In the fast-paced world of biohacking, optimizing brain health is a top priority for those seeking enhanced cognition, mood stability, and long-term neuroprotection. Dave Asprey, the founder of Bulletproof and a pioneer in biohacking, along with other experts like Andrew Huberman and Ben Greenfield, emphasize natural compounds that support mental performance without the downsides of pharmaceuticals. Among these, saffron stands out for its potent antidepressant and cognitive benefits, but to truly maximize effects, combining it with complementary supplements creates a synergistic stack. Based on recommendations from these gurus, as well as my own experiences and tests of products, I’ll explore saffron alongside lion’s mane mushroom and omega-3 fatty acids (particularly from krill oil).
These three form a powerful trio: saffron for mood and memory, lion’s mane for neurogenesis, and omega-3s for inflammation control and brain structure. Backed by clinical research and expert insights, this combination can elevate focus, resilience, and overall brain function. There is one hitch… the Lion’s Mane mushroom must be extracted in a specific way. Dave Asprey led me to try it when I watched multiple podcasts of his on sleep. It turns out that a specific brand he claimed increases Deep Sleep by 40% or more for the night when used. I of course had to test it out myself. My own scores using Oura showed at 30-47% increase! I was blown away. More below with my Lion’s Mane info.
Saffron: The Golden Spice for Mood and Cognitive Clarity
Saffron, derived from the Crocus sativus flower, has been revered for centuries in traditional medicine and is now validated by modern science as a brain-boosting powerhouse. Its key compounds—crocin, crocetin, and safranal—act as antioxidants and neuromodulators, influencing serotonin, dopamine, and other neurotransmitters. One of saffron’s most compelling benefits is its antidepressant properties. Multiple randomized controlled trials (RCTs) show that 30 mg daily rivals SSRIs like fluoxetine for mild-to-moderate depression, with fewer side effects. A 2020 meta-analysis of 23 studies confirmed this, noting significant improvements in Hamilton Depression Rating Scale scores. For cognition, saffron enhances memory and learning by boosting brain-derived neurotrophic factor (BDNF), a protein essential for neuron growth. In Alzheimer’s patients, 30 mg daily for 22 weeks matched donepezil’s efficacy in improving cognitive scores, per a 2010 study.
On Saffron (via Nootropic Stack): “Saffron is a spice derived from the dried stigmata of the plant Crocus sativus. It has a number of functions in the brain, including influencing the reuptake by neurons of some neurotransmitters (e.g., dopamine, norepinephrine, serotonin) reuptake and activity of others (e.g., GABA, glutamate). Saffron also supports brain-derived neurotrophic factor (BDNF) and vision.”
Dave Asprey highlights saffron’s role in his protocols, noting its ability to “upgrade your mind” by reducing oxidative stress and supporting neurotransmitter balance. Other gurus agree: Andrew Huberman discusses its potential for mood regulation on his podcast, while Ben Greenfield incorporates it into nootropic stacks for focus during high-performance days. To integrate saffron, start with 15-30 mg twice daily as threads steeped in tea or capsules. It’s water-soluble, so pairing it with fats like those in Bulletproof Coffee enhances absorption.
The specific brands I settled on for Saffron are the following. I alternate between them. I once thought the ProHealth Longevity one was better, but it may have been Placebo…. they are both good. You can click any of the pics below for links to them. As always – I DO NOT make anything if you buy any of them. I’m only here to help you.
Lion’s Mane Mushroom: Fueling Neurogenesis and Nerve Repair
Lion’s mane (Hericium erinaceus) is a medicinal mushroom gaining traction in biohacking circles for its unique ability to stimulate nerve growth factor (NGF), promoting neurogenesis—the birth of new brain cells. This makes it an ideal complement to saffron, as it addresses structural brain health while saffron handles chemical balance. Research shows lion’s mane improves cognitive function in older adults. A 2009 double-blind study found 1g daily for 16 weeks enhanced scores on the Revised Hasegawa Dementia Scale, with benefits persisting post-treatment. It also reduces anxiety and depression by modulating inflammatory pathways, as evidenced in a 2010 trial where women reported lower irritation after four weeks. Animal studies reveal it accelerates myelin sheath repair, potentially aiding conditions like multiple sclerosis. Dave Asprey recommends lion’s mane in his “brain food” lineup, calling it essential for cognition and neuroprotection in his Ultimate Guide to Keeping Your Brain Young.
On Lion’s Mane: “There are good data showing that 1000mg… of lion’s mane per day and/or… chaga mushroom at 500-1500mg per day can act as adaptogens in, again, reducing cortisol but also in mainly reducing some of the anti-inflammatory cytokines…” – Andrew Huberman
I tested our 3 supplements of Lion’s Mane and until I bought the specific brand that Asprey speaks about, I saw no change in my Deep Sleep or REM times at night. The brand I now use thanks to Asprey is the following. And BAM…. It does exactly as he said. My sleep improved and you feel so much more refreshed in the morning. It took much trial and error to find the specific product, and it is a company in Australia that has it. Their extraction method is just the best. Try it – and if you are smart and already using a wearable like the Oura Ring which I used to use for years, you will literally watch your deep sleep improve within just 2 days of using it. You can click the pic below for a link to the company. I of course DO NOT make anything from them…. I do this ONLY for you and improving YOUR sleep as it has done now for thousands of others, mostly thanks to Dave Asprey and his interviews with them over the years.
Dave suggests 500-1000 mg daily, often in dual-extract form for hericenones and erinacines—the active compounds. Ben Greenfield echoes this, using it for recovery and mental clarity in his routines, while Huberman cites its BDNF-boosting effects for learning. In a stack with saffron, lion’s mane amplifies neuroplasticity, helping the brain adapt and form new connections faster. Take it in the morning with coffee for sustained focus, or at night for restorative effects during sleep. My coffee is seriously SUPER coffee every morning. Normal coffee until 12 or 1 pm at latest though as the caffeine stays in most people’s systems for 10-12 hrs and you don’t want it to effect your falling asleep.
Dave Asprey on Lion’s Mane: “Lion’s Mane Builds your brain.”
Omega-3 Fatty Acids (Krill Oil): Everyone out there loves Fish Oil.
But only a small percentage get the BEST for of the supplement for the BEST EPA and DHA that is most absorbable by your body. The brand I settled on after testing four of them, is the following: The Foundation for Brain Structure and Anti-InflammationOmega-3s, especially EPA and DHA from sources like krill oil, form the structural backbone of brain cell membranes, comprising up to 60% of the brain’s fat content. They combat inflammation, a key driver of cognitive decline, making them a staple in guru-recommended stacks. High-dose omega-3s (1-2g EPA/DHA daily) improve attention and reduce ADHD symptoms, per a 2017 meta-analysis of 16 RCTs.
For depression, they enhance antidepressant efficacy, with a 2019 review showing mood improvements in major depressive disorder. Krill oil’s phospholipid form crosses the blood-brain barrier more efficiently than fish oil, leading to better bioavailability. Asprey strongly advocates krill oil over fish oil for its astaxanthin content, which adds antioxidant protection. In his supplement list, it’s a non-negotiable for brain health, inflammation control, and mitochondrial function.
Huberman recommends 1-3g daily for neurotransmitter support, noting its role in dopamine and serotonin pathways. Greenfield pairs it with other fats for synaptic health. Synergizing with saffron and lion’s mane, omega-3s reduce oxidative stress, allowing the others to work more effectively—saffron’s mood lift is amplified in a less inflamed brain, while lion’s mane’s growth factors thrive in omega-rich membranes.
The Brand I use now… Premium Antarctic Krill Oil Omega-3 EPA DHA Non-GMO – 1,000 mg
Synergistic Stacking: Maximizing Brain Health Effects
To “max out” brain benefits, stack these supplements thoughtfully. A sample daily protocol: 30 mg saffron in morning tea for mood, 1g lion’s mane with breakfast for neurogenesis, and 1-2g krill oil omega-3s split across meals for sustained anti-inflammation. This trio targets multiple pathways—neurotransmitters (saffron), growth factors (lion’s mane), and cellular integrity (omega-3s)—creating a compounding effect.Proven synergies include saffron’s BDNF enhancement pairing with lion’s mane’s NGF boost, potentially doubling neuroplasticity. Omega-3s mitigate any mild inflammation from increased brain activity. Gurus like Asprey use similar stacks; in his routines, he combines these with biohacks like red light therapy for amplified results.
Dave Asprey on Omega-3 (Krill Oil): “To boost your mitochondrial function, eat more omega-3 fats and take a high-quality omega-3 supplement like krill oil… Because your mitochondria love using ketones as fuel, and if you give them what they want, they’ll love you back. Your microscopic mitochondria are in charge, but only to the extent that you let them rule you.”
Huberman warns of starting low to assess tolerance, while Greenfield suggests cycling every 8-12 weeks to prevent adaptation. Real-world results: Users report sharper focus, reduced brain fog, and better stress resilience. A 2021 study on combined nootropics showed improved executive function in healthy adults. it is always smart to cycle off of ALL supplements, as it helps to reset your body, which is always looking to do things in the most efficient way for your health. You don’t have to do as I do, but with this stack my plan is I take it for 3 days, then I do not take them for 2. My Deep Sleep stays at the superior level first night, then on night 2 it is still incredible, but diminishes slightly.
By day 3, I will have a normal night sleep and lose the 40%-50% better Deep Sleep from this stack. You might read this and think, why not just stay on all the time? Well… It is just my opinion after testing so many supplements and coming up with this info for year, which literally took me a few years to finalize, it is still better to cycle off. Plus, not everyone spends all of their money on their health as I do. All of these supplements can get expensive. 40 plus percent better and more Deep Sleep though affects your health greatly, so the expense is up to you. As for me I will continue to cycle it, just for safety, resetting my body and brain and then watching the amazing results once more as I take the stack yet again.
For longevity, this stack supports telomere health and reduces neurodegeneration risks.
Potential Considerations and Getting Started
While safe for most, consult a doctor if on medications—saffron may interact with SSRIs, lion’s mane with blood thinners, and omega-3s with anticoagulants. Source high-quality: ISO-certified saffron, organic lion’s mane extracts, and sustainable krill oil. Track progress with apps monitoring mood and cognition. This combination, endorsed by Asprey and peers, offers a natural path to peak brain performance. Whether combating daily stress or pursuing cognitive excellence, integrating saffron, lion’s mane, and omega-3s can transform your mental edge.
There are other supplements that I now take as well, and I’ll discuss them in other articles to come.
Mal Antoni at Whatfinger News 10/26/2025
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