: An Impressive Range of Health Benefits from this Age-old – Kerry Bone

Saffron ( sativus) is the world’s most More positive news in expensive spice. That’s because it is still hand- harvested from the beautiful lilac-purple Since that article, many more trials of a small low-growing crocus. Each demonstrating a diverse range of health yields only three small threadlike benefits for saffron have been published. In stigmas that are bright -red and form the case of depression, there have been two the spice as we know it. This intense orange- new trials that looked at the effect of red colour comes from an extraordinarily high combining saffron with in content of molecules, mainly the depressed patients suffering from sexual crocins. When we consume saffron, the dysfunction as a side effect of the drug. The crocins release the carotenoid into first trial tested the influence of saffron on our bloodstream. In a sense, the saffron fluoxetine-induced sexual dysfunction in vi is a super-concentrated source of men. This was a 4-week randomised, double highly bioavailable , with health- blind, placebo-controlled study. Thirty-six promoting properties similar to, but unique married male patients with major depressive from, other key carotenoids such as disorder whose depressive symptoms had astaxanthin and lutein. been stabilised on fluoxetine and had subjective complaints of sexual impairment entered the study. The patients were I first wrote about the new clinical research randomly assigned to saffron extract (15 mg on saffron in this journal five years ago. In twice per day) or placebo for 4 weeks. The that article I outlined the results of 5 clinical International Index of Erectile Function scale trials where saffron was shown to be more was used to assess sexual function at baseline effective than placebo at alleviating and weeks 2 and 4. i,ii depression and just as active as conventional drugs, including fluoxetine (Prozac).iii,iv,v Thirty patients finished the study. Baseline characteristics as well as baseline and final depressive symptoms scores were similar between the two groups. By week 4, saffron

For the education of healthcare professionals only 1 resulted in significantly greater improvement pathways influenced by saffron. It appears on in erectile function, intercourse satisfaction current evidence to have minimal impact on domains and total scores than the placebo serotonin metabolism. Rather research group. Nine patients (60%) in the saffron attention is focused on the impact of its group and one patient (7%) in the placebo on NMDA (N-methyl-D- group achieved normal erectile function aspartate) and Sigma-1 receptors in the (score >25 on erectile function domain) at the brain.viii,ix Saffron extracts and trans-crocetin end of the study. The frequency of side effects demonstrated a clear binding capacity at the was similar between the two groups. (PCP) binding site of the NMDA receptor and at the Sigma-1 receptor,

whereas the crocins were not effective.viii The In the second trial, the impact of saffron on authors suggested that it can be assumed that fluoxetine-induced sexual dysfunction was the binding of saffron and crocetin to the assessed in women.vii Using a similar trial NMDA receptor will lead to an antagonistic design to above, 38 women with major effect, because agents that attach to the PCP depression who were stabilised on fluoxetine binding site block the channel pore of the 40 mg/day for a minimum of 6 weeks and had NMDA receptor system. This could explain the experienced subjective feelings of sexual antidepressant and other central nervous dysfunction entered the study. The patients system effects of saffron. Moreover, excess were randomly assigned to saffron extract neuron excitation caused by activating these (30 mg/daily) or placebo for 4 weeks. receptors can lead to neuronal dysfunction or Measurement was performed at baseline, even cell death (excitotoxicity). , a week 2 and week 4 using the Female Sexual drug used to treat Alzheimer’s disease is an Function Index (FSFI). Side effects were NMDA receptor channel blocker. Many systematically recorded. central and peripheral effects are modulated by the mysterious Sigma-1 receptors, including possible activity in clinical Thirty-four women had at least one post- depression and schizophrenia and for viii baseline measurement and completed the . study. At the end of the fourth week, patients in the saffron group experienced significantly greater improvement in total FSFI, and for the Follow-up work by the same research centre arousal, lubrication and pain domains of the confirmed these results for an extract of FSFI. Frequency of side effects was similar saffron and trans-crocetin on postsynaptic between the two groups. NMDA receptors and demonstrated an inhibitory effect for saffron extract only on postsynaptic kainate receptors.ix Other Safe to combine with conventional researchers have found that saffron extract and (a monoterpenoid antidepressants component of saffron) interact with the These new trials highlight an important GABAA receptor complex, thereby mediating advantage of saffron in depression; it appears anticonvulsant and potential anxiolytic to be quite safe to add to conventional activities.x,xi antidepressant drugs. To date, there is only preliminary information as to the neurological

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The important message from the mechanistic we can all benefit from. Based on preclinical studies is that saffron is highly unlikely to and clinical studies reporting positive anti- interact adversely with modern antidepressant anxiety and antidepressant effects for saffron, drugs, especially selective serotonin re-uptake a team of French scientists wondered if the inhibitors (SSRIs). Specifically, there is little might balance mood and reduce suggestion from current research that the herb snacking and the desire to eat, making it a substantially influences serotonin metabolism. suitable supplement for people undertaking weight loss programs. To test this hypothesis

a placebo-controlled, randomised clinical trial Saffron benefits the brain and was done using a proprietary extract of saffron stigma in 60 healthy women who were women’s health mildly overweight (body mass index (BMI) 25 xvi Preliminary trials of saffron’s impact on brain to 28 kg/m2). Over 8 weeks the participants function are also promising. In a comparative consumed one capsule of saffron extract trial in 54 people with moderate Alzheimer’s (exact details not provided, but probably disease, saffron stigma extract (30 mg/day) corresponding to 100 to 150 mg of original was as effective as the modern drug stigma) twice a day or a matching placebo. (10 mg/day) on cognitive functioning over 22 Caloric intake was left unrestricted during the weeks.xii It was also more effective than study. placebo at the same dose in 46 patients with mild to moderate Alzheimer’s over 16 weeks.xiii Saffron treatment resulted in a significantly greater body weight reduction than placebo. But the main result was a striking reduction in The impact of saffron extends to women’s weekly snacking events with saffron (reduced health. Saffron stigma (30 mg/day of extract) from 6.1 to 2.9) compared to the placebo over 2 menstrual cycles significantly relieved group (reduced from 6.3 to 4.5). This was symptoms of (PMS) in evaluated only in those women who exhibited a double blind, placebo-controlled clinical ‘snacking’ behaviour (16 in each trial group). trial.xiv Patients on saffron also had Saffron also scored significantly higher for the significantly better depression scores. A questions: “Did you feel less hungry before combination of saffron, and meals?” and “Did the product help reduce relieved dysmenorrhea (period pain) your need for snacking between meals?”. symptoms in a 3-arm placebo-controlled trial There were no differences between the involving 180 women.xv The saffron and placebo groups in terms of combination actually worked better than tolerance, and the noted side effects were mefenamic acid, a commonly used drug for mild and transient. this problem. A super-carotenoid for the eyes

A new development in helping Finally, as you might expect given its high weight loss levels of carotenoids, saffron is showing promise in eye health, especially for the retina. Saffron seems to be a valuable discovery to The influence of saffron on retinal health was reduce food craving and snacking, something first clinically investigated by researchers from

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Italy and Australia in a double blind trial that nine patients with early AMD were recruited was reported in December 2010. Twenty-five from an outpatient eye clinic.xix As was the patients with early age-related macular case with the previous study, the patients degeneration (AMD) were randomly divided were not taking known to affect into two groups, either taking saffron or macular function or to interfere with placebo for a period of 90 days. The groups carotenoid absorption. They received ongoing were then crossed over to receive the other treatment with the same saffron tablet treatment, with a washout period of 15 days described above (providing 20 mg/day between them.xvii Patients took saffron at a powdered dried stigma). Two patients daily dose of 20 mg of powdered dried stigma. completed 6 only months of treatment, with 7 Very low, sub-therapeutic doses of , and 20 patients completing 12 and 15 months. and DHA were also present in the tablets. Compared to the start of the trial, after 3

months of treatment retinal function improved Retinal flicker sensitivity was assessed. Flicker and the mean visual acuity improved by two sensitivity, evaluated by the focal electro- Snellen lines with saffron. These results were retinogram, provides an estimation of the statistically significant and remained stable macular dysfunction in age-related macular over the treatment period (6 to 15 months). In degeneration, because it analyses the addition, all the patients volunteered an functioning of the cones in the retina. From improvement in their quality of vision, most each patient, one eye, typically the eye with commonly reporting an improvement in the best visual acuity (sharpness of vision), was contrast and colour perception, reading ability selected and designated as the study eye. and vision in low light. Perhaps because of these improvements, everyone indicated an

enhancement in their quality of life. Daily intake of saffron for 90 days was associated with a significant improvement in retinal function. No changes were observed in How much to take? the same patients after administration of placebo. There was also a small but statistically As mentioned above, saffron is very expensive, significant increase in average visual acuity but fortunately it is so highly concentrated in after taking saffron.xvii (A calibrated standard carotenoids that effective clinical doses are Snellen chart was used to evaluate visual not high, helping to keep the cost down. The acuity, and means for example, that a number trials in AMD used just 20 mg of dried stigma of patients were able to read one or two lines per day. Most of the other trials used on the eye chart that were smaller than the 30 mg/day of a concentrated extract, probably lines they could read before treatment with corresponding to around 180 mg/day of saffron.xviii) stigma.

The same research team conducted further Acknowledgment research with the aim of finding out whether Thanks to Michelle Morgan for contributing to the benefits observed from saffron treatment this review. would extend over a longer duration. Twenty-

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References

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xix Piccardi M, Marangoni D, Minnella AM et xviii Professor Silvia Bisti. Researchers strike al. A longitudinal follow-up study of saffron gold - saffron found to help vision loss in supplementation in early age-related elderly. The University of Sydney News, 5 macular degeneration: sustained benefits to February 2010. central retinal function. Evid Based http://sydney.edu.au/news/84.html?newsstor Complement Alternat Med 2012; 2012: yid=4452. Accessed January 2013. 429124

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