I’ve been eying up this new brain supplement called ultrabrain by Ari Whitten. I always listen to his podcasts and he has some very interesting speakers and I find him very informative and credible. This has coffee fruit in it amongst many other things but it is expensive.
Actually his 3 products energenesis, ultrabrain and energy essentials look like they have almost every compound I’ve seen discussed in this forum so for anyone who can afford it it looks like it might be worth a try. It’s certainly going to be cheaper and easier than everything individually.
Let me know if you try it! 2 of the 3 products are powders you take as a scoop which is better than heaps of capsules, the ultrabrain is capsules.
This is one of the most powerful compounds for mitochondrial regeneration, probably the single most impressive individual supplement ever tested to help people overcome fatigue.
NTFactor® is a compound used in lipid replacement therapy, a method of replacing damaged membrane phospholipids that accumulate during aging and in various clinical conditions in order to restore cellular and mitochondrial function.
It has been shown to increase energy levels by a whopping 24–43% in people with chronic fatigue syndrome in just 4 weeks. [1-4]
And it has been shown to many other types of fatigue, including age-related fatigue, fatigue from chemical exposure, as well as reduce cancer-associated fatigue and the fatigue effects of cancer therapy by similar amounts, again, in just a few weeks of use! [5,6]
How does it work?
Mitochondria are wrapped in membranes composed of phospholipids.
These membranes (i.e. the phospholipids that compose them) get damaged. And when they’re damaged, they do two things:
1. The mitochondria don’t produce as much energy
2. The mitochondria create more oxidative stress and inflammation (basically, they create a vicious cycle whereby damaged mitochondria lead to more damaged mitochondria)
NTFactor® is a specially formulated and patented phospholipid formulation that consists of phospholipids that actually get absorbed into your bloodstream intact, and then get delivered to the cells and to the damaged mitochondria where they literally replace the old damaged phospholipids with new healthy ones.
That’s why this is such an amazing supplement — it’s literally like taking your mitochondria to the mechanic to be repaired. (That’s why it’s one of the key ingredients in Energenesis.)
Where else are you going to take ANYTHING that is proven in numerous studies to increase energy levels (in people with chronic fatigue) by up to 43% in just a few weeks?
This is an incredibly powerful supplement, and it’s truly a must-have supplement in your arsenal to increase your energy.
Astaxanthin
Astaxanthin is one of the most powerful non-stimulant ways to build up your cellular energy production. And it works through multiple powerful mechanisms, and has a massive amount of research supporting all kinds of seemingly miraculous health benefits.
Astaxanthin is the red pigment in shrimp, salmon, krill and various other seafood, but it is originally made by algae (mainly Haematococcus pluvialis).
It is thought to be one of the most effective antioxidants known to man. It’s also one of the most powerful protectors of our cellular energy generators (our mitochondria) in existence.
How does that translate into meaningful effects?
One study where male students ages 17 to 19 who took 4mg per day of astaxanthin for six months found that it improved their strength and endurance by an impressive 62 percent! Moreover, their endurance increased 300% faster than the control group! [7]
Obviously, if you’re looking for something to increase your energy levels, the implications of that are pretty obvious.
Astaxanthin is able to:
Protect mitochondria and support optimal cellular energy production [8-10]
Dramatically reduce inflammation [11]
Increase blood flow [12]
Support heart health and reduce the oxidation of LDL [13]
Help modulate blood glucose [14]
Improve cognitive function [15]
Protect neurons from damage (and likely help prevent dementia and neurological disease)
Decrease anxiety [16]
Decrease depression [17]
Decrease muscle inflammation by more than 50%
Improve physical endurance and exercise performance [8, 9, 18, 19]
Increase muscle strength and mobility [20]
Act as an internal sunscreen and dramatically increase the skin’s tolerance to sun exposure [16, 21]
Improve the “heart-brain axis” (both mental and physical health) [22]
Improve energy levels [8, 23-27]
Importantly for our purposes here, astaxanthin is a very unique compound because it has the ability to penetrate inside of cells and actually incorporate itself inside of mitochondrial membranes, where it protects them from damage and supports energy production. [11, 28] Because of that, it is one of the most powerful ingredients for supporting mitochondrial health and energy levels.
Astaxanthin is a must-have energy and mitochondria-supporting compound that has literally dozens of positive side effects on everything from heart health, to brain health, to eye health, to skin health, to energy levels, and much more. It is one of nature’s most powerful health and energy-supporting nutrients. [29]
PQQ (Pyrroloquinoline Quinone)
Pyrroloquinoline quinone (PQQ) is one of the most powerful promoters of mitochondrial biogenesis ever discovered. [30, 31] Mitochondrial biogenesis is the process of your cells literally building more new mitochondria — cellular energy generators — from scratch. Since loss of mitochondria is one of the key drivers of fatigue (especially aging-associated fatigue), stimulating mitochondrial biogenesis is absolutely critical. And few things do it better than PQQ!
Interesting fact: PQQ is a growth factor in the human body, and our cells manufacture about 100-400 nanograms each day.
PQQ is a small quinone molecule which has the ability to be a REDOX agent, capable of reducing damaging oxidants (“free radicals”) that contribute to cellular and mitochondrial damage. It’s a remarkably powerful antioxidant — with some estimates being around 100 times more effective than vitamin C at eliminating free radicals. Via its actions as a REDOX agent in cells, it can modify signalling and supports mitochondrial function, which in turn can boost energy levels. [30-32]
But most importantly, it’s a powerful booster of mitochondrial growth and stimulator of mitochondrial biogenesis.
Studies have shown that PQQ can help with:
Decreasing systemic inflammation [33]
Improving sleep [34]
Improving brain function [35]
Speeding up metabolism, decreasing insulin resistance and increasing weight loss [36, 37]
Improving immune function [38]
Improving mitochondrial health and stimulating mitochondrial biogenesis [30, 38]
Panax Ginseng
Panax ginseng is probably the single most powerful herbal/botanical compound for boosting energy levels.
Panax Ginseng is commonly referred to as the ‘True Ginseng’ (being the most researched ‘Ginseng’ actually belonging to the plant family of ‘Ginseng’).
Panax Ginseng has proven benefits for:
Increasing energy levels (decreasing fatigue)
Boosting mitochondrial health/function [39-44]
Mood optimization [45]
Improving immune function [46]
Anti-cancer effects [39]
Anti-inflammatory and anti-oxidant effects [39, 40]
Increased resistance to stress [39-41]
Improving brain function and cognition [47-50]
Let’s talk a bit more about the research on fatigue specifically…
One study in 52 people showed that a ginseng extract caused highly significant reductions in fatigue severity. [51]
Another study in 364 participants found that ginseng dramatically reduced cancer-related fatigue. [52]
Another placebo-controlled study in 90 people with chronic fatigue found that ginseng increased levels of internal antioxidants like glutathione, decreased oxidative stress, and reduced fatigue scores by about 30% in just 8 weeks. [53]
The researchers concluded “Taken together, these data lead us to conclude that P. ginseng can be used to combat chronic fatigue.” [53]
A review of 4 different studies with a total of over 400 healthy (non-fatigued) participants found significant increases in energy levels. [54]
Cordyceps
Cordyceps is a medicinal mushroom traditionally used in the east for thousands of years. It grows on the bodies of caterpillars, but is now more typically farmed (no caterpillars necessary).
Cordyceps is perhaps the most prized energy booster within Eastern medicine traditions.
So it has long been known as an energizer and fatigue fighter, and importantly, modern research backs these traditional claims up.
Cordyceps has been proven to:
Exert anti-aging effects at the cellular level [55]
Combat several types of cancer [56]
Boost immune function [57]
Fight inflammation [58]
Combat insulin resistance and type II diabetes [59]
Dramatically increase cellular energy production and improve exercise performance [60, 61]
Creatine Monohydrate
Creatine is among the most well-researched, safe, and effective supplements for performance enhancement, especially activities involving short bursts of high-intensity activity, but also even endurance exercise (cardio) to some extent. [62-64]
It is proven to improve strength, increase lean muscle mass, and help the muscles recover more quickly during exercise. [64, 65]
Much less known by most people is that creatine also been shown to have neuroprotective and cardioprotective benefits and to improve brain function. [66-69]
In addition, it has been shown to increase both physical and mental energy in people with chronic fatigue syndrome. [70]
Creatine has also been shown to improve mitochondrial function. [66]
Overall, it’s one of the most evidence-backed supplements for physical energy enhancement — especially during physical activity.
D-Ribose
D-ribose is a special type of sugar that is required to create energy and DNA. [75] Some evidence suggests that D-ribose can help boost energy and physical function in situations where energy levels are reduced, such as people who have suffered from heart disease or stroke, or people engaging in regular intense exercise. [76-80]
D-ribose has been shown to dramatically improve energy levels in people with fibromyalgia or chronic fatigue syndrome by over 30%!
There were also big improvements in sleep, well-being and decreased sensitivity to pain.
But that’s not the best part. The best part is that it accomplished this huge improvement in just three weeks! [81]
Another study reported similar findings after using 10 grams per day, with all benefits disappearing within a week of stopping supplementation. [82]
Coenzyme Q10
Coenzyme Q10 (CoQ10) is a molecule found in mitochondria that has a critical role in energy production.
Several diseases and low-energy conditions are associated with low CoQ10 levels, including people who have fibromyalgia, [83-85] have survived heart attacks or heart failure, [86, 87] have multiple sclerosis, [88, 89] are infertile, [90-92] or suffer migraines. [93, 94]
Generally speaking, CoQ10 will enhance blood flow, protect blood vessels, lower oxidative stress, and boost vitality in anyone who suffers from fatigue, but especially those people with the aforementioned conditions.
Additionally, statin drugs are known to deplete CoQ10 levels, [95] so supplementation is mandatory in people taking a statin (even doctors know this and will co-prescribe CoQ10 with a statin). [96]
Curcumin
Curcumin is the yellow pigment and primary bioactive substance in turmeric. It possesses powerful anti-inflammatory and antioxidant properties that can help reduce depression and anxiety. [107, 108]
There is also evidence that curcumin can help slow cognitive decline with aging, promote cardiovascular health, reduce the risk of developing diabetes, and alleviate other inflammation-related conditions. [109]
One of the key mechanisms by which it exerts these effects is through protecting and stabilizing mitochondrial membranes, and helping the body build more mitochondria from scratch (mitochondrial biogenesis). [110, 111]
Quercetin
Quercetin is a well-known bioflavonoid found in fruits and vegetables, particularly onions and apples. It is a potent antioxidant and anti-inflammatory molecule that affects an array of mitochondrial processes, including mitochondrial biogenesis, mitochondrial energy production, and the protection of mitochondria from oxidative stress. [113, 114]
It is also involved in helping the mitochondria to regenerate NAD+ — a key molecule that supports mitochondrial health and energy production.
Taurine
Taurine is a sulfur-containing amino acid essential for cardiovascular function and the development and function of skeletal muscle, the retina, and the brain. [115] It can help fight muscle loss with aging, [116] as well as benefit many other disease states, including neurodegenerative diseases, diseases of the eye, diabetes, heart failure, high blood pressure, and muscular dystrophies. [117]
Taurine is also essential for the proper function of mitochondria. [118, 119]
Magnesium
Magnesium is an essential dietary mineral, and the second most prevalent electrolyte in the human body. Magnesium deficiencies are common in developed countries because prominent sources of magnesium, like leafy vegetables, are not often eaten.
A deficiency increases blood pressure, reduces glucose tolerance, and causes abnormal neural excitations that impair sleep. [120] It’s also a critical cofactor for mitochondrial energy production.
Energenesis provides two types of magnesium — malate and citrate — which provide other cofactors for mitochondrial energy production as well.
Acetyl-L-Carnitine
Acetyl L-Carnitine (ALCAR) is a unique form of L-Carnitine that has incredible brain- and body-boosting properties.
Most importantly, it is one of the most evidence-backed anti-aging, and mitochondrial boosting (cellular energy-enhancing) compounds ever discovered.
ALCAR has been proven to:
Reduce depression with a potency comparable to antidepressant drugs (with far less side effects) [121]
Protect and repair neurons from damage (like that caused by diabetes) [122, 123]
Improve insulin sensitivity [124]
Improve cardiovascular health [125, 126]
Combat the side effects of aging, like neurological decline and chronic fatigue [127-131]
Increase mitochondrial function by increasing their ability to produce energy [132-134]
Notably, ALCAR has been known to cause fat loss, not because of any mechanism intrinsic to ALCAR, but simply because those taking it become more physically active due to the increased energy and vitality it provides.
Between powerful anti-depressant effects (likely even better than drugs like Prozac, but with far less side effects), general anti-aging/longevity benefits, brain protection, increased fat burning/weight loss, and increased energy levels, this is a must-have supplement.
Alpha-Lipoic Acid (ideally R-ALA)
Alpha-lipoic acid (ALA) is a mitochondrial compound involved in energy metabolism and the antioxidant system. [141] It provides a short but potent reduction of oxidation by increasing antioxidant enzymes, which protects against a variety of inflammatory and oxidative diseases like neurodegeneration. [142] ALA accumulates in various brain regions as soon as an hour after ingestion, [143, 144] and it has been shown to protect against neuronal cell death. [145]
ALA (especially R-ALA) is one of the most powerful evidence-backed compounds for mitochondrial repair and optimization.
Hesperidin is the primary bioactive compound in orange peels, alongside naringenin. They are powerful antioxidant and anti-inflammatory molecules, [148, 149] capable of protecting against several degenerative diseases and particularly brain diseases. [150] These effects are mediated, in part, by their ability to prevent mitochondrial dysfunction, to boost NAD+ and to combat oxidative stress. [151]
Green Tea Catechins
Green tea (Camellia Sinensis) catechins are four phytochemical molecules, the most potent one being epigallocatechin-3-gallate (EGCG). It has been implicated in benefiting almost every organ system in the body in doses you can obtain easily from simply drinking green tea. [152-154] EGCG is neuroprotective, [155,156] cardioprotective, [157, 158] anti-obesity, [159-161] anti-carcinogenic, [162, 163] anti-diabetic, [164] and an overall powerful protector of your mitochondria. [165-167]
In a 12-week double-blind trial published in the American Journal of Clinical Nutrition, researchers gave 38 overweight adults (ages 20 to 50) a daily polyphenol supplement or a placebo pill. The polyphenol supplement contained a mixture of EGCG (epigallocatechin-3-gallate, found in green tea) and resveratrol (which is also in Energenesis). People taking the polyphenol supplement had a highly significant increase in the function of mitochondria in their muscles compared to people given a placebo.
Cacao/Cocoa
Like green tea extract, cacao is packed with several powerful phytochemicals, including flavan3-ol and epicatechin.
These catechins have wideranging health benefits, including everything from anti-aging effects in the skin, to boosting mood, to boosting mitochondrial energy production.
It’s also one of the richest sources of PQQ, which is a powerful stimulator of mitochondrial biogenesis. (The base for Energenesis is made from cacao for this reason. Plus it tastes delicious!)
The unique phytochemical combination in cacao of epicatechin, flavan-3-ol, and PQQ likely have synergistic effects — making cacao an extremely potent concoction for energy and mitochondrial health.
B3 Variants (NMN, NR, Niacin & Niacinamide)
NAD+ has received a ton of attention in the last few years as possibly one of the most important compounds for anti-aging, disease prevention, prevention of DNA damage, and longevity. It also happens to be one of the most important compounds in regulating mitochondrial energy production.
Several studies have now found that boosting levels of NAD+ can have profound anti-aging effects, and can even “make old rats young again” (to steal some of the media headlines). [168-170]
This is where vitamin B3 (and versions of it, like niacin, niacinamide, nicotinamide riboside and nicotinamide mononucleotide) come in… They boost levels of NAD+. [171]
While much focus is now on nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), the best available research indicates that these extremely expensive ingredients may not be significantly superior to plain old niacin and niacinamide (which are far cheaper, and easier to take in larger quantities). In fact, some research suggests that NR and NMN actually get broken down in the digestive tract into niacinamide anyway. [168]
In other words, it likely does not make a whole lot of sense to spend exorbitant amounts of money on these fancy versions of niacin/niacinamide (NR or NMN) when they may actually be getting digested into niacinamide anyway before being absorbed into the bloodstream.
It is, however, true that NAD+ is a critically important compound for promoting youthful mitochondrial function and energy production. All these B3 derivatives boost NAD+ levels significantly.
B3 Variants (NMN, NR, Niacin & Niacinamide)
NAD+ has received a ton of attention in the last few years as possibly one of the most important compounds for anti-aging, disease prevention, prevention of DNA damage, and longevity. It also happens to be one of the most important compounds in regulating mitochondrial energy production.
Several studies have now found that boosting levels of NAD+ can have profound anti-aging effects, and can even “make old rats young again” (to steal some of the media headlines). [168-170]
This is where vitamin B3 (and versions of it, like niacin, niacinamide, nicotinamide riboside and nicotinamide mononucleotide) come in… They boost levels of NAD+. [171]
While much focus is now on nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), the best available research indicates that these extremely expensive ingredients may not be significantly superior to plain old niacin and niacinamide (which are far cheaper, and easier to take in larger quantities). In fact, some research suggests that NR and NMN actually get broken down in the digestive tract into niacinamide anyway. [168]
In other words, it likely does not make a whole lot of sense to spend exorbitant amounts of money on these fancy versions of niacin/niacinamide (NR or NMN) when they may actually be getting digested into niacinamide anyway before being absorbed into the bloodstream.
It is, however, true that NAD+ is a critically important compound for promoting youthful mitochondrial function and energy production. All these B3 derivatives boost NAD+ levels significantly.
N-Acetyl Cysteine (NAC)
N-acetyl cysteine is special variant of the sulfur-rich amino acid cysteine.
It is actually a commonly used medicine in conventional medicine, in the context of acetaminophen (tylenol) toxicity – which is a commonly used drug that is also highly toxic to the liver (and depletes one of the body’s most important compounds for detoxification and antioxidant protection – glutathione). [172]
Why is NAC used for this purpose? Because it has a uniquely powerful ability to quickly rebuild healthy levels of glutathione.
NAC has been very thoroughly studied, with close to 1,000 clinical trials already done as of 2020. It has countless proven benefits:
Its antioxidant effects protect DNA [173]
It supports liver health and detoxification [172, 174]
Treating COPD and other respiratory symptoms
It boosts brain function and improves mental health [175, 176, 177]
Improves skin health
It improves mood (combats depression, and bipolar disorder) [175, 178]
Reduces fatigue after exercise [179]
It dramatically improves mitochondrial function (and protect the mitochondria from damage) [179-182]
Resveratrol (Ideally Trans-Resveratrol)
Resveratrol is a beneficial compound found in red wine that is associated with life extension. It is produced in grape skins as a defense against insects.
The primary way it works to exert its energy- and longevity-boosting effects is through a compound called SIRT1 and another called NAD+. Together, these two compounds are part of our most important anti-aging, mitochondria-boosting and longevity circuit.
When the body is under stress and chronic inflammation/oxidative stress, certain cellular proteins (things like enzymes, and even DNA) get acetylated — an acetyl gets added to them. This essentially damages the structure and function of these important cellular proteins (that may be involved with key cellular processes, for example, in producing energy).
SIRT1 is a sort of a pac-man enzyme that “chews” off acetyl groups from other proteins (including DNA). By getting rid of the acetyl groups, it allows these proteins to still function optimally and can even help prevent and repair damage to genes.
Think of it like bringing your cellular proteins, enzymes and DNA back into the state when you were young.
De-acetylated proteins = young proteins
Acetylated proteins = old proteins
So again, SIRT1 basically helps turn older proteins into younger proteins. SIRT1 has been recognized to help protect against age-related diseases, such as cardiovascular disease, cancer, and neurodegeneration.
So where does resveratrol come in
Resveratrol is direct booster of this SIRT1 pathway, and boosts NAD+ — which is like the accelerator pedal for the SIRT1 pathway.
It is a potent booster of our mitochondria and internal antioxidant defense system [184, 185] and is proven to have all sorts of incredible anti-aging effects, like:
Activating longevity genes [111, 185, 186]
Stimulating mitochondrial biogenesis [111, 185]
Increasing levels of NAD+ (a key energy, longevity and anti-aging compound) [187, 188]
Protecting against heart disease [111, 185, 186, 189]
Combating insulin resistance [190]
Increasing blood flow (and oxygen and nutrient delivery) to the brain [189]
Fighting senescent cells (immortal cells that produce inflammatory compounds that are one of the main mechanisms of aging)
Activating autophagy (another key pathway of longevity) [111, 185]
Improving immune function [191, 192]
Fighting oxidative stress and inflammation [191, 192, 193]
Combating/preventing cancer [189]
Mood-boosting and antidepressant effects [187, 194]
Improving physical energy, stamina and endurance [187, 195-198]
Moreover, unlike other antioxidants that interfere with exercise-induced adaptations, [199] like muscle protein synthesis and mitochondrial biogenesis, resveratrol appears to enhance the physiological benefits of exercise. [196, 197] In fact, research shows that in animals, it DOUBLES the time it takes for animals to run to the point of exhaustion (i.e. they had energy for much longer than animals not taking resveratrol.)
Reduces feelings of exhaustion, irritability, and burnout
Increases resilience (resistance to stress)
Functions as an antioxidant and anti-inflammatory
Fast-acting
In first-year medical students, taking rhodiola rosea for 3 weeks before exams improved mental performance by 50% and reduced mental fatigue by 42%.[1]
A large study of over 100 adults with chronic work- and life-related stress found that 400 mg/d of rhodiola rosea significantly reduced feelings of exhaustion, irritability, and anxiety in as little as three days![2]
In adults with chronic fatigue syndrome, 400 mg per day of rhodiola improved every aspect of fatigue after just 1 week, with further improvements seen after 8 weeks. [3]
Ultimately, 83% of the participants reported “very much” or “much” improved conditions, with every aspect of fatigue, stress, and global impairment being cut in half.
Lion's Mane Powder
Reduces anxiety and depression
Helps improve memory, concentration, and overall cognitive function
Promotes nerve growth and regeneration in the brain
Reduces inflammation
Stabilizes mood
Restores key neurotransmitters
Research has found that 1,500 mg per day for 8 weeks reduced feelings of anxiety by 27% and feelings of depression by 39%. [4]
Alpha-GPC
Protects neurons in the brain and supports neurotransmission
Increases dopamine and serotonin signaling in the brain
Decreases risk of vascular dementia
More effective than Alzheimer drug (Aricept) at improving cognition
The choline supplied by alpha-GPC plays a critical role in neuronal plasticity, membrane stability, signaling events, and neurotransmission. [5] Choline is, without a doubt, neuroprotective, and a low brain concentration is one of the primary causes of vascular dementia (loss of memory and ability to think). [6],[7]
As of 2007, alpha-GPC has been investigated in 14 clinical trials enrolling individuals with neurodegenerative disorders, vascular dementia, or stroke, and the results have been very positive. For example, compared to drug therapy for Alzheimer’s disease (the cholinesterase inhibitor called donepezil or Aricept), alpha-GPC was more effective at improving cognition over 6 months. [8]
CDP-choline
Promotes health of cell membranes
Improves memory and overall brain cognition
Improves motor function
Increases focus and reduces impulsive behavior
Improves neuroplasticity (helps the brain adapt to new situations)
Unlike alpha-GPC, however, CDP-choline is the direct precursor for the synthesis of phosphatidylcholine, one of the most abundant and important structural components of cell membranes. [9]
Research in humans has suggested that taking CDP-choline increases phosphatidylcholine synthesis within the brain.[10] Indeed, 6 weeks of daily supplementation with 500 mg of CDP-choline increases brain phospholipid concentrations.
A Cochrane Systematic Review of 14 double-blind, placebo-controlled trials of older adults with cognitive deficits like dementia reported that CDP-choline was able to improve memory, correct abnormal behaviors, and increase the global impression that physicians have towards the participants. [11]
In healthy elderly adults (average 73 years), 300 mg/d of bacopa (50% bacosides) for 12 weeks significantly improved multiple measures of cognitive performance and mood state compared to placebo, including memory, reaction time, depression, and anxiety compared to placebo [12]
In young medical students, 300 mg/d of bacopa (50% bacosides) for 6 weeks significantly improved efficiency of attention, freedom from distractibility, and working memory. [13]
In healthy adults, 300 mg/d of bacopa (50% bacosides) for 12 weeks significantly improved speed of visual information processing, learning rate, memory consolidation, and decreased anxiety compared to placebo. [14]
Gingko Biloba
Neuroprotective
Improves memory and cognitive performance
Works as an antioxidant
Counteracts cognitive impairment
Improves neuroplasticity
Preserves brain receptors in aging adults
Ginkgo biloba possesses an array of activities relevant to brain health and neurological function, with numerous studies showing that it is neuroprotective, an antioxidant, preserves brain receptors susceptible to age-related loss, counteracts cognitive impairment, enhances neuronal plasticity, and improves memory.[15]
A systematic review of 12 meta-analyses found that ginkgo biloba improves cognitive performance, activities of daily living, and clinical global impression in the treatment of dementia at doses greater than 200mg/day (usually 240mg/day) administered for at least 22 weeks (5 months).[16]
Helps grow new neurons and prevent neurodegeneration
Improves long-term memory
NeuroFactor is a patented extract of the whole coffee fruit, including both the fruiting body and the coffee bean it contains. While many are familiar with the coffee bean and the joy it brings through brewing into a morning cup of Joe, the fruit contains powerful antioxidant compounds that benefit our brain and body[17], [18]
Clinical studies in healthy adults have shown that 100 mg of NeuroFactor nearly doubles concentrations of brain-derived neurotrophic factor (BDNF) after 1–2 hours,[19],[20] beating out other forms of coffee bioactives, caffeine, and the phytochemical-rich grape seed extract.
BDNF is a key protein involved in brain health, well established to be critical for neuroplasticity (helps the brain adapt to new situations), [21] neurogenesis (the growth, regeneration and creation of new neurons and synapses), [22], [23] long-term memory, [24] prevention of neurodegeneration.[25]
Huperzine A
Promotes learning
Used for centuries to treat brain-based illnesses
Improves cognition, especially in people with Alzheimer’s and vascular dementia
Naturally occurring acetylcholinesterase inhibitor (primary class of drugs for treating Alzheimer’s and dementia)
Huperzine-A is an alkaloid derived from the moss Huperzia serrata, which itself has been used in traditional Chinese Medicine for centuries.
It’s a naturally occurring acetylcholinesterase inhibitor, which represents the primary class of drugs for treating Alzheimer’s dementia, and functions to inhibit the enzyme that degrades acetylcholine, the neurotransmitter responsible for learning new information. [26]
At least 20 randomized controlled trials have evaluated the efficacy of huperzine A in patients with Alzheimer’s disease, with a meta-analysis showing improvements for cognitive function, daily living activity, and global clinical assessments over 8–36 weeks.[27]
Other meta-analyses have reported that huperzine A improves cognition in those with vascular dementia, [28] as well as in those with major depression. [29]
Acetyl-L Carnitine
Improves brain function, especially memory and attention
Reduces oxidative stress
Protects against β-amlyoid neurotoxicity
Reduces mental and physical fatigue
Reduces depression – more effective than antidepressant drugs! (And with far less side effects)
Reduces pain and increases nerve conduction
Prevents progression of brain-related disease
Carnitine is an essential component of mitochondria, responsible for shuttling fatty acids across the mitochondrial membranes so that they can be used for energy production. Acetyl L-Carnitine (ALCAR) is a unique form of L-Carnitine that has incredible brain- and body-boosting properties.
Why? Because supplementation is well-established to increase mitochondrial function and energy production,[30], [31] particularly within the brain thanks to ALCAR’s ability to easily cross the blood-brain barrier.[32], [33], [34], [35], [36] It also protects against β-amlyoid neurotoxicity and reduces oxidative stress. [37]
Notably, ALCAR concentrations slowly decline as cognitive impairment progresses, ultimately being 36% lower in Alzheimer’s patients than healthy adults. [38]
In elderly adults suffering from excessive fatigue, ALCAR supplementation improved cognitive function, reduced mental and physical fatigue, and improved the ability to function in daily life.[39]
A meta-analysis of 21 randomized controlled trials involving patients with mild cognitive impairment or Alzheimer’s disease found that ALCAR significantly improved cognitive function and prevented the progression of Alzheimer’s after as little as 3 months! [40]
A meta-analysis of 12 randomized controlled trials found ALCAR to significantly reduce depressive symptoms with an efficacy similar to antidepressant drugs, but with far less side effects. [41]
Trimethylglycine
Reduces oxidative stress and inflammation
Enhances proper protein synthesis
Improves cognitive function, especially memory
Reduces depression
One of the principal benefits of TMG supplementation is its ability to reduce homocysteine concentrations, [42], [43] which reduces exposure to oxidative stress and inflammation. [44], [45] TMG levels in the body have been linked to better cognitive function, particularly memory and executive function,[46] and the hippocampus of the brain selectively accumulates betaine.[47]
Additionally, TMG’s methylation abilities may hold effectiveness for reducing depression when paired with SAMe, [48], [49] potentially being equivalent to antidepressant drugs but with less side effects. [50]
Saffron Extract
As effective as prescription drugs (with less side effects) in:
Reducing depression
Treating obsessive compulsive disorder (OCD)
Improving cognitive function
Antioxidant and anti-inflammatory
Neuroprotective
Saffron is one of the most well-researched antidepressant compounds available, with three separate meta-analyses of randomized controlled trials indicating that 30 mg/d has a potency comparable to prescription drugs but with less side effects. [51], [52], [53]
Other studies have shown that saffron reduces PMS symptoms, [54] is as effective as prescription drugs for treating obsessive compulsive disorder (OCD), [54] and boosts cognitive function to the same extent as prescription drugs in those with Alzheimer’s disease. [55], [56]
While the precise mechanisms of action isn’t clear, research indicates that saffron increases serotonin signaling in the brain, has antioxidant and anti-inflammatory properties, and has neuroprotective effects. [57], [58]
Uridine Monophosphate
Part of nucleic acids in DNA and RNA
Critical for creation of brain phospholipids
Induces nerve growth
Increases learning
Improves depression
Uridine is one of the five standard nucleosides that make up the nucleic acids of genetic material (DNA and RNA). It is known to pass the blood-brain barrier, [59] and is involved in several neurologically critical functions, like synthesis of synthesis of brain phospholipids, [60] the formation of brain synapses that are required for learning and communications, [61], [62] and inducing nerve growth and differentiation. [63],[64]
In depressed adolescents with bipolar disorder, uridine supplementation for six weeks reduced depression by 58%. [65]
GABA
Critical for relaxation and stress management
Strong emotional regulator
Improves memory, focus, and attention
Increases empathy
Improves resiliency
Decreases depression and anxiety
GABA is the most potent inhibitory neurotransmitter in human brains. It regulates many of the sedative actions in brain tissue and is critical for relaxation. [66], [67] It is also critical for the regulation of neuronal communication, cognition, emotion, and memory. [68], [69], [70]
It’s been suggested that higher GABA levels help reduce distraction in the brain, which makes it possible to react and make decisions more quickly. [71] A single dose of 800 mg of GABA has been shown to improve attention and task switching in healthy young adults. [72], [73]
It has also been shown to potently combat anxiety.
Agmatine sulfate
Important neurotransmitter
Improves learning and memory
Reduces anxiety and depression
Protects neurons and enhances cell growth
Protects mitochondria
More effective at relieving pain than conventional medications
Clinical research has demonstrated agmatine’s pain-relieving properties. In a randomized, double-blind, placebo-controlled study of individuals with back pain from herniated lumbar discs, agmatine sulfate supplementation for two weeks reduced pain by 25–28% and improved parameters of general health by 65–76%. [74] Moreover, these benefits persisted for 2 months after supplementation ended.
In a pilot study of two men and one woman with clinical depression and currently in the grip of a major depressive disorder episode, supplementing agmatine for 3–4 weeks “showed total/incontrovertible remission of depression.” [75] Their depressive rating dropped from 32, with >17 indicating severe depression, to a depression-free score of 3. All without apparent adverse effects.
Polygala tenuifolia
Improves memory and combats forgetfulness
Supports neurotransmitters required for learning, memory, and mental health
Promotes growth of new neurons in the brain
Increases neuroplasticity and cognitive function
Polygala tenuifolia is one of the fundamental herbs used in traditional Chinese medicine, used to improve memory and combat forgetfulness with aging. There are several mechanisms through with Polygala tenuifolia may accomplish these goals:
Inhibiting the breakdown of acetylcholine, dopamine, serotonin, and noradrenaline, neurotransmitters required for learning new information, memory storage, and overall mental health. [76], [77]
Increasing the expression of brain derived neurotrophic factor (BDNF), which is fundamental for neuroplasticity and neurogenesis. [78]
Promoting the growth of new neurons in the brain.[79]
Several studies have shown improved cognitive function and brain performance with polygala supplementation.
N-Acetyl-L-Tyrosine
Critical for stress management
Boosts cognition, alertness, and information processing
Improves memory and mental health
L-tyrosine is a conditionally essential amino acid that serves as the precursor molecule from which we create the catecholamines: dopamine, adrenaline, and noradrenaline. Your brain needs a steady supply of tyrosine to make the catecholamines and keep your mental health at its peak, [80], [81] particularly if you are under a lot of stress. [82]
Several clinical trials have shown that tyrosine supplementation boosts cognition, alertness, and memory in stressful and demanding situations in otherwise healthy adults. [83], [84]
Pine Bark Extract
Potent antioxidant and anti-inflammatory compound
Improves memory and focus
Boosts brain function
Enzogenol is a patented pine bark extract containing over 80% proanthocyanidins, which are potent antioxidant and antiinflammatory compounds found naturally in many fruits and vegetables, but especially apples, grapes, red wine, blueberries, and chocolate. [85]
In a double-blind, randomized controlled trial of older men, 5 weeks of supplementation with 980 mg/d of Enzogenol significantly improved working memory. [86] Daily supplementation has also been shown to improve cognitive function in those with traumatic brain injury after 6 weeks. [87]
Other studies have also documented cognitive improvements following supplementation with Pycnogenol, a similar pine bark extract containing ~70% proanthocyanidins.
In healthy middle-aged adults, 150 mg per day of pine bark extract for 12 weeks reduced oxidative stress by 30% while improving cognitive performance and mood. [88]
In older adults with high levels of oxidative stress, 100 mg per day of pine bark extract for one year reduced oxidative stress by 28% and improved cognitive function, attention, and memory. [89]
In adults with mild cognitive impairment, 100 mg per day of pine bark extract for 8 weeks improved cognitive function by 18%.[90]
Magnesium taurate
Over 300 enzymes require magnesium to function properly!
Required for optimal nerve transmission
Protects against cell death
Prevents mitochondrial dysfunction
Prevents migraines
Improves anxiety and depression
Slows development of and severity of Parkinson’s and Alzheimer’s
Reduces risk of stroke
Magnesium is required for over 300 enzymes to function properly. [91] We need it for our muscles to contract, to regulate blood pressure, for proper insulin signaling, and for the synthesis of DNA and proteins. Within the brain and nervous system, magnesium is required for optimal nerve transmission and protection against excitotoxicity (excessive excitation leading to cell death). [92], [93]
Not all forms of magnesium are the same. You’ll find many types on the market, and the evidence is clear that magnesium taurate demonstrates a superior ability to enter into the brain and increase the brain’s magnesium status.
One study compared the tissue distribution of magnesium 8 hours after taking equal amounts of magnesium citrate, malate, oxide, sulfate, and taurate. [94] It was shown that magnesium taurate increased brain magnesium concentrations 10–20% more than the other forms.
A meta-analysis of 8 randomized controlled trials found that supplementing with magnesium reduced the frequency and intensity of migraines regardless of age, sex, or dose. [95]
A systematic review of 18 studies found that magnesium supplementation could help reduce feelings of anxiety in susceptible individuals. [96]
Dietary magnesium intake is associated with a lower risk for depression, [97] and supplementation with 500 mg of magnesium oxide or magnesium chloride reduces depressive symptoms in adults with mild to moderate depression. [98], [99] Some case reports have even shown rapid recovery (less than 7 days) from major depression using 125–300 mg of magnesium (as glycinate and taurinate) with each meal and at bedtime.[100]
B3 Variants (NMN, NR, Niacin & Niacinamide)
NAD+ has received a ton of attention in the last few years as possibly one of the most important compounds for anti-aging, disease prevention, prevention of DNA damage, and longevity. It also happens to be one of the most important compounds in regulating mitochondrial energy production.
Several studies have now found that boosting levels of NAD+ can have profound anti-aging effects, and can even “make old rats young again” (to steal some of the media headlines). [168-170]
This is where vitamin B3 (and versions of it, like niacin, niacinamide, nicotinamide riboside and nicotinamide mononucleotide) come in… They boost levels of NAD+. [171]
While much focus is now on nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), the best available research indicates that these extremely expensive ingredients may not be significantly superior to plain old niacin and niacinamide (which are far cheaper, and easier to take in larger quantities). In fact, some research suggests that NR and NMN actually get broken down in the digestive tract into niacinamide anyway. [168]
In other words, it likely does not make a whole lot of sense to spend exorbitant amounts of money on these fancy versions of niacin/niacinamide (NR or NMN) when they may actually be getting digested into niacinamide anyway before being absorbed into the bloodstream.
It is, however, true that NAD+ is a critically important compound for promoting youthful mitochondrial function and energy production. All these B3 derivatives boost NAD+ levels significantly.
Thank you. This is certainly a comprehensive list and I do take quite a few of these. I read an article about DCA turning damaged mitochondria back on and am wondering if you can confirm this.
I have no idea sorry. I am not any kind of expert on these I am just reporting a product I saw. My husband also takes a lot of these things so was wondering what people think of it.
I feel like after I started Lion's Mane and Phosphatidyl Serine that my brain fog improved. I take many of these as well since I feel like I have at least some dementia, need all the help I can get.
Vitamin A refers to a group of fat-soluble retinoids and carotenoids, the main dietary ones being retinol and beta-carotene. Only retinol has biological activity within the body and can be considered “true” vitamin A. Beta-carotene can be converted by the body into vitamin A, but due to genetic differences, some people do this very poorly, so we’ve included retinol in its bioactive form in addition to beta-carotene.
Retinol is involved in regulating the growth and specialization of nearly every cell in the human body. In adults, it is critical for vision and immune function, with insufficient intakes leading to worsening eyesight (particularly at night) and a greater risk of infections and autoimmunity.1–3
We have the ability to make retinol from beta-carotene and a couple other carotenoids, which is why these precursors are considered a source of vitamin A. The problem is that the efficiency of the conversion process varies widely between individuals and populations due to genetic variations.4 The bioavailability of beta-carotene is also highly variable, depending on factors such as the food matrix, food preparation method, and one’s digestive and absorptive capacities.5 As such, beta-carotene is not a reliable source of vitamin A and we have provided most of one’s daily vitamin A requirement in the form of retinol.
B-complex Vitamins
The B-complex vitamins include 8 different vitamins that are critical for methylation and energy production. Without them, we wouldn’t be able to turn the food we eat into cellular energy, our mitochondria couldn’t function, and we wouldn’t be able to turn the expression of certain genes on or off depending on our body’s needs.
Thiamine (B1) is required to harvest energy from glucose, for the synthesis of energy-carrying molecules within mitochondria, and for nerve conduction.
Riboflavin (B2) is the central unit for flavoproteins, which are necessary for mitochondrial energy production, antioxidant reactions and glutathione recycling, neurotransmitter regulation, and the metabolism of niacin, vitamin B6, and folate.
Niacin (B3) is the central unit for NAD+ and NADP, which are required central to energy production, antioxidant reactions, detoxification, folate metabolism, the repair and regeneration of DNA and proteins, and the biosynthesis of fatty acids, cholesterol, and steroid hormones.
Pantothenic acid (B5) is the central unit of coenzyme A, which plays a vital role in energy production and the metabolism of many nutrients, such as the breakdown of fats, carbohydrates, and proteins, the synthesis of fatty acids, ketones, cholesterol, steroid hormones, and neurotransmitters, genetic expression, and detoxification.
Pyridoxal (B6) is required for amino acid metabolism, gene expression, and the breakdown of homocysteine.
Biotin (B7) is the central component of several enzymes involved in energy production, amino acid metabolism, gene expression, and cell growth.
Folate (B9) is required for methylation throughout our cells and mitochondria, DNA synthesis, cell division, the metabolism of glycine, and the breakdown of homocysteine.
Cobalamin (B12) is necessary for just two important reactions in the body: (1) the breakdown of homocysteine alongside folate and, by virtue of this reaction, the recycling of folate, and (2) the breakdown of certain amino acids and fatty acids.
While all B-vitamin jobs are important, methylation and the breakdown of homocysteine are the ones that many people struggle with because of inadequate B-vitamin intakes and genetic mutations. Inappropriate methylation plays a role in many diseases, including cancer,6,7 neurodegeneration,8,9 and mood disorders like depression.10,11
Elevated levels of homocysteine is a major risk factor for cardiovascular diseases by directly causing blood vessel damage, reducing the flexibility of blood vessels, and altering processes involved in regulating blood fluidity.12 Additionally, high levels of homocysteine are strongly implicated in vascular dementia and impaired cognitive function for several reasons:13–16
Neurotoxic
Increases oxidative stress and inflammation
Related to brain lesions and shrinkage
Interferes with proper protein synthesis
Ensuring ample B-vitamin intake and status is a fundamental aspect of optimal health.
Benfotiamine
Benfotiamine is a special fat-soluble form of thiamin that is capable of easily passing through cell membranes and providing free thiamine directly to the cell, particularly red blood cells and liver cells.17 Bioavailability studies have shown that benfotiamine increases serum thiamine concentrations 5- to 10-fold more than other forms of thiamine.18,19
Benfotiamine works to protect the body in several key ways:
Activates an enzyme (transketolase) that reduces the creation of advanced glycation endproducts (AGEs) and protects against oxidative stress.25,26
Increases cell survival and regeneration.27–29
Reduces inflammation.30,31
Improves brain health.32
Through these mechanisms, research has shown benfotiamine and thiamine supplementation to have notable health benefits, especially in those with diabetes:
In healthy smokers, 1050 mg/d of benfotiamine was able to cut the smoking-induced impairment of endothelial function in half.33
In type 2 diabetes, 1050 mg/d was able to completely prevent the 35% decline in blood vessel function after eating a meal rich in glycation endproducts.34
In type 2 diabetes, 150 mg/d of thiamine for 1 month was able to significantly reduce fasting glucose concentrations and improve leptin sensitivity.35
Several studies have shown 200–600 mg/d of benfotiamine to improve diabetic neuropathy.36–39
In adults with osteoarthritis, just 50 mg/d was able to reduce AGE concentrations, reduce pain, and improve physical function.40
In Alzheimer’s disease, 300 mg/d for 18 months was able to improve cognitive function.41
Riboflavin 5’ Phosphate
Riboflavin is critical for numerous functions in the body, but its most important role for most people is ensuring the proper function of the methylenetetrahydrofolate reductase (MTHFR) enzyme, which is necessary to recycle folate and detoxify homocysteine.
A significant number of people have a mutation in MTHFR (the 677C→T variant) that reduces this enzymes activity, making them slow to convert 5,10-methylene-THF to 5-methyl-THF, the primary circulatory form of folate utilized in homocysteine detoxification.42
The mutation makes it more difficult for MTHFR to bind to a riboflavin-containing molecule (FAD) that is required for it to function.43,44 Supplementing riboflavin and saturating riboflavin stores in the body overcomes this reduced binding ability by having more FAD available to bind to, making the enzyme function normally again.
In other words, this mutation only causes a problem when riboflavin intake is inadequate. When you divide up people based on their riboflavin status, only those who are deficient in riboflavin have elevated homocysteine even in the presence of the MTHFR polymorphism.45
Although the dietary reference intake is set at 1–2 mg/d for healthy adults, this amount is not sufficient to saturate riboflavin stores for most people, particularly those with chronic inflammation that reduces riboflavin absorption.46
A meta-analysis of 14 studies found that supplementing with 2–5 mg/d above-and-beyond this reference intake leads to improved riboflavin status.47 Moreover, supplementing with just 2 mg/d has been shown to drop homocysteine by 40% in those with the MTHFR polymorphism.48
It’s also worth noting that riboflavin can lower blood pressure in those with the MTHFR polymorphism,49 which may be secondary to reducing homocysteine. Several interventions have noted significant reductions in blood pressure (5–10 mmHg) with less than 2 mg/d of riboflavin supplementation.50–52
Niacinamide
Niacinamide is a direct precursor to NAD+, which is involved in numerous notable health benefits like protecting against neurodegeneration, enhancing insulin sensitivity, increasing mitochondrial biogenesis, and sirtuin functions involved in “healthy aging”.55–57
Pantesin
Pantesin (pantethine) is a form of pantothenic acid that not only satisfies our requirements but also has unique blood lipid-lowering properties. A 2005 review of 28 small clinical trials with 646 participants with dyslipidemia reported 1- and 4-month reductions in LDL-C of 10% and 20%, triglycerides of 14% and 33%, and increases in HDL-C of 6% and 8%, respectively.58
Pyridoxal 5’ Phosphate
Pyridoxal 5’ Phosphate (P5P) is the only biologically active form of vitamin B6, playing a vital role in the function of over 100 enzymes that catalyze essential chemical reactions in the human body. Adequate B6 is essential for various aspects of protein metabolism, the synthesis of glutathione from homocysteine via the transsulfuration pathway, and the metabolism of folate.
Biotin
Biotin (also known as vitamin H) is a key factor in helping our body convert food into energy. Biotin is also critical for hair, skin and nail health.
Folate
A notable percentage of the population harbors variants in the methylenetetrahydrofolate reductase (MTHFR) enzyme, which is necessary to recycle folate and detoxify homocysteine. These variants reduce the ability of the MTHFR enzyme to turn 5,10-methylenetetrahydrofolate (5,10-methylene THF) into 5-methyl THF, which is the form required to recycle homocysteine.
Supplementing metafolin (5-methyl THF), bypasses this issue entirely, providing bioavailable folate for the body to use regardless of polymorphisms.
Betaine
Trimethylglycine (TMG; also known as betaine) is a metabolite of choline that plays a critical role in methylation reactions throughout the body. One of the principal benefits of TMG supplementation is its ability to reduce homocysteine concentrations,59,60 which reduces exposure to oxidative stress and inflammation.61,62 TMG levels in the body have been linked to better cognitive function, particularly memory and executive function, and improved mood.6367
Vitamin D
Vitamin D is a unique nutrient because, although dietary sources of vitamin D do exist, our principle supply is through sunlight exposure. Making vitamin D wasn’t much of an issue throughout evolutionary history. A sunbathing adult produces the dietary equivalent of 10,000 to 25,000 IU when exposed to one minimal erythemal dose of UVB radiation, which is just enough to cause a slight pinkness to the skin 24 hours after exposure.
But things are a lot different today than they were 100, let alone 1 million years ago. The most obvious difference is that we spend most of our time indoors and away from sunlight. When we do go outside, we are wearing clothes that prevent sunlight from reaching the skin. When we go to the beach, we use sunscreen that blocks more than 99% of UVB radiation. This exposure problem becomes all the more ominous when we consider the role that skin pigmentation, geographical location, and genetics play in determining our ability to synthesize and utilize vitamin D.
Adding a little vitamin D into the diet can be a saving grace for those who cannot obtain sufficient sun exposure. While everyone will require different amounts, the Endocrine Society has recommended that people require 2,000 to 10,000 IU per day to achieve vitamin D sufficiency.112
Numerous meta-analyses have also linked low vitamin D levels to an increased risk of dying from any cause,113–117 cardiovascular diseases,113,114,116,118 and cancer.113,114,116,119,120
Vitamin E
Vitamin E is not one single chemical, but instead refers to eight related fat-soluble compounds: four tocopherols and four tocotrienols. Most supplements use alpha-tocopherol as the source of vitamin E, but the tocotrienols have unique biologic functions not shared by the tocopherols.121
Gamma-tocopherol and delta-tocotrienol have emerged as vitamin E molecules with functions in health and disease that are clearly distinct from that of alpha-tocopherol.
Studies in humans suggest that tocotrienols possess incredibly potent antioxidant and antiinflammatory effects that lend them benefits towards cardiovascular health, immune function, neuroprotection, and healthy aging. They have shown powerful benefits to preventing:122,123 124,125, 126
Cardiovascular disease (the #1 killer)
Brain disease
Cancer (including breast, colon, liver, lung, stomach, skin, pancreas, and prostate)
Metabolic Minerals
The Metabolic minerals blend provides most of the major minerals needed by the body as highly bioavailable amino acid chelates:
Calcium is the major structural mineral of our bones and teeth and a critical messenger in cell-signaling pathways. When dietary calcium is inadequate, the body draws upon its reserves in the skeleton to supply what is needed.
Magnesium is required for over 300 enzymes in the body to function properly, thereby regulating muscle contractions, blood pressure, insulin signaling, and the synthesis of DNA and proteins.
Manganese plays an important role as both a constituent of enzymes and activator of other enzyme’s activity, including those involved in antioxidant protection, metabolism, and bone development.
Selenium exerts various biological effects as part of larger amino acid structures, with some of the best known being involved in glutathione and thyroid hormone production.
Zinc plays an important role in regulating gene expression, ensuring the proper function of proteins, and catalyzing vital chemical reactions within the body.
Copper is an essential cofactor for numerous redox reactions within energy production, iron metabolism, neurotransmission, and connective tissue development. It also serves as an essential component of the antioxidant enzyme, superoxide dismutase.
Boron has key benefits for the skeletal system, anti-inflammatory benefits, dental health and hormonal health (particularly testosterone and estrogen).180,182,183
Molybdenum is a component of several enzymes within the body required for the metabolism of amino acids, DNA and RNA, and drugs.
Chromium is critical for blood sugar management and correcting insulin resistance.
Fulvic and Humic Acid
Our formula also contains the wonder compounds fulvic and humic acid. Shilajit is a mixture of minerals used traditionally in Ayurveda, with the main bioactives being fulvic and humic acids. It’s believed to help transport other nutrients in the body, facilitate energy production within mitochondria, and supports the body’s detoxification processes.184,185 Clinical trials have shown that fulvic and humic acid supplementation can:
Improve mitochondrial health and decrease fatigue (increases energy levels).
Increase total and free testosterone levels in men.186,187
Improve sperm parameters.187
Binds and detoxifies heavy metals and other pollutants.
Supports gut health.
Improves immune function.
Reduce oxidative stress.187
Improves skin health.
Improves brain health.
Favorably alter gene expression in skeletal muscle for improved neuromuscular signaling and regeneration (faster recovery from workouts).188
Enhance absorption of other compounds it is paired with.
Citrus Bioflavonoids
Citrus bioflavonoids are the phytonutrients found in citrus fruits, the most notable being hesperidin and naringenin. They are powerful antioxidant, immune-boosting, and anti-inflammatory compounds that have shown efficacy for preventing decreases in NAD+ that occur from metabolic dysfunction.68
Their antiinflammatory effects have led to intensive investigation for battling cancer and cardiovascular disease.69,70 Of course, part of this benefit comes from preventing mitochondrial dysfunction.71
To give an idea of the energy-boosting properties of citrus bioflavonoids, one study found that supplementation in combination with another citrus compound, synephrine, could increase metabolic rate by 18%.72
Acerola Berry Extract
Acerola berries are a rich source of vitamin C (1–4.5%) and phytochemicals.73,74 In fact, the vitamin C of acerola berries is more bioavailable and better retained in the body than vitamin C supplements.75
Research has implicated acerola in numerous beneficial aspects of our health:
Protects against DNA damage.76–79
Reduces fat cell dysfunction, oxidative stress, and low-grade inflammation that develop alongside obesity.78,80
Promotes greater antioxidant potential within detoxification organs like the liver.81
Increases brain mitochondrial function and energy production.82
Camu Camu
Camu camu is a berry native to the Amazon rainforest. It’s renowned for its high levels of vitamin C (2.4–3%) and phytochemicals that have been consistently associated with health benefits.83–86 Compared to other exotic fruits, camu camu has some of the highest phytochemical concentrations and antioxidant abilities.87,88
In animals, camu camu has been shown to reduce inflammation,89 reduce fat gain and mitigate metabolic dysfunction,90 protect the liver from injury,91
In humans, drinking 70 mL/d (1/3rd cup) of camu camu juice for just one week reduced markers of oxidative stress and inflammation.92 Camu camu has also been shown to blunt the glycemic response to eating,93 and improve blood vessel function.94
Amla
Amla is an Ayurvedic herb used traditionally for enhancing vitality and promoting longevity. It’s a potent supplier of vitamin C and bioactive phytochemicals that are able to promote mitochondrial biogenesis, up-regulate antioxidant systems, and facilitate energy production.95 These effects also lend it great therapeutic potential as a neuroprotective,96 anti-cancer,97 and general health agent.98
In particular, amla has incredible benefits towards blood glucose and blood lipids that have been documented in both healthy adults and adults with metabolic dysfunction (type 2 diabetes, metabolic syndrome, and dyslipidemia). The effects are comparable to that from diabetes drugs and statins.
In a study of non-diabetic and type 2 diabetic adults, 1–3 g/d of amla for 3 weeks reduced fasting blood glucose by 15–30% in non-diabetic adults and by 34–37% in those with type 2 diabetes, being as effective as the drug glibenclamide.99 It also lowered LDL-C and triglycerides, while HDL-C increased.
In healthy adults, taking 500 mg/d of amla for 4 weeks improved vascular fluidity, reduced an index for vascular age, and reduced markers of oxidative stress.100
A double-blind, randomized controlled trial using 1000 mg/d of amla for 12 weeks in dyslipidemic patients found that it reduced the atherogenic index by 39%, triglycerides by 15%, and LDL-C by 20%.101
A randomized controlled trial comparing 500–1000 mg/d of amla with a statin in people with type 2 diabetes found that all were equivalently effective at improving endothelial function, increasing nitric oxide, reducing oxidative stress, and reducing inflammation.102 Amla was nearly as effective at improving blood lipids too.
In a study of individuals with GERD, 2000 mg/d of amla for 4 weeks significantly reduced the frequency and severity of heartburn.105
In a double-blind, randomized controlled trial comparing 500 and 1000 mg/d of amla for 12 weeks in individuals with metabolic syndrome, both doses similarly reduced oxidative stress (20–30%), increased glutathione concentrations (24–50%), increased nitric oxide (40–50%), and reduced inflammation (40–54%).103 It also positively affected blood lipids.
A clinical study of adults with dyslipidemia found that 500 mg/d of amla for 6 weeks was as effective as a statin at correcting the blood lipid abnormalities.104
Rutin
Rutin is one of the most well-researched phytochemicals in existence, documented to provide potent protection against oxidative stress and protect cells throughout the body from insult and injury.106 Research has shown that rutin is protective against numerous diseases and conditions, including:107–109
Neuroinflammation
Nerve damage
Alzheimer’s disease
Depression
Stroke
Arthritis
Diabetes
Hyperlipidemia
Hypothyroidism
High blood pressure
Ulcers
Asthma
Osteoporosis
Cataracts
Cancer
Fatigue
Organ damage
In individuals with type 2 diabetes, 180 mg/d of rutin plus 480 mg/d of vitamin C for 8 weeks reduced fasting blood glucose by 14% and improved quality of life.110 An earlier study in diabetics using 500 mg/d for 8 weeks also found reductions in fasting glucose.111
Chlorella Thin Cell Wall Algae
Chlorella is a microalgae providing what’s called the Chlorella Growth Factor (CGF) — an extract composed of amino acids, peptides, proteins, vitamins, sugars, and nucleic acids.128
Studies have shown that chlorella has potent anti-inflammatory properties through activating the master anti-inflammatory regulator nuclear factor kappa B (NFκB).129 It also reduces levels of oxidative stress and increases markers of antioxidant activity.130
A meta-analysis of 19 randomized control trials with 797 participants revealed that Chlorella significantly decreases fasting blood glucose, blood pressure, and blood lipids.131 Additionally, it enhances immune function through stimulating the innate and adaptive immune soldiers.132 Other research has shown that it helps detoxify the body through enhancing the excretion of toxicants, including heavy metals.133,134 It’s an all-around amazing superfood for cardiovascular health, detoxification and metabolic health.
Moringa Leaf
Moringa leaf is an important herb in Ayurvedic medicine, native to the Himalayan mountains and India, used to treat infections, high blood pressure, and diabetes. Research has demonstrated it has several beneficial health effects:135
Reducing blood pressure and blood lipids
Reducing inflammation and oxidative stress
Reducing insulin resistance and blood glucose
Reducing DNA damage and causing cancer cell death
Protecting the liver
Broccoli & Cabbage
Broccoli and cabbage are two powerful cruciferous vegetables that contain notable amounts of sulforaphane, a sulfur-containing compound that upregulates phase II of the liver’s detoxification pathways.139,140 This helps the body neutralize toxicants and prepare them for excretion.
Dandelion Root Extract
Dandelion is one of the best-known detoxification herbs. Despite being a common weed, it’s been used for centuries in traditional medicine throughout the world for treating diabetes and digestive disorders.143 Dandelion has:
Protected cells from damage and oxidation.144
Reduced inflammation.144–147
Killed cancer cells.148–150
Ultimately, dandelion root is protective against oxidative stress, fights infections, and has diuretic effects to help expel neutralized toxicants.151–153
Spirulina
Spirulina are a group of cyanobacteria (not true algae as many believe) traditionally eaten by native African populations and the Aztecs of Central America.154 It is, by far, one of the most potent health supplements in existence thanks to a little molecule it contains called C-Phycocyanin.
This bioactive constituent of spirulina has powerful anti-inflammatory, antioxidant, antitumor, and immunostimulating properties thanks to its ability to inhibit NADPH oxidase activity,155,156 which serves as an important source of oxidative stress in many disease states.157,158 For example, it’s NADPH oxidase that drives the glucotoxicity and pancreatic damage seen in type 2 diabetes.159 Spirulina also protects against mitochondrial dysfunction and degeneration.160
The incredible health benefits of spirulina are evidenced in Gilbert’s Syndrome, a genetic condition where individuals have elevated levels of bilirubin,161 which is structurally similar to C-Phycocyanin and also inhibits NADPH oxidase.162 People with Gilbert’s Syndrome have:
A 50% lower risk of death from any cause compared to the general population.163
Less oxidative stress.164
Improved blood vessel function.164
Lower rates of cardiovascular disease and mortality.165,166
Longer telomeres.167
Turmeric Root
Turmeric is an Ayurvedic spice most well-known for its curcumin bioactive constituents, but is also rich in numerous other bioactive compounds that may exert health benefits. Due to the lower bioavailability of curcumin from turmeric, most of it passes through the digestive tract unabsorbed.
Numerous lines of evidence suggest that turmeric and curcumin are able to exert potent antioxidative and anti-inflammatory effects in the digestive tract, particularly within the colon thanks to beneficial metabolism of turmeric by the microbiome. This can help alleviate inflammatory bowel diseases and irritable bowel syndromes,189,190 maintain intestinal barrier integrity,191 and increase microbiome diversity.192,193
Of the curcumin that is absorbed, There is also evidence that curcumin can help slow cognitive decline with aging, promote cardiovascular health, reduce the risk of developing diabetes, and alleviate other inflammation-related conditions.194 One of the key mechanisms by which it exerts these effects is through protecting and stabilizing mitochondrial membranes, and helping the body build more mitochondria from scratch (mitochondrial biogenesis).195
Ginger Root
Ginger is a culinary and medicinal herb in many cultures, with modern research confirming it has potent health benefits. While most people are familiar with its benefits for treating nausea, the effects extend far beyond that. Ginger supplementation has been shown to help battle:206,207
Oxidative stress
Inflammation
Cancer
Allergies
Cognitive decline
Diabetes
Inflammatory bowel diseases
Heart disease
Dyslipidemia
Acai
Acai berries are a Brazilian superfruit native to the Amazon rainforest. They have an incredibly high amount of antioxidants, edging out other antioxidant-rich fruits like blueberries and cranberries.213,214 It’s also been shown to bolster mitochondrial function and energy production.215
Research has strongly suggested that acai berries hold promise for battling chronic diseases through reducing inflammation and oxidative stress:
Battle cardiovascular disease through reducing blood lipid oxidation.216–218
Fight cognitive decline with aging.219–222
Protect against cancer and reduce its ability to spread and proliferate.223
Reduce biomarkers of muscle damage following strenuous exercise, increase serum antioxidant status, and lower blood lipids.224
Protects against liver damage and inflammation.225
Prevent diabetes by improving insulin sensitivity and glycemic control.226–228
Bilberry Extract
Bilberries are a dark purple berry originating in Europe and closely related to blueberries. They possess a diverse array of anthocyanin phytochemicals similar to blueberries,229,230 which have potent antioxidant and anti-inflammatory effects.231
Regular intake could help fight cardiovascular disease, diabetes, and worsening vision.232,233
Over just 3 weeks, supplementing with 300 mg/d of bilberry anthocyanins reduced inflammatory biomarkers by 38–60%, including suppressing the activation of the master inflammatory regulator, NF-kappaB.234 Similar observations have been made with bilberry juice,235 as well as fresh bilberries.236
After just one dose of bilberry extract (470 mg), the glucose and insulin response to a glucose tolerance test was reduced by 18% each.237 Regular consumption of bilberries over 2 months improves fasting glucose and insulin secretion.238
Over 2 months, consuming a mixture of berries, including bilberries, improved platelet function, blood pressure, and blood lipids.239 Supplementation with 320 mg bilberry anthocyanins reduced LDL by 14% and increased HDL by 11%.240
In those with glaucoma, daily intake of 120 mg of bilberry anthocyanins for 2 years improved visual function by 30% compared to placebo, whose vision worsened.241
In those with dry eyes, supplementing with 160 mg/d of bilberry extract for just one month improved dry eye symptoms by 55%.242
In office workers suffering from eye strain, 160–480 mg/d of bilberry extract reduced eye fatigue caused by working with video display terminals.243–245
Maqui Berry
Maqui berries are an exotic, dark-purple fruit native to South America. They are a rich source of anthocyanins that possess strong antioxidant abilities,247,248 and ultimately provide up to three times more antioxidants than blackberries, blueberries, strawberries, or raspberries.249,250
Studies have shown that maqui berries could be a powerful ally against inflammatory diseases.251
In particular, they have been shown to reduce inflammation of blood vessels,252 which could help prevent cardiovascular diseases.
In smokers, 2 grams per day reduced markers of lung inflammation.253
In a three-month clinical study in people with prediabetes, 180 mg of maqui berry extract once daily reduced average blood sugar levels by 5%, which was enough to bring their blood glucose levels back into normal range.254 It also reduced their LDL-c and increased their HDL-c.
A small 30-day study in 13 people with dry eyes found that 30–60 mg of a concentrated maqui berry extract each day increased tear production by roughly 50%.255 Follow-up research demonstrated similar effects after just a month, along with reduced eye fatigue.256
Blueberry
Blueberries are a rich source of anthocyanins and pterostilbene (phytochemicals), and have been shown to increase the activity of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF),270,271 neuropeptides that help neurons grow, branch toward each other, and thus communicate better.272 Studies have shown profound benefits of blueberry consumption:
In older adults, blueberry juice improved learning and memory while reducing depression after 12 weeks of regular consumption.274
Consuming 390 mg of blueberry anthocyanins for 12 weeks improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.275
Increases in brain activity have also been seen in those with mild cognitive impairment after regular supplementation with the equivalent of 1 cup of whole blueberries daily.276
Consuming 100 mg of blueberry extract for 3 months improves memory.277
Supplementing with 160 mg of anthocyanins improved memory and executive cognitive function after 16 weeks.278
In young and healthy adults, just 300 grams of mixed berries (¼ blueberries and half the phytochemical content coming from the blueberries) improved cognitive function for 6 hours after consumption.279
A systematic review of human clinical trials found that six of seven studies reported improvements in cognition, including learning and memory, after anthocyanin-rich food consumption (like blueberries and bilberries).280
Blueberries and their constituent phytochemicals are also protective against the development of cancer, obesity, cardiovascular diseases, diabetes, bone loss, poor immune function, fatty liver, vision loss, and chronic inflammation.281
Cranberry
Cranberries are best-known for their use in treating urinary tract infections. And they work. A meta-analysis of 10 studies found that cranberry juice reduces the likelihood of developing urinary tract infections,282 especially in women with recurrent episodes.283
These benefits are owed to the fact that cranberries are rich in A-type proanthocyanidins (PACs), in contrast to the B-type PACs present in most other fruits. Studies in humans and animals have shown cranberries to lower inflammation, increase nitric oxide synthesis, reduce blood pressure, manage blood lipids, improve endothelial function, and lower oxidative stress.284–286
Drinking cranberry juice suppresses the growth of H. pylori infections in both adults and
Don’t know. I was just wondering if anyone has tried it. Most ingredients have been mentioned on this site. I listened to a podcast he did on the ingredients in energenesis and they did sound good. He reckons that most things are in quantities that are strong enough to have a benefit. That is his criticism of other so called brain boosting supplements on the market. Lots of the ingredients are in say 300mg which seems a standard amount for a lot of supplements.
My husband has been taking most things in the energenesis as they are in the hardys DEN, greens, and restored gold, and some of the things in the other 2 products too but not all the botanicals or at the same concentrations.
Don’t forget you eat platefuls of food each day with thousands or millions of compounds in it especially on a plant based diet so when you think of it like that it is not so many. This just adds extra diversity of things you wouldn’t normally eat in a western country.
The problem is except for vitamins and minerals in these items (of which we know a daily value to maintain health) we are totally ignorant of any therapeutic dose for any of the other exotic items on the list.
To take just one example - Moringa, which at the moment is under discussion along with broccoli seed extract as items of therapeutic interest for those with PD. From a paper presented by wriga, park_bear zeroed in on a reference that provided a framework for calculating a therapeutic dose of Moringa.
“A Strategy to Deliver Precise Oral Doses of the Glucosinolates or Isothiocyanates from Moringa oleifera Leaves for Use in Clinical Studies“
park_bear calculated that 10gm of Moringa powder would be needed to deliver a therapeutic dose on a daily basis.
From the product ‘Energy Facts’ [Supplemental Facts]
Organic Moringa Leaf - 300mg.
There is a hell of a difference between 300mg and 10gm.
As these natural items all have varying degrees of efficacy depending on species, growth conditions and harvesting and processing methods, let’s discount - for your benefit - @park_bear calculation by 50%. So we need 5gm. Still a long way off.
You may find my remarks ‘discouraging’, but feel free to ignore them.
So if you do try these expensive supplements give us some feedback on your results.
Just make sure there is no misunderstanding I should mention that 10 g was just a guesstimate on my part - wriga said that would be an overdose, and he is more knowledgeable than I.
By my extrapolation of this paper’s findings I think a therapeutic dose is 4 gm of Moringa. Another guesstimate.
The fact is we do not know. But I am willing to bet it is not 300 mg.
And I am certain, from my readings on the matter that another item on the supplemental list - 150mg of ‘Organic Broccoli’ would not cut it either.
The argument that would be provided is that these small amounts work synergistically with each other. This may be so, but I have not seen much evidence to bear this out.
I await feedback on results from those who are willing to give it a go 🌺
P.S: I am experimenting with 5gm of Moringa as per cold diffusion technique. Problems with taste. Trying a few masking agents. Will let you know how it goes 🤗
I wonder though if some of these compounds do the same thing or serve the same purpose. If they do 300mg of a few of them might be better than 1 g of one of them as they might enhance the effect of each other?
Also in food compounds are much weaker. The Japanese have a rule that you should eat 30 different foods including herbs and spices each day. I wonder if the same is true with supplements, that it is better to have a variety rather than large amounts of one thing every day. I do wonder if large amounts of some things become toxic after time.
Our bodies seem to be able to take what they need from a varied diet as it passes through and presumably storing a few molecules for later if there is too much of one thing. Maybe we should try mixing up the supplements and rotate them.
“The argument that would be provided is that these small amounts work synergistically with each other. This may be so, but I have not seen much evidence to bear this out.”
And I would agree that there is some evidence that a wider food range leads to a more diverse microbiome and consequently a better response to environmental stress.
But these companies use this observation to throw together a bunch of exotic compounds and claim fantastic benefits.
And all have vitamin/mineral formulations: how do we know that nutritional gaps are being filled and thus the glowing recommendations.
Finally the 150mg of ‘Organic Broccoli’ is a red flag. It is not a concentrate. I eat a whole lot more broccoli when I make roasted vegetables.
The jury is out on this approach. But try the products and give us some feedback 🌺
Yes, we don’t know. All any one can do is try and see if it works for themselves as we all have different deficiencies, problems and diets so likely it won’t work for every one anyway. It just seemed to have a lot of good things in it. I agree the broccoli seems pointless. It is a concentrate in that the water is taken out but not likely more than a gram of whole broccoli.
It’s not necessarily synergy, but the likelihood that some compounds actually act the same way or are interchangeable So you wouldn’t need the full dose of each.
Did Hardy's decrease their commission rates on the DEN? 😋
Ha ha😁I wish they paid commission for all the people I have got onto them but no, not even a thank you!
Have you tried it though?
This seems to have the same things as the hardys den, hardys greens and probiotics, the restore gold all combined so maybe the price isn’t that different if I just swap. It has a lot of compounds for stress anxiety and depression and hubby has been extremely anxious this winter. When he first started the hardys his anxiety completely disappeared after. 3 days and he has been pretty good for 2 years but it is back. I’m thinking he may be depleted in something different now. I tried half and half hardys den and another one neuro natural serenity but it didn’t help him.
The thing to watch though is if you start on one of these with so many compounds you would need to inspect the labels of everything else you take so you aren’t overdosing on anything. Eg green tea is in lots of things but is not good in high doses.
It helps that I’m a bit of a science geek so I do find it all very interesting, and to be honest I think the change of diet and the extra research hobby has improved my physical and brain health as I was tending to be a little lazy and eat badly some days. Now I know better!
Oh he is not on it. I’m deciding if the expense is worth it! Two of the products you take as scoops so that’s got to be easier but it would mean he’d have to stop hardys and the restore gold as it would double up on too many things. Which would of course offset the expense.
With all his anxiety this winter I gave him a break on all supplements for a few weeks just in case it was one of those interacting with his medication and he deteriorated rapidly so he is back on them again but he still hasn’t been able to shake off the anxiety which makes things worse.
The specialist nurse said he should try the levodopa medication for his stiffness early in the year. It was really his only symptom. He was doing well back then Mood wise but the stiffness was annoying. . He tried the Kinson C/L which really made him sick, And that’s when the anxiety started. so they switched him to madopar 62.5 and he tried 3, then 4 of those. Made no difference to the stiffness and made the anxiety and tremors worse. So he’s dropped slowly back to 3, then 2 madopar Yesterday and he felt a little better last night. Seriously I don’t think he can tolerate these medications the doctors give him. Every time he tries one they insist on it makes him worse. It hasn’t improved his stiffness and on 4 he was having horrible juddering fits and freezing . At the lower dose that’s stopped. None of it has helped stiffness And it made him shakier so not sure what the point of it is. I think it is just way too strong for him. So I’m back looking for anything which help reduce anxiety and this looks like it has lots of things that could. But I’m staring at my big cupboard of half used bottles and wondering is it worth spending more.
What I need him to do is start some of the hand and shoulder exercises as that is the area he is losing use of. His hands don’t work at bridge to rearrange his cards which makes him anxious and upset. But I can’t get him to try anything Physical to help it. So I wonder what the point of buying supplements is if he will not do the physical movement to help himself. I’m frustrated.
LAJ my good friend , i have a whole bunch of ideas but most of them involve more trials and errors of supplements, so i'll just spare you that. What it sounds like to me is that the manufacturing of dopamine is stealing from the production of serotonin, as the two compete for amino acid precursors. Also, the Carbidoopa suppresses peripheral production of serotonin. I get bouts of anxiety as well as depression that come and go, lasting anywhere from weeks to months. It's miserable! Right now I'm alright, i bumped up my lithium orotate from 5mg to 10mg a day without fail. Takes about 2 weeks to kick in . I've been alright ever since . Hope it lasts! Thank you for taking such good care of him! You're a saint.
Gosh never been called that before 😆. There is some lithium orotate in the hardys but I bought some of that ages ago but haven’t ever used it. Might start adding a wee bit to his daily vitamin bottle to see if it helps. Will keep you posted.
Always keen for new idea too.
Does your anxiety and depression seem to coincide with the middle of autumn/ daylight savings finishing? It always does for him. But this time it was also the same time as the medication Kinson C/l started . Too many variables as usual. I need 30 of him so I can do a proper trial🤣🤣🤣
Mine comes and goes seemingly without rhyme or reason. Remember that if you do try lithium orotate , it takes about 2 weeks to see a difference. You can expect a big difference though! 10 to 20mg once a day is what was recommended to me by my doctor. Good luck and follow up with me in 2 weeks!
LAJ, have you read about Ketamine? I was at our doctor's today and read about it in a magazine. Sounded pretty amazing. Of course, I have to search more about it.
Hi, not for PD or anxiety but The psych department at my daughters university was recruiting students for a trial taking ketamine to see if helped with the fear of spiders! I guess that is a test for anxiety. I will try and find out the results if they have released the findings.
This is the study. Not sure when results are available but I can email them. Sometimes these guys are very cagey though as they don’t want people trialling things on themselves I suppose.
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