Saffron for Depression: Science, Studies, and Recipes

We will review the RCT data, meta-analysis, and biological mechanisms showing that saffron can act as an antidepressant and alleviate anxiety. And you'll get therapeutically dosed recipes as well!

What if I told you that a common kitchen spice could work as well as prescription antidepressants?

Sounds too good to be true, right? Well, the science on saffron is shockingly strong. In this letter, I’ll walk you through some mind-blowing human clinical studies, explain the neuroscience, and show you how this golden spice might be the next big thing in mental health—plus, for premium subscribers, I’ll even give you delicious AND therapeutically dosed recipes to try at home!

Background on Saffron

The name derives from the Persian ‘za'farān’ meaning “gold strung,” referring to the golden stamens of the flower, which is basically a flower’s... umm... let’s say, male reproductive organ. So, you know, handle with care.

Now, as you may know, saffron is the world’s most expensive spice, at around $5,000 per pound. But before you start selling your belongings to afford it, let me reassure you—it costs less than a cup of coffee per day at therapeutic doses. But more on dosing math later.

Anyway, saffron has historically been used in traditional Persian medicine for depression, but rigorous human studies on its mental health benefits started in the early 2000s, which brings us to the first of our studies…

Saffron vs SSRI - Randomized Controlled Trial 1

In this 2005 double-blind randomized controlled trial comparing 6 weeks of saffron supplementation to fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor (SSRI) sold under the brand name Prozac, in 38 patients.

Impressively, the saffron capsule, dosed at 30 mg/day, performed equal to the fluoxetine. You can see the results over 6 weeks here, with the Hamilton Rating Scale for Depression dropping in lock step between the treatments.

The absolute decrease in both treatments was >12.

Now, what does that number mean?

Well, in clinical trials, there’s a key distinction between a “statistically significant” difference and a “clinically significant” difference.

• A “statistically significant” difference means there was a detectable numeric difference, as in over time or between groups.

• Conversely, a “clinically significant” difference means that size of the change was detectable and meaningful for the patient.

Now while it’s somewhat arbitrary, a clinically meaningful change in this depression scale is ~5 points, which means a ~12-point drop is impressive and is clinically substantial!

And, quickly, before I move on to the next study, I’ll point out that one presumed advantage of saffron is that it could have fewer side effects than prescription medications. In this first small pilot trial, no statistical difference was detected between the groups, but that may be because the trial was too small and underpowered to detect the differences. If you look at the actual numbers, shown here, I think I see a clear trend to lower side effects in the saffron group. Do you?

Saffron vs Placebo - Randomized Controlled Trial 2

Now, moving on to our second double-blinded randomized controlled trial because in science, we like to reproduce our results!

This trial, however, compared 50 mg twice per day of saffron to a placebo control for 12 weeks.

So, whereas in the last trial it was good to see saffron perform equal to the control, an SSRI, here we’d hope to see saffron perform better than the control, a placebo. Indeed, in this trial including 54 completing participants, the saffron improved scores on the Beck Depression Inventory and Beck Anxiety Inventory significantly more than the placebo control.

Saffron for Mental Health - Meta-Analysis

Now, rather than working through another 20+ studies, I want to read you some excerpts from a meta-analysis of 23 randomized controlled trials conducted on saffron for mental health, including depression and anxiety:

• [M] eta-analysis found a significant and large positive effect size for saffron reducing symptoms of depression in comparison with placebo.

• When compared with antidepressants medications, there was no significant difference between saffron and medications.

• Meta-analysis of studies that investigated the effect of saffron as an adjunct to pharmacotherapy reported a large significant benefit from saffron supplementation.

In simpler terms:

• Saffron’s effect alone with large and positive for mental health

• Saffron performed as well as commonly prescribed medications

• Saffron provided additional benefit when stacked on prescription medications

Below is shown the meta-analysis for effects of saffron on symptoms of depression in comparison with antidepressant medications (red) comparison with placebo (blue). Sorry, I know it’s very fuzzy.

Effects on anxiety were similar.

And, if you end up reading the paper, you may note they report “publication bias.” But correcting for publication bias only strengthened the results, increasing the effect size of saffron. If that went over your head, focus on the big picture: in these controlled human trials, saffron showed significant effects on depression and anxiety.

Now, I’m sure you’re wondering, how does saffron work?

Mechanism of Action

While the exact mechanism isn’t worked out, it is known that components of saffron, including “crocin,” which is responsible for its color, and “safranal,” which imparts its aroma, inhibit reuptake of dopamine and serotonin to boost levels of these critical mood-regulating neurotransmitters in the brain, similar to the mechanism of action of medications used in psychiatry.

Saffron also has anti-inflammatory and antioxidant properties, which can help soothe and calm the brain from a metabolic perspective.

Saffron can also lower the stress hormone, cortisol, and increase levels of a brain healing factor, BDNF.

Of note, at a population level, depression and other mental health disorders are associated with inflammation, oxidative stress, higher stress hormones and lower BDNF.

Thus, these mechanisms by which saffron impacts metabolism provide a clear biological rationale to support the clinical effects seen in the randomized controlled human trials we reviewed. The puzzle pieces fit perfectly!

Saffron Dosing & Recipes…

I’m working on generating extra value for the premium (paid) subscribers to this Newsletter. As much as I’d love to provide 100% of my content for free, I’m coming realize that to make maximum impact on my life’s mission to Make Metabolic Mainstream my content also needs to has a viable business model. To that end, I’ll be titrating (yes, I did say titrating) in exclusive content for paid subscribers of this newsletter. Today, that includes commentary on saffron dosing and 3 therapeutically dosed recipes.