Qualified by the World Health Organization (WHO) as the health epidemic of the 21st Century, stress has become a pervasive issue, affecting millions worldwide across all age groups.
Unmanaged stress not only diminishes productivity and mental wellbeing but also contributes to severe health conditions, including anxiety and depression.¹ It can also further exacerbate physical health issues, such as cardiovascular diseases and immune dysfunction.²
According to the American Psychological Association, in the US, nearly 8 in 10 adults report regularly feeling the effects of stress, which has significant ramifications for their quality of life and broader healthcare systems.
Stress’s widespread impact underscores the urgent need for increased awareness, preventive measures, and effective management strategies to mitigate its long-term consequences.
Stress as a key driver of health conditions
Chronic stress extends beyond mental and emotional strain; it significantly contributes to a variety of health conditions. For women, stress exacerbates hormonal imbalances, intensifying symptoms of premenstrual syndrome (PMS) such as irritability, fatigue, and emotional instability.
During menopause, it can worsen challenges like insomnia, hot flashes, and anxiety. Sleep, a cornerstone of physical and mental wellbeing, is often severely disrupted by stress, leading to difficulties in falling asleep, maintaining sleep, or achieving restorative rest.
Over time, this sleep disruption further compounds stress, creating a vicious cycle that undermines health. These complex interconnections highlight the necessity of holistic approaches that address the direct and indirect impacts of stress on physical and mental health.
Solutions for managing stress and improving wellbeing
Managing stress effectively requires a multifaceted approach that combines lifestyle adjustments, behavioral strategies, and in some cases, therapeutic interventions. Regular physical activity, mindfulness practices like meditation and yoga, and prioritizing quality sleep are foundational tools for reducing stress levels. Alongside these methods, dietary changes and supplementation have gained attention for their potential role in stress management.
Natural remedies, in particular, are becoming increasingly popular. Among them, saffron – a spice derived from the flower crocus sativus – has emerged as a promising option, with clinical evidence showing its ability to reduce symptoms of anxiety and depression while promoting emotional balance.
The effectiveness of saffron is closely tied to its purity and authenticity. Adulteration is a common issue in the saffron market, as saffron is one of the most expensive spices globally. Ensuring high-quality saffron involves rigorous sourcing standards, with laboratory analyses to verify the concentration of active compounds.
Only genuine, unadulterated saffron delivers the full spectrum of health benefits, making purity a critical factor in its therapeutic applications. Saffron’s effectiveness is largely due to its bioactive compounds, particularly safranal and crocin, which contribute to its antioxidant, anti-inflammatory, and neuroprotective effects.
Crocin, the carotenoid pigments responsible for saffron’s vibrant color, are linked to wellbeing enhancement through their action on dopamine. Meanwhile safranal, the compound responsible for saffron’s distinct aroma, exerts calming effects by influencing serotonin levels. Crocin and safranal support emotional balance and mental wellbeing.
Safranal: Modulating serotonin
Safranal, the primary volatile compound in saffron responsible for its characteristic aroma, is also one of its most extensively studied bioactive molecules. It plays a significant role in modulating serotonin, often called the ‘happiness neurotransmitter’, with studies highlighting its interaction with serotonin receptors.³⁻⁴
Under stress, serotonin levels are disrupted, with reduced transmission and increased reuptake and recycling, leading to emotional and physiological imbalances. Safranal could restore normal serotonin transmission by inhibiting its reuptake and recycling, thus enhancing wellbeing. Beyond stress management, serotonin is intricately connected to other health areas:
- Serotonin and premenstrual syndrome During the late luteal phase, a drop in estrogen is linked to serotonin dysregulation, contributing to symptoms like irritability, emotional instability, and sleep disturbances.
- Serotonin and menopause Declining estrogen levels during menopause reduce serotonin synthesis and enhance its reuptake. This imbalance is associated with symptoms like hot flashes and night sweats, as serotonin receptors also play a role in temperature regulation.
- Serotonin and sleep As a precursor to melatonin, serotonin is essential for regulating sleep cycles, promoting restful and restorative sleep.
By influencing serotonin pathways, safranal could not only aid in managing stress but also offer potential benefits across sleep, hormonal health, and menopause-related challenges. This underscores saffron as a valuable natural solution for holistic health support, contingent upon its high content of safranal.
Innovation in saffron extraction
Safr’Inside™ is a natural solution for stress management, preserving the full spectrum of saffron with the highest concentration of safranal (0.2% HPLC). As described above, safranal is a key-molecule for saffron’s efficacy, but its volatile nature makes it difficult to preserve during extraction processes.
With a low boiling point (70°C), safranal tends to evaporate before water or ethanol, which explains why many saffron extracts lack its characteristic molecule. To preserve saffron’s full therapeutic potential, advanced extraction technologies are crucial.
To address this challenge, Activ’Inside has developed and patented a cutting-edge technology called Tech’Care extraction™, inspired by ancestral recipes which, despite cooking at 100°C, naturally preserves saffron’s aromatic profile – including its typical scent from safranal.
By impregnating saffron metabolites into a rice starch matrix, this process preserves the integrity of the bioactive compounds from heat and solvent degradation.
This significant innovation in saffron extraction ensures that the bioactive compounds, particularly safranal, are preserved effectively. By utilizing a rice starch matrix to protect these compounds, Tech’Care extraction process preserves the full spectrum of molecules originally found in saffron.
This technology also ensures the richest concentration of safranal (0.2% HPLC), the key-molecule for saffron’s efficacy, offering reliable and potent natural remedy for stress and other health conditions.
Thanks to this innovative approach, Safr’Inside™ is the only saffron extract covered by a European patent in the stress area, which has also been patented in more than 20 countries in the five continents, including the US, Australia, and South Korea.⁵
This global patent protection ensures the exclusivity and innovation of Safr’Inside™, solidifying its position as a leading natural stress-relief solution in the global market.
Clinically proven effectiveness
Safr’Inside™ is supported by clinical trials for its ability to manage stress. In a randomized, double-blind, placebo-controlled study, a single dose of 30mg of Safr’Inside™ provided protection against acute stress within just 30 minutes, delivering a rapid relaxing effect.⁶
Over a two-month supplementation period, Safr’Inside™ further improved emotional balance and increased crocetin levels in urine, confirming both the bioavailability of this saffron extract and its direct link to enhanced emotional health. These results were echoed by consumer feedback, with participants reporting improved daily morale and reduced stress after only seven days of use.
Addressing stress effectively requires not targeting a single mechanism, but adopting a holistic approach that considers the interplay of multiple factors. With the highest concentration of safranal, Safr’Inside™ is a saffron extract with six published mechanisms of action, proven to act at several levels of the body:⁶⁻¹⁰
- In human neurons, Safr’Inside™ has been shown to enhance the transmission of serotonin, thanks to its high safranal content. Additionally, it significantly reduces reactive oxygen species while increasing levels of brain-derived neurotrophic factors, indicating a protective effect against damage caused by oxidative stress.
- Safr’Inside™ effectively regulates the secretion of cortisol, the ‘stress hormone’, while also supporting the nervous system. Remarkably, just 30 minutes after intake, it activates the parasympathetic system, producing a calming and relaxing effect.
- Safr’Inside™ has shown significant effects on the gut-brain axis, including modulation of the gut microbiota, notably by increasing the levels of Akkermansia bacteria, while also impacting the gut microbiome and brain proteome.
- Lastly, Safr’Inside™ has been shown to reduce inflammatory markers in both joint and intestinal cells, highlighting its broad anti-inflammatory properties.
These multi-level effects position Safr’Inside™ as a powerful and holistic solution for managing stress and supporting overall wellbeing.
By combining cutting-edge science with nature’s richness, Safr’Inside™ sets a new standard for stress management solutions, offering individuals a holistic and effective path toward resilience and improved quality of life.
References
1. CAMH. Stress.
2. National Institute of Mental Health. I’m So Stressed Out! Fact Sheet.
3. Amin, F.; et al. Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis. Molecules. 2022 Dec 7;27(24):8658.
4. Hosseinzadeh, H.; et al. Effect of Crocus sativus L. Stigma Extracts and their Constituents, Crocin and Safranal, in Mice. Acta Hortic. Acta Hort 650, ISHS 2004.
5. European Patent Office. Registre européen des brevets.
6. Jackson, PA. ; et al. Effects of Saffron Extract Supplementation on Mood, Well-Being, and Response to a Psychosocial Stressor in Healthy Adults: A Randomized, Double-Blind, Parallel Group, Clinical Trial. Front Nutr. 2021.
7. Wauquier, F.; et al. Circulating Human Serum Metabolites Derived from the Intake of a Saffron Extract (Safr’InsideTM) Protect Neurons from Oxidative Stress: Consideration for Depressive Disorders. Nutrients. 2022.
8. Pouchieu, C.; et al. Acute Effect of a Saffron Extract (Safr’InsideTM) and Its Main Volatile Compound on the Stress Response in Healthy Young Men: A Randomized, Double Blind, Placebo-Controlled, Crossover Study. Nutrients. 2023.
9. Pontifex, MG.; et al. Saffron extract (Safr’InsideTM) improves anxiety related behaviour in a mouse model of low-grade inflammation through the modulation of the microbiota and gut derived metabolites. Food Funct. 2022.
10. Pourtau, L.; et al. Reduced Production of Pro-Inflammatory and Pro-Catabolic Factors by Human Serum Metabolites Derived from a Patented Saffron Extract Intake. Pharmaceutics. 2024.
