Safflower

Safflower (Carthamus tinctorius L.): A Comprehensive Reference

1. Identity and Botanical Description

Safflower (Carthamus tinctorius L.) belongs to the family Asteraceae. It is an annual or biennial herbal plant, and its tubular flowers have been used as the medicinal material. Safflower is a bushy annual that reaches approximately 1 m in height, with shiny, oval, spiny-edged leaves that alternate around a single, smooth, upright stem. The plant produces profuse yellow to deep red flowers and a dry, one-seeded fruit known as an "achene" that is generally small and white and used for its edible oil.

Safflower is native to the Middle East and is widely cultivated throughout Europe, China, India, and the United States. The plant is known under numerous names across cultures and medicinal traditions. In Persian it is called Kafesheh, and in English, safflower. In Traditional Chinese Medicine, it is known as Hong Hua (红花). In medieval Europe it was sometimes called bastard saffron due to its use as a less expensive substitute for true saffron (Crocus sativus).

Safflower is an oilseed crop that possesses great potential for the production of edible oil and is a source of protein. It is abundantly grown in Asia, North America, and South America. The oil content of safflower seeds is about 38–48%, with 15–22% protein; this oil content is significantly higher than those of soybean, sunflower, corn, and cottonseed.

Common Forms and Preparations

Multiple distinct parts of the safflower plant are used, and each yields different preparations:

• Seed oil: The plant is cultivated mainly for its seed, which is used as edible oil. It is available as refined cooking oil and as dietary supplement softgels or liquid capsules.
• Flower/floret extract: Florets have been diversely applied as a dye, coloring, flavoring, rouge, potion, and unguent. Standardized aqueous and ethanolic extracts of the dried florets are used in dietary supplement forms.
• Herbal infusion (tea): Fresh or dried safflower blossoms are infused in hot water to extract their healing compounds.
• Powdered florets: The dried and pulverized safflower blossoms can be prepared as a paste to treat skin irritations, or infused in oil or alcohol for topical use.
• Injectable pharmaceutical preparation (China): In clinic, the safflor yellow injection, which mainly contains about 80% hydroxysafflor yellow A (HSYA), was approved by the China State Food and Drug Administration and used to treat cardiac diseases such as angina pectoris.
• Traditional decoction: Used extensively in Traditional Chinese Medicine, where the dried flowers are boiled in water or wine, often with companion herbs.

2. Traditional and Historical Use

Ancient Egypt

The exact origin of safflower remains unknown; however, the oldest records of its domestication date back 4,000 years ago to Ancient Egypt, where it was widely cultivated both east and west of the Fertile Crescent. From a historical perspective, safflower seeds and packets, and garlands of florets were widely found in the presence of mummies across ancient Egypt. In Ancient Egypt, safflower brightly dyed the bindings used to wrap mummies, as well as provided an orange tint to ceremonial ointments used in religious rituals. Garlands of safflower blossoms were placed in tombs such as that of the pharaoh Tutankhamun, with the intent of providing comfort to the deceased in the afterlife. In Egypt, dye from safflower was used for coloring cotton and silk, as well as ceremonial ointment in religious ceremonies and to anoint mummies.

Traditional Chinese Medicine (TCM)

HSYA is a primary active product derived from safflower, a plant used to improve blood circulation, eliminate blood stasis, and relieve menstrual pain as early as recorded in the Kaibao Bencao. The Kaibao Bencao (Song Dynasty) notes its use for postpartum issues and abdominal pain, while the Bencao Gangmu (Ming Dynasty) praises it for "invigorating blood, relieving pain, and reducing swelling."

In traditional Chinese medicine, the herb (called Hong Hua) is referred to as "pungent, warm; and interacting with the heart and liver meridians" and indicated in amenorrhea due to stasis, to unblock menstruation, abdominal pain, post-partum dizziness, lochioschesis, dysmenorrhea, and postpartum abdominal stagnant pain. In Traditional Chinese Medicine, Hong Hua is classified as a warm herb that primarily enters the Heart and Liver meridians. In the theory of Traditional Chinese Medicine (TCM), safflower is considered to promote blood circulation to remove blood stasis, promote menstruation and alleviate pain.

According to traditional Chinese medicine, safflower petals promoted blood circulation and facilitated the healing of fractures, contusions, and strains. Safflower was also utilized in ancient Chinese cosmetics — including blush — as far back as 1760 BCE, and as a clothing dye.

Iranian / Persian Medicine

In Persian traditional medicine, safflower is vastly utilized for various medical conditions, namely dysmenorrhea, amenorrhea, postpartum abdominal pain and mass, trauma and pain of joints. Safflower is consumed raw in wide regions of Iran. It was also cultivated in Persia (modern-day Iran) and used as a natural colorant for creating the iconic Persian rugs.

European and Mediterranean Use

Safflower made its way into Europe from Egypt in 1551. Safflower dye was used in Italian, French, and British cuisine as a flavoring and a coloring. Safflower dyes were especially of utmost importance for the carpet-weaving industries in Eastern Europe, the Middle East, and the Indian subcontinent. In medieval Europe, safflower petals were used as a cheaper substitute for saffron in culinary applications, or in regions where saffron was not easily obtained.

Other Cultures

For a long time, Carthamus tinctorius has been used in traditional medicines as a purgative, analgesic, antipyretic, and an antidote to poisoning. It is a useful plant in traditional treatment of painful menstrual problems, post-partum hemorrhage, and osteoporosis. Safflower was cultivated in Egypt, Morocco, China, and India for carthamin, a yellow or red colored dye material, in ancient times, as early as 4500 BCE.

Commercial production of safflower oil began in the 1950s due to its use in the paint industry, but it is now sought after for edible products such as margarine and salad oil because of its presence of unsaturated fats, which are associated with lowering cholesterol.

3. Key Constituents and Active Compounds

Flower Constituents

Carthamin and safflower yellow are the main constituents in the flower of C. tinctorius. Carthamidin, isocarthamidin, hydroxysafflor yellow A (HSYA), safflor yellow A, safflamin C, and luteolin are the main constituents which are reported from this plant.

From 1978 to April 2025, various active metabolites have been identified, primarily comprising flavonoids, polyacetylenes, and alkaloids, with flavonoids being the predominant group. Currently, over 104 compounds from this plant have been isolated and identified, including quinochalcones, flavonoids, alkaloids, polyacetylene, aromatic glucosides, organic acids, and more.

Caryophyllene, p-allyltoluene, 1-acetoxytetralin, and heneicosane were identified as the major components of C. tinctorius flowers' essential oil.

Seed Oil Constituents

Safflower oil contains two main unsaturated fatty acids: oleic acid (18:1) and linoleic acid (18:2). Together they account for about 90% of total fatty acids. The remaining 10% corresponds to the saturated fatty acids palmitic (16:0) and stearic acid (18:0).

There are two major commercial chemotypes of safflower oil based on fatty acid profile: linoleic types contain 70–75% linoleic acid, whereas oleic types contain 75–80% oleic acid. Standard safflower oil contains about 6–8% palmitic acid, 2–3% stearic acid, 16–20% oleic acid, and 71–75% linoleic acid. However, considerable variability exists among cultivars; fatty acid compositions in 200 safflower accessions originating from 37 countries show that oleic and linoleic acid have a tremendous range of variation, from 3.1% to 90.60% and from 3.9% to 88.8%, respectively.

Three types of tocopherols are found in safflower oil in various amounts: α-tocopherol ranging from 46.05 to 70.93 mg/100 g, β-tocopherol from 0.85 to 2.16 mg/100 g, and γ-tocopherol present in trace to 0.45 mg/100 g of oil. Safflower also contains vitamins A and E, as well as small amounts of flavonoids, alkaloids, and polyalkenes.

Hydroxysafflor Yellow A (HSYA): The Principal Bioactive

Hydroxysafflor yellow A (HSYA) is one of the major bioactive and water-soluble compounds isolated from Carthami Flos, the flower of safflower. As a natural pigment with favorable medical use, HSYA has gained extensive attention due to broad and effective pharmacological activities since first isolation in 1993.

HSYA has significant pharmacological activities, such as antioxidant, anti-inflammatory, anticoagulant, and anticancer effects. However, chemical instability and low bioavailability have been severely hampering the clinical applications of HSYA during the treatment of cardiovascular and cerebrovascular disease.

4. Mechanisms of Action

Cardiovascular and Cerebrovascular

HSYA acts as an antioxidant, anti-inflammatory, and anticoagulant agent, playing an exceptional role in the treatment of cardiovascular and cerebrovascular diseases by down-regulating NF-κB signaling pathways, inhibiting MAPK signaling pathways, and attenuating the activation of Nrf-2/HO-1 signaling pathways.

HSYA has been found to offer the potential for reducing blood pressure. The mean arterial pressure and heart rate in both normotensive rats and spontaneously hypertensive rats could be markedly reduced by HSYA. Further study disclosed that HSYA could downregulate left ventricular systolic pressure, left ventricular end-diastolic pressure, and the maximum rate of increase of left ventricular pressure. Mechanistically, large conductance Ca²⁺-activated K⁺ channels (BKCa) and ATP-sensitive potassium channels (KATP) were responsible for the effects of HSYA on blood pressure and cardiac function. These findings are derived from animal models, not human studies.

Anti-inflammatory

HSYA could significantly inhibit platelet activating factor (PAF)-induced inflammatory activation in human small airway epithelial cells by inhibiting the PKC and MAPK signaling pathways and suppressing the activities of NFκB and AP1.

Comprehensive analysis indicated that safflower alleviated inflammatory effects by downregulating the expression of NFκB1, IL-6, IL-1β, IL-18, TNFα, and MCP-1 and upregulating NFκBia. Safflower shows a significant cardioprotective effect by activating multiple inflammation-related signaling pathways, including the NFκB, HIF-1α, MAPK, TNF, and PI3K/AKT signaling pathways.

Antidiabetic

In vivo and in vitro pharmacological research indicated that the antidiabetic activities of HSYA were based mainly on its antioxidant and anti-inflammatory mechanisms via JNK/c-jun pathway, NOX4 pathway, and macrophage differentiation.

Lipid Modulation (Seed Oil)

Both linoleic and oleic fatty acids reduce LDL cholesterol levels to help prevent cardiovascular disease. One proposed dietary strategy for decreasing cardiovascular risk factors involves replacing a portion of dietary saturated fatty acids with mono- and polyunsaturated fatty acids. The essential omega-6 PUFA, linoleic acid (LA), is suggested to decrease the risk for CVD by affecting these lipid risk markers.

5. Scientific Evidence by Area of Use

5.1 Cardiovascular Health and Lipid Modification

Cholesterol and LDL: Evidence from a review of human intervention trials provided evidence that linoleic acid consumption decreases CVD lipid risk markers in healthy individuals. A small dietary intervention study (6 weeks, 12 participants) found that a salad dressing containing 21 g safflower oil providing 16 g linoleic acid per day was added to subjects' daily diets. Although linoleic acid intake increased significantly during the dietary intervention, plasma CLA concentrations were not affected. Plasma total cholesterol and LDL-cholesterol concentrations were significantly lower after addition of safflower oil to the diet.

The Sydney Diet Heart Study (SDHS) — a critical reanalysis: Increasing n-6 linoleic acid from safflower oil in the SDHS significantly reduced total cholesterol; however, these reductions were not associated with mortality outcomes. Moreover, the increased risk of death in the intervention group presented fairly rapidly and persisted throughout the trial. These observations, combined with recent progress in the field of fatty acid metabolism, point to a mechanism of cardiovascular disease pathogenesis independent of the traditional understanding of cholesterol lowering. This reanalysis underscores the complexity of interpreting lipid-focused trials using high-linoleic safflower oil without accounting for competing n-3 fatty acids.

Meta-analytic data: A secondary analysis of a small clinical trial conducted in the 1960s suggested that substituting high-linoleic acid (LA) safflower oil for saturated fat increased cardiovascular mortality. In addition, an updated meta-analysis of LA intervention trials — high-LA oils without n-3 fatty acids such as corn oil and safflower oil — showed non-significant trends toward increased risks of CHD death, whereas the trials using high-LA oils with n-3 fatty acids (e.g., soybean oil) showed opposite trends. However, these trials were small with limited power, and most of them were conducted in patients with existing heart diseases.

Evidence appraisal: The totality of clinical evidence on safflower oil's cardiovascular effects is mixed and remains inconclusive. Reductions in LDL-cholesterol are consistently observed, but their translation into reduced cardiovascular mortality has not been demonstrated. The field lacks large-scale modern randomized controlled trials using safflower oil specifically.

5.2 Metabolic Syndrome, Glycemia, and Abdominal Obesity

Ruyvaran et al. (2022) — Randomized, double-blind, placebo-controlled trial: In this randomized, double-blind, placebo-controlled clinical trial, 67 patients with metabolic syndrome were administered either divided 8 g safflower oil or placebo daily for 12 weeks. Safflower oil resulted in significant reductions in waist circumference (−2.42 ± 3.24 vs. 0.97 ± 2.53, p<0.001), systolic blood pressure (−8.80 ± 9.77 vs. −2.26 ± 8.56, p=0.021), diastolic blood pressure (−3.53 ± 7.52 vs. −0.70 ± 6.21, p=0.041), fasting blood sugar (−5.03 ± 10.62 vs. 2.94 ± 7.57, p=0.003), and insulin resistance (−0.59 ± 1.43 vs. 0.50 ± 1, p=0.012), as well as an increase in adiponectin level in the treatment group compared to the placebo group. The study concluded that safflower oil without lifestyle modification improved abdominal obesity, blood pressure, and insulin resistance in patients with metabolic syndrome.

Belury et al. (2009) — Randomized, double-masked, crossover study: This was a 36-week randomized, double-masked, crossover study. Fifty-five obese postmenopausal women with type 2 diabetes received safflower oil (SAF) or conjugated linoleic acid (CLA) at 8 g oil per day during two 16-week diet periods separated by a 4-week washout period. After 16 weeks of supplementation with safflower oil, the study found reduced fat in the trunk area, lowered blood sugar, and increased muscle tissue in the women participants. The daily supplementation contained 6.4 grams of the oil's active fatty acid, linoleic acid. Among the most surprising findings was that in 16 weeks, these women could lose between about two and four pounds of trunk fat simply by taking safflower oil supplements.

Asp et al. (2011) — Secondary analysis of the same cohort: The study objective was to evaluate effects of conjugated linoleic acid and safflower oils on glycemia, blood lipids, and inflammation. The hypothesis tested was that dietary oils improve glycemia, lipids, and inflammatory markers in a time-dependent way that follows accumulation of linoleic acid and CLA isomers in serum of subjects supplemented with dietary oils.

Evidence appraisal: The Belury research group's findings are notable but are limited by the specific and narrow population (obese, postmenopausal women with type 2 diabetes). The 2022 metabolic syndrome trial, while randomized and placebo-controlled, involved only 67 participants and 12 weeks of follow-up. Larger, longer trials with broader populations are needed before generalizable conclusions can be drawn.

5.3 Cardiovascular Angina Pectoris — Safflower Yellow Injection (China)

The safflor yellow injection, which mainly contains about 80% HSYA, was approved by the China State Food and Drug Administration and used to treat cardiac diseases such as angina pectoris. In the case of acute ischemic stroke, a Phase 3 clinical trial has been completed, and the drug has demonstrated favorable clinical outcomes. However, these applications are primarily within the Chinese regulatory framework and have not been validated through international regulatory review processes. Most mechanistic data for HSYA-based injectable products come from animal models and in vitro studies.

5.4 Dysmenorrhea and Gynecological Conditions

Safflower, with a wide spectrum of pharmacological effects, has been used to treat dysmenorrhea, amenorrhea, postpartum abdominal pain and mass, trauma, and pain of joints. Due to its main efficacy in the treatment of primary dysmenorrhea, the potential targets and mechanism of action of safflower in the treatment of primary dysmenorrhea have been analyzed using network pharmacology and metabolomics methods. Robust human clinical trial evidence specifically for safflower in dysmenorrhea is limited, and much of the available data comes from traditional use records and computational (network pharmacology) analyses rather than controlled clinical studies.

5.5 Anti-inflammatory and Analgesic Activity

C. tinctorius has recently been shown to have antioxidant, analgesic, anti-inflammatory, and antidiabetic activities. The whole plant of C. tinctorius possesses pharmacological activities including antifibrosis, antidiabetic, antitumor, anti-inflammatory, hepatoprotective, antihyperlipidemic, anticoagulant, and antioxidant activities. The large majority of these findings derive from in vitro cell culture experiments and animal models. Preliminary animal and in vitro data suggest potential benefits for cardiovascular health, but robust human clinical trials are needed to confirm efficacy and safety in humans before widespread recommendation.

5.6 Anticancer Research

HSYA, a natural pigment with a chalcone structure extracted from safflower, has been widely studied for good efficacy on cardiovascular diseases, atherosclerosis, cancer, and diabetes. In the last 10 years, many studies have analyzed the effect of HSYA on various cancer cells and revealed that HSYA has a good anticancer effect in preclinical models; till date, HSYA has made the most progress in the study of hepatocellular carcinoma compared to other cancers. All anticancer evidence for HSYA currently derives from in vitro and animal studies. No clinical trials in humans on cancer outcomes have been identified in the peer-reviewed literature.

5.7 Neuroprotection, Liver and Lung Protection

HSYA has been proved to exhibit a broad spectrum of biological effects that include, but are not limited to, cardiovascular effect, neuroprotection, liver and lung protection, antitumor activity, metabolism regulation, and endothelium cell protection. HSYA has shown protective and mitigation effects in acute lung injury, chronic obstructive pulmonary disease, and pulmonary hypertension in animal and in vitro studies. As with anticancer research, the evidence base here is predominantly preclinical; human clinical data in these areas remain sparse.

6. Body Systems and Health Areas of Association

• Cardiovascular system: Lipid modification via linoleic and oleic acids; antiplatelet and anticoagulant activity of HSYA; vasodilatory effects observed in animal models; angina treatment with safflower yellow injection in China.
• Metabolic / endocrine: Effects on insulin resistance, fasting blood glucose, adiponectin signaling, and abdominal adiposity, as seen in clinical trials with safflower oil.
• Reproductive system: Traditional use for dysmenorrhea, amenorrhea, and postpartum complications across multiple medical traditions; uterine stimulant activity, which is both a therapeutic attribute and a safety concern.
• Hepatic system: Extracts and metabolites derived from safflower have demonstrated hepatoprotective bioactivity.
• Musculoskeletal: Traditional use for trauma, contusions, fractures, and joint pain.
• Immune / inflammatory: In vitro and animal evidence for modulation of NF-κB, MAPK, and related inflammatory pathways.
• Integumentary (skin): Topical application of floret preparations; safflower oil widely used as an emollient and cosmetic skin conditioning agent.

7. Dosage Forms and Reported Dosages

There is no universally standardized dose for safflower or safflower oil. The following dosages are reported specifically in identified clinical or human intervention studies:

• Safflower oil — metabolic syndrome: In a randomized, double-blind, placebo-controlled clinical trial, 67 patients with metabolic syndrome were administered either divided 8 g safflower oil or placebo daily for 12 weeks.
• Safflower oil — obese postmenopausal women with type 2 diabetes: Fifty-five obese postmenopausal women with type 2 diabetes received safflower oil or conjugated linoleic acid at 8 g oil per day during two 16-week diet periods. The daily supplementation contained 6.4 grams of linoleic acid (the active fatty acid in safflower oil).
• Safflower oil — cholesterol study: A dietary intervention used 21 g of safflower oil per day, providing 16 g of linoleic acid daily, for 6 weeks.
• CLA vs. safflower oil — cardiovascular risk in overweight men: Eighty-five overweight men (aged 45–68 years, BMI 25–35 kg/m²) were randomized to receive 4.5 g/d of CLA isomeric mixture, safflower oil, heated safflower oil, or olive oil in a 4-week double-blind study.
• Delivery format: In the Belury study, supplements were contained in eight pills; the women took two pills four times per day, at meals and bedtime.
• There is no standardized human dosage for safflower extract (flower) due to limited clinical trials.

8. Safety Considerations and Interactions

Pregnancy — Flower Preparations

Safflower is contraindicated in pregnancy. Use is contraindicated in pregnancy; abortifacient and emmenagogue effects have been suggested. Safflower flower preparations should not be taken during pregnancy. They are considered likely unsafe, as they can bring on menstrual periods, make the uterus contract, and cause miscarriages. Traditional Chinese Medicine texts note that the decoction can "excite uterus and intestinal smooth muscles" and that labour can be induced by a preparation of safflower, ideally along with rupture of membranes.

The regulatory picture for seed oil is different: safflower seed oil is considered possibly safe to take by mouth during pregnancy. However, it is not known if products made from the flower could affect pregnancy or cause harm to a fetus.

Regarding formal toxicology, a guideline-compliant study found no indication of adverse effects on fertility, reproductive performance, or early postnatal development from a food-grade safflower petal extract; however, earlier publications raised concerns about fertility-impairing, maternal toxicity, fetotoxic, and teratogenic properties in rodents. As the tested extracts were poorly characterized and the studies were not performed according to guidelines, a need for further evaluation was seen.

Anticoagulant and Antiplatelet Activity

Due to its platelet aggregation inhibition properties, safflower extract may increase the risk of bleeding when combined with anticoagulant or antiplatelet medications. Pre-surgical patients should discontinue safflower flower preparations at least 1–2 weeks before planned surgery due to anticoagulant and antiplatelet effects. Patients with bleeding disorders such as hemophilia or thrombocytopenia, or those on anticoagulant/antiplatelet therapy without close medical supervision, are at elevated risk. Patients with peptic ulcers with active bleeding should also exercise caution, as the herb's blood-invigorating action can aggravate gastrointestinal hemorrhage.

Allergy

Allergy to the flowers has been reported. Given that safflower is a member of the Asteraceae (Compositae) family, cross-reactivity with other members of this family (such as ragweed, chrysanthemums, and marigolds) is theoretically possible, though this has not been systematically studied in the clinical literature identified here.

General Tolerability of the Seed Oil

Safflower oil was generally well tolerated when used as a control in clinical trials. A few cases of acute liver disease have been associated with the use of safflower oil supplements.

Drug Interactions

Long-term effects and interactions with other medications are not fully understood, given the lack of comprehensive human safety data. The primary pharmacologically relevant interaction concern is with anticoagulants (e.g., warfarin) and antiplatelet agents (e.g., aspirin, clopidogrel), where additive bleeding risk is plausible based on the documented platelet-inhibiting activity of safflower flower constituents. No pharmacokinetic interaction studies in humans have been identified in the peer-reviewed literature.

Bioavailability Limitations of HSYA

Chemical instability and low bioavailability have been severely hampering the clinical applications of HSYA during the treatment of cardiovascular and cerebrovascular disease. This is a relevant consideration when evaluating the translatability of in vitro and animal HSYA data to oral supplement use in humans.

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