By Kerry Bone
Saffron (Crocus sativus) is the world’s most expensive spice. That’s because it is still hand-harvested from the beautiful lilac-purple flowers of a small low-growing crocus. Each flower yields only three small threadlike stigmas that are bright orange-red and form the spice as we know it. This intense orange-red color comes from an extraordinarily high content of carotenoid molecules, mainly the crocins. When we consume saffron, the crocins release the carotenoid crocetin into our bloodstream. The saffron stigma is a super-concentrated source of highly bioavailable carotenoids, with health-promoting properties similar to, but unique from, other key carotenoids such as astaxanthin and lutein.
I first wrote about the new clinical research on saffron in this column five years ago (see N&H 15(2) March 2008). In that article I outlined the results of five clinical trials where saffron was shown to be more effective than placebo at alleviating depression1,2 and just as active as conventional drugs, including fluoxetine (Prozac).3,4,5
Saffron successfully relieved sexual dysfunction
Since that article, many more published trials have demonstrated that saffron has a wide range of health benefits. In the case of depression, there have been two new trials that looked at the effect of using saffron in depressed patients suffering from sexual dysfunction as a side effect of the drug fluoxetine. The first trial tested the influence of saffron on fluoxetine-induced sexual dysfunction in men.6 This was a four-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 extract (15 mg twice per day) or placebo for four weeks. The International Index of Erectile Function scale was used to assess sexual function at baseline and weeks 2 and 4.
Improved erectile function and intercourse satisfaction
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 resulted in significant improvement in erectile function, intercourse satisfaction, and total scores than the placebo group. 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) by the end of the study. The frequency of side effects was similar between the two groups.
In the second trial, the impact of saffron on fluoxetine-induced sexual dysfunction was assessed in women.7 Using a similar trial design to above, 38 women with major depression who were stabilized on fluoxetine 40 mg/day for a minimum of six weeks and had experienced subjective feelings of sexual dysfunction entered the study. The patients were randomly assigned to saffron extract (30 mg/daily) or placebo for four weeks. Measurement was performed at baseline, week 2 and week 4 using the Female Sexual Function Index (FSFI). Side effects were systematically recorded.
Improved sexual function and arousal in women
Thirty-four women had at least one post-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 arousal, lubrication, and pain domains of the FSFI. Frequency of side effects was similar between the two groups.
These new trials highlight an important advantage of saffron in depression, it appears to be quite safe to add to conventional antidepressant drugs. For further information on this topic please see the sidebar on page 4—I have separated this discussion from the main article as it is quite complex and only suitable for the technical reader.
The take away from these studies is that saffron is highly unlikely to adversely interact with modern antidepressant drugs, especially selective serotonin re-uptake inhibitors (SSRIs). Specifically, there’s absolutely no suggestion from current research that the herb substantially influences serotonin metabolism.
In next month’s column I will discuss exciting new discoveries for saffron including its ability to help with weight loss, and improve brain, eye, and women’s health.
Saffron and brain chemistry
To date, there is only preliminary information as to the neurological pathways influenced by saffron. It appears on current evidence to have minimal impact on serotonin metabolism. Rather research attention is focused on the impact of its phytochemicals on NMDA (N-methyl-D-aspartate) and Sigma-1 receptors in the brain.8,9 Saffron extracts and trans-crocetin demonstrated a clear binding capacity at the phencyclidine (PCP) binding site of the NMDA receptor and at the Sigma-1 receptor, whereas the crocins were not effective.8 The authors suggested that it can be assumed that the binding of saffron and crocetin to the NMDA receptor will lead to an antagonistic effect, because agents that attach to the PCP binding site block the channel pore of the NMDA receptor system. This could explain the antidepressant and other central nervous system effects of saffron. Moreover, excess neuron excitation caused by activating these receptors can lead to neuronal dysfunction or even cell death (excitotoxicity). Memantine, a drug used to treat Alzheimer’s disease is an NMDA receptor channel blocker. Many central and peripheral effects are modulated by the mysterious Sigma-1 receptors, including possible activity in clinical depression and schizophrenia and for neuroprotection.8
Follow-up work by the same research centre confirmed these results for an extract of saffron and trans-crocetin on postsynaptic NMDA receptors and also demonstrated an inhibitory effect for saffron extract only on postsynaptic kainate receptors.9 Other researchers have found that saffron extract and safranal (a monoterpenoid essential oil component of saffron) interact with the GABAA receptor complex, thereby mediating anticonvulsant and potential anxiolytic activities.10,11
