Scientific Name(s): Carthamus tinctorius L.
Common Name(s): American saffron, Bastard saffron, Dyer's saffron, False saffron, Gami-Honghwain, Hong hua, Safflower, Zafran
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
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
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
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.
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
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
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
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
Animal/In vitro data
There are no animal or in vitro data regarding the use of safflower for obesity.
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
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
There are no clinical data regarding the use of safflower for its effects on the CNS.
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
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
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
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
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
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
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
None well documented.
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.
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
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