Recommended by Health Professionals

Oxygen bubble

COVID-19 Virus
Oxygen For Life SA (Pty) Ltd has been certified as a supplier of Essential Goods and Services during the COVID-19 Virus Outbreak by Companies & Intellectual Property Commission (CIPC).

This entitles Oxygen For Life SA (Pty) Ltd to continue operating during the Lock Down period announced by the South African President.

Click here to view the Ceritficate

Search Oxygen For Life
Click here to search the Oxygen For Life website.

Cellfood specials at

Click here for current specials on Cellfood at Dischem

Social responsibility

Click here to view what Oxygen For Life SA and Cellfood are up to.
New Cellfood study by Dr Stefan Schoeman.

Click here to read about the study and the results


The science behind cellfood

Master documents

Click on the headings below to view more information

Cellfood®: a free radical scavenger

Background

Cellfood® (Deutrosulfazyme, NuScience Corporation, USA) is a non-addictive, non-invasive, and completely non-toxic proprietary colloidal-ionic formula containing the finest all-natural, plant-based organic substances including ionic minerals, enzymes, amino acids and deuterium sulphate as traces (Iorio, 2003). Cellfood® was shown to be useful in the modulation of oxygen bioavailability in athletes (Van Heerden et al., 2001; Iorio, 2005) and in the lowering of d-ROMs test values (Alberti et al., 2000) in subjects at risk of oxidative stress (Coyle, 2004). In an analytical test for dissolved oxygen (conducted at an independent FDA certified laboratory), Cellfood® increased the amount of dissolved oxygen in water over a 60 minute period by 58%. According to Cromarty (2006) the product has no toxic effects and could possibly stimulate the immune system as verified in an in vitro lymphocyte study.

Introduction

A free radical (also known as an oxidant) can be defined as an individual or group of atoms that posses at least one unpaired electron thus making it highly reactive and unstable. Free radicals may interact with key cell components causing irreversible damage resulting in the increased development of diseases such as cancer, cardiovascular disease and other age related diseases. It is believed that anti-oxidants aid in the fight off of free radicals (Wiendow, 2009).

Why are free radicals so harmful?

It is a scientific fact that the accumulation of free radicals over an extended period of time can lead to oxidative stress. According to Heilbronn and co-workers (2006), oxidative stress refers to oxidative damage caused by reactive oxygen species (ROS). ROS is produced by various cell types and includes immune and endothelial cells, and inner cellular organelles like the mitochondria (Carter et al., 2007). These free radicals play a maladaptive role in the body by attacking lipids, protein and DNA and in the process generate a variety of products such as harmful oxidized lipids, less functional proteins, carbohydrates and nucleic acids that negatively affect normal cellular function (Heilbronn et al., 2006). It is scientifically documented that free radicals also increase in the body during stress and exercise (van der Merwe, 2004).

In the human body low levels of antioxidants, or inhibition of the antioxidant enzymes, can also cause oxidative stress. Consequently, humans have a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage. In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell. However, since ROS do have useful functions in cells, such as redox signaling, the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level (Mathews and van Holde, 1990).

As oxidative stress might be an important part of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases.

Cellfood® reduces oxidative stress

Several compounds in the blood (plasma) can oppose the oxidant potential of ROS. Virtually any compound either endogenous (GSH, thiols, proteins, uric acid, bilirubin, etc), or exogenous (b carotene, vitamins C and E, etc.), if able to donate an electron, have the ability to scavenge free radicals (Mathews and van Holde, 1990).

The effectiveness of the antioxidant plasma barrier can be evaluated by testing its ability to reduce a determined substrate (donate one or more electrons to the oxidant substance). A simple, automated test measuring the ferric reducing ability of plasma (the FRAP assay), is a novel method for assessing "antioxidant power." Ferric to ferrous ion reduction at low pH causes a colored ferrous-tripyridyltriazine complex to form. FRAP values are obtained by comparing the absorbance change at 593 nm in test reaction mixtures with those containing ferrous ions in known concentration. Absorbance changes are linear over a wide concentration range with antioxidant mixtures, including plasma, and with solutions containing one antioxidant in purified form. There is no apparent interaction between antioxidants. The FRAP assay offers a putative index of antioxidant, or reducing potential of biological fluids within the technological reach of every laboratory and researcher interested in oxidative stress and its effects (Benzie and Strain, 1996).

Using a FRAS d-Rom system (a commercial kit version of the FRAP assay), Coyle (2004) measured the reactive oxygen metabolites of 5 000 healthy subjects to establish a base value. The subject's hydroxyperoxide levels had a unimodal distribution that picked between 250 and 300 Carratelli Units (i. e. between 20 and 24 mg/dL H2O2). One Carratelli Unit (CARR U) corresponds to 0.08 mg/100 ml H2O2. The baseline chart is shown below.

CARR U

Oxidative stress level

300-320

Borderline range

321-340

Low level of oxidative stress

341-400

Medium level of oxidative stress

401-500

High level of oxidative stress

> 500

Very high level of oxidative stress


As part of the experiment, 60 subjects (32 males and 28 females) were then divided into six categories: smokers (ages 18-30 and 31-50), athletes (ages 18-30 and 31-50), obese (BMI > 30) ages 18-30 and 31-50. Each subject continued their normal lifestyle during the six week study consuming 8 drops of Cellfood® 3 times per day. Blood measurements were taken once weekly and averaged.

Before supplementation commenced, the smoker group (ages 31-50) and the athlete group (ages 18-30) experienced high levels of oxidative stress (Carr U values were higher than 400). After six weeks of Cellfood® supplementation there was a reduction of 25% and 27.5% respectively in the oxidative stress levels. The other four groups also experienced a reduction between 10 and 17%. It was interesting to note that both the athlete and smoker groups experienced high levels of oxidative stress, thus warranting the additional need to combat free radical activity and cellular damage in these populations.

Cellfood® a powerful antioxidant

It has been established that high d-ROMs values (reactive oxygen metabolites) can be reduced in both healthy and health-challenged individuals by the administration of liquid formulas containing low concentrations of antioxidants. Iorio and co-workers (2006) tested the hypothesis that Cellfood® would be able to reduce the oxidative stress in vivo due to its intrinsic antioxidant properties in vitro (Coyle, 2004).

The antioxidant activity of Cellfood® was measured by means of the BAP (Biological Antioxidant Potential) test performed with FRAS4 (Free Radical Analytical System 4). The biological antioxidant potential of Cellfood® measured 64 747 ± 3 660.5 mM (CV 5.7%) which is almost 30 times higher than the normal value of human plasma (2 200 mM). The authors concluded that the powerful antioxidant potential of Cellfood® may be ascribable to some of the specific active principles of Cellfood®, including natural extracts and antioxidant enzymes. This property can reasonably explain the ability of Cellfood® to reduce in vivo the d-ROMS test values (Coyle, 2004; Iorio et al., 2006).

References

Alberti, A., Bolognini, L., Macciantelli, D., and Carratelli, M. 2000. The radical cation N,N-diethyl-para-phenylendiamine: a possible indicator of oxidative stress in biological samples. Res Chem Intermed 26 (3): 253-267

Benzie, I.F.F and Strain, J.J. 1996. The ferric reducing ability of plasma (FRAP) as a measure of “Antioxidant Power”: the FRAP assay. Analytical Biochemistry 239: 70-76

Carter, C.S., Hofer, T., Seo, A.Y. and Leeiwenburgh, C. 2007. Molecular mechanisms of life and health-span extension: Role of calorie restriction and exercise intervention. Nutr. Metab. 32: 954-966

Coyle, M. 2004. Free radical clinical study by laboratory tests. NuScience Corporation. Health products update

Cromarty, A.D. 2006. Toxicity test results: Lymphocyte survival/proliferation assay using varying concentrations of three tested compounds: Cellfood, NCODE and Switch. Research report - Department of Pharmacology and Biomedical Research, University of Pretoria (RSA)

Heilbronn, L.K., de Jonge, L. and Frisard, M.I. 2006. Effects of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals. American Medical Association 295 (13):1539-1547

Iorio, E.L. 2003. Deutrosulfazyme (Cellfood®). Overview clinico-farmacologica. Proceedings International Conference Safety Evaluation of Complementary and Alternative Medicine October 24-25

Iorio, E.L. 2005. Oxidative stress, sport trauma and rehabilitation. New proposals for an integrated approach. Proceedings XIV International Congress on Sports Rehabilitation and Traumatology. “The accelerated rehabilitation of the injured athlete” April 9-10: pp 127

Iorio, E.L., Bianchi, L., and Storti, A. 2006. Cellfood® (Deutrosulfazyme): a powerful antioxidant. Preliminary scientific study (International Observatory of Oxidative Stress, Free Radicals and Antioxidant Systems - Parma, Italy)

Mathews, C.K. and van Holde, K.E. 1990. Biochemistry. The Benjamin/Cummings Publishing Company Inc

Van der Merwe, A. 2004. Stress solutions. Understand and manage your stress for a balanced, energised life. Tafelberg Publishers, Cape Town

Van Heerden, J, De Ath, K, and Nolte, H. 2001. Product Efficacy Report. The study on the effects of Cellfood® on elite athletes. Institute for Sport Research, University of Pretoria (South Africa)

Wiendow, R.A. 2009. Biological and physiological ageing. Research Starters 1-5

Free radicals and oxidative stress

Introduction

Free radicals are normally present in the body in relative small amounts. An excess can be produced by different factors such as exposure to radiation (sun rays or medical x-rays), exposure to environmental pollutants such as vehicle exhaust fumes and tobacco smoke, exposure to medicines, toxins, chemicals and foods high in fat and unhealthy oils.

A free radical can be defined as an individual or group of atoms that posses at least one unpaired electron thus making it highly reactive and unstable. It interacts with key cell components causing irreversible damage to a cell resulting in the increased development of diseases such as cancer, cardiovascular disease and other age related diseases. It is believed that anti-oxidants aid in the fight off of free radicals (Wiendow, 2009).

2. Why are free radicals so harmful?

Free radicals are compounds such as oxygen, hydrogen peroxide, or hydroxyl groups that have lost an electron. These unstable molecules latch onto another molecule, "stealing" its electrons, which in turn try to steal an electron from another molecule. This process happens usually at a nearby cell membrane, setting off a chain reaction of free-radical formations called lipid peroxidation, which ultimately leads to damage.

Free radicals, also known as oxidants, are increasingly recognised as being responsible for tissue and organ damage, which could lead to the functional disturbances associated with chronic degenerative diseases (Serfontein, 2001). Free radicals can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins. Damage to DNA can cause mutations and possibly cancer, if not reversed by DNA repair mechanisms, while damage to proteins causes enzyme inhibition, denaturation and protein degradation (Mathews and van Holde, 1990).

Accumulation of free radicals over an extended period of time can lead to oxidative stress. According to Heilbronn and co-workers (2006), oxidative stress refers to oxidative damage caused by reactive oxygen species (ROS) resulting in cancer, premature aging and ultimately death.

ROS is produced by various cell types and includes immune and endothelial cells, and inner cellular organelles like the mitochondria (Carter et al., 2007). ROS plays a maladaptive role in the body by attacking lipids, protein and DNA and in the process generates a variety of products such as harmful oxidized lipids, less functional proteins, carbohydrates and nucleic acids that negatively affect normal cellular function (Heilbronn et al., 2006).

Free radicals increase in the body during stress and exercise (van der Merwe, 2004). They cause oxidative stress to the body and may contribute to more than sixty other health conditions, including:

  • atherosclerosis and heart disease
  • increased aging of bones, organs, brain and skin
  • interference with cell replication
  • malignant tissue formation
  • enzyme malfunction

3. How does the body cope?

An antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons from a substance to an oxidizing agent. Oxidation reactions can produce free radicals, which start chain reactions that damage cells. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions by being oxidized themselves. As a result, antioxidants are often reducing agents such as thiols, ascorbic acid or polyphenols (Mathews and van Holde, 1990; Serfontein, 2001).

Although oxidation reactions are crucial for life, they can also be damaging; hence, plants and animals maintain complex systems of multiple types of antioxidants, such as glutathione, vitamin C, and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases.

Low levels of antioxidants, or inhibition of the antioxidant enzymes, causes oxidative stress and may damage or kill cells. Consequently, organisms contain a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage to cellular components such as DNA, proteins and lipids. In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell. However, since reactive oxygen species do have useful functions in cells, such as redox signaling, the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level.

As oxidative stress might be an important part of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases.

4. Oxidative stress in disease

Oxidative stress is thought to contribute to the development of a wide range of diseases including Alzheimer's disease, Parkinson's disease, the pathologies caused by diabetes, rheumatoid arthritis, and neurodegeneration in motor neuron diseases. In many of these cases, it is unclear if oxidants trigger the disease, or if they are produced as a secondary consequence of the disease and from general tissue damage. One case in which this link is particularly well-understood is the role of oxidative stress in cardiovascular disease. Here, low density lipoprotein (LDL) oxidation appears to trigger the process of atherogenesis, which results in atherosclerosis, and finally cardiovascular disease (Serfontein, 2001).

The brain is uniquely vulnerable to oxidative injury, due to its high metabolic rate and elevated levels of polyunsaturated lipids, the target of lipid peroxidation. Consequently, antioxidants are commonly used as medications to treat various forms of brain injury. These compounds appear to prevent oxidative stress in neurons and prevent apoptosis and neurological damage. Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and as a way to prevent noise-induced hearing loss.

Antioxidants can cancel out the cell-damaging effects of free radicals. Furthermore, people who eat fruits and vegetables, which happen to be good sources of antioxidants, have a lower risk of heart disease and some neurological diseases, and there is evidence that some types of vegetables, and fruits in general, protect against a number of cancers (Serfontein, 2001). There is also evidence that antioxidants might help prevent other diseases such as suppressed immunity due to poor nutrition, neurodegeneration, and macular degeneration.

5. Classification of antioxidants

Antioxidants are generally classified into two broad divisions, depending on whether they are soluble in water (hydrophilic) or in lipids (hydrophobic). Hydrophilic antioxidants react with oxidants (free radicals) in the cell cytosol and the blood plasma, while lipid-soluble antioxidants protect cell membranes from lipid peroxidation. These compounds may be synthesized in the body or obtained from the diet.

The different antioxidants are present at a wide range of concentrations in body fluids and tissues, with some such as glutathione or ubiquinone mostly present within cells, while others such as uric acid are more evenly distributed. Some antioxidants are only found in a few organisms and these compounds can be important in pathogens and can be virulence factors.

The relative importance and interactions between these different antioxidants is a very complex question, with the various metabolites and enzyme systems having synergistic and interdependent effects on one another. The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system. The amount of protection provided by any one antioxidant will also depend on its concentration, its reactivity towards the particular reactive oxygen species being considered, and the status of the antioxidants with which it interacts.

Some compounds contribute to antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. Particularly important is the ability to sequester iron, which is the function of iron-binding proteins such as transferrin and ferritin. Selenium and zinc are commonly referred to as antioxidant nutrients, but these chemical elements have no antioxidant action themselves and are instead required for the activity of some antioxidant enzymes.

5.1 Ascorbic acid

Ascorbic acid is a monosaccharide antioxidant found in both animals and plants. As one of the enzymes needed to make ascorbic acid has been lost by mutation, it must be obtained from the diet and is a vitamin. Most other animals are able to produce this compound in their bodies and do not require it in their diets. In cells, it is maintained in its reduced form by reaction with glutathione, which can be catalysed by protein disulfide isomerase and glutaredoxins. Ascorbic acid is a reducing agent and can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide. In addition to its direct antioxidant effects, ascorbic acid is also a substrate for the antioxidant enzyme ascorbate peroxidase, a function that is particularly important in stress resistance in plants.

5.2 Glutathione

Glutathione is a cysteine-containing peptide found in most forms of aerobic life. It is not required in the diet and is instead synthesized in cells from its constituent amino acids. Glutathione has antioxidant properties since the thiol group in its cysteine moiety is a reducing agent and can be reversibly oxidized and reduced. In cells, glutathione is maintained in the reduced form by the enzyme glutathione reductase and in turn reduces other metabolites and enzyme systems, such as ascorbate in the glutathione-ascorbate cycle, glutathione peroxidases and glutaredoxins, as well as reacting directly with oxidants. Due to its high concentration and its central role in maintaining the cell's redox state, glutathione is one of the most important cellular antioxidants (Mathews and van Holde, 1990).

5.3 Melatonin

Melatonin is a powerful antioxidant that can easily cross cell membranes and the blood-brain barrier. Unlike other antioxidants, melatonin does not undergo redox cycling, which is the ability of a molecule to undergo repeated reduction and oxidation. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants and promote free radical formation. Melatonin, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.

5.4 Vitamin E

Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties. Of these, α-tocopherol has been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolising this form.

It has been claimed that the α-tocopherol form is the most important lipid-soluble antioxidant, and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. This removes the free radical intermediates and prevents the propagation reaction from continuing. This reaction produces oxidised α-tocopheroxyl radicals that can be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol (Mathews and van Holde, 1990).

6. Pro-oxidant activities

Antioxidants that are reducing agents can also act as pro-oxidants. For example, vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide, however, it will also reduce metal ions that generate free radicals through the Fenton reaction.

2 Fe3+ + ascorbate → 2 Fe2+ + dehydroascorbate
2 Fe2+ + 2 H2O2 → 2 Fe3+ + 2 OH• + 2 OH−

The relative importance of the antioxidant and pro-oxidant activities of antioxidants are an area of current research, but vitamin C, for example, appears to have a mostly antioxidant action in the body.

7. Enzyme systems

As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes. Here, the superoxide released by processes such as oxidative phosphorylation is first converted to hydrogen peroxide and then further reduced to give water. This detoxification pathway is the result of multiple enzymes, with superoxide dismutases catalysing the first step and then catalases and various peroxidases removing hydrogen peroxide (Mathews and van Holde, 1990).

7.1 Superoxide dismutase, catalase and peroxiredoxins

Superoxide dismutases (SODs) are a class of closely related enzymes that catalyse the breakdown of the superoxide anion into oxygen and hydrogen peroxide. SOD enzymes are present in almost all aerobic cells and in extracellular fluids. Superoxide dismutase enzymes contain metal ion cofactors that, depending on the isozyme, can be copper, zinc, manganese or iron. In humans, the copper/zinc SOD is present in the cytosol, while manganese SOD is present in the mitochondrion. There also exists a third form of SOD in extracellular fluids, which contains copper and zinc in its active sites.

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor. This protein is localized to peroxisomes in most eukaryotic cells.

Peroxiredoxins are peroxidases that catalyze the reduction of hydrogen peroxide, organic hydroperoxides, as well as peroxynitrite. These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the active site is oxidized to a sulfenic acid by the peroxide substrate.

In its active state, thioredoxin acts as an efficient reducing agent, scavenging reactive oxygen species and maintaining other proteins in their reduced state. After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using NADPH as an electron donor.

The glutathione system includes glutathione, glutathione reductase, glutathione peroxidases and glutathione S-transferases. Glutathione peroxidase is an enzyme containing four selenium-cofactors that catalyzes the breakdown of hydrogen peroxide and organic hydroperoxides. There are at least four different glutathione peroxidase isozymes in animals. Glutathione peroxidase 1 is the most abundant and is a very efficient scavenger of hydrogen peroxide, while glutathione peroxidase 4 is most active with lipid hydroperoxides. In addition, the glutathione S-transferases show high activity with lipid peroxides. These enzymes are at particularly high levels in the liver and also serve in detoxification metabolism (Mathews and van Holde, 1990).

8. Physical exercise

During exercise, oxygen consumption can increase by a factor 10 or more. Energy production involves reduction of molecular oxygen (O2); the reduction is not always complete, and about 2-5% of the molecular oxygen turns into the superoxide radical, O2-. This increase in free radicals may result in damage that contributes to muscular fatigue during and after exercise (Burke and Deakin, 2010

The inflammatory response that occurs after strenuous exercise is also associated with oxidative stress, especially in the 24 hours after an exercise session. The immune system response to the damage done by exercise peaks 2 to 7 days after exercise, which is the period during which most of the adaptation that leads to greater fitness, occurs. During this process, free radicals are also produced by neutrophils to remove damaged tissue.

References

Burke, L. and Deakin, C. 2010. Clinical sports nutrition. 4th ed. McGraw-Hill Australia.

Carter, C.S., Hofer, T., Seo, A.Y. and Leeiwenburgh, C. 2007. Molecular mechanisms of life and health-span extension: Role of calorie restriction and exercise intervention. Nutr. Metab. 32: 954-966.

Heilbronn, L.K., de Jonge, L. and Frisard, M.I. 2006. Effects of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals. American Medical Association. 295 (13):1539-1547.

Mathews, C.K. and van Holde, K.E. 1990. Biochemistry. The Benjamin/Cummings Publishing Company Inc.

Serfontein, W. 2001. New nutrition. Transform your life. Tafelberg Publishers, Cape Town.

Van der Merwe, A. 2004. Stress solutions. Understand and manage your stress for a balanced, energised life. Tafelberg Publishers, Cape Town.

Wiendow, R.A. 2009. Biological and physiological ageing. Research Starters. 1-5.

Homocysteine and diabetes mellitus

What is the link between high levels of homocysteine and diabetes mellitus with reference to the risk for coronary heart disease?

Introduction

Over 200 million people world-wide suffer from diabetes mellitus (DM). The incidence is increasing and some scientists predict that in the next 20-25 years, as life expectancy increases, this number will exceed 300 million. DM is characterised by hyperglycaemia. Two major types of DM are described: type I or more commonly known as insulin dependent diabetes mellitus (IDDM), and type II known as non-insulin dependent diabetes mellitus (NIDDM). Type I affects approximately 15% of all people with diabetes whereas type II affects approximately 85%. In normal individuals, blood glucose levels in the body are tightly regulated between 3.5 and 5.5 mmol/l by a myriad of hormones acting on a number of tissues including the kidney, liver, muscle and adipose tissues (Mathai et al., 2007).

Diabetes and vascular disease

“Diabetic complications are predominantly due to microvascular and macrovascular damage. Microvascular complications include renal failure, blindness and symptomatic sensorimotor neuropathy; macrovascular complications include coronary artery and peripheral vascular disease. In the last 10 years, large scale clinical studies have shown the link between good long term glycaemic control and a reduction in these complications in type I and II diabetes.

The molecular and cellular mechanisms underlying the vascular pathology in DM are probably multifactorial. The primary target is the endothelial cell which lines both large and small blood vessels and maintains vascular integrity by acting as a selective barrier to transvascular flux. The endothelial cell has a myriad of functions including regulation of cell adhesion, fibrinolysis, thrombosis, extracellular matrix production and in maintaining vascular tone. These functions are stimulated by flow and mechanical stress and mediated through the production of antioxidants, antithrombotics and anti-adhesives. These mechanisms afford protection to the integrity of the microvessel. Vasoactive regulators produced by the endothelium include arachidonic acid products and nitric oxide. Nitric oxide is the major regulator of flow dependent dilatation after increased arteriolar flow. The failure of tissues to regulate blood flow is one of the major functional problems thought to contribute to vascular damage in diabetes.” - Mathai et al., 2007.

Homocysteine and vascular disease (Mathai et al., 2007)

“McCully first postulated a link between elevated homocysteine concentrations and vascular disease in homocystinuric patients. Patients with this condition have fasting homocysteine levels over 100 mmol/l compared with general population concentrations of less than 10 mmol/l. In homocystinuria, 50% of patients suffer thromboembolic or atherosclerotic events before 30 years. Homocystinuria is essentially a metabolic disorder characterised by defects in the remethylation or catabolism of homocysteine resulting in elevated homocysteine concentrations. Irrespective of the underlying metabolic defect the risk of vasculopathy is the same. This suggests that homocysteine, and not the metabolic block, is responsible for disease.

In the last 25 years a large number of prospective studies have confirmed that homocysteine is an independent risk factor for vascular disease in the general population. One in seventy people show elevated levels, the majority of which are due to genetic or nutritional factors. Evidence for causality comes from a number of studies of which a synthesis is listed below:

  • Elevations in homocysteine occur before the onset of vascular disease.
  • Elevated homocysteine levels show the same strong graded risk effect for both micro and macrovascular complications, performed across different continents, using different research methodologies. These studies include genetic and other causes of raised homocysteine levels.
  • Homocysteine lowering treatment decreases blood pressure, reverses endothelial dysfunction and decreases the rate of coronary re-stenosis.
  • In vitro and in vivo work confirm that homocysteine is both atherogenic and thrombogenic, providing biological plausibility for causality.

 

What are the mechanisms through which homocysteine may promote damage?

An association between elevated levels of homocysteine and the vascular complications of diabetes has been reported by several research groups (Hoogeveen et al., 1998). In patients with diabetes, elevated homocysteine levels have been reported to be associated with endothelial dysfunction (Hofmann et al., 1998), insulin resistance (Meigs et al., 2001), prothrombotic state (Aso et al., 2004), macroangiopathy Smulders et al., 1999; Buysshaert et al., 2000) and nephropathy (Buysschaert et al., 2000; Davies et al., 2001; Emoto et al., 2001).

A host of mechanisms through which homocysteine may promote vascular damage (Welch and Loscalzo, 1998), as well as a synergism between homocysteine and diabetic status have been reported (Hofmann et al., 1998). Of note, several studies have demonstrated that elevated homocysteine levels predict the risk of death or coronary events in patients with type 2 diabetes mellitus (Kark et al., 1999; Stehouwer et al., 1999; Hoogeveen et al., 2000). In patients with type 2 diabetes, however, plasma homocysteine levels have been reported to be increased, unchanged or decreased. Conflicting results regarding the circulating levels of homocysteine in patients with diabetes may relate to heterogeneity of the patients included, particularly with regard to renal function status and presence of vascular arterial disease. Another important reason for conflicting results may relate to the remarkably small numbers of patients included in the studies assessing circulating homocysteine levels in patients with diabetes (Ndrepepa et al., 2008).

Only a few studies have dealt with the link between hyperhomocysteinemia and macroangiopathy in diabetic patients. However, all these studies report a strong association between total homocysteine (tHcy) and macrovascular lesions (see review by Buysshaert et al. (2007). Buysshaert and co-workers (2000) studied 122 type 2 diabetic subjects and presented evidence that the prevalence of macroangiopathy was higher in individuals with hyperhomocysteinemia than in those without hyperhomocysteinemia (70% versus 42%, p < 0.01), even when other confounding risk factors were taken into account (in particular renal function).

In a study by Rudy and co-workers (2005) diabetic patients with coronary artery disease had higher tHcy in comparison with diabetic individuals without vascular lesions; homocysteine levels correlated significantly with incidence of ischemic heart disease. These results are in keeping with data from Becker et al. (2003), who showed that among type 2 diabetic individuals, the risk of coronary events increased by 28% for each 5 mmol/l increment of tHcy, independent of traditional cardiovascular risk factors. The study of Hoogeveen et al. (2000) indicated that hyperhomocysteinemia appeared to be a higher (1.9-fold) risk factor for mortality in type 2 diabetic patients than in non-diabetic subjects. Soinio et al. (2004) extended these results by showing that type 2 diabetic patients with tHcy above 15 mmol/l had a heightened risk of coronary heart disease mortality during a 7-year follow-up than those with levels below 15 mmol/l, even after adjustment for confounding variables.

In type 1 diabetic patients, Hofmann and co-workers (1998) observed a macroangiopathy prevalence of 57 and 33%, respectively, in the presence and absence of hyperhomocysteinemia. This increased prevalence was confirmed by Agullo´-Ortuno and co-workers (2002).

Can homocysteine levels be lowered by nutritional supplements?

Homocysteine is either re-methylated to methionine by a vitamin B12 and folate-dependent enzyme (5-methyltetrahydrofolate-homocysteine methyltransferase), or is irreversibly catabolised by the transsulphuration pathway, which utilises vitamin B6 (pyridoxal-5'-phosphate) in at least one enzyme-catalysed reaction (Figure 1). Defects in either of these pathways will result in hyperhomocysteinemia. Such a defect can either be caused by a) a deficiency of one of the essential co-factors for normal homocysteine metabolism; vitamin B12, vitamin B6 or folate, or b) certain enzyme variants, which may also cause hyperhomocysteinemia.

For efficient homocysteine metabolism, an adequate supply of vitamin B12, vitamin B6, folic acid, zinc and trimethylglycine (betaine) is required. However, during food refinement and processing, losses of these nutrients may occur (Van Brummelen 2005 and 2007).

Vitamin and mineral supplementation and homocysteine

A daily vitamin supplement (containing vitamin B6, folic acid and vitamin B12) normalised elevated circulating homocysteine levels in patients within six weeks of treatment (Ubbink et al., 1993). This was in agreement with Brattstrom's studies (Brattstrom et al., 1988), which investigated the effect of vitamin B12, vitamin B6 and folic acid on circulating homocysteine levels. Magnesium is also an essential co-factor for the enzyme methionine adenosyl transferase, which forms SAM from L-methionine. It is thus clear that the vitamin and mineral status is an important determinant of circulating homocysteine levels (Van Brummelen, 2005).

In a clinical trial conducted at the ISR (University of Pretoria), Kruger and co-workers (2009) studied the efficacy of NCODE (Cellfood Longevity) on physical performance and selected markers of health status in males. Twenty healthy sedentary volunteers between the ages of 30 and 60 years with a homocysteine level higher than 10 mmol/l were included in the study. Some of the findings were as follow:

  • Statistically significant increase in serum folate
  • Statistically significant reduction in homocysteine (15%) 
  • No change in urate levels

 

Conclusion

Reducing homocysteine will not only benefit diabetics, but also non-diabetics suffering from other chronic conditions.


References

Agullo´-Ortuno M, Albaladejo M, Parra S, Rodriguez-Manotas M, Fenollar M, and Ruiz-Espejo F. 2002. Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus. Clin Chim Acta; 326:105-112.

Aso Y, Yoshida N, Okumura K, Wakabayashi S, Matsutomo R, and Takebayashi K. 2004. Coagulation and inflammation in overt diabetic nephropathy: association with hyperhomocysteinemia. Clin Chim Acta; 348:139-145.

Becker A, Kostense P, Bos G, Heine R, Dekker J, and Nijpels G. 2003. Hyperhomocysteinemia is associated with coronary events in type 2 diabetes. J Intern Med; 253:293-300.

Brattstrom LE, Israelson B, Jeppson JO, and Hultberg BL. 1988. Folic acid an innocuous means to reduce plasma homocysteine. Scandinavian Journal Clinical and Laboratory Investigation;48: 215-221.

Buysschaert M, Dramais AS, Wallemacq P, and Hermans MP. 2000. Hyperhomocysteinemia in type 2 diabetes. Diabetes Care; 23:1816-1822.

Buysshaert M, Preumont V, and Hermans M P. 2007. Hyperhomocysteinemia and diabetic macroangiopathy: guilty or innocent bystander? A literature review of the current dilemma. Diabetes and Metabolic Syndrome: Clinical Research and Reviews; 1: 53-59.

Davies L, Wilmshurst EG, McElduff A, Gunton J, Clifton-Bligh P, and Fulcher GR. 2001. The relationship between homocysteine, creatinine clearance, and albuminuria in patients with type 2 diabetes. Diabetes Care; 24: 1805-1809.

Emoto M, Kanda H, Shoji T, Kawagishi T, Komatsu M, and Mori Kl. 2001. Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes. Diabetes Care; 24:533-538.

Hofmann MA, Kohl B, Zumbach M, Borcea V, Bierhaus A, and Henkels M. 1998 Homocysteinaemia and endothelial dysfunction in IDDM. Diabetes Care; 21:841-848.

Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, and Bouter LM. 1998. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol; 18:133-138.

Hoogeveen EK, Kostense PJ, Jakobs C, Dekker J, Nijpels G, and Heine RJ. 2000. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation; 101:1506-1511.

Kark JD, Selhub J, Bostom A, Adler B, and Rosenberg IH. 1999. Plasma homocysteine and all-cause mortality in diabetes. Lancet; 353:1936-1937.

Kruger PE, Wood PS, Grant R, and Clark J. 2009. Efficacy of NCODE (Cellfood Longevity) on physical performance and selected markers of health status in males. Research report, Institute for Sports Research, University of Pretoria.

Mathai M, Radford SE, and Holland P. 2007. Progressive glycosylation of albumin and its effect on the binding of homocysteine may be a key step in the pathogenesis of vascular damage in diabetes mellitus. Medical Hypotheses; 69: 166–172.

Meigs JB, Jacques PF, Selhub J, Singer DE, Nathan DM, and Rifai N. 2001. Framingham Offspring Study. Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study. Diabetes Care; 24: 1403-1410.

Ndrepepa G, Kastrati A, Braun S, Koch W, Kolling K, Mehilli J, and Schomig A. 2008. Circulating homocysteine levels in patients with type 2 diabetes mellitus. Nutrition, Metabolism and Cardiovascular Diseases; 18: 66-73.

Rudy A, Kowalska I, Straczkowski M, and Kinalska I. 2005. Homocysteine concentrations and vascular complications in patients with type 2 diabetes. Diabetes Metab; 31:112-117.

Santora R, and Kozar RA. 2009. Research review. Molecular mechanisms of pharmaconutrients. Journal of Surgical Research; 1-7.

Smulders YM, Rakic M, Slaats EH, Treskes M, Sijbrands EJ, and Odekerken DA. 1999. Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and cardiovascular disease. Diabetes Care; 22:125-132.

Soinio M, Marniemi J, Laakso M, Lehto S, and Ronnemaa T. 2004. Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus. Ann Intern Med; 140:94-100.

Stehouwer CD, Gall MA, Hougaard P, Jakobs C, and Parving HH. 1999. Plasma homocysteine concentration predicts mortality in non-insulin-dependent diabetic patients with and without albuminuria. Kidney Int; 55:308-314.

Ubbink JB, Vermaak WJH, Bennett JM, Becker PJ, Van Staden DA and Bissbort S. 1991. The prevalence of homocysteinemia and hypercholesterolemia in angiographically defined coronary heart disease. Klinische Wochenschribe;69: 527-534.

Ubbink JB, Vermaak WJH, Van der Merwe A, and Becker PJ. 1993. The nutritional status of vitamin B-12, vitamin B-6 and folate in men with hyperhomocysteinemia. The American Journal of Clinical Nutrition;57: 47-53.

Ueland PM, and Refsum H. 1989. Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease, and drug therapy. The Journal of Laboratory and Clinical Medicine;114: 473- 501.

Van Brummelen R. 2005. L-methionine as immune-supportive supplement in HIV and other immune-deficient conditions: a clinical study. Doctoral thesis, Tshwane University of Technology, Pretoria, South Africa.

Van Brummelen R, and du Toit D. 2007. L-methionine as immune supportive supplement: a clinical evaluation. Amino Acids; 33: 157-163.

Verhoef et al. 1996. American Journal of Epidemiology; 143: 845 – 859.

Welch GN, and Loscalzo J. 1998. Homocysteine and atherothrombosis. N Engl J Med; 338:1042-1050.

Health benefits of supplemental nucleic acids

By Todd Ovokaitys MD

Introduction

In this era of an increasingly enlightened public about the health benefits of nutritional supplements, there is a new area perhaps more overlooked than any other. This central area of health and nutrition is the ingestion of dietary nucleic acid bases - the essential building blocks of DNA and RNA.

The main reason these highly important nutrients have been neglected is that the body is able to manufacture nucleic acid bases from amino acids and other basic nutrients. In general, if the body can make a substance from other nutrients that substance is not considered to be essential. However, under certain conditions, the body is not able to make enough DNA and RNA bases to support the needs of the body’s tissues and organs, equating to a drastic reduction in the potential for good health.

Numerous studies in animals and humans show dramatic benefits in health, function, and survival with the supplementation of nucleic acid elements. These effects are so powerful that survival in life threatening assaults, ranging from radiation to infection to shock, has been markedly increased. From the standpoint of longevity studies, no single method has increased longevity more than supplementing DNA and RNA elements.

Metabolism of DNA and RNA (Cosgrove, 1998)

Five nucleic acid bases make up the information code of life. Both DNA and RNA share three of the bases - adenine, guanine, and cytosine. In DNA, the fourth base is thymine, whereas in RNA it is uracil. In DNA, each base combines with a five-carbon sugar called deoxyribose, hence the term DNA stands for deoxyribonucleic acid. In RNA, each base combines with the five-carbon sugar ribose, thus RNA stands for ribonucleic acid. 

The information code in DNA in the cell nucleus is transcribed to RNA, which is then translated to all the enzymes and proteins made in the body. The DNA to RNA to protein translation mechanism makes possible the vast diversity of life on earth.

When DNA and RNA are ingested intact, they are intensely metabolized by intestinal bacteria and the intestinal lining. Over 95% of the pyrimidines bases cytosine, thymine, and uracil are degraded by the intestinal lining before reaching the blood stream. Only about 3% of the pyrimidines make it to the liver for further use in the body. The fate of the purine bases adenine and guanine is even more extreme. Over 99% of the purines are broken down to uric acid before being absorbed into the bloodstream.  Therefore only a tiny fraction of ingested DNA or RNA becomes available for the numerous functions required of them throughout all the cells of the body.

In addition to ingested DNA and RNA elements, the body can make DNA and RNA bases from simpler nutrients in the diet. In particular, the amino acids glycine, glutamine, serine, and aspartic acid, along with vitamin cofactors are used to make DNA and RNA bases from scratch.

In order to make nucleic acids from simpler substances requires having all of the precursors and cofactors in adequate amounts at the time of production. In addition, it requires having sufficient amounts of numerous enzymes in the correct proportions and locations in the cell.

Recent evidence indicates that the body is often not able to make enough DNA and RNA to protect, repair, and regenerate cells to their optimum function. This is especially true for cells that have high turnover rates such as the intestinal lining that may fully replace itself every week. The demand for production may particularly exceed synthetic capacity under conditions of stress in which the demand for greater cell activity and function becomes acute, particularly for the dynamic populations of cells in the immune system.

When demand exceeds production capacity, DNA and RNA base components become essential nutrients for protecting and preserving health. Numerous lines of evidence will be presented to show the far reaching health benefits of supplementing DNA and RNA during health stresses and even for general well being and longevity (Mathers, 2006).

Advantages of an Oral Spray Delivery System

Providing the nucleic acid base components in this form can increase their absorption into the bloodstream highly significantly. Instead of only 1-3% delivery to the blood stream for systemic use, the oral spray may effectively deliver 90% or more of the nucleic acids ingested to cells and tissues throughout the body.

It is very important to make the distinction between chains of DNA and the individual bases of DNA.  Intact DNA strands are long chains of individual bases strung together into a double helix that may have over 10 million bases linked together into a single enormous molecule. Intact DNA strands provide a linear code for the production of proteins and enzymes. Therefore intact strands of DNA bases are information containing and have a small but real potential for influencing DNA information in the cell nucleus. Long chains of DNA require extensive digestion to extract individual bases, resulting in poor absorption and only a small fraction of the bases being available for the body to use.

In contrast, the individual bases of DNA do not give sequence information. They are simply building blocks, much as the letters of the alphabet are the building blocks for words. Their small molecular size makes them highly and rapidly absorbable, greatly increasing their ability to be assimilated and used in cells and tissues throughout the entire body. They are nutritional and not informational. They are very safe and help the body repair and rebuild the DNA and RNA needed for health and cell regeneration.

absorption_chart

Research studies with supplemental DNA and RNA (Carver and Walker, 1995)

Numerous published scientific studies indicate very significant health benefits from DNA and RNA component supplementation (Slobodianik, 2003). Almost every system of the body has documentation of improved health, vitality, or function from providing supplements of these fundamentally important cellular elements, from infancy to advanced age. The following is a brief summary from the vast literature supporting the many published benefits of the supplemental nucleic acids and related metabolic systems.

3A. Infections

Staph aureus is one of the most aggressive bacterial infections faced in medical treatment. It tends to cause deep-seated abscess forming infections, often associated with extensive tissue destruction, high fever, and resistance to treatment. Surgical drainage is often required to clear pockets of infection. Without surgery, antibiotics alone are often ineffective at eradicating this invasive pathogen. Epidemics of Staph aureus resistant to all antibiotics have become a devastating problem in hospitals and treatment centers around the world.

A study in mice was performed to assess the ability of supplemental nucleic acid components to modify the course of virulent Staph aureus infection. The control animals that received no additional RNA or DNA elements showed a raging 71% mortality. In contrast, the animals that were supplemented with nucleic acid bases by injection showed vastly reduced mortality to 21% (Odens, 1970).

Candida is a form of yeast that frequently causes infections in humans. If Candida gets into the human bloodstream and persists, medical complications and mortality tend to be very significant. In experimental blood borne Candida infections in mice, the nucleic acid supplemented animals had a much higher survival rate than the untreated control animals.   

These experiments suggest that supplemental DNA and RNA bases given in a form with absorption comparable to injection may strengthen the body to combat serious infections. This is likely to occur through improved immune function, although factors related to generally strengthening the vitality of tissues may also be a factor.

The very high absorbability individual nucleic acid bases by oral spray may support the immune system and general tissue vitality with a high degree of potency. Such supplemental support can help provide an added measure of resilience to sustain health or recover from infection.

3B. Cancer

A study in mice assessed whether RNA supplementation improved survival from an aggressive cancer (Rigby, 1971). The animals received a tumor vaccine and then transplants of a tumor cell line. The animals that only received the tumor vaccine all died within three weeks. In sharp contrast, the animals that received injections of RNA after the tumor vaccine had a 40% long-term survival. Thus the support of an anti-tumor program with only supplemental RNA provided a dramatic improvement in survival and outcome.

3C. Radiation injury

Ionizing radiation causes intense free radical generation and molecular fragmentation; the greater the intensity and dose, the greater the harm that occurs to all exposed tissues. The greatest harm tends to occur to cells that are dividing the most rapidly. Radiation is often used for cancer treatment because the tumor cells are more sensitive to radiation than the more slowly dividing normal cells; however, all the cells in the beam path sustain dose related injury.

In a study in mice to determine the protective effects of nucleic acid supplementation, all the animals were exposed to a very high dose of radiation. The survival rate in the control animals was extremely low at 5%. In contrast, the animals that received nucleic acid injections had vastly improved survival – ten times higher at 50%.

This suggests a generally strongly protective effect of nucleic acid supplements for all forms of ionizing radiation exposure, whether therapeutic or accidental. Even persons who use airline travel regularly may benefit from protecting their cells from the relatively higher exposure that tends to occur at altitude.

3D. Tissue regeneration (Cosgrove, 1998)

In order to sustain health, virtually every tissue in the body must regenerate itself regularly. It is now known for example that even neurons in the brain have the capacity to regenerate. Having adequate supplies of all the nucleic acid bases may be one of the most significant limiting factors on whether a tissue will be able to express its greatest capacity for regeneration and self repair.

A study in rats looked at the ability of the liver to regenerate depending on whether or not injections of nucleic acid bases were given. In this study, the rats had 70% of their livers surgically removed. The animals that received IV nucleic acids showed liver regeneration rates that were significantly greater than the untreated control animals.

Any tissue, in order to regenerate, requires the ability to make DNA and RNA to support the process of making new cells. Providing readily absorbed and assimilated DNA and RNA bases can be one of the most powerful ways to assist any tissue to repair and renew itself.

3E. Wound healing

A wound, surgical or otherwise, results in severing the usual integrity of tissue organization. It is a special case of tissue regeneration in which cells migrate into the area of the wound to either regenerate new tissue or to fill the defect with scar tissue. The type of healing depends on the tissue – the liver will tend to restore normal liver cells in the wound, whereas the skin will tend to fill the breach with scar to heal the opening and restore strength.

Several studies in wound healing have assessed the effects of supplemental nucleic acids on wound healing, especially of surgical wounds. Compared to the control group, those receiving the supplements showed more rapid healing, greater tensile strength of the skin, and significantly reduced scarring.

3F. Endocrine gland repair

Some of the tiniest organs in the body have the most profound effects on our health and well-being. These are the endocrine glands that secrete minute amounts of hormones into the blood without which every function of the body can suffer.

The tissues that are most susceptible to reduced function from nucleotide deficiency have been found to extract high proportions of nucleic acids from blood. These studies have examined the relative amounts of nucleic acid bases a tissue will incorporate if the nucleic acids are given through the GI tract versus being given intravenously.

The incorporation level of the administered nucleic acid bases is measured by giving nucleic acids that have been labeled with a radioactive marker. The amount of radioactivity measured in a tissue when it is given through GI absorption versus IV delivery then gives the assimilation ratio of the two routes of administration. Highly metabolically active tissues that are the most sensitive to stress-induced nucleic acid deficiency are those that have the highest IV: GI assimilation ratios.

In animal studies, the highest IV: GI assimilation ratios were found in the vitally important pituitary, thymus, thymus, salivary, and adrenal glands. The measured ratios ranged from 29-59:1 for IV delivery versus GI absorption. Other dynamic tissues that showed similarly high ratios were the intestinal lining and the lymphoid tissue of the immune system.

The pituitary gland located at the base of the skull has been called the “master gland” because it makes hormones that control the functions of other endocrine glands. It secretes hormones that regulate the thyroid and adrenal glands, the ovaries and testes, and the production of breast milk. The posterior region of the gland exerts control over the kidneys to adjust fluid balances throughout the body. Perhaps most important for longevity, the pituitary also makes growth hormone, that has been shown to have some of the most powerful age-reversing effects of any hormone ever studied. Inadequate nutritional support to this gland can have devastating and far-reaching effects throughout the body.
 
The adrenal glands, situated atop the kidneys, secrete adrenaline and noradrenaline, the fight or flight hormones. These powerful hormones increase heart rate and blood flow to muscle so that the body is immediately prepared for vigorous physical activity. In our ancestral past, this rapid preparation was a key to surviving in a hostile environment. However, modern living often puts a chronic stress on the adrenal glands, the myriad stimuli that surround us tending to keep the fight or flight mechanism constantly activated. The result is often varying degrees of adrenal burnout, exhausting the reserves of the gland to make the fight or flight hormones when really needed. Burned out adrenals give rise to a chronic low energy state, fatigue, and poor stress tolerance, like depleted batteries that fail to get recharged. These glands are especially prone to nucleotide deficiency under chronic stress, a condition that supplemental nucleic acids can help to restore, much as giving a long needed recharge to a nearly totally drained battery.

The thymus gland, residing behind the breastbone, is often considered the organ of rejuvenation and longevity. It is the gland in which the T cells of the immune system are formed and given identity.  Upon release it is the T cells in particular that help find and destroy cancer cells and cells that have become afflicted with viruses. The thymus gland tends to shrink with time, yet specific supplementation has been found to bring this vital organ back to more youthful function. In particular, providing nucleic acid bases for this gland with very dynamic cell turnover can significantly rejuvenate this gland and its life preserving activities.

The thyroid gland, at the base of the neck in front of the windpipe, produces thyroid hormones, the main control mechanism for setting basal metabolic rate. In some circles it is believed that we are in the midst of an epidemic of undetected deficiency of thyroid function. Tests of thyroid function may not show overt clinical disease, but low-level deficiency can significantly reduce quality of life. Effects are subtle and can include generally low energy, sluggish bowel function, lack of initiative, tendency to depressed mood, and weight gain with great difficulty losing the added pounds. Dietary iodine and the amino acid tyrosine are important building blocks to make thyroid hormone naturally from the gland. In addition, correcting insufficient nucleic acid production under stress will also support recovery of a sluggish gland.

The salivary glands reside in several pockets in the mouth. Although not as essential as the other glands to sustain life, they provide a vital role in the first stages of preparing food for complete digestion. These metabolically active glands also require a rich supply of nucleic acids to maintain adequate salivary flow.

Supplemental nucleic acids can thus be a very powerful tonic to sustain and boost the functions of the most vital glands in the body. These glands set our level of energy, our ability to respond to stress, our capacity to maintain strong immune defenses, the hydration of our bodies, and a wide range of hormone balances essential to a high quality of life. 

3G. Intestinal integrity, maturation, and bowel flora (Cosgrove, 1998)

The intestinal lining replaces all of its cells every seven days. Only a single layer thick, this lining is highly dependent on a sufficient supply of nucleic acids to completely regenerate itself every week. If nutritional support is inadequate, defective regeneration of the intestinal mucosal lining impairs the enzymatic stages of digestion, which can lead to a vicious cycle of deteriorating digestion and nutritional status.

In a study in young rats with chronic diarrhea, the effects of nucleic acid supplementation was tested. In the untreated animals the intestinal villi, finger-like absorptive projections, showed a dramatic reduction in height, like a forest that had been chopped down to stumps. The intestinal lining cells showed a drastic reduction of digestive enzymes, the essential final step of digestion that breaks nutrients down to the building block levels that the body can use. These animals were clearly failing to thrive. Upon administration of supplemental nucleic acids, the appearance of the intestinal lining greatly improved, with regeneration of the height of the absorptive intestinal villi. In addition, the enzyme content and function of the intestinal lining also greatly improved, permitting the animals to recover and thrive robustly (Uauy et al., 1990).

Human infants also require dietary nucleotides for optimum health, development, and well-being. Human breast milk has a significantly higher content of certain nucleic acid bases than does cows milk. Infants fed formula milk instead of breast milk have been found to have pathological intestinal bacteria that greatly increase their risk of outbreaks of diarrhea; especially in developing countries, such outbreaks can be life threatening (Schaller et al., 2007).

Studies have shown that if formula milk is supplemented with a nucleic acid profile similar to that in breast milk, infants thus fed have a much healthier profile of intestinal bacteria, typical of infants that have actually been breast fed. In the nucleic acid supplemented infants, the incidence and severity of diarrhea is reduced significantly to the level seen in breast fed infants. One of the most vital components of breast milk that confers its health and developmental advantages over formula milk thus appears to be its higher content of nucleic acids, making a strong case for such supplementing of all formula milk (Aggett et al., 2003; Santora and Kozar, 2009).

3H. HDL cholesterol levels (Cosgrove, 1998)

An additional finding in infants who received nucleic acid supplementation was an improvement in their blood lipid profiles. In particular, the infants receiving added nucleic acids were found to have higher HDL cholesterol levels, the cholesterol fraction that protects against cardiovascular disease the higher the level. It is possible that establishing higher HDL levels early in life may confer an ongoing tendency to cardiac protection.

3I. Growth and development

Studies in young laboratory animals have assessed the effects of supplementing DNA and RNA elements. Compared to control animals, the supplemented animals grew, developed, and increased muscle mass at a greater rate. Other vital proteins were also built more readily in the treated animals. The intestinal lining in particular matured more robustly in the supplemented animals. Research thus far indicates that the tremendous need for nucleic acids in growth and development is strongly beneficially supported through supplementing these vital nutritional elements (Mathers, 2006).

3J. Cellular immunity

Cellular immunity refers in particular to immune cells that have the role of identifying cells in the body that have become abnormal, so that the abnormal cells can be removed. The main cellular changes sought through the cellular immune system are the development of cancer cells or various types of intracellular infection. The goal of the cellular immune system is to eliminate cancer cells or infected cells before they can become established in the body to cause serious illness.

The main effectors of cellular immunity are cells that arise in the thymus gland. These cells are often called T cells for their thymic derivation, of which there are several types with varying functions. A special type of T cell called a cytotoxic T cell has the role of finding and sticking to abnormal cells, then releasing substances that selectively digest and clear the renegade cells.

Whereas cytotoxic T cells are generally active in seeking and clearing a wide range of abnormal cells, natural killer cells have a more targeted mission: seeking and destroying any cell that has become a cancer cell. The integrity of cellular immune function, most especially natural killer cell function, is the first line of defense of preventing tumor cells from establishing a stronghold in the body. Many studies have correlated reductions of cellular immune and natural killer cell function with increasing risks of developing cancer; some scientists feel that cancer is primarily a problem of inadequate cellular immunity.

Cytotoxic T cells, natural killer cells, and other types of T cells are also known as lymphocytes. These cells are a major component of the body’s lymphoid tissues that protect us from infections and cancers of many types. In addition to the T cells of several types there are also B cell lymphocytes whose role is the production of antibodies. Unlike T cells that act directly cell-to-cell, antibodies are released into the bloodstream to hunt down specific infectious, toxic, or tumor cell molecules. Lymphoid tissues that coordinate the functions of the immune system include the spleen, tonsils, lymph nodes, Peyer’s patches widespread throughout the intestines, regions of the bone marrow, and most importantly the thymus gland.

The lymphoid tissue and especially cellular immunity has been found to be highly vulnerable to nucleic acid depletion under conditions of stress. In other words, at the time of greatest need for protection, inadequate supplies of DNA and RNA bases can weaken the ability of the body to respond to the threat. An insult or tumor or infection the body might otherwise easily handle can escape control if the lymphoid does not have adequate nutrition to respond.

Numerous studies in animals and humans have shown that supplementing nucleic acid elements has profoundly beneficial effects on boosting the function of lymphoid tissue. In part, the reason for this is that lymphoid tissue is highly dynamic such that cells that have become sensitized to microbial invaders or cancer cells need to divide rapidly to make an army of specifically targeted cells to eliminate the invader.  A rich supply of nucleic acids, often beyond that the body can readily make, may be required for all the activities required for expanding the cells that prevent a minor invasion from becoming an overwhelming infection or uncontrolled malignancy.

Published studies have particularly demonstrated that cellular immunity is significantly strengthened with nucleic acid supplementation. Research that has examined natural killer cell function has shown especially dramatic effects on increasing the activity and function of these tumor surveillance and elimination cells. Improved health of body tissues in general and enhanced cellular immunity in particular, likely accounts for the vastly improved outcomes observed in the face of a wide range of minor to life threatening insults. The most well-defined models that demonstrate the influence of nucleotides on immune function are those evaluating the host response against allografts. Preformed nucleotides are postulated to be required for optimal T cell proliferation and responsiveness to antigens. Functional in vivo studies evaluating lymphocytes have shown decreased lymphocyte proliferation in response to mitogens and decreased IL-2 production, which is restored with RNA and uracil supplementation. These findings translated into improved cardiac allograft survival in animals fed a nucleotide-free diet.

Overall, these studies suggest that dietary nucleotides are substrates needed for optimal T cell maturation, which influences T cell effector functions. Nucleotide supplementation is also thought to augment the nonspecific host response to infection by altering the intestinal microflora environment, which is best demonstrated by reduced infections in infants receiving nucleotide supplemented formulas. In these instances, nucleotides are thought to act as prebiotics, facilitating the proliferation of beneficial flora. Finally, nucleotides are also thought to maintain the integrity of gut mucosal barrier function. Nucleotide supplementation mitigates the effects of endotoxin-induced mucosal damage. This mechanism leads to reduced bacterial translocation in LPS-induced sepsis models.

3K. Memory enhancement (Liu et al., 2009)

It is not generally well recognized that forming long-term memories requires significant quantities of nucleic acids. Especially the availability of an adequate pool of RNA is needed to manufacture new proteins that are essential to memory function. Although other support nutrients are an important factor, optimum memory function is not possible without a rich supply of nucleic acids.

Many studies in animals and humans have found a dramatic improvement in memory function with nucleic acid supplementation. Whether it is the ability to remember the right pathway to get through a maze for a prize of cheese, or to remember facts and figures, giving supplements of DNA and RNA elements has highly significantly increased performance.

Perhaps most dramatically, one researcher has focused on giving nucleic acids to persons with dementia. Even with advanced cases, if he went to high enough delivery levels to his patients, in almost every case memory improvement was very significant. The doctor reported that even in advanced cases of dementia dramatic memory recovery occurred if high enough levels of nucleic acids were given.

3L. Longevity (Bowles, 1998)

It is perhaps functional nucleic acid deficiency that limits our potential for healthy longevity more than any other single factor. Of all the interventions that have ever been attempted to increase the life span of mammals, no method ever studied has been more powerful for mammalian life extension than nucleic acid supplementation. Compared to other techniques that have increased longevity of experimental animals up to 50%, administering nucleic acids has doubled and even tripled the usual maximum life span.

In a landmark study, a strain of rats was used that had a usual life span of 800-900 days. The study began with all of the animals at day 750, rather advanced in age at the entry of the test protocol. Half of the animals were used as controls and received their standard diet, housing, and care. The treatment group animals were given identical conditions with the exception of receiving weekly injections of DNA and RNA (Savaiano et al., 1981; Selhub et al., 1995).

After eight weeks the control rats looked much worse than at the start of the study, losing fur and muscle mass, and showing reduced physical activity. In sharp contrast, at this time in the study, the treated animals actually looked and behaved like younger animals. They regrew fur and increased their muscle mass, had renewed libido, and were significantly more active.

By day 150 of the study, all of the untreated control animals had died.  In dramatic contrast, the minimum additional life span in the treated animals was 850 days, minimally doubling the usual life span of the animals. Perhaps most noteworthy, the longest lived animal in the treatment group survived 1500 days from the start of the study. 

This is the greatest life extension ever reported for a mammal; nearly triple the usual maximum life span. It is especially remarkable because the animals were of advanced age at the start of the study. Weekly injections of DNA effectively increased the remaining life spans of the animals by 500-900%.

It is as yet unknown whether even greater degrees of life extension could be achieved by beginning nucleic acid supplementation at an even earlier age, before any organ deterioration had occurred. It is likely that the longevity achieved would be at least as great or greater.

It is important to note that the doubling and tripling of the animal’s life span resulted from an ongoing program of nucleic acid delivery. This suggests that optimum longevity effects from DNA and RNA component supplementation requires continuous delivery of nucleic acid bases; this assures that the major glands and tissues of the body always have the elements needed for peak rejuvenation and repair (Mathers, 2006).

4. Laser enhancement technology

As a byproduct of research into the development of novel laser technologies for treating major diseases, a new form of laser energy was created. This new form of laser energy is so powerful it can be used to reshape molecules into a form that the body can use more efficiently, thus delivering greater bioavailability.

In essence, a typically manufactured nutritional supplement is subjected to chemical extraction, purification, and drying steps. All of these processes can cause numerous random distortions of nutrient shape. Enzymes of the body are highly shape sensitive for the molecules they will accept or reject. When the body receives a nutrient in a wide range of random shapes, some will fit and many others will not. The nutrients that don’t fit will either be excreted or broken down to relatively useless compounds. 

The breakthrough embodied in the laser reshaping technology is the ability to produce ultra short pulses in resonance with the natural frequency of the nutrients. The natural frequency of any structure is the frequency it will naturally tend to vibrate at when stimulated. If impulses are provided at the natural frequency even tiny amounts of energy given in each cycle build up to very large amounts of energy in the structure, in a patented process known as photoacoustic resonance, or PAR.

The basic analogy is kicking your legs to propel a swing. If you kick your legs at just the right time in the swing, the swing will go higher and higher. If you kick your legs randomly the swing will jiggle around at its lowest point, gathering no momentum. Normal laser action is like kicking your legs continuously. The impulses are out of phase with the natural frequency and the swing is not moved other than random small movements. In contrast, the laser impulses generated through PAR technology provides impulses at the right phase of the molecular vibration to build the energy in the molecule, to up to several times the baseline energy in the molecule.

The net effect of resonant laser stimulation is to create small flat stretched molecules that most importantly are consistent in shape from molecule to molecule. Homogenizing the shape of the molecules greatly reduces the enzyme energy needed to bind the next molecule, which can greatly increase the efficiency of nutrient utilization. This allows the cells to make much more of the desired products from the same quantity of ingested nutrients.

Using this laser molecular resonance technology, crystals of important nutrients have been made that show the predicted effects. Crystals prepared without the laser show numerous defects in crystal formation, indicating the diversity of shapes. In contrast, laser treated crystals are perfectly formed and free of defects, attesting to consistency of form.

Using X-ray crystallography, the predicted effects of flattening and stretching molecular bonds has been observed. X-ray crystallography is the scientific gold standard for determining the explicit three-dimensional shape of molecules and can place the location of each atom in the molecule to tiny fractions of Angstroms (1 Angstrom = one ten billionth of a meter). X-ray crystallography has also shown tremendous homogenization of molecular shape in an important nutrient known to have a wide variety of shapes after the usual manufacturing processes.

At the level of the test tube, cells fed equal amounts of ordinary versus laser treated nutrients have been tested. Milligram for milligram, cells fed the laser treated nutrients have produced statistically significantly more of the biologically desirable internal products.

Several amino acid effects in particular have been shown to be enhanced in vitro or clinically through laser treatment. Laser treatment of nutrients can thus work to create the most potently absorbed and utilized nutrition ever offered. 

5. Benefits of ATP (Agteresch et al., 1999)

ATP stands for adenosine triphosphate, perhaps the most important of all the nucleic acid derivatives in the body. Its effects are so powerful and essential to cellular function, a description of its unique properties warrants special attention. 

ATP is the fundamental currency of every cell in the body. Virtually every activity in the body that requires energy uses ATP as the source of power. Whether the function is building complex molecules from building blocks, maintaining the electric potential of cell membranes, or allowing muscle fibers to contract for mobility, speed, and strength, it is ATP that provides the electrochemical fuel.

5A. Cellular energy

There are two fundamental ways ATP is generated in the body, one very efficient and one very wasteful. Efficient ATP production occurs through aerobic metabolism in the mitochondria, tiny organs or organelles within the cell that burn fuels like fat and glucose to generate ATP. Aerobic means that oxygen is used to completely “burn” a fuel for maximum ATP production. For example, the complete combustion of a single glucose molecule to carbon dioxide and water yields a rich harvest of 36 molecules of ATP. 

Inefficient ATP production occurs through anaerobic metabolism. Anaerobic means without oxygen, so very little energy and ATP are extracted from fuels. When glucose is broken down through anaerobic metabolism, each molecule of glucose only gives rise to 2 molecules of ATP, wasting 95% of the potential glucose energy. Further, the byproduct of this reaction is two molecules of lactic acid, which makes the cells more acidic and less functional. In athletes, lactic acid accumulation causes muscle fatigue and the “burn”, whereas in cancer cells lactic acidosis is a recognized metabolic disturbance that contributes to diminished cellular function

5B. Neurological effects

ATP is the primary fuel that drives learning, memory, and concentration functions. ATP is essential to maintain the membrane potentials that permit nerves to integrate and transmit signals throughout the central and peripheral nervous systems.

In addition, giving ATP or its breakdown product adenosine intravenously has shown pain relief comparable to injected morphine for pain due to ischemia (impaired blood flow). Two surgical studies have shown a 25% reduction in the need for postoperative narcotic pain relievers when adenosine was given IV. 

Perhaps most remarkable, peripheral neuropathic pain is one of the most difficult pain syndromes to manage. Excruciating constant pain may resist all but the most drastic measures. IV adenosine for 45-60 minutes reduced neuropathic pain for 6 hours to 4 days in 86% of persons tested.

5C. Cardiac strengthening

The cyclic contraction of cardiac muscle is highly ATP intensive and thrives on aerobic metabolism. The ATP delivery effects of ATP in an oral spray provide the heart with an enhanced energy supply for efficient function.

Providing intravenous ATP has been shown to slow conduction through the AV node, which has been used to slow down certain excessively fast heart rate called tachycardias. Occasionally chest symptoms can occur with rapid intravenous infusions of ATP that resolve within seconds after stopping the infusion. ATP is not known to cause excessively slow heart rates in persons whose heart rates are normal. 

5D. Muscle performance

Skeletal muscle also requires abundant quantities of ATP for muscular contraction. Supplemental ATP has been described as an “explosive performance enhancer.” Especially if given with two other nutrient supporters of muscle function, creatine monohydrate and creatine pyruvate, muscle endurance, performance, and recovery can be significantly boosted.

5E. Lung function

ATP administration has been shown to have numerous beneficial effects on lung function, particularly the delicate lining membranes of the airways and alveoli. In the lung, branching tubes called bronchi and then bronchioles deliver air to and from the tiny air sacs called alveoli. The alveoli form a large membrane only a single cell in thickness through which capillary blood can pick up a new supply of oxygen and unload carbon dioxide with every breath.

In vitro, or test tube level research, has shown that ATP increases secretion of surfactant in the alveoli. Surfactant is an essential substance that keeps the alveoli from collapsing when the breath is exhaled, preserving integrity of functional gas exchange.

The bronchial tubes are lined with tiny brush like structures called cilia that are constantly sweeping particulates that get into the lung upward and outward. ATP not only increases the ciliary beat frequency, it also increases the secretion of mucus and water from the bronchial lining, to help keep the lungs clear at all times.

In some conditions, the blood pressure in the vessels in the lungs can raise too high, a condition known as pulmonary hypertension. When given intravenously, ATP binds to the lining of the pulmonary vessels and stimulates a cascade of events that cause the blood vessels to relax and lower the pressure.

Cystic fibrosis is one of the most common inherited genetic diseases. Impaired water and electrolyte secretion from the bronchial lining results in thick secretions that block the bronchial tubes and result in recurring infections. ATP has been found to increase electrolyte and water secretion with improved clearance of secretions, offering hope of a new and useful intervention in this often aggressively progressive condition.

5F. Cellular immune enhancement

Natural killer cells and cytotoxic T cells as reviewed are subtypes of effector lymphocytes that have a vital role in immune defense against tumors and virus-infected cells. Recent research suggests that ATP may play an important role in the mechanism through which these effector cells eliminate the target abnormal cells. In test tube studies, ATP has been shown to enhance the ability of cytotoxic lymphocytes to rupture the membranes of tumor cells.

5G. Anti-tumor effects

In test tube studies, adding ATP has shown the ability to inhibit the growth of several types of human cancer cell lines. The types of cancer cells inhibited include pancreatic cancer, colon cancer, melanoma, androgen-independent prostate cancer (i.e., not responsive to male hormone manipulation, the most aggressive variant), breast cancer, myeloid and monocytic leukemia (bone marrow derived tumors of blood forming cells), and multi-drug resistant colon cancer. In contrast, normal cells from these tissues showed less inhibition of growth or no inhibition at all, suggesting that increasing ATP outside cells may have a selective inhibitory effect on several cancer cell lines.

Mice injected with the untreated leukemia cell line L1210 died of leukemia within 18 days. In contrast, if the leukemic cells were treated with ATP before injection, 85% of the recipient mice survived for more than 70 days, a highly significant increase in survival.

In mice and rats, injections of ATP into the abdominal cavity have significantly slowed the growth of several different types of tumor cell lines, including colon cancer, lymphomas, and breast cancer. ATP administration resulted in significantly prolonged survival in the treated animals.

Administering ATP may also enhance the effectiveness of cancer chemotherapeutic agents, increasing the anti-tumor effect of a given dose, or greatly reducing the dose required for a therapeutic effect. In particular, decreasing the dose of the treatment agents can dramatically reduce the toxicity of these anti-tumor drugs.

For example adding ATP to the drug doxorubicin to cultures of human ovarian cancer cells doubled the tumor cells eliminated compared to using doxorubicin alone. When ATP was given, 30-50% more doxorubicin accumulated in the cancer cells, whereas giving ATP to healthy human cells did not increase the accumulation of the drug. 

In mouse melanoma cell lines, ATP increased the entry of several chemotherapeutic agents. The anti-tumor effects of these agents were additively increased with ATP treatment. Even more remarkable was the synergistic anti-tumor effect seen with the drug vincristine; the effective therapeutic dose of this agent was reduced to one-tenth to one-fiftieth of the dose usually required.

In mice with melanoma addition of the ATP derivative adenosine to the treatment program significantly increased the tumor elimination. In addition, a protective effect was seen on the healthy bone marrow, preventing the usual decrease in white blood cells due to treatment.

Beyond growth inhibition, ATP may cause some types of tumor cells to burst. In human acute myeloid leukemia, a dose-dependent rupture of the cancer cells was seen using ATP.

In a randomized human clinical study, intravenous ATP was given to patients with advanced lung cancer at 2-4 week intervals. Whereas the control patients lost 2 pounds per month, the treated patients had stable to slightly increased weight. Over the six months of the study, the control patients lost one third of their muscular strength, while the ATP treated patients lost no strength. Although some medications may maintain weight in cancer patients, this is usually due to fat gain while muscle is lost. Intravenous ATP is the first intervention ever studied that appears to be able to maintain muscle mass, body weight, and muscle function in advanced cancer patients.

Thus ATP may be broadly beneficial in supporting anti-tumor cell biology. ATP enhances cellular immune function, inhibits the growth of several types of tumors, and in some cases may be able to cause direct elimination of tumor cells. In addition, ATP protects from radiation injury and may preserve weight and muscle strength. Further study will be needed to assess the full range of benefits it may provide. Given its high safety profile, ATP use may be one of the most beneficial adjuncts developed for supportive care, enhancing the results of conventional treatments.

5H. Improved human survival of shock

Under conditions of metabolic stress, such as depriving a tissue of oxygen through reduced blood supply, a rapid and massive depletion of ATP within cells occurs. Giving ATP or its metabolite adenosine has been described as a “natural defense system” to protect the tissues from the effects of severe oxygen deprivation. These protective effects include improved function of energy generating mitochondria, better electrolyte transport, increased ATP within cells, reduced oxygen consumption, and improved function of messenger molecules within the cells.

Shock is a condition in which there is a generalized reduction of blood flow and oxygenation to tissues below that required for their function. If shock is sustained, organ failure or death may occur. Once shock is reversed, supportive measures to assist tissue recovery can significantly affect quality of outcome.

In a study of 32 patients with acute kidney failure or multiple organ failure due to shock, highly beneficial effects of intravenous ATP were observed. The patients were randomly divided into the treatment group that received intravenous ATP or the control group that did not. The survival rate of 73% in the control group was increased to 100% survival in the ATP treatment group, showing the powerful tissue restorative effect of this intervention.

5I. Sexual function

In human tissue studies, the administration of ATP and adenosine has been found to induce the smooth muscle relaxation that is essential for erectile function. In diabetic men, erectile dysfunction is common through several mechanisms. The erectile tissue of diabetic men has been found to be especially sensitive to the smooth muscle relaxation effects of ATP, offering them a hopeful avenue of recovery of erectile function (Gur and Ozturk, 2000).

6. Safety

Supplemental nucleic acids have an outstanding safety profile. The levels of nucleic acid elements provided in one ml of an oral spray formula, a typical serving, ideally falls within the internationally approved safety guidelines for supplementing nucleic acids in infant formulas (Aggett et al., 2003).

The one precaution is that the purine nucleic acids adenine and guanine are metabolized to uric acid in the body. Persons with elevated uric acid or a history of gout may have a very slightly increased risk of an episode of gout while taking nucleic acid supplements. Because of the very high potency and bioavailability of the nucleic acid elements in oral spray form, the specific quantities of purine bases are well below that usually associated with an increased risk of elevating uric acid.

Some persons find that they are highly energized with mucosally administered ATP and may have difficulty falling asleep if they take it too late in the day. For such persons it is best to use the formula earlier in the day to enjoy the energy effects without interference with sleep.

For any person with medical issues, it is always advised that their physician be consulted before beginning any new nutritional program.

7. Summary and conclusion

The health benefits of nucleic acids delivered as an oral spray may be further increased by applying the proprietary PAR process. Providing highly bioactive nucleic acid elements, this delivery system can help rebuild and boost the function of every cell in the body.

Precautions:

It is advised that people consult their physicians before embarking on any health program. Persons who have gout in particular should consult their physicians before use. A byproduct of some of the DNA and RNA bases is uric acid, which can aggravate gout. The content of these bases in the formula is quite low compared to the level usually observed to be a possible problem for gout.

How long should Cellfood Longevity be used?

Use even for a short while will provide the body with building blocks to repair DNA and tissue.  For the most profound effects on longevity, the best were seen if DNA and RNA building blocks were given continuously, week after week. Although occasional holidays may even be helpful, long-term use is most likely to give the greatest benefits. 

References

Aggett P, Leach JL, Rueda R, and MacLean WC. 2003. Innovation in infant formula development: A reassessment of ribonucleotides in 2002. Nutrition 19: 375-384.

Agteresch HJ, et al. 1999. Adenosine triphosphate: established and potential clinical applications. Drugs; 58 (2): 211-232.

Bohoun C, and Caillard L. 1971. S-adenosyl-methionine in human blood. Clinica Chimica Acta; 33: 256.

Bowles JT. 1998. The evolution of aging: a new approach to an old problem of biology. Medical Hypotheses; 51: 179-221.

Carver JD, and Walker WA. 1995. The role of nucleotides in human nutrition. Nutritional Biochemistry 6: 58-72.

Cosgrove M. 1998. Nucleotides. Nutrition; 14 (10): 748-751.

Grimble GK. 1994. Dietary nucleotides and gut mucosal defense. Gut; 1: S46-S51.

Gur S, and Ozturk B. 2000. Altered relaxant response to adenosine and adenosine 5’-triphosphate in the corpus cavernosum from men and rats with diabetes. Pharmacology; 60: 105-112.

Kishi T, et al. 1994. Effect of betaine on SAMe levels in the cerebrospinal fluid of a patient with methylenetetrahydrofolate reductase deficiency and peripheral neuropathy. Journal of Inherited Metabolic Disease; 17(5): 560-566.

Liu L, van Groen T, Kadish I, and Tollefsbol TO. 2009. DNA methylation impacts on learning and memory in aging. Neurobiology of Aging 30: 549-560.

Mathers JC. 2006. Nutritional modulation of aging: genomic and epigenetic approaches. Mechanisms of ageing and development 127: 584-589.

Odens M. 1970. Prolongation of the life span in rats. J Am Geriatr Soc; 21(10): 450-451.

Rigby PG. 1971. The effect of “exogenous” RNA on the improvement of syngeneic tumor immunity. Cancer Research; 31: 4-6.

Santora R, and Kozar RA. 2009. Research review. Molecular mechanisms of pharmaconutrients. In press: Journal of Surgical Research; 1-7.

Sanchez-Pozo A, Rueda R, Fontanna L, and Gil A. 1998. Dietary nucleotides and cell growth. Trends Comparative Biochem Physiol; 5: 99-111.

Savaiano DA, Ho CY, Chu V, and Clifford AJ. 1981. Metabolism of orally and intravenously administered purines in rats. J Nutr; 110: 1793-1804.

Schaller JP, Buck RH and Rueda R. 2007. Ribonucleotides: Conditionally essential nutrients shown to enhance immune function and reduce diarrheal disease in infants. Seminars in Fetal and Neonatal Medicine 12: 35-44.

Selhub J. et al. 1995. Association between plasma homocysteine concentrations and extra cranial carotid artery stenosis. New England Journal of Medicine, 332, (5): 286-291.

Slobodianik NH. 2003. Dietary ribonucleotides and health. Nutrition; 19 (1): 68-69.

Uauy R, Quan R, and Gil A. 1994. Role of nucleotides in intestinal development and repair: implications for infant nutrition. J Nutr; 124: 1436S-1441S.

Stress and quality of life

Introduction

The body perceives any outside factor that tends to impose change on it and thereby to disturb its homeostasis as 'stress'. Stressors can be physical (heat, trauma, cold), physiological (toxins, disease, deficiency of nutrients) or psychological (work and marital pressures, dissatisfaction, arguments, financial problems, envy, hatred, etc.).

In its reaction (which can be short or long term), the body responds by means of a number of biological and hormone-dependent changes known as the general adaptation syndrome (GAS) which occurs in three phases triggered by hormones produced in the adrenal glands (Serfontein, 2003).

The alarm reaction

This is the immediate 'fight or flight' response. The reaction is triggered by the hormones adrenaline and noradrenaline produced in the adrenal medulla. Some of the physiological consequences include elevated blood sugar, increased heart rate, increased respiration and peripheral vasoconstriction, all of which facilitate the immediate physical response. Since the reaction is usually of short duration, it is in general not particularly harmful. Coffee, tea and smoking have the same effect since they contain substances (caffeine, nicotine) that stimulate that release of adrenaline.

The resistance and adaptation phase

This phase represents the longer term response to the stressor mediated through hormones produced in the adrenal cortex:

  • The mineralocorticoids (e.g. aldosterone) also affect mineral distribution with a view towards increasing the body's capacity to resist immediate physical damage. The hormones increase sodium retention in the kidneys, thus raising blood pressure. This is coupled with increased loss of potassium which further tends to increase blood pressure and which, in the longer term, may have other serious health consequences unless corrective physiological steps are taken.
  • The glucocorticoids (e.g. cortisol) have different physiological effects of which the most important is energy production by raising blood sugar levels. It also increases blood flow in certain areas and reduces it in other areas, while simultaneously reducing other functions such as digestion in order to enable the body to fight physical damage (fighting infections, healing of tissues), as efficiently as possible.

The exhaustion phase

If the stressful challenge is too strong or persists for too long, the body may reach a stage where it is no longer able to cope. At this stage the defense mechanisms collapse and serious illness may result, including immune system deficiency and adrenal collapse. There are usually two major causes, namely continued loss of potassium and depletion of cortisol which leads to low blood sugar levels and chronic fatigue.

In most people the stress cascade does not progress to the final exhaustion phase when, due to the severity of the symptoms, the patient is forced to take remedial action. A very large percentage of the adult population in the industrialised Western world is somewhere in the resistance phase, some cases being more severe than others.

Chronic long-term stress is associated with overactivity of the hormonal system in which there may be increased plasma levels of adrenaline, cortisol, thyroid hormone, antidiuretic hormone, plasma lipids (triglycerides, cholesterol) and others. In addition there is a constant increased loss of potassium. All of these abnormalities may have many long-term consequences, the most common ones being high blood pressure, gastric ulcers, and adrenal atrophy. Most of the chronic metabolic diseases are aggravated by increased stress levels (Serfontein, 2003).

What are the effects of stress?

Stress involves a number of physiological responses, the ultimate aim of which is to restore balance within the body. The brain for example regulates the secretion of hormones and the nervous system to ensure that the muscles have enough energy and oxygen to fuel the familiar ‘fight or flight’ response (McKune, 2009). Some people handle stress well. Others are very negatively influenced by it.

Researchers estimate that stress contributes to as many as 80 percent of all major illnesses, including cancer, cardiovascular disease, endocrine and metabolic disease, skin disorders, and infectious ailments of all kinds. Stress is also a common precursor of psychological difficulties such as anxiety and depression.

While stress is often viewed as a mental or psychological problem, it has very real physical effects. The body responds to stress with a series of physiological changes that include increased secretion of adrenaline, elevation of blood pressure, acceleration of the heartbeat, and greater tension in the muscles. Digestion slows or stops, fats and sugars are released from stores in the body, cholesterol levels rise, and the composition of the blood changes slightly, making it more prone to clotting. Almost all body functions and organs react to stress. The pituitary gland increases its production of adrenocorticotropic hormone (ACTH), which in turn stimulates the release of the hormones cortisone and cortisol. These have the effect of inhibiting the functioning of disease-fighting white blood cells and suppressing the immune response. This complex of physical changes is called the" fight or flight" response, and is designed to prepare one to face an immediate danger. Today, most of our stresses are not the result of physical threats, but the body still responds as if they were (Balch and Balch, 1997).

Some consequences of chronically elevated cortisol levels

In moderate physiological amounts, cortisol is essential for life, especially for survival under stress. However, chronically elevated cortisol levels such as may result from chronic stress are associated with decreased immunocompetence, significantly reduced lifespan as well as accelerated ageing. This has been convincingly demonstrated in experimental animals and for this reason cortisol has been called the 'death hormone'. As we grow older the dangers associated with high cortisol levels are increased because the hormones that normally hold cortisol in check (pregnenolone, DHEA) decrease with age (Serfontein, 2003).

  • Cortisol and brain damage

    Evidence of a possible link between high cortisol levels and degenerative diseases associated with brain cell death such as Alzheimer's and Parkinson's diseases are appearing more and more in scientific journals . Excessive cortisol levels such as those that may be associated with chronic stress may be an important cause of brain cell death and ageing.

  • Cortisol and the immune system

    Cortisol is also a very strong suppressant of the immune system. As we grow older, blood cortisol levels increase while those of most other hormones and blood antioxidants decline. This means that whereas the protectors of the immune system (antioxidants) decline with age, cortisol - a potent suppressor of the immune system - increases. Collectively these effects are responsible for the substantial weakening of the immune system during stressful periods and as we grow older (Serfontein, 2003).

NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and stress

This protein complex controls the transcription of DNA. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, UV, oxidized LDL, and bacterial or viral antigens. It plays a key role in regulating the immune response to infection (kappa light chains are critical components of immunoglobulins). Incorrect regulation of NF-κB has been linked to cancer, inflammatory and septic shock, autoimmune diseases, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory (Gilmore, 2006).

NF-KB is paradoxically activated during healthy and diseased conditions. NF-KB is responsive to acute cellular stress. However, the frequency and severity of stress ultimately determine whether the organism responds with favourable adaptations, or, in the case of inadequate recovery (exhaustion), NF-KB becomes chronically activated in diseases such as diabetes and cachexia, where constant stress is associated with oxidative and metabolic perturbations, and skeletal muscle inflammation induces tissue degeneration.

Stress and free radicals

It is a scientific fact that the accumulation of free radicals over an extended period of time can lead to oxidative stress. According to Heilbronn and co-workers (2006), oxidative stress refers to oxidative damage caused by reactive oxygen species (ROS). ROS is produced by various cell types and includes immune and endothelial cells, and inner cellular organelles like the mitochondria (Carter et al., 2007). These free radicals play a maladaptive role in the body by attacking lipids, protein and DNA and in the process generate a variety of products such as harmful oxidized lipids, less functional proteins, carbohydrates and nucleic acids that negatively affect normal cellular function (Heilbronn et al., 2006). It is scientifically documented that free radicals also increase in the body during stress and exercise (van der Merwe, 2004).

Free radicals may interact with key cell components causing irreversible damage resulting in the increased development of diseases such as cancer, cardiovascular disease and other age related diseases. It is believed that antioxidants aid in the fight off of free radicals (Wiendow, 2009). In the human body low levels of antioxidants, or inhibition of the antioxidant enzymes, can also cause oxidative stress. Consequently, humans have a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage. In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell. However, since ROS do have useful functions in cells, such as redox signaling, the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level (Mathews and van Holde, 1990).

As oxidative stress might be an important part of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases.

Stress and nutritional deficiencies

The increased production of adrenal hormones is responsible for most of the symptoms associated with stress; it is also the reason why stress can lead to nutritional deficiencies. Increased adrenaline production enhances the metabolism of fats, proteins, and carbohydrates to quickly produce energy for the body to use. This response causes the body to excrete amino acids, potassium, and phosphorus; to deplete magnesium stored in muscle tissue; and to store less calcium. Further, the body does not absorb ingested nutrients well when under stress. The result is that, especially with prolonged or recurrent stress, the body becomes at once deficient in many nutrients and unable to replace them adequately. Many of the disorders that arise from stress are the result of nutritional deficiencies, especially deficiencies of the B-complex vitamins, which are very important for proper functioning of the nervous system, and of certain electrolytes, which are depleted by the body’s stress response (Balch and Balch, 1997).

Supplements that can assist with nutritional deficiencies due to stress are:

  • Multivitamin/mineral combinations [beta-carotene, selenium, zinc, and vitamins C and E - work together as antioxidants to neutralize damaging free radicals caused by stress and to support the immune system. Vitamin C with bioflavonoids is essential to adrenal gland function – stress depletes the adrenal gland hormones (anti-stress hormones). All B vitamins are necessary for health and proper functioning of the nervous system. Minerals like calcium, magnesium and potassium are lost during stressful episodes and need to be replaced].
  • Amino acids [to supply protein, which is used rapidly by the body at stressful times. L-tyrosine helps reduce stress, is an effective and safe sleeping aid, and is also good for depression. L-lysine is effective against cold sores, often an early indicator of stress. It helps reduce stress while Gamma-aminobutyric acid (GABA) acts as a tranquilizer and is important for proper brain function].
  • Melatonin - a natural hormone that promotes sound sleep; helpful if stress leads to occasional sleeplessness.
  • Omega 3 fish oils (DHA and EPA) play an important role in brain function and mood regulation.
  • Herbs [Bilberry, Ginkgo biloba, Milk thistle, Catnip, Chamomile, Dong quai, Hops, Passionflower, Skullcap, Valerian, etc.]. Plant extracts from Rhodiola rosea and Ashwgandha prevent the adrenals from producing excessive cortisol and adrenaline, while also directly protecting the heart and brain from raised blood pressure, heart attack and the symptoms of stress such as memory loss, insomnia, fatigue and feeling overwhelmed (Murphy, 2008).
  • Cellfood for extra oxygen, essential minerals and trace elements, amino acids and antioxidant enzymes.

Conclusion

The world of the new millennium is the world of the individual - people expect to get more out of life and improve their quality of life. By following a balanced diet, exercising regularly and taking nutritional supplements people can cope with stress while getting the most out of life.

References

Balch, J.F., and Balch, P.A. 1997. Prescription for nutritional healing. 2nd Ed. Avery.

Carter, C.S., Hofer, T., Seo, A.Y. and Leeiwenburgh, C. 2007. Molecular mechanisms of life and health-span extension: Role of calorie restriction and exercise intervention. Nutr. Metab. 32: 954-966

Gilmore, T.D (2006). Introduction to NF-κB: players, pathways, perspectives. Oncogene 25 (51): 6680-6684

Heilbronn, L.K., de Jonge, L. and Frisard, M.I. 2006. Effects of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals. American Medical Association 295 (13):1539-1547

Mathews, C.K. and van Holde, K.E. 1990. Biochemistry. The Benjamin/Cummings Publishing Company Inc

McKune, A. 2009. Fight or flight. Discovery 40-42.

Murphy, B. 2008. What you don’t know about stress can kill you. SANJM 39: 54-59.

Serfontein, W.J. 2003. Stress – hormonal and nutrient control. SANJM 9: 17-20.

Van der Merwe, A. 2004. Stress solutions. Understand and manage your stress for a balanced, energised life. Tafelberg Publishers, Cape Town

Wiendow, R.A. 2009. Biological and physiological ageing. Research Starters 1-5


<< Back to the Technology Behind Cellfood page

Home    |   About us   |   Gallery   |   Articles & Ads    |   Contact Us    |   Oxygen Information   |   Products  

 

twitter twitter twitter instagram

facebook

facebook

facebook

facebook

facebook

 
 

  Email

 Feedback

 Twitter

  Instagram

Humans

Pets

Farm Animals

Cell-Pet India

Cell-Vet India  
© Oxygen For Life 2019