Saffron herb health benefit, depression, PMS, macular degeneration - Medicinal properties and aphrodisiac effects by Ray Sahelian, M.D.
November 1 2017

Saffron is an expensive spice known for flavoring Mediterranean cuisine. There are many beneficial herbs used in cooking, including garlic, thyme, fennel, etc.

Medicinal use of saffron herb
Traditionally, this spice has been advocated for stomach pain, digestive problems and low mood. Some claim saffron herb is a natural aphrodisiac. Additional claims that I have seen mention the following, but we need more studies to confirm these claims:

Alzheimer's disease prevention or benefit
Reduces anxiety and stress
Helps improve mood
Reduces PMS symptoms
Stimulates cognitive properties

Alzheimmer's disease prevention or benefit
J Agric Food Chem. 2017. A Perspective on Crocus sativus Saffron Constituent Crocin: A Potent Water-Soluble Antioxidant and Potential Therapy for Alzheimer's Disease. Crocin is a unique antioxidant because it is a water-soluble carotenoid. Crocin has shown potential to improve learning and memory as well as protect brain cells. A search of the studies on saffron and crocin that have been published in recent years for their impact on AD as well as crocin's effects on Aβ and tau protein has been conducted. This review demonstrates that crocin exhibits multifunctional protective activities in the brain and could be a promising agent applied as a supplement or drug for prevention or treatment of AD.

ACS Chem Neurosci. 2017. Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice.

Blood pressure
Hypotensive effect of aqueous saffron extract (Crocus sativus) and its constituents, safranal and crocin, in normotensive and hypertensive rats.
Phytother Res.. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.
In this study, the effects of saffron (Crocus sativus) stigma aqueous extract and two active constituents, crocin and safranal, were investigated on blood pressure of normotensive and desoxycorticosterone acetate-induced hypertensive rats. Three doses of crocin, safranal and the aqueous extract were administered intravenously in different groups of normotensive and hypertensive animals and their effects on mean arterial blood pressure (MABP) and heart rate (HR) were evaluated. The aqueous extract of saffron stigma, safranal and crocin reduced the MABP in normotensive and hypertensive anaesthetized rats in a dose-dependent manner. It can be concluded that the aqueous extract of saffron stigma has hypotensive properties which appear to be attributable, in part, to the actions of two major constitutes of this plant, crocin and safranal. It seems that safranal is more important than crocin for lowering down blood pressure of rats.

Depression and mood
J Affect Disord. 2015. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: A randomized, double-blind, placebo-controlled, pilot clinical trial. The aim of this study was to assess the efficacy of crocin, the main active constituent of saffron, as an adjunctive treatment in major depressive disorder. This study was carried out during 4 weeks in two groups (placebo and treatment) on 40 patients between 24 and 50 years old in Ibn-e-Sina psychiatric hospital, Mashhad, Iran. The crocin group was given one selective serotonin reuptake inhibitor (SSRI) drug (fluoxetine 20mg/day or sertraline 50mg/day or citalopram 20mg/day) plus crocin tablets (30mg/day; 15mg BID) and placebo group was administered one SSRI (fluoxetine 20mg/day or sertraline 50mg/day or citalopram 20mg/day) plus placebo (two placebo tablets per day) for 4 weeks. The crocin group showed significantly improved scores. These results demonstrated the effect of crocin in depression and could be administered in treatment of depression.

J Integr Med. 2015. A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes. Throughout the past three decades, increased scientific attention has been given to examining saffron's (Crocus sativus.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. Findings from initial clinical trials suggest that saffron may improve the symptoms and the effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings.

J Integr Med. November 2013. Saffron (Crocus sativus) and major depressive disorder: a meta-analysis of randomized clinical trials. Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron's efficacy and safety for treating depressive symptoms.

J Affect Disord. February 2014. A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients. A significant correlation exists between coronary artery diseases and depression. The aim of this trial was to compare the efficacy and safety of saffron versus fluoxetine in improving depressive symptoms of patients who were suffering from depression after performing percutaneous coronary intervention (PCI). :In this randomized double-blind parallel-group study, 40 patients with a diagnosis of mild to moderate depression who had undergone PCI in the last six months were randomized to receive either fluoexetine (40mg/day) or saffron (30mg/day) capsule for six weeks. Participants were evaluated by Hamilton depression rating scale (HDRS) at weeks 3 and 6 and the adverse events were systemically recorded. By the study endpoint, no significant difference was detected between two groups in reduction of HDRS scores. Remission and response rates were not significantly different as well. There was no significant difference between two groups in the frequency of adverse events during this trial. Short-term therapy with saffron capsules showed the same antidepressant efficacy compared with fluoxetine in patients with a prior history of PCI who were suffering from depression.

Erectile dysfunction, impotence, sexual health
Hum Psychopharmacol. 2013. Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study. This was a randomized double-blind placebo-controlled study. Thirty-eight women with major depression who were stabilized on fluoxetine 40 mg/day for a minimum of 6 weeks and had experienced subjective feeling of sexual dysfunction entered the study. The patients were randomly assigned to saffron (30 mg/daily) or placebo for 4 weeks.  Results show saffron may safely and effectively improve some of the fluoxetine-induced sexual problems including arousal, lubrication, and pain.

Arch Ital Urol Androl. 2013. An improvement in sexual function is related to better quality of life, regardless of urinary function improvement: Results from the IDIProst® Gold Study. The relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) has recently received increased attention. The aim of this study was to evaluate the efficacy of the Alfa-5® association of Serenoa repens, Pinus massoniana Bark Extract (PMBE) and Crocus sativus (IDIProst® Gold) in improvement of patient's quality of life, when compared with Serenoa repens alone. Materials and Methods. All patients with clinical and instrumental diagnosis of LUTS due to Benign Prostatic Hyperplasia (BPH) and ED, attending 5 Italians Urological Institutions from May to December 2012 were enrolled in this prospective, multicentre, phase 3 study. Participants were assigned to receive oral capsules of IDIProst® Gold (one capsule q24 h) or Serenoa repens 320 mg (one capsule q24h) for 3 months. Clinical and instrumental analyses were carried out at the enrolment and at the end of therapy. IPSS, IIEF-5 and SF-36 questionnaires have been used. The main outcome measure was the improvement of quality of life at the end of the whole study period. Results. 129 (mean age 45-71) men were randomly allocated to IDIProst Gold (n = 83) or Serenoa repens (n = 46. At the follow-up examination, statistically significant differences have been reported in terms of IPSS, IIEF-5 and SF-36 mean scores. Moreover, statistically significant differences were then reported between the two visits, in terms of IPSS, IIEF-5 and SF-36 scores, only in the IDIProst® Gold group. Conclusions. In conclusions, we found that IDIProst® Gold significantly improve the quality of life of patients affected by LUTS due to BPH and ED, specifically in terms of sexual function, highlighting that a better sexual quality of life is correlated with an higher overall quality of life regardless of the urinary function.

Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial
Psychopharmacology, 2012
To assess the efficacy and tolerability of saffron in fluoxetine-related sexual dysfunction. This was a 4-week randomized double-blind placebo-controlled study. Thirty-six married male patients with major depressive disorder whose depressive symptoms had been stabilized on fluoxetine and had subjective complaints of sexual impairment entered the study. The patients were randomly assigned to saffron (15 mg twice per day) or placebo for 4 weeks. International Index of Erectile Function scale was used to assess sexual function at baseline and weeks 2 and 4. Thirty patients finished the study. Baseline characteristics as well as baseline and final depressive symptoms scores were similar between the two groups. Effect of time × treatment interaction on the total score was significant. By week 4, saffron resulted in significantly greater improvement in erectile function and intercourse satisfaction domains, and total scores than the placebo group. Effect of saffron did not differ significantly from that of placebo in orgasmic function, overall satisfaction, and sexual desire domains scores. Nine patients (60%) in the saffron group and one patient (7%) in the placebo group achieved normal erectile function (score > 25 on erectile function domain) at the end of the study. Frequency of side effects were similar between the two groups. Saffron is a tolerable and efficacious treatment for fluoxetine-related erectile dysfunction.

Pharmacogn Rev. 2010. Crocus sativus: A comprehensive review. Faculty of Pharmacy, Babu Banarasi Das National Institute of Technology and Management, Dr. Akhilesh Das Nagar, Faizabad Road, Lucknow, Uttar Pradesh, India . Crocus sativus belonging to the family Iridaceae (syn - kesar) comprises the dried red stigma and is widely cultivated in Iran and other countries such as India and Greece. Saffron contains more than 150 volatile and aroma-yielding compounds mainly terpenes, terpene alcohol, and their esters. The bitter taste and an iodoform or hay-like fragrance are caused by chemicals picrocrocin and safranal. C. sativus possesses a number of medicinally important activities such as antihypertensive, anticonvulsant, antitussive, antigenototoxic and cytotoxic effects, anxiolytic aphrodisiac, antioxidant, antidepressant, antinociceptive , anti-inflammatory, and relaxant activity. It also improves memory and learning skills, and increases blood flow in retina and choroid. The present review explores the historical background, chemical constituents, pharmacological actions, uses, substitutes and adulterants, and toxicity. It also deals with its evaluation, formulations, and chemical tests in detail.

An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus) for treating erectile dysfunction in men naļve to treatment;
International Journal of Impotence Research 2010.
Saffron (Crocus sativus) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. No significant improvements were observed. The mean changes from baseline values in IIEF-EF domain were +87% and +9% in sildenafil and placebo groups, respectively. These findings do not support a beneficial effect of saffron administration in men with ED.
   Comments: Was the dosage used too low?

The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats.
Phytomedicine. 2007.
The aphrodisiac activities of saffron stigma aqueous extract and its constituents, safranal and crocin, were evaluated in male rats. The aqueous extract crocin, safranal, sildenafil as a positive control and saline were administered intraperitoneally to male rats. Mounting frequency (MF), intromission frequency (IF), erection frequency (EF), mount latency (ML), intromission latency (IL) and ejaculation latency (EL) were the factors evaluated during the sexual behavior study. Crocin, at all doses, and the extract, especially at doses 160 and 320mg/kg body wt., increased MF, IF and EF behaviors and reduced EL, IL and ML parameters. Safranal did not show aphrodisiac effects. The present study reveals an aphrodisiac activity of saffron aqueous extract and its constituent crocin.

Heart health
The effect of saffron consumption on biochemical and histopathological heart indices of rats with myocardial infarction.
Cardiovasc Toxicol. 2010; Joukar S, Najafipour H, Khaksari M, Sepehri G, Shahrokhi N, Gholamhoseinian A. Physiology Research Center and Department of Physiology and Pharmacology, Kerman University of Medical Sciences, Iran.
This study was designed to assess the effects of saffron (Crocus sativus) on rats' heart with isoproterenol-induced myocardial injury. Animals were divided randomly into four groups: vehicle-control group (CTL); ISO group, administrated with Isoproterenol; saffron group; and finally combined Saffron + ISO group. Basal and final serum levels of heart troponin I, heart tissue antioxidants and histopathological indices were assessed in all groups. Isoproterenol administration significantly increased serum level of troponin I when compared to control group and reduced significantly the glutathione peroxidase activity of heart muscle. The grade of heart muscle damages was severe in more than 70% of ISO group animals. Saffron + ISO group showed remarkably decreased intensity of tissue destruction and significantly decreased serum levels of heart troponin I, when compared to ISO group. The level of glutathione peroxidase activity in Saffron + ISO animals did not have significant decline compared to saffron alone. These results suggest the protective role of saffron on ischemic hearts by biochemical and histopathological findings.

Kidney damage from antibiotic use
Effect of crocus sativus on gentamicin induced nephrotoxicity.
Biol Res. 2010. Department of Nutrition, Iran University of Medical Sciences, Tehran, Iran.
Our results suggest that saffron treatment reduces gentamicin-induced nephrotoxicity and this effect seems to be dose dependent.

Lung cancer
Appl Biochem Biotechnol. 2010.
Suppression of Pulmonary Tumor Promotion and Induction of Apoptosis by Crocus sativus. Extraction. Samarghandian S, Tavakkol Afshari J, Davoodi S. Department of Physiology, School of Medicine, Mashhad University Medical Sciences, Mashhad, Iran,
Saffron is the raw material for one of the most expensive spice in the world, and it has been used in folk medicine for centuries. We investigated the potential of the ethanolic extract of saffron to induce cytotoxic and apoptosis effects in carcinomic human alveolar basal epithelial cells (A549), a commonly used cell culture system for in vitro studies on lung cancer. We found that saffron could cause cell death in the A549 cells, in which apoptosis plays an important role. It could be considered as a promising chemotherapeutic agent in lung cancer treatment in future.

Macular degeneration
There has been one study with saffron lasting 3 months with some improvement noted. However, other carotenoids, such as lutein and zeaxanthin, are likely to have more benefits.

Invest Ophthalmol Vis Sci. 2010. Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Dipartimento di Scienze Oftalmologiche e Otorinolaringologiche, Rome, Italy.
Twenty-five patients with AMD were randomly assigned to oral saffron 20 mg/d or placebo supplementation over a 3-month period and then reverted to placebo or saffron for a further 3 months. Focal electroretinograms (fERGs) and clinical findings were recorded at baseline and after 3 months of saffron or placebo supplementation. The results indicate that short-term saffron supplementation improves retinal flicker sensitivity in early AMD. Although the results must be further replicated and the clinical significance is yet to be evaluated, they provide important clues that nutritional carotenoids may affect AMD in novel and unexpected ways, possibly beyond their antioxidant properties.

Memory
I am a MD PhD and have my undergraduate training in nutrition. I found your web site as I was searching the internet for the impact of neurotransmitters on human behavior, and mood. Thank you very much for all the good information you have provided and the references to the research articles related to each topic. I am particularly interested in learning about the effects of saffron on memory and dementia. In one of the meetings in regards to Alzheimer's disease one of the participants mentioned that a combination of sesame seeds and saffron has been used as a home remedy it improve memory among Persians in Tehran.
   There have been a few animal studies that show promise in terms of cognitive enhancement, but, as of 2011, I have not seen human trials.

The involvement of water-soluble carotenoids, crocins, as the main and active components of Crocus sativus L. extract in learning and memory processes has been proposed. In the present study, the effect of crocins on sporadic Alzheimer's disease induced by intracerebroventricular (icv) streptozocin (STZ) in male rats was investigated. Our results demonstrate the effectiveness of crocin (30 mg/kg) in antagonizing the cognitive deficits caused by STZ-icv in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease. Iran Biomed J. 2010 Jan-Apr. Effects of active constituents of Crocus sativus, crocin on streptozocin-induced model of sporadic Alzheimer's disease in male rats. Khalili M, Hamzeh F. Dept. of Physiology, Shahed University of Medical Sciences, Tehran, Iran.

Crocus sativus L. is a plant cultivated in various parts of the world. Its involvement in learning and memory processes has been proposed. Crocins are water-soluble carotenoids and are among the active components of C. sativus. The present study was designed to investigate in the rat the effects of crocins on recognition and spatial memory. The present results support and extend the enhancing effects of crocins on memory and, then, to our knowledge, for the first time, demonstrate its implication in the mechanisms underlying recognition and spatial memory. Behav Brain Res. 2007 Nov. Effects of the active constituents of Crocus sativus L., crocins on recognition and spatial rats' memory. Pitsikas N, Zisopoulou S, Tarantilis PA, Kanakis CD. Department of Pharmacology, School of Medicine, University of Thessaly, Larissa, Greece.
  
PMS
Dr. M. Agha-Hosseini and colleagues at Tehran University of Medical Sciences randomly assigned 50 women with symptoms of PMS to take either saffron capsules or a placebo twice a day over two menstrual cycles. The majority of the women on saffron capsules reported fewer PMS symptoms. Those taking saffron capsules had improved mood. BJOG, 2008.

How long does it take to see the results of saffron herb for anxiety and pms relief?
    I have not used this herb in clinical practice yet so I don't know how quickly it works and how effective it is.

Snacking and weight loss
Q.
I'm working on an article in a women's magazine about Satiereal saffron extract supplements. I was hoping I could get your expert opinion on how Satiereal can help curb cravings and excessive snacking.  
   A. I have seen one human study on this topic. In my opinion, I would prefer to see many more studies from multiple centers that confirm this initial finding before making recommendations to general public through a TV program. Plus, I do not know how independent the research team was from the company that supplied the product. It is important that several independent research centers confirm these initial findings, and to have a better understanding of potential risks and interactions with medications, before promoting this product widely to millions of TV viewers as I understand Dr. Oz has done.

Nutr Res. 2010 May. Satiereal, a Crocus sativus extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy women. Biomedical and Global Clinical Solutions, Parc Technologique du Canal, Ramonville Saint-Agne, France. We hypothesized that oral supplementation with Satiereal (Inoreal Ltd, Plerin, France), a novel extract of saffron stigma, may reduce snacking and enhance satiety through its suggested mood-improving effect, and thus contribute to weight loss. 60 Healthy, mildly overweight women participated in this randomized, placebo-controlled, double-blind study that evaluated the efficacy of Satiereal supplementation on body weight changes over an 8-week period. Twice a day, enrolled subjects consumed 1 capsule of Satiereal (176.5 mg extract per day or a matching placebo. Caloric intake was left unrestricted during the study. At baseline, both groups were homogeneous for age, body weight, and snacking frequency. Satiereal caused a reduction in snacking and a greater body weight reduction than placebo after 8 weeks.

How saffron works
Saffron spice might influence mood by influencing serotonin activity in the brain.

Emails received
I have seen a few articles on saffron helping folks with age related macular degeneration and just sight in general. Do you have any studies or info on this?
    I have not seen human clinical trials regarding the use of this spice for age related macular degeneration.

I wanted to let you know that at a store I saw an extract of Saffron 0.3% with 0.3% Safranal & 0.3% Crocin at a health food store.
   I am aware of one supplier that has sells saffron extract titrated at 2% safranal.