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Exciting New Ingredients for Improving Cognition

Pyrroloquinoline Quinone (PQQ)

PQQ is a relatively large molecule that was first discovered in bacteria, by scientists in 1979. The significance of this molecule wasn’t fully realized until a few years later when researchers found that the PQQ molecule could take part in redox reactions. These reactions are vital to the body for energy generation. Energy is the key, since it is required in carrying out virtually all the functions in a cell including: growth, repair, reproduction, synthesis, breakdown, waste removal and others. If energy isn’t produced rapidly and efficiently then cells die.

How PQQ Functions in the Body

PQQ research was taken up by the Japanese; the mechanism of action was painstakingly worked out and attributed to these redox reactions. Redox reactions are a two way street where both oxidation (gain of oxygen or loss of electrons) and reduction (loss of oxygen or gain of electrons) occur simultaneously. In other words, while one molecule is being oxidized, the second is being reduced. Redox reactions allow cells to do two things at once, while saving considerable amounts of energy rather than performing these reactions separately. Redox reactions are an essential part of cells’ existence, and tens of thousands of these reactions occur at any one time. In this regard, PQQ is detected in various tissues and in bodily fluids such as saliva and tears and breast milk.PQQ acts as a catalyst by speeding up reactions, thus saving cells even more energy. Some researchers have classified this as a co-enzyme and a vital ingredient for cell survival, and thus have pushed for PQQ to be classified as a B vitamin; the jury is still out on the latter request. Nonetheless, researchers and clinicians have come to realize and appreciate the importance of PQQ in various diseases but especially in cognitive health.

PQQ’s Role in Cognitive Health

Researchers realized early on that people who consumed quantities of foods rich in PQQ such as tofu, celery, bell peppers and various fermented foods, had better brain function than people consuming lower quantities. This led scientists to look at the effect of PQQ on memory, learning, and other related cognitive functions. At first they looked at PQQ’s mode of action in animals and then in humans.

The Research on PQQAnimal

studies have shown that PQQ protects nerve cells from damage caused by various toxins, it prevents oxidation of nerve tissue by quenching free radicals that otherwise cause much destruction, it increases the production of nerve growth factor which protects nerve cells and was shown to improve the memory tasks that the animals performed. In addition, it was discovered that PQQ’s effectiveness was enhanced when used in combination with another important molecule called Coenzyme Q10.Recently, two human studies have looked at the PQQ+CoQ10 combination and the effects on memory. The first study of 12 week’s duration and which was a double-blind placebo controlled randomised study in healthy patients, looked at three different supplement groups: (i) 22 patients received 20mg of PQQ, (ii) 24 patients received 20mg of PQQ plus 300mg CoQ10 and, (iii) 23 patients received a placebo. Patients performed various verbal and identification memory tests for the study. Both the PQQ and PQQ+CoQ10 groups performed much better than the placebo group in terms of improved memory scores. However, the PQQ+CoQ10 group was even better than the PQQ group on its own; thus indicating the synergy between the two molecules.A second study published in 2012 showed that when 20mg of PQQ alone was administered for 8 weeks, it significantly improved sleep quality and duration, reduced anxiety and fatigue, and improved overall quality of life.PQQ+CoQ10 presents a novel and a safe approach to maintaining healthy brain function in terms of memory and learning.

Vivimind

In the pharmaceutical world, all drugs have to go through extensive testing and studies from preclinical (test tube and animal), phase I (usually to determine pharmacokinetic profile, absorption, distribution of the drug in various tissues, and its excretion), Phase II (which determines the safety and establishes the dose required), and finally phase III which is the last, most expensive part, and involves hundreds to thousands of patients to determine a clinical end point (such as a reduction in pain or inflammation or an improvement of memory or any other positive/negative outcome). It is rare to find a natural health product that has a completed phase III study. The costs are just too high. At best, most natural health products stop at phase I and the odd one proceeds to a phase II study. Vivimind is one of the very few natural health products that has successfully completed all the phases that are normally required for a drug approval, and has thus generated unprecedented safety and efficacy data unlike any other natural health product Researchers at Queen’s University in Kingston, Ontario discovered a unique molecule that was found in certain seaweeds and which had remarkable properties in improving memory, learning, and slowed the normal aging process of the brain. The molecule was identified as homotaurine, a close relative of the amino acid taurine, but with unique and distinctive properties that taurine does not possess. A Canadian drug discovery company decided to test this molecule and conduct all the studies required, from pre-clinical all the way to phase III studies. The company spent over two hundred million dollars and took fifteen years to conduct testing in over two thousand patients across sixty-seven centres in Canada, US and Europe to complete sixteen studies in total (see Table 1). Unfortunately, homotaurine just missed the relevant statistical significance value in conclusively demonstrating the efficacy using the standard psychometric tests. Health Canada required additional studies to be conducted before any Alzheimer’s disease claim would be granted. The company decided to abandon the drug application as this would cost a lot more money and time.Subsequent analysis of the data however, showed a clear statistically significant evidence of effectiveness in several cognitive functions including: memory preservation, maintenance of verbal skills and execution of various tasks, all of which are severely affected in Alzheimer’s disease (see Figure 1). In addition, homotaurine demonstrated a highly significant effect in a high-risk group of Alzheimer’s disease patients, those carrying the ApoE4 gene (see Figure 2). Approximately, a quarter of the AD population carry this aggressive gene.

The company decided to market homotaurine as a natural health product under the trade name “Vivimind”, for maintaining optimal cognitive health. Health Canada allowed the following claim for Vivimind, “May help support the specific area of the brain known as the hippocampus.”The hippocampus is the part of the brain that is responsible for learning and memory. As we age, this area of the brain starts to shrink due to a loss of brain tissue and nerve cells. This is a normal part of ageing, but in Alzheimer’s disease this process is greatly accelerated. Magnetic Resonance Imaging (MRI) of the brain shows that Vivimind greatly reduces the loss of brain tissues by an incredible 68% (see Figure 3) as compared with placebo group. What is the mechanism of action of Vivimind? Studies have shown that Vivimind acts via two distinct pathways:•It reduces and helps clear the glue-like deposits of the highly toxic beta-amyloid peptide that forms plaques in the brain.•It inhibits the formation of the amyloid tendrils which can literally “choke” the nerve cells (see Figure 4)Not only does Vivimind reduce the formation of these toxic plaques and fibril-like projections, but Vivimind may also help clear any such deposits from the brain.One of the key requirements of any product that can help improve cognition and/or prevent accelerated ageing of the brain, is for that molecule to be able to get into the brain by by-passing the super fastidious gatekeeper known as the blood brain barrier. Vivimind actually gets into the brain easily and thus is able to perform its function.Finally, Vivimind does not interfere with important liver detoxification enzymes such as Cytochrome P450, or even interact with blood thinning drugs like warfarin, unlike supplements such as Ginkgo biloba and vitamin E. Vivimind has extensive data showing both safety and effectiveness in improving various cognitive parameters (see Table 2).

References

1. Aisen PS, Gauthier S, Ferris S et al “Tramiprosate in mild-to-moderate Alzheimer’s disease- a randomised, double blind, placebo-controlled, multi-centre study” Arch Med Sci. 2011; 1: 102-111

2. Caltagirone C, Ferrannini L, Marchionni N et al “The potential protective effect of Tramiprosate (homotaurine) against Alzheimer disease: a review” Aging Clin. Exp. Res. Sept 5 2012

3. Greenberg S M, Rosand J, Schneider AT et al “A phase 2 study of tramiprosate for cerebral amyloid angiopathy” Alzheimer Dis. Assoc. Discord. 2006; 20: 269-274

4. Koikeda T, NereNo M, and Masuda K et al “Pyrroloquinoline quinone disodium salt improves higher brain function.” Med Consult New Remedies, 2011; 48: 519-527

5. Nakano M, Yamamoto T, Okamura H et al “Effect of pyrroloquinoline quinone(PQQ) on mental status of middle-aged and elderly persons.” FOOD style, 2008; 21 13: 50-53 (Japanese)

6. Nakano M, Takeda H, Yamazaki M et-al “Effects of oral supplementation with pyrroloquinoline quinone on stress, fatigue, and sleep.” Functional foods in health and disease, 2012; 2: 307-324

7. Ohwada K, Takeda H, Yamazaki M et al “Pyrroloquinoline quinone(PQQ) prevents cognitive deficit caused by oxidative stress in rats.” J Clin Biochem Nutri, 2008; 42: 29-34.

8. Saumier D, Duong A, Haine D et al “Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer’s disease: ADSS-cog subscale results from the Alphase study” J Nutr Health Aging, 2009; 13: 808-812

9. Zhang Y, Feustel PJ, Kimelberg HK et al “Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat.” Brain Res, 2009; 1094: 200-206.

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