In my last post, I claimed that the evidence for saffron was surprisingly positive. This statement demands further explanations. Saffron contains crocetin, an aglycone of crocin naturally occurring in saffron. Crocetin is said to have a wide range of effects, e.g. cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties. The more important question, thowever, is this:
How good is the clinical evidence?
Here are a few recent systematic reviews on the subject:
Meta-analysis of 8 studies assessing depression outcomes revealed a nonsignificant difference between saffron and SSRIs in reducing depressive symptoms (SMD = 0.10l 95% CI: -0.09 to 0.29). Four studies reporting anxiety outcomes showed a nonsignificant difference between saffron and SSRIs in reducing anxiety symptoms (SMD = 0.04; 95% CI: -0.22 to 0.29). With regard to safety, participants receiving saffron had fewer adverse events than the SSRI group (risk difference: -0.06; 95% CI: -0.09, -0.04; I2: 0%). Conclusion: Saffron could be a potential SSRI alternative to reduce depressive and anxiety symptoms with fewer adverse events. Further research with larger sample sizes and in diverse populations is warranted to validate these findings and explore potential moderators of treatment response.
PREMENSTRUAL SYNDROME AND DYSMENORRHEA (2025)
saffron had a significant positive effect on the symptoms of PMS in women (standardized mean difference [SMD], -0.64; 95% confidence interval [CI], -0.84 to -0.44). Furthermore, saffron was effective in reducing dysmenorrhea (SMD, -0.51; 95% CI, -1.01 to -0.01. Conclusion: saffron exerts beneficial effects on the symptoms of both PMS and dysmenorrhea in women.
Four studies met the inclusion criteria with a total of 118 patients. The results suggested an efficient role of saffron as either an adjuvant therapy to MPH or a single therapy against ADHD, without significant safety issues. Conclusion: Saffron demonstrates promise in improving ADHD symptoms, with an acceptable safety profile. Future well-designed multicentral studies are suggested.
NEUROLOGICAL/PSYCHIATRIC DISORDERS (2024)
Forty-six RCTs were enrolled, and the duration of these trials ranged from 4 to 48 weeks with saffron or its extracts, both alone or in combination with conventional drugs. Saffron was more effective than placebo in improving cognition, depression with an overall effect size of -4.26 (95% CI: -5.76, -2.77), anxiety of -3.75 (95% CI: -5.83, -1.67), and sleep disorders of -1.91 (95% CI: -2.88, -0.93). Conclusion: Saffron was non-inferior to conventional drugs for treating cognitive disorders, depression, anxiety, ADHD, and OCD, and it exhibited good tolerance with few side effects. Saffron may exert protective roles for neurological and psychiatric disorders and represents a relatively favorable and safe treatment.
ten RCTs were included in the systematic review and meta-analysis. A total of 562 participants were enrolled, with 292 assigned to the intervention group and 270 to the control group. Saffron was administered at a dose of 5 mg/day to 1 g/day. Compared with placebo, saffron supplementation significantly reduced FPG (WMD = -8.42 mg/dL; 95% CI: -13.37, -3.47; p = 0.001) and HbA1c (WMD = -0.22%; 95% CI: -0.33, -0.10; p < 0.001). However, there was no significant effect on insulin levels, QUICKI and HOMA-IR. Conclusion: Saffron is effective for patients with diabetes in terms of FPG and HbA1c, therefore, it appears to be a promising adjuvant for the glycemic control of DM. However, the overall methodological quality of the identified studies is heterogeneous, limiting the interpretation of the benefit of saffron in diabetes. More long-term follow-up, well-designed and large-scale clinical trials are warranted to draw definitive conclusions.
FEMALE REPRODUCTIVE SYSTEM DISORDERS (2024)
A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. cONCLUSION: C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal.
Eight articles were included, involving 431 participants. Crocus sativus reduced insomnia severity (SMD: 0.53; 95%CI: -0.05 to 1.11; I2 statistic = 59%; p = 0.08) and increased sleep quality (SMD 0.89, 95% CI 0.10 to 1.68; I2 statistic = 90%; p = 0.03; 6 studies, 308 participants, very low-quality evidence) and duration (SMD: 0.57; 95%CI: 0.21 to 0.93; I2 statistic = 40%; p = 0.002; 5 studies; 220 participants, moderate-quality evidence) compared with the placebos. Conclusion: Although there is limited evidence of a very low- to moderate-quality, Crocus sativus may benefit people with insomnia. This non-pharmacological intervention may reduce the chance of adults with insomnia taking sedative-hypnotic medication, thus reducing dependency and withdrawal symptoms.
20 articles met the criteria for analysis. Of the 20 articles, 3 were in-vitro studies, 13 were animal studies, and 4 were human studies. Conclusion: The findings of this systematic study (Except for two studies) suggest that saffron supplementation with potential anti-inflammatory properties may reduce the expression of the inflammatory pathway and the production of inflammatory products in diabetes.
Nine RCTs were included in the meta-analysis, and their quality was assessed using the Cochrane risk of bias tool. The pooled analysis showed that saffron supplementation had no significant effect on serum urea concentrations (WMD: – 1.05 mg/dl; 95% CI – 5.1 to 3; P = 0.6, I2 = 93%, P < 0.001) and serum creatinine levels (WMD: – 0.006 mg/dl; 95% CI – 0.08 to 0.06; P = 0.8, I2 = 79%, P < 0.001) when compared to the placebo group. In the dose-response analysis, we observed a significant non-linear relationship between the duration of saffron supplementation and serum urea and creatinine levels. Conclusions: Saffron supplementation had no significant effect on renal function markers, including urea and creatinine. However, further trials are required to determine the actual effect and safety of saffron intervention in human studies.
CARDIOVASCULAR RISK FACTORS (2022)
32 studies were taken into account (n = 1674). Consumption of saffron significantly decreased triglyceride (TG) (WMD = -8.81 mg/dl, 95%CI: -14.33, -3.28; P = 0.002), total cholesterol (TC) (WMD = -6.87 mg/dl, 95%CI: -11.19, -2.56; P = 0.002), low density lipoprotein (LDL) (WMD = -6.71 mg/dl, 95%CI: -10.51, -2.91; P = 0.001), (P = 0.660), fasting blood glucose (FBG) level (WMD = -7.59 mg/dl, 95%CI: -11.88, -3.30; P = 0.001), HbA1c (WMD = -0.18%, 95%CI: -0.21, -0.07; P < 0.001), homeostasis model assessment-insulin resistance (HOMA-IR) (WMD = -0.49, 95%CI: -0.89, -0.09; P = 0.016), systolic blood pressure (SBP) (WMD = -3.42 mmHg, 95%CI: -5.80, -1.04; P = 0.005), tumor necrosis factor α (TNF-α) (WMD = -2.54 pg/ml, 95%CI: -4.43, -0.65; P = 0.008), waist circumference (WC) (WMD = -1.50 cm; 95%CI: -2.83, -0.18; P = 0.026), malondialdehyde (MDA) (WMD = -1.50 uM/L, 95%CI: -2.42, -0.57; P = 0.001), and alanine transferase (ALT) (WMD = -2.16 U/L, 95%CI: -4.10, -0.23; P = 0.028). Also, we observed that saffron had an increasing effect on total antioxidant capacity (TAC) (WMD = 0.07 mM/L, 95%CI: 0.01, 0.13; P = 0.032). There was linear regression between FBG and the duration of saffron intake. Additionally, the non-linear dose-response analysis has shown a significant association of saffron intervention with HDL (P = 0.049), HOMA-IR (P = 0.002), weight (P = 0.036), ALP (P = 0.016), FBG (P = 0.011), HbA1c (P = 0.002), and TNF-α (P = 0.042). A non-linear association between the length of the intervention and the level of HDL and DBP was also found. Conclusion: saffron could effectively improve TG, TC, LDL, FBG, HbA1c, HOMA-IR, SBP, CRP, TNF-α, WC, MDA, TAC, and ALT.
Eight studies (n = 463 participants) were included in the systematic review. The saffron intake was associated with a statistically significant decrease in aspartate aminotransferase (AST) (SMD: -0.18; 95% CI: -0.34, -0.02; I2 = 0%) in comparison to placebo intake. Our results also indicated that saffron consumption did not have a significant effect on alanine aminotransferase (ALT) (SMD: -0.14; 95% CI: -0.36, 0.09; I2 = 47.0%) and alkaline phosphatase (ALP) levels (SMD: 0.14; 95% CI: -0.18, 0.46; I2 = 42.9%) compared to placebo. Conclusions: Saffron intake showed beneficial impacts on circulating AST levels. However, larger well-designed RCTs are still needed to clarify the effect of saffron intake on these and other liver enzymes.
Eight RCTs were eligible. Saffron supplementation resulted in a significant decrease in systolic blood pressure (weighted mean difference (WMD): -0.65 mmHg; 95% CI: -1.12 to -0.18, p = 0.006) and diastolic blood pressure (DBP) (WMD: -1.23 mmHg; 95% CI: -1.64 to -0.81, p < 0.001). Moreover, saffron supplementation reduced DBP in a non-linear fashion, based on duration (r = -2.45, p-nonlinearity = 0.008). Conclusion: Saffron supplementation may significantly improve both systolic and diastolic blood pressure in adults. It should be noted that the hypotensive effects of saffron supplementation were small and may not reach clinical importance.
COGNITIVE IMPAIRMENT/DEMENTIA (2020)
A total of four RCTs were included in this review. The analysis revealed that saffron significantly improves cognitive function measured by the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinical Dementia Rating Scale-Sums of Boxes (CDR-SB), compared to placebo groups. In addition, there was no significant difference between saffron and conventional medicine, as measured by cognitive scales such as ADAS-cog and CDR-SB. Saffron improved daily living function, but the changes were not statistically significant. No serious adverse events were reported in the included studies. Conclusions: Saffron may have the potential to improve cognitive function and activities of daily living in patients with Alzheimer’s disease and mild cognitive impairment (MCI). However, due to limited high-quality studies there is insufficient evidence to make any recommendations for clinical use. Further clinical trials on larger sample sizes are warranted to shed more light on its efficacy and safety.
BODY WEIGHT/LIPID PROFILE (2019)
We identified and analyzed 14 eligible studies in this meta-analysis. Our study found a significant reduction in cholesterol and TG following saffron intervention (weighted mean difference [WMD]: -6.36 mg/dl, 95% confidence interval, CI, [-10.58, -2.18] and WMD: -5.37 mg/dl, 95% CI [-10.25, -0.48], respectively). There was no significant effect on weight and LDL concentration. A meta-regression analysis showed that long-term saffron intervention can increase the high-density lipoprotein (HDL) levels. conclusion: findings indicate some benefits of saffron on cholesterol, HDL, and TG compared with placebo. However, we recommend the conduct of adequately powered, high-quality RCTs with short- and long-term follow-up, evaluating relevant clinical outcomes to allow for making definitive recommendations.
A total of 5 studies comprising 173 participants were included in this systematic review and meta-analysis. The analysis showed a statistically significant positive effect of saffron on sexual dysfunction (Std diff in means=0.811; 95% CI, 0.356-1.265) and its subscales (Std diff in means=0.493; 95% CI, 0.261-0.724). Heterogeneity indexes such as Cochran Q index and indicated a heterogeneity among the included studies (Q=9:981, df:4, (p=0.041), I2=59.92%). There was no evidence of publication bias in these studies. Conclusion: saffron was proven effective in improving sexual dysfunction and its subscales among participants; this effect was different on different dimensions of sexual dysfunction. Further studies are required to extend these initial findings.
A total of six trials was ultimately included. All statistical analyses were done by Comprehensive Meta-analysis (CMA) Version 2. Only in one study conducted on sperm parameters, the mean percentage of sperm with normal morphology (p<0.001) and sperm motility (p<0.001) were increased. Quantitative analysis showed that saffron had a significantly positive effect on all dimensions of Erectile Function questionnaire (MD for Erectile function=5.36(p=0.00), Orgasmic function=1.12 (p=0.007), Overall satisfaction=1.23 (p=0.005), Satisfaction with intercourse=2.18 (p=0.00) and Sexual desire=0.78 (p=0.00), Fixed effects model using 3 trials). The result of subgroup analysis based on dimensions of Erectile Function questionnaire showed statistically significant differences among subgroups (p=0.00). Conclusion: saffron has a positive effect on erectile dysfunction. However, our study showed contradictory results about semen parameters. So, interpretation of results is limited because of methodological flaws of the included studies, erectile dysfunction status and a large heterogeneity among them. Further trials are still needed to confirm the current findings.
Twelve studies met THE inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes of: major depressive disorder (n=6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n=4), and weight loss/snacking behaviors (n=1). The data from these studies support the efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior. Conclusion: saffron may improve the symptoms and the effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings.
Six studies were identified. In the placebo-comparison trials, saffron had large treatment effects and, when compared with antidepressant medications, had similar antidepressant efficacy. Saffron’s antidepressant effects potentially are due to its serotonergic, antioxidant, anti-inflammatory, neuro-endocrine and neuroprotective effects. Concusion: Research conducted so far provides initial support for the use of saffron for the treatment of mild-to-moderate depression. Further research is required to expand our understanding of the role and actions of saffron in major depression.
___________________________
Collectively, these systematic reviews render saffron unquestionably an interesting herbal remedy. Of course, not all the primary studies are of the highest standard, and neither all all the systematic reviews. But still, for once, I am impressed!
A wonder drug?
No!
But one that deserves our attention.
8 Responses to SAFFRON, a wonder-drug?
Leave a Reply
This site uses Akismet to reduce spam. Learn how your comment data is processed.
Isn’t it rather implausible that saffron has so many positive effects on such a wide range of clinical targets? I am usually sceptical when something appears to be a cure-all.
yes, me too – even me foremost!
but, in my view, implausibility has its limits as an argument; it’s better to scrutinise the evidence. and, as far as I can see, it’s better than for most SCAMs.
@Les Rose
These almost universally positive results remind me of a phenomenon called PAINS – but with the big difference that we’re not talking about in-vitro here, but actual clinical results. Then again, several compounds in the human body are known to serve completely different roles, depending on the location. E.g. serotonin is not just a ‘feelgood’ neurotransmitter in the brain, but also has completely different signalling functions in the intestine. But it is indeed pretty unlikely that a foreign substance turns out to have so many different clinical effects.
So maybe there is a common but not yet identified reason for these peculiar observations …
Don’t get me wrong. I am just mad about Saffron. However, to get these results, I think that the researchers must have mixed the Saffron with some mellow yellow.
in contrast to the spice, supplements are affordable [they use different parts of the plant]
At up to 20 USD per gram of threads… hurry up pharmacognosists!
in contrast to the spice, supplements are affordable [they use different parts of the plant]
an interesting addition: https://pmc.ncbi.nlm.nih.gov/articles/PMC13121846/