidation in nude mice. J Nutr. 2004;134(5):1162-1166.15113964
14. Walser B, Giordano RM, Stebbins CL. Supplementation with omega-3 polyunsaturated fatty acids augments brachial artery dilation and blood flow during forearm contraction. Eur J Appl Physiol. 2006;97(3):347-354.16770472
15. Bloomer RJ, Fry A, Schilling B, Chiu L, Hori N, Weiss L. Astaxanthin supplementation does not attenuate muscle injury following eccentric exercise in resistance-trained men. Int J Sport Nutr Exerc Metab. 2005;15(4):401-412.16286671
16. Barre DE, Mizier-Barre KA, Griscti O, Hafez K. High dose flaxseed oil supplementation may affect fasting blood serum glucose management in human type 2 diabetics. J Oleo Sci. 2008;57(5):269-273.18391475
17. Burton-Freeman B, Davis PA, Schneeman BO. Interaction of fat availability and sex on postprandial satiety and cholecystokinin after mixed-food meals. Am J Clin Nutr. 2004;80(5):1207-1214.15531667
18. Close RN, Schoeller DA, Watras AC, Nora EH. Conjugated linoleic acid supplementation alters the 6-mo change in fat oxidation during sleep. Am J Clin Nutr. 2007;86(3):797-804.17823448
19. Steck SE, Chalecki AM, Miller P, et al. Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans. J Nutr. 2007;137(5):1188-1193.17449580
20. Wan LH, Chen J, Li L, Xiong WB, Zhou LM. Protective effects of Carthamus tinctorius injection on isoprenaline-induced myocardial injury in rats. Pharm Biol. 2011;49(11):1204-1209.22014268
21. Iwata T, Kamegai T, Yamauchi-Sato Y, et al. Safety of dietary conjugated linoleic acid (CLA) in a 12-weeks trial in healthy overweight Japanese male volunteers. J Oleo Sci. 2007;56(10):517-525.17898458
22. Cox C, Sutherland W, Mann J, de Jong S, Chisholm A, Skeaff M. Effects of dietary coconut oil, butter and safflower oil on plasma lipids, lipoproteins and lathosterol levels. Eur J Clin Nutr. 1998;52(9):650-654.9756121
23. Wardlaw GM, Snook JT, Lin MC, Puangco MA, Kwon JS. Serum lipid and apolipoprotein concentrations in healthy men on diets enriched in either canola oil or safflower oil. Am J Clin Nutr. 1991;54(1):104-110.1905474
24. Williams MJA, Sutherland WH, McCormick MP, Yeoman D, de Jong SA, Walker RJ. Normal endothelial function after meals rich in olive or safflower oil previously used for deep frying. Nutr Metab Cardiovasc Dis. 2001;11(3):147-152.11590989
25. Jackson KG, Wolstencroft EJ, Bateman PA, Yaqoob P, Williams CM. Greater enrichment of triacylglycerol-rich lipoproteins with apolipoproteins E and C-III after meals rich in saturated fatty acids than after meals rich in unsaturated fatty acids. Am J Clin Nutr. 2005;81(1):25-34.15640456
26. Solanki K, Matnani M, Kale M, et al. Transcutaneous absorption of topically massaged oil in neonates. Indian Pediatr. 2005;42(10):998-1005.16269830
27. Joseph SV, Jacques H, Plourde M, Mitchell PL, McLeod RS, Jones PJ. Conjugated linoleic acid supplementation for 8 weeks does not affect body composition, lipid profile, or safety biomarkers in overweight, hyperlipidemic men. J Nutr. 2011;141(7):1286-1291.21593349
28. Cohn JS, Wat E, Kamili A, Tandy S. Dietary phospholipids, hepatic lipid metabolism and cardiovascular disease. Curr Opin Lipidol. 2008;19(3):257-262.18460916
29. Rallidis LS, Paschos G, Papaioannou ML, et al. The effect of diet enriched with alpha-linolenic acid on soluble cellular adhesion molecules in dyslipidaemic patients. Atherosclerosis. 2004;174(1):127-132.15135261
30. Nicholls SJ, Lundman P, Harmer JA, et al. Consumption of saturated fat impairs the anti-inflammatory properties of high-density lipoproteins and endothelial function. J Am Coll Cardiol. 2006;48(4):715-720.16904539
31. Herbel BK, McGuire MK, McGuire MA, Shultz TD. Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans. Am J Clin Nutr. 1998;67(2):332-337.9459383
32. Takahashi T, Miyazawa M. Potent α-glucosidase inhibitors from safflower (Carthamus tinctorius L.) seed. Phytother Res. 2012;26(5):722-726.22021176
33. Qazi N, Khan RA, Rizwani GH, Feroz Z. Effect of Carthamus tinctorius (Safflower) on fasting blood glucose and insulin levels in alloxan induced diabetic rabbits. Pak J Pharm Sci. 2014;27(2):377-380.24577929
34. Asgary S, Rahimi P, Mahzouni P, Madani H. Antidiabetic effect of hydroalcoholic extract of Carthamus tinctorius L. in alloxan-induced diabetic rats. J Res Med Sci. 2012;17(4):386-392.23267403
35. Asp ML, Collene AL, Norris LE, et al. Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized, double-masked, crossover study. Clin Nutr. 2011;30(4):443-449.21295383
36. Norris LE, Collene AL, Asp ML, et al. Comparison of dietary conjugated linoleic acid with safflower oil on body composition in obese postmenopausal women with type 2 diabetes mellitus. Am J Clin Nutr. 2009;90(3):468-476.19535429
37. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(suppl 1):S14-S80. http://care.diabetesjournals.org/content/37/Supplement_1/S14.long. Accessed May 5, 2015.24357209
38. Pfeuffer M, Fielitz K, Laue C, et al. CLA does not impair endothelial function and decreases body weight as compared with safflower oil in overweight and obese male subjects. J Am Coll Nutr. 2011;30(1):19-28.21697535
39. Okuyama H. Minimum requirements of n-3 and n-6 essential fatty acids for the function of the central nervous system and for the prevention of chronic disease. Proc Soc Exp Biol Med. 1992;200(2):174-176.1579578
40. Calon F, Lim GP, Morihara T, et al. Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease. Eur J Neurosci. 2005;22(3):617-626.16101743
41. Zhao L, Teter B, Morihara T, et al. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention. J Neurosci. 2004;24(49):11120-11126.15590928
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44. Louw L. Effects of conjugated linoleic acid and high oleic acid safflower oil in the treatment of children with HPV-induced laryngeal papillomatosis: a randomized, double-blinded and crossover preliminary study. Lipids Health Dis. 2012;11:136.23061633
45. Junlatat J, Sripanidkulchai B. Hair growth-promoting effect of Carthamus tinctorius floret extract. Phytother Res. 2014;28(7):1030-1036.24338940
46. Bahmanpour S, Vojdani Z, Penjehshahin MR, Hoballah H, Kassas H. Effects of Carthamus tinctorius on semen quality and gonadal hormone levels in partially sterile male rats. Korean J Urol. 2012;53(10):705-710.23136631
47. Mirhoseini M, Mohamadpout M, Khorsandi L. Toxic effects of Carthamus tinctorius L. (safflower) extract on mouse spermatogenesis. J Assist Reprod Genet. 2012;29(5):457-461.22395857
48. Wang C, Wang C, Ma C, et al. Hydroxysafflor yellow A of Carthamus tinctorius attenuates lung injury of aged rats exposed to gasoline engine exhaust by down-regulating platelet activation. Phytomedicine. 2014;21(3):199-206.24192212
49. Brinker FJ. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998.
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51. Monfared AL, Salati AP. The effects of Carthamus tinctorius L. on placental histomorphology and survival of the neonates in mice. Avicenna J Phytomed. 2011;2:146-152.
52. Higa R, Kurtz M, Mazzucco MB, Musikant D, White V, Jawerbaum A. Folic acid and safflower oil supplementation interacts and protects embryos from maternal diabetes-induced damage. Mol Hum Reprod. 2012;18(5):253-264.22180326
53. Compes E, Bartolomé B, Fernández-Nieto M, Sastre J, Cuesta J. Occupational asthma from dried flowers of Carthamus tinctorious (safflower) and Achillea millefolium (yarrow). Allergy. 2006;61(10):1239-1240.16942580
54. Sun Z, Lian F, Zhang J, Sun J, Guo Y, Zhang Y. A literature analysis on 14 cases of allergic shock caused by safflower injection. Aft J Tradit Complement Altern Med. 2013;10(6):563-567.24311889
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