HOLY BASIL COMMON NAME

Holy Basil | Sacred Basil | Tulsi | Tulasi

TOP BENEFITS OF HOLY BASIL

Supports a calm mood
Supports cognitive function
Support a healthy stress response
Supports general immune health

WHAT IS HOLY BASIL?

Holy Basil (Ocimum sanctum; synonym Ocimum tenuiflorum) is a culinary and medicinal aromatic herb that has been used within Ayurvedic medicine for more than 3000 years[1]. In Ayurvedic medicine holy basil is called “tulsi,” which translates as “the incomparable one.” It is one of a small number of herbs categorized as Rasayana, the category applied to elixirs and tonic herbs prized for rejuvenation and revitalization. It was believed to guard the body from stress of all types while keeping the mind sharp and the body healthy. In modern times, holy basil is categorized as an adaptogen, supporting a healthy stress response. Holy basil also supports mood, cognition and immunity. Holy basil’s bioactive molecules include ursolic acid, rosmarinic acid, eugenol, ocimumosides A and B, ocimarin, apigenin and lutein[2,3].

NEUROHACKER’S HOLY BASIL SOURCING

Holy Basil is a leaf extract standardized to contain not less than 2% ursolic acid.

Holy Basil is Non-GMO and Vegan.

HOLY BASIL DOSING PRINCIPLES AND RATIONALE

Because holy basil is an Ayurvedic Rasayana herb, we consider dosing to follow hormetic principles similar to herbal adaptogens (see Neurohacker Dosing Principles ). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. For herbs that are adaptogens, especially when they will be used for extended periods of time, we think it’s important to identify the lowest dose that can produce many of the desired responses. Different doses of holy basil have been used in human studies. Functional benefits have occurred at low doses (~300mg) and at doses four-fold higher (1200mg). Considered collectively, human studies suggest holy basil dosing may be somewhat akin to the Pareto Principle (i.e., 80-20 rule), where 80%+ of the benefits happen at 20% of the dose. Our goal with holy basil, as with all ingredient choices, is to select the appropriate dose keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other adaptogen extracts, we are likely to use less holy basil than if the only herbal adaptogen we were using was holy basil.

HOLY BASIL KEY MECHANISMS

Mood and stress response
Supports a calm mood
Supports a positive mental-emotional bias
Supports healthy stress hormone levels

Brain function
Supports memory and learning
Supports working memory
Supports executive function
Supports attention
Supports sleep
Supports serotonin signaling
Supports dopamine signaling
Supports adrenergic signaling
Supports acetylcholine signaling
Down-regulates acetylcholinesterase (AChE) activity
Up-regulates choline acetyltransferase (ChAT) expression
Supports brain antioxidant defenses
Supports neuroprotective functions

Immune System
Supports innate immunity
Supports adaptive immunity

General health
Supports gastroprotective functions
Supports healthy metabolism

SAFFRON COMMON NAME

Saffron | Saffron Crocus

TOP BENEFITS OF SAFFRON

• Supports mood
• Supports cognitive function
• Supports vision

WHAT IS SAFFRON?

Saffron is a spice derived from the flowers of Crocus sativus. It’s been used and traded as a spice for at least 4000 years and is considered the world’s most costly spice by weight. Saffron has had a wide range and long list of traditional uses. In Traditional Iranian Medicine saffron was thought to be useful for supporting sleep and mood, and to be a heart tonic. And in India it was used as a nerve and heart tonic, and for relaxation and sleep support. Iran produces the majority of saffron: Greece, Kashmir, Morocco, Spain and Turkey are also fairly large growers. Saffron, as a spice, refers to the deep red-maroon colored stigma and styles (called threads). Not all saffron is of the same quality and strength, with price increasing substantially for the highest grades. In general, content of several of saffron’s active compounds are used to determine strength. A greater content of crocin (responsible for saffron’s color), picrocrocin (a bitter compound giving the characteristic taste), and safranal (which gives the fragrance) would be graded as higher strength. In addition to these marker compounds, saffron also contains zeaxanthin, lycopene, and other carotenoids. Crocin also belongs to the carotenoid family. Most carotenoids only dissolve in oil (i.e., are fat-soluble). Crocin is water-soluble, which is part of the reason it is used in rice dishes and other water-based food recipes. There’s been a growing interest in the use of saffron for health purposes, including in areas such as mood, cognition, vision, sports performance, appetite regulation, metabolic function, sleep, and women’s health.

NEUROHACKER’S SAFFRON SOURCING

There’s a long history of saffron adulteration. Because of this, Neurohacker feels it is critical to use a standardized saffron extract purchased from an ingredient supplier that can authenticate quality and strength.

The saffron extract we use has been clinically studied, is DNA authenticated, and has a patented profile for marker compounds including crocin, picrocrocin and safranal.

Saffron extract used in our products is GRAS, non-GMO, gluten-free, vegan, Kosher certified and Halal compliant.

SAFFRON DOSING PRINCIPLES AND RATIONALE

Most saffron studies have used standardized extracts, with doses typically in the range of 20-30 mg per day. While a few studies have used 60 mg, in general, we consider 30 mg to be at the top end of what’s needed when using saffron extracts for specific clinical reasons. Since studies comparing multiple doses or different standardizations have not been published, there’s no information of whether saffron has a threshold effect (i.e., an amount or range less than the full dose where the majority of the response would occur; see Neurohacker Dosing Principles). However, individual (i.e. N of 1) subjective response to saffron does vary considerably, with some persons reporting noticeable differences when taking as little as 1-3 mg of a standardized saffron extract. Depending on the purpose Neurohacker is using saffron for, and the other ingredients it’s combined with, it might be dosed anywhere ranging from a more micro-dose level up (3 mg) up to a studied dose of 30 mg per day.

SAFFRON KEY MECHANISMS

Mood

• Supports a positive mental-emotional bias
• Supports a calm mood

Brain function

• Supports focus and attention
• Supports healthy brain aging
• Supports sleep
• Supports dopamine signaling
• Supports GABA-glutamate signaling
• Supports acetylcholinesterase activity
• Supports brain-derived neurotrophic factor (BDNF) levels
• Supports neuroprotective functions
• Supports long-term potentiation

Vision

• Supports retinal function
• Protects macular health
• Supports visual acuity
• Protects retinal cells against light-induced damage
• Protects retinal cells against damage and degeneration
• Supports healthy intraocular pressure

Exercise performance

• Enhances reaction times
• Supports muscle strength
• Supports muscle recovery functions

Antioxidant defenses

• Supports antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx])
• Replenishes glutathione (GSH) levels
• Supports free-radical scavenging
• Promotes healthy prooxidant-antioxidant balance

Mitochondrial function

• Supports the activity of mitochondrial enzymes
• Supports mitochondrial membrane potential

Metabolic function

• Supports cytokine balance
• Supports appetite regulation
• Supports healthy lipid levels and blood pressure regulation

VINEATROL®20 COMMON NAME

Common Grapevine

TOP BENEFITS OF VINEATROL®20

Supports healthy aging

Supports cognitive function

Supports mood

Supports antioxidant defenses

WHAT IS VINEATROL®20?

Vineatrol®20 is a grapevine shoot extract rich in resveratrol monomers and oligomers. Resveratrol is best known as a calorie restriction mimetic (i.e., supports healthy aging functions), and for supporting metabolism, heart health, immunity, and cognition. Resveratrol derivatives have been the subject of thousands of pre-clinical and clinical research studies. While trans-resveratrol is the most studied of the resveratrol derivative family, some of the other resveratrol derivatives may have structure/function benefits not shared by trans-resveratrol, which could be more potent than trans-resveratrol for certain functions, and tend to be complementary when given together. In other words, there’s a synergy in the mix of resveratrol derivatives that naturally occur in the grape plant. This synergy has shown up in experiments done on Vineatrol®, where it was a stronger antioxidant than resveratrol alone and a more potent sirtuin 1 (Sirt-1) activator than a resveratrol dimer. But what exactly are resveratrol monomers and oligomers? Trans-resveratrol is an example of a resveratrol monomer—a monomer is a molecule that can be bonded to other identical molecules—so think of it as one unit of resveratrol. Trans-ε-viniferin is a resveratrol dimer, which means it’s two identical resveratrol molecules bound together into an oligomer: Think of it as two units of resveratrol. But there are quite a few other resveratrol derivatives in the resveratrol oligomer family, since up to eight resveratrol molecules can couple together. The advantage of Vineatrol®20 is that it is standardized to contain at least 20% of these different resveratrols.

NEUROHACKER’S VINEATROL®20 SOURCING

Vineatrol®20 is a grapevine shoot extract from Vitis vinifera (i.e., the common grapevine) grown and harvested in the famous Bordeaux vineyards.

Vineatrol®20 is triple standardized for: (1) trans-resveratrol >5%; (2) trans-ε-viniferin >5%; and (3) total resveratrol monomers and oligomers >20% (hence the 20 in the name).

Vineatrol®20 is a registered trademark of ACTICHEM, a French company specializing in the development of resveratrol and resveratrol derivatives extracted from grapevines.

Vineatrol®20 is Non-GMO and Vegan.

VINEATROL®20 DOSING PRINCIPLES AND RATIONALE

When thinking about the dose of Vineatrol®20 there are a few things to keep in mind. This grapevine extract has been standardized to contain at least 5% trans-resveratrol and not less than 20% resveratrol monomers and oligomers. When we include this extract in a formulation it’s because we want to give a range of resveratrol monomers and oligomers (not just trans-resveratrol). Focusing only on the trans-resveratrol content misses the big picture. The other thing to keep in mind is that resveratrols are not examples of more is better compounds. They are better thought of as a hormetic; something that in low to moderate amounts helps promote an adaptive response to stress, but which might not be as beneficial at very high doses especially if taken long-term (see Neurohacker Dosing Principles). Our goal with Vineatrol®20, as with all ingredient choices, is to select the appropriate dose keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other extracts with complimentary polyphenols, we are likely to use less than if the only polyphenol-containing ingredient we were using was Vineatrol®20. Lastly, while high amounts of trans-resveratrol have been studied, when used as part of a grape extract, the amount of resveratrol in studies has typically been less than 10 mg and as low as 1 mg.

VINEATROL®20 – RESVERATROL KEY MECHANISMS

Brain function

Supports cerebral blood flow

Supports neural stem cell functions

Supports neurogenesis

Supports brain-derived neurotrophic factor (BDNF)

Supports HPA axis signaling

Supports neuroprotective functions

Supports executive function

Supports learning and memory (animals)

Cardiovascular function

Supports healthy vascular function

Supports cardiac function

Exercise performance

Supports endurance performance

Supports muscle structure and function

Supports glucose uptake in muscles

Metabolic Function

Supports healthy insulin sensitivity

Supports healthy lipid levels

Supports thermogenesis

Supports adiponectin levels

Mitochondrial structure and function

Supports peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)

Supports nuclear transcriptional factors of mitochondrial biogenesis (nuclear respiratory factor-1 [NRF1], NRF2, mitochondrial transcription factor A [TFAM])

Supports mitochondrial size and number

Supports inner mitochondrial membrane folding (cristae)

Supports mitochondrial DNA (mtDNA)

Supports mitochondrial membrane potential

Supports citrate synthase

Supports ATP production

Supports NAD+ pool

Supports components of the electron transport chain – complex I-V

Supports β-oxidation

Signaling pathways

Supports AMPK signaling

Supports liver kinase B1 (LKB1) signaling

Supports peroxisome proliferator-activated receptor alpha (PPARα)

Supports peroxisome proliferator-activated receptor gamma (PPARγ)

Supports estrogen-related receptor alpha (ERRα)

Supports forkhead transcription factor O 1 (FOXO1)

Downregulates phosphodiesterase (PDE) 1 and 4 and supports adenylate cyclase/cAMP levels

Antioxidant defenses

Supports antioxidant activity

Supports antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx])

Downregulates pro-oxidant enzymes (NADPH oxidase)

Gut microbiota

Supports healthy gut microbiota

Healthy aging and longevity

Supports stem cells

Supports telomerase activity

Supports anti-senescence functions

Activates SIRT1

Supports mitochondrial uncoupling proteins UCP1, UCP2, and UCP3

Supports Klotho

Supports mTOR signaling

Delays age-related physiological changes

Extends lifespan (mice on high-calorie diet, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae)

Circadian rhythms

Supports circadian rhythms

Supports clock gene expression

Ingredient Synergies

Apigenin

Piperine

REISHI MUSHROOM COMMON NAME

Reishi | Lingzhi | Ganoderma

TOP BENEFITS OF REISHI MUSHROOM

• Supports general immune health
• Supports sleep

WHAT IS REISHI MUSHROOM?

Ganoderma lucidum is considered the “mushroom of immortality” and called Reishi in Japanese—this is the name it’s most known as in America—and Lingzhi in Chinese. In Traditional Chinese Medicine, it is considered to be a shen tonic. Shen tonics were believed to play roles in supporting peace of mind, joy, emotional balance, optimism, sound sleep, and clear thinking. Reishi’s traditional uses, which included replenishing Qi, easing and centering the mind, increasing resistance to fatigue, promoting well-being, and supporting sleep, are consistent with this role as a shen tonic. It was thought to be ideal for countering restlessness and quieting an overactive mind. In addition to these traditional uses, modern research on reishi mushrooms has focused on immune system support and rejuvenating processes, including stem cell function.*

Reishi extracts contain a variety of compounds, most notably, polysaccharides (including beta glucans), peptidoglycans, and triterpenoid compounds (including lucidenic acids). Reishi also contains low amounts of nucleosides (adenosine, cytidine, guanosine, inosine, thymidine, uridine), nucleotide bases (adenine, guanine, hypoxanthine, thymine and uracil), and the neurotransmitter GABA[1–3].

NEUROHACKER’S REISHI MUSHROOM SOURCING

Reishi mushroom extract is from the fruiting body, not the mycelium. The fruiting body is what is usually thought of as the “actual” mushroom, as opposed to the mycelium, which is akin to the “root” system of a mushroom.

Reishi mushroom is concentrated through the extraction process (i.e., grams of mushroom are needed to produce one gram of the extract) resulting in a final extract with not less than 30% polysaccharides, since these compounds are linked to general immune support.

Reishi mushroom is Non-GMO and Vegan.

REISHI MUSHROOM DOSING PRINCIPLES AND RATIONALE

Because reishi is thought of as being an adaptogenic mushroom, we consider dosing to follow hormetic principles similar to herbal adaptogens (see Neurohacker Dosing Principles). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone, so our focus with reishi is to provide an amount within this range. When deciding on a dose for a mushroom like reishi, it’s also important to consider the concentration, because more concentrated extracts require lower mg amounts than crude extracts. And finally, it’s important to consider whether the extract is made from fruiting bodies only, or uses mycelium, since the fruiting bodies are the part of a mushroom that concentrates active compounds. Our goal with reishi, as with all ingredient choices, is to select the appropriate dose keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other adaptogen extracts, we are likely to use less reishi than if the only adaptogen we were using was reishi.

REISHI MUSHROOM KEY MECHANISMS

Brain function

• Supports learning and memory
• Supports sleep
• Supports neurogenesis
• Upregulates neural progenitor cell (NPC) proliferation
• Supports brain mitochondrial function
• Supports nerve growth factor (NGF)
• Supports neuroprotective functions
• Supports brain antioxidant defenses

Stress

• Supports healthy behavioral and physiological responses to stress

Gut Microbiota

• Supports the composition of the gut microbiota
• Supports microbial metabolism
• Supports gut immunity
• Supports intestinal barrier function

Immune System

• Supports general immune health
• Supports innate immunity
• Supports adaptive immunity
• Supports mucosal immunity
• Supports immune tolerance
• Supports cellular intrinsic immune defenses
• Supports immune signaling
• Supports healthy dendritic cell function
• Supports healthy natural killer cell function
• Supports healthy macrophage function
• Supports healthy microglial function
• Supports healthy B cell function
• Supports healthy T cell function

Healthy aging

• Supports mitochondrial function
• Supports mitochondrial biogenesis
• Supports autophagy
• Supports AMPK signaling
• Supports mTOR signaling
• Supports stem cell proliferation
• Supports stem cell differentiation
• Supports antioxidant defenses
• Supports Nrf2

WITHANIA SOMNIFERA COMMON NAME

Ashwagandha | Indian ginseng

TOP BENEFITS OF WITHANIA SOMNIFERA

Supports sleep
Supports stress relief
Supports memory and cognition
Supports muscle strength and endurance
Supports sexual health
Supports a healthy body weight
Supports thyroid health

WHAT IS WITHANIA SOMNIFERA

Withania somnifera is commonly called ashwagandha. Ashwagandha (i.e., Indian ginseng) is a Rasayana—the category of elixirs and tonic herbs prized by the branch of Ayurvedic medicine concerned with rejuvenation and focused on promoting a youthful state of physical and mental health. Ashwagandha holds a prominent place among the Rasayana herbs, where it was used for many reasons including as general tonic and to infuse energy and vigor in circumstances characterized by exhaustion or a lack of physical energy. A key attribute is that ashwagandha promotes balance. As the English name Indian ginseng implies, ashwagandha was believed to share some of the attributes of ginseng, in essence supporting multiple areas of health and well-being, especially under conditions characterized by increased stress. Herbs that produce these types of nonspecific resistance to and recovery from stress—and which typically also support general well-being, healthy energy, and homeostasis—are called adaptogens. Among its studied benefits, ashwagandha supports sleep quality, relaxation, muscle recovery, cognitive function, immunity and a healthier stress response.

NEUROHACKER’S WITHANIA SOMNIFERA SOURCING

KSM-66 Ashwagandha® was the product of 14 years of R&D. It is the most researched brand of ashwagandha, with a research focus on what happens in healthy people when they take the ingredient.

Created by Ixoreal Biomed Inc., the world’s ashwagandha experts. Ixoreal owns the entire production chain from farm to the finished ingredient, allowing them to deliver high-quality ashwagandha with batch-to-batch consistency.

KSM-66 Ashwagandha® is a “full-spectrum” root extract, which means it is designed to maintain the balance of the various constituents found in the root. It is standardized for ≥5% withanolides and <0.1% withaferin A.

KSM-66 Ashwagandha® has won awards as an innovative ingredient and for sports nutrition. It has also qualified for an extensive number of certifications including Organic, Non-GMO, GRAS, Vegan and Gluten-Free.

KSM-66 Ashwagandha® is a registered trademark of Ixoreal Biomed Inc.

WITHANIA SOMNIFERA DOSING PRINCIPLES AND RATIONALE

We consider Withania somnifera (i.e., ashwagandha) to be an herbal adaptogen, so expect it to follow hormetic dosing principles. Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. Based on studies where different doses have been given in the same study, we also consider ashwagandha dosing to be somewhat akin to the Pareto Principle (i.e., 80-20 rule), because much of the benefits have occurred at a lower dose, and relatively modest additional gains are achieved at doses two- to four-fold higher (see Neurohacker Dosing Principles). Because of both of these reasons, it’s important to identify the lowest dose that can produce many of the desired responses when using ashwagandha. Since we also use ashwagandha in more than one product, it’s also important to us to ensure that a user taking several of our products will not inadvertently take too much ashwagandha. The most common dose of KSM-66 Ashwagandha® in human studies has been 300 mg taken twice a day (i.e., 600 mg a day total). We consider this to be the upper end of the total amount of daily ashwagandha that we’d want a customer to take over a long period of time, and 300 mg to be the maximum at a given time of day (i.e., if being taken at dinner as an example). We consider the lower end of the beneficial range to be about 125-150 mg depending on the ashwagandha extract being used.

WITHANIA SOMNIFERA KEY MECHANISMS

Sleep

Supports sleep onset

Supports sleep efficiency

Supports quality of sleep

Supports slow-wave sleep

Supports total sleep time

Mood and stress

Supports a calm mood

Supports stress management

Supports health cortisol levels

Brain function

Supports cognitive and psychomotor performance

Supports memory, executive function, attention, and information processing speed

Supports GABAergic neurotransmission

Supports GABA receptor signaling

Supports dopamine levels

Downregulates the basal activity levels of acetylcholine esterase

Supports neuroprotection – protects from neuronal mitochondrial swelling and apoptosis; protects cognitive function (ischemia, oxidative stress)
Protects from neurotoxicity

Immune system

Supports innate immunity

Supports adaptive immunity

Supports immune system communication

Mitochondrial function

Supports mitochondrial membrane potential and structural integrity

Protects from mitochondrial damage

Protects from mitochondrial membrane permeabilization

Protects from complex I-V Inhibition (protects electron transport chain and oxidative phosphorylation performance)

Supports citric acid cycle enzymes

Exercise and sports

Supports endurance performance

Supports muscle strength

Supports post-exercise recovery

Metabolic function

Supports healthy insulin sensitivity

Supports healthy blood glucose levels

Supports healthy leptin signaling

Supports healthy body weight

Supports healthy feeding behaviors

Supports lean mass

Antioxidant defenses

Supports antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT],glutathione peroxidase [GPx])

Replenishes glutathione (GSH) levels

Counters oxidative stress and reactive oxygen species levels

Cellular signaling

Downregulates the expression of some cytokines including tumor necrosis factor alpha(TNFα), interleukin 1 beta (IL-1β), and IL-6

Thyroid function

Supports thyroid function

Healthy aging and longevity

Lifespan extension effects (Caenorhabditis elegans)

Upregulates insulin-like growth factor-1 (IGF-1) signaling pathway

Downregulates α-synuclein and amyloid-β aggregation

Upregulates FOXO3A and SIRT3