Why 28 mg standardised saffron extract: the crocin and safranal questi

Q: Why did 22 mg of saffron extract not work in the Kell et al. trial when 28 mg did?

The Kell et al. (2017) trial was designed as a dose-finding study. The finding that 22 mg showed no statistically significant effect while 28 mg produced a large effect (p<0.001, d=-1.10) suggests that 22 mg sits below the threshold concentration required to produce a measurable change in the POMS Total Mood Disturbance outcome. Small differences in dose can sit on either side of a response threshold. It does not mean the difference is large in absolute terms; it means the biology has a threshold.

Q: Is saffron extract safe at this dose?

All saffron extract trials reviewed here reported no significant adverse effects at 28 mg per day. Saffron at very high doses (grams rather than milligrams) has been associated with adverse effects in historical and case reports, but these doses are far above the 28 mg used in supplement research. Always speak to your GP if you are taking medication.

Q: Does saffron extract contain any actual saffron, or is it all synthetic?

saffron extract is derived from real saffron stigmas — the same part of the Crocus sativus flower used in cooking. It is produced through an aqueous extraction process from cultivated saffron in Spain, not synthesised. The standardisation process concentrates the active compounds and verifies their levels, but the source material is agricultural saffron.

Q: If the Lopresti 2021 trial found 14 mg and 28 mg similarly effective for sleep, why use 28 mg?

In the Lopresti et al. (2021) sleep trial, both doses exceeded placebo on the primary outcome. However, the Kell et al. (2017) mood trial found a clear separation between 22 mg (no effect) and 28 mg (large effect). The 28 mg dose is the one with consistent evidence across both mood and sleep research contexts.

Q: Does the melatonin increase found in the Lopresti 2021 trial mean saffron makes you drowsy?

Melatonin is a circadian regulator rather than a sedative in the conventional sense. The Lopresti et al. (2021) trial measured increases in evening salivary melatonin concentrations, consistent with the expected circadian timing of melatonin secretion. The mechanism appears to support the body's natural sleep-onset signalling rather than inducing sedation. None of the saffron extract trials reported drowsiness or impaired daytime function as an adverse effect.

By The Krevie Team | Last reviewed: May 2026

28 mg of saffron extract is not a small dose — it is the precise dose identified in published clinical research as the effective threshold for measurable outcomes. saffron extract is a standardised extract from saffron stigmas, concentrated to a specific ratio of active compounds. 28 mg of saffron extract is not comparable to 28 mg of raw saffron powder. The dose-response data from Kell et al. (2017) demonstrates that 28 mg produced statistically significant results while 22 mg — just 6 mg less — did not.

What saffron extract is — and why saffron dose numbers are not comparable

Saffron (Crocus sativus L.) is the dried stigma of the saffron crocus. In culinary use, one kilogram of saffron requires approximately 150,000 flowers to produce. The active compounds responsible for saffron's studied biological effects are primarily crocins (a family of carotenoid glycosides, of which trans-crocin-4 is the most prominent) and safranal (a volatile aromatic compound). Together, these are sometimes referred to as Lepticrosalides.

Raw saffron contains these compounds, but in variable concentrations depending on the growing region, harvest timing, post-harvest processing, and storage conditions. A 28 mg portion of raw saffron powder does not contain a consistent or reliably measured quantity of crocins or safranal. This is the central problem with comparing doses across saffron products: without standardisation, the number on the label tells you very little about the active compound content.

saffron extract is a branded saffron extract manufactured by Pharmactive Biotech Products in Spain. It is produced from saffron stigmas cultivated in Alborea, Albacete, and standardised to contain more than 3.5% Lepticrosalides — meaning at least 3.5% of the extract by weight consists of the defined bioactive compounds (crocin isomers and safranal). At 28 mg of saffron extract, this translates to at least 0.98 mg of Lepticrosalides per dose. A 28 mg serving of non-standardised saffron powder would contain an unpredictable fraction of that.

This is also why the comparisons sometimes made between "28 mg saffron" in a supplement and raw saffron in cooking are not meaningful. Culinary saffron contributes negligible amounts of bioactive compounds per serving, because the amounts used in cooking are small and the cooking process degrades volatile compounds. The studies on saffron extract used a consistent, controlled extract at a verified active compound concentration.

What the research shows

Kell et al. (2017) — the dose-response trial that established 28 mg

Kell, Rao, Beccaria, Clayton, Inarejos-García and Prodanov (2017) conducted a three-arm randomised, double-blind, placebo-controlled trial in 128 participants — men and women of varying ages — who self-reported reduced mood but had no diagnosed mood disorder. Participants received saffron extract at 28 mg per day, saffron extract at 22 mg per day, or placebo for four weeks. Mood was measured as the primary outcome using the POMS (Profile of Mood States) questionnaire, supported by the PANAS (Positive and Negative Affect Schedule) and DASS-21 validated assessment tools. Sleep quality was monitored using the Pittsburgh Sleep Quality Index (PSQI).

The results are the most important piece of evidence for the 28 mg dose specifically. The 28 mg per day group showed a statistically significant decrease in negative mood and stress-related symptoms compared to placebo, with a significant difference on the POMS Total Mood Disturbance scale (p<0.001, effect size d=-1.10 — a large effect by convention). The 22 mg per day group showed no statistically significant treatment effect on any primary outcome measure.

This 6 mg difference — between a dose that worked and a dose that did not — is the empirical basis for using 28 mg rather than any lower figure. It is not an arbitrary threshold. PubMed 28735826

Lopresti et al. (2020) — sleep quality in adults with self-reported poor sleep

Lopresti, Smith, Metse and Drummond (2020) recruited 63 healthy adults aged 18–70 with self-reported poor sleep quality. Participants received saffron extract at 14 mg twice daily (total 28 mg per day) or placebo for 28 days. Data were analysed from 55 completers. The primary outcome — the ISI (Sleep Severity Index) total score — showed significantly greater improvement in the saffron extract group compared to placebo (p=0.017). Secondary outcomes including the Restorative Sleep Questionnaire (RSQ) total score (p=0.029) and Pittsburgh Sleep Diary (PSD) sleep quality ratings (p=0.014) also showed significant improvements. Saffron was well tolerated with no adverse effects reported. PubMed 32056539

Lopresti et al. (2021) — three-arm dose validation with melatonin measurement

A subsequent three-arm trial by Lopresti, Smith and Drummond (2021) enrolled 120 adults with unsatisfactory sleep and randomised them to placebo, 14 mg saffron extract, or 28 mg saffron extract (taken one hour before bed). The trial ran for 28 days with the primary outcome being Pittsburgh Sleep Diary sleep quality ratings. Compared to placebo, both saffron doses were associated with greater improvements in sleep quality ratings, mood upon awakening, and ISQ (Sleep Symptom Questionnaire) total score and ISQ sleep classifications. No significant differences between the 14 mg and 28 mg saffron doses were observed for most measures, though both exceeded placebo. Saffron supplementation was associated with increases in evening melatonin concentrations compared to placebo. This mechanistic finding is notable: saffron at this dose appears to modulate melatonin, which is one proposed explanation for the observed sleep effects. PubMed 34438361

The dose-response summary: In the Kell et al. (2017) mood trial, 22 mg did not produce a significant effect but 28 mg did. In the Lopresti et al. (2021) sleep trial, 14 mg and 28 mg both produced improvements above placebo. These results are not contradictory — the mood and sleep outcomes involve different measurement tools, different populations, and potentially different threshold concentrations. The consistent finding across all saffron extract trials is that 28 mg is the dose with the most robust evidence across both domains.

The crocin and safranal question

The two primary bioactive compound families in saffron — crocins and safranal — appear to operate through distinct mechanisms, and it is likely that both contribute to the measured outcomes in the saffron extract research.

Crocins are water-soluble carotenoid glycosides. In preclinical studies, crocin has been observed to interact with serotonin, dopamine, and norepinephrine signalling, and has shown neuroprotective properties in cell culture and animal models. In the context of the mood outcomes measured by Kell et al. (2017), monoaminergic neurotransmitter modulation is the most plausible biochemical explanation.

Safranal is the compound most associated with saffron's characteristic aroma. In preclinical research, safranal has demonstrated effects on GABA receptor activity and melatonin secretion. The Lopresti et al. (2021) finding of increased evening melatonin concentrations in saffron extract users is consistent with safranal's proposed mechanism on the circadian pathway. GABA activity is also closely linked to sleep architecture.

This dual mechanism — monoaminergic via crocins, GABAergic and melatonin-related via safranal — is why both mood and sleep outcomes have been measured in the saffron extract research, and why both appear to respond at similar doses. A saffron extract that is rich in crocins but low in safranal, or vice versa, would not be expected to replicate these results. The standardisation of saffron extract to its full Lepticrosalides profile (both crocins and safranal) is therefore directly relevant to the research outcomes.

How saffron extract is used in The Foundation

The Foundation contains saffron extract standardised saffron extract at 28 mg per daily serving — the dose used in the Kell et al. (2017) mood trial and the Lopresti et al. (2020 and 2021) sleep quality trials. The ingredient is saffron extract specifically, standardised to more than 3.5% Lepticrosalides (crocin isomers and safranal). Non-standardised or differently standardised saffron extracts are not equivalent and do not inherit this research base.

The Foundation contains saffron extract 28 mg — the dose from Kell et al. (2017) and Lopresti et al. (2020, 2021). View The Foundation.

Frequently asked questions

Why did 22 mg of saffron extract not work in the Kell et al. trial when 28 mg did?

The Kell et al. (2017) trial was specifically designed as a dose-finding study with three arms: 28 mg, 22 mg, and placebo. The finding that 22 mg showed no statistically significant treatment effect while 28 mg produced a large effect (p<0.001, d=-1.10) suggests that 22 mg sits below the threshold concentration required to produce a measurable change in the POMS Total Mood Disturbance outcome. This kind of dose-threshold effect is common in pharmacological and nutritional research — small differences in dose can sit on either side of a response threshold. It does not mean the difference is large in absolute terms; it means the biology has a threshold.

Is saffron extract safe at this dose?

All saffron extract trials reviewed here reported no significant adverse effects at 28 mg per day. The Lopresti et al. (2020) trial specifically noted that saffron intake was well tolerated, with no adverse events reported across the 28-day intervention period. The Kell et al. (2017) four-week trial similarly reported no safety concerns. Saffron at very high doses (grams rather than milligrams) has been associated with adverse effects in historical and case reports, but these doses are far above the 28 mg used in supplement research. Always speak to your GP if you are taking medication.

Does saffron extract contain any actual saffron, or is it all synthetic?

saffron extract is derived from real saffron stigmas — the same part of the Crocus sativus flower used in cooking. It is produced through an aqueous extraction process from cultivated saffron in Spain, not synthesised. The standardisation process concentrates the active compounds and verifies their levels, but the source material is agricultural saffron. It is not synthetic.

If the Lopresti 2021 trial found 14 mg and 28 mg similarly effective for sleep, why use 28 mg?

In the Lopresti et al. (2021) sleep trial, both doses exceeded placebo on the primary outcome. However, the Kell et al. (2017) mood trial — using a different primary outcome measure and a different study design — found a clear separation between 22 mg (no effect) and 28 mg (large effect). The 28 mg dose is the one with consistent evidence across both mood and sleep research contexts. Using 14 mg would replicate only part of the evidence base, and would sit closer to the dose that showed no effect in the mood context.

Does the melatonin increase found in the Lopresti 2021 trial mean saffron makes you drowsy?

Melatonin is a circadian regulator rather than a sedative in the conventional sense. The Lopresti et al. (2021) trial measured increases in evening salivary melatonin concentrations, which is consistent with the expected circadian timing of melatonin secretion. The mechanism appears to support the body's natural sleep-onset signalling rather than inducing sedation. None of the saffron extract trials reported drowsiness or impaired daytime function as an adverse effect.

References

Kell G, Rao A, Beccaria G, Clayton P, Inarejos-García AM, Prodanov M. saffron extract a novel saffron extract (Crocus sativus L.) improves mood in healthy adults over 4 weeks in a double-blind, parallel, randomized, placebo-controlled clinical trial. Complement Ther Med. 2017;33:58–64. PubMed 28735826
Lopresti AL, Smith SJ, Metse AP, Drummond PD. Effects of saffron on sleep quality in healthy adults with self-reported poor sleep: a randomized, double-blind, placebo-controlled trial. J Clin Sleep Med. 2020;16(6):937–947. PubMed 32056539
Lopresti AL, Smith SJ, Drummond PD. An investigation into an evening intake of a saffron extract on sleep quality, cortisol, and melatonin concentrations in adults with poor sleep: a randomised, double-blind, placebo-controlled, multi-dose study. Sleep Med. 2021;86:7–18. PubMed 34438361

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Why 28 mg standardised saffron extract: the crocin and safranal question