Categories & Effectiveness

Brain Health

Brain Antioxidant Shield

7/10

Strong evidence of effectiveness

Neuro-Repair Support

7/10

Strong evidence of effectiveness

Excitotoxicity Defense

4/10

Moderate evidence of effectiveness

Serotonin Support

4/10

Moderate evidence of effectiveness

Cognition

Memory & Recall

7/10

Strong evidence of effectiveness

Mental Acuity

7/10

Strong evidence of effectiveness

Mood & Stress

Mood Elevation

7/10

Strong evidence of effectiveness

Wellbeing Boost

4/10

Moderate evidence of effectiveness

Systemic Health

Anti-Inflammatory (Systemic)

7/10

Strong evidence of effectiveness

Systemic Antioxidant

4/10

Moderate evidence of effectiveness

Dosage & Side Effects

Recommended Dosage

The most commonly studied and recommended dose for adults is 30 mg of saffron extract per day, often split into two 15 mg doses. While effective doses in clinical trials range from 20 mg up to 200 mg daily depending on the condition, doses above 5 grams per day are considered toxic, and doses exceeding 10 grams per day have been linked to severe adverse effects including abortion. Animal studies have used a wide range of doses, but human clinical data points to 30-50 mg/day as a generally effective and safe range.

Potential Side Effects

At typical therapeutic doses (like 30 mg/day), saffron is generally well-tolerated with side effects comparable to placebo, potentially including mild nausea, dizziness, or dry mouth. High doses (>5 g/day) can lead to toxicity, including organ damage and teratogenic effects (harm to fetal development); doses above 10 g/day are reported to potentially induce abortion, and 20 g/day may be lethal. Due to the risk at high doses, especially concerning pregnancy, sticking to recommended dosages is crucial.

Bioavailability & Half-Life

When taken orally, saffron's main water-soluble compounds, crocins, are not absorbed directly but are first hydrolyzed (broken down) into crocetin, either before or during intestinal absorption. This absorbed crocetin is then partly metabolized into mono- and diglucuronide conjugates, which are the forms found in blood plasma. Specific details regarding absorption speed, time to reach peak concentration, and elimination half-life require further investigation.

Interactions & Stacks

Studies have investigated co-administration of saffron extract (40-80 mg/day) with fluoxetine (30 mg/day) for depression, finding the combination effective, with the higher saffron dose showing greater benefit. While specific synergistic or negative interactions with other nootropics aren't detailed in the reviewed studies, saffron appears generally safe when used appropriately alongside standard treatments like donepezil or memantine in clinical settings. User reports and meta-analyses are needed to clarify broader stacking compatibility.

Benefits by Use Case

Mild-to-Moderate Depression

May improve mood symptoms effectively, showing results comparable to conventional antidepressants like fluoxetine and imipramine in some 6-8 week trials. Further large-scale studies are needed to confirm long-term efficacy.

Mild-to-Moderate Alzheimer's Disease

Can support cognitive function, with studies suggesting efficacy similar to standard AD drugs like donepezil and memantine over 16-22 weeks. Evidence is promising but limited by study quality and size.

Neuroprotection & Brain Health

Offers antioxidant and anti-inflammatory effects that may protect brain cells from damage caused by oxidative stress, ischemia, or toxins like aluminum. Mechanisms involve scavenging free radicals and modulating inflammatory pathways.

Premenstrual Syndrome (PMS)

May alleviate PMS symptoms, with significant effects observed after 3-4 cycles of use in clinical trials. It appears effective for both physical and mood-related symptoms.

Mechanism of Action

Saffron exerts its effects through multiple pathways involving its main constituents like crocin, crocetin, and safranal. Its potent antioxidant activity helps neutralize harmful free radicals and reduce oxidative stress, while its anti-inflammatory properties inhibit inflammatory reactions, potentially protecting against neuroinflammation and conditions like EAE. Saffron modulates several neurotransmitter systems: it appears to have serotonergic effects similar to SSRIs, increases brain levels of dopamine and glutamate, interacts with the GABAergic system (safranal modifies GABAA receptors), inhibits acetylcholinesterase (AChE) like some AD drugs, and may act as an NMDA receptor antagonist. Additionally, it interacts with the opioid system, reducing morphine withdrawal signs and reward pathways, inhibits the aggregation of amyloid-beta fibrils implicated in Alzheimer's disease, suppresses ER stress, protects against neuronal apoptosis by inhibiting caspases (like caspase-3, -8, -9) and modulating the Bcl-2/BAX ratio via pathways like PI3K/AKT, and may promote angiogenesis.

Frequently Asked Questions

Is Saffron safe to take daily?

Can Saffron replace my antidepressant?

Does Saffron help with anxiety?

How long does it take for Saffron to work?

Can Saffron improve memory?

Are there any major risks with Saffron?

What part of the Saffron plant is used?

Does Saffron interact with other medications?

Summary & Expert Opinion

Overall, saffron emerges as a promising natural compound with significant evidence supporting its use for improving symptoms of mild-to-moderate depression and Alzheimer's disease. Its key strengths lie in clinical trial results showing efficacy comparable to standard pharmaceutical treatments at doses around 30 mg/day, coupled with a generally favorable safety profile at these therapeutic levels. However, limitations include the need for more large-scale, high-quality randomized controlled trials to confirm findings and reduce potential bias noted in some existing studies, particularly those conducted in specific regions. Individuals experiencing mild-to-moderate mood or cognitive issues may find saffron a beneficial option, while those taking very high doses or who are pregnant should avoid it due to toxicity and potential abortifacient effects.

Research Studies

Showing 5 of 9 studies

A review of therapeutic impacts of saffron (Crocus sativus L.) and its constituents (2023)

anti-inflammatory scavenging

Authors:

Fatemeh Anaeigoudari

Findings:

Human and animal experiments indicate that therapeutic impacts of saffron and its constituents (crocin, crocetin, safranal) are mainly mediated via inhibiting inflammatory reactions and scavenging.

Participants:

Human and animal experiments

Study Quality Assessment:

Mentions human and animal experiments

Neuroprotection in glaucoma (2022)

dietary supplementation gene therapy glaucoma +2 more

Authors:

C R Vishwaraj, Rengaraj Venkatesh, Srinivasan Kavitha

Findings:

This review summarizes recent (last 5 years) progress in neuroprotection for glaucoma, covering modulation of neuroinflammation, gene and cell therapy, dietary supplementation, and sustained-release systems.

Study Quality Assessment:

Review summarizing progress over 5 years.

All Effects:

dietary supplementation gene therapy glaucoma neuroinflammation neuroprotection

Diet and Anxiety: A Scoping Review (2021)

The effects of twenty-one nutrients and phytonutrients on cognitive function: A narrative review (2021)

anxiety reduction attention cognitive function +3 more

Authors:

Jillian Poles, John E Lewis

Findings:

This narrative review summarized 96 clinical trials on the effects of 21 nutrients and phytonutrients on cognitive function in various human populations. Many nutrients/phytonutrients showed potential for improving aspects of cognition (e.g., memory, attention, executive function, reaction time) and mood/anxiety, particularly in populations with cognitive impairment like AD, though effects were not consistent across all studies or populations. Adverse effects reported in the reviewed trials were generally minimal or nonexistent. The authors conclude that some nutrients/phytonutrients (e.g., aloe polysaccharides, Bacopa monnieri, curcumin, Rhodiola rosea, saffron, Withania somnifera, xanthines) are promising but require further large, well-controlled studies.

Participants:

The review included clinical trials conducted in humans between 2000 and 2021. Participants varied across the reviewed studies and included healthy adults (young, middle-aged, elderly), individuals with cognitive impairments (Mild Cognitive Impairment (MCI), Alzheimer's Disease (AD), dementia), patients with specific conditions (Multiple Sclerosis (MS), Parkinson's disease, stroke, traumatic brain injury (TBI), schizophrenia, psychosis, bipolar disorder, brain tumor survivors), and specific groups like college students or physicians. Sample sizes and specific demographics (e.g., age ranges, specific diagnoses) are detailed for individual studies within the text's table.

Dosage:

Dosages varied widely across the 96 reviewed studies depending on the specific nutrient or phytonutrient. Examples include: α-lipoic acid (600mg/day), Vitamin E (800-2000 IU/day), NAC (up to 3600mg/day), B vitamins (various combinations/doses), Citicoline (500-1000mg/day), Phosphatidylserine (100-300mg/day), Vitamin D (400-10000 IU/day), Omega-3 fatty acids (1.8-3g/day), Bacopa monnieri (300-600mg/day), Ginkgo biloba (40-240mg/day), Ginseng (100mg-9g/day), Saffron (30mg/day), Curcumin formulations (providing ~80mg curcumin up to 1500mg formulation/day), Ashwagandha (500-600mg/day), Caffeine (37.5-180mg per dose). Specific dosages for each reviewed study are detailed in the text, particularly in Table 1.

Study Quality Assessment:

This is a narrative review based on a comprehensive literature search of PubMed for human clinical trials published in English (2000-2021). Six independent reviewers evaluated articles for inclusion. The review summarizes findings from 96 articles. The text notes that while many included studies were randomized, double-blind, placebo-controlled trials, others had limitations such as small sample sizes, lack of blinding, placebo, or control groups. Heterogeneity in study design, treatment dosages, duration, outcome measures (neuropsychological tests), lack of dietary analysis, bioavailability issues, and potential variability in plant supplement composition are mentioned as limitations affecting generalizability. Specific sample sizes (N=X) and study designs (e.g., crossover, open-label) for individual trials are listed in the provided table.

All Effects:

anxiety reduction attention cognitive function executive function memory mood

Effects of saffron (Crocus Sativus L) on cognitive function. A systematic review of RCTs (2020)

Alzheimer's disease cognitive function functional status +2 more

Authors:

Konstantinos I Avgerinos

Findings:

This systematic review found evidence suggesting oral saffron intake in patients with AD may have similar efficacy to common anti-AD drugs (donepezil, memantine) regarding cognitive function and functional status, and was superior to placebo in some comparisons. Saffron appeared safe, with no significant difference in side effects compared to placebo or comparator drugs. However, conclusions should be interpreted cautiously due to potential risk of bias in included studies.

Participants:

Systematic review included studies with participants described as: Healthy or Mild Cognitive Impairment/Alzheimer’s Disease (MCI/AD) patients. Specifically, four studies involved subjects with AD or MCI (Mild/moderate AD, Probable AD, Moderate/severe AD, aMCI), and one study involved non-cognitively impaired subjects (CABG patients). Total participants across five studies: N=325.

Dosage:

30 mg daily saffron dose reported in four out of five included RCTs. One study did not report the dose (N/R).

Study Quality Assessment:

Systematic review of Randomized Controlled Trials (RCTs) or cross-over RCTs. Followed PRISMA guidelines. Assessed Risk of Bias (ROB) using Cochrane Collaboration's tool (evaluating selection bias, performance bias, detection bias, attrition bias, reporting bias). Results of ROB assessment: 3 studies 'unclear' risk, 1 study 'low' risk, 1 study 'high' risk. Limitations acknowledged: only five studies included, potential ROB in several studies, meta-analysis not feasible due to heterogeneity in comparators and outcomes, potential lack of generalizability (4/5 studies from Iran).

All Effects:

Alzheimer's disease cognitive function functional status mild cognitive impairment safety

Safety and toxicity of saffron (2020)

dose-response safety teratogenic effects +2 more

Authors:

Bibi-Marjan Razavi, Hossein Hosseinzadeh, Soghra Mehri

Findings:

Acute toxicity tests indicate saffron, safranal, and crocin are low or nontoxic. However, organ toxicities and teratogenic effects were observed at high doses in subacute exposure studies. Clinical studies show effective doses (e.g., 30-50mg/day) are significantly lower than toxic doses (>5g/day), suggesting a wide therapeutic index.

Participants:

Experimental studies (including BALB/c mice for LD50 testing) and clinical studies (including patients with CNS diseases like Alzheimer's and psychological disorders like depression).

Dosage:

Effective doses in clinical practice (e.g., 30-50 mg/day; 20-200 mg/day for CNS/depression) are lower than toxic doses. Toxic effects noted >5 g/day; lethal effects at 20 g/day. Doses >10 g/day reported to induce abortion and other adverse effects. Acute oral LD50 of aqueous extract in mice reported as 4120 mg/kg.

Study Quality Assessment:

Mentions evaluation based on 'experimental and clinical studies', including 'Acute toxicity tests' and 'subacute exposure' studies. Cites 'Clinical trials' for effectiveness data. Provides specific LD50 value from mouse study (4120 mg/kg). Notes LD50 can be affected by administration route, strain, age, sex, and weight.

All Effects:

dose-response safety teratogenic effects therapeutic index toxicity

The effects of Crocus sativus (saffron) and its constituents on nervous system: A review (2015)

anti-Alzheimer anticonvulsant antidepressant +2 more

Authors:

Mohammad Reza Khazdair

Findings:

This review summarizes evidence suggesting Crocus sativus (saffron) and its constituents (crocin, safranal) possess antioxidant, anti-inflammatory, anticonvulsant, anti-Alzheimer, antidepressant, anti-Parkinson, and neuroprotective properties relevant to nervous system disorders. Human trials indicate efficacy comparable to standard drugs for mild-to-moderate depression and Alzheimer's disease. Effects may involve interactions with cholinergic, dopaminergic, glutamatergic, GABAergic, opioid, serotonergic, and noradrenergic systems.

Participants:

Review covers human clinical trials (mild-moderate depression, mild-moderate Alzheimer's disease, PMS, schizophrenia, N=30, N=40, N=46, N=60 patients mentioned in specific trials), animal studies (rats, mice models for epilepsy, AD, depression, Parkinson's, ischemia, neurotoxicity, opioid interactions), and in vitro studies (e.g., PC12 cells, amyloid beta fibrillogenesis).

Dosage:

Review mentions various dosages across studies: Human trials often used 30 mg/day saffron extract/stigma/petal (sometimes 15mg twice daily) for depression, AD, or PMS; combination trials used 40-80mg saffron extract plus fluoxetine. Animal studies reported wide dose ranges depending on model and compound, e.g., saffron extracts (30 mg/kg to 800 mg/kg), crocin (30 mg/kg to 600 mg/kg), safranal (0.15 ml/kg to 291 mg/kg), crocetin (25-75 µg/kg). In vitro studies used concentrations like 10-50 µM crocin or 5-25 mg/ml saffron extract.

Study Quality Assessment:

Review cites studies including randomized controlled trials (RCTs), double-blind designs, placebo controls, and specific sample sizes (e.g., N=30, N=40, N=46, N=60). Mentions methods like Hamilton Depression Rating Scale (HAM-D), forced swimming test, maximal electroshock seizure (MES) and pentylenetetrazole (PTZ) models, streptozotocin (STZ)/6-hydroxydopamine (6-OHDA)/MPTP models, middle cerebral artery occlusion (MCAO) model, conditioning place preference (CPP) test, acetylcholinesterase (AChE) inhibition assays, neurochemical measurements (dopamine, glutamate, SOD, etc.), and histological analysis (TH immunochemistry). LD50 values reported. Concludes more mechanistic investigations are highly advised.

All Effects:

anti-Alzheimer anticonvulsant antidepressant neuroprotection neurotransmitter modulation

Effects of Saffron on Cognition, Anxiety, and Depression in Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Double-Blind Placebo-Controlled Trial

Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action

antidepressant depression efficacy +2 more

Findings:

In placebo-comparison trials, saffron showed large treatment effects for depression. Compared to antidepressant medications, saffron demonstrated similar antidepressant efficacy. Potential mechanisms include serotonergic, antioxidant, anti-inflammatory, neuro-endocrine, and neuroprotective effects, providing initial support for treating mild-to-moderate depression.

Study Quality Assessment:

Systematic review searched for high-quality, randomised, double-blind studies, with placebo or antidepressant controls. Six studies were identified for the systematic review. A narrative review of in vivo and in vitro studies was also conducted. Acknowledges need for further research.

All Effects:

antidepressant depression efficacy neuroprotective serotonergic

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Categories & Effectiveness

Brain Health

Brain Antioxidant Shield

Neuro-Repair Support

Excitotoxicity Defense

Serotonin Support

Cognition

Memory & Recall

Mental Acuity

Mood & Stress

Mood Elevation

Wellbeing Boost

Systemic Health

Anti-Inflammatory (Systemic)

Systemic Antioxidant

Dosage & Side Effects

Recommended Dosage

Potential Side Effects

Bioavailability & Half-Life

Interactions & Stacks

Benefits by Use Case

Mild-to-Moderate Depression

Mild-to-Moderate Alzheimer's Disease

Neuroprotection & Brain Health

Premenstrual Syndrome (PMS)

Mechanism of Action

Frequently Asked Questions

Summary & Expert Opinion

Research Studies

A review of therapeutic impacts of saffron (Crocus sativus L.) and its constituents (2023)

Authors:

Findings:

Participants:

Study Quality Assessment:

Neuroprotection in glaucoma (2022)

Authors:

Findings:

Study Quality Assessment:

All Effects:

Diet and Anxiety: A Scoping Review (2021)

Authors:

Study Quality Assessment:

The effects of twenty-one nutrients and phytonutrients on cognitive function: A narrative review (2021)

Authors:

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

Effects of saffron (Crocus Sativus L) on cognitive function. A systematic review of RCTs (2020)

Authors:

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

Safety and toxicity of saffron (2020)

Authors:

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

The effects of Crocus sativus (saffron) and its constituents on nervous system: A review (2015)

Authors:

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

Effects of Saffron on Cognition, Anxiety, and Depression in Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Double-Blind Placebo-Controlled Trial

Participants:

Study Quality Assessment:

Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action

Findings:

Study Quality Assessment:

All Effects:

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