Saffron Research

July 23, 2010 Written by JP       [Font too small?]

Foods and natural remedies are frequently classified according to their most prominent features. Echinacea flowers and roots are generally thought of as immune boosters. Ginkgo biloba leaves are widely regarded as memory enhancers. And saffron stigmas are associated with the deep red color they impart to countless Eurasian dishes. Of the three examples, saffron is probably the least familiar in terms of medicinal potential. However, that is likely to change thanks to recent studies that are beginning to reveal new talents for this ancient spice.

In May 2010, a small trial was published in the journal of Nutrition Research. It initially caught my attention while I was researching the topic of snacking. In the study, a natural medicine by the name of Satiereal was under investigation as a satiety enhancer. The active ingredient in Satiereal is Crocus sativus or saffron. Why test the hunger suppressing effects of saffron? The authors of the study report that saffron appears to possess a “mood-improving effect” which they hypothesized would result in reduced appetite and snacking.

To test this theory, 60 overweight women were enrolled in an 8 week placebo-controlled trial. Twice-daily, the women were provided with 1 capsule of Satiereal (176.5 mg/day) or an inactive placebo. All of the test subjects were asked to eat an unrestricted, normal diet. After two months, the participants using the saffron extract reported a decline in snacking and lost more weight than the control group. None of the women dropped out of the study due to side effects. (1)

By most accounts, the best selling natural mood enhancer is St. John’s wort and with good reason. It’s no exaggeration to say that hundreds of published studies attest to the psychoactive properties of this medicinal herb. Saffron can’t hold a candle to the sheer volume of research conducted on St. John’s wort. But the studies that have been published illustrate real promise in the field of mood disorders. (2)

Several of the more interesting trials involving saffron have compared it to conventional antidepressant medications: fluoxetine (Prozac) and imipramine (Tofranil). What’s more, all of the head-to-head studies utilized the preferred double-blind, randomized design which tends to yield the most reliable results.

  • An 8 week trial involving 40 clinically depressed patients found that 30 mg/day of saffron extract was equally effective as 20 mg of fluoxetine. In addition, both treatment groups demonstrated an identical remission rate of 25%. (3)
  • A 6 week trial also compared a “hydro-alcoholic” saffron extract with fluoxetine/Prozac. Once again, 40 patients with major depression participated in the experiment. The efficacy of saffron was found to be “similar to fluoxetine in the treatment of mild to moderate depression“. No significant differences in side effects were noted between the two treatments. (4)
  • The September 2004 issue of the journal BMC Complementary and Alternative Medicine matched saffron vs. imipramine. Over the course of 6 weeks, 30 patients with clinical depression were asked to take either 30 mg/day of saffron extract or 100 mg/day of imipramine. Both treatments provided comparable symptomatic relief. However, the saffron extract was less likely to cause select adverse reactions – dry mouth and sedation. (5)

Two other trials from 2005 and 2006 examined the efficacy and safety of saffron vs. a placebo. In both instances, the depressed patients receiving saffron demonstrated better outcomes as assessed by improvements on the Hamilton Depression Rating Scale. The side effect profiles were deemed equivalent. (6,7)

Saffron May Reduce the Severity of PMS Symptoms
Source: BJOG. 2008 Mar;115(4):515-9. (link)

Stress related overeating and snacking are hallmarks of the current obesity epidemic. Preliminary experiments in animal models point to an anxiolytic effect of saffron and its components. The first observation made was that a water-based extract of saffron reduced anxiety and increased total sleep time in mice. Further testing in rats identified two phytochemicals contained in saffron, crocin and safranal, which appear to be partially responsible for the relaxing and sleep enhancing effects. (8,9)

Other mind-body conditions including premenstrual syndrome (PMS) may also respond to saffron therapy. The administration of 30 mg/day of saffron over the course of two menstrual cycles significantly improved PMS discomfort in a group of women aged 20 to 45. The symptomatic relief was evidenced via changes in two objective measures: a Daily Symptom Report and the Hamilton Depression Rating Scale. The authors of the study urge further investigation into the applicability of saffron as an alternative treatment for PMS. However, they also emphasize the need to firmly establish the safety of chronic saffron use. (10)

The issue of safety cannot be overemphasized. Thus far, the majority of research published on saffron has reported an acceptable safety profile. But this appears to be mostly based on the subjective responses of the study volunteers. By that, I mean reports of adverse reactions such as dry mouth, headaches, nausea and the like. Unfortunately, blood tests and other laboratory indicators were not regularly employed in the studies I reviewed. The one exception is a safety trial that involved 30 men and women who were given a placebo or 200 mg to 400 mg of saffron daily for one week. Various blood tests, blood pressure and electrocardiographic parameters were reviewed in the analysis. Both dosages of saffron exhibited some potentially positive activity – improvements in mood and significantly lower arterial and systolic blood pressure. However, there were also a few distressing signs: a slight reduction in red blood cells, hematocrit, hemoglobin and platelets. There were also indications of possible kidney stress as evidenced by increased blood urea nitrogen and creatinine. The conclusion of the experiment states that “these alterations were in normal ranges and they were not important clinically”. The higher dosages used in the safety study should also be taken into account. Nonetheless, this an important reminder that even natural supplements need to be used cautiously and evaluated objectively. (11)

Be well!

JP

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12 Comments & Updates to “Saffron Research”

  1. Nina K. Says:

    Good Morning, JP :-)

    very interessting article. I would use saffron more often but its a very expensive spice. But we love it, not often but then total ;-)

    Wish you and yours a very nice weekend ☼☼☼
    Nina K.

  2. JP Says:

    Good day and thank you, Nina! :)

    I wish you and husband the same!

    Be well!

    JP

  3. Mark S Says:

    Another eye opener. I know it’s a worthwhile read when it makes me google :) . The research so far seems to show very positive results.

    I think it deserves a “Healthy Fellow” recipe of the week.

  4. JP Says:

    Thank you, Mark! :)

    I’ll get to work on that saffron dish! But next up in the recipe department – ceviche! Just tried it out tonight and I think it’s a winner.

    Be well!

    JP

  5. Susana Curatolo Says:

    Could you please explain the medicinal effect of the crocus sativus combined with pipe nigra, and in particular the apetite suppressant effect-is it less than just crocus sativus by itself or is it enhanced?

  6. Susana Curatolo Says:

    typo–PIPER NIGRUM

  7. JP Says:

    Hi Susana,

    Black pepper extract, standardized for piperine content, are sometimes combined with herbal extracts to enhance bioavailability. However, in this case, black pepper may also contribute to weight management goals – though the research for this is preliminary.

    https://www.jstage.jst.go.jp/article/bbb/74/8/74_100117/_article

    http://www.bioperine.com/about-bioperine.html

    Be well!

    JP

  8. JP Says:

    Update: fluoxetine = Prozac

    http://www.jad-journal.com/article/S0165-0327%2813%2900797-0/abstract

    J Affect Disord. 2014 Feb;155:216-22. doi: 10.1016/j.jad.2013.11.003. Epub 2013 Nov 16.

    A randomized, double-blind, clinical trial comparing the efficacy and safety of Crocus sativus L. with fluoxetine for improving mild to moderate depression in post percutaneous coronary intervention patients.

    OBJECTIVE:

    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).

    METHODS:

    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.

    RESULTS:

    By the study endpoint, no significant difference was detected between two groups in reduction of HDRS scores (P=0.62). Remission and response rates were not significantly different as well (P=1.00 and P=0.67; respectively). There was no significant difference between two groups in the frequency of adverse events during this trial.

    LIMITATIONS:

    Relatively small sample size and short observational period were the major limitations of this study.

    CONCLUSION:

    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.

    Be well!

    JP

  9. JP Says:

    Update:

    http://onlinelibrary.wiley.com/doi/10.1002/hup.2282/full

    Hum Psychopharmacol. 2013 Jan;28(1):54-60.

    Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study.

    OBJECTIVE:

    Saffron (Crocus sativus L.) has shown beneficial aphrodisiac effects in some animal and human studies. The aim of the present study was to assess the safety and efficacy of saffron on selective serotonin reuptake inhibitor-induced sexual dysfunction in women.

    METHODS:

    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. Measurement was performed at baseline, week 2, and week 4 using the Female Sexual Function Index (FSFI). Side effects were systematically recorded.

    RESULTS:

    Thirty-four women had at least one post-baseline measurement and completed the study. Two-factor repeated measure analysis of variance showed significant effect of time × treatment interaction [Greenhouse-Geisser's corrected: F(1.580, 50.567) = 5.366, p = 0.012] and treatment for FSFI total score [F(1, 32) = 4.243, p = 0.048]. At the end of the fourth week, patients in the saffron group had experienced significantly more improvement in total FSFI (p < 0.001), arousal (p = 0.028), lubrication (p = 0.035), and pain (p = 0.016) domains of FSFI but not in desire (p = 0.196), satisfaction (p = 0.206), and orgasm (p = 0.354) domains. Frequency of side effects was similar between the two groups.

    CONCLUSIONS:

    It seems saffron may safely and effectively improve some of the fluoxetine-induced sexual problems including arousal, lubrication, and pain.

    Be well!

    JP

  10. JP Says:

    Update:

    http://link.springer.com/article/10.1007%2Fs00213-012-2729-6

    Psychopharmacology (Berl). 2012 Oct;223(4):381-8.

    Effect of saffron on fluoxetine-induced sexual impairment in men: randomized double-blind placebo-controlled trial.

    RATIONALE:

    Saffron (Crocus sativus L.) has shown aphrodisiac effects in some animal and human studies.

    OBJECTIVES:

    To assess the efficacy and tolerability of saffron in fluoxetine-related sexual dysfunction.

    METHODS:

    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.

    RESULTS:

    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 [Greenhouse-Geisser-corrected, F (1.444, 40.434) = 6.154, P = 0.009]. By week 4, saffron resulted in significantly greater improvement in erectile function (P <  0.001) and intercourse satisfaction domains (P = 0.001), and total scores (P < 0.001) than the placebo group. Effect of saffron did not differ significantly from that of placebo in orgasmic function (P = 0.095), overall satisfaction (P = 0.334), and sexual desire (P = 0.517) 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 (P value of Fisher’s exact test = 0.005). Frequency of side effects were similar between the two groups.

    CONCLUSIONS:

    Saffron is a tolerable and efficacious treatment for fluoxetine-related erectile dysfunction.

    Be well!

    JP

  11. JP Says:

    Update: Saffron may also be of value for a variety of age-related eye conditions …

    http://www.biomedcentral.com/1472-6882/14/399

    BMC Complement Altern Med. 2014 Oct 15;14:399.

    The ocular hypotensive effect of saffron extract in primary open angle glaucoma: a pilot study.

    BACKGROUND:

    The progressive nature of glaucoma and its growing incidence make its therapy an important target for research. The role of oxidative damage in the pathogenesis of glaucoma makes antioxidants such as saffron extract an attractive target for potential clinical use. Herein, we evaluate the effect of aqueous saffron extract on intraocular pressure (IOP) in eyes with primary open-angle glaucoma (POAG).

    METHODS:

    Thirty-four eyes of 34 clinically stable POAG patients receiving treatment with timolol and dorzolamide eye drops were enrolled in this prospective, comparative, randomized interventional pilot study. Eligible subjects were randomized to receive 30 mg/day aqueous saffron extract orally (17 subjects, 17 eyes) or placebo (17 subjects, 17 eyes) for one month as an adjunct to timolol and dorzolamide. Following treatment, both study groups entered a one-month wash-out period. The main outcome measure was IOP during treatment and after the wash-out period.

    RESULTS:

    Mean baseline IOP was 12.9 ± 3.7 versus 14.0 ± 2.5 mmHg in the saffron and control groups, respectively (p = 0.31). After three weeks of treatment, IOP was significantly decreased to 10.9 ± 3.3 mmHg in the saffron group as compared to 13.5 ± 2.3 mmHg in the control group (p = 0.013). At four weeks, IOP was still significantly lower in the saffron group (10.6 ± 3.0 versus 13.8 ± 2.2 mmHg, p = 0.001). At the end of the wash-out period, IOP was 12.9 ± 3.0 in the saffron group versus 14.2 ± 2.0 mmHg in the control group (p = 0.175). None of the patients experienced side effects during the study and wash-out period.

    CONCLUSIONS:

    Oral aqueous saffron extract seems to exert an ocular hypotensive effect in primary open-angle glaucoma. This effect became evident after three weeks of therapy.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850693/

    J Transl Med. 2013 Sep 25;11:228.

    Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report.

    BACKGROUND:

    To determine whether the functional effects of oral supplementation with Saffron, a natural compound that proved to be neuroprotective in early age-related macular degeneration, are influenced by complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk genotypes.

    METHODS:

    Thirty-three early AMD patients, screened for CFH (rs1061170) and ARMS2 (rs10490924) polymorphisms and receiving Saffron oral supplementation (20 mg/day) over an average period of treatment of 11 months (range, 6-12), were longitudinally evaluated by clinical examination and focal electroretinogram (fERG)-derived macular (18°) flicker sensitivity estimate. fERG amplitude and macular sensitivity, the reciprocal value of the estimated fERG amplitude threshold, were the main outcome measures.

    RESULTS:

    After three months of supplementation, mean fERG amplitude and fERG sensitivity improved significantly when compared to baseline values (p < 0.01). These changes were stable throughout the follow-up period. No significant differences in clinical and fERG improvements were observed across different CFH or ARMS2 genotypes.

    CONCLUSIONS:

    The present results indicate that the functional effect of Saffron supplementation in individual AMD patients is not related to the major risk genotypes of disease.

    http://www.iovs.org/content/51/12/6118.long

    Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6118-24.

    Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration.

    PURPOSE:

    To evaluate the functional effect of short-term supplementation of saffron, a spice containing the antioxidant carotenoids crocin and crocetin, in early age-related macular degeneration (AMD).

    METHODS:

    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. fERGs were recorded in response to a sinusoidally modulated (41 Hz), uniform field presented to the macular region (18°) at different modulations between 16.5% and 93.5%. Main outcome measures were fERG amplitude (in microvolts), phase (in degrees), and modulation thresholds.

    RESULTS:

    After saffron, patients’ fERGs were increased in amplitude, compared with either baseline or values found after placebo supplementation (mean change after saffron, 0.25 log μV; mean change after placebo, -0.003 log μV; P < 0.01). fERG thresholds were decreased after saffron supplementation but not placebo, compared with baseline (mean change after saffron, -0.26 log units; mean change after placebo, 0.0003 log units).

    CONCLUSIONS:

    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.

    Be well!

    JP

  12. JP Says:

    Update 05/08/15:

    http://chp.sagepub.com/content/early/2015/05/03/2156587215583756.abstract

    Effects of a Topical Saffron (Crocus sativus L) Gel on Erectile Dysfunction in Diabetics

    A Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Trial

    Erectile dysfunction is a man’s persistent or recurrent inability to achieve and maintain erection for a satisfactory sexual relationship. As diabetes is a major risk factor for erectile dysfunction, the prevalence of erectile dysfunction among diabetic men has been reported as 35% to 90%. This randomized, parallel-group, double-blind, placebo-controlled trial investigated the effects of a topical saffron (Crocus sativus L) gel on erectile dysfunction in diabetic men. Patients were randomly allocated to 2 equal groups (with 25 patients each). The intervention group was treated with topical saffron, and the control received a similar treatment with placebo. The 2 groups were assessed using the International Index of Erectile Function Questionnaire before the intervention and 1 month after the intervention. Compared to placebo, the prepared saffron gel could significantly improve erectile dysfunction in diabetic patients (P < .001). This preliminary evidence suggests that saffron can be considered as a treatment option for diabetic men with erectile dysfunction.

    Be well!

    JP

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