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6, 2016
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THE VITAL ROLE OF METHYLATION AMPK, THE METABOLIC SIGNALLER THE VERSATILITY OF NAD+ PROTEINS, SUGARS, OXYGEN & AGE SPECIAL OFFERS INSIDE
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TOMORROW’S TREATMENTS TODAY™ IAS is dedicated to helping you access the world’s latest commercially available supplements to give you and your family real choices in health and wellness. IAS promises you: Quality: We stock the best quality products because the right materials and formulas give you the best possible results. Brands: We carry original brands - i.e. the same ones used by top health professionals. Choice: We have the largest range of medicines, hormones and supplements. If you are looking for things that use words like bioidentical, efficacy and synergy then you’ve come to the right place. Pricing: Our prices are competitive and we regularly have special offers to help you save money on the things that are important to you and your family.
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Declaration: The IAS Aging Matters™ magazine is intended for IAS private club members (and therefore is not intended for the public). It focuses on the latest international nutritional, hormonal and drug therapies to help combat the signs of aging. These signs include the physical, mental and internal changes consisting of the diseases and disorders such as caåncer, arthritis and senile dementias etc. However, the main focus is upon the prevention of such aging diseases and disorders for the ‘healthy-aging’ individual. Copyright 2016: All copyrights are acknowledged. Whilst every effort has been made to ensure accuracy, no responsibility can be accepted for illustrations, photographs, artwork or advertising materials while in transmission or with the publisher or their agents. Disclaimer: All educational information is offered under IAS terms and conditions. This information does not replace the advice of your physician and restrictions may apply in some countries. The opinions expressed by the writers may not be those of IAS or the magazine. All prices shown are in US Dollars and are for reference purposes only and they do not include taxes (where applicable), nor do they include shipping & handling fees. Prices, conditions and terms are subject to change without notice.
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WELCOME This issue we look into some of the major ‘aging pathways.’ These biochemical developments take place within the body can lead to deleterious effects. But all is not lost, since these pathways can be blocked or supported, (whichever is necessary) to improve the outcomes. We’re delighted that Dr. Marios Kyriazis has written all of these articles. We’ve worked alongside him for many years, within the British Longevity Society and at his Cyprus based foundation for indefinite lifespans. He is a respected bio-gerontologist as well as a Medical Doctor, which means he undertakes research as well as sees patients. Recently, the Cyprus authorities, supported by the President of Cyprus, have decided to nominate Dr. Marios Kyriazis for the 2017 Nobel Prize in Medicine. Dr. Kyriazis has described how the interaction of humans with modern technology is changing our biology and could result in the elimination of aging, expanding on Darwin’s theory of evolution by natural selection; it provides a totally new framework for studying the aging process. We wish him the best of luck and we hope that you enjoy reading Dr. Kyriazis latest submissions right here and now.
PHIL MICANS, MS, PHARMB
Editor, Aging Matters™ Magazine
WARD DEAN, M.D. Medical Director
CONTENTS WELCOME
Thanks for finding the time...................................................................................3
FOREFRONT
Interesting items in the news................................................................................4
THE VITAL ROLE OF METHYLATION
How nutrition creates hormones..........................................................................6
AMPK, THE METABOLIC SIGNALLER
A significant biochemical pathway.....................................................................12
THE VERSATILITY OF NAD+
A molecule that’s in the news.............................................................................18
PROTEINS, SUGARS, OXYGEN AND AGE
What reduces this multi-aging process?............................................................25
A-Z PRODUCT LISTING AND PRICES
Find everything in-stock here...........................................................Centre Pages
FEATURED PRODUCTS
Best sellers and new items.................................................................................30
CROSS-REFERENCE LISTS
Find what you need here....................................................................................41
TESTIMONIALS & EXPLANATIONS
Nice comments from nice people......................................................................50
CONTACT DETAILS
Get in touch with IAS today................................................................................51
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FOREFRONT
SLOWING DOWN CHRONOLOGICAL CELL AGING WITH PLANT EXTRACTS
A
recent study conducted at Concordia University and Idunn Technologies, has educated scientists on how to slow the chronological age of yeast in lab experiments. Using six plant extracts, they were able to decelerate the aging process in samples of yeast more so than in any other experiment conducted before. The researchers discovered compounds that inhibit the yeast’s pro-aging pathways and proteins.
Although no human trials have commenced yet, the same plant extracts used in the yeast experiments are readily available on the market in supplement form.
Yeast cells were used in the experiment, because their aging rate is similar to that of human cells. Monitored the rate of chronological aging in the yeast at a cellular level, scientists were measuring pro-aging and anti-aging processes. Each plant extract gave different readings, but the extract from the White Willow tree (Salix alba) was the most potent at slowing the aging process down in the cultured yeast.
This lead the authors of the study to hypothesize that inhibiting the pathways of post-mitotic cells in humans could delay and slow the growth of many chronic diseases. Some of the diseases noted include heart disease, diabetes, arthritis, Alzheimer’s, Parkinson’s, stroke, and cancer.
The most surprising observation was that human post-mitotic cells are also affected by similar nutrient sensing pathways, suggesting that manipulation of these beneficial plant compounds may lead to decelerating old age and diseases in humans.
The six extracts used to slow aging in yeast, are commercially available and approved for human consumption by Health Canada. Five of the extracts have been approved for use in health supplements. The six extracts were obtained from the following plant groups: • Cimicifuga • Valeriana
• Passiflora incarnata • Ginkgo biloba
• Apium graveolens L. • Salix alba
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A senior author of the study stated that, the yeast have nutrient-sensing pathways that accelerate their aging under normal growth conditions. The chemical compounds in the plant extracts obstruct these pathway signals and are responsible for the measured delay in aging of the yeast.
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FOREFRONT
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TELOMERE LENGTHENING IN HUMANS
I
n recent times the discovery that the telomerase enzyme can lengthen telomeres has caused a great buzz in the antiaging and medical fraternity, causing both controversy and excitement, as the initial animal studies carried out have been showing that shorter telomeres not only appear to equate to a shorter life, but also poorer health too and vice-versa, that longer telomeres could equate to a longer and healthier life. Regular customers of IAS will be familiar with the TA65® capsules available on www.antiaging-systems. com, that are a patented, all natural,
plant-based compound which can help maintain or rebuild the telomeres that diminish as people get older. The exciting news is that the First Randomized, Double-Blind, PlaceboControlled Study to Show Telomere Lengthening in Humans has been conducted by T.A. Sciences using TA65 products on 97 men and women (53-87 years old) and shows statistically significant lengthening of telomeres in humans. The study called “Telomere Lengthening in Humans“ is available to read in full on the IAS website.
DO MENOPAUSE AND INSOMNIA CAUSE AGING?
M
enopause occurs on average at the age of 51, and is when the ovaries stop producing estrogen and progesterone. Although it affects each woman differently, the symptoms of menopause may include: hot flashes, trouble sleeping, changes in mood, and vaginal and bladder problems. It may seem that aging is a natural process that triggers menopause but some researchers are wondering if, in fact, it is the other way around and menopause causes aging. New research involving 3,100 women
indicates that the latter is true and that the younger a woman is when she starts her menopause, the faster she will age. It also appears that insomnia, common in menopause, may speed up cellular aging for post-menopausal women by as much as 6%. Symptoms of insomnia include restlessness, problems falling asleep, disrupted sleep, trouble getting back to sleep, and waking early. Being unable to sleep well not only affects how you function the next day; it may also influence the rate at which your “body clock” ticks.
To test this theory, researchers monitored methylation (a chemical biomarker of cellular aging), in the DNA samples of 2,078 women. Using samples of blood, saliva and cells from the inside of the cheek, the team was able to measure the biological age of the women and compare it with their chronological age. Results showed that women with insomnia were almost two years older (biologically) than women without insomnia, even though their chronological age was the same.
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of methylation A
s we interact with our environment, there are definite changes in our epigenetic profile. This means that information from our surroundings (such as interactions with society and culture, use of internet, communication with people, reading etc.) is reflected on how our genes are ultimately expressed. Monozygotic (identical) twins who have been exposed to different environments have different epigenetic characteristics (1). Information from the environment has an impact on DNA methylation, and it changes the expression of factors such as 5-methylcytosine
(the methylated version of cytosine, which is involved in the regulation of gene transcription). An altered DNA methylation profile translates into health consequences (good or bad), depending on several other factors. We know that methylation (and 5-methylcytosine function) decreases with age (2). Although this process is variable, and some individuals may display a lesser degree of deterioration compared to others, it has been suggested by many researchers that maintaining DNA methylation is crucial to health. For example, age-related decrease in methylation can cause adult somatic cells to revert back to a stem-cell
like status, which then predisposes to cancer (because the now young stem cells grow uncontrollably). But the issue of methylation is quite complicated because reduced methylation can have health benefits, too. In any case, certain nutrients or compounds may modulate (increase or decrease) DNA methylation. One such example are the methyl donor molecules (compounds that carry and incorporate methyl groups onto the DNA molecule) betaine, methionine and choline. On the other hand, selenium, polyphenols and bioflavonoids (e.g. epigallocatechin-
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Aminopropylation
Methylation CH3
SAMe
deca-SAMe Spermidine Putrescine Spermidine Spermine MTA
SAH PPi
DNA, proteins phospholipids, neurotransmitters
Transsulfuration Cystathionine
ATP
Hcy
Cysteine
B-12
Methionine
THF
MTHF
Sulfate (SO4) GSH
Figure 1. Relationship between methionine, SAMe, ATP (adenosine tri-phos-
some practitioners advise adding ATP supplements to a methylation
phate), and methylation. Other processes are also involved, and the entire
regimen (3). After all, SAMe is a molecule composed of adenosine (which is
reaction can proceed or slow down depending on the different factors. This
derived from ATP) and methionine.
shows that SAMe depends on ATP in order to function effectively, therefore
3-gallate, genistein, quercetin and fisetin) reduce methylation. A reduced methylation is not necessarily a bad thing, as it is the balance of methylation that counts. By following a well-adjusted mix of both promoting and decreasing factors, the body is allowed to make its own choices according to local needs, for optimum results. It is not a matter of just indiscriminately using promethylation compounds, expecting to inevitably experience health benefits. Biology is not as simple as that. The mechanisms rely on several mutuallybalancing effects. There is significant cross-talk between cell metabolism and the epigenome, which balances
homoeostasis for normal cell function. This depends on the ratio of hyper- vs hypo- methylation compounds, such as methionine and serine, as well as idebenone and SAMe (S-adenosylmethionine, or SAM) which then affect ATP synthesis and function (3), (Figure 1).
S-ADENOSYL-METHIONINE Researches claimed that supplementation with SAMe and polyunsaturated fatty acids (PUFA) may be useful in reducing the impact of mild dementia (4). The researchers focused on dietary supplementation as applied both in pre-dementia
syndromes and Alzheimer’s disease. They found that SAMe plays a critical role as a neuroprotective nutritional supplement, and that it works much better if it is used in association with other compounds, particularly PUFA. SAMe can also improve the mechanisms leading to the reprogramming of stem cells (5). This is achieved by enhancing the methylation and by fine-tuning the processes involved in stem cell function. By the way, SAMe is also used against depression and can be as effective as prescription antidepressants (6). SAMe is involved in several biochemical reactions
“SAMe plays a critical role as a neuroprotective nutritional supplement...” 8
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“SAMe is also used against depression and can be as effective as prescription antidepressants...” (such as those which methylate folate), donating methyl groups in order to methylate neurotransmitters (Figure 2). It was shown that a low concentration of SAMe in the cerebrospinal fluid is also associated with reduced levels of neurotransmitters, and is one of the biochemical reasons leading to clinical depression (7).
Idebenone is involved in both hyperand hypo- methylation of genes, which results in regulated apoptosis and antioxidant protection. This, once again, shows that a health benefit related to methylation may be achieved not only through high or through low methylation, but through a balanced action (9).
IDEBENONE
Idebenone is also an antioxidant which can modulate apoptosis (increases cell death in cancer, and decreases cell death in aging). It inhibits lipid peroxidation and can be used in the treatment or prevention of atherosclerosis (10).
In another study, idebenone (a synthetic equivalent of co-enzyme Q10), in association with resveratrol, improved DNA methylation and mitochondrial function in a model of Parkinson’s disease; the relevance of this finding is that it is best to use a suitable combination of compounds in order to address any given health problem. Many research projects repeatedly highlight the importance of using combinations, rather than single agents (8).
CONCLUSIONS Health benefits result from both upand down-regulation of methylation. So where does this leave us with regards to offering clinical advice on methylation supplements? Should we
Figure 2. Human methyltransferase (the enzyme that catalyzes the transfer of methyl groups), in complex with SAMe. This image hints at the 3-D complexity of the molecules involved. In reality, the enzyme is much more complicated, functioning in 4 dimensions (over time) and, like all other enzymes, it is more accurately described as a ‘cloud-like’ ensemble structure.
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“SAMe plays a critical role as a neuroprotective nutritional supplement...” O H3CO
OH
Figure 3. Chemical structure of Idebenone, ready to
H3CO
donate 2 methyl groups (CH3)
O aim for a low dose, a high dose, or a compromise between the two? A few facts may seem relevant: The commonly-recommended methylationenhancer compounds (such as SAMe, idebenone, methionine, etc.) appear to be a valid suggestion, but this does not mean that by taking a very high dose we should also expect a corresponding very beneficial result.
A moderate dose in association with other supplements and a balanced diet, is a more reasonable option. If we provide our body with the raw materials, then nature will do the rest. But it is also important to maintain a good and active interest in our surroundings (which includes integration of technology, social interactions, and increased cognitive lifestyle). The information
we are exposed to then results in suitable modifications of the DNA via methylation, leading to adaptations in our metabolism, making us healthier and better able to cope with the rigours of aging. Got an opinion on this article? Share your views with us: feedback@antiaging-systems.com
REFERENCES 1. Fraga et al. 2005. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9 2. Heyn et al. Distinct DNA methylomes of newborns and centenarians.Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10522-7 3. Maddocks OD, Labuschagne CF, Adams PD, Vousden KH. Serine Metabolism Supports the Methionine Cycle and DNA/RNA Methylation through De Novo ATP Synthesis in Cancer Cells. Mol Cell. 2016 Jan 21; 61(2):210-21 4. Panza F, Frisardi V, Capurso C, et al. Polyunsaturated fatty acid and S-adenosylmethionine supplementation in predementia syndromes and Alzheimer’s disease: a review. Scientific World Journal. 2009 May 22;9: 373-89 5. Fernández-Arroyo S, Cuyàs E, et al. Activation of the methylation cycle in cells reprogrammed into a stem cell-like state. Oncoscience. 2016 Jan 5;2(12):958-67 6. Sarris J, et al. S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of response. J Affect Disord. 2014 Aug; 164:76-81 7. Miller AL.The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008 Sep;13(3):216-26 8. Gerhardt E, et al. Idebenone and resveratrol extend lifespan and improve motor function of HtrA2 knockout mice. PLoS One. 2011;6(12):e28855 9. Quesada MP, et al. Novel aberrant genetic and epigenetic events in Friedreich’s ataxia. Exp Cell Res. 2015 Jul 1; 335(1):51-61 10. Lin P, et al. Idebenone protects against oxidized low density lipoprotein induced mitochondrial dysfunction in vascular endothelial cells via GSK3β/β-catenin signalling pathways. Biochem Biophys Res Commun. 2015 Sep 25;465(3):548-55
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AMPK: the metabolic signaller by Marios Kyriazis, M.D.
C
ellular homoeostasis is a crucial prerequisite for health and good function. Although the study of all the mechanisms involved in maintaining homoeostasis is extremely complicated and confusing, it is nevertheless possible to examine certain processes which play an important role in the orchestration of events designed to maintain efficient cell function. One such process is the role of AMPK (5’ adenosine monophosphate-activated protein kinase), an enzyme which is present both in lower (yeast) and higher (human) organisms. This plays a part in energy homoeostasis that is thought to be an ‘energy sensor’ which detects any changes in energy compounds such as adenosine monophosphate (AMP), adenosine diphosphate (ADP) and adenosine triphosphate (ATP) (1) – see figure 1.
of AMP increases), this leads to AMPK activation which re-balances the energy needed for the process. Activation of the AMPK molecule happens through a complex process which depends on several other factors.
What happens is that energy needed for muscle contraction (for example), is provided by ATP, a high-energy molecule, which releases energy and may be hydrolysed to AMP, a lower-energy molecule. When the ratio between AMP - ATP changes (for example, when the concentration
This is a complicated process that depends on other factors, so the function of AMPK is best described as a ‘modulation’. One way AMPK
AMPK stimulates the oxidation of fatty acids in the liver, regulates the uptake of glucose by the cell, inhibits the lysis of fat cells (adipocytes) and stimulates energy production in muscle and in other tissues. AMPK plays an active role in weight control. For example, when the function of AMPK is blocked in laboratory animals, it results in the animals having a reduced appetite and so they lose weight. But when AMPK activity is enhanced, the animals eat more and their weight is increased.
is implicated in weight control is via its influence on compounds such as leptin and adiponectin. These regulate appetite, improve utilization of glucose in both muscle and brain, and control fatty acid metabolism (2). There are several compounds and drugs that affect the function of AMPK. Below is a short list of some examples.
A. METFORMIN Metformin, a well-known antidiabetic agent, has gained increasing popularity as a possible anti-aging drug. It is an AMPK activator and regulates energy metabolism in the entire organism. It regulates neuronal apoptosis through both AMPKdependent and AMPK-independent processes (4). Metformin decreases energy levels in cells and acts as a stimulus for AMPK activation. Following this, there is a decrease in insulin growth factor 1 (IGF-1). In this
“Metformin, a well-known antidiabetic agent, has gained increasing popularity as a possible anti-aging drug.”
ADP ATP AMP
Figure 1: When energy is required, ATP is hydrolysed into ADP and then AMP, releasing energy. Increasing levels of AMP stimulates AMPK, but increasing levels of ATP blocks it.
BLOCK AMPK
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HYPOTHALAMUS FOOD INTAKE
SKELETAL MUSCLE
HEART
FA OXIDATION GLUCOSE UPTAKE EXPRESSION OF GLUT4 MITOCHONDRIA
GLUCOSE UPTAKE GLYCOLYSIS FA OXIDATION
AMPK
ADIPOSE TISSUE
PANCREAS
FA SYNTHESIS LIPOLYSIS
INSULIN SECRETION
LIVER FA SYNTHESIS CHOLESTEROL SYNTHESIS GLUCONEOGENESIS
RESPONSE
Figure 2: The action of AMPK on different organs.
STRESS EFFECT WITHOUT ‘AN’
EFFECT WITH ‘AN’
TIME Figure 3: The function of adaptogens: these reduce both the duration and
An image of gynostemma pentaphyllum, its
the magnitude of the stress response over time. Note, their effects are
name ‘pentaphyllum’ means ‘five leaves’, which makes
significantly improved when combined with Nicotinamide Riboside (NR).
the plant easily identifiable.
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way, metformin acts as a potential anticancer agent. This action also depends on another signalling pathway, that of mTOR (see issue 3, 2015 of the Aging Matters™ magazine).
AMPK (5). Quercetin’s anti-cancer effect may also be related to its ability to activate the AMPK and Mammalian Target of Rapamycin (mTOR) signaling pathways (6), like metformin.
B. BERBERINE
D. GYNOSTEMMA PENTAPHYLLUM
This is an alkaloid, a typical AMPK activator molecule, which is also used as an anti-bacterial and antiinflammatory compound. Berberine is an extract from various plants, and is well known in traditional Chinese medicine for its anti-inflammation effects. Berberine has been found to up-regulate AMPK and regulate the function of both mitochondria and neurons (3).
C. QUERCETIN Quercetin is a well-researched polyphenol with a variety of health benefits. It has been shown to improve cancer risk in the prostate, breast and liver. Research shows one of its mechanisms to be an inhibitor of bladder cancer via activation of
This is an herbal remedy used in traditional medicine as a regulator of glucose and lipid metabolism. It facilitates activation of AMPK and improves metabolic dysfunction. Gynostemma contains two specific ingredients called damulin A and damulin B, which are strong activators of AMPK (7). These two compounds also improve the uptake of glucose by the cells. This research sheds light on how AMPK is being activated. Another study showed an anti-obesity benefit of gynostemma, which is thought to be due to AMPK activation and lipid regulation (8). The process of activation is mediated by another ingredient of gynostemma called
actiponin. Gynostemma has a variety of effects on metabolism due to its different chemical components, which work to regulate AMPK signalling. A combination of Gynostemma with Rosehip extracts may provide an additive effect regarding AMPK activation. Rosehips contain the compound tiliroside which improves the action of AMPK, but employs different metabolic pathways compared to gynostemma. In other words, both compounds have the same end result but use different ways to achieve it. This allows for a certain robustness of the signalling pathways which may provide the same result even if some of the intermediate steps are blocked or inhibited (9). Rosehip also regulate lipid metabolism and protect against weight gain and build-up of visceral fat (which is a known risk factor for several chronic conditions) (10), an action which has been confirmed in several experiments (11).
b AMPK AND NEUROGENESIS New neurons are normally formed throughout our life, particularly in the hippocampus area. Aging slows down the formation of these new neurons. This is thought to be, at least in part, due to an abnormal AMPK response. The authors of the study emphasized that it is beneficial to not only increase the levels of AMPK, but the
sensitivity of the neurons to AMPK as well. Receptor sensitivity to most hormones and cell signallers decreases with age. This study provided a useful model which confirmed that increasing the dose of a certain beneficial compound does not necessarily increase its therapeutic benefit, if the receptor sensitivity is impaired (13).
“Quercetin is a well-researched polyphenol with a variety of health benefits. It has been shown to improve cancer risk in the prostate, breast and liver.” WWW.ANTIAGING-SYSTEMS.COM • ORDER HOTLINE: 1-866-800-4677 • E-MAIL: IAS@ANTIAGING-SYSTEMS.COM
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BRAIN BENEFITS Finally, AMPK plays a role in regulating energy supply in the brain, in association with other agents such as HIF (hypoxia-inducible factor), nitric oxide and other kinases, orchestrating an efficient use of glucose by the neurons, assisting in synaptic transmission and in information processing (12). AMPK is particularly useful in situations where there is high energy demand but low energy storage
capabilities, such as in the retina. Factors such as gynostemma extracts act as adaptogens--i.e. they regulate the stress response in the brain and protect against oxidation (see figure 3). This is important because during high neuronal activity there is increased production of reactive oxygen species which may cause mitochondrial damage in the brain. Combinations of AMPK boosters may be able to
both cause improved energy and protect against the consequences of this energy (i.e. oxidation, see box 1). Rosehip extracts act like adaptogens too, and reduce anxiety and cognitive dysfunction. It appears that this combination (gynostemma plus rosehips) may provide an overall beneficial effect to the neurons.
“AMPK is particularly useful in situations where there is high energy demand but low energy storage capabilities, such as in the retina.”
REFERENCES 1. Ronnett GV, Ramamurthy S, Kleman AM, Landree LE, Aja S. AMPK in the Brain: Its Roles in Energy Balance and Neuroprotection. Journal of Neurochemistry. 2009;109(Suppl 1):17-23 2. Greco SJ et al. Leptin boosts cellular metabolism by activating AMPK and the sirtuins to reduce tau phosphorylation and β-amyloid in neurons. Biochem Biophys Res Commun. 2011 Oct 14;414(1):170-4 3. Lu J et al. Berberine regulates neurite outgrowth through AMPK-dependent pathways by lowering energy status. Exp Cell Res. 2015 Jun 10;334(2):194-206 4. Lu M et al. Metformin Prevents Dopaminergic Neuron Death in MPTP/P-Induced Mouse Model of Parkinson’s Disease via Autophagy and Mitochondrial ROS Clearance. Int J Neuropsychopharmacol. 2016 May 23. pii: pyw047. doi: 10.1093/ijnp/pyw047. [Epub ahead of print] 5. Su Q, et al. Quercetin induces bladder cancer cells apoptosis by activation of AMPK signaling pathway. Am J Cancer Res. 2016 Jan 15;6(2):498-508 6. Rivera Rivera A, Castillo-Pichardo L, Gerena Y, Dharmawardhane S. Anti-Breast Cancer Potential of Quercetin via the Akt/AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Cascade. PLoS One. 2016 Jun 10;11(6):e015725 7. Nguyen PH et al. New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum. Bioorg Med Chem. 2011 Nov 1;19(21):6254-60 8. Park SH, et al. Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): a randomized, double-blind, placebo-controlled trial. Obesity (Silver Spring). 2014 Jan;22(1):63-71 9. Shi L, et al. Tiliroside-derivatives enhance GLUT4 translocation via AMPK in muscle cells. Diabetes Res Clin Pract. 2011 May;92(2):e41-6 10. Nagatomo A, et al. Rosehip Extract Inhibits Lipid Accumulation in White Adipose Tissue by Suppressing the Expression of Peroxisome Proliferator-activated Receptor Gamma. Prev Nutr Food Sci. 2013 Jun;18(2):85-91 11. Ninomiya K, Matsuda H, Kubo M, Morikawa T, Nishida N, Yoshikawa M. Potent anti-obese principle from Rosa canina: structural requirements and mode of action of transtiliroside. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3059-64 12. Bolaños JP. Bioenergetics and redox adaptations of astrocytes to neuronal activity. J Neurochem. 2016 Mar 10. doi: 10.1111/jnc.13486. [Epub ahead of print] 13. Jang S, et al. Blunted response of hippocampal AMPK associated with reduced neurogenesis in older versus younger mice. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jun 22;71:57-65. doi: 10.1016/j.pnpbp.2016.06.011. [Epub ahead of print]
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The versatility of NAD+ by Marios Kyriazis, M.D.
R
eactive oxygen species (ROS) have been implicated in the pathogenesis of many agerelated diseases such as diabetes, inflammation, neurodegeneration and cancer. If there is a way to control excessive production of ROS, then it is likely that the impact of such diseases will lessen. One compound which may be relevant in this respect is NAD (Nicotinamide Adenine Dinucleotide). It has a key role in many signaling pathways in humans, and its homoeostasis is essential in preventing irreversible, age-related damage to our tissues (1).
NADH is a reduced form of NAD, and it is the ratio of these two (and the ratio of absolute and oxidized forms of NAD) that has clinical and biochemical relevance. A change in the regulation of the formation and degradation of NAD may underpin a defective ability to deal with ROS and thus contribute to several age-related degenerative conditions (2). This regulation of NAD metabolism, and also the regulation of NAD-replacement therapy used against aging, depends on the activity of several other enzymes, such as one called CD38. This is mentioned here to highlight the complexity of using a certain oral supplement, the function of which may depend on ratios, other enzymes and distant, seemingly unrelated biochemical events (3). Nevertheless, the use of NAD as a supplement is becoming very popular and there are studies which support its clinical use. There is a need for a continual supply of NAD. Its synthesis is based on the supply of precursors such as nicotinamide, nicotinic acid and nicotinamide riboside (NR) (see figure 1). We now know that replacement of the oxidized form of NAD
through the precursor NR improves mitochondrial function, supports stem-cell production, and enhances lifespan in mice (4). It is also important to highlight that different cell types may be able to supply different precursors and mutually facilitate each other’s supply of NAD. This is a process called ‘degeneration’ which aims to provide an efficient end-function based on different biochemical starting points (5). It is worth dwelling for a while on the function of Nicotinamide Riboside (NR). Nicotinamide Riboside is crucial in the metabolism of NAD and it mediates, or causes many of the benefits attributed to NAD itself. NR is a metabolic regulator, a form of vitamin B3 found in milk and beer. Through its anti-inflammatory effect, it can regulate glucose control, insulin and adiponectin (a compound that regulates glucose and lipid function, and thus weight control), repair the cells in the liver of diabetic or obese individuals, reduces inflammatory markers such as TNFa (tumor necrosis factor) and Interleukins (6). Therefore, the function of NR with regards to weight loss and lipid regulation is becoming increasingly recognized. For instance, research shows that NR supplements in laboratory animals activate SIRT1 and SIRT3 genes and improve protection against oxidation originating from a high fat diet (7). Therefore, based on the SIRT1 activation action, both NR and NAD can be considered as a calorie restriction mimetic (8), i.e. an agent that has similar biological benefits as calorie restriction itself. The researchers concluded: “Consequently, our results indicate that the natural vitamin
Nicotinamide Riboside could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function”. NR has been beneficially used in animal models of type-II diabetes and neuropathy (9). Pre-diabetic and diabetic mice treated with NR showed an improved glucose tolerance, and a reduced rate of weight gain. These animals also experienced protection from diabetic neuropathy and exhibited improved liver health. The authors said: “The data justify testing of Nicotinamide Riboside in human models of obesity, Type 2 Diabetes and associated neuropathies”. Alterations in the levels of NAD (and in certain other molecules such as acetyl-CoA), may also result in abnormal histone acetylation patterns, which means that the control of gene expression becomes defective. It is not just the immediate effect of NAD on oxidation that is relevant. It is clear that there are other effects which involve epigenetic regulation and gene expression (10), which add to the overall benefit of the NAD molecule.
“We now know that replacement of the oxidized form of NAD through the precursor NR improves mitochondrial function, supports stem-cell production, and enhances lifespan in mice.”
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Left & Below: Nicotinamide Riboside (NR) is found naturally in milk and beer.
disease in Western countries is nonalcoholic fatty liver disease (NAFLD), related both to obesity and in aging processes. Research with human fatty liver cells and mice models, shows that NAFLD is associated with
“...the function of NR with regards to weight loss and lipid regulation is becoming increasingly recognized.”
of 300mg/kg/day (14). This is equivalent to around 2 grams of Nicotinamide Riboside a day for an average human. Considering that available forms of NR are 260 mg a day, this shows that there is a good safety profile.
“...both NR and NAD can be considered as a calorie restriction mimetic...”
For example, we know that NAD and its associated metabolites play a vital role in maintaining the genome. Abnormal, fast-proliferating cells such as cancer cells need NAD for their function, so there are several metabolic pathways that regulate any excessive demands for NAD. Although the details of this are complicated, there is a lot of research aiming to clarify the different steps involved. The research is concentrating mainly on sirtuins and other protectors of genomic stability such as PARP (poly-ADP-ribose polymerase). The most common chronic liver
low levels of NAD. Supplementation with either nicotinamide riboside (the precursor of NAD mentioned above) or NAD itself can prevent the disease and reverse any damage (11, 12). This shows the overall benefit of both NR and NAD in improving oxidation damage. NAD metabolism is also relevant in kidney disease. Research in mice with damaged kidneys shows that NAD improves lipid metabolism and overall function through a complicated biochemical pathway. It can, for example, enhance breakdown of fatty cells by increasing production of certain stress resistance factors such as PGC1α (13). Finally, some comments about the safety of the treatment. Nicotinamide Riboside was shown not to cause any toxicity of the liver, kidneys, ovaries and testes in mice tested with a dose
CONCLUSION There has been a lot of media hype about the benefits of NAD, with stories suggesting that it will ‘reverse aging’, or presenting it as the ‘elixir of youth’. In this article I presented a short overview of some of its effects, as found in published research and highlighted a general aspect of its benefits (namely, the regulation of oxidation). It is obvious that NAD and its related compounds will not ‘reverse aging’ in the clinical, everyday sense. It is not the pill of immortality. However, used in association with other appropriate strategies, it can prove beneficial in lowering the risk of some age-related degenerative conditions. Some people believe that because NAD has been effective at prolonging the lifespan of mice and worms in
“Consequently, our results indicate that the natural vitamin Nicotinamide Riboside could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.”
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“The data justify testing of Nicotinamide Riboside in human models of obesity, Type 2 Diabetes and associated neuropathies.”
the laboratory, it may also prolong human lifespan. Although this has yet to be proven, it is not only the prolongation of life we are aiming for. Our immediate goal is to diminish the impact of degeneration, and it seems that NAD is a promising compound in this respect.
REFERENCES 1. Magni G, et al. Enzymology of mammalian NAD metabolism in health and disease. Front Biosci. 2008 May 1;13:6135-54 2. Schultz MB, Sinclair DA. Why NAD(+) Declines during Aging: It’s Destroyed. Cell Metab. 2016 Jun 14;23(6):965-6 3. Camacho-Pereira J, et al. CD38 Dictates Age-
Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 2016 Jun 14;23(6):1127-39
12. Zhou CC, et al. Hepatic NAD+ deficiency as a therapeutic target for NAFLD in aging. Br J Pharmacol. 2016 May 12. doi: 10.1111/bph.13513. [Epub ahead of print]
4. Zhang H et al. NAD+ repletion improves mitochondrial and neural stem cell function and enhances life span in mice. Science. 2016 Apr 28. pii: aaf2693. [Epub ahead of print]
13. Tran MT, et al. PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection. Nature. 2016 Mar 24;531(7595):528-32. doi: 10.1038/ nature17184
5. Kyriazis M. Degeneracy. https://scienceblog. com/77250/we-are-all-degenerates-and-it-is-good/
14. Conze DB, Crespo-Barreto J, Kruger CL. Safety assessment of nicotinamide riboside, a form of vitamin B3. Hum Exp Toxicol. 2016 Jan 20. pii: 0960327115626254. [Epub ahead of print]).
6. Lee HJ, et al. Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes. J Med Food. 2015 Nov;18(11):1207-13 7. Cantó C, et al. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47
“Our immediate goal is to diminish the impact of degeneration, and it seems that NAD is a promising compound in this respect.”
8. Handschin C. Caloric restriction and exercise “mimetics’’: Ready for prime time? Pharmacol Res. 2016 Jan;103:158-66. doi: 10.1016/j. phrs.2015.11.009 9. Trammell SA, et al. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice. Sci Rep. 2016 May 27;6:26933 10. Peleg S, Feller C, Ladurner AG, Imhof A. The Metabolic Impact on Histone Acetylation and Transcription in Ageing. Trends Biochem Sci. 2016 Jun 6. pii: S0968-0004(16)30040-8 11. Gariani K, et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology. 2016 Apr;63(4):1190-204
O
NH2 N
N N
N
O O
P O-
O
O O
P
NH2 O
O-
O
+ N Figure 2: The chemical structure of NAD+
HO
OH
HO
OH
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Proteins, sugars, oxygen and AGE by Marios Kyriazis, M.D.
E
ven people who have no training in chemistry or biology, but who are interested in the aging process, have heard of the Maillard reaction. This is a chemical reaction between proteins (specifically, amino acids) and sugar molecules, a process called glycation. The reaction was described for the first time in 1912, and it takes its name from the French chemist Louis-Camille Maillard. Over the years, this reaction has been studied in detail. Among other things, it plays a crucial role during the process of aging.
The end-products of this reaction are called AGEs (Advanced Glycation End-products). AGEs react with other molecules in the body to bring about damage to our tissues. AGEs can be of either high or low molecular weight, and interact with receptors on the surface of cells (appropriately called RAGEs-- i.e. Receptors for AGEs) causing a variety of damage. Examples of AGE-associated involvement in age-related complications include diabetes, stiffening of the arteries (with increased risk of high blood pressure
b Some anti-glycators (other than alagebrium and aminoguanidine) are: • Carnosine • Thiazolidinedione’s such as Pioglitazone (Actos), Rosiglitazone (Avandia), and Lobeglitazone (Duvie) – there are certain restrictions or warnings relating to these • Pyridoxamine • Benfotiamine (a fat-soluble form of thiamine [Vitamin B1]) • Angiotensin converting enzyme inhibitors (ACE inhibitors) (Enalapril, Captopril, Lisinopril and Perindopril are the commonest in clinical use) and angiotensin receptor blockers (ARBs). • Metformin • Not yet available for clinical use: o ALT-946 o OPB-9195 o Tenilsetam o Others less well-studied such as LR-90, TM2002, sRAGE and PEDF (1) • Natural anti-glycating compounds include polyphenols, anthocyanins and other flavonoids
and possible stroke), cataracts, and skin damage. AGEs can originate externally (from cooked food, for example), or internally, through free radical reactions, ionizing radiation, and other age-related processes. Only low molecular weight AGEs are absorbed from the gut. Glycation reactions may also happen between sugar molecules and DNA; not just between sugar and amino acids. This shows that the potential for glycation damage is considerable. Therefore, research into finding ways to lessen the impact of glycation has a high priority.
“AGE-associated involvement in agerelated complications include diabetes, stiffening of the arteries (with increased risk of high blood pressure and possible stroke), cataracts, and skin damage.”
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“AGE-associated involvement in age-related complications include diabetes, stiffening of the arteries (with increased risk of high blood pressure and possible stroke), cataracts, and skin damage.” Several agents capable of reversing or retarding the process of glycation include alagebrium (ALT 711) and aminoguanidine. I discussed many other anti-glycators in a previous Aging Matters™ edition (see box 1).
ALAGEBRIUM (ALT 711) ALT 711--also known as thiazolium chloride—is one of the best-known crosslink breakers in existence, although its development has been hampered by financial and other issues. Alagebrium diminishes the effect of AGEs and has positive effects in diabetes, arterial stiffening, and age-related myocardial disease (2). One significant effect of alagebrium is that it lessens the impact of atherosclerosis in diabetes. Diabetes is associated with increased production of AGEs and risk of atherosclerosis. Alagebrium or pyridoxamine (another anti-glycator) inhibited the accumulation of AGEs and slowed down the progression of atherosclerosis in mice. (3) Other benefits of Alagebrium include improved memory function and delayed neuronal degeneration in diabetic animals, suggesting that
alagebrium has a potential neuroprotective effect (4). Methylglyoxal is a by-product of the glycation reaction. Methylglyoxal induces AGE formation, and results in increased inflammation and cell death through apoptosis. Many studies have concentrated on ways to reduce methylglyoxal, with variable success, such as by supplementation with carnosine. Alagebrium, in particular, when applied to rat heart muscles, reduced methylglyoxal and subsequently also reduced excessive inflammation and cell death (5). Alagebrium may be acting as both a preventative as well as a curative agent. From the above list (as per box 2), we know that Alagebrium is effective against pentosidine (6), carboxy-methyl-lysine (CML) (7) and methylglyoxal, (5) but not against glucosepane. This is unfortunate, because glucosepane is the most abundant glycation product in humans.
THE ISSUE WITH GLUCOSEPANE Glucosepane is a complex protein
resulting from the glycation process (see figure 1). Although present in all organisms, it plays a significant role in human aging (8). Together with methylglyoxal, glucosepane is a marker of glycation, and its presence is used to monitor glycation damage (9). In fact, methylglyoxal is a precursor of glucosepane. It has been suggested that glucosepane makes up the vast majority of cross-links in older people and there is no efficient way to eliminate this molecule from our body (although several researchers have their doubts about the validity of this statement). Currently, there is a race to discover an efficient compound that can eliminate glucosepane from our aging bodies, in the hope that this will result in a reduction of age-related pathology.
H Lys N
OH
N
N N
Figure 1: The
OH
glucosepane molecule
c There are several chemical entities forming part of the group of Advanced Glycation End-products (AGEs). Some examples are:
• N-ε-carboxy-ethyl-lysine (CEL) and N-ε-carboxy-methyl-lysine (CML) • Imidazolone • Methyl-glyoxal-lysine dimer (MOLD) and glyoxal-lysine dimer (GOLD) • Pyrraline • Pentosidine • Glucosepane • Amadori products, (although these are more precisely described as intermediate products, leading to the formation of other AGEs)
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Arg
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Sugar (including glucose and other reducing sugars) + Protein
Glycemic control
Exogenous AGEs
Benfotiamine
Amadori products (Glycated proteins) Reactive carbonyls Aminoguanidine ALT-946 OPB-9195 Pyridoxamine ACE inhibitors All receptor blockers Metformin Advanced glycation end products (AGEs)
sRAGE
Crosslink breakers (PTB, alagebrium) Figure 2: A simplified image showing the different pathways and compounds involved in
AMINOGUANIDINE Also known as Pimagedine, this compound is an inhibitor of Nitric Oxide (NO) synthase and an antiglycator. It reduces AGE concentrations and has the potential to reduce age-related degeneration. Aminoguanidine as well as pyridoxamine are potent carbonyl and free radical scavengers. During the process of glycation, intermediaries such as dicarbonyl
AGE receptors groups are formed. However, aminoguanidine has the ability to inactivate these dicarbonyl groups (10) and helps prevent complications of diabetes such as kidney damage, vascular disease and neuropathy. The age-related glycation of collagen causes a series of skin changes (wrinkles and skin thickening, for example). Aminoguanidine prevents these changes in the laboratory
anti-glycation
environment, and clinical research in human age-related skin changes is underway. Recent research (11) shows that aminoguanidine applied as a skin cream can reduce the levels of Nε-carboxymethyl lysine (CML) (see box 2) and may be useful in delaying skin aging. Aminoguanidine also increases the phagocyte response and improves antibacterial actions in white blood
“Recent research shows that aminoguanidine applied as a skin cream can reduce the levels of Nε-carboxymethyl lysine (CML) and may be useful in delaying skin aging.”
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cells, reducing inflammation (12). This mechanism is believed to be via aminoguanidine’s anti-glycating action which reduces oxidation and normalizes the function of signaling pathways. It is therefore becoming clear that aminoguanidine has a range of anti-glycating activities, working at multiple levels, (as shown in figure 2).
CONCLUSION Although certain researchers are not entirely convinced of the clinical effectiveness of anti-glycators (13) others are satisfied that there is significant potential. Overall, the information available appears optimistic, with many thousands of people using the various anti-glycation compounds.
“Although certain researchers are not entirely convinced of the clinical effectiveness of anti-glycators others are satisfied that there is significant potential. ” REFERENCES 1. Nenna A. et al. Pharmacologic Approaches Against Advanced Glycation End Products (AGEs) in Diabetic Cardiovascular Disease. Res Cardiovasc Med. 2015 May 23;4(2):e26949 2. Krautwald M. et al. The advanced glycation end product-lowering agent ALT-711 is a low-affinity inhibitor of thiamine diphosphokinase. Rejuvenation Res. 2011 Aug;14(4):383-91 3. Watson AM et al. Delayed intervention with AGE inhibitors attenuates the progression of diabetes-accelerated atherosclerosis in diabetic apolipoprotein E knockout mice. Diabetologia. 2011 Mar;54(3):681-9 4. Zakaria MN, El-Bassossy HM, Barakat W. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats. Adv Pharmacol Sci. 2015;2015:346259 5. Dhar A, Dhar I, Bhat A, Desai KM. Alagebrium attenuates methylglyoxal induced oxidative stress and AGE formation in H9C2 cardiac myocytes. Life Sci. 2016 Feb 1;146:8-14 6. Park J. et al. Renoprotective antioxidant effect of alagebrium in experimental diabetes. Nephrol Dial Transplant. 2011 Nov;26(11):3474-84 7. Peppa M, et al. J Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711). Am J Nephrol. 2006;26(5):430-6 8. Draghici C, Wang T, Spiegel DA. Concise total synthesis of glucosepane. Science. 2015 Oct 16;350(6258):294-8. doi: 10.1126/science.aac9655 9. Monnier VM, Genuth S, Sell DR. The pecking order of skin Advanced Glycation Endproducts (AGEs) as long-term markers of glycemic damage and risk factors for micro- and subclinical macrovascular disease progression in Type 1 diabetes. Glycoconj J. 2016 Jun 25. [Epub ahead of print] 10. Thornalley PJ. Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts. Arch Biochem Biophys. 2003;419:31–40 11. Lee KH. et al. Molecular characterization of glycation-associated skin ageing: An alternative skin model to study topical anti-glycation activity in vitro of a cosmeceutical and pharmaceutical formulation. Br J Dermatol. 2016 Jul 1. doi: 10.1111/bjd.14832. [Epub ahead of print] 12. de Souza Ferreira C. et al. Aminoguanidine treatment increased NOX2 response in diabetic rats: Improved phagocytosis and killing of Candida albicans by neutrophils. Eur J Pharmacol. 2016 Feb 5;772:83-91 13. Engelen L, Stehouwer CD, Schalkwijk CG. Current therapeutic interventions in the glycation pathway: evidence from clinical studies. Diabetes Obes Metab. 2013 Aug;15(8):677-89
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SPOTLIGHT: BIOIDENTICAL HORMONES OX Y TOCIN FOR PA SSION AND SE X IAS carries a wide range of bioidentical hormones - a term that means ‘natural to and in the body’. In this featured section we are focusing on oxytocin. What is oxytocin? Oxytocin is a hormone produced by the hypothalamus, but excreted via the pituitary gland. Its orthodox medicine role is to help women give birth, since the large dose that’s injected helps relaxes the uterus and alleviates the passage of the child into the world for the mother.
Above: Dr. Thierry Hertoghe
However, as we will discover and has been highlighted by Dr. Thierry Hertoghe’s book; ‘passion, sex and longevity, the oxytocin adventure’ -it has many other roles to play too.
The love hormone Oxytocin has been dubbed ‘the love hormone’, why would this be? Principally because oxytocin can induce feelings of bonding and care and not just
between individuals, but even with animals too! Oxytocin measurements have been taken between lovers, friends, relatives, parents and their children etc. From those results, it has been noted that oxytocin levels are higher when they are in their presence. Mothers naturally bond with their children, but even men, (especially those who experience the live birth), express their emotions as wanting to care and protect their offspring, these effects may be attributable to the release of oxytocin hence triggering the bond. On the other side of the coin, psychopaths are notoriously low in their oxytocin levels, which may be a cause of their uncaring feelings towards other humans.
The pain and orgasm connection Fibromyalgia can be a very debilitating disorder with a lot of pain, sometimes constant for those who suffer with it. In women it was noted that when they were experiencing an orgasm they felt no pain
at all. Later, it transpired that women undergo a burst of oxytocin during orgasm. Trials were undertaken to see if oxytocin supplementation could alleviate the pain of fibromyalgia, there was some success, but the side-effect noted was that those women now enjoyed multiple orgasms! This was a fact picked up on by the popular press and is probably singularly the action most responsible for bringing oxytocin into the public gaze.
Synergy Dr. Hertoghe has explained that some folks will not feel the effects of oxytocin. This is principally because of two reasons, (if we consider that the dose is correct for that individual). Firstly, that some people are ‘low’ in their own principal sexhormone, so if a man is low testosterone, or if a woman is low estrogen, it is possible that oxytocin will not elicit its full potential in those persons. The other issue could be low vasopressin; vasopressin is a counterpart
“...oxytocin can induce feelings of bonding and care and not just between individuals, but even with animals too!” Dr. Thierry Hertoghe’s book, “Passion, sex and longevity - the oxytocin adventure”, details its roles and uses in a ‘how to’ guide form.
to oxytocin, produced and released via the same glands. In cases of vasopressin deficiency, the patient may enhance the oxytocin experience by adding one or two sprays (10 IU each) of vasopressin via the Vaso-Pro™ nasal spray.
Dosing As might be expected doses are very dependent upon its use. However for social or sexual enhancement, one can consider 5 IU to 10 IU a ‘typical’ dose. In fact, Dr. Hertoghe has somewhat reduced the doses that he recommends in his book, (transmitted via personal conversation to me). Currently IAS is providing Oxy-Sub™ in 20 IU trouches (a soft sublingual tablet), these can therefore be cut into half or quarter for a dose of 5 or 10 IU and should be placed under the tongue and allowed to melt. The other option is Oxy-Pro™ which is applied intranasally delivering 10 IU per spray.
SPOTLIGHT: CAN-C
™
A B R E AK THROUG H FOR C ATAR AC T Can-C™ eye-drops are the original™ brand- developed by Innovative Vision Products (IVP). This group were the first to research, publish and prove how eye-drops can reduce and even eradicate cataract. Accordingly there are active US and EU patents (and others pending) on this unique and special product. Unique formula: Can-C™ eye-drops are the formula from the original published human trials. They contain a purified and racemized form of n-acetylcarnosine (made in Japan); this natural di-peptide has potent anti-glycating and antioxidant properties that prevents lipid peroxidation. Note that the formula is important- it’s not all about the n-acetylcarnosine; the specific carrier agents and their purity are also important. If you look at the Can-C™ formula you will see differences to the copycats, (remember it is only Can-C™ that is patented in recognition of the original work). If you want the best possible results in the fastest possible time, then choose Can-C™ to deliver them according to the clinical trials.
Clinical trial: Patients placed two-drops of Can-C™ into their eyes twice daily for a 6-month
period, the outcome was:
• 90% saw an improvement in their visual acuity.
• 88.9% of patients showed improvement in the clarity of their lens. There have been numerous reports of cataract shrinkage and even disappearance with documented evidence that Can-C™ eye-drops remain effective (and safe) more than 24-months later. The most commonly expressed initial reports are that glare is significantly improved, (for example night driving is much safer) and color perception is enhanced.
Improving eye-sight: More evidence is mounting that Can-C™ is efficacious for many conditions including: • Cataracts (particularly the senile version) • Glaucoma • Presbyopia • Corneal disorders • Eye strain • Ocular inflammation • Blurred vision
• Vitreous opacities and lesions • Diabetes mellitus complications • Contact lens users • Dry eye syndrome Of special interest may be to persons who wear contact lenses. This is because Can-C™ inhibits the accumulation of lactic acid and therefore contacts can be worn for longer periods without pain. We have also received reports that Can-C™ not only aids dry-eye syndrome with its lubricants, but that Can-C™ helps to unclog proteins from the lacrimal ducts, thus releasing more natural tears onto the eye.
Can-C™ Plus capsules In addition to the eye-drops, Can-C™ Plus capsules are also available. They are strongly recommended to be used in combination with the eye-drops- if you have ripe (long existing) cataracts. Dr. Kyriazis book, ‘The Cataract Cure’, details the usefulness and evidence of Can-C™ eyedrops. It is now available as a FREE e-book at:
www.antiaging-systems.com/ can-c-ebook
In a similar way, it is also believed that the unclogging of proteins in the eye’s drain, (the Schlemm valve), helps to reduce intraocular pressure and thus aids glaucoma.
Before:
After:
Right: A woman’s eye shows the cataract before treatment. Far Right: 5-months later after use of Can-C eye-drops (two drops twice daily), there is no longer a visible cataract and eyesight has improved. WWW.ANTIAGING-SYSTEMS.COM • ORDER HOTLINE: 1-866-800-4677 • E-MAIL: IAS@ANTIAGING-SYSTEMS.COM
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SPOTLIGHT: GHRPS A R E AL ‘OR AL’ ALTER NATIVE TO G H IN JEC TION S
Ever since Dr. Rudman’s work in the 1980s and then the release of Dr. Klatz’s book ‘grow young with HGH’ in the 1990s, there has been a strong interest in the use of growth hormone (GH) in antiaging medicine. Dr. Rudman’s research concluded that after injecting his elderly patients with GH, many of them had reversals of their biological age markers by as much as 20-years; specifically having noted improved skin, hair, muscle mass, decreased fat levels and enhanced levels of stamina, strength and well-being. It’s not entirely surprising given the multi-faceted role of growth hormone, plus as its name suggests it is involved in the growth and repair of tissues, but unfortunately blood levels of it decline dramatically past the age of 35 (see figure 1), despite the fact that there is evidence that the pituitary gland continues making significant amounts of it.
GH injections The issue with injecting GH, (brand names include Genotropin®, Saizen® and Zomacton®), other than its expense, is that it does have to be injected to be effective, this is because as a 191 chain aminoacid it simply can’t be absorbed via any other route, thus daily injections can become a chore. Furthermore, many countries have decided that GH injections be classified as a controlled substance, partly because of its anabolic actions. Controlled substances often require special import and export licenses; this is over-and-above the requirement for a prescription. Furthermore, the research of Dr. Richard Walker has highlighted that bolus injections of GH are not bioidentical and that as they induce spikes of GH 32
into the blood they could end up damaging the pituitary gland, leading to a down-regulation of its own production of GH, or even to stop GH production altogether.
GHRPs But meanwhile, Dr. Walker’s research has shown that the use of GHRPs, (growth hormone releasing peptides) have a much safer profile whilst enjoying the same benefitseven if they provide them a little more slowly. We would recommend that you read his extensive article in the Aging Matters™ magazine, No3, 2014 to understand fully how they operate. What we can say is that GHRPs, (GHRP2, GHRP6 and sermorelin) have the following benefits: • They can be sublingually, intra-nasally and even orally, passing into blood and thus avoiding the need for needles. • Their feedback loop means that they cannot cause the pituitary to down-regulate. • GHRPs are not controlled substances. • Rather than inducing a spike of GH in the blood, GHRPs augment (improve) each release of GH naturally into the blood, for which there are several peaks daily, (although the rising from bed peak is the highest one) - see figure 2.
Synergy Sermorelin is actually the precursor to GH, being the
first 29 amino acids and is applied via the sublingual route. Sermorelin’s function may be to release existing stores of GH from the pituitary- rather than encourage more production as a pure agonist would. Dr. Walker has highlighted that combining sermorelin with GHRP2 or GHRP6 has a highly synergistic effect, in some cases eliciting up to a 5x greater quantity of GH into blood, an action that can be equivocated to using injectable GH itself. Note: You can also hear Dr. Walker discuss this with us on the IAS video page:
www.youtube.com/ watch?v=S5OlEhbM7lQ
Differences • GHRP6 may induce more hunger feelings than GHRP2 and could improve levels of IGF-1 more. Therefore this option may be better recommend for those who want to put on muscle mass. • GHRP2 may create less hunger feelings and therefore could be preferable to those who want to stimulate GH for fat loss. Also as the GHRP6 (Releasing-Pro™) is a nasal spray, those who don’t like that feeling may prefer GHRP2-Pro™ since it is an oral liquid simply swallowed.
Figure 1 (top): The typical GH levels in blood with age, note that ‘geriatric’ levels are reached as early as during the 30’s. Figure 2 (middle) shows the 24 hour profile of subcutaneous (and also intravenous) GH. Compare that to figure 3 (bottom), the natural peaks of GH in both young and elderly patients. Only GHRPs naturally amplify these bioidentical patterns.
Summary GHRPs have created a genuine efficacious alternative; they are simpler/ easier to use and at the same time they have a better/ safer profile than injectable GH.
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®
90 58
3mg Amount Per Serving
* % Daily Value
Servings per container: 60 Serving Size: 1 tablet
Supplement facts:
Description: MZS is Dr. Walter Pierpaoli’s original melatonin formula containing the additional and supportive agents zinc and selenium. MZS is produced to pharmaceutical standards in Italy and unlike other melatonin preparations MZS has been designed to produce a night peak of melatonin between 1AM and 3AM to mimic the natural behavior of the pineal gland. Dr. Pierpaoli’s extensive animal and human research has shown that this is important because this action helps to stabilize circadian rhythms, improve hormonal cyclicity and boost immunity.
MZS
www.profound-products.com
Dr. Pierpaoli’s original formula+
™
Formulated and distributed by Profound Products, PO Box 19, Sark GY9 0SB, Great Britain
MZS Dr. Pierpaoli’s original formula ™
Dr. Pierpaoli
MZS Dr. Pierpaoli’s original formula
®
®
Dr. Pierpaoli MZS Dr. Pierpaoli’s original formula
™
50mcg 8.7mg
Melatonin
Dr. Pierpaoli MZS Dr. Pierpaoli’s original formula
Directions: Take 1 tablet before bedtime, ideally between 10PM and 11PM.
% Daily Value * not established Other ingredients: Avicel, mannitol, povidonum and magnesium sterate Selenium Zinc
B EC AU S E NOT ALL MEL ATONIN S AR E CR E ATED EQUAL
Disclaimer: This product and its statements have not been evaluated by the FDA. This product is not intended to treat, cure or prevent any disease.
™
Note: Keep in cool dark conditions, out of the reach of children and consume before end of expiry date. Not for use by pregnant or lactating women.
SPOTLIGHT: MZS
™
Our melatonin has been formulated by the world’s foremost melatonin expert Dr. Walter Pierpaoli, his Melatonin Zn Se, or MZS™, is totally unique since it is designed to mimic the natural night peak of melatonin- to leave you feeling refreshed and alert the following day.
What does Melatonin do? Melatonin is vital to protect our hormonal system, regulate immunity and repair our body’s cells. It is commonly used by shift workers and also to treat jet lag and age related sleep disorders, but its abilities go far beyond simply its sleep inducing properties.
The antioxidant effects of melatonin Melatonin is an extremely effective antioxidant; in fact on a molecule to molecule basis; melatonin has proved to be significantly more efficient in neutralizing toxic hydroxyl-
radicals than the two wellknown free radical scavengers, glutathione and mannitol.
ARMD. Remarkably this was true for both the wet and dry forms!
Melatonin’s effects on longevity
Why is Dr. Pierpaoli’s MZS™ more effective than other melatonin supplements?
Melatonin’s effect on longevity is well documented; in fact laboratory tests on rats and mice have demonstrated that melatonin increased their lifespans by 20%. Experts believe melatonin is a vital antiaging product because of its positive effect on aging. MZS™ and age-related macular degeneration Age related macular degeneration (ARMD) comes in two forms, wet and dry and is a notoriously difficult disorder to treat and is linked to blindness. A 24-month study, (published in NY Academy of Science, 2005, 1057:384-392) on 100 patients showed that after 3 months, the majority of patients taking 3 mg of Melatonin Zn Se nightly had halted the progression of their age related macular degeneration and at 6 months many showed reversal of their
There are three principal reasons, firstly it is of pharmaceutical quality at a dose of 3 mg, secondly it contains the synergistic ingredients of selenium and zinc, but thirdly and most importantly- it is designed to release at a very specific time. Dr. Pierpaoli’s research led him to perfect a formula that exactly mimics the pineal gland’s release of melatonin. Thus means that MZS™ is the only melatonin supplement to follow nature’s own night peak.
+
60 tablets Dietary Supplement
™
Melatonin is produced by the pineal gland at night to regulate our circadian rhythm, (sometimes called the sleep wake cycle). As we age the amount of melatonin we produce reduces resulting in many older people sleeping less and having a lower quality of sleep.
Dr. Pierpaoli
®
MZS Dr. Pierpaoli’s original formula ™
Dr. Pierpaoli
®
MZS™ is so much more than a sleep aid Melatonin has had so many published benefits it is impossible to list them all here. From jet lag and shift work to well-being and antiaging, no other melatonin supplement offers the endorsement of Dr. Pierpaoli, or the exact formula used in all of his renowned clinical trials. If you’ve tried other melatonin and didn’t notice any significant effect, then we highly recommend you try Dr Pierpaoli’s MZS™ for a superior experience. Dr. Pierpaoli’s free ebook ‘The key of Life’ can be read here:
http://bit.ly/1vdB31y
How much should I take? Take half to one 3 mg tablet at bedtime only; do not take more than two tablets. By taking MZS™ between 9pm and 11pm you will create a night peak between 1am and 3am, this is the most natural and normal time to have the highest melatonin levels.
Left: Melatonin levels in blood over 24-hours This graph compares Dr Pierpaoli’s melatonin formula (red line) to the natural release of melatonin (dark blue). Two other common types of melatonin supplements (light blue and green lines) demonstrate that sublingual melatonin peaks too soon and that time released formulas peak too late.
Above: Here are some before and after Fundus photos showing the benefit of Melatonin Zn Se. (Top before, below: after treatment).
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33
SPOTLIGHT: PEOS
®
S U PPLYING AND BAL ANCING OMEGA S NATU R ALLY Most people are familiar with the benefits of omega oils for their health and in particular to reduce inflammation. Indeed cod-liver oil supplements are the world’s most popular supplement, but recently Professor Brian Peskin’s research which is all contained in his new book – the PEO solution - is causing quite a stir and may make many folks to rethink and change their stance.
Professor Brian Peskin and the cover of his latest book - the PEO solution
We are referring to his discovery that the body naturally uses plant oils to make its own omega 3 and 6, thereby satisfying a precise balance according to need- providing the ‘raw materials’ are available. Professor Peskin has termed the phrase PEO as the acronym for ‘parent essential oils.’ Professor Peskin states openly that he has found this information hidden in the scientific literature and never once found it referred to in the medical literature. Why does it matter? Because as he says, it means that physicians are unaware of these facts and therefore they continue to advocate super-physiological doses of omegas from fish oil, which may be actually doing more harm than good! It’s a lot to swallow, (no pun
intended) and we can’t do his research justice on a single page, which is why we recommend his book, or take a look at the Aging Matters™ magazine No1, 2015 in which Professor Peskin’s article is the lead story. Let’s summarise the advantages of the PEOs: • The plant oils live in our environment, (typically around 50-60°F); hence they do not go rancid at room temperature. Cold water fish live in a cold environment (typically around 30-40°F), therefore PEOs represent a much more stable product. • The PEOs are obviously a nonanimal source and therefore can be considered more suitable for those wanting to avoid animal based products. • The PEOs represent a sustainable source, since there is already too much ‘pressure’ on the seas to provide both fish and even krill stocks. • The PEOs enable the body to produce its own internal essential fatty acids (EFAs) and correct its own balance. This has not been shown to be the case with fish oil supplements.
Why not fish oil?
Figure: How is fish oil made? It often does not start as the healthiest possible source!
Professor Peskin maintains that the super-high doses in fish oils are extreme when compared to those manufactured within the body. Furthermore, even the omega 3 to
omega 6 balance OXYGEN MAGNETS! they provide could be EFAs work like tiny “magnets” drawing Oxygen EFAs oxygen into all cells, tissues wrong and that the and vital organs. O O body may actually Reduce oxygen by only 1/3 and a cell O turns cancerous, forever! require more omega HEART LUNGS 6 than is currently being advocated today. Did you know that when a bear eats a fish he throws away the body? Could it be that the bear Figure: Essential fatty acids provided via wants the omega 6 provided PEOs work like magnets, drawing oxygen into cells and tissues. Reduce oxygen by the fish brain and not the content in cells by one third and they can omega 3 that is within its body? become cancerous. (The fish uses omega 3 as an anti-freeze due to its cold water contains organically produced, environment). cold-pressed seed oils, these include high linoleic safflower PEO-Pro™ oil, sunflower oil, evening IAS has always been ‘on the primrose oil and flax oil, all in cutting-edge.’ It may remain the proportions derived from controversial, however we have Professor Peskin’s research. taken the decision to remove Maintenance doses are 1 or fish and krill based oils from 2 capsules daily; for those with our range and replace them greater need, 1 capsule per 40 with PEOs that are contained in lbs (18 Kg) bodyweight per day PEO-Pro™. may be more suitable. The PEO-Pro™ supplement 2
2
2
Oxygen Magnets
Appetite
• Less Cravings • Less Hunger • Better Appetite Fulfilment
Heart Health
• Flexible Arteries • Clean Arteries • Fast Blood Flow • Lower Blood Pressure • Improves Lipids
Beauty
• Healthier Skin • Less Dandruff • Less Cellulite • Healthier Hair • Eczema Improved
• Less Sweet Cravings • Lower Blood Sugar • Less Neuropathy/ Retinopathy
PEOs
Anti-inflammation
SUPPORT
• Less Arthritis • Less Joint Pain/Swelling • Faster Healing
Hormones/ Endocrine
Brain Health
Endurance
Diabetes
• Better Sexual Function • Smoother Pregnancies • Less PMS • Fewer Headaches
• Better Clarity • Better Focus • Improved Memory • Helps Improve ADD & ADHD
• More Energy • Less Fatigue • Greater Intensity • Faster Recuperation
Figure: This diagram highlights the benefits of EFAs (essential fatty acids) that PEOs can deliver.
SPOTLIGHT: PEPTIDE BIOREGUL ATORS THE DI SCOVERY OF G ENE SWITCHES IN FOOD Today Professor Vladimir Khavinson is the President of the European Academy of Gerontology and Geriatrics, but in the 1980’s he was a Colonel in the Soviet Union military medical corps. At the time, he and his team were approached by Kremlin officials, they wanted them to find a way to protect their troops from a myriad of problems; issues such as radiation for submariners in nuclear submarines to troops that may be blinded from known, (but thankfully unused) new weapons such as battlefield lasers.
A former Soviet military secret!
obtained from food, to act as a ‘short-cut’ to initiate protein synthesis. These peptides, What their research uncovered unlike proteins, can enter the - that was used for two blood through the stomach. decades on many thousands Through a comprehensive of men and women - was a list of patents and even remarkable link between copyrighted PowerPoint short chain peptides and DNA. slides, the Russian research This former military secret is group have shown that each now available to the public of the concentrated peptide as peptide bioregulators. bioregulators so far examined, Their published research has interact with particular strands identified that each organ / of DNA - effectively and very gland / tissue uses a highly specifically activating repair specific short chain peptide, and regenerative processes. This is a remarkable story since what we are describing here are peptides that act as individualised gene switches. To date, they have been tested for many years on thousands Above: A short-chain peptide bioregulator
of individuals, without report of any serious side effects or contraindications. We believe that they could be set to ‘out do’ stem cells. Why? Because this peptide therapy is relatively cheap, highly specific, can be taken orally and doesn’t require any suppression of the immune system to operate fully (as stem cells do).
Original material from the trials The peptide bioregulators available via IAS are the bovine originals; sourced from carefully chosen Danish calves and processed through pharmaceutical processes and filters. They are not the synthetic versions which have not been studied/ proven. Peptide bioregulators act as they sound- to regulate; for example, Thyreogen®
the thyroid peptide would increase thyroid activity if it were too low, but decrease it if it were too high!
Dosing Doses are very dependent upon the need and unlike hormones these peptides do not have to be taken every day, hence making them a cost effective regime. A typical/ average use could be considered as follows: • Start with an intensive course: 2 capsules once a day for 30-days. • Thereafter use 2 capsules once a day for 10-days, repeat every 2, 3, 4 or even as little as 6-months. The story of the peptide bioregulators is a remarkable one and we recommend that you to read the articles and interviews and see the video on the IAS website.
interacting with DNA
PEPTIDES CURRENTLY AVAIL ABLE: Bone Marrow bioregulator: Parathyroid bioregulator: Brain peptide bioregulator: Heart peptide bioregulator: Bladder peptide bioregulator: Pineal peptide bioregulator: Adrenal peptide bioregulator: Muscle peptide bioregulator: Prostate gland peptide bioregulator: Kidney peptide bioregulator: Cartilage peptide bioregulator:
Bonomarlot® Bonotirk® Cerluten® Chelohart® Chitomur® Endoluten® Glandokort® Gotratix® Libidon® Pielotax® Sigumir®
Pancreas peptide bioregulator: Stomach mucus peptide bioregulator: Liver peptide bioregulator: Lung peptide bioregulator: Testes peptide bioregulator: Thyroid peptide bioregulator: Blood vessel peptide bioregulator: Retina peptide bioregulator: Thymus peptide bioregulator: Ovary peptide bioregulator:
Suprefort® Stamakort® Svetinorm® Taxorest® Testoluten® Thyreogen® Ventfort® Visoluten® Vladonix® Zhenoluten®
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35
SPOTLIGHT: SMART DRUGS AND NUTRIENTS PIR ACE TAM, THE ORIGINAL NOOTROPIC Smart drugs and nutrients, or to give them their correct medical terminologynootropics, are agents that can not only improve conditions of senile dementias, but in recent times have become popular for older individuals to improve their mental and cognitive processes. It was Ward Dean, M.D. who highlighted these facts through his very popular ‘Smart Drug’ series of books in the 1980s, since then the term ‘smart drugs’ has become mainstream.
Piracetam, the original nootropic The smart-drug we focus on here was in fact the first, developed as it was by Dr. Giurgea for UCB laboratories in Belgium in the 1960s. Originally it was designed to assist with travel and altitude sickness, but shortly afterward individuals realised that piracetam had positive cognitive enhancement effects.
What can piracetam do for me? Piracetam is a cognition agent that has been used successfully to treat a
wide range of conditions, for example it has been shown to increase a person’s attention levels and improve memory and intelligence. Piracetam can help to slow down ‘senile involution’, dementia and Alzheimer’s disease. In tests and trials, piracetam induces significant improvement to memory consolidation and recall in those suffering from ‘age-associated memory impairment’. Piracetam has also been used to improve patient’s recovery from strokes, particularly improving post stroke speech impairment (aphasia). Another use has been in cases of acute and chronic cerebral ischaemia, (decreased blood flow to the brain). Using piracetam has restored speech and the use of limbs in these patients; it has also increased neuronal activity in the brain when measured with EEG.
For regular individuals, piracetam has been shown to enhance idea creation and the ability to ‘see things through,’ in other words to have ideas and bring them to fruition. The level of clarity piracetam creates is often described/ perceived as; “the fog has lifted.”
How does piracetam work? Piracetam’s key and unique method of action is upon the Corpus Callosum, the region of the brain that links the two hemispheres. It is this that most experts believe is the key that gives piracetam users the ability to channel greater brain potential by connecting the logical side of the brain with the creative side more effectively, Yin and Yang if you will.
“Piracetam can help to slow down ‘senile involution’, dementia and Alzheimer’s disease.” 36
What are the doses of piracetam? A common dose is 800mg tablets three times a day, then lowering to 800 mg twice a day after the first month. Note: The effects of piracetam can be enhanced if taken concurrently with centrophenoxine or Hydergine®. Side effects are minimal and seldom experienced, but should you experience nausea or headache then it is usually caused by an overdose, so in which case reduce the dose and build up more slowly, (if it is necessary). Note: There are many articles and videos on the IAS website about smart drugs and nutrients.
Right: The Corpus Callosum
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SPOTLIGHT: THYROID SUPPORT FOR THE HYPOTHYROID EPIDEMIC Dr. Broda Barnes in the 1970s estimated that 40% of the adult population was deficient in thyroid hormones; he published this statement in his excellent book‘hypothyroidism, the unsuspected epidemic.’ Since then, pupils of Dr. Barnes, such as Dr. Richard Wilkinson, have suggested that this figure could be even greater now! This is important because the thyroid gland is of pivotal importance to our overall health, but like the majority of hormones as we age the production of thyroid hormones decline. This lack of thyroid function is the root cause of a wide variety of agerelated health disorders. Ergo, supplementation with a synthetic or a natural thyroid can have a significant positive effect on a wide range of agerelated problems.
The importance of the thyroid gland The hormones produced by the thyroid control the body’s metabolism- the rate at which it burns calories for energy. It also controls the body’s utilization of fat, so a decline in the secretion of hormones from the thyroid gland, (known as hypothyroidism) can result in wide range of symptoms such as poor concentration, confusion, memory problems, cold hands and feet and weight gain. Another serious condition which can be caused by and result from an underactive thyroid are painful musculoskeletal issues that affect tendons, muscles and ligaments.
How can I be sure if I need a thyroid supplement? Above: The position of the thyroid gland
Apart from recognising the types of effects listed above, your doctor can of course get your blood
levels of thyroid checked, but another, simpler method is to take your body temperature when you wake in the morning. It should be in the range of 97.8 to 98.2 degrees Fahrenheit, if it is regularly lower you could be hypothyroid and if higher then hyper-thyroid.
Choosing between synthetic and natural thyroid supplements IAS stocks a comprehensive range of both synthetic and natural thyroids, although we advocate the use of a natural supplement over a synthetic, this is because products such as Armour® are of a porcine origin, so they naturally contain the full spectrum of T1, T2, T3 and T4 thyroid hormones, (note the bottles only list the amounts of T3 and T4 because very few physicians are familiar with T1 and T2).
Conversion between synthetic and natural thyroid products The table provided is a helpful guide to what the suggested conversion rates are for those wishing to make the switch between synthetic thyroids and natural versions. As always we recommend consulting with a physician before making changes to your program.
Thyroid doses Natural desiccated thyroids are measured in grains; with one grain being equivalent to approximately 60 mg. IAS carries doses from ¼ grain to 2 grains, with brands including Armour®, ERFA® and Nature®. IAS also provides synthetic T3 in 20 mcg and T4 in 100 mcg tablets.
Thyroid supplements provide potent antiaging protection Many aging individuals can benefit from taking a thyroid supplement because this remarkable hormone has such a profound affect across so many different conditions. Many antiaging physicians consider thyroid support an essential part of any serious attempt to improve a person’s health-span and longevity.
Dose of Desiccated thyroid (grains)
Equivalents (mg)
Dose of T3 (lithyronine) (μg)
Dose of T4 (levothyroxine) (μg)
0.5
32
12.5
0.05
1
65
25
0.1
2
130
50
0.2
3
200
75
0.3
4
260
100
0.4
5
325
125
0.5
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37
SPOTLIGHT: YOUTH GEMS
®
THE PEP TIDE B IOR EG U L ATOR S FOR SKIN Four peptide bioregulators have now been combined into topical skin preparations so that their unique gene-switching performance can be bought to the field of aesthetic medicine. What does each peptide provide for? The beauty product line Youth Gems® contains the following four peptides and a ginseng extract called Neovitin®. They represent the very latest developed program of complex skin care designed for the face, neck, hands and the body. The line includes four unique active ingredients of shortchain peptides that have a directed tissue-specific action to improve all basic skin structures: • Thymus peptide: This stimulates tissue regeneration and the synthesis of tissue-specific proteins. Thus, cells proliferative and metabolic activity is enhancedaccelerating the renewal of various cell tissues. It also has an anti-inflammatory action, improving the healing time of wounds, as well as antioxidant, immune stimulating and anti-stress actions. • Pineal peptide: This regulates metabolic processes and increases protein synthesis in skin cells. It also possesses potent antioxidant activity, normalizes the lipid peroxidation processes in skin cells that in turn 38
promotes the elimination of negative influences on the skin from external factors. • Cartilaginous peptide. This stimulates regeneration of fibroblasts and keratinocytes and interferes with the destructive changes in collagen skin structure; it also strengthens collagen structure of elastic skin fibers and increases elasticity. • Blood vessel peptide: This regulates metabolic processes in the vascular wall, normalizes vascular tone and restores disturbed skin microcirculation. It strengthens and regulates the permeability of the vascular walls of skin vessels and improves skin turgor.
What else is included in Youth Gems® in addition to the four peptides? In addition to the four peptides, the Youth Gems® also contain an incredible array of beneficial natural agents- which just by themselves would make other antiaging creams jealous! The range includes: Neovitin® (a complex isolated from ginseng), olive oil, raisin-seed oil, Argon oil, Soya oil, Jojoba oil, Bisabolol (extract from chamomile), Peony extract,
sodium hyaluronate (a derivative of hyaluronic acid), green tea extract, cocoa oil, carrageenan (from seaweed), winter bloom, almond extract and vitamin E.
What results have been seen? Clinical trials and examinations have been conducted at the St. Petersburg Biogerontology Institute and they have concluded that these short chain peptides, when applied to skin cells, have many beneficial activities, shown below are some of those results. These include improved metabolism in vascular wall cells, the growth of new skin cells, enhanced antioxidant activity; increased blood flow circulation and greater moisturization. The skin’s appearance becomes smoother, with fewer wrinkles and with more elasticity, all of which helps to lift the face contours producing a more radiant, youthful appearance. These beneficial effects were noted in 100% of women who took part in the voluntary clinica trial.
What’s available? • Body milk: The body milk is a very light cream that can be applied to most areas of the body. • Day cream: The day cream is the core product designed to be applied to the face and hands. • Serum: The serum is designed to be used sparingly against the most noticeable skin aging effects on the face and neck. • Tonic: This cleanser can be used to help any area become more firm and taught and may be splashed on as required. All of the Youth Gems® should be applied onto clean, dry skin- avoiding the eyes; makeup can be applied after absorption - if required.
Right: A 68 year old female before (top) and after (below) application of Youth Gems®
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SPOTLIGHT: BIOCLIP ® CUFF MONITORING YOU R VA SCU L AR CONDITION The BioClip® Cuff is a simple way of assessing both your blood pressure condition and your arterial flexibility; plus, you can use the BioClip® Cuff in the comfort of your own home because you simply attach the device to your arm just like an ordinary blood pressure cuff. What does the BioClip® Cuff measure? The BioClip® Cuff provides a series of metabolic indicators that you can use to improve your lifestyle and so help to prevent the causes of cardiovascular disease. We all know the risks of being overweight, of having high cholesterol or suffering from high blood pressure. We also know how to reduce those risks – by exercising more, not smoking, reducing our alcohol intake and eating a balanced diet.
These include: • Diastolic blood pressure • Systolic blood pressure • The heart rate • Vascular condition – which linked to arterial flexibility. Few of us know about the hidden dangers of arterial inflexibility, or how to measure it. This is where the BioClip® Cuff is unique being as it is the first at-home device able of delivering this information to you within minutes.
What is arterial flexibility? The BioClip® Cuff works by evaluating your arterial flexibility, which experts say is one of the most important
Above: The BioClip® Cuff readout, showing both blood pressure, heart rate and vascular flexibility results.
risk factors when it comes to assessing the likelihood of a heart attack or stroke. Arteries are important because they’re responsible for blood flow around your body via your cardiovascular system. To work properly, it’s crucial that your arteries are kept healthy.
The poorer your vascular condition, the greater your chances of serious health issues Our arteries usually stiffen with advancing age. This brings with it a greater risk of a potentially fatal heart attack, heart failure or stroke, as is shown in figure 1.
You may not recognise the heart failure symptoms as your arteries begin to stiffen Unfortunately arterial stiffness can occur without warning. Often there are no symptoms of cardiovascular disease and
people don’t suspect they are in danger until they suffer an attack. Figure 2 highlights that arterial stiffness is strongly correlated with mortality The BioClip® Cuff provides a cardiovascular condition scale, shown by LED bars - that are either within the green zone (good), yellow zone (fair) or red zone (poor). It is important to note that like blood pressure, vascular condition should be monitored over time and not just taken as one reading. The BioClip® Cuff makes this simple by averaging your tests over time and therefore provides a more accurate result. BioClip® Cuff provides reassurance and a vital early warning system that helps you to be aware of changes and therefore keep your vascular condition in check.
Left: Arterial stiffness is a biomarker of aging, as shown here arterial stiffness tends to increase with age. Source: Millasseau et al., Clinical Science, 2002.
The BioClip® Cuff is easy to use The BioClip® Cuff doesn’t puncture your skin and is used on its own, without any additional attachments. The procedure is straightforward and you don’t need to link to a computer, as the results are shown on the BioClip® Cuff screen. Note: If you want to see it in action there is a video available at the IAS website. Armed with this information it’s easy to keep a check on your cardiovascular health and the risks associated with arterial stiffness, such as heart attacks and strokes. Armed with this information it is possible to make changes to your lifestyle and supplement program to improve results and keep you biologically younger! Above all, the BioClip® Cuff provides reassurance and a vital early warning system that helps you to be aware of changes and therefore keep your vascular condition in check.
Left: Three groups (each approximately 80 persons) were monitored over 140 months for their survivability. Those in the flexible artery groups (marked as PWV <9.4 m/s and 9.4-12.0 m/s) survive best losing approx. 25%. But those in the hard artery group (marked as PWV >12.0 m/s) 90% of them die in the same period. Source: ESRD, Blacher et al. Journal of Circulation, 1999
SPOTLIGHT: SMART DRUGS AND NUTRIENTS DEPR ENYL FOR FOCU S AND CONCENTR ATION Deprenyl is also known as selegiline, it was created in the 1960s by Professor Joseph Knoll from Hungary, principally as an aid to Parkinson’s patients - because deprenyl has a significant benefit to improve dopamine levels in the brain. Dopamine is the neurotransmitter most affected in Parkinson’s disease, in fact, deprenyl still remains a front line treatment for that disease.
Significant longevity studies
Morgenthaler, (as published in the book, Smart Drugs and Nutrients I), produced figure 2. It highlights that the loss of dopamine in humans with age, can be mapped against both the development of Parkinson’s and even death.
Mode of action For a long time deprenyl has been expressed as a MAO-b inhibitor, that it to say that is prevents the enzyme monoamine-oxidase type-b from destroying dopamine, ergo leading to its greater availability in the brain. The inhibition of the more common MAO-a can be problematic, leading to something called ‘the cheese effect,’ therefore this is not a side effect of deprenyl, although it should be noted that dopamine can inhibit type-a, but usually only at very high doses of 20mg. In more recent times, Professor Knoll has noted that there is another significant action of deprenyl and this is the raising, (albeit briefly) of PEA levels. PEA is a catecholamine activity enhancer that raises
Professor Joseph Knoll; now aged in his 90s but still active in pharmacological research.
Professor Knoll’s experiments with rats produced some of the most incredible longevity benefits that have ever been seen. When they were fed deprenyl in their food, they lived so much longer than those that were not, so much so, that even after the last non-treated rat died, the first of the deprenyl treated rats was yet to die! These results are shown in figure one: Note; interestingly and importantly, these results were verified independently in another study not conducted by Professor Knoll. Based on this research, Dean, Fowkes and
norepinephrine levels; this is a significant attention agent that is behind the primary mechanism of the famous Eugeroic drug- modafinil (Provigil®). To learn a great deal more about dopamine and deprenyl, we would recommend Professor Knoll’s books; ‘the brain and its self’, or ‘how selegiline/ deprenyl slows brain aging.’
Typical patient responses In patients who have mild cognitive impairment, or age related minor cognitive dysfunction, the most common report is of a significant improvement in their focus and concentration. Persons with higher dopamine levels often appear more ‘driven’ and ‘dedicated.’ Avoid overuse since it can lead to what may appear to be an oppressive behavior, as others around you are not so focused and ‘on the ball’ as you! This is why we recommend occasional breaks from deprenyl use, some advocate one week off in the month and others use it during the
75
Dopamine Level (%)
% of animals alive
100
Deprenyl Treated Rats
50
Control Rats
25 0 140
150
160
170
180
190
200
210
220
Age of rats in weeks
Figure 1: Professor Knoll’s experiment showed that when deprenyl is given to animals it significantly extends their lifespan and their latter life activity.
100 90 80 70 60 50 40 30 20 10 0
Average Parkinson’s Patients Rapid Parkinson’s Patients
weekdays but not at the weekends.
Dosing Doses are as normal, based upon need and age. Whilst Parkinson’s patient will require large doses, a person wanting to improve their cognitive performance may want to typically consider 1mg to 3mg per day, with occasional breaks. Note: These doses do not take into account synergy with other dopamine enhancing agents and persons using anti-depressants should consult with their physician beforehand. Deprenyl tablets are typically provided in 5mg form (Jumex®); some persons like to take ½ to 1 of these tablets 3-times a week; however the use of the deprenyl liquid (Dep-Pro™) is particularly attractive for those using deprenyl to generally support, protect and improve neurological function, since 1 drop = 1mg. Therefore the liquid can be dosed very precisely by simply placing those drops into a cold drink. Avoid use in the late evening to prevent any sleep disruption.
Slow Aging People Normal People
PARKINSON’S SYMPTOMS DEATH 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140
Figure 2: For humans, the normal loss of dopamine past the age of 40 is 13% per decade. As the lines suggest, if we all live long enough we all become senile!
CONDITION CROSS-REFERENCE LIST This cross-reference list highlights individual products that have been used for these disorders. Note: It does not mean that all these products are synergistic together. Addison’s disease Aldosterone, peptide bioregulator (adrenal)
Anti-biotics Ciproflaxin, doxycycline, roxithromycin, tetracycline
ADHD (ADD, attention deficit disorder, see mental stimulants)
Anti-depressants Lithium, milnacipran (Ixel®), reboxetine (Edronax®), Stablon®, Valdoxan®, venlafaxine (Efexor®)
Adrenal fatigue Aldosterone, hydrocortisone, peptide bioregulator (adrenal) AGE (advanced glycated end-product inhibitors) ACF228™, aminoguanidine, Can-C™ Plus, carnosine, metformin Age Related Macular Degeneration (see eyesight) Age Related Mental Decline (see cognitive) Aids (see HIV) Alcoholism (also see compulsive disorders) 5HTP, L-tryptophan, memantine Allergies Pregnenolone, thymus ALS (amyotrophic lateral sclerosis, Lou Gehrig’s disease) Naltrexone, TRH Alzheimer’s disease (see senile dementia) Anabolic (see growth hormone & testosterone) Anginas (see heart, arterial & blood)
Anti-oxidants (see free radical scavengers) Anxiety (see stress) ARMD (see eyesight) Arterial (See heart, arterial & blood) Arthritis (rheumatoid & osteo) Andro-Pro™, Gerovital-H3®, Novisyn®, PEO pregnenolone, SAMe, thymus, Asthma (see Allergies) Autism (also see chelation agents) Oxytocin, piracetam Back problems (see spine) Bell’s palsy Vitamin B12 Blood disorders (see heart, arterial & blood) Blood pressure Magnesium, Neo40®, oxytocin, potassium, propranolol, vinpocetine
Animal use Can-C™ eye-drops, deprenyl, L-tryptophan, peptide bioregulators (all)
Bone problems (also see joints & arthritis) Andro-Pro™, Bone-Pro2™, Esnatri™, peptide bioregulator (Bone), progesterone, SAMe, thyroid
Antiaging (as impacting on a particular theory of aging)
Breathing (see lungs)
Calorie Restriction Carnosine, metformin, resveratrol
Hayflick Carnosine, Peptide Bioregulator (pineal), TA65®
Cancer (also see anti-oxidants & radiation) 1st Line™, anastrozole, BEC5® Curaderm, bromocriptine, curcumin, DIM-Pro2™, laetrile, melatonin, metformin, naltrexone, oxaloacetate, progesterone, resveratrol, thymus, TRH
Membrane Centrophenoxine
Cardiovascular (see heart & arterial disorders)
Free radical ACF228™ Glycation Aminoguanidine
Mitochondrial HyPro2™, PQQ Neuroendocrine Metformin, TRH Rotational Melatonin
Cataplexy (sudden fatigue) Adrafinil, picamilone Cataract (see eyesight)
Telomeres Peptide biomarker (pineal), TA65®
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Central Nervous System (CNS) Peptide bioregulator (brain) Peptide bioregulator (Cerluten®) Chelation agents Carnosine, centrophenoxine, DMSA, EDTA, zeolite Cholesterol (see blood disorders) Crohn’s disease Naltrexone Chronic fatigue syndrome (see mental stimulants & physical energy improvement) Cognitive (also see memory & senile dementias)
Digestive issues peptide bioregulator (Stomach), Symprove® DNA support (also see telomeres) Carnosine, CoQ10, PEO, peptide bioregulator (pineal), PQQ, resveratrol, TA65® Down’s syndrome Melatonin, piracetam Energy improvement (see physical energy & mental stimulants) Enzymes Boluoke®
Alertness Adrafinil, Xan-Pro™
Epilepsy GABOB, phenytoin
Creativity Aniracetam, piracetam, pramiracetam Focus/ concentration Deprenyl, desmopressin, vasopressin
Erectile dysfunction (also see sex-libido & premature ejaculation) Andro-Pro™, cabergoline, deprenyl, Neo40®, oxytocin, sildenafil, Vielight®, VigorPro2™
Energy ATP-Boost™, centrophenoxine, Mito-Pro2™, NADH, picamilone
Eyesight
General support Gerovital-H3®, vinpocetine Intelligence HyPro2™ Work load HyPro2™, thyroid Compulsive disorder treatment (also see alcoholism) 5HTP, GABOB, L-tryptophan, picamilone Cortisol alteration (also see stress) Aldosterone, DHEA, GABOB, Gerovital-H3®, hydrocortisone, peptide bioregulator (adrenal), phenytoin Cross linking (see AGE) Deep vein thrombosis (see frequent fliers) Dental (see teeth & gums) Depression (also see well-being & anti-depressants) 5HTP, aniracetam, ATP-Boost™, curcumin, deprenyl, Gerovital-H3®, lithium, L-tryptophan, milnacipran, picamilone, piracetam, pramiracetam, pregnenolone, SAMe, thymus, thyroid DHT alternation (dihydrotestosterone) Dutasteride, finasteride, peptide bioregulator (prostate), progesterone Diabetes Acarbose, aminoguanidine, ATP-Boost™, benfotiamine, L-carnosine, metformin, Mito-Pro2™, PEO, peptide bioregulator (pancreas), pyridoxamine, thyroid, TRH Diabetes insipidus (see urination)
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Dieting (see weight loss)
ARMD MZS™ Cataracts Can-C™, Can-C™ Plus Contact lenses Can-C™ Dry eyes Can-C™ General support Aminoguanidine, peptide bioregulator (retina), vinpocetine Glaucoma Can-C™ Retinal MZS™, picamilone Retinal pigmentosa Picamilone, peptide bioregulator (retina) Excitotoxins (reduction) Carnosine, deprenyl, idebenone, lithium, memantine Fertility Melatonin, metformin, peptide bioregulator (ovaries), TRH Fibromyalgia (also see physical energy & mental stimulants & pain relief) 1st Line™, milnacipran, naltrexone, oxytocin Free radical scavengers ACF228™, ATP-Boost™, BHT, glutathione, idebenone, melatonin, Mito-Pro2™ Gastrointestinal (see digestive) Glaucoma (see eyesight) Glucose control (see diabetes) Glycation prevention (see AGE)
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Gout Colchicine
Homocysteine (see heart, arterial and blood)
Growth hormone (improvement) Bromocriptine, deprenyl, GABOB, GHRP2, GHRP6, HyPro2™, IGF-1 Neo40®, sermorelin, thymus, thyroid
HRT (hormone replacement therapy for women) DHEA, Esnatri™, melatonin, progesterone
Hashimoto’s Iodine, peptide bioregulator (Thyroid), thyroid Hair improvement Dercos®, dutasteride, finasteride, Gerovital-H3®, MinMaxPro™, PEO Headaches (see migraines) Heath diagnostics (see at home test kits) Hearing disorders Aldosterone, picamilone, vinpocetine Heart, arterial & blood (includes blood markers) Arteries (hard) Aminoguanidine, BioClip™-CUFF, carnosine, resveratrol Blood pressure (high) Magnesium, Neo40®, potassium, propranolol, vinpocetine Calcium Peptide bioregulator (parathyroid) Cholesterol (high) CoQ10, Gerovital-H3®, MitoQ®, TRH, Xan-Pro™ Dilation (nitric-oxide) Deprenyl, Neo40®, Vielight® Fibrinogen Curcumin, TRH General support CoQ10, PEO, peptide bioregulators (heart and blood vessel), PQQ, vinpocetine
Human growth hormone (see growth hormone) Hypertension (see blood pressure) Hypothyroidism Iodine, peptide bioregulator (thyroid), thyroid IBS (irritable bowel syndrome) Symprove® Immune system improvement (also see infections) 1st Line™, ATP-Boost™, beta-glucans, carnosine, melatonin, peptide bioregulator (thymua), peptide bioregulator (thyroid), resveratrol, thymus, thyroid Infections (also see immune system improvement, anti-biotics & influenzas) 1st Line™, beta-glucans, fluconazole, silver Inflammation (reduction) Boluoke®, curcumin, PEO, pregnenolone, thymus Influenzas (also see anti-biotics, infections & immune system improvement) 1st Line™, beta-glucans, vitamin D3 Injectable products Gerovital®, IGF-1, vitamin B12 Insulin & glucose control (see diabetes)
Glucose (high) Acarbose, metformin, TRH
Intestinal flora (see probiotics)
Glycated end-products ACF228®, aminoguanidine, metformin
Intra-ear products Aldo-Spray™
Heart pulse (irregular) ATP-Boost™, thyroid
Intra-nasal products Desmopressin, GHRP6, HCGPro™, vasopressin, Vielight®
Heavy metals (chelate) DMSA, EDTA, zeolite Homocysteine TRH Lipofuscin Centrophenoxine Plaques (clots) Boluoke® Triglycerides Curcumin, PEO, TRH Hepatitis (see liver and infections)
Joints (also see bones & arthritis) Boluoke®, Novisyn®, PEO, peptide bioregulator (cartilage), pregnenolone, SAMe, thymus Kidney disorders (also see infections) Aminoguanidine, peptide bioregulator (kidney) SAMe, TRH
Herpes (also see anti-biotics) 1st Line™, ACF228™, BHT, silver
Learning (also see memory & mental stimulants) Aniracetam, desmopressin, HyPro2™, piracetam, pramiracetam, vasopressin
HIV (also see immune system improvement) 1st Line™, melatonin, naltrexone, thymus
Libido (see sex)
HCG (see HCG-Pro™) HGH (see growth hormone)
Lipids (see blood disorders) Liver disorders (also see infections) CoQ10, idebenone, peptide bioregulator (liver), pregnenolone, SAMe, silver
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Longevity enhancement (significant lifespan increases seen in animal studies) Centrophenoxine, deprenyl, melatonin, peptide bioregulator (pineal) vasopressin Lou Gehrig’s disease (see ALS) Lungs ACF228™ Breathe-Easy, centrophenoxine, glutathione, peptide bioregulator (lungs) Lupus Milnacipran, naltrexone Lyme’s 1st Line™, beta-glucans, silver Macular degeneration (see eyesight) Malaria (see anti-biotics) Menopause (see HRT) Mental stimulants (also see physical stimulants) Adrafinil, aniracetam, centrophenoxine, deprenyl, desmopressin, picamilone, piracetam, pramiracetam, vasopressin, Xan-Pro™ Memory (also see cognitive & senile dementia) General support PEO, picamilone, vinpocetine Imprinting (for later recall) Desmopressin, vasopressin Medium-long term HyPro2™ Short term Aniracetam, piracetam, pramiracetam Speed of recall Centrophenoxine Methylation (conversion of one chemical into another inside the body) ATP-Boost™, Boluoke®, Mito-Pro2™, SAMe, Xan-Pro™ Migraines (also see pain relief) Nicergoline, memantine, picamilone, vitamin B12 Mitochondrial support ATP-Boost™, CoQ10, deprenyl, glutathione, HyPro2™, idebenone, MitoQ™, NADH, oxaloacetate, PQQ, pregnenolone, SAMe Mtor inhibitors Curcumin, oxaloacetate, resveratrol Multiple Sclerosis (also see mitochondrial support) Melatonin, naltrexone, TRH Muscles (see sarcopenia) NAD+ activators NAD+Pro™
Nitric Oxide release Neo40®, Nitric Oxide saliva test strips, Vielight® Oral health care (see teeth & gums) Osteoporosis (see bone problems) Pain relief (general) ATP-Boost™, Gerovital-H3®, memantine, milnacipran, oxytocin Parasites (see infections) Parkinson’s disease (see senile dementia) Pets (see animal use) Photoaging (see skin problems) Ph balance (rebalancing) Symprove® Physical energy improvement (also see mental stimulants) ATP-Boost™, carnosine, CoQ10, idebenone, MitoQ™, NADH, oxaloacetate, PQQ, pregnenolone, SAMe PMS (pre-menstrual syndrome) PEO, peptide bioregulator (ovaries), vinpocetine Premature ejaculation/ ejaculate (also see erectile dysfunction & sex-libido) Oxytocin Probiotics Symprove® Prostate (also see cancer) DIM-Pro2™, dutasteride, finasteride, melatonin, peptide bioregulators (bladder and prostate), Prostate-Pro2™ Prolactin alteration Bromocriptine, cabergoline, GABOB PSA (prostate specific antigen- see prostate) Urination (frequent) Peptide bioregulator (bladder), vasopressin RNA (see DNA support) Sarcopenia (muscle atrophy/ wastage) GHRP2, GHRP6, peptide bioregulator (muscle), sermorelin Senile dementia (also see cognitive & memory) Alzheimer’s Centrophenoxine, curcumin, galantamine, HyPro2™, memantine, nicergoline
Nail condition Gerovital-H3®, PEO
General support aniracetam, PEO, piracetam, pramiracetam, vinpocetine
Narcolepsy (sleeping in the daytime) Adrafinil, melatonin, picamilone
Parkinson’s Bromocriptine, cabergoline, deprenyl, NADH, memantine, rasagiline
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Senility Gerovital-H3® Sex (libido, also see erectile dysfunction & premature ejaculation) Andro-Pro™, deprenyl, MSH2, oxytocin, VigorPro2™ Skin problems (also see herpes and tanning) Acne Beta-glucans Age (liver) spots Centrophenoxine, Youth Gems® face mask Anti-glycation Aminoguanidine, carnosine, Youth Gems® serum Anti-oxidant Youth Gems® day cream and night cream Cancer (non-melanoma) BEC5® Curaderm Cellulite Youth Gems® body milk Collagen Novisyn® Environmental Youth Gems® serum and face mask General support Gerovital-H3®, melatonin, PEO, thyroid Infections Silver, thymus Moisturizer Youth Gems® day cream and night cream Psoriasis Beta-glucans Scars RetinPro™ Sun spots (keratosis) BEC5® Curaderm
Stroke Aniracetam, Boluoke®, HyPro2™, idebenone, PEO, picamilone, piracetam, PQQ, pramiracetam, pregnenolone, vinpocetine Stomach (see digestive) Sublingual products Oxytocin, sermorelin, TRH Sunburn (see skin problems) Syndrome X (metabolic syndrome) Aminoguanidine, ATP-Boost™, melatonin, metformin, Mito-Pro2™, PEO Tanning (darkening the coloration of skin) MSH2 Teeth & gum disorders Doxycycline, Min-Mouth™ mouthwash, NeyDent® toothpaste, silver, zeolite Telomeres (also see DNA support) Carnosine, PEO, peptide bioregulator (pineal), TA65® Testosterone & testes (also see fertility and prostate) Anastrozole, Andro-Pro™, DIM-Pro2™, melatonin, oxytocin, peptide bioregulator (testes), TRH, VigorPro2™, zinc Topical products BEC5®, beta-glucans, Can-C™ eyedrops, Esnatri™, progesterone, RetinPro™, silver, Youth Gems® Triglycerides (see blood disorders)
Wounds Silver
Veterinarian (see animal use)
Wrinkles RetinPro™
Weight gain (muscle mass) Andro-Pro™, GABOB, GHRP6, sermorelin
Sleep disorders For less sleep Adrafinil, ATP-Boost™ For more sleep 5HTP, gabapentin, L-tryptophan, melatonin Smoking cessation 5HTP Spine issues (also see growth hormone) Novisyn®, peptide bioregulator (cartilage) Sports (see growth hormone, estrogen alteration, physical energy & testosterone)
Weight loss (appetite suppressants and fat burners) 5HTP, acarbose, aminoguanidine, ATP-Boost™, DHEA, DIM-Pro2™, galantamine, GHRP2, HCG, L-tryptophan, metformin, Mito-Pro2™, MSH2, thyroid, TRH, Xan-Pro™ Well-being (also see depression) 5HTP, aniracetam, ATP-Boost™, deprenyl, GABA, Gerovital-H3®, L-tryptophan, melatonin, Mito-Pro2™, PEO, picamilone, piracetam, pramiracetam, SAMe, thymus, thyroid, zeolite
Stem Cells Stem Cell Worx® Stress (also see cortisol) 5HTP, GABA, Gerovital-H3®, L-tryptophan, melatonin, oxytocin, picamilone, phenytoin, pregnenolone, propranolol
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A-Z INGREDIENT LIST The following list is intended to highlight the key ingredients in some products and cross reference them to the most relevant product brand names. Note: Those products with the same name as the ingredients are not shown here as they are within the A-Z product list. If you want this-
look for:
5-hydroxy-tryptophan
5HTP
Acetyl-L-Carnitine (ALC)
ATP-Boost™, Vigor-Pro2™
Adenosine triphosphate (ATP)
ATP-Boost™
Aglomelatine
Valdoxan®
Allicin (garlic)
EDTA-Pro™
Alpha lipoic acid (R-lipoic acid)
ATP-Boost™, Mito-Pro2™
Aminexil
Blueberry extracts
Andro-Pro™
Borate
Andro-Pro™, Can-C™
Boron
Andro-Pro™
Buxamin (GABOB)
Gamibetal®
Caffeine
Minox-Pro™
Calcium
Bone-Pro2™
Carboxymethylcellulose
Can-C™
Catalase
ACF228™
Dercos®
Chelation agents
Amino acids (includes di-peptides)
5HTP, ACF228™, ATPBoost™, carnosine, L-tryptophan, Mito-Pro2™
Carnosine, centrophenoxine, DMSA, EDTA-Pro™, zeolite
Choline
Centrophenoxine
Aminohydroxybutyric acid (GABOB)
Gamibetal®
Chromium polynicotinate
ACF228™
Citrulline
Neo40®
Aminosyn
Hair-Pro™
Co-dergocrine mesilate
Hydergine®
Anti-biotics
Ciproxin, doxycycline, penicillin, roxithromycin, tetracycline
Coenzyme Q10
CoQ10, Mito-Pro2™
Colloidal Silver
Silver
Colostrum
Stem Cell Worx®
Cortisol (cortisone)
Fludrocortisone, hydrocortisone
Cranberry extracts
Andro-Pro™
Creatine
Mito-Pro2™
Cresote bush
ACF228®
Cycloastragenol
TA65®
Cyclodextrin
CoQ10-SR™, Curcumin-SR™, resveratrol
Dehydroepiandrosterone
DHEA
Detox
DIM-Pro2™, EDTA-Pro™, zeolite
DHA (docosahexaenoic acid)
PEO-Pro™
Diapid®
Vasopressin
Di-IndolylMethane (DIM)
ACF228™, DIM-Pro2™
Dilantin®
Phenytoin
DMAE (dimethylaminoethanol)
Centrophenoxine
Anti-depressants
Lithium, milnacipran, moclobemide, reboxetine, Stablon®, Valdoxan®, venlafaxine
Anti-oxidants
See free radical scavengers,
Arginine
Mito-Pro2™
Arimidex®
Anastrozole
Astragalus extracts
TA65®
Azelaic acid
Minox-Pro™
Azilect®
Rasagiline
Benzoic acid
Gerovital®
Beta blocker
Propranolol
Beta alistine
Carnosine, ACF228®, Can-C™, Can-C Plus™
Beta glucan
BG-Cream™, BG-Pro™
bFGF
Hair-Pro™
BHT (butylhydroxytoluene)
ACF228™, BHT-Pro™
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DMSA (dimercaptosuccinic acid)
ACF228™, DMSA-Pro™
D-pantethine
Can-C Plus™
Dr. Dean’s recommendations
Acarbose, centrophenoxine, CurcuminSR™, Hydergine®, metformin, piracetam, Xan-Pro™
Dr. Pierpaoli’s recommendations
Melatonin, TRH
Dr. Wright’s recommendations
DHEA, Esnatri™, progesterone
Ebixa®
Memantine
EDTA (ethylene diamine tetraacetic acid)
EDTA-Pro™
Eldepryl®
Deprenyl
Electrolytes
Volt-Pro™
Enzymes
Boluoke®
EPA (eicosapentaenoic acid)
Hormones (includes hormonal support supplements)
Bio-identical: Aldosterone, DHEA, Esnatri™, melatonin, MSH, oxytocin, pregnenolone, progesterone, TRH Natural (animal): Armour® thyroid, ERFA® thyroid, Nature® thyroid, thymus, vasopressin Synthetic: Desmopressin, Eutirox® thyroid, fludrocortisone, hydrocortisone, T3-Pro™ Supporting agents: DIMPro2™, GHRP2, GHRP6, peptide bioregulators, SAMe, sermorelin
HRT (hormone replacement therapy for women)
DHEA, Esnatri™, melatonin, progesterone
PEO-Pro™
Hyaluronic acid (hyaluronan)
Hair-Pro™, Novisyn®
Ergoloid mesylate
Hydergine®, nicergoline
Hy-Pro™
Estrogens (estradiol, estriol, estrone)
Esnatri™
Hydergine (ergoloid mesylates)
Finasteride
Hair-Pro™
IGF-1 (insulin like growth factor one)
IGF-1 (LR3)
Florinef®
Fludrocortisone
Indol-3-Carbinol (I3C)
DIM
Folic acid (folate)
ACF228™, DIM-Pro2™§
Free radical scavengers
ACF228™, ATP-Boost™, BHT, glutathione, idebenone, melatonin, Mito-Pro2™, pyritinol
Fructoborate
Andro-Pro™
Iodide/ Iodine Ixel® Ketoconazole L-arginine L-carnitine L-carnosine
ACF228™, Iodine-Pro™ Milnacipran Nizoral® Mito-Pro2™ Mito-Pro2™ Carnosine, ACF228®, Can-C™, Can-C Plus™ Neo40® Can-C Plus™ ATP-Boost™, Mito-Pro2™
Fucoidan
Stem Cell Worx®
GABA (gamma-aminohydroxybutyric acid)
picamilone
GABOB
Gamibetal®
GHRP6
Release-Pro™
Ginseng
Youth Gems®
Glucophage®
Metformin
Glutathione
ACF228®, ACG
Glycerine (glycerin)
Can-C™
Glycosides
BEC5 Curaderm®
Hawthorne Berry (crataegus)
Neo40®
HGH (human growth hormone/ somatropin)
GABOB, GHRP2, GHRP6, sermorelin
L-citrulline L-histidine Lipoic acid (includes R-lipoic acid) L-methione Lucidril® Lumbrokinase Magnesium Malic Acid Manganese Meclofenoxane Melanocyte stimulating hormone Mild Silver Protein
ACF228™, Can-C Plus™ Centrophenoxine Boluoke® Andro-Pro™, Bone-Pro2™, Magnesium-Pro™, Mito-Pro2™ EDTA-Pro™ Mito-Pro2™ Centrophenoxine MSH2 Silver
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Milk protein Minerals (general) Minoxidil N-acetylcarnosine N-acetylcysteine Namenda® Neurontin® Nettle root extract Niacin (nicotinate, niacinamide, vitamin B3) Nicotinamide adenine dinucleotide Nootropil®/ Nootropyl® Nordihydroguaiaretic acid (NDGA) Omega 3 (DHA) Omega 6 (linoleic acid, GLA) Omega 9 (oleic acid) Oxythiocynate (OCSN) Parent Essential Oils (PEO) PABA (para-aminobenzoic acid) Panthenol (pantothenic acid) PCPA (paarachlorophenoxyacetic acid) Pepermint Oil Peptides Pimagedine Pomegranate extracts Potassium Prasterone Propionyl-L-carnitine Probiotics Procaine (Novocain®) Pygeum africanum Pyroloquinoline quinone Red clover herb extracts Reminyl® Resveratrol Retinolic acid (tretinoin) Ribonucleic acids (RNA)
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Bone-Pro2™ Min-Mouth™ (mouthwash), Volt-Pro™ Minox-Pro™ Can-C™ ACF228™, Can-C™ Plus Memantine Gabapentin Prostate-Pro2™ Picamilone, Xan-Pro™ NADH, PQQ Piracetam ACF228™
Salicylic acid S-Adenosyl-L-Methionine Saw palmetto (Serena Repens) Selenium
Seligiline Silver Solasodine glycosides Thiocynates Thyroids
PEO-Pro™ PEO-Pro™ PEO-Pro™ 1st Line™ PEO-Pro™ Gerovital® Mito-Pro2™ Centrophenoxine Min-Mouth™ mouth rinse GHRP2, GHRP6, peptide bioregulators, sermorelin, TRH, Youth Gems® Aminoguanidine Andro-Pro™ Gerovital®, Potassium-Pro™ DHEA Vigor-Pro2™ Symprove® Gerovital® Prostate-Pro2™ PQQ Prostate-Pro2™ Galantamine Resveratrol-SR™, Stem Cell Worx® Retirides® NeyDent® toothpaste
Thyrotropin releasing hormone Tribulus terrestris TRX Turmeric
Ubiquinone, ubiquinol
VEGF Vincamine Vinpocetine Vitamin B1 (thiamine) Vitamin B2 (riboflavin) Vitamin B3 (niacin, niacinamide) Vitamin B6 (pyridoxal, pyridoxine) Vitamin B12 (cobalamin) Vitamin C (ascorbic acid) Vitamin E (tocopherols) Vitamin K2 (menatretrenone) Yohimbine Zeolite Zinc
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HEALTH THIERRY HERTOGHE, M.D.
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GARRY GORDON, MD,DO,MD(H)
JONATHAN WRIGHT, M.D.
NICHOLAS PERRICONE, M.D.
THIERRY HERTOGHE, M.D.
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A remarkable hormone for a thinner body
HCGProâ&#x201E;¢ 250IU/5ml nasal spray Usually:$59.99 Offer price:$49.99 ONLINE CODE: HCGPRO-10-OFF-AMM6 Restrictions may apply please see IAS terms and conditions for full details. Offer valid until 31st December 2016.