Saffron

Crocus sativus is a stemless flower commonly known as saffron and used as a Spice. Low dose supplementation appears to confer antidepressive properties.

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Crocus sativus, more commonly referred to as saffron, is the world’s most expensive spice. The high labor costs associated with the spice have resulted in a limited supply.

Saffron has traditionally been used to flavor food, though it has occasionally been used medicinally as well. Recent research has examined saffron’s antidepressant properties.

Though there are limited human studies on the subject of saffron and depression, they are of high quality. The studies include trials against placebo and trials against reference drugs, such as the SSRI fluoxetine. These studies show that saffron, at the recommended dose, has antidepressant properties comparable to the reference drugs. These studies were conducted in Iran, which produces 90% of the world’s saffron. While this should not discredit the results of the studies, replication from other researchers would go a long way toward solidifying saffron’s effects.

Saffron’s antidepressant properties are related to serotonin metabolism. Saffron’s side effects, like reduced snacking and an elevated mood, could be the result of increased serotonin action in the body. Further research is needed to determine the exact functioning of this mechanism.

Using saffron in food will provide the same effects as supplementation, since saffron supplements are dehydrated extracts of the spice. Saffron does not have a high margin of safety, so care should be taken during supplementation. The standard daily dose is 30mg, used for up to eight weeks. It is possible that even double the dose could result in harm to the body. Further research is needed to determine the safe level of saffron supplementation. Prudent supplementation is advised until more information is available.

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Also Known As

Crocus sativus


Do Not Confuse With

Turmeric (Indian saffron)


Things to Note

  • Due to traditional usage as an abortifacient and (infrequent) reports of irregular vaginal bleeding at higher doses (200-400mg) of saffron, it may be prudent to avoid supplementation during pregnancy
  • Chronic usage of saffron (over eight weeks continuous) should be approached cautiously, as double the recommended dose may result in harm to the body. Double the recommended dose is still a relatively small overall amount (60mg) and it is possible usage of saffron as a spice could exceed this

Is a Form of


Caution Notice

Possible interactions with pregnancy

Examine.com Medical Disclaimer

For chronic supplementation, take 15mg of saffron, twice a day. This is the advised upper limit for constant supplementation. Preliminary evidence suggests that doubling this dose may have a toxic effect after eight weeks of continuous usage. Acute, single doses of saffron, can be as high as 200mg.

Saffron can be supplemented by taking water extracts of the stigma (the red part of the plant, used as a spice) or by using the dehydrated stigma itself. Some evidence suggests that the petals of saffron may also be effective.

Saffron can be taken twice a day in a supplement form, or at meals as a spice.

Doses above 1,200mg may cause nasea and vomiting.


The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Saffron has in your body, and how strong these effects are.
GradeLevel of Evidence
ARobust research conducted with repeated double blind clinical trials
BMultiple studies where at least two are double-blind and placebo controlled
CSingle double blind study or multiple cohort studies
DUncontrolled or observational studies only
Level of Evidence
EffectChange
Magnitude of Effect Size
Scientific ConsensusComments
ADepression

Notable

30mg saffron daily (both petals and stigma) appear to be effective in reducing depressive symptoms in persons with major depressive disorder, and the potency has been noted... show

CImmunoglobulin A

No significant influence on circulating IgA concentrations following saffron ingestion.

CImmunoglobulin G

Minor

An increase in IgG concentrations has been noted to occur with saffron supplementation alongside a decrease in IgM and no influence on IgA.

CImmunoglobulin M

Minor

A decrease in IgM concentrations has been noted to occur following supplementation of saffron.

CNeutrophil count

Neutrophil concentrations in serum are unaffected by supplementation of saffron.

CEosinophil count

Eosinophil concentrations are not affected by saffron supplementation in otherwise healthy persons.

CBasophil count

Minor

Basophil count has been noted to mildly decrease following saffron supplementation alongside a reduction in IgM concentrations.

CMonocyte count

Minor

Supplementation of saffron appears to be able to cause a mild increase in monocyte concentrations in serum.

CWhite Blood Cell Count

Minor

A decrease in white blood cell count has been noted with supplementation of saffron at 60mg for over eight weeks.

CRed Blood Cell Count

Minor

A decrease in RBCs has been noted in one study suggesting saffron toxicity with prolonged supplementation of a double dose (60mg).

CLiver Enzymes

Supplementation of 100mg saffron extract for six weeks failed to increase liver enzymes in otherwise healthy persons.

CCreatinine

Creatinine does not appear to be influenced in serum following supplementation of saffron.

CSymptoms of Alzheimers

Minor

Mixed evidence on the efficacy of saffron, but it is possible that supplementation could delay an increase in symptoms without a therapeutic effect.

CVisual Acuity

Minor

Supplementation of saffron appears to increase visual acuity in persons with age-related macular degeneration.

CSexual Function

Minor

SSRI related sexual dysfunction in both men and women appears to be reduced with coingestion of saffron, although saffron does not alter the efficacy of SSRI therapy on depression.

CErections

The best evidence to date does not support a pro-erectile effect of saffron supplementation per se, although it may have a particular role in combating SSRI related... show

CWeight

Minor

A reduction in weight has been noted to a very mild degree which may be wholly related to a reduction in snacking that has been observed with saffron supplementation in... show

CFood Intake

Minor

Secondary to reducing snacking (thought to be via increasing satiety from meals) saffron appears to reduce overall food intake.

CAppetite

Minor

High dose (176.5mg) saffron extract appears to be able to reduce snacking and increase self-reported satiety in otherwise healthy overweight women.

It should be... show

CSymptoms of PMS

Notable

One study assessing saffron on PMS symptoms noted that supplementation caused 76% of the participants to have more than a halving of overall symptoms (placebo reaching... show

CSperm Count

Saffron supplementation does not appear to be effective in increasing sperm count in infertile men.

CSeminal motility

The best evidence to date does not support a role for saffron supplementation in increasing seminal motility.

CSperm Quality

While preliminary evidence suggested benefit to seminal morphology, the best evidence to date does not support a role for saffron in enhancing seminal quality.

CTestosterone

Neither aromatherapy nor oral supplementation appear to significantly influence testosterone concentrations in serum.

CLuteinizing Hormone

LH concentrations are unaffected by saffron supplementation at 60mg in infertile men.

CFollicle-Stimulating Hormone

FSH is unaffected in infertile men given 60mg saffron daily over the course of 26 weeks.

CProlactin

Supplementation of 60mg saffron for 26 weeks does not significantly influence prolactin in infertile men.

CEjaculate Volume

Saffron does not appear to influence ejaculate volume in men with infertility.

CHemoglobin

Minor

Hemoglobin has been noted to be decreased in one study and thought to be related to possible toxic effects of moderately high dose saffron (60mg for more than 8 weeks).

CSerum Platelets

Minor

Supplementation of 60mg saffron was able to reduce platelet counts in serum following eight weeks of exposure (increasing in magnitude until study cessation at 26 weeks)... show

CBlood Pressure

Minor

A decrease in blood pressure was noted in otherwise healthy (normotensive) men following 26 weeks of saffron supplementation at 60mg daily, although this was thought to... show

CEstrogen

Minor

The aroma of saffron appears to cause a mild increase in circulating estrogen concentrations in otherwise healthy women following 20 minutes of exposure.

CCortisol

Minor

The aroma of saffron has been noted to reduce cortisol concentrations to a mild degree in otherwise healthy women, and this occurred alongside a reduction in state anxiety.

CAnxiety

Minor

The aroma of saffron has once been noted to cause a mild (approximately 10%) reduction in state anxiety following 20 minutes of exposure in otherwise healthy women.

DPenile Girth

Minor

In men with erectile dysfunction, saffron appeared to increase nighttime tumescence at both the tip and base.

DOxidation of LDL

Minor

Supplementation of saffron appears to be capable of reducing LDL oxidation when tested ex vivo in both healthy controls and persons with cardiovascular disease,... show

DSkin Moisture

Acute topical application of a cream containing saffron has failed to cause significant changes in skin moisture content over the course of seven hours.


Studies Excluded from Consideration

  • Confounded with fennel and celery[1]

Disagree? Join the Saffron Discussion

Table of Contents:


Edit1. Sources and Composition

1.1. Sources and Composition

Crocus sativus (of the family iridaceae) is a Spice commonly referred to as saffron, which is derived from the arabic word za-faran meaning "be yellow"[2] and a previous name for it (pre-Grecian) was Krokos.[3] Saffron's history is mostly culinary where it was a prized spice, and the medicinal uses were limited although ancient Romans attempted to prevent hangovers by putting saffron in their wine,[3] and it has been reported to have anxiolytic and sedative uses[4] while also being used as an antidepressive agent in traditional Persian medicine.[5]

Saffron is a traditionally used spice, and does not have an extensive historical use for medicine. Most historical usage is culinary, to flavor fish and seafood dishes.

Saffron is mostly produced in Iran, where it accounts for up to 90% of the world's supply[6] although spanish saffron (the former world leader in production) is reported to be of higher culinary quality.[3]

Its production is usually labour intensive, with saffron production thought to total 190kg annually and anywhere between 150,000-200,000 flowers and 400 hours of labor to produce 1kg of dried stigma (the main component of the spice used), due in part to only three stigma existing in one plant and each weighing only 2mg.[7][8] The petals of saffron are a byproduct of production, despite being much more plentiful and accounted to about 10,000 tonnes annually.[2] This labour-intensive process mostly explains why saffron is currently the world's most expensive spice.[9]

Saffron js very expensive because harvesting adequate amounts of the stigma (the main culinary and supplemental part of the plant) is very labor-intensive, and because the labour produces a low yield of stigma.

Saffron stigma contains:

  • Picrocrocin (hydroxysafranal β-D-glucoside) which is the main bitter component of saffron[10] as well as picrocrocin acid form[11]
  • Safranol and hydroxysafranol, which are monoterpene aldehydes which result in the characteristic aroma and taste of saffron[12] and are lysed from the picrocrocin molecule after heat treatment
  • Crocin molecules, which are water soluble carotenoids.[13] These are divided into Crocin 1 (17.823mg/g of the water extract[13]), Crocin 2 (trans-crocin-2, cis-crocin-2, and trans-crocin-2';[13] the former being 7% of the total carotenoids[11]), Crocin 3 (trans-crocin-3 and cis-crocin-3, with the former at 26% total carotenoids[11]), Crocin-4 (trans-crocin-4 and cis-crocin-4, with the former amounting to 46% total carotenoids and the latter 12%[11]) and Crocin 5 (cis-crocin-5[11])
  • Zeaxanthin, a fat soluble carotenoid[14]

Saffron components can be divided into either small aromatic aldehydes (safranal and its glycoside, known as picrocrocin) and the carotenoids, known as crocins, which have varying forms depending on the sugars bound to them.

Saffron crom tends to contain:

The term 'crocin' tends to refer to the basic carotenoid structure in saffron, which are atypically water soluble (majority of carotenoids such as Astaxanthin or β-carotene being fat soluble). Different variations of crocin (ie. crocin-4 or crocin-1) refer to different sugar molecules added to each end of the molecule.

1.2. Physicochemical Properties

Processing of saffron (after growing) requires a drying phase, with a few methods (sun drying, toasting, or putting the stigma into a dark and temperature-controlled room) being used, all with the goal of reducing the moisture content to 10-12%;[12][16] the goal of heat treatment also being to cause picrocrocin to release safranal for the aroma.[17] Variations in processing are mostly of concern for the aromatic properties of saffron, as both low temperature (less than 30°C) with long duration as well as the inverse (over 60°C) reduce quality of saffron by increasing degradation of the pigmentation (crocins).[16]

Processing of saffron tends to free up safranal and reduce picrocrocin, which results in a more desirable taste and aromatic properties.


Edit2. Neurology

2.1. Serotonergic Neurotransmission

Crocins in saffron are thought to hinder 5-HT2C signalling due to antagonizing the effects of m-Chlorophenylpiperazine (mCPP), a serotonin receptor agonist,[18] in a rat model.[19]

In vivo evidence in rat models suggests that the crocins found in saffron have serotonergic effects.

2.2. Analgesia

Intraperitoneal injections of saffron extracts from both the stigma and petal (360-1,400mg/kg) have shown analgesic properties in an acetic acid writhing test, in a manner partially blocked by naxolone (an opioid antagonist), without any effects in a hot plate test in mice, which may suggest that the extract acts as an analgesic non-centrally. [20]

High doses of saffron may have analgesic properties in rats, although the dosage used and method of administration (injections) makes it questionable whether these results would occur with oral ingestion of saffron.

2.3. Food Intake and Appetite

Supplementation of saffron stigma (176.5mg daily) in overweight women without eating disorders and not on a controlled diet resulted in less snacking with saffron (55% reduction) than with placebo (28%) combined with less reported hunger after eight weeks;[21] this was thought to underlie a modest reduction in body weight (0.96+/-0.26kg).[21]

One study on overweight women has noted a reduction in snacking frequency and subjective hunger associated with moderate weight loss.

2.4. Sedation

In the rat, crocins at an oral dose of 30 and 50mg/kg have failed to alter locomotor activity[19] whereas intraperitoneal administration of higher doses (up to 600mg/kg) of crocin in mice can reduce locomotor activity to a small degree[4] and 50mg/kg injections have been implicated in both a minor reduction in motor activity[4] or no significant changes.[22]

Standard doses of saffron in rodents do not appear to be associated with sedation, although higher injected doses appear to induce sleepiness. Currently there is no human evidence investigating this property of saffron.

2.5. Anxiety and Stress

Injections of saffron water extract (56-80mg/kg) appears to have anxiolytic properties in mice while higher doses up to 560mg/kg lose their efficacy, and isolated crocins (50-600mg/kg) do not appear to be effective.[4] The potency of the water extract in the open field test and elevated plus maze appears to be comparable to 3mg/kg diazepam.[4] This anxiolytic effect has been noted elsewhere with isolated crocins at 50mg/kg, although lower doses (15-30mg/kg) were ineffective.[22]

The crocins of saffron appear to have anxiolytic propeties in mice at moderate, but not lower, doses. No studies exist on humans investigating oral supplementation of saffron.

In humans, one study attempting aromatherapy in a double blind manner (ethanol as placebo, saffron diluted in ethanol below the detectable limit for experimental) noted that 20 minutes exposure to the aroma of saffron was sufficient to cause a mild (approximately 10%) reduction of anxiety as assessed by the STAI.[23]

One study has noted that the aroma of saffron resulted in minor reductions in anxiety, suggesting relaxing properties via aromatherapy.

2.6. Depression

Oral ingestion of 150-600mg/kg of crude saffron extract in rats reduced depressive symptoms in a dose-dependent manner with the highest dose being comparable to 100mg/kg fluoxetine.[13] Most efficacy being seen in the petroleum ether and dichloromethane extracts of the corm or the water extract of the stigma, although the major components in the corm (Octadecadienoic and Hexadecanoic acids) differed from that of the stigma (crocins).[13]

Saffron appears to have antidepressant properties secondary to the crocin content, as safranal appears to be mostly inactive.

A meta-analysis on the usage of saffron on depressive symptoms[6] (against either placebo or antidepressant reference drugs) found that the usage of saffron supplementation in five trials at 30mg noted that saffron was more effective than placebo in two studies[5][24] although the studies comparing it to reference drugs (imiprazole and fluoxetine) failed to find a significant difference in efficacy although saffron appeared to be associated with less side-effects.[25][26][27]

At least one study has investigated the petals of saffron rather than the stigma (flowers being an industrial byproduct) and over eight weeks in depressive people given 15mg saffron petal extract twice daily (300-350µg safranal per capsule) performed equally to fluoxetine 10mg twice daily.[25] Both treatments caused a time-dependent reduction in depressive symptoms on the HAM-D rating scale and s similar amount of people reached a 50% reduction in depressive symptoms (75-85%) and remission (25%).[25]

The petals of saffron, perhaps a cheaper option due to being an industrial byproduct not used in spice making, also appear to be effective for the treatment of depression, with a potency comparable to reference drugs.

Two studies, one in men and one in women, have found that saffron as an ajuvant to fluoxetine may alleviate the sexual dysfunction related to floxetine treatment while having no additional effects on its antidepressive action.[28][29]

When used as an adjuvant for SSRI (fluoxetine) therapy, saffron neither hinders nor augments the antidepressive effects of fluoxetine, despite counteracting floxetine-induced sexual dysfunction.

One study assessing the safety of saffron supplementation in the 200-400mg dosage range noted that, following a week of supplementation, 40% of subjects taking the higher dose of saffron reported elevations in mood.[30]

One study noted that saffron elevated mood in healthy people.

2.7. Obsession and Compulsion

Crocins from saffron could be beneficial for OCD, as crocins are able to reverse a chemically-induced model of OCD in rats.[19] In this study, rats undergoing chemically-induced OCD after being administered mCPP had their symptoms reduced by approximately half when given 30 and 50mg/kg crocins, although symptoms remained higher than that of controls not given mCPP;[19] crocins failed to prevent the reduction in locomotor behaviour of the rats given mCPP.[19]

Saffron may affect the symptoms of obsessive compulsive disorder, but there is no human evidence that this is the case, and the rodent evidence is sparse.


Edit3. Cardiovascular Health

3.1. Cholesterol

50mg of saffron stigma dissolved in milk and given twice daily for six weeks appears to cause a time-dependent reduction in the susceptability of LDL to oxidation in both healthy controls and persons with coronary artery disease.[31]

One study has noted a reduction in LDL oxidation susceptability, although further testing is needed, as the lone study was small and not placebo controlled.


Edit4. Inflammation and Immunology

4.1. Immunoglobulins and Interferons

Supplementation of 100mg saffron extract (crude powder of the stigma) in healthy men once daily for three weeks increased serum IgG concentrations (24.2%) while reducing IgM concentrations (42.5%), although these differences were normalized after an additional three weeks; IgA was unaffected at all times.[32]

Higher-than-normal doses of saffron have been noted to temporarily alter immunoglobulin concentrations in the serum of healthy men, with lower doses not yet tested.

4.2. Macrophages

Following oral ingestion of 100mg crude saffron extract (stigma), monocyte concentrations increased (9%) after three weeks alongside changes in immunoglobulins while the change was not detectable after six weeks.[32]

4.3. T Cells

Total lymphocytes (including T and B cells) are not affected following supplementation of 100mg crude saffron extract in otherwise healthy men over six weeks relative to placebo.[32]

4.4. Basophils

Following oral ingestion of 100mg crude saffron extract (stigma), basophil concentrations decreased (20%) after three weeks alongside changes in immunoglobulins while the change was not detectable after six weeks.[32]


Edit5. Interactions with Hormones

5.1. Estrogen

Saffron as aromatherapy (20 minutes of exposure) in otherwise healthy women appears to cause a mild increase in estradiol concentrations in saliva in both the luteal and follicular phases relative to baseline.[23]

Aromatherapy of saffron has resulted in an acute increase in estrogen in otherwise healthy women; prolonged oral supplementation has not been tested and the practical significance of this information is not yet known.

5.2. Testosterone

Saffron as aromatherapy (20 minutes of exposure) in otherwise healthy women does not appear to significantly influence testosterone concentrations[23] and supplementation of saffron at 60mg (30mg twice daily) over the course of 26 weeks in infertile men has failed to modify circulating testosterone concentrations relative to placebo.[33]

Both oral supplementation in men as well as aromatherapy in women have failed to significantly influence testosterone concentrations.

5.3. Corticosteroids

Saffron as aromatherapy (20 minutes of exposure) in otherwise healthy women appears to cause a reduction in cortisol from approximately 1.6µg/dL to 1.0µg/dL (luteal phase) and from 0.135µg/dL to 0.09µg/dL (follicular phase).[23] This reduction in cortisol occurred alongside a mild reduction in state anxiety as assessed by STAI.[23]

Aromatherapy of saffron has been implicated in reducing cortisol mildly in otherwise healthy women.


Edit6. Interactions with Oxidation

6.1. DNA Damage

Crocetin appears to be able to bind to DNA and form adducts in various cancerous lines (HeLa, A-549, and VA-13)in vitro [34] while crocetin and other compounds derived from saffron (dihydrocrocetin and safranal) also have this property in normal cells,[35] with the binding constants in normal cells being in the range of 18.5µM (dihydrocrocetin) to 1.24mM (safranal).[35] Crocetin is thought to act in the nucleus, since it exhibits similar potency in inhibiting DNA and RNA synthesis in whole cells as in isolated nuclei.[34]

Crocetin in saffron appears to associate with DNA, and while this is speculated to act in an antioxidative manner when bound to DNA, its exact role is not yet ascertained.


Edit7. Interactions with Aesthetics

7.1. Skin

When assessing the UV radiation protective effects of saffron, a cream containing 4% dried and powdered saffron appears to have a similar sun protection factor (SPF) as an 8% homosalate solution (as reference drug) in vitro whereas an 8% saffron cream outperformed homosalate.[36]

Topical application of a cream containing 2-8% saffron to volunteers does not appear to modify moisture content of the skin after seven hours following a single administration.[36]

Topical application of saffron-containing cream may have solar protective (sunscreen) properties with a potency comparable to or greater than an agent commonly used in sunscreens (homosalate).


Edit8. Sexuality and Pregnancy

8.1. Menstruation

One study assessing the effects of saffron on PMS symptoms noted time-dependent benefits of 30mg saffron taken daily over the course of two menstrual cycles, where at the end of the second cycle 76% of women reported over a halving of total symptoms (versus 8% in placebo).[37] Depressive symptoms as assessed by the HAM-D were reduced by over half in 60% of women taking saffron, while only 4% of women taking placebo achieved this.[37] The only other study on the topic which used saffron also used fennel and celery seed concurrently, so conclusions regarding the effects of saffron alone cannot be deduced from this study.[1]

8.2. Libido

Saffron has been tested for its ability to prevent or attenuate SSRI-related sexual dysfunction, in part due to its ability to increase measures of libido in male rats, a property traced back to saffron's crocin content, but not its safranal content.[38]

In women who benefitted from SSRI therapy for depression but reported sexual dysfunction, supplementation of 15mg saffron stigma extract twice daily (3.3-3.5mg crocin daily) had statistically significant improvements on the self-reported Female Sexual Function Index (FSFI) in the subscales of arousal, lubrication, pain, but not in desire, sexual satisfaction, or orgasm after 4 weeks of supplementation.[28] Similar effects were seen in men with major depressive disorder stabilized on SSRI therapy, where supplementation of the same dose of saffron for four weeks improved erectile function and satisfaction with intercourse but not sexual desire, orgasm, and overall sexual satisfaction.[29]

A small pilot study investigating the effects of saffron on men with erectile dysfunction found benefits with supplementation for 10 days with a high dose of saffron (200mg daily)[39] although a later and larger study also assessing erectile dysfunction in men using 15mg of the petal extract twice daily for four weeks failed to note any improvement on the same rating scale (IIEF) or other self-reported measures of erectile function.[40] This study noted that the majority of cases of erectile dysfunction (72.2%) were vascular in nature, with lower amounts being traced back to neurogenic (3.5%) or psychogenic (24.3%) causes.

Saffron has been noted to improve parameters of sexual function in both men and women experiencing sexual dysfunction from SSRI therapy, although the one larger study in men with general erectile dysfunction did not find any improvements.

8.3. Fertility

One uncontrolled study assessing the effects of saffron on male seminal parameters noted that, when given 50mg of saffron in milk thrice a week, seminal motility and morphology improved without any alterations in sperm count.[41] This was reinvestigated in a double blind controlled trial with 30mg saffron twice daily (60mg total each day) for 26 weeks in men with primary infertility but it failed to improve any measured seminal parameter (morphology, motility, density) and ejaculate volume relative to placebo.[33]

The best evidence at this point in time does not support the hypothesis that saffron improves seminal parameters associated with male fertility.


Edit9. Peripheral Organ Systems

9.1. Eyes

Saffron has been tested for its retinal protective properties as this is a function common to many carotenoids (Astaxanthin and Lutein) and the crocins have been implicated in similar protective effects.[42] Preliminary evidence suggests that oral ingestion of 1mg/kg saffron extract (stigma) in rats exposed to continuous bright light prevented damage[43][44] and performed mostly comparable to the reference drug (1mg/kg β-carotene).[44] Supplementation for 10 days in rats appears to be more protective than supplementation over shorter periods of time (2-5 days) for light-induced retinal damage.[45] In rodents, the protective effects appear to extend beyond light-induced damage, as as saffron prevents selenite-induced cataract formation.[46]

The crocins, a type of carotenoid found in saffron, have protective effects in retinal tissue similar to other carotenoids, and their potency in rats seems comparable to other dietary carotenoids.

In patients with age-related macular degeneration (AMD), supplementation of 20mg saffron for three months increased the amplitude of focal electroretinograms (fERGs, which assesses cone sensitivity in early AMD[47]) and reduced thresholds relative to baseline and placebo, which is suggestive of improvements in eye function; ophthalmoscopic appearance was unchanged, however.[48] This has been noted elsewhere with saffron at 20mg daily when assessing whether the major risk genotypes of AMD, the complement factor H (CFH[49]) and the age-related maculopathy susceptibility 2 (ARMS2[50]) polymorphisms, affected the protective effects of saffron; neither did.[51]

A human study failed to find carryover effects of saffron carotenoids through a crossover design, which suggests that, unlike other carotenoids, there is not a significant buildup of saffron carotenoids with supplementation, perhaps because saffron carotenoids are water-soluble, which is atypical for carotenoids.[48] Animal data suggests there may be a minor buildup, however, as 10 days supplementation in rats is more effective than two or five days.[45]

Human studies on age-related macular degeneration have noted benefits to visual acuity with saffron supplementation at slightly less than the standard oral dose. The benefits of supplementation have a rapid onset and lack prolonged benefits once supplementation is stopped, possibly due to the water solubility of these carotenoids, which leads to rapid elimination from the body.


Edit10. Interactions with Cancer

10.1. Prostate

PC-3 (prostatic cancer) cells incubated with 5-20µg/mL safranal were induced to undergo apoptosis by safranal, with an IC50 value of 13.0+/-0.07µg/mL and 6.4+/-0.09µg/mL at 48 and 72 hours respectively, while nonmalignant cells (MRC-5) failed to undergo apoptosis when incubated with up to 20µg/mL safranal for over 72 hours.[52]


Edit11. Other Medical Conditions

11.1. Alzheimer's Disease

When tested in vitro, crocins from the stigma of saffron appear to attenuate the formation of Aβ1-40 protein fibrils in a concentration-dependent manner, with trans-crocin-4 inhibiting 15-40% of formation at 15−50μM.[11] As trans-crocin-4 comprised around 10% of the crude extract and was 10-fold more potent than the crude extract and more effective than dimethylcrocetin, it was thought that trans-crocin-4 was then major active ingredient which worked through its antioxidant properties,[11], as fibrillogenesis requires oxidation.[53]

Crocins in saffron have been shown to reduce the formation of β-amyloid protein aggregates in vitro.

One 16-week study using saffron (15mg twice daily; conferring 260-300µg safranal and 3.3-3.5mg crocins) against placebo in persons with Alzheimer's disease noted significant benefits on ADAS-cog scores relative to placebo (3.69+/-1.69 point reduction versus placebo) and CDR-SB (0.67+/-0.24 reduction versus placebo).[54]

A 22-week trial in people with mild to moderate Alzheimer's disease given 15mg saffron extract twice daily (once daily for the first four weeks) relative to the reference drug of 5mg donpezil twice daily and assessed by a variety of measurement scales on cognition (MMSE, ADAS-cog, and CDR-SB) found that although there was no difference found between the saffron and donpezil arms, both groups failed to show significant changes on ADAS-cog and CDR-SB from their baselines.[55]

There is mixed human evidence as to the benefits of saffron on symptoms of mild to moderate Alzheimer's disease, with the only positive study being a reduced rate of decline (but not necessarily reduction of symptoms from baseline) while the other study noted that while saffron performed similarly to the reference drug donepezil, both failed to benefit symptoms.


Edit12. Safety and Toxicology

12.1. General

The LD50 of saffron petal and stigma extracts in mice via injections are 6g/kg and 1.6g/kg respectively[56] while up to 3g/kg oral ingestion in mice is not acutely lethal.[56]

Supplementation of saffron at doses higher than normal (200mg) in humans has been associated with some alterations in blood and hemodynamic parameters that, while statistically significant, where not of large enough magnitude to be considered adverse, although abnormal uterine bleeding was found in two women at doses of 200-400mg.[30] Doses of 1,200-2,000mg saffron in humans can acutely cause symptoms such as nausea, vomiting, diarrhea, and bleeding.[57]

More prolonged supplementation (26 weeks) with 60mg saffron daily in men was associated with reductions in red and white blood cell counts as well as platelets, along with a drop in systolic and diastolic blood pressure of 10.8-11.7% and complaints of sedation, hypomania, and changes in appetite which started to occur after 8 weeks of exposure and increased in magnitude as the study proceded.[33]

Saffron appears to be well-tolerated acutely at the normal doses (30mg daily), whereas higher doses for more prolonged periods can induce adverse effects.

References

  1. Nahid K, et al. The effect of an Iranian herbal drug on primary dysmenorrhea: a clinical controlled trial. J Midwifery Womens Health. (2009)
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