THE SCIENCE

Sibelius sage™ is a specifically grown and harvested extract of sage (Salvia officianalis) that has been tested and clinically trialled for its effects on cognitive processes. Sibelius sage™ is grown just outside Hampshire in the UK on our farm which is dedicated just to the sage to prevent risk of cross contamination. The plants are managed under Good Agricultural Practice standards and are harvested between November and March each year.

Sage extract is known to promote healthy levels of the important neurotransmitter acetylcholine, as well as other neurochemicals needed for optimal brain function, and to support mood and cognitive performance. Sibelius Sage ™ (Salvia officinalis L.) is a novel type of sage extract, which has been shown to support brain and cognitive function. It derives from a proprietary, non-GMO cultivar grown in the UK with proven cognitive benefits. In a clinical study, Sibelius™:Sage improved accuracy of attention, working memory and recognition and recall. However, the real X factor lies in its ability to effectively provide immediate cognitive improvements within 1 hour after supplementation.

We have selected Sibelius Sage in our formula based on its premium quality, robust testing, and its proven broad cognitive benefits across all ages.

Benefits:

Improve Cognitive Performance

A double-blind placebo study has shown for the first time that administration of a standardised Salvia extract can improve cognitive function in healthy older individuals, with significant improvement in the working memory. The study demonstrated the overall superiority for secondary memory of the most effective (333 mg) dose to placebo was approximately 30 units (see Fig. 1a). This comfortably exceeds that seen previously for a ginkgo–ginseng combination in healthy middle-aged volunteers (Wesnes et al. 2000). Comparing a normal population of the age-range in the present study to that in healthy 18 to 25 year olds shows a decline in the secondary memory factor of 43.2 units (95% confidence intervals 36.4 to 50.2). The benefits seen in the present study thus reflect a substantial reversal of the deterioration which typically occurs over approximately five decades of normal ageing. Furthermore, it is worth emphasising that this was a high-functioning sample (3).

Improves short-term memory and learning

An acute, double-blind, placebo-controlled study (1) was conducted with two single doses of Sibelius™: Sage (150 mg and 300 mg). Cognitive performance was evaluated using CogTrack™, which probes aspects of cognitive performance covering attention, working memory and episodic/declarative memory through a series of computer-based tasks. Consistent with previous study of Sibelius™: Sage a significant effect was seen on the Immediate Word Recall task in young adults, suggesting acute treatment benefits to verbal episodic/declarative memory performance.

Adaptation to stress, memory, mathematic and word processing, and response time

In a double blind, placebo controlled crossover study, 30 healthy participants (ranging in age from 20 years to 29 years) were given a Salvia officinalis extract or placebo and tested for stress, mathematical processing, word processing, response time and memory as well as mood. Improved mood and cognitive performance were noted after single dose administration at 300mg. (2)

Cognitive performance and recall

In 2010, a clinical study of Salvia officinalis and Salvia lavandulifolia essential oil investigated the effect on cognition and mood in 135 healthy adults. The S. officinalis group performed significantly better than the S. lavandulifolia and control groups on the quality of memory, specifically long-term or secondary memory with no impact on working memory performance. (2)

A 2005 placebo-controlled, double-blind, balanced, crossover study investigating the effect of sage on mood and cognition in 24 healthy young volunteers (18-37 years old) found that both 25ml and 50ml a standardized essential oil produced improvement in speed of memory, alertness, calmness and contentedness when compared to placebo.

Strong antioxidant properties

Sage is full of antioxidants that may help enhance brain health, support energy levels and improve your short-term memory.

References

1 Kieron D. Edwards (2021) Assessment of the Effects of a Sage (Salvia officinalis) Extract on Cognitive Performance and Mood in Adolescents and Young Adults. American Journal of Phytomedicine and Clinical Therapeutics ISSN 2321-2748

(2) Studies published on the Sibelius Sage research website

(3) Andrew B. Scholey & Nicola T. J. Tildesley & Clive G. Ballard & Keith A. Wesnes & Andrea Tasker & Elaine K. Perry & David O. Kennedy. An extract of Salvia (sage) with anticholinesterase properties improves memory and attention in healthy older volunteers. Psychopharmacology (2008) 198:127–139. DOI 10.1007/s00213-008-1101-3

(4) Mohsen Hamidpour, Rafie Hamidpour, Soheila Hamidpour, and Mina Shahlari. Chemistry, Pharmacology, and Medicinal Property of Sage (Salvia) to Prevent and Cure Illnesses such as Obesity, Diabetes, Depression, Dementia, Lupus, Autism, Heart Disease, and Cancer. J Tradit Complement Med. 2014 Apr-Jun; 4(2): 82–88.doi: 10.4103/2225-4110.130373

Headquartered in Japan, Kaneka is dedicated to the development of world-class technology in the field of pharmaceuticals. Backed up by more than 10 years of research, development, and testing, Kaneka Ubiquinol™ is the only supplemental Ubiquinol ingredient available today and is utilised in hundreds of consumer products around the world. Kaneka Ubiquinol™ is now being shown in repeated clinical trials to be the most effective and powerful form of CoQ10 available.

Ubiquinol is an antioxidant found naturally in the body that is responsible for supporting energy production in your cells. When Ubiquinol levels are depleted it can contribute to feelings of sluggishness and tiredness. We selected Kaneka® due to its world leading patented position. This highest quality form of CoQ10 displays superior results in energising the cells throughout the body, enhancing cognitive endurance and overall performance.

Benefits:

Enhance recovery, endurance and adaptation to stress

As you age, your levels of Ubiquinol decrease. Lower Ubiquinol levels mean that your body’s natural energy levels can drop, which can make it harder and harder to bounce back from your workouts.

A 2013 study (1) showed Ubiquinol can also boost the power production of trained athletes. Athletes who received Ubiquinol increased their power per kilogram of body weight by over 2.5 percent in just six weeks, showing significantly enhanced physical performance compared to athletes who received a placebo.

A 2016 study (2) demonstrated that supplementing with Ubiquinol may lower the degree of inflammation after exertion and intense physical exercise, which may help with muscle recovery and cognitive endurance.

Reduce mental fatigue

Ubiquinol is the “spark plug” that helps fire energy production in your cells. When your energy production is low, it affects your natural energy levels. This could contribute to feelings of sluggishness and tiredness.

As we age, or when we are under prolonged stress due to lifestyle, diet or environmental factors, our natural CoQ10 and Ubiquinol levels become depleted and the ability to produce Ubiquinol declines. (3,4) In addition to this, the free radical activity and oxidative stress that occurs in our body from normal metabolism, even in healthy individuals, increases as we get older.(5)

One of the main roles of antioxidants in the body is to help combat free radical activity and oxidative stress. As such, antioxidants like Ubiquinol may help to minimise the impairment of normal functioning cells and restore essential levels of Ubiquinol back into your system. (6)

References

(1) Alf D, Schmidt ME, Siebrecht SC. Ubiquinol supplementation enhances peak power production in trained athletes: a double-blind, placebo controlled study. Journal of the International Society of Sports Nutrition. 2013;10:24.

(2) Sarmiento, A., Diaz-Castro, J., Pulido-Moran, M., Moreno-Fernandez, J., Kajarabille, N., Chirosa, I., Guisado, I. M., Javier Chirosa, L., Guisado, R. and Ochoa, J. J. (2016), Short-term ubiquinol supplementation reduces oxidative stress associated with strenuous exercise in healthy adults: A randomized trial. BioFactors, 42: 612–622.

(3) Zhang, Y.; Liu, J.; Chen, X.-q.; Oliver Chen, C. Y., Ubiquinol is superior to ubiquinone to enhance Coenzyme Q10 status in older men. Food & Function 2018, 9 (11), 5653-5659.

(4) Linnane, A. W., Zhang, C., Yarovaya, N., Kopsidas, G., Kovalenko, S., Papakostopoulos, P., … & Richardson, M. Human aging and global function of coenzyme Q10. Annals of the New York Academy of Sciences, (2002). 959(1), 396-411.

(5) Garrido-Maraver J, Cordero MD, Oropesa-Ávila M, et al. Coenzyme Q10 Therapy. Molecular Syndromology. 2014;5(3-4):187-197.

(6) Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy Reviews. 2010;4(8):118-126.

BacoMind® is a patented, clinically tested ’memory and cognition enhancing’ standardised phytochemical composition containing unique full-spectrum extract with 9 different bioactive ingredients derived from Bacopa monnieri. BacoMind® is used for improving memory and age related neurodegenerative disorders. BacoMind® has 20 publications.

Bacopa monnieri is a nootropic herb also called ‘brahmi’, a staple in traditional Ayurvedic medicine - the traditional medicine of India. It has been used by Ayurvedic medical practitioners for centuries and used today for a variety of purposes, including improving memory, overall brain function, reducing stress and mild anxiety.

We have selected Bacomind based on the extensive clinical studies confirming its safety-enhancing cognitive and memory performance.

Benefits:

Improve visual information processing, learning and memory

A double blind placebo study of 46 healthy adults observed that taking 300 mg of Bacopa monnieri daily significantly improved the speed of processing visual information, learning rate, and memory, compared with the placebo treatment (1).

Another 12-week study in 60 older adults found that taking either 300 mg or 600 mg of Bacopa monnieri extract daily improved memory, attention, and the ability to process information, compared with the placebo treatment (2).

BacoMind® reduced learning problems in 78% of participants in a study completed over 6 months (7).

Bacomind®, in a Randomized Double Blind Palcebo Controlled clinical study on the Normal Cognition in health Elderly Individuals showed improved memory acquisition and retention in healthy older Australians. Also showed a 50% improvement in the ability to recall information, a 24% improvement in immediate recall memory, and a significant positive improvement in learning. (8)

Support adaptation to stress and mild anxiety

Research out of Australia and New Zealand suggests Bacopa has positive mood effects and reduction in cortisol levels, pointing to a physiological mechanism for stress reduction (3).

In a meta-analysis, Bacopa twice daily equiv. to 12g dry of crude extract, for a month long clinical trial in 35 patients with diagnosed anxiety neurosis, demonstrated a significant decrease in anxiety symptoms, level of anxiety, level of disability and mental fatigue and an increase in immediate memory span (6).

Bacomind® reduced learning problems in 78% of children, reduced Impulsivity in 67% of children, and reduced psychiatric problems in 52% of the participants. (7)

Supports acetylcholine, dopamine & serotonin

Current evidence suggests Bacopa acts via the following mechanisms—antioxidant neuroprotection, acetylcholinesterase inhibition and/or choline acetyltransferase activation, increased cerebral blood flow, and neurotransmitter modulation (acetylcholine, 5-hydroxytryptamine, dopamine) (5).

References

(1) Stough C, Lloyd J, Clarke J, Downey LA, Hutchison CW, Rodgers T, Nathan PJ (2015). The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl). 2001 Aug;156(4):481-4. doi: 10.1007/s002130100815. Erratum in: Psychopharmacology (Berl). 2015 Jul;232(13):2427. Dosage error in article text. PMID: 11498727.

(2) Peth-Nui T, Wattanathorn J, Muchimapura S, Tong-Un T, Piyavhatkul N, Rangseekajee P, Ingkaninan K, Vittaya-Areekul S (2012). Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing, Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy Elderly Volunteers. Evid Based Complement Alternat Med. 2012;2012:606424. doi: 10.1155/2012/606424. Epub 2012 Dec 18. PMID: 23320031; PMCID: PMC3537209.

(3)Benson S, Downey LA, Stough C, Wetherell M, Zangara A, Scholey A (2014). An acute, double-blind, placebo-controlled cross-over study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on multitasking stress reactivity and mood. Phytother Res. 2014 Apr;28(4):551-9. doi: 10.1002/ptr.5029. Epub 2013 Jun 21. PMID: 23788517.

(4) Dave UP, Dingankar SR, Saxena VS, Joseph JA, Bethapudi B, Agarwal A, Kudiganti V (2014). An open-label study to elucidate the effects of standardized Bacopa monnieri extract in the management of symptoms of attention-deficit hyperactivity disorder in children. Adv Mind Body Med. 2014 Spring;28(2):10-5. PMID: 24682000.

(5) Aguiar, S., & Borowski, T. (2013). Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation research, 16(4), 313–326.

(6) Gohil, K., & Patel, J. (2010). A review on Bacopa monnieri : Current research and future prospects. International Journal of Green Pharmacy, 4(1), 1.

(7) Dave UP, Dingankar SR, Sax VS, Joseph JA, Bethapudi B, Agarwal A, Kudiganti V. An Open-label Study to Elicidate the Effects of Standardized Bacopa monnieri Extract in the Management of Symptoms of Attention-deficit Hyperactivity Disorder in Children. Advances in Mind-Body Medicine 2014, 28 (2):10-15.

(8) Mogan A, Stevens, J. Does Bacopa monniero improve memory performance in older persons? Results in randomized, placebo controlled double-blind trail. The Journal of Alternative and Complimentary Medicine 2010, 16(7): 753-759

Ancient Chinese practitioners have been using the Cordyceps mushroom (Cordyceps Sinensis), a medicinal mushroom, for its purported mental and physical wellness benefits since at least 1757 AD.

Studies have shown statistically significant effects on improved learning and reduced memory impairment from Cordyceps, in addition to significant neuroprotective properties (reduction of neuronal cell death) in the hippocampal region, including the treatment of kidney disease and low libido.

Benefits:

Improve brain health

Cordyceps have a neuroprotective function, helping to prevent damage and protect the brain. The benefit of Cordyceps to brain health can help to minimise the impact of ageing and so reduce the risk of age-related cognitive decline (3).

Increase cognitive energy

Cordyceps have been shown to improve many aspects of cognitive performance including learning capacity and memory. This in turn can help to increase mental clarity, banish brain fog and improve productivity.(3)

Increased energy and oxygen supply to muscles (VO2 max)

Multiple studies involving average, non-athletes have shown a slight increase in VO2 max for participants taking Cordyceps supplements over those taking a placebo pill. VO2 max is a measure of how fast the body delivers oxygen to the muscles so that the muscles can use that oxygen to produce energy (1).

In one study, researchers tested their effects on exercise capacity in 30 healthy older adults using a stationary bike. Participants received either 3 grams per day of a synthetic strain of Cordyceps or a placebo pill for six weeks. By the end of the study, VO2 max had increased by 7% in participants who had taken Cordyceps, while participants given the placebo pill showed no change. (2).

References

(1) Hirsch, K. R., Smith-Ryan, A. E., Roelofs, E. J., Trexler, E. T., & Mock, M. G. (2017). Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation. Journal of dietary supplements, 14(1), 42–53.

(2) Yi, X., Xi-zhen, H. & Jia-shi, Z (2004). Randomized double-blind placebo-controlled clinical trial and assessment of fermentation product of Cordyceps sinensis (Cs-4) in enhancing aerobic capacity and respiratory function of the healthy elderly volunteers. Chin. J. Integr. Med. 10, 187–192 (2004).

(3) Guangxin Yuan ,  Liping An ,  Yunpeng Sun ,  Guangyu Xu , and  Peige Du . Improvement of Learning and Memory Induced by Cordyceps Polypeptide Treatment and the Underlying Mechanism. National Library of Medicine 2018. PMCID: PMC5874985

Sourced from the pine tree (Pinus pinaster), native to the Mediterranean region. It is used primarily to increase cerebral blood flow, also helps prevent decreases in dopamine and norepinephrine.

Benefits:

Enhance brain health

New research shows that adults over the age of 55, supplementing with Pinus Pinaster bark extract over the course of one year, showed superior results in brain related tasks compared to placebo groups (1).

Improve blood flow

Pine bark extract has a significant impact on nitric oxide (NO) levels in the body, which are responsible for vasodilation and improving blood flow. A recent study found the combination of pine bark extract and arginine (an amino acid that also boosts NO production) were effective for improving mild to moderate erectile dysfunction. If you struggle with low libido or erectile dysfunction, or suffer from high blood pressure, boosting NO levels in the body is an effective strategy for helping to reverse these conditions.

References

(1) Mahsa Malekahmadi,  Mahdi Shadnoush, Sheikh Mohammed Shariful Islam, Armin Shirvani, Naseh Pahlavani, Jamshid Gholizadeh Navashenaq, Safieh Firouzi, Jenna McVicar, Mohsen Nematy, Mohammad Reza Zali, Omid Moradi Moghaddam, Abdolreza Norouzy. The effect of French maritime pine bark extract supplementation on inflammation, nutritional and clinical status in critically ill patients with traumatic brain injury: A randomized controlled trial. Phytother Res. 2021 Sep;35(9):5178-5188;

(2) R Stanislavov, V Nikolova. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. May-Jun 2003;29(3):207-13

A nonessential amino acid the body makes from another amino acid called phenylalanine. It is an essential component for producing several important brain chemicals called neurotransmitters, including epinephrine, norepinephrine, and dopamine.

Epinephrine and norepinephrine are the main actors in the body's response to acute stress, whereas dopamine helps to support a positive mood and mental alertness. Dopamine is associated with motivation, reward and the feeling of enjoyment.

Benefits:

Memory and executive function

Studies on the effects of a single dose of tyrosine supplements revealed short-term benefits on working memory performance and executive functions” (1)

Two studies suggest that tyrosine significantly improved working memory during a mentally demanding task, compared to a placebo and was also found to improve cognitive flexibility (3,4)

Supports dopamine

Tyrosine acts as the precursor to dopamine and is known to “increases dopamine availability” (2)

Tyrosine supports L dopa which is converted to Dopamine. Catecholamine synthesis begins with the amino acid tyrosine, which comes from the diet. L-tyrosine is converted to (dopa) by tyrosine hydroxylase (7)

Tyrosine is the precursor of the catecholamines, converted to dopamine via L-dopa and the enzymes Tyrosine hydroxylase (TH) and aromatic l-amino acid decarboxylase and to noradrenaline by dopamine β-hydroxylase (5)

Dopamine is one of the three main signaling molecules from the catecholamine family. The other two are the famous (or perhaps infamous) fight-or-flight response molecules epinephrine (adrenaline) and norepinephrine (noradrenaline)(6)

L-tyrosine does not seem to enhance the release of catecholamines when neurons are firing at their basal rates, but it does when firing rates are increased by stress (8)

References

(1) Jongkees, B. J., Hommel, B., Kühn, S., & Colzato, L. S. (2015). Effect of tyrosine supplementation on clinical and healthy populations under stress or cognitive demands—A review. Journal of Psychiatric Research, 70, 50–57.

(2) Kühn, S, Düzel, S, Colzato, L. (2019) Food for thought: association between dietary tyrosine and cognitive performance in younger and older adults. Psychological Research 83, 1097–1106

(3) Colzato, L. S., Jongkees, B. J., Sellaro, R., & Hommel, B. (2013). Working memory reloaded: tyrosine repletes updating in the N-back task. Frontiers in behavioral neuroscience, 7, 200.

(4) Steenbergen L, Sellaro R, Hommel B, Colzato LS. (2015). Tyrosine promotes cognitive flexibility: evidence from proactive vs. reactive control during task switching performance. Neuropsychologia. 2015 Mar;69:50-5. doi: 10.1016/j.neuropsychologia.2015.01.022. Epub 2015 Jan 16. PMID: 25598314.

(5) Bloemendaal, M., Froböse, M. I., Wegman, J., Zandbelt, B. B., van de Rest, O., Cools, R., & Aarts, E. (2018). Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and Proactive Response Inhibition in Healthy Older Adults. eNeuro, 5(2), ENEURO.0035-17.2018.

(6) M.E. Gnegy, in: S.T. Brady, G.J. Siegel, R.W. Albers, D.L. Price (2012). Basic Neurochemistry (Eighth Edition), Academic Press, New York, 2012, pp. 283–299.

(7) Jameson JL, De Groot LJ, Weir GC, De Kretser DM, Giudice LC, Grossman AB, Melmed S, Potts Jr JT, (2016). Endocrinology: Adult and Paediatric. Book • Seventh Edition •

(8) Young S. N. (2007). L-tyrosine to alleviate the effects of stress?. Journal of psychiatry & neuroscience : JPN, 32(3), 224.

Quatrefolic® is a world-leading patented “finished folate”, meaning the body can use it immediately without any kind of metabolization.

Clinical research states that daily supplementation with folate helps improve cognitive performances, including memory and information processing. We have selected this patented form to ensure maximum bioavailability and in turn, maximum cognitive outcomes.

Benefits:

Improve immune and brain function, reduce fatigue

Thanks to its various health claims (EFSA APPROVED) related to psychological functions, reduction of tiredness and fatigue, cell division, normal homocysteine metabolism, and well function of the immune system, folate is a good solution for elderly people.

For older adults, the supplementation of the proper form of folate is essential to quickly re-establish the plasma folate levels and counter the variety of physiologic changes that influence folate status.

In 2000, Bottiglieri and Reynolds (1) showed that the concentration of folate in the cerebrospinal fluid (CSF) decreases with age, particularly in older adults over 70 of age. This provided further evidence of a link between folate concentration and age, and for the first time, highlighted this connection directly in the nervous system.

Quatrefolic® supplementation is suggested to guarantee the right dosage of biologically active folate and to efficiently support brain function since it is the only folate form able to cross the blood-brain barrier.

Promotes learning ability and memory

Quatrefolic® sustains healthy cell, tissue growth, digestive, and immune systems. It can improve energy production and the formation of red blood cells while promoting normal brain development and function. Moreover, the 5-MTHF can boost learning ability and memory. Quatrefolic® use levels will be the same as that of folate. (2)

References

(1) Bottiglieri T., Reynolds E. et al. J Neurol Neurosurg Psychiatry 2000

(2) Seshadri S. at al. N Engl J Med 2002

Rhodiola Rosea, also known as Golden Root, is a plant from Siberia that grows well in dry and cold arctic climates.

The medicinal compounds of Rhodiola Rosea come from the root of the plant and are considered adaptogens, meaning they help your body adapt to stress when consumed. This root contains more than 140 active ingredients, the two most potent of which are Rosavin and Salidroside. People in Russia and Scandinavian countries have used Rhodiola for centuries to treat mild anxiety and fatigue, and today Rhodiola has also been shown to improve symptoms of burnout and fatigue, which can occur with chronic stress.

Benefits:

Stress and mild anxiety

One study investigated the effects of Rhodiola extract in 101 people with life- and work-related stress. It found significant improvements in symptoms of stress, such as fatigue, exhaustion and mild anxiety, after just three days. These improvements continued throughout the study (1)

Fatigue, cognitive performance and endurance

A Rhodiola study tested its effects on mental fatigue in 56 physicians working night shift. The physicians were randomly assigned to receive either 170 mg of Rhodiola or a placebo pill per day for two weeks. Rhodiola reduced mental fatigue and improved performance on work-related tasks by 20%, compared to the placebo (2).

Rhodiola helps improve exercise endurance and capacity. One study demonstrates that those given 200 mg of Rhodiola before a cycling test were able to exercise for an average of 24 seconds longer than those given a placebo (3).

Enhance brain health and reduce symptoms of mild anxiety

Pharmacological research suggests that Rhodiola may facilitate the production and proliferation of dopamine-producing cells (4).

References

(1) Edwards D, Heufelder A, Zimmermann A (2012). Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms--results of an open-label study. Phytother Res. 2012 Aug;26(8):1220-5. doi: 10.1002/ptr.3712. Epub 2012 Jan 6. PMID: 22228617.

(2) Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner (2000). Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000 Oct;7(5):365-71. Doi: 10.1016/S0944-7113(00)80055-0. PMID: 11081987.

(3) De Bock K, Eijnde BO, Ramaekers M, Hespel P. Acute (2004). Rhodiola rosea intake can improve endurance exercise performance. Int J Sport Nutr Exerc Metab. 2004 Jun;14(3):298-307. doi: 10.1123/ijsnem.14.3.298. PMID: 15256690.

(4) Zhuang, W., Yue, L., Dang, X., Chen, F., Gong, Y., Lin, X., & Luo, Y. (2019). Rosenroot (Rhodiola): Potential Applications in Aging-related Diseases. Aging and disease, 10(1), 134–146.

Vitamin B6, or Pyridoxine, is primarily known to help keep the nervous system and brain at peak performance, allowing it to function at a healthy rate and improving nerve communications throughout the body and brain.

The body does not store Vitamin B6 and releases any excess in urine, so people need to get enough vitamin B6 daily to avoid running low.

Benefits:

Supports neurotransmitter synthesis

B6 is particularly well known for its important function in the synthesis of neurotransmitters like dopamine from L-dopa, serotonin from 5-HTP, and gamma‐aminobutyric acid (GABA) from glutamate” (1).

The role of vitamin B6 in amino acid metabolism makes it a rate limiting cofactor in the synthesis of neurotransmitters such as dopamine, serotonin, γ-aminobutyric acid (GABA), noradrenaline and the hormone melatonin. The synthesis of these neurotransmitters is differentially sensitive to vitamin B6 levels, with even mild deficiency resulting in preferential down-regulation of GABA and serotonin synthesis (2).

Improve Mood and Reduce Symptoms of mild anxiety

Vitamin B6 plays an important role in mood regulation. This is partly because this vitamin is necessary for creating neurotransmitters that regulate emotions, including serotonin, dopamine and gamma-aminobutyric acid (GABA) (3)

Vitamin B6 may also play a role in decreasing high blood levels of the amino acid homocysteine, which have been linked to various mood related issues (4)

Several studies have shown that mood is associated with low blood levels and intakes of vitamin B6, especially in older adults who are at high risk for B vitamin deficiency (5)

References

(1) Calderón-Ospina CA, Nava‐Mesa MO (2020). B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. Journal of Clinical Otolaryngology

(2) Kennedy D. O. (2016). B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review. Nutrients, 8(2), 68.

(3) Dakshinamurti S, Dakshinamurti K. Vitamin B6. In: Zempleni J, Rucker RB, McCormick DB, Suttie JW, eds. Handbook of Vitamins. 4th ed. New York: CRC Press (Taylor & Fracis Group); 2007:315-359.

(4) Marshal Folstein 1 , Timothy Liu ,  Inga Peter, Jennifer Buell, Lisa Arsenault, Tammy Scott, Wendy W Qiu. The homocysteine hypothesis of depression. Am J Psychiatr7. 2007 Jun; 164(6):861-7. doi: 0.1176/ajp.2007.164.6.861.

(5) Anne-Mette Hvas 1, Svend Juul, Per Bech, Ebba Nexø Vitamin B6 level is associated with symptoms of depression Psychother Psychosom Nov-Dec 2004;73(6):340-3. doi: 10.1159/000080386.

Perhaps the most well-known B vitamin, B12, is vital for neurological function, DNA production, and red blood cell development. A deficiency in this key vitamin can cause serious symptoms, including fatigue, nerve damage, digestive issues, and neurological problems linked to mood and memory loss.

B12 is widely proven to Improve cognitive function in ageing, including memory. Unlike many supplements our Brain formula uses a pure B12 methylcobalamin, which is a naturally occurring form of vitamin B12, as opposed to the inferior synthetic versions.

Benefits:

Cognitive performance

To date observational studies have found correlations between low serum vitamin B12 concentrations alone or in combination with high folate concentrations and poor cognitive function (3-8). For example, an analysis of cross-sectional 2011–2014 NHANES data on 2,420 adults aged 60 years or older found that low vitamin B12 (MMA greater than 0.27 micromol/L or serum vitamin B12 less than 203 pg/mL [150 pmol/L]) combined with high folic acid—unmetabolized serum folic acid greater than 0.44 mcg/L (1 nmol/L) or serum total folate higher than 32.7 mcg/L (74.1 nmol/L)—was associated an almost two to three times higher risk of cognitive impairment (3).

Energy and endurance

Because of its role in energy metabolism, vitamin B12 is often promoted as an energy enhancer and an athletic performance and endurance booster (1,2).

References

(1) Lukaski HC. Vitamin and mineral status: Effects on physical performance. Nutrition 2004;20:632-44. [PubMed abstract]

(2) Jung YP, Earnest CP, Koozehchian M, Galvan E, Dalton R, Walker D, et al. Effects of acute ingestion of a pre-workout dietary supplement with and without p-synephrine on resting energy expenditure, cognitive function and exercise performance. J Int Soc Sports Nutr 2017;14:3. [PubMed abstract]

(3) Bailey RL, Jun S, Murphy L, Green R, Gahche JJ, Dwyer JT, et al. High folic acid or folate combined with low vitamin B-12 status: Potential but inconsistent association with cognitive function in a nationally representative cross-sectional sample of US older adults participating in the NHANES. Am J Clin Nutr 2020;112:1547-57. [PubMed abstract]

(4) Horvat P, Gardiner J, Kubinova R, Pajak A, Tamosiunas A, Schöttker B, et al. Serum folate, vitamin B-12 and cognitive function in middle and older age: The HAPIEE study. Exp Gerontol 2016;76:33-8. [PubMed abstract]

(5) Lildballe DL, Fedosov S, Sherliker P, Hin H, Clarke R, Nexo E. Association of cognitive impairment with combinations of vitamin B₁₂-related parameters. Clin Chem 2011;57:1436-43. [PubMed abstract]

(6) Miles LM, Mills K, Clarke R, Dangour AD. Is there an association of vitamin B12 status with neurological function in older people? A systematic review. Br J Nutr 2015;114:503-8. [PubMed abstract]

(7) O’Connor DMA, Laird EJ, Carey D, O’Halloran AM, Clarke R, Kenny RA, et al. Plasma concentrations of vitamin B12 and folate and global cognitive function in an older population: cross-sectional findings from The Irish Longitudinal Study on Ageing (TILDA). Br J Nutr 2020;124:602-10. [PubMed abstract]

(8) Boumenna T, Scott TM, Lee JS, Palacios N, Tucker KL. Folate, vitamin B-12, and cognitive function in the Boston Puerto Rican Health Study. Am J Clin Nutr 2020;113:179-86. [PubMed abstract]

Panax Ginseng is a plant that grows in Korea, China, and Siberia. It's considered an adaptogen, which are natural substances that are believed to stimulate the body's resistance to stressors. Panax ginseng contains many active chemicals. The most important are called ginsenosides or panaxosides.

Benefits

Improve cognitive performance and memory

A small study (1) of 20 healthy young volunteers who received a single 400-mg dose of ginseng found improvement in cognitive performance, secondary memory performance, speed of performing memory tasks, and accuracy of attentional tasks.

Additionally, the results of two separate studies (2, 3) each including about 30 young, healthy volunteers who received 200 mg of G115 daily for eight weeks, showed improvement in certain psychomotor functions (i.e., better attention, processing, and auditory reaction time), social functioning, and mental health.

References

(1) Kennedy DO, Scholey AB, Wesnes KA. Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults. Physiol Behav. 2002;75:739–51.

(2) D'Angelo L, Grimaldi R, Caravaggi M, Marcoli M, Perucca E, Lecchini S, et al. A double-blind, placebo-controlled clinical study on the effect of a standardized ginseng extract on psychomotor performance in healthy volunteers. J Ethnopharmacol. 1986;16:15–22.

(3) Ellis JM, Reddy P. Effects of Panax ginseng on quality of life. Ann Pharmacother. 2002;36:375–9.

Zinc is a trace mineral, meaning that the body only needs small amounts, and yet it is necessary for almost 100 enzymes to carry out vital chemical reactions. It is a major player in the creation of DNA, growth of cells, building proteins, healing damaged tissue, and supporting a healthy immune system. Because it helps cells to grow and multiply, adequate zinc is required during times of rapid growth, such as childhood, adolescence, and pregnancy. Zinc is also involved with the senses of taste and smell.

Benefits:

Increased cognitive performance

A randomised double-blind placebo-controlled design (1) was employed to investigate the effects of Zn supplementation on cognitive function in 387 healthy adults aged 55–87 years. Several measures of visual memory, working memory, attention and reaction time were obtained using the Cambridge Automated Neuropsychological Test Battery at baseline and then after 3 and 6 months of 0 (placebo), 15 or 30 mg Zn/d. Younger adults (<70 years) performed significantly better on all tests than older adults (>70 years)

References

(1) Effects of zinc supplementation on cognitive function in healthy middle-aged and older adults: the ZENITH study. British Journal of Nutrition , Volume 96 , Issue 4 , October 2006 , pp. 752 - 760 DOI: https://doi.org/10.1079/BJN20061911

KSM-66® is the gold standard of Ashwagandha root extract.KSM-66® unlocks the full potential of ashwagandha root thanks to its unique aqueous green extraction process yielding the highest concentration of actives and the largest suite of clinical studies that have proven benefits for health.

These human studies offer extensive clinical evidence showing KSM-66® to be effective in supporting a variety of health conditions, including reducing stress and anxiety, improving memory and cognitive function, and promoting strength, cardio-respiratory endurance and immunity in athletes.

Benefits:

Promote adaptation to stress and reduce mild anxiety

A prospective, randomized, double-blind, placebo-controlled study of the safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha root reduces stress and anxiety in adults. (1)

Results: The treatment group given the high-concentration full-spectrum Ashwagandha root extract exhibited a significant reduction (P<0.0001) in scores on all the stress-assessment scales on Day 60, relative to the placebo group. The serum cortisol levels were substantially reduced (P=0.0006) in the Ashwagandha group, relative to the placebo group. The adverse effects were mild in nature and were comparable in both the groups. No serious adverse events were reported.

Conclusion: The findings of this study suggest that a high-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual’s resistance towards stress and thereby improves self-assessed quality of life.

Testosterone Male Sexual Function

Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study(2)

Results: There was a 167% increase in sperm count (9.59 ± 4.37 × 106/mL to 25.61 ± 8.6 × 106/mL; ), 53% increase in semen volume (1.74 ± 0.58 mL to 2.76 ± 0.60 mL; ), and 57% increase in sperm motility (18.62 ± 6.11% to 29.19 ± 6.31%; ) on day 90 from baseline. The improvement in these parameters was minimal in the placebo-treated group. Furthermore, a significantly greater improvement and regulation were observed in serum testosterone levels with the Ashwagandha treatment as compared to the placebo (p<0.001).

Conclusion: The present study adds to the evidence on the therapeutic value of Ashwagandha (Withania somnifera), as attributed in Ayurveda for the treatment of oligospermia leading to infertility.

Cardio respiratory Endurance

Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults (3)

Results: There was a greater increase from baseline (P < 0.0001) in the mean VO2 max with KSM-66 Ashwagandha (n = 24) compared to placebo (n = 25) at 8 weeks (4.91 and 1.42, respectively) and at 12 weeks (5.67 and 1.86 respectively). The QOL scores for all subdomains significantly improved to a greater extent in the Ashwagandha group at 12 weeks compared to placebo (P < 0.05).

Conclusion: The findings suggest that Ashwagandha root extract enhances the cardiorespiratory endurance and improves QOL in healthy athletic adults.

Testosterone, Muscle Strength And Recovery

Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial (4)

Results: Compared to the placebo subjects, the group treated with ashwagandha had significantly greater increases in muscle strength on the bench-press exercise (Placebo: 26.4 kg, 95 % CI, 19.5, 33.3 vs. Ashwagandha: 46.0 kg, 95 % CI 36.6, 55.5; p = 0.001) and the leg-extension exercise (Placebo: 9.8 kg, 95 % CI, 7.2,12.3 vs. Ashwagandha: 14.5 kg, 95 % CI, 10.8,18.2; p = 0.04), and significantly greater muscle size increase at the arms (Placebo: 5.3 cm2, 95 % CI, 3.3,7.2 vs. Ashwagandha: 8.6 cm2, 95 % CI, 6.9,10.8; p = 0.01) and chest (Placebo: 1.4 cm, 95 % CI, 0.8, 2.0 vs. Ashwagandha: 3.3 cm, 95 % CI, 2.6, 4.1; p < 0.001). Compared to the placebo subjects, the subjects receiving ashwagandha also had significantly greater reduction of exercise-induced muscle damage as indicated by the stabilization of serum creatine kinase (Placebo: 1307.5 U/L, 95 % CI, 1202.8, 1412.1, vs. Ashwagandha: 1462.6 U/L, 95 % CI, 1366.2, 1559.1; p = 0.03), significantly greater increase in testosterone level (Placebo: 18.0 ng/dL, 95 % CI, -15.8, 51.8 vs. Ashwagandha: 96.2 ng/dL, 95 % CI, 54.7, 137.5; p = 0.004), and a significantly greater decrease in body fat percentage (Placebo: 1.5 %, 95 % CI, 0.4 %, 2.6 % vs. Ashwagandha: 3.5 %, 95 % CI, 2.0 %, 4.9 %; p = 0.03).

Conclusion: This study reports that ashwagandha supplementation is associated with significant increases in muscle mass and strength and suggests that ashwagandha supplementation may be useful in conjunction with a resistance training program.

Female Sexual Function

Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study (5)

Results: The analysis indicates that treatment with HCARE leads to significantly higher improvement, relative to placebo, in the FSFI Total score (p < 0.001), FSFI domain score for “arousal” (p < 0.001), “lubrication” (p < 0.001), “orgasm” (p = 0.004), and “satisfaction” (p < 0.001), and also FSDS score (p < 0.001) and the number of successful sexual encounters (p < 0.001) at the endof the treatment.

Conclusion: This study demonstrated that oral administration of HCARE may improve sexual function in healthy women.

Memory And Cognition

Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions (6)

Results: After eight weeks of study, the ashwagandha treatment group demonstrated significant improvements compared with the placebo group in both immediate and general memory, as evidenced by Wechsler Memory Scale III subtest scores for logical memory I (p = 0.007), verbal paired associates I (p = 0.042), faces I (p = 0.020), family pictures I (p = 0.006), logical memory II (p = 0.006), verbal paired associates II (p = 0.031), faces II (p = 0.014), and family pictures II (p = 0.006). The treatment group also demonstrated significantly greater improvement in executive function, sustained attention, and information-processing speed as indicated by scores on the Eriksen Flanker task (p = 0.002), Wisconsin Card Sort test (p = 0.014), Trail-Making test part A (p = 0.006), and the Mackworth Clock test (p = 0.009).

Conclusion: Ashwagandha may be effective in enhancing both immediate and general memory in people with MCI as well as improving executive function, attention, and information processing speed.

Stress And Weight Management

Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial (7)

Results: KSM-66 Ashwagandha caused significant reduction in Perceived Stress among the subjects. At the end of the study, KSM-66 Ashwagandha produced a 32.74% reduction in PSS scores from the baseline compared to placebo group. KSM-66 Ashwagandha reduced desire or cravings for food in the study subjects. The FCQ scores for Planning, Positive and Negative reinforcement, Lack of control, Emotion and Environment domains were reduced significantly (P < 0.05) in the Ashwagandha supplemented subjects. A statistically significant (P < 0.05) decrease of 22.2% was observed in serum cortisol (a stress hormone) levels as a result of KSM-66 Ashwagandha supplementation compared to placebo group. KSM-66 Ashwagandha supplementation resulted in a 3.0% and 2.9% reduction in bodyweight (P < 0.05) and BMI (P < 0.05) respectively. Supplementation with KSM-66 Ashwagandha resulted in a significant (P < 0.05) increase in OHQ scores and a significant (P < 0.05) reduction in TFEQ scores for ‘Uncontrolled’ and ‘Emotional Eating behavior’ compared to placebo group.

Conclusion: The outcome of this study suggests that Ashwagandha root extract can be used for body weight management in adults under chronic stress.

Quality Sleep

Clinical evaluation of the pharmacological impact of ashwagandha root extract on sleep in healthy volunteers and insomnia patients: A double-blind, randomized, parallel group, placebo-controlled study. (8)

Results: At the end of the 8-week study, Ashwagandha root extract supplemented groups demonstrated a significant improvement in the sleep parameters in both healthy and insomnia subjects. The improvement was found more significant in insomnia subjects compared to healthy subjects. The repeat measure analysis of variance (ANOVA) confirmed the significant improvement in SOL (p = 0.013), HAM-A outcomes (p < 0.05), mental alertness (p = 0.01), and sleep quality (p < 0.05) of the insomnia patients. A two-way ANOVA was used to confirm these outcomes that denote Sleep Onset Latency (p < 0.0001) and Sleep Efficiency (p < 0.0001) as the most improved parameters, followed by Total Sleep Time (p < 0.002) and Wake After Sleep Onset (p < 0.040). After 8-weeks of study, there was a significant decrease in the mean score of mental alertness on rising in both the arms in the Ashwagandha supplemented group compared to the placebo group. All these parameters, SOL, TST, WASO, TIB, SE, including PSQI, HAM-A, Mental Alertness, and Sleep Quality, were also statistically assessed for the significant improvement within the group both for the treatment and the placebo groups in the healthy and the insomnia datasets. The obtained results suggest statistically significant (p < 0.0001) changes between the baseline values and the end of the study results except for the HAM-A and the mental alertness scores of the healthy subject group.

Conclusion: This study confirms that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Ashwagandha root extract was well-tolerated by all the participants irrespective of their health condition and age.

General Health Improvement

Efficacy and Tolerability of Ashwagandha Root Extract in the Elderly for Improvement of General Well-being and Sleep: A Prospective, Randomized, Double-blind, Placebo-controlled Study. (9)

Results: Statistically significant (P<0.0001) improvement was observed in the Ashwagandha treatment group compared to the placebo. The mean (SD) total score of WHOQOL-BREF improved from 140.53 (8.25) at the baseline to 161.84(9.32) at the end of the study. The individual domain scores were also improved. At baseline, the sleep quality and the mental alertness on rising were comparatively low in both the groups. However, upon intervention, a significant increase in the quality of sleep (P<0.0001) and mental alertness (P<0.034) was observed in the Ashwagandha treatment group when compared to the placebo group. Overall improvement was observed for the general wellbeing, sleep quality, and mental alertness in the study population. The experimental group population displayed good tolerability to the test product and it was reported as safe and beneficial by the study participants.

Conclusion: The study outcomes suggest that Ashwagandha root extract efficiently improved the QoL, sleep quality, and mental alertness as self-assessed by older adults. The recommended dose used in this study could be effective for the elderly population.

Thyroid Function

Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. (10)

Results: A total of four subjects (two from each group) withdrew their consent before the second visit. Eight weeks of treatment with ashwagandha improved serum TSH (p < 0.001), T3 (p = 0.0031), and T4 (p = 0.0096) levels significantly compared to placebo. Ashwagandha treatment effectively normalized the serum thyroid indices during the 8-week treatment period in a significant manner (time-effects: TSH [p < 0.001], T3 [p < 0.001], and T4 [p < 0.001]). Four subjects (8%) (ashwagandha: 1[4%]; Placebo: 3[12%]) out of 50 reported few mild and temporary adverse effects during this study.

Conclusion: Treatment with ashwagandha may be beneficial for normalizing thyroid indices in subclinical hypothyroid patients.

References

(1) Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). Indian journal of psychological medicine, 34(3), 255.

(2) Ambiye, V. R., Langade, D., Dongre, S., Aptikar, P., Kulkarni, M., & Dongre, A. (2013). Evidence-Based Complementary and Alternative Medicine, 2013.

(3) Choudhary, B., Shetty, A., & Langade, D. G. (2015). Ayu, 36(1), 63.

(4) Wankhede, S., Langade, D., Joshi, K., Sinha, S. R., & Bhattacharyya, S. (2015). Journal of the International Society of Sports Nutrition, 12(1), 43.

(5) Dongre, S., Langade, D., & Bhattacharyya, S. (2015). BioMed research international, 2015.

(6) Choudhary, D., Bhattacharyya, S., & Bose, S. (2017). Journal of Dietary Supplements, 1-14. Chicago

(7) Choudhary, D., Bhattacharyya, S., & Joshi, K. (2017). Journal of evidence-based complementary & alternative medicine, 22(1), 96-106.

(8) Langade, D., Thakare, V., Kanchi, S., & Kelgane, S. (2020). Journal of Ethnopharmacology: 264:113276.

(9) Kelgane, S. B., Salve, J., Sampara, P., & Debnath, K. (2020)l. Cureus, 12(2), e7083.

(10) Sharma, A. K., Basu, I., & Singh, S. (2017).The Journal of Alternative and Complementary Medicine.

Holy basil, or tulsi, is an aromatic perennial plant native to India used by herbalists to treat stress, anxiety, fatigue, headaches, and inflammation. It has anti-inflammatory and antioxidant properties and immunomodulatory effects—meaning it produces antibodies. Our team loves this ingredient for its calming properties.

Benefits:

Cognition-enhancing and stress-relieving effects

Holy basil (Ocimum sanctum Linn.) leaf extract enhances specific cognitive parameters in healthy adult volunteers: A placebo controlled study (1)

Introduction: Ocimum sanctum (OS), known as Holy basil, has been documented to possess neuroprotective, cognition-enhancing and stress relieving effects in animal models. However there is paucity of clinical studies to document these effects.

Materials and methods: Effect of OS on parameters related to cognition and stress in humans was evaluated with administration of 300 milligram capsules of ethanolic leaf extracts of Ocimum sanctum (EtOS) or placebo per day, over 30 days.

Results: Intra-group comparison of Sternberg and Stroop test showed improvement in both the placebo and EtOS groups, however, the improvement stabilized after day 15 in the placebo group. Intergroup comparison revealed a significant improvement of the following cognitive parameters in the EtOS as compared to the placebo: reaction time (RT) and error rate (ER) of Sternberg test, RT of neutral task of Stroop, RT and ER of interference task of Stroop. The intra-group comparison of P300 latency, salivary cortisol, and State-Trait Anxiety Inventory showed improvement over time in the EtOS group alone, though the inter-group difference was significant in the P300 latency alone. There were no changes in heart rate (HR), AHR, or galvanic skin response (GSR) or AGSR.

Conclusion: Ocimum sanctum leaf extract seems to have potential cognition-enhancing properties in humans.

Up-regulating antioxidant defences

Ocimum sanctum Linn. (Holy Basil) ethanolic leaf extract protects against 7,12-dimethylbenz(a)anthracene-induced genotoxicity, oxidative stress, and imbalance in xenobiotic-metabolizing enzymes (2)

The present study (2) was designed to evaluate the protective effects of ethanolic Ocimum sanctum leaf extract against 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity, oxidative stress, and imbalance in xenobiotic-metabolizing enzymes. Four different concentrations of ethanolic O. sanctum leaf extract (100, 200, 300, and 400 mg/kg of body weight) were administered to Wistar rats by intragastric intubation for five consecutive days followed by intraperitoneal injection of DMBA (35 mg/kg of body weight) 90 minutes after the final dose of the extract. Administration of DMBA increased bone marrow micronuclei, phase I enzymes, lipid peroxidation, and protein carbonyl formation. This was accompanied by a significant decrease in the activities of phase II detoxification enzymes and antioxidants in the liver, erythrocytes, and bone marrow. Pretreatment with ethanolic O. sanctum leaf extract at a concentration of 300 mg/kg of body weight significantly reduced micronuclei formation and phase I enzymes as well as lipid and protein oxidation with enhanced antioxidant and phase II enzyme activities. The results of the present study suggest that ethanolic O. sanctum leaf extract inhibits DMBA-induced genotoxicity and oxidative stress by modulating xenobiotic-metabolising enzymes, reducing the extent of lipid and protein oxidation and up-regulating antioxidant defences.

References

(1) Suneetha Sampath, S C Mahapatra, M M Padhi, Ratna Sharma, Anjana Talwar. Indian J Physiol Pharmacol. Jan-Mar 2015;59(1):69-77.

(2) P. Manikandan 1, R Senthil Murugan, H Abbas, S K Abraham, S Nagini. J Med Food

2007 Sep;10(3):495-502. doi: 10.1089/jmf.2006.125.

This ingredient is sourced from the world's leading specialist in saffron extraction and characterisation, Activ’Inside proposes a range of saffron extracts with the highest concentration in crocins and safranal. We have selected this ingredient as the extracts are exclusively made from the richest part of 100% pure Crocus sativus L. stigmas.

Benefits:

Stress and emotional wellbeing

Orally consumed at 30 mg/day (1), Iranian saffron extracts provide the same effectiveness as well- known drugs, such as fluoxetine, and imipramine. Safr’Inside™ acute and chronic efficacy has been clinically tested. Physical measures and psychological tests highlighted Safr’Inside™ to decrease depressive tendencies, improve social relationship and have a protective effect against stress.

Serotonin amplification

Effects of Saffron Extract Supplementation on Mood, Well-Being, and Response to a Psychosocial Stressor in Healthy Adults: A Randomized, Double-Blind, Parallel Group, Clinical Trial (2).

Anxiety, stress, and low mood are closely related and may contribute to depressive symptoms. Among non-pharmacological solutions to improve subclinical mood symptoms and resilience to stress, natural products such as saffron—identified as promising following preliminary beneficial effects in major depressive disorder—represent a relevant strategy. This study aimed to assess the efficacy of 8 weeks' supplementation with 30 mg standardized saffron extract on emotional well-being in healthy adults with subclinical feelings of low mood and anxiety and/or stress and evaluate the acute effect of saffron in response to a lab-based psychosocial stressor. The study adopted a double-blind, randomized, parallel groups design in which 56 healthy male and female individuals (18–54 years) received either a saffron extract or a placebo for 8 weeks. Chronic effects of saffron on subjective anxiety, stress, and depressive feelings were assessed using a questionnaire battery [including Profile of Mood State-2, (POMS)] and acute effects in response to a lab-based psychosocial stressor were measured through psychological and physiological parameters. Urinary crocetin levels were quantified. Participants who received the saffron extract reported reduced depression scores and improved social relationships at the end of the study. Urinary crocetin levels increased significantly with saffron supplementation and were correlated with change in depression scores. The typical stress-induced decrease in heart rate variability (HRV) during exposure to the stressor was attenuated following acute saffron intake. Saffron extract appears to improve subclinical depressive symptoms in healthy individuals and may contribute to increased resilience against the development of stress-related psychiatric disorders.

References

(1) Activ’Inside clinical research https://activinside.com/health-applications/mood-anti-stress/

(2) Philippa A. Jackson Front. Nutr., 01 February 2021 | https://doi.org/10.3389/fnut.2020.606124

Relora is a world-class patent-pending combination of Magnolia bark extract and Phellodendron bark extract, shown to reduce cortisol exposure and perceived daily stress while improving various mood state parameters, including lower fatigue and higher vigour.

Benefits:

Cortisol, stress, and emotional wellbeing

Magnolia (Magnolia officinalis) and Phellodendron (Phellodendron amurense) barks are medicinal plants commonly used as traditional remedies for reducing stress and anxiety. Modern dietary supplements are intended to induce relaxation and reduce stress as well as stress-related eating. Previous studies have shown the combination of Magnolia/Phellodendron (MP) to reduce both cortisol exposure and the perception of stress/anxiety, while improving weight loss in subjects with stress-related eating. Competitive athletes are “stressed” by their intense exercise regimens in addition to their normal activities of daily living and thus may benefit from a natural therapy intended to modulate baseline perceptions of stress and stress hormone exposure.

The study assessed salivary cortisol exposure and psychological mood state in 56 subjects (35 men and 21 women) screened for moderate stress and supplemented with a standardized/patented MP combination (Relora®, Next Pharmaceuticals) or Placebo for 4 weeks. (1)

After 4 weeks of supplementation, salivary cortisol exposure was significantly (p<0.05) lower (−18%) in the Relora group compared to Placebo. Compared to Placebo, the Relora group had significantly better (p<0.05) mood state parameters, including lower indices of Overall Stress (−11%), Tension (−13%), Depression (−20%), Anger (−42%), Fatigue (−31%), and Confusion (−27%), and higher indices of Global Mood State (+11%) and Vigor (+18%).

References

(1) Shawn M Talbott,Julie A Talbott, and Mike Pugh Effect of Magnolia officinalis and Phellodendron amurense (Relora®) on cortisol and psychological mood state in moderately stressed subjects

J Int Soc Sports Nutr. 2013; 10: 37.

Magnesium works calming wonders by blocking the activity of more stimulating neurotransmitters and binds to calming receptors, resulting in a more peaceful, resting state. It helps to regulate the release of stress hormones like cortisol, acting like a brake on your body's nervous system. Magnesium plays a critical role in brain function and mood and reduces brain fog. Low levels are linked to an increased risk of depression.

Benefits

Neuroprotective Benefit

Observational data suggests that having sufficient levels of circulating Magnesium (Mg) or higher dietary intake of Mg may prevent dementia.

Human research suggests that magnesium may prevent dementia: In one pilot RCT using magnesium L-threonate (MgT), 44 patients with subjective memory complaints and anxiety and sleep disorders were given 25 mg/kg/day of MgT for 12 weeks. The authors reported an improvement in overall cognitive ability in MgT patients vs controls (1). No other clinical trials in humans have tested if raising magnesium levels, either through diet or supplement use, can prevent dementia or cognitive impairment.

Brain health

Several meta-analyses suggest that increased consumption or circulating levels of Mg is associated with a decreased risk of several age-related diseases. There is little evidence to suggest that Mg supplementation can increase lifespan, per se. However, one study using rat cardiac tissue found that acute Mg deficiency can down-regulate telomerase activity, as well as increase oxidative damage to DNA and potentially contribute to the atherogenic disease process (2)

Meta-analyses suggest that circulating levels of Mg or dietary Mg intake may reduce risks for age-related diseases. Two meta-analyses of circulating Mg and magnesium intake reported a reduced risk of cardiovascular disease by 30% and 14%, respectively (3)(4)

Sleep and cortisol

Nearly 50% of older adults have insomnia, with difficulty in getting to sleep, early awakening, or feeling unrefreshed on waking. With ageing, several changes occur that can place one at risk for insomnia, including age-related changes in various circadian rhythms, environmental and lifestyle changes, and decreased nutrients intake, absorption, retention, and utilisation.

One 2012 double-blind RCT in 46 elderly adults with insomnia treated for 8 weeks with 500 mg magnesium sulphate daily reported improved sleep duration, lower cortisol levels and decreased early-morning waking (5)

References

(1) Guosong Liu , Jason G Weinger , Zhong-Lin Lu , Feng Xue , Safa Sadeghpour Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. J Alzheimers Dis. 2016;49(4):971-90.

(2) Nilank C Shah , Gatha J Shah , Zhiqiang Li , Xian-Cheng Jiang , Bella T Altura , Burton M Altura Short-term magnesium deficiency downregulates telomerase, upregulates neutral sphingomyelinase and induces oxidative DNA damage in cardiovascular tissues: relevance to atherogenesis, cardiovascular diseases and aging. Int J Clin Exp Med 2014 Mar 15;7(3):497-514. eCollection 2014.

(3) Liana C Del Gobbo , Fumiaki Imamura, Jason H Y Wu, Marcia C de Oliveira Otto, Stephanie E Chiuve, Dariush Mozaffarian Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr 2013 Jul;98(1):160-73. doi: 10.3945/ajcn.112.053132.

(4) Xin Fang , Chun Liang , Mei Li , Scott Montgomery , Katja Fall , Jan Aaseth , Yang Cao Dose-response relationship between dietary magnesium intake and cardiovascular mortality: A systematic review and dose-based meta-regression analysis of prospective studies. J Trace Elem Med Biol 2016 Dec;38:64-73. doi: 10.1016/j.jtemb.2016.03.014

(5) Behnood Abbasi, Masud Kimiagar, Khosro Sadeghniiat, Minoo M Shirazi, Mehdi Hedayati, Bahram Rashidkhani The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. J Res Med Sci 2012 Dec;17(12):1161-9

Passiflora incarnata (Wild Passion Flower) is a commonly used supplement for anxiety and sleep problems, as well as for pain, heart rhythm problems, menopausal symptoms, and attention-deficit hyperactivity disorder. Passionflower modulates GABA in your brain, which is your primary inhibitory neurotransmitter.

Benefits:

Improved sleep and memory

Recently, there have been reports that chronic insomnia acts as an insult in the brain, causing memory loss through the production of ROS, inflammation, and Alzheimer's disease if persistent. Insomnia remains the leading cause of sleep disturbance and as such has serious implications for public health.

A study to test the possibility that repeated administration of PF could improve the memory by promoting hippocampal neurogenesis at the DBA/2 mice known have inherited sleep disorders, as well as preventive effects of Alzheimer's disease. (1)

This study found that short-term oral administration of PF displayed improved memory according to the water maze test. Quantitative analysis of Tau protein, which is a marker of Alzheimer's disease, was performed in the SD rats and DBA/2 mice by repeated PF oral administration and pTau/Tau values were significantly decreased in PF-treated group than vehicle-treated group. In conclusion, our results suggest that PF lead high hippocampal neurogenesis in the animals even in inherited sleep-disturbed animals. The increased hippocampal neurogenesis functionally enhanced memory and learning functions by repeated PF oral administration. These results identify PF as a potential therapy for enhancing memory functions and prevention of Alzheimer's disease through actions on the hippocampus.

GABA uptake

Passiflora incarnata L. (Passifloraceae) is important in herbal medicine for treating anxiety or nervousness, GAD, symptoms of opiate withdrawal, insomnia, neuralgia, convulsion, spasmodic asthma, ADHD, palpitations, cardiac rhythm abnormalities, hypertension, sexual dysfunction, and menopause. However, the mechanism of action is still under discussion. Despite gaps in our understanding of neurophysiological processes, it is increasingly being recognized that dysfunction of the GABA system is implicated in many neuropsychiatric conditions, including anxiety and depressive disorders. Therefore, we investigated the in vitro effects of a dry extract of Passiflora incarnata (sole active ingredient in Pascoflair ® 425mg) on the GABA system. The extract inhibited [³H]-GABA uptake into rat cortical synaptosomes but had no effect on GABA release and GABA transaminase activity. Passiflora incarnata inhibited concentration dependent the binding of [³H]- SR95531 to GABA A-receptors and of [ 3H]-CGP 54626 to GABA B-receptors. Using the [35S]-GTP γS binding assay Passiflora could be classified as an antagonist of the GABA B receptor. In contrast, the ethanol- and the benzodiazepine-site of the GABA A-receptor were not affected by this extract. In conclusion, we show the first evidence that numerous pharmacological effects of Passiflora incarnata are mediated via modulation of the GABA system including affinity to GABA A and GABA B receptors, and effects on GABA uptake.

The Passiflora incarnata extract investigated in this study (2) inhibited the binding of [ 3H]- CGP 54626 to GABA B-receptors in a concentration dependent manner. This could be verified using the [35S]-GTP γS binding assay. It was found that Passiflora incarnata has a lower IC50 value in the antagonist mode than in the agonist mode. Therefore Passiflora incarnata needs to be classified as an antagonist of the GABA B receptor. This opens possibilities for further investigations because GABA B antagonists may provide a pharmacological therapy for cognitive impairment (Helm et al. 2005).

References

(1) Gwang-Ho Kim , Kyunghyun Lim , Hae Sung Yang , Ji-Kwang Lee , Yehlim Kim , Sang-Kyu Park , So-Hyeon Kim, Suhyeon Park , Tae-Hee Kim , Jong-Seok Moon, In Koo Hwang , Yeo Sung Yoon , Hyung Seok Seo , Sung Min Nam , Mi-Yeon Kim , Seul Gi Yoon , Je Kyung Seong , Sun Shin Yi. Improvement in neurogenesis and memory function by administration of Passiflora incarnata L. extract applied to sleep disorder in rodent models. J Chem Neuroanat. 2019 Jul;98:27-40. doi: 10.1016/j.jchemneu.2019.03.005. Epub 2019 Apr 2.

(2) Kurt Appel, Thorsten Rose, Bernd Fiebich, Thomas Kammler, Christine Hoffmann, et al.. Modulation of the γ-aminobutric acid (GABA) system by Passiflora incarnata L.. Phytotherapy Research, Wiley, 2010, ff10.1002/ptr.3352ff. ffhal-00599846

Vitamin B6, or Pyridoxine, is primarily known to help keep the nervous system and brain at peak performance, allowing it to function at a healthy rate and improving nerve communications throughout the body and brain.

The body does not store Vitamin B6, and releases any excess in urine, so people need to get enough vitamin B6 every day to avoid running low.

Benefits:

Supports neurotransmitter synthesis

B6 it is particularly well known for its important function in the synthesis of neurotransmitters like dopamine from L-dopa, serotonin from 5-HTP, and gamma‐aminobutyric acid (GABA) from glutamate” (1).

The role of vitamin B6 in amino acid metabolism makes it a rate limiting cofactor in the synthesis of neurotransmitters such as dopamine, serotonin, γ-aminobutyric acid (GABA), noradrenaline and the hormone melatonin. The synthesis of these neurotransmitters is differentially sensitive to vitamin B6 levels, with even mild deficiency resulting in preferential down-regulation of GABA and serotonin synthesis (2).

References

(1) Calderón-Ospina CA, Nava‐Mesa MO (2020). B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. Journal of Clinical Otolaryngology

(2) Kennedy D. O. (2016). B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review. Nutrients, 8(2), 68.

Zynamite® is a patented specialized extract from Mango leaves that has in nine human clinical trials, shown to exert superior focus, energy, and brain function. Zynamite® has won numerous global industry awards for research, innovation, and sports. 

Pre-clinical studies demonstrated that Zynamite® crosses the blood-brain barrier, modulates neurotransmitter response and increases long-term memory.

Under cognitive stress conditions, Zynamite® modulates the neurotransmitter response, enhancing attention during cognitive task performance, improving reaction time and reducing cognitive fatigue while keeping the heart-rate and blood pressure without change. It also improves brain oxygenation during physical activity, improving cognitive function and reducing blood lactate levels. Additionally, Zynamite® accelerates recovery after strong physical exercise.

Benefits:

Nootropic activity

Improves cognitive function and decision-making. Speeds up reaction time and improves performance. Decreases fatigue

Sports Performance

Provides energy boosts and supports muscle performance, increases peak and mean power output, increases VO2 max and brain oxygenation and reduces muscular fatigue.

Sports Recovery

Enhances the acceleration of recovery and contributes to pain reduction. Supports the reduction of muscle damage.

References:

Wightman, E., et al. Acute Effects of a Polyphenol-Rich Leaf Extract of Mangifera indica L. (Zynamite®) on Cognitive Function in Healthy Adults: A Double-Blind, Placebo-Controlled Crossover Study. Nutrients (2020).

López-Ríos, L. et al. Central nervous system activities of extract Mangifera indica L. Journal of Ethnopharmacology, 260, 112996 (2020).

Gelabert-Rebato, et al. A Single Dose of The Mango Leaf Extract Zynamite® in Combination with Quercetin Enhances Peak Power Output During Repeated Sprint Exercise in Men and Women. Nutrients, 11 (11), 2592 (2019).

Martin-Rinco, M., et al. Supplementation with a Mango Leaf Extract (Zynamite®) in Combination with Quercetin Attenuates Muscle Damage and Pain and Accelerates Recovery After Strenuous Damaging Exercise. Nutrients (2020).

Gelabert-Rebato, M. et al. Mangifera indica L. Leaf Extract in Combination With Luteolin or Quercetin Enhances VO2 peak and Peak Power Output, and Preserves Skeletal Muscle Function During Ischemia-Reperfusion in Humans. Frontiers in Physiology, 9, 740 (2018).

Gelabert-Rebato, M. et al. Enhancement of Exercise Performance by 48 Hours, and 15-Day Supplementation with Mangiferin and Luteolin in Men. Nutrients, 11, 344 (2019).

Panax ginseng is a plant used in traditional Chinese medicine (also known as Korean or Asian ginseng). Its root contains compounds called ginsenosides, which have antioxidative and anti-inflammatory effects. Panax ginseng is reported in various clinical trials to enhance longevity, promote cognitive functions, and alleviate fatigue. Taking panax ginseng alone is ineffective in improving memory, but taking it with ginkgo leaf extract seems to improve memory in healthy people.

Benefits:

Memory, behaviour and mood

A study (1) examined how single doses of either 200 or 400 mg of Panax ginseng affected mental performance, mental fatigue and blood sugar levels in 30 healthy adults before and after a 10-minute mental test.

The 200-mg dose, as opposed to the 400-mg dose, was more effective at improving mental performance and fatigue during the test

It is possible that ginseng assisted the uptake of blood sugar by cells, which could have enhanced performance and reduced mental fatigue. Yet it is not clear why the lower dose was more effective than the higher one.

Antioxidant and reduce inflammation.

A larger study followed 71 postmenopausal women who took 3 grams of red ginseng or a placebo daily for 12 weeks. Antioxidant activity and oxidative stress markers were then measured.

Researchers concluded that red ginseng may help reduce oxidative stress by increasing antioxidant enzyme activities.

Energy levels

One four-week study explored the effects of giving 1 or 2 grams of Panax ginseng or a placebo to 90 people with chronic fatigue.

Those given Panax ginseng experienced less physical and mental fatigue, as well as reductions in oxidative stress, than those taking the placebo (3)

Furthermore, a review of over 155 studies suggested that ginseng supplements may not only help reduce fatigue but also enhance physical activity.

Executive functions

A double-blind randomized controlled trial of 52 healthy individuals reported that Panax ginseng treatment (1 g/day) for eight weeks significantly increased the volume of a brain region important for memory and improved scores on executive function, attention, and memory, effects that were not seen in the placebo group (5)

References

(1) Jonathon L Reay , David O Kennedy, Andrew B Scholey. Single doses of Panax ginseng (G115) reduce blood glucose levels and improve cognitive performance during sustained mental activity. J Psychopharmacol. 2005 Jul;19(4):357-65. doi: 10.1177/0269881105053286.

(2) Seok Kyo Seo , Yeon Hong , Bo Hyon Yun , Seung Joo Chon , Yeon Soo Jung , Joo Hyun Park , SiHyun Cho , Young Sik Choi 1, Byung Seok Lee. Antioxidative effects of Korean red ginseng in postmenopausal women: a double-blind randomized controlled trial. J Ethnopharmacol. 2014 Jul 3;154(3):753-7. doi: 10.1016/j.jep.2014.04.051. Epub 2014 May 9.

(3) Hyeong-Geug Kim 1, Jung-Hyo Cho, Sa-Ra Yoo, Jin-Seok Lee, Jong-Min Han, Nam-Hun Lee, Yo-Chan Ahn, Chang-Gue Son. Antifatigue effects of Panax ginseng C.A. Meyer: a randomised, double-blind, placebo-controlled trial. PLoS One 2013 Apr 17;8(4):e61271. doi: 10.1371/journal.pone.0061271. Print 2013.

(4) Hoang Viet Bach, Jeongseon Kim, Seung Kwon Myung, Young Ae Cho Efficacy of Ginseng Supplements on Fatigue and Physical Performance: a Meta-analysis. J Korean Med Sci. 2016 Dec;31(12):1879-1886. doi: 10.3346/jkms.2016.31.12.1879.

(5) LaSala GS, McKeever RG, Patel U et al. (2015) Effect of single-dose Ginkgo biloba and Panax ginseng on driving performance. Clin Toxicol (Phila) 53, 108-112.

Ginkgo (Ginkgo biloba) is one of the oldest living tree species. Ginkgo biloba is an antioxidant-rich herb and has been a part of traditional Chinese medicine for centuries. It is used to enhance brain health and treat a variety of conditions, including circulatory problems and respiratory conditions. It may also increase blood flow and play a role in how neurotransmitters in the brain operate.

Benefits:

Working memory

Ginkgo Biloba extract (GBE) is increasingly used to alleviate symptoms of age related cognitive impairment, with preclinical evidence pointing to a pro-cholinergic effect. While a number of behavioral studies have reported improvements to working memory (WM) associated with GBE, electrophysiological studies of GBE have typically been limited to recordings during a resting state. The current study investigated the chronic effects of GBE on steady state visually evoked potential (SSVEP) topography in nineteen healthy middle-aged (50-61 year old) male participants whilst completing an object WM task. A randomized double-blind crossover design was employed in which participants were allocated to receive 14 days GBE and 14 days placebo in random order.

GBE was found to improve behavioural performance on the WM task. GBE was also found to increase the SSVEP amplitude at occipital and frontal sites and increase SSVEP latency at left temporal and left frontal sites during the hold component of the WM task. These SSVEP changes associated with GBE may represent more efficient processing during WM task completion. (1)

Neuroprotective agent

G. biloba derivatives have a proven beneficial effect on cognitive disorders in the course of dementia, including mild and moderate AD. Unfortunately, there are not many randomized trials proving the clinical effectiveness in AD. Despite its recognized position in the treatment of neurodegenerative diseases, there is still controversy over the exact mechanism of its action, as well as its clinical effectiveness and application. It seems reasonable to assume that the effect of G. biloba derivatives will be individual and will depend on the duration of the treatment as well as the applied dose. (2)

References

(1) R. B. Silberstein, A. Pipingas, J. Song, D. A. Camfield, P. J. Nathan, and C. Stough. Examining Brain-Cognition Effects of Ginkgo Biloba Extract: Brain Activation in the Left Temporal and Left Prefrontal Cortex in an Object Working Memory Task. Evid Based Complement Alternat Med v.2011; 2011 PMC3166615

(2) Anna Nowak, Klaudyna Kojder, Joanna Zielonka-Brzezicka, Jacek Wróbel, Mateusz Bosiacki, Marta Fabiańska, Mariola Wróbel, Joanna Sołek-Pastuszka and Adam Klimowicz. The Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer’s Disease. Front. Pharmacol., 04 November 2021

Rhodiola Rosea, also known as Golden Root, is a plant from Siberia that grows well in dry and cold arctic climates.

The medicinal compounds of Rhodiola Rosea come from the root of the plant and are considered adaptogens, meaning they help your body adapt to stress when consumed. This root contains more than 140 active ingredients, the two most potent of which are Rosavin and Salidroside. People in Russia and Scandinavian countries have used Rhodiola for centuries to treat anxiety, fatigue and depression and today Rhodiola has also been shown to improve symptoms of burnout and fatigue, which can occur with chronic stress.

Benefits:

Enhance adaptation to stress and reduce mild anxiety

One study investigated the effects of Rhodiola extract in 101 people with life- and work-related stress. It found significant improvements in symptoms of stress, such as fatigue, exhaustion and anxiety, after just three days. These improvements continued throughout the study (1).

Fatigue, cognitive performance and endurance

A Rhodiola study tested its effects on mental fatigue in 56 physicians working night shift. The physicians were randomly assigned to receive either 170 mg of Rhodiola or a placebo pill per day for two weeks. Rhodiola reduced mental fatigue and improved performance on work-related tasks by 20%, compared to the placebo (2).

Rhodiola helps improve exercise endurance and capacity. One study demonstrates that those given 200 mg of Rhodiola before a cycling test were able to exercise for an average of 24 seconds longer than those given a placebo (3).

Supports dopamine

Pharmacological research suggests that Rhodolia may facilitate the production and proliferation of dopamine-producing cells (4).

References

(1) Edwards D, Heufelder A, Zimmermann A (2012). Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 in subjects with life-stress symptoms--results of an open-label study. Phytother Res. 2012 Aug;26(8):1220-5. doi: 10.1002/ptr.3712. Epub 2012 Jan 6. PMID: 22228617.

(2) Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner (2000). Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000 Oct;7(5):365-71. Doi: 10.1016/S0944-7113(00)80055-0. PMID: 11081987.

(3) De Bock K, Eijnde BO, Ramaekers M, Hespel P. Acute (2004). Rhodiola rosea intake can improve endurance exercise performance. Int J Sport Nutr Exerc Metab. 2004 Jun;14(3):298-307. doi: 10.1123/ijsnem.14.3.298. PMID: 15256690.

(4) Zhuang, W., Yue, L., Dang, X., Chen, F., Gong, Y., Lin, X., & Luo, Y. (2019). Rosenroot (Rhodiola): Potential Applications in Aging-related Diseases. Aging and disease, 10(1), 134–146.

People often use magnesium glycinate instead of other magnesium supplements, as the body finds it easier to absorb magnesium in this form

Magnesium promotes calm focus blocking the activity of more stimulating neurotransmitters and binds to calming receptors, resulting in a more peaceful, resting state. It helps to regulate the release of stress hormones like cortisol, acting like the brake on your body's nervous system.Magnesium plays a critical role in brain function and mood, and reduces brain fog. Low levels are linked to an increased risk of depression.

Benefits:

Neuroprotective Benefit

Observational data suggests that having sufficient levels of circulating Magnesium (Mg) or a higher dietary intake of Mg may prevent dementia.

Human research suggests magnesium may prevent dementia: In one pilot RCT using magnesium L-threonate (MgT), 44 patients with subjective memory complaints and anxiety and sleep disorders were given 25 mg/kg/day of MgT for 12 weeks. The authors reported an improvement in overall cognitive ability in MgT patients vs controls (1). No other clinical trials in humans have tested if raising magnesium levels, either through diet or supplement use, can prevent dementia or cognitive impairment.

Brain health and endurance

Several meta-analyses suggest that increased consumption or circulating levels of Mg is associated with a decreased risk of several age-related diseases.

There is little evidence to suggest that Mg supplementation can increase lifespan, per se. However, one study using rat cardiac tissue found that acute Mg deficiency can down-regulate telomerase activity, as well as increase oxidative damage to DNA and potentially contribute to the atherogenic disease process (20.

Meta-analyses suggest that circulating levels of Mg or dietary Mg intake may reduce risks for age-related diseases. Two meta-analyses of circulating Mg and magnesium intake reported a reduced risk of cardiovascular disease by 30% and 14%, respectively (3)(4)

Sleep and cortisol

Nearly 50% of older adults have insomnia, with difficulty in getting to sleep, early awakening, or feeling unrefreshed on waking. With ageing, several changes occur that can place one at risk for insomnia, including age-related changes in various circadian rhythms, environmental and lifestyle changes, and decreased nutrients intake, absorption, retention, and utilisation.

One 2012 double-blind RCT in 46 elderly adults with insomnia treated for 8 weeks with 500 mg magnesium sulphate daily reported improved sleep duration, lower cortisol levels and decreased early-morning waking (5)

References

(1) Guosong Liu , Jason G Weinger , Zhong-Lin Lu , Feng Xue , Safa Sadeghpour Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. J Alzheimers Dis. 2016;49(4):971-90.

(2) Nilank C Shah , Gatha J Shah , Zhiqiang Li , Xian-Cheng Jiang , Bella T Altura , Burton M Altura Short-term magnesium deficiency downregulates telomerase, upregulates neutral sphingomyelinase and induces oxidative DNA damage in cardiovascular tissues: relevance to atherogenesis, cardiovascular diseases and aging. Int J Clin Exp Med 2014 Mar 15;7(3):497-514. eCollection 2014.

(3) Liana C Del Gobbo , Fumiaki Imamura, Jason H Y Wu, Marcia C de Oliveira Otto, Stephanie E Chiuve, Dariush Mozaffarian Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr 2013 Jul;98(1):160-73. doi: 10.3945/ajcn.112.053132.

(4) Xin Fang , Chun Liang , Mei Li , Scott Montgomery , Katja Fall , Jan Aaseth , Yang Cao Dose-response relationship between dietary magnesium intake and cardiovascular mortality: A systematic review and dose-based meta-regression analysis of prospective studies. J Trace Elem Med Biol 2016 Dec;38:64-73. doi: 10.1016/j.jtemb.2016.03.014

(5) Behnood Abbasi, Masud Kimiagar, Khosro Sadeghniiat, Minoo M Shirazi, Mehdi Hedayati, Bahram Rashidkhani The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. J Res Med Sci 2012 Dec;17(12):1161-9

Ubiquinol is an antioxidant found naturally in the body that is responsible for supporting energy production in your cells. When Ubiquinol levels are depleted, it can contribute to feelings of sluggishness and tiredness.

CoQ10 energises the cells throughout the body, enhancing cognitive endurance and overall performance.

Benefits:

Enhance recovery and endurance, enhance adaptation to stress

As you age, your levels of Ubiquinol decrease. Lower Ubiquinol levels mean that your body’s natural energy levels can drop, which can make it harder and harder to bounce back from your workouts.

A 2013 study (1) showed Ubiquinol can also boost the power production of trained athletes. Athletes who received Ubiquinol increased their power per kilogram of body weight by over 2.5 percent in just six weeks, showing significantly enhanced physical performance compared to athletes who received a placebo.

A 2016 study (2) demonstrated that supplementing with Ubiquinol may lower the degree of inflammation after exertion and intense physical exercise, which may help with muscle recovery and cognitive endurance.

Reduce mental fatigue

Ubiquinol is the “spark plug” that helps fire energy production in your cells.

When your energy production is low, it affects your natural energy levels. This could contribute to feelings of sluggishness and tiredness.

As we age, or when we are under prolonged stress due to lifestyle, diet or environmental factors, our natural CoQ10 and Ubiquinol levels become depleted and the ability to produce Ubiquinol declines. (3,4) In addition to this, the free radical activity and oxidative stress that occurs in our body from normal metabolism, even in healthy individuals, increases as we get older.(5)

One of the main roles of antioxidants in the body is to help combat free radical activity and oxidative stress. As such, antioxidants like Ubiquinol may help to minimise the impairment of normal functioning cells and restore essential levels of Ubiquinol back into your system. (6)

Heart health

The Australian Heart Foundation reports that 33 percent of Australians have high total cholesterol8 (levels higher than 5.5 mmol/L) – quite a significant number.

Cholesterol is an essential type of fat that is carried in the blood. All cells in the body need cholesterol for internal and external membranes, however, too much cholesterol in the blood can lead to health issues.(7)

Many factors can affect cholesterol including heredity, age, and gender. But many are preventable as well as controllable. For example, diet, weight, and exercise are factors that you can control and can also be used to prevent cholesterol from becoming a health issue.

Small studies (8,9) have shown that because Ubiquinol is a powerful antioxidant, it may help to prevent the oxidation of small dense LDL cholesterol particles (10) and support healthy cholesterol levels.

One of the studies(11) showed that two weeks’ supplementation with 150mg Ubiquinol per day in healthy men reduced LDL cholesterol levels by 12 percent.

Male Fertility

Ubiquinol is one of the most potent antioxidants our body produces and helps protect cells, from the oxidative damage caused by free radicals and ROS (Reactive Oxygen Species).

Ubiquinol is important in maintaining the health, motility and production of sperm

Supplementation of Ubiquinol has been shown to improve sperm density and motility and improving male fertility.

Sperm cell mitochondria have high concentrations of Ubiquinol, playing an integral role for energy production, the production of ATP.

Healthy sperm count and motility have been co-related with healthy ubiquinol levels.

Ubiquinol supports energy to power sperm: supporting motility and the ability of the sperm to reach the egg for fertilisation.

Ubiquinol is a powerful antioxidant helping to protect sperm cells from oxidative damage: Ubiquinol is the form of CoQ10 capable of neutralising ROS attack on the mitochondria and therefore helps protect this important cellular structure from damage. (12)

Multiple studies on the effects of Ubiquinol on sperm health parameters have shown a positive influence on sperm concentration, morphology, and motility.

Female fertility

The importance of oxidative stress in various conditions linked to female infertility, including pituitary disorders, PCOS and endometriosis, suggesting the possible clinical usefulness of Ubiquinol.(13)

Coenzyme Q10 or Ubiquinol is an essential part of the cell energy-producing system of mitochondria. However, it is also a powerful lipophilic antioxidant, which may help reduce autooxidation of lipoproteins and cell membranes.

CoQ10 supplementation may support ovarian reserve by helping to reduce mitochondrial ovarian ageing and physiological programmed ovarian ageing.

Ubiquinol protects ovarian reserve: Ubiquinol may counteract mitochondrial ovarian ageing.

Ubiquinol is a powerful antioxidant protecting oocytes from oxidative stress: Ubiquinol is a powerful lipophilic antioxidant.

References

(1) Alf D, Schmidt ME, Siebrecht SC. Ubiquinol supplementation enhances peak power production in trained athletes: a double-blind, placebo controlled study. Journal of the International Society of Sports Nutrition. 2013;10:24.

(2) Sarmiento, A., Diaz-Castro, J., Pulido-Moran, M., Moreno-Fernandez, J., Kajarabille, N., Chirosa, I., Guisado, I. M., Javier Chirosa, L., Guisado, R. and Ochoa, J. J. (2016), Short-term ubiquinol supplementation reduces oxidative stress associated with strenuous exercise in healthy adults: A randomized trial. BioFactors, 42: 612–622.

(3) Zhang, Y.; Liu, J.; Chen, X.-q.; Oliver Chen, C. Y., Ubiquinol is superior to ubiquinone to enhance Coenzyme Q10 status in older men. Food & Function 2018, 9 (11), 5653-5659.

(4) Linnane, A. W., Zhang, C., Yarovaya, N., Kopsidas, G., Kovalenko, S., Papakostopoulos, P., … & Richardson, M. Human aging and global function of coenzyme Q10. Annals of the New York Academy of Sciences, (2002). 959(1), 396-411.

(5) Garrido-Maraver J, Cordero MD, Oropesa-Ávila M, et al. Coenzyme Q10 Therapy. Molecular Syndromology. 2014;5(3-4):187-197.

(6) Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy Reviews. 2010;4(8):118-126.

(7) National Heart Foundation of Australia. 2012. High cholesterol statistics. [ONLINE] Available at: https://www.heartfoundation.org.au/about-us/what-we-do/heart-disease-in-australia/high-cholesterol-statistics. [Accessed 15 July 2017].

(8) Black, P.H et al., 2002. Stress, inflammation and cardiovascular disease. Journal of Psychosomatic Research, [Online]. Volume 52, Issue 1, 1-23. Available at: https://www.ncbi.nlm.nih.gov/pubmed/11801260 [Accessed 14 July 2017].

(9) Schmelzer, C., Niklowitz, P., Okun, J. G., Haas, D., Menke, T. and Döring, F. (2011), Ubiquinol-induced gene expression signatures are translated into altered parameters of erythropoiesis and reduced low density lipoprotein cholesterol levels in humans. IUBMB Life, 63: 42–48.

(10) Thomas, S.R., 1996. Cosupplementation With Coenzyme Q Prevents the Prooxidant Effect of α-Tocopherol and Increases the Resistance of LDL to Transition Metal–Dependent Oxidation Initiation. Arteriosclerosis, Thrombosis, and Vascular Biology, [Online]. Volume 16, Issue 5, 687-696. Available at: http://atvb.ahajournals.org/content/16/5/687.long [Accessed 15 July 2017].

(11) St-Pierre, A.C. et al., 2005. Low-Density Lipoprotein Subfractions and the Long-Term Risk of Ischemic Heart Disease in Men: 13-Year Follow-Up Data From the Que´bec Cardiovascular Study. Arteriosclerosis, Thrombosis, and Vascular Biology, [Online]. Volume 25, Issue 3, 553-559. Available at: http://atvb.ahajournals.org/content/25/3/553.long [Accessed 15 July 2017].

(12) Thakur, A., Littaru, G., Funahashi, I., Painkara, U., Dange, N. and Chauhan, P., 2015. Effect of Ubiquinol on Serum Reproductive Hormones of Amenorrhic Patients. Indian Journal of Clinical Biochemistry, 31(3), pp.342-348.

(13) Al-Qadhi, H. I., Kadhim, E. J., & Ali, R. H. (2017). Coenzyme Q10 effects on body weight, serum testosterone level and oxidative stress.

Alpha-lipoic acid is a mitochondrial compound crucial for digestion, absorption, and the creation of energy. It helps enzymes turn nutrients into energy and power the body and brain. It is also a well-researched antioxidant that may reduce inflammation and skin aging, promote healthy nerve function, lower heart disease risk factors, and slow the progression of memory loss disorders.

Benefits:

Neuroprotective and energy

The aging process comprises a series of organic alterations, affecting multiple systems, including the nervous system. Aging has been considered the main risk factor for the advance of neurodegenerative diseases, many of which are accompanied by cognitive impairment. Aged individuals show cognitive decline, which has been associated with oxidative stress, as well as mitochondrial, and consequently energetic failure.

Accordingly, LA (Lipoic Acid) displays antioxidant, antiapoptotic, and anti-inflammatory properties in both in vivo and in vitro studies. In addition, it has been shown that LA reverses age-associated loss of neurotransmitters and their receptors, which can underlie its effects on cognitive functions.

Compelling evidence indicates that LA displays memory-ameliorating properties in a variety of experimental models of neurodegenerative diseases, as well as in memory decline. Studies aiming to assess the neuroprotective effects of LA on behavioural outcomes showed that LA can reduce memory deficits in different behavioural paradigms on AD (Quinn et al., 2007; Farr et al., 2012), HD (Mehrotra et al., 2015), (3) oxidative stress (Stoll et al., 1993, 1994; Liu et al., 2002a; Farr et al., 2003; Manda et al., 2007), and age-associated cognitive dysfunction (Cui et al., 2006; Mahboob et al., 2016) models. In humans, two studies in AD patients have supported the positive cognitive effects of LA (Hager et al., 2001, 2007). (1) (2)

References

(1) Hager K., Kenklies M., McAfoose J., Engel J., Munch G. (2007). Alpha-lipoic acid as a new treatment option for Alzheimer's disease–a 48 months follow-up analysis. J. Neural Transm. Suppl. 72, 189–193.

(2) Hager K., Marahrens A., Kenklies M., Riederer P., Munch G. (2001). Alpha-lipoic acid as a new treatment option for Alzheimer type dementia. Arch. Gerontol. Geriatr. 32, 275–282. 10.1016/S0167-4943(01)00104-2

(3) Mehrotra A., Kanwal A., Banerjee S. K., Sandhir R. (2015). Mitochondrial modulators in experimental Huntington's disease: reversal of mitochondrial dysfunctions and cognitive deficits. Neurobiol. Aging 36, 2186–2200. 10.1016/j.neurobiolaging.2015.02.004

Commonly known as Vitamin B1, is known for improving concentration and memory. Because of its positive effect on attitude and brain function, it is also known as a "morale vitamin". Thiamine is the B vitamin that helps your body to use carbohydrates for energy.

Benefits:

Neuroprotective

Reductions in brain glucose metabolism and increased oxidative stress invariably occur in Alzheimer's disease (AD) and thiamine (vitamin B1) deficiency. Both conditions cause irreversible cognitive impairment; their behavioural consequences overlap but are not identical. Thiamine-dependent processes are critical in glucose metabolism, and recent studies implicate thiamine in oxidative stress, protein processing, peroxisomal function, and gene expression.

Adding thiamine or more absorbable forms of thiamine to tested treatments for the abnormality in glucose metabolism in AD may increase their efficacy. (1)

References

(1) Gary E Gibson , John P Blass Thiamine-dependent processes and treatment strategies in neurodegeneration Antioxid Redox Signal 2007 Oct;9(10):1605-19. doi: 10.1089/ars.2007.1766.