Spices and herbs have been used for centuries for not only enhancing the flavor, aroma, and color of food and beverages, but also as protection from various ailments and chronic diseases.
Saffron is a popular spice derived from the dried thread-like parts of the Crocus sativus flower, commonly known as the "saffron crocus". It is used in different food dishes and drinks, such as paella in Spain, Milanese risotto in Italy, lussekatter buns in Sweden, and alcoholic beverages. It is considered a high-priced spice ($1600–2400 /kg) due to the considerable labor involved in its production, as it requires manual harvesting, laborious sorting, drying, and storage. Its main producers are Iran and Spain. Due to its tiny size, it can take about 75,000 saffron blossoms to produce a single pound of saffron spice. For this reason, and because of the saffron color, it is known as “red gold”.
Growing popularity of traditional medicine: Despite the widespread use of synthetic drugs for the treatment of diseases, about 80% of the world population, primarily in the developing world, relies on traditional medicinal plants to promote better health. However, the many health benefits of phytochemicals also attract the attention of medical researchers and the health industry, as natural compounds are relatively inexpensive, widely available, safe, effective, and they have lower side effects as the chemical constituents of plants have better compatibility with the human body than synthetic drugs.
Among numerous herbs and spices, saffron possesses therapeutic properties indicated centuries ago. Saffron’s medicinal properties were illustrated in paintings dated 1627 BC found on the island of Santorini, and it is included in the Catalogues of Medicinal Plants and in the European Pharmacopoeias as a part of compounded formulas from the 16th to the 20th centuries. The medicinal and pharmaceutical uses of this plant have largely disappeared with the advent of synthetic chemistry-produced drugs, but now it is being revived.
Universal health benefits of saffron: In recent years, there has been growing interest in the health benefits of saffron and in demonstrating its bioactivity attributed to its specific, primarily carotenoid components, and to the synergy between the compounds that are present in this spice. Saffron also contains small amounts of proteins, fats, minerals, sugars, and vitamins B2 (riboflavin) and B1 (thiamine), with the majority of its weight made up of carbohydrates.
Carotenoids are the most important constituents of the spice, from which it derives its color. They include fat-soluble carotenoids, such as α- and β-carotene, lycopene, and zeaxanthin, and water-soluble carotenoids like crocetin (C20H24O4) and its glycosidic esters, called crocins. Carotenoids make up 3.5% of the weight of the stigmas in the plant. Other carotenoid compounds include picrocrocin, which contributes to the herb’s bitter taste, and safranal, which contributes to its aroma.
Saffron has many health enhancing effects when used alone or when it is enriched in some of its components as an extract. It can also be applied as an adjunct to targeted supplementation, in order to address various health concerns, including:
MOOD AND MENTAL HEALTH
The biological activity and benefits of saffron-active molecules in the central nervous system have been studied for over two decades. Its pharmacological effects include improving memory and learning, neurodegenerative diseases, depression, and anxiety, among others. Saffron and its major constituent, crocin, were shown to enhance learning, memory, non-rapid eye movement (NREM) sleep, and inhibit depression and neuronal cell death due to its strong antioxidant and anti-inflammation activities.
Mood: Saffron and its metabolites have proven to be effective in treating various psychiatric disorders, including depression and anxiety. Various clinical studies have concluded that the daily administration of 30 mg of saffron could be useful in the management of depression (Akhondzadeh et al., 2004; Akhondzadeh et al., 2005; Noorbala et al., 2005; Shahmansouri et al., 2014). Some studies have also demonstrated the usefulness of crocin when administered in conjunction with pharmaceutical drugs such as imipramine or fluoxetine [Talaei et al., 2015]. In a trial involving 66 patients with anxiety-depressive disorder, researchers compared treatment with saffron (30 mg/day) or citalopram (40 mg/day) for 6 weeks. The results showed no significant difference between the use of saffron and the drug, and it was proposed that saffron could be an effective and tolerable treatment for this debilitating disorder (Ghajar et al., 2016).
Sleep: Saffron may help improve sleep quality and duration. A randomized, double-blind, placebo-controlled study concluded that saffron supplementation for 28 days at a dose of 14 and 28 mg taken 1 hour before bedtime was associated with greater improvements in several sleep-related measures. Compared to a placebo, participants supplemented with saffron had better sleep quality, mood after awakening, and other positive effects. (Lopresti et al., 2021).
Recent meta-analysis of relevant studies have found that saffron supplementation improved sleep quality with no serious adverse events (Lian et al., 2022).
Neurodegenerative conditions:
Alzheimer’s Disease is one of the most common diseases that leads to a significant deterioration in cognitive function. It is characterized by the formation of brain plaques loaded with polypeptide β-amyloid and prominent tangles of tau protein. Although more human clinical trials are needed, some studies have pointed to the neuroprotective character of saffron and its components in treating Alzheimer’s patients, and they have identified effects that are similar to those obtained from pharmaceutical drugs including donepezil and memantine (D’Onofrio et al., 2021). There are also clinical findings showing the effectiveness of saffron in treating mild to moderate Alzheimer’s disease. Additionally, multiple clinical trials involving patients with Alzheimer’s disease have demonstrated the direct and indirect anti-dementia activities of crocin and saffron.
Multiple Sclerosis (MS) progresses with acute attacks and inflammation of the myelin, and studies have shown that glycosidic esters of crocetin may prevent demyelination and neurodegeneration. Such findings show that saffron may potentially be useful in the treatment of MS through the inhibition of oxidative stress and the infiltration of leukocytes to the central nervous system (Deslauriers et al., 2011; Kouchaki et al., 2024).
Diabetes-related neuropathy is one of the most severe complications that develops in more than half of diabetic patients. It is manifested as neuronal damage caused by a decrease in blood flow. In this respect, saffron has shown multiple protective effects, presumably because of its antioxidant properties (Sani et al., 2022).
VISION
Saffron contains carotenoids that may improve eye health and protect against retinal stress. Studies, both in vitro and in vivo, show that the administration of crocetin has protective effects against damage to the retina by inhibiting the degeneration of photoreceptors and retinal dysfunction (Bagur et al., 2017; Liou et al., 2018).
Coronary heart disease: The effects of the intake of 30 mg/day of crocin and 30 mg/day of saffron extract for 8 weeks were evaluated in patients with coronary artery disease by assessing oxidants, antioxidants, and inflammatory parameters. The results of this study indicated that crocin increased various positive effects such as increased expression of SIRT1, which protects against oxidative DNA damage, apoptosis, and cell senescence. Crocin and saffron intake also suppressed inflammation, oxidative stress, and foam cell formation in atherosclerosis plaques. Other benefits included an increase in adenosine monophosphate-activated protein kinase (AMPK), which facilitates the efflux of cholesterol from cells and increases bioenergy production, lowers oxidized LDL levels and proinflammatory factors (NF-κB). In addition, both crocin and saffron extract decreased monocyte chemoattractant protein-1 (MCP-1) levels (Abedimanesh et al., 2020).
Another study involving atherosclerosis patients taking 100 mg saffron for 6 weeks showed an improvement in the physical and social aspects of their quality of life when compared to a placebo (Ahmadikhatir et al., 2022).
High blood pressure (hypertension): Beneficial cardiovascular effects of crocetin extract from saffron were related to the control of endothelial vascular function. Studies have shown that crocetin can improve the nitric oxide-endothelium-dependent relaxation of blood vessels, which is damaged in hypertension (Mancini et al., 2014). At the same time, endothelium-modulated vascular relaxation can reduce over-reactive arterial response, which is a hallmark of hypertension (Llorens et al., 2015).
In a study involving 60 to 70 year-old men with hypertension, 200 mg of saffron combined with resistance training decreased systolic blood pressure, diastolic blood pressure, and mean arterial pressure. These beneficial effects of saffron were accompanied by a significant increase in nitric oxide (NO) and adiponectin levels, and a noticeable reduction in the concentration of endothelin-1 (Hooshmand-Moghadam et al., 2021).
In another randomized controlled clinical study, the consumption of 200 mg of saffron combined with resistance training ameliorated inflammation and reduced cardiovascular risk factors in old hypertensive men (Mojtahedi et al. 2022).
Stroke: Numerous studies claim that crocetin from saffron increases the oxygenation of various tissues involved in strokes (Gainer et al., 2017; Gainer, 2008; Giassi et al,, 2003). In one study, Yang and coworkers (Yang et al., 2011) demonstrated that the administration of crocetin (2 mg/kg) to experimental animals that had hemorrhagic shock, significantly improved survival and reduced cell death after resuscitation.
APPETITE AND WEIGHT CONTROL
A randomized, placebo-controlled, double-blind study in 60 healthy, mildly overweight women showed that supplementation with saffron extract for 8-weeks resulted in a significantly greater reduction of bodyweight and decreased the frequency of snacking, when compared to a placebo (Gout et al., 2010). In addition, high-quality evidence has recently emerged through meta-analytic approaches, which provides data showing that saffron supplementation in obese adults can significantly modify their body size and shape by reducing their waist-to-hip ratio (Tahmasbi et al., 2022).
GASTROINTESTINAL HEALTH
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gastrointestinal tract, and they are becoming more prevalent worldwide.
Various in vitro and in vivo studies have demonstrated multiple beneficial effects of saffron, carotenoid, crocin and crocetin on inflammatory disorders including gastritis and peptic ulcer, irritable bowel syndrome, inflammatory bowel disease, and hepatitis (Ashktorab et al., 2019; Rashid et al., 2024). Saffron can inhibit stress-induced ulcers and histamines, and saffron shows hepatoprotective effects. The antioxidant and anti-inflammatory components of saffron could also be beneficial in treating various forms of liver injuries such as drug-induced liver damage, viral hepatitis, and alcoholic and non-alcoholic steatohepatitis.
ANTI-INFLAMMATORY AND ANTIOXIDANT PROPERTIES
More than 100 different diseases, including several types of cancers, heart and vascular diseases, obesity, neurodegenerative disorders, as well as age-related disorders are closely associated with oxidative damage in the body. Saffron contains numerous antioxidants that can help protect the body from oxidative stress and alleviate the risk of diseases. Saffron’s antioxidant activity is due to its phenolic and flavonoid components, such as gallic acid and pyrogallol, but also crocin, crocetin, safranal, picrocrocin, and kaempferol which also act as antioxidants. Estimated antioxidant content is 44.5 mmol/100 g in dried ground saffron, and 17.5 mmol/100g in whole stigmas (Paur et al., 2011). Saffron extracts have also further enhanced antioxidant activity. For example, an alcohol extract of saffron stigma at a concentration of 300 μg/mL had a free-radical scavenging activity of 68.2% (Karimi et al., 2010). In its anti-inflammatory capacity, saffron down-regulates key pro-inflammatory enzymes such as myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phospholipase A2, and proteinoids (Zeinali et al., 2019).
OTHER POTENTIAL HEALTH BENEFITS
Sexual health: Saffron may help with sexual dysfunction in both men and women. A clinical trial found that saffron tablets improved erectile function and other sexual function subscales in 20 men with erectile dysfunction. (Shamsa et al., 2009 ). A review and meta-analysis of five studies comprising 173 participants found that saffron showed a statistically significant positive effect on sexual dysfunction (Ranjbar et al., 2019).
Premenstrual syndrome (PMS): A double-blind, randomized and placebo-controlled trial in women concluded that 76% of women who had taken saffron (30 mg/day) reported a 50% reduction in the severity of PMS symptoms, whereas such an effect was observed in only 8% of women receiving a placebo (Agha-Hosseini et al., 2008). A recent review of 20 randomized controlled trials showed that saffron has positive effects on labor and childbirth, including labor progress, and reducing fatigue and labor pain intensity. Additionally, saffron has been shown to improve mood and other psychological symptoms of menopause and PMS. The results of two studies showed that saffron also has a positive effect on treating postpartum depression (Irani et al., 2023).
Saffron has many health benefits and is generally safe. However, like many natural compounds, it has not been adopted in common medical practice because demonstrating the health benefits of natural compounds remains challenging, particularly when compared to the standards that are applied to pharmaceutical agents. Pharmaceuticals are small, chemically synthesized molecules consumed in a purified and concentrated form. Natural compounds are more difficult to study, being an integral part of foods that are present in various quantities and are combined with other nutrients. There is also an economic aspect behind the low investment into natural health research, as natural compounds generate much less profits when compared to chemical drugs. However, the growing evidence of positive health experiences of using natural compounds, including herbs and spices, increases the recognition of natural health and puts pressure on researchers to confirm them by scientific means.