"Double blind, Placebo controlled Clinical Study
Has Profound Implications for Health and Longevity"

By Todd Ovokaitys, MD

We are excited to share with you soon of Gematria's early results of our major double blind, placebo controlled clinical study. Slowing, stopping, and even reversing the biological aging process is likely to be found at the level of DNA chemistry. Recent research suggests that all the proposed mechanisms of aging have as a final common pathway discreet structural changes in DNA. The ability to intervene in these changes and recreate the structures of earlier physiologic age is now an achievable feat that may mark the birth of increasingly powerful rejuvenation technologies.

We will review the basics of DNA chemistry and the ways DNA marks the passage of time. In understanding these mechanisms we will see how methyl group transfers are intimate to these timing events and their potential reversal. Once these processes are defined, we will reveal the breakthrough discovery of high spin methyl group chemistry and suggest its implications for sustained anti-aging.

For the first time in scientific history, a randomized double blind placebo controlled clinical study has established the dose response to activated methyl group chemistry. The results indicate a dramatic reduction of physiologic aging chemistry. In addition, several clinical symptom scales showed highly statistically significant improvement in the active treatment group.

Basic DNA Chemistry: As elegant the process of translating the triplet code of a gene into a completed protein, even more sophisticated is how a cell knows which of its 100,000 genes to transcribe, how many copies, and in what timing and sequence. The 3 billion base pairs of DNA organizes coding information uniquely in each of the hundreds of different types of cells in the human body. Although many mechanisms of gene regulation are being defined, perhaps the most important single organizing principle is achieved through methyl group transfer chemistry.

The name of the simplest organic chemical group with this shape is the methyl group. A methyl group has a carbon atom in the center, a hydrogen atom at three points of a tetrahedron, and a fourth point free for the attachment to another atom or molecular group. A tetrahedron is a four-sided pyramid with triangular faces; the three hydrogen atoms make up an equilateral face that points out from the attachment bond of the methyl group.

Methyl groups modify a specific DNA base at birth to create a fifth element of DNA - cytosine bases with a methyl group bonded to the number 5 position in the cytosine ring. This modified DNA base is called 5-methyl-cytosine. The level of cytosine methylation at birth is quite significant, and varies from 2 - 6%, depending on the type of cell.

The placement of methyl groups on cytosine bases is highly information dense and creates a fingerprint that differentiates each type of cell. The presence of a methyl group tells the cell which parts of the DNA code not to transcribe for that kind of cell. These tetrahedral anchor points thus tell a muscle cell not to transcribe brain proteins, and so forth, for all cell types and functions throughout the body.

In addition, methyl groups prevent the activation of genes that could accelerate aging or induce aberrant cell growth. The placement and presence of these groups is intimate and vital to maintaining the healthy organized function of cells and tissues. The dynamics of tetrahedral methyl groups may prove to be at the core of regulating the potential for longevity.

DNA Timing Mechanisms: Recent research suggests that the final common pathway of aging is the gradual loss of methyl groups from DNA. Current proposed mechanisms of aging, such as oxidant stress, environmental toxins, vitamin and nutrient deficiencies, and activation of harmful genes all appear to accelerate methyl group loss.

Different levels of reduced DNA methylation are associated with the risk of specific health problems. A 20% loss of cytosine methylation increases the risk of certain tumors, particularly of the linings of the digestive and reproductive tracts. This represents a loss of information organization both of replication of the tissues and of ideal immune surveillance.

An approximately 40% loss of methyl groups from birth levels, for humans and other mammalian species, is usually associated with degenerative demise of the organism. Displacement of methyl groups interferes with regulating DNA functions and preserving the integrity of cells and tissues. Slowing, stopping, and reversing the loss of methyl groups from DNA is a process of slowing and even reversing aging at the level of DNA itself.

A related DNA timing mechanism is the length of the telomeres. Telos is the Greek word for 'end' so the telomeres are the ends of the chromosomes. When cells divide, the initially long sequence of telomere codons tends to chip off to a shorter length. Telomeres are likened to the protective coatings at the ends of shoestrings that prevent them from fraying. When telomere length reduces to a critical level, cells tend to lose their ability to replicate further.

The blood chemistry marker for impaired DNA methylation is elevation of homocysteine. High homocysteine levels also accelerate shortening of the telomeres. Supporting and supplementing the same chemistry that lowers homocysteine has the dual rejuvenation benefit of preserving and even boosting DNA methylation and sustaining the length of the telomeres.

Homocysteine the Overall Functional Barometer: The level of homocysteine in the blood gives a general reading of the condition of methyl group transfer chemistry in the body. The higher the homocysteine level above 6.3, the poorer the DNA methylation and the greater the associated health risks.

Homocysteine is a metabolic breakdown product of the essential amino acid methionine. It is necessary to have some homocysteine in the blood for its role in vital metabolic cycles, but beyond a relatively low threshold it becomes increasingly toxic.

Homocysteine above low levels combines with LDL cholesterol to promote oxidation. Unoxidized cholesterol even at high levels appears to be harmless to blood vessels. However, even a small amount of oxidation renders it an agent of inducing atherosclerotic changes.

Elevated homocysteine also increases the tendency of blood to clot to precipitate acute vascular thromboses, as in heart attacks and strokes. In addition, high homocysteine accelerates telomere shortening of vascular lining cells and impairs endothelial nitric oxide production, predisposing to blood vessel spasm that can restrict blood flow to tissues.

Based on all these factors, cardiovascular risks rise exponentially above a homocysteine level of 6.3, as the following chart from a large population study shows:

Thus at a level of 15, the risk of a major cardiac event is 4 times that of the general population. Also a recent study from Boston University indicates that a level over 14 carries double the risk of Alzheimer's disease. Noteworthy is that many labs call a level of up to 15 normal, resulting in what is likely widespread undertreatment of hazardously elevated levels.

In addition, homocysteine accumulates in malignant cells, altering the structure of proteins and DNA. Elevated homocysteine may thus directly increase the risk of tumor formation. Encouraging vigorous intervention, studies that have aggressively lowered homocysteine have reversed premalignant cells to normal cells and have even reversed the blood vessel narrowing of atherosclerosis.

There are three principal pathways through which the body detoxifies homocysteine. The first of these pathways uses vitamin B6 (pyridoxine) and zinc to convert homocysteine to the beneficial sulfur amino acid cysteine. The cysteine thus formed may then be used to synthesize glutathione, one of the most powerful antiaging antitumor antioxidants ever studied.

The second pathway requires folic acid and vitamin B12 and converts homocysteine to the beneficial and lipotropic amino acid methionine. Deficiencies of B12 and folic acid are well known to cause anemia, neurologic, and psychiatric problems, preventable and even reversible with supplementation.

The third and most potent pathway uses a nutrient known as trimethylglycine, or TMG. Also called betaine because it is derived naturally from beets, it has a rich supply of three methyl groups to donate. Through a specific enzyme present primarily in the liver (betaine-homocysteine methyltransferase), TMG donates a methyl group to homocysteine. This process not only drives the production of methionine, it also boosts the generation of SAMe, or S-adenosyl-methionine.

The most versatile and important methyl group donor in the body, SAMe, is formed when methionine combines with the energy molecule ATP (adenosine triphosphate). Of the few hundred known methyl group transfer reactions in the body, SAMe is the methyl group donor in about half of them. Most significantly, all of the enzymes that restore methyl groups to DNA use SAMe as the exclusive methyl group donor.

Methyl Groups - Root Currency of All Organic Chemistry: Methyl groups are used for far more than key anchors on DNA. The single carbon transfer in the form of a methyl group is the basic currency of all organic chemistry.

Methyl groups are used to make serotonin, melatonin, and other neurotransmitters. Methyl group donors support the myelination of nerves and the rebuilding of joint tissues. Numerous proteins, enzymes, and membrane lipids require methylation for optimum function. There is even an enzyme (protein isoaspartyl methyltransferase) that uses methyl group donors to rejuvenate faltering enzymes and proteins to a functional state again.

Studies using SAMe directly have shown antidepressant effects as potent as antidepressant drugs. Even more significant, SAMe can work four to six times faster and is free of serious side effects. Other studies have shown marked relief of joint pain in arthritis, and the repair of liver tissue even with cirrhosis.

The main drawback of using SAMe directly is cost - the suggested therapeutic doses of 800-1600mg per day typically cost $5-$10 per day. The second potential drawback is possible homocysteine elevation. Once SAMe donates its methyl group, it becomes homocysteine.

The Potent TMG: A safer and more cost effective method of boosting SAMe is providing TMG, which also lowers homocysteine levels. In a study conducted in the early 1950's persons who had just had a heart attack received either high dose TMG, 9 grams per day, or placebo. After one year, mortality was 25% in the placebo group, whereas the treatment group had no mortality whatsoever.

Animals fed TMG have reduced body fat and increased muscle. Supplemental TMG may increase liver SAMe levels up to fourfold and protect the liver from the harmful effects of alcohol and other hepatic toxins. TMG has also been shown to enhance athletic performance and increase endurance.

The most drastic defect of methyl group chemistry is a hereditary condition known as homocystinuria. The enzyme defects in this condition may raise homocysteine levels into the 100's. In the most severe forms even young children may develop severe vascular and neurologic disease. Although vitamins B6, B12, and folic acid may reduce homocysteine to some degree (and possibly raise SAMe), they tend to do little for clinical symptoms in this condition. In contrast, high dose TMG has not only further lowered homocysteine; in many cases it has reversed neurologic symptoms and premature aging. The only way that women with homocystinuria have conceived and had normal deliveries has been with vitamins supplemented with high levels of TMG.

Laser Molecular Stimulation for High Energy Methyl Groups: Through a patented technology used at Gematria Products, pulsed laser waves have been used to resonate TMG methyl groups to a high-energy state. This phenomenon has been measured with X-ray crystallography, a procedure that locates atoms within a crystal lattice to a high degree of precision. The crystallography readings show a significant increase in the bond angles of TMG methyl groups consistent with a marked increase in spin rate and increased free energy of the methyl group bonds.

The enhanced free energy is likely to accelerate enzymatic processes of methyl group transfers. This may facilitate DNA remethylation and even generate aging resistant DNA.

In a pilot test of activated TMG, one gram of activated TMG plus cofactors was compared to 800mg of SAMe for the ability to raise SAMe levels. Taking SAMe resulted in a low normal level of 4.9, whereas taking activated TMG gave a much higher level of 6.2 at less that one fifth the price. Joint pain that was partly relieved with SAMe achieved even greater relief with the activated TMG.

First Ever Dose Response Study: We have just completed the initial phase of data analysis of the first ever dose response study of the effects of activated TMG. A formal double blind randomized placebo controlled clinical study, the first phase of the study focused on the Heart Gems formula with activated TMG and cofactors and its effects on blood chemistry and clinical symptoms. The dramatically positive results and their implications are as follows.

In our double blind study, 40 subjects were split randomly into treatment and placebo control groups. The treatment group took increasing daily amounts of the Heart Gems formula equivalent to 2, 4, and 6 grams of activated TMG balanced with vitamin, mineral, and lipotropic cofactors for one month at each dosage level. The placebo group only received capsules of maltodextrin, a low glycemic sugar.

Statistical analysis was done on the results to derive scientific p values. A p value is the probability that a result will occur by chance alone. For example, the p value for tossing a tail in a coin flip is .5 or 50%. Values below .05 or 5% are felt to be statistically significant - the lower the value, the greater the significance of the results. A value of .001 is felt to be highly significant, and anything at or below .0001 is very highly significant for the difference between the treatment and control groups.
Homocysteine results for the treatment group at baseline, 1, 2, and 3 months were as follows:

The p values are treatment values compared to baseline, which are all very highly significant. The entire group, on average reduced to the lowest cardiac risk level.

For the placebo control group the values were as follows:

The abbreviation ns means "not significant". There was no significant change in control group levels throughout the course of the study period.

Even more dramatic is the reduction in homocysteine for the treatment group subjects that started with high homocysteine levels at or above 10.

This drop in homocysteine level is comparable to the chemistry of persons in their 60's becoming that of persons in their 20's or 30's. As each one-point drop in homocysteine may reduce cardiac risks 10-12%, this suggests an up to 60-70% risk reduction for this group.

Subjects also took intensive symptom surveys that compared them to the general population. The scores are in percentile rank, the higher the percentile the greater the symptoms. A person at the 60th percentile has more symptoms of that type than 60% of the general population.

For the anxiety scale, persons in the treatment group had the following results:

This indicates a very highly significant reduction in anxiety scale for the treatment group. There was no significant reduction in the placebo group.

Further analysis also indicates significant reductions in depression, obsessive compulsive, paranoid, hostility and global symptom scales in the active treatment group.

Blood samples have also been collected for the direct measurement of the dose response of SAMe and DNA methylation levels. This is the first such dose response study in scientific history and may give us a specific measure of the antiaging effect achieved directly at the DNA level.

As the data analysis continues we will strive to share more information as appropriate.

Based on these results, it can be strongly recommended to take 3-6 Heart Gems daily for antiaging effects at the DNA level and for general health and well being. Persons with known elevated homocysteine levels may require higher intake amounts for optimum results, best assessed with follow-up blood testing.