Ashwagandha is a herb that belongs to the night shade family of plants. The nightshade family of plants is a very interesting one and includes a lot of vegetables that make up large parts of many diets. Notable nightshade members are potatoes, tomatoes, chili peppers, goji berries and even tobacco! Another name for the nightshade family is Solanaceae. This is where Ashwagandha gets its Latin name from; Withania somnifera. Ashwagandha is a short perennial shrub, with a large root system that develops small deep orange fruits. The fruits resemble a small cherry and the leaves look frosty due to the many tiny hairs that are on them. This one of the reasons why Ashwagandha is also referred to as ‘winter cherry’. Traditionally, the Ashwagandha root is used, however new research has found high concentrations of key components in the leaves too. Various manufacturers have taken notice of this. One of the most notable being Natreon who produce a specialized extract of Ashwagandha called Sensoril. Sensoril is made from the leaves of Ashwagandha, giving it a unique chemical composition, which produces noticeable calming effects.

The stigmas of Crocus sativus are feather light, and that means you need A LOT of them to produce the saffron spice. On average, it takes about 150 Crocus sativus flowers to produce just a single gram of saffron spice. That means, for a mere kilogram of saffron, you need to harvest an absolutely mind boggling amount of Crocus sativus flowers, about 150,000 flowers! To make matters worse, all of these flowers have to be harvested early in the early morning, so your harvesting window is incredibly narrow. In addition to the complexity of harvesting, the processing of saffron is where things get even more tricky. By hand, the three tiny and delicate stigmas need to be removed. Now imagine doing that 150,000 times to produce just a single kilogram of the spice! After the stigmas have been harvested, they also have to be precisely dried, because without the crucial drying stage, the aromatic compound in saffron, safranal, will not be present.

Now that you know just how much work goes into cultivating, harvesting and processing saffron, the question becomes, why go through all of this trouble and why have we been cultivating and using it for thousands of years? On the culinary side, saffron produces a complex array of aromas, flavors and colors that are hard to achieve with other spices. When properly cultivated and dried, the aroma of saffron can be intoxicating, providing a beautiful bouquet of honey, tobacco, leather and hay. These aroma’s also transfer to the taste of saffron, providing a deep yet delicate flavor profile that is also highlighted by a unique bitterness. Tasting saffron pure, can however be slightly unpleasant, with the bitterness taking on a metallic quality, but used in the right amounts, it can bring many layers of complexity to your food. Another hallmark of saffron's culinary use is its ability to color food a deep, vibrant yellow. It can bring life and color to practically any dish!

On the medicinal side, saffron has also seen widespread use for thousands of years! This is no surprise, because the bioactives in saffron produce some really unique effects. One of the primary traditional uses, appears to be as a mood brightener and saffron is still renowned for this effect today. Branching off from the mood brightening effects, saffron was also often used during menstruation, as a way to lift spirits but also to dampen pain. In fact, saffron was often utilized as a pain management herb! Saffron also appears to have been used traditionally for enhancing eye health. Now this is where things get interesting, the list of traditional uses simply doesn’t stop! It seems like saffron was used as a bit of an “panacea herb”, with there being a seemingly endless number of uses for it. Saffron was considered to be good for the kidneys, liver, lungs, brain, eyes, joints, cardiovascular system, metabolic system, reproductive system and our skin!

Within its traditional medicinal use, the saffron stigmas are often extracted into water, which makes a lot of sense because the majority of the compounds within saffron are highly water soluble. These water preparations were then used both internally and externally on the skin. In addition to the water extracts, it also appears that saffron was sometimes extracted into sesame or olive oil for a number of days. This oil extract was then also used both internally and externally on the skin. However, likely the most common way saffron was consumed, is simply through food as this is where perhaps the largest quantities of saffron were consumed. This is common in cultures where highly bioactive herbs are used in relatively large quantities in food, and gives an interesting functional twist to the majority of dishes consumed during the day!

One of the most interesting things about saffron is its biochemistry. When the Crocus sativus stigmas are immature, they are bright yellow, and over time this transitions to orange and eventually into crimson red. This color change reflects what is happening biochemically within the Crocus sativus stigmas. When the stigmas are immature and yellow-orange, they contain a high concentration of the carotenoid zeaxanthin, which just so happens to be bright yellow-orange in its pure form. During the maturation of the stigmas, enzyme systems kick on which oxidatively cleave zeaxanthin at both ends to liberate 3-OH-β-cyclocitral and dialdehyde. As stigma maturation progresses further, the liberated dialdehyde then converts into crocetins which then converts into crocins. At this stage of stigma maturation, the stigmas are becoming bright crimson red, which directly mirrors the appearance of crocetins and crocins. This makes a lot of sense, because in their pure form, crocin and crocetin are bright crimson red and are in fact entirely responsible for the unique color of saffron!

At the crimson red stage of stigma maturity, you would notice a distinct lack of aroma that is commonly associated with saffron spice. The reason for this is because the aroma molecule, safranal, has not appeared yet. As we mentioned earlier, zeaxanthin gets converted in 3-OH-β-cyclocitral and dialdehyde. The 3-OH-β-cyclocitral is converted to picrocrocin during maturation, and this is one of the compounds within saffron that gives it its unique deep bitter flavor. The picrocrocin is then converted to safranal, the unique aroma compound, but this actually only occurs during the crucial drying stage! This is quite fascinating, and a concept we see pop up fairly frequently, and is not talked about nearly enough! For example, raw undried maca doesn't contain the macamides, which only form during the drying stage. Another great example is that raw vanilla pods don’t smell or taste like vanilla, these aromas and flavors only occur during the curing and drying stage. This further highlights just how difficult it can be to produce the saffron spice, because the safranal content is both crucial for culinary applications and medicinal applications!

Now that we know where saffron potentially comes from, how it is cultivated and processed, its traditional uses, and its biochemical pathways, it's time to dive into the science behind its unique array of benefits! Let’s start with the mood effects, as this is one of the primary traditional uses.

Saffron has a fairly wide array of effects on mood, hitting many different neurotransmitter systems. First and foremost, it is a mild serotonin reuptake inhibitor. What this means is that the bioactives in saffron can block a transporter which normally removes serotonin from the synaptic cleft following its release from neurons. When we block this transporter, it means serotonin can reside in the synaptic cleft a little bit longer, thus allowing it to bind to serotonin receptors for a longer period of time. Since serotonin is highly involved in mood, boosting its levels subtly can be very beneficial for overall mood state. However, inhibiting this transporter too much can actually lead to quite a lot of negative effects. This is what makes saffron unique, because the effect on the serotonin transporter is quite mild, and thus the effects are very natural and balanced.

Focusing on serotonin a little bit more, perhaps brings us to one of the most interesting effects of saffron. Sparse research has indicated that saffron bioactives may act as a serotonin 5-HT2C antagonist. The serotonin 5-HT2C receptor is very unique because it actually controls the release of dopamine and norepinephrine. When 5-HT2C is activated, it blocks the release of dopamine and norepinephrine, on the flipside when you block this receptor, dopamine and norepinephrine release is enhanced. This means that if saffron is indeed a 5-HT2C antagonist, then it will increase the release of both dopamine and norepinephrine! Another theory is that saffron blocks the dopamine and norepinephrine transporters, thereby also enhancing their levels. Either way, studies have shown that saffron bioactives can significantly enhance dopamine and norepinephrine levels, so regardless of the mechanism by which this is happening, the dopamine and norepinephrine increases play a major role in the mood brightening effects of saffron!

Saffron may also help enhance the levels of dopamine, norepinephrine and serotonin by acting as mild non-competitive monoamine oxidase (MAO) inhibitors, targeting both MAO-A and MAO-B. The MAO enzymes degrade dopamine, norepinephrine and serotonin, thus by inhibiting their activity, the levels of dopamine, norepinephrine and serotonin will increase. Summing everything up, from the reuptake inhibition effects, to potential 5-HT2C antagonism and MAO-A & B inhibition, saffron has a very significant impact on monoamines in the brain!

Switching gears to the amino acid neurotransmitters GABA and glutamate, saffron also plays a unique role here. GABA is an inhibitory neurotransmitter and is often associated with calming effects and muscle relaxation, whereas glutamate is an excitatory neurotransmitter and is often associated with memory but also nervousness and agitation. Saffron bioactives activate GABAergic signaling, and inhibit glutaminergic NMDA signaling which when combined, produces very unique mood elevating and relaxing effects. When paired with the monoaminergic effects of saffron, this produces incredibly comprehensive effects on mood! However, saffron has another trick up its sleeve, neuroplasticity.

When we are stressed, the levels of a unique peptide called pituitary adenylate cyclase-activating polypeptide (PACAP) drops. This negatively affects neuroplasticity because PACAP phosphorylates extracellular regulated protein kinases (ERK) and response element binding protein (CREB), both of which are crucial for the expression of synaptic plasticity proteins like brain derived neurotrophic factor (BDNF). Saffron bioactives can reverse this negative effect of stress on neuroplasticity, by enhancing the expression of PACAP and thereby helping to increase neuroplasticity! When combined with its monoaminergic, NMDA antagonist and GABA agonist effects, this makes saffron an absolute powerhouse for mood!

All of the neurological effects that we just covered, will also produce a fairly prominent nootropic effect, helping to enhance overall cognitive function. Saffron bioactives also strongly modulate oxidation and inflammation, even in the brain, and when combined with the neuroplasticity effects, you end up with a significant neuroprotective effect! This protective effect also extends further out into our visual system, with the saffron bioactives being strongly protective of our eyes! It partially achieves this through its oxidation and inflammation regulating effects, however, saffron has an additional trick up its sleeve. Saffron bioactives can help protect the eyes from the negative effects of too much ATP, by blocking one of the receptors ATP activates, P2X7. Via this pathway, saffron appears to be very protective of the visual system, and thus it is no surprise this was often a highly touted traditional use!

The pain management effects of saffron are also often cited as one of the primary traditional uses, and this can be partially traced back to saffron bioactives effects on NMDA and GABA signaling. The NMDA receptors are crucial in controlling neurological nociceptive signaling. When NMDA receptors are blocked, nociceptive signaling is dampened and this produces a unique neurological pain management effect. This also applies to GABAergic signaling, where increased GABAergic signaling can lead to muscle relaxation and a dampening of nociceptive signaling. Nociceptive processing is also highly influenced by serotonergic and dopaminergic signaling, and thus, saffron is incredibly comprehensive when it comes to tackling pain via neurological mechanisms!

Stepping outside of the CNS, saffron bioactives also produce prominent pain management effects by modulating inflammation and oxidation. For a deeper explanation on how these processes influence pain, check out our pain blog or our pain podcast. Anecdotally, we have found that the pain management effects of saffron are surprisingly potent! Combining the mood elevating effects with the pain management effects, then also provides a good scientific explanation as to why saffron was often used to offset the negative mood and pain that menstruation can induce.

Moving to the cardiovascular effects, saffron bioactives produce two distinct effects. The first of which is controlling oxidation throughout the cardiovascular system which can be highly beneficial. Secondly, saffron bioactives appear to increase the bioavailability of an important vasodilator called nitric oxide. Through this effect, saffron can increase blood flow, which can have positive impacts on overall cardiovascular function. Running with the nitric oxide effects a little further, also identifies an exercise performance benefit. More blood flow is often a highly desired effect when working out, as it will increase the “pump” experienced when blood rushes into muscle that are being worked out. This will especially be the case when saffron is stacked with other nitric oxide boosters like citrulline, arginine, and agmatine!