WO2010111218A1

WO2010111218A1 - Method for increasing energy in hiv and/or aids patients

Info

Publication number: WO2010111218A1
Application number: PCT/US2010/028232
Authority: WO
Inventors: Lucy Tyler
Original assignee: Individual
Current assignee: Individual
Priority date: 2009-03-23
Filing date: 2010-03-23
Publication date: 2010-09-30
Anticipated expiration: 2011-09-23

Abstract

A method for increasing energy in a patient by administering an effective amount of a palladium lipoic acid complex. In one embodiment of the invention, the method provides treatment for an HIV/AIDS patient.

Description

METHOD FOR INCREASING ENERGY IN HIV AND/OR AIDS PATIENTS BACKGROUND OF THE INVENTION

The present invention relates to methods for increasing energy. Specifically, the invention provides a method for increasing cellular energy in HIV and/or AIDS patients.

Human Immunodeficiency Virus (HIV) is a condition that is associated with a decrease in energy, i.e. fatigue and/or low energy. HIV is a complex retrovirus which attacks T4 helper lymphocytes (CD4+ T cells). When HIV kills CD4+ T cells to the extent that there are fewer than 200 CD4+ T cells per microliter (μL) of blood, cellular immunity is lost, leading to Acquired Immune Deficiency Syndrome (AIDS). AIDS results from a compromised immune system, which leaves individuals prone to opportunistic infections and tumors.

As mentioned above, fatigue and/or low energy is a common and troubling symptom in patients with HIV and/or AIDS, resulting in significant disability and adverse effects on quality of life. The prevalence rate of fatigue and/or low energy among patients with HIV and/or AIDS is estimated to be up to 60%, and as the disease worsens, fatigue and/or low energy may become even more prevalent. Its etiology remains complex and is most likely multifactorial in nature. The causes of HIV and/or AIDS-related fatigue and/or low energy may be physiological, and include a lack of rest or exercise, an improper or inadequate diet, anemia, abnormalities of the thyroid or adrenal gland, hypogonadism, impaired liver function, infections, side effects of medications, and/or fever.

The psychological causes of fatigue and/or low energy in HIV and/or AIDS patients may be attributed to stress, depression or anxiety. Thus, fatigue and/or low energy is widely recognized as a significant problem in patients suffering from HIV and/or AIDS. Many biological processes, including energy production, are hampered by HIV activity within the body. Cellular respiration is the method by which cells produce adenosine triphosphate (ATP), the source of all cellular energy. Cellular respiration involves the breakdown of glucose through a series of oxidation and reduction reactions. The anaerobic portion of cellular respiration occurs in the cytoplasm, while the aerobic portion of cellular respiration occurs in the mitochondria.

The chain of oxidation and reduction reactions that occur during cellular respiration are mediated by enzymes, which facilitate electron movement. The last destination for an electron, derived from the breakdown of, for example, pyruvate, is an oxygen molecule. Oxygen is required for aerobic cellular respiration to take place. Normally oxygen is continually reduced by electrons to produce water. In normal cells, electrons passing through the mitochondrial chain reduce oxygen in stages. This results in the production of the free oxyradical intermediates of the electron transport chain. These are superoxide, hydrogen peroxide, perhydroxy radical, and hydroxyl radical. It is important to note that the beneficial energy producing effects of these radicals depend on their localization within the electron transport chain. The displacement of radicals outside the mitochondria produces a group of reactions generally regarded as pathologic denaturations of proteins. However the main effect of displacement of oxyradicals is the loss of their energy contribution.

Superoxide (O₂ ^") is a free radical that is the first activated oxygen form in the electron transport chain. It forms in Complex I of the mitochondria. In excess at ectopic sites, it can oxidize cysteines, inactivate specific enzymes, or initiate lipid peroxidation. Normally, superoxide progresses to donate its unpaired electron to Complex II to form peroxide. Peroxide then continues the oxyradical based transfer of electrons in the normal mitochondrial chain. Excess ectopic peroxide can donate unpaired electrons to cell membrane phospholipids, and to mitochondrial membrane phospholipids, inducing exaggerated membrane permeability. When mitochondrial membranes become too permeable, they release well characterized membrane cleavage enzymes. This is referred to as apoptosis or programmed cell death. Healthy cells are able to remove damaged mitochondria through autophagy. In certain individuals, such as, for example, those with HIV and/or AIDS, there is an inability to repair damaged mitochondria. This leads to ectopic release of reactive oxygen species, which then are no longer in the structural continuum in which they produce cellular energy. Age, medication, and illness further hamper an organism's ability to remove and repair damaged mitochondria thereby often leading to chronic fatigue and/or low energy.

Mitochondrial toxicity and mitochondrial diseases have been known since

1940. In 1959, the first patient was diagnosed with a mitochondrial disorder. In 1963, researchers discovered that mitochondria have their own DNA or "blueprint" (mtDNA), which is different than the nuclear DNA (nDNA) found in the cells' nucleus.

Mitochondrial and metabolic medical conditions are now referred to as mitochondrial cytopathies. Mitochondrial cytopathies actually include more than 40 different identified diseases that have different genetic features. The common factor among these diseases is that the mitochondria are unable to completely burn food and oxygen in order to generate energy.

The process of converting food (fuel) into energy requires hundreds of chemical reactions, and each chemical reaction must run almost perfectly in order to have a continuous supply of energy. When one or more components of these chemical reactions do not run perfectly, there is an energy crisis, and the cells cannot function normally. As a result, the incompletely burned food might accumulate as poison inside the body.

This poison can stop other chemical reactions that are important for the cells to survive, making the energy crisis even worse. In addition, these poisons can act as free radicals (reactive substances that readily form harmful compounds with other molecules) that can damage the mitochondria over time, causing damage that cannot be reversed. Unlike nuclear DNA, mitochondrial DNA has very limited repair abilities and almost no protective capacity to shield the mitochondria from free radical damage.

Fatigue and/or low energy extends beyond somatic fatigue and/or low energy, causing neural and cognitive energy reduction. When the interlocked processes of cellular respiration and the production of reactive oxygen are compromised, energy is compromised.

Many models have been proposed to address fatigue and/or low energy. These include decreased cellular respiration, decreased mitochondrial transport chain activity, and diminished and displaced reactive oxygen species. Exercise, and caffeine or other stimulants are often used to decrease fatigue and/or low energy. However, stimulants can cause loss of appetite, paranoid behavior, heart problems and sleeplessness.

Additionally, fatigue and/or low energy can decrease motivation, and energy available for exercise. Treatments for fatigue and/or low energy caused on a cellular level often include some form of dietary supplementation. However, issues relating to compliance, side effects, and intolerance such as an inability to absorb nutrients, create a need for alternate, more effective treatments.

SUMMARY

The present invention provides a method for increasing energy in a host in need thereof by administering an effective amount of a palladium lipoic acid complex to the host.

In one embodiment of the invention, the host in need thereof is a host suffering from HIV and/or AIDS. In another embodiment, the host in need thereof is a chronologically old host. In another embodiment, the host in need thereof is a physiologically old host. In yet another embodiment, the host in need thereof is a host suffering from mitochondrial toxicity, a mitochondrial disease and/or mitochondrial cytopathies.

In an embodiment of the invention, the palladium lipoic acid complex further comprises one or more antioxidants. In one embodiment, the palladium lipoic acid complex is administered at least once per day. In another embodiment, administration of the palladium lipoic acid is in an amount from about O.OlmL/kg of host body weight to about 10 mL/kg of host body weight. In yet another embodiment, administration is from about 0.05 mL/Kg of host body weight to about 5 mL/kg of host body weight.

According to the invention, the increased energy is an increase in cellular respiration. In a particular embodiment, the increased energy is an increase in mitochondrial electron transport chain activity. In another embodiment, the increased energy is caused by a reduction or displacement in cellular reactive oxygen species.

DETAILED DESCRIPTION

It has now been discovered that administration of a palladium lipoic acid complex to a host in need thereof is effective for increasing energy in the host.

PALLADIUM LIPOIC ACID COMPLEX

According to the invention, a palladium lipoic acid complex is represented as (palladium)_m(lipoic acid)_n, wherein m and n are each independently 1 or 2. In a preferred embodiment, both m and n are 1. The bonds of the palladium lipoic acid complex are coordinate covalent. Both of the carboxylic oxygen atoms and the two sulfur atoms of lipoic acid are involved in formation of these coordinate covalent bonds. The lipoic acid in the complex comprises a bent carbon chain with the ends of the chain bonded to the palladium. Crystal studies imply the structure of palladium lipoic acid to be three dimensional with the palladium in the center of the complex. The lipoic acid moieties of the palladium lipoic acid complex can be either in oxidized or reduced form. Lipoic acid analogues having a shortened or elongated carbon chain can also be used. Lipoic acid derivatives having one to three additional side groups can also be used. The side groups can be attached to one of the sulfur atoms or can be substituted for the hydroxyl group in the carboxyl of the lipoic acid moiety.

The palladium lipoic acid complex of the present invention can further comprise at least one ligand to the palladium lipoic acid complex. The additional ligand can be, for example, acetate, acetylacetonate, amine,bromide, chloride, fluoride, iodide, nitrate, nitrite, oxalate, oxide, pyridine, sulfate and sulfide. The palladium lipoic acid complex can also comprise additional cations such as, for example, sodium, potassium, magnesium, calcium, zinc and tin and anions such as vanadate and molybdate. Other derivatives of lipoic acid known in the art can also be used in the present invention.

Palladium is a transition metal of group VIII of the periodic table. Salts of palladium can also be employed in preparing the Palladium lipoic acid complexes of the present invention. Palladium salts can be selected from, for example, palladium acetate, palladium acetylacetonate, palladium ammonium chloride, palladium ammonium nitrate, palladium bromide, palladium chloride, palladium diamine nitrate, palladium diamylamine nitrate, palladium dibromide, palladium difluoride, palladium dioxide, palladium dipyridine nitrite, palladium ethylenediamine nitrite, palladium iodide, palladium monoxide, palladium nitrate, palladium oxalate, palladium oxide, palladium sulfate, palladium sulfide, palladium tetramine dichloride, palladous potassium bromide, palladous potassium chloride, palladous sodium bromide, and palladous sodium chloride. The preferred palladium salts are palladium chloride, palladium bromide, palladium iodide, palladium nitrate, palladium oxide and palladium sulfide.

The palladium lipoic acid complex of the present invention can be produced by dissolving lipoic acid in a basic solution and adding an acidic solution containing palladium or a salt thereof. The resulting solution is heated to a boil, e.g., to about 100⁰C, to produce the palladium lipoic acid complex. More specifically, the palladium lipoic acid complex of the present invention can be synthesized, for example, by the following procedure: (a) adding palladium or a salt thereof to an acidic solution;

(b) heating the palladium-acidic solution to at least about 100⁰C;

(c) filtering the palladium-acidic solution from step (b);

(d) dissolving lipoic acid in a basic solution;

(e) adding the dissolved acidic palladium solution from step (c) to the dissolved basic lipoic acid solution from step (d); and

(f) heating the red mixture of lipoic acid and palladium solution to at least about 100⁰C, for an amount of time sufficient to obtain the dark brown palladium lipoic acid complex.

The palladium or salt thereof is added to the acidic solution in a mole ratio of between about 1 and about 2 moles palladium to between 2 and about 4 moles of acid. Any method for mixing the palladium and acidic solution can be used, for example, stirring or agitation. The palladium-acidic solution can then be heated to a gentle boil, e.g., at least about 100⁰C, preferably between about 100° and about 200⁰C, and most preferably at about 100⁰C.

The acidic solution to which the palladium is added is selected from acids well known in the art. Such acids include perchloric acid, sulfuric acid, hyriodic acid, hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, nitrous acid, acetic acid, carbonic acid, and hydrogen sulfide. Preferably, the acidic solution is hydrochloric acid.

The palladium-acidic solution can be filtered by any method generally known in the art. Such methods include, for example, gravity filtration, suction filtration, centrifugation or the like. In a separate container lipoic acid is added to the basic solution in a molar ratio of between about 1 mole of lipoic acid per 7 moles of base. Any method of mixing the lipoic acid-base solution can be used, for example, stirring or agitation. Any of the above methods of filtration can then be used to eliminate any undissolved residue. The solution is preferably filtered to complete clarity.

The basic solution in which the lipoic acid is dissolved can be selected from bases known in the art, for example, sodium hydroxide, ethanolamine, potassium hydroxide, sodium acetate, dimethylamine, and the like. Preferably, the basic solution is sodium hydroxide.

Next, the dissolved palladium acid solution is added to the lipoic acid basic solution. The initially red mixture of palladium tetra chloride and base-dissolved lipoic acid solution is heated to a gentle boil, e.g., to at least about 100⁰C, preferably between 100 and 200⁰C, and most preferably to about 100⁰C. The solution is generally allowed to boil for about 10 minutes, though this is increased during manufacturing scale-up. The reaction mixture of the palladium and lipoic acid complex converts to a clear dark brown solution. The pH of the palladium lipoic acid complex solution can be adjusted preferably to a pH between about 6 and about 9, and more preferably to a pH of about 7.

Water can be added to the palladium lipoic acid complex solution in an amount sufficient to obtain a concentration of the palladium lipoic acid complex of at least about 0.01M, preferably between about 0.01M and about 0.08M, and most preferably 0.04M.

The palladium lipoic acid complex can also contain trace micronutrients such as for example, antioxidants, molybdenum, rhodium, ruthenium, thiamine, riboflavin, cyanocobalamin, N-acetyl cysteine, and N-formyl methionine. Other antioxidants that can be included in the complex include, for example, selenium, zinc, ascorbic acid, glutathione, lipoic acid, uric acid, carotenes, α-tocopherol, ubiquinol, and melatonin. Carotenoids, vitamins, minerals, flavonoids and other polyphenols antioxidants can also be added.

HOST

A host in need of increased energy includes any organism that could benefit from an increase in energy. In a preferred embodiment, the host in need of increased energy is an individual with HIV and/or AIDS. In another embodiment, the host in need suffers from mitochondrial toxicity, a mitochondrial disease and/or mitochondrial cytopathy. In addition, a host in need thereof is a chronologically old host or a physiologically old host.

The host can be a single cell or multi-celled organism. The host can be a domestic animal, such as, for example a dog or cat. The host can be a farm animal, such as, cattle, sheep, pigs or chickens. The host can be a laboratory animal, such as, rats, mice, or monkeys. The host can be a human.

The host in need is any host that would benefit from increased cellular respiration, increased mitochondrial electron transport chain activity, and/or reduced cellular reactive oxygen species.

HIV and/or AIDS

HIV and/or AIDS, as discussed above, is caused by a complex retrovirus which attacks T4 helper lymphocytes (CD4+ T cells). An individual suffering from HIV according to the invention, is any individual that has tested seropositive for HIV. An individual suffering from HIV may or may not have AIDS.

An individual suffering from AIDS, according to the invention, is an individual that has tested seropositive for HIV plus at least one of the following: • The development of an opportunistic infection — an infection that occurs when your immune system is impaired — such as Pneumocystis carinii pneumonia (PCP); and/or

• A CD4 lymphocyte count of 200 or less — a normal count ranges from 800 to 1,200

AGE OF HOST

A chronologically old host according to the invention can be, for example, a human of greater than about 60 years old, greater than about 70 years old, or greater than about 80 years old. Chronological age is often associated with increased senescence.

A physiologically old host is a host at any age that exhibits senescence. Senescence, according to the invention, is characterized by a declining ability to respond to stress. Senescence is also a reduction in the efficiency of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) repair, effectiveness of antioxidant enzymes, or the rate of free radical production. Senescence can be caused by chemical damage, such as, for example, cigarette smoking, pollution, or environmental chemicals. Free radicals, for example, displaced superoxide or hydroxyl radicals, in the body lead to senescence. Excessive alcohol consumption is yet another cause of senescence. Diseases, such as progeria, can also lead to senescence. Physiologically old individuals are in need of a replacement of diminished or displaced reactive oxygen species, and an increase in cellular respiration and electron transport chain activity.

MITOCHONDRIAL DISEASE, TOXICITY AND/OR CYTOPATHY

According to the invention, mitochondrial disease, toxicity and/or cytopathy is the result of any condition that results in the mitochondria being unable to completely burn food in order to generate energy. For example, a mitochondrial disease can be an inherited condition that runs in families (genetic). An uncertain percentage of patients acquire symptoms due to other factors, including mitochondrial toxins.

The types of mitochondrial disease inheritance include, for example, nDNA

(DNA contained in the nucleus of the cell) inheritance, also called autosomal inheritance. If this gene trait is recessive (one gene from each parent), often no other family members appear to be affected. There is a 25 percent chance of the trait occurring in other siblings. If this gene trait is dominant (a gene from either parent), the disease often occurs in other family members. There is a 50 percent chance of the trait occurring in other siblings.

In the case of mtDNA (DNA contained in the mitochondria) inheritance, there is a 100 percent chance of the trait occurring in other siblings, since all mitochondria are inherited from the mother, although symptoms might be either more or less severe.

A combination of mtDNA and nDNA defects can occur in which the relationship between nDNA and mtDNA and their correlation in mitochondrial formation is unknown.

Mitochondrial diseases can also be idiopathic and/or random occurrences. In particular, diseases that result from specific deletions of large parts of the mitochondrial DNA molecule are usually sporadic without affecting other family members.

Medicines or other toxic substances can trigger mitochondrial disease. Specific mitochondrial toxins include, for example, oxazolidinone, which inhibits mitochondrial protein synthesis, or ribovarin, often used in the treatment of hepatitis- C. FATIGUE AND/OR LOW ENERGY

Fatigue and/or low energy is defined herein as physical weakness or loss of strength. Physical weakness can be displayed in a host as actual muscle atrophy or an inability to complete tasks previously completed with ease. Fatigue and/or low energy can lead to other symptoms such as depression, tiredness, and exhaustion. Fatigue and/or low energy can affect any organism.

Fatigue and/or low energy can be general fatigue and/or low energy, affecting all systems of the body, or organ specific fatigue and/or low energy. The host can have fatigue and/or low energy associated with a disease of the muscles, for example, a myopathy.

INCREASING ENERGY

According to the invention, an increase in energy includes any measurable increase in mental or physical energy. Such an increase can be measured by any means known to the skilled practitioner. For example, an increase in energy can be measured by a patient describing an increase in mental of physical energy levels. It can be exhibited by an ability to maintain a physically or mentally active state for a longer period of time compared with energy levels prior to administration of the palladium lipoic acid complex. Energy can come from the breakdown of nutrients or an enhancement in an organism's ability to utilize broken down nutrients.

An increase in energy can also be measured by a specific increase in the concentration of cell respiratory substrates, and respiratory enzymes, and/or increased electron transport chain intermediates, enzymes, and mitochondrial complexes within a host; and/or a reduction or displacement of cellular reactive oxygen species. ENHANCING CELLULAR RESPIRATION

Enhancing cellular respiration includes increasing the activity of any of the reactions involved in cellular respiration. The reactions of cellular respiration are defined in standard Biochemistry texts and in the abundant electron transport literature, as is well known in the art.

Cellular energy can be increased by providing intermediates required for reactions, or providing sufficient substitutes for the reaction intermediates. Cellular energy can be increased by providing a reaction catalyst to improve the reaction rate or diminish electron loss. The use of palladium lipoic acid complex provides such a catalyst due to the paramagnetic nature of the palladium. The use of palladium catalysis in industry is extensive and includes for example the use of palladium in catalytic converters in automobiles. Use of palladium catalysis in industry is known for over one hundred years as, for example, in the Wacker process. Palladium has also been used in hydrogen storage devices due to its affinity for, and its exchange reactions with, electrons. The paramagnetic or spin character of palladium lowers the activation energy of palladium-electron interactions.

When bonded to palladium, the lipoic acid is a ligand, and the mitochondrial redox electrons of lipoic acid are subject to the paramagnetic influence of the palladium. In this way, the reactivity of lipoic acid electron exchange is spin-coupled and the electron transport chain (ETC) is catalyzed.

ELECTRON TRANSPORT CHAIN (ETC) ACTIVITY

Administration of palladium lipoic acid complex is useful for treating any host in need of an increase in mitochondrial ETC activity, an increase in cellular respiration and/or a substitute for displaced reactive oxygen species. Palladium lipoic acid complex influence impacts each component in the mitochondrial aerobic respiration cycle to a different extent. The process of energy production, cellular respiration, from the Krebs cycle through the electron transport chain, is greatly enhanced by the administration of a palladium lipoic acid complex.

Palladium lipoic acid complex functions as an electron acceptor from membrane phospholipids (M.Garnett, W.Garnett, Impedance spectroscopy of DNA, J.Inorg.Biochem.V.74, 1999). Palladium lipoic acid complex functions as a more efficient electron donor to the electron transport chain at Complex I than does free lipoic acid. Palladium lipoic acid acts as a competitive inhibitor at electron acceptor sites such as Rhodamine dye and Complex I ( M.Garnett, First Pulse - A Personal Journey in Cancer Research, P.I 17, First Pulse Projects, New York, 1998).

ADMINISTRATION

Administration of the palladium lipoic acid complex can be by any means known to the skilled practitioner. For example, administration can be oral, parenteral, topical, injection, or infusion. Parenteral administration includes, for example, intraveneous, intramuscular, subcutaneous, intradermal, topical, intrathecal, and interarterial administration. Most preferably, the administration method is oral.

The dose of palladium lipoic acid administered can be from about 0.ImL per day to about 4OmL per day. Preferably, the dosage is about 10 mL per day.

EXAMPLES

EXAMPLES 1 AND 2 - Palladium lipoic acid complex treated rats

Male albino rats of Wistar strain were used in the first two examples. The rats weighed approximately 350 ± 50g and were greater than 24 months of age. Rats were divided into three groups, six mice per group. The first group received nothing, the second received 5mg/Kg of α-lipoic acid dissolved in 0.5%NaOH, w/v of saline. The third group received Palladium lipoic acid formulation of 0.05mL/Kg.

The Palladium lipoic acid formulation used in these examples contained: palladium α-lipoic acid complex, traces of molybdenum, rhodium, ruthenium, thiamine, riboflavin, cyanocobalamin, N-acetyl cysteine and N-formyl methionine.

After thirty days of treatment animals were decapitated and the heart was excised. Excised hearts were stored at -70⁰C.

EXAMPLE 1 - Rat Mitochondrial Enzyme Activity

Activity was measured for the following Krebs cycle enzymes: isocitrate dehydrogenase; α-ketoglutarate; dehydrogenase; succinate dehydrogenase, and malate dehydrogenase. A heart tissue homogenate consisting of 10% heart tissue, was prepared in 5OmM phosphate buffer (pH 7.0) containing 0.25M (w/v) sucrose. The homogenate was centrifuged at 3000g for 10 min. and then the supernatant was centrifuged at 1 l,000g for 10 minutes at 4°C. The resulting mitochondrial pellets were washed twice with phosphate buffer to remove the sucrose. The fraction was then suspended in phosphate buffer.

Isocitrate dehydrogenase activity was determined by combining approximately 40μg mitochondrial protein, 100mmol/L trisodium isocitrate, 15mmol manganese chloride, 100mmol/L NAD⁺ and 100mmol/L Tris HCL (pH 7.5). This mixture was monitored at 340nm for 2min. with an interval of 30 sec. after the addition OfNAD⁺.

Activity of α-ketoglutarate dehydrogenase was determined by combining 40μg mitochondrial protein, 10mmol/L magnesium chloride, 20mmol/L thiamine pyrophosphate, 3mmol/L Co-A, 100mmol/L potassium α-ketoglutarate, and 0.5M potassium phosphate buffer (pH 8). Following addition of the α-ketoglutarate, the reaction was monitored at 340nm for 2 minutes at 30 second intervals.

Succinate dehydrogenase activity was determined by combining 20μg mitochondrial protein, 10mmol/L sodium succinate, 0.5mg BSA, 0.9 mmol/L potassium cyanide, 80μmol/L DCIP, 100mmol/L phosphate buffer (pH 7.4). Following DCIP addition, the reaction was monitored at 600nm for 2 minutes at 30 second intervals.

Malate dehydrogenase activity was determined using 40μg mitochondrial protein, 1.5mmol/L NADH (nicotinamide adenine dinucleotide), 7.6millimol/L oxaloacetate, 0.1M Tris-HCL buffer (pH 7.5), diluted to 3mL with distilled water. Following addition of NADH, the reaction was monitored at 340nm for 2 minutes at 30 second intervals.

Table 1. Krebs cycle enzymes activity measured in rat mitochondria

As shown in Table 1, the aged control group exhibited the lowest levels of enzyme activity. In contrast, the group receiving both the DL-α-lipoic acid and the palladium lipoic acid complex each showed a markedly significant increase in activity of all enzymes. Free lipoic acid (not actively bound to another molecule) is believed to neutralize reactive oxygen species. The free lipoic acid is used in these examples as a positive control.

It is significant to note that the palladium lipoic acid complex contains no free lipoic acid. Additionally, the amount of lipoic acid present, bound to palladium, in palladium lipoic acid complex is one thirteenth the dosage administered in the DL- α- lipoic acid.

The isocitrate dehydrogenase activity for both the lipoic acid and the palladium lipoic acid complex groups was increased by approximately four times the control groups levels. The activity level for the α-ketoglutaric dehydrogenase was increased 1.2 fold for the palladium lipoic acid complex and 1.8 fold for the lipoic acid group. Succinate dehydrogenase activity was increased 1.6 fold for the palladium lipoic acid complex group and only 1.0 fold for the lipoic acid only group. Finally, the malate dehydrogenase activity for the palladium lipoic acid complex group was increased 4.4 fold while the lipoic acid group experienced only a 3.9 fold difference.

EXAMPLE 2 - Rat Electron Transport Chain Enzyme Activity

The mitochondrial fraction obtained from centrifugation and washing of the mitochondrial pellet above, was frozen and thawed three to five times to release the enzymes of ETC complexes I, II, and III. Extraction of complex IV was performed with 0.5% Tween 80 phosphate buffer, v/v.

Complex I activity was determined by mixing 40μg mitochondrial protein, lμmol/L antimycin A, 3 mg BSA, 2mmol/L potassium cyanide, 5mmol/L magnesium chloride, 65μmol/L ubiquinone, 80μmol/L DCIP and diluting to a volume of ImL with 25mM phosphate buffer (pH 7.2). Following the addition of NADH, absorbance at 600 nm was monitored at 15s intervals for 2 minutes at room temperature. One micromole/L of rotenone was added after the 2 min. had passed and the absorbance was again measured for 2min. at 30sec intervals.

Complex II activity was determined by combining 40μg mitochondrial protein, 3mg/ml BSA, 2mmol/L EDTA, 2mmol/L potassium cyanide, lμmol/L antimycin A, lμmol/L rotenone, 20mmol/L sodium succinate, 65μmol/L decyl ubiquinone, and 50mmol/L phosphate buffer (pH 7.2). Following addition of 60μmol/L DCIP, the mixture was monitored at 600nm for 4minutes at 15 second intervals.

Complex III was evaluated using 20μg mitochondrial protein, lOOμmol/L EDTA, 2mg BSA, 3mmol/L sodium azide, 60μmol/L ferricytochrome-C, 1.3mmol/L decylubiquinol (the decylubiquinol had been mixed with a few grains of sodium dithionate and centrifuged at 12,00Og for lOmin. to form a transparent solution) and diluted to ImL with 50mM/L phosphate buffer (pH 8). Following addition of the decylubiquinol the reaction was monitored at 550nm for 2 minutes. Following the addition of lμmol/L of antimycin A the reaction was again monitored for 2 minutes.

Complex IV activity was determined using lOμg mitochondrial protein extracted in 0.5% Tween 80 in 3OmM phosphate buffer at pH 7.4. To this was added ImL ferrocytochrome -C and diluted with phosphate buffer to 1.3mL.Following the addition of ferrocytochrome-C, the absorbance was measured at 550nm at an interval of 15sec. for 4 minutes. Results are listed in Table 2, below.

Table 2. Rat Electron Transport Chain Enzyme Activity

While the DL-α-lipoic acid did show significant effects, the dosage required was thirteen times that of the lipoic acid content of the palladium lipoic acid complex. Both the lipoic acid and the palladium lipoic acid complex exhibited similar results for complex I, III, and IV. Neither the lipoic acid nor the palladium lipoic acid complex had a significant effect on complex III. Complex I was increased 2 fold by both the lipoic acid and the palladium lipoic acid complex. Complex IV was increased approximately 1.3 times by both the lipoic acid and the palladium lipoic acid complex.

It is interesting to note that with regard to Complex II, the palladium lipoic acid complex had almost twice the effect of the lipoic acid alone. As stated above, Complex II is believed to be the location within the ETC where the most electron loss, and subsequent ectopic superoxide production, occurs.

The results of this example show that palladium lipoic acid complex effectively increases the activity of the electron transport chain. EXAMPLE 3 - Palladium lipoic acid complex treated dogs

The urine of five dogs was collected and measured for mitochondrial metabolites before and two weeks after receiving palladium lipoic acid. The dosage was lOOμL /lOlbs. Table 3 represents the values of metabolites prior to administration of the palladium lipoic acid complex and Table 4 after the administration.

Table 3 : Amount of Metabolites in Urine Prior to Palladium Lipoic Acid Complex

Administration

Table 4: Amount of Metabolites in Urine Post Palladium Lipoic Acid Complex

Administration

A comparison of the data in Tables 3 and 4 shows an increase in all Krebs cycle byproducts. Accordingly, palladium lipoic acid complex administration appears to increase the activity of the Krebs cycle. This results in the generation of additional ATP and high energy intermediates NADH and FADH₂ to be used in the ETC.

EXAMPLE 4 - Human AIDS Patients and Energy

A study of 22 patients having the HIV virus presenting as AIDS was initiated. Patients exhibited a variety of symptoms including depression, lack of energy, weakness, and AIDS-wasting. Each patient was receiving medical treatment for the virus but treatment regimens varied. Treatment regimens included, for example, acyclovir, efavirenz/emtricitabine/tenofovir disoproxil fumarate, olanzapine, lopinavir/ritonavir, and stavudine; or treatment with atazanavir sulfate, ritonavir, and abacavir sulfate/lamivudine.

Each patient was given, as an adjunct to their present treatment regimen, palladium lipoic acid complex. The dosage given each patient was 3 tsp (15mL) twice daily. In addition to palladium lipoic acid, the complex included: N-acetyl cysteine; vitamin A acetate; vitamin Bi and B₂; trace amounts Of Bi₂, N-formyl methionine, molybdenum, rhodium, and ruthenium.

Patients immediately reported increased energy, reduced depression, increased appetite and increased strength. After several months of treatment, certain patients exhibited a decreased HIV viral load and increased CD4 counts.

Claims

1. A method for increasing energy in a host in need thereof comprising administering an effective amount of a palladium lipoic acid complex to said host.

2. A method according to claim 1, wherein said host in need thereof is a host suffering from HIV and/or AIDS.

3. A method according to claim 1, wherein said host in need thereof is a chronologically old host.

4. A method according to claim 1, wherein said host suffers from mitochondrial disease, toxicity and/or cytopathies.

5. A method according to claim 1, wherein said host in need thereof is a physiologically old host.

6. A method according to claim 1, wherein said palladium lipoic acid complex further comprises one or more antioxidants.

7. A method according to claim 1, wherein said palladium lipoic acid complex administered at least once per day.

8. A method according to claim 1, wherein said administration is in an amount from about O.OlmL/kg of host body weight to about 10 mL/kg of host body weight.

9. A method according to claim 1, wherein said administration is from about 0.05 mL/Kg of host body weight to about 5 mL/kg of host body weight.

10. A method according to claim 1, wherein said increased energy is an increase in cellular respiration.

11. A method according to claim 1, wherein said increased energy is an increase in mitochondrial electron transport chain activity.

12. A method according to claim 1, wherein said increased energy is a reduction or displacement of cellular reactive oxygen species.