Research of Magnesium + Potassium Aspartates

[Sean R]

http://curezone.com/forums/fm.asp?i=1869088#i

The term “chronic fatigue syndrome” is a recent one, but there’s no reason to believe that it’s a new disease. Clinicians recognized the soul-draining exhaustion, poor stamina, flu-like symptoms, unrefreshing sleep, and problems with concentration and short-term memory that characterize the disorder as early as the times of Queen Victoria, when it was termed neurasthenia. The disorder achieved greater recognition the 1950s, although under the dismissive term “housewife syndrome,” and researchers began to look for its biological basis.

The Hunt

Dr. Henri Laborit, a researcher with the French navy who went on to make many fundamental discoveries in psychiatric pharmacology, hypothesized that the exhaustion of body and brain associated with chronic fatigue might be the result of a failure of cellular bioenergetics. Accordingly, he began looking for a treatment by testing a variety of compounds already known, in his day, to be metabolites in the body’s energy cycles, looking for natural molecules that could restore neuromuscle function to exhausted laboratory animals.

Laborit screened a wide range of substances involved in various ways with energy production at the cellular level, including glutamate, glutamine, isotonic ion mixtures, and assorted sugars, vitamins, and amino acids and their mineral salts – and found that fully-reacted magnesium and potassium aspartates most consistently offset metabolic exhaustion in his models.

These compounds exert a range of important influences on the energy-producing tricarboxylic acid (TCA) cycle in the mitochondrial matrix. Aspartic acid is a critical energy-carrying TCA intermediate produced from oxaloacetate, as well as being an excitatory neurotransmitter in the central nervous system. Magnesium plays a critical role in the production and stabilization of ATP: it activates almost all the enzymes of glycolytic and the tricarboxylic acid cycle, and forms a complex with ATP, without which it is quickly broken down into the low-energy adenosine diphosphate (ADP) and inorganic phosphate and cannot fuel cell metabolism and transport. And while widely underappreciated, potassium is an essential electrolyte involved in both electrical and cellular functions in the body, which assists in the regulation of the body’s acid-base balance and is needed for the proper functioning of nerve cells, being essential for the transmission of neurochemical messages along the axon. Potassium deficiency results in symptoms very similar to aspects of chronic fatigue, featuring muscular weakness, depression, fatigue, and malaise. Furthermore, magnesium and potassium are known to cooperate in the body: magnesium enhances the cellular transport of potassium.

The Trials

Laborit’s work was picked up by the pharmaceutical giant Wyeth, who moved the energizing combination through further animal experiments and ultimately into multiple uncontrolled and ultimately double-blind studies involving over 3 000 patients under the trade name “Spartase.” Consistently across these trials, 65 to 91% of chronic fatigue sufferers taking fully-reacted magnesium and potassium aspartates (500 mg of each, twice daily) experienced clear-cut alleviation of their symptoms. Victims typically began to notice the effects within a week: improvements were usually noted within five days, and rarely took more than 10 days to set in.

In one double-blind clinical trial involving 145 patients, 85% of those given potassium and magnesium aspartates reported an increase in strength or physical activity, versus to only 9% of patients taking the placebo. This study included patients whose fatigue had no obvious physical cause, along with patients with fatigue associated with anxiety neuroses, gastrointestinal disturbances, menopause, the postpartum period, and a previous influenza infection.

A second placebo-controlled study involved 84 women and 16 men who had been suffering with fatigue symptoms unrelated to depression for more than two years. Participants in the trial took either the aspartate mixture or dummy pills for periods of either two or 4-6 weeks. Over the course of 4-10 days, people taking the supplement began to awaken from their fatigue, with 87% of the fully-reacted magnesium and potassium aspartate supplementers experiencing relief.

Researchers associated with the company, in collaboration with the Homestead Air Force Base in Florida and the University of Tennessee College of Medicine, performed an additional series of studies. One of these studies was a placebo-controlled clinical trial, in which 32 patients who had some organic disease (including 24 people with arthritis, with the remainder made up of persons with headache, depression, rheumatic fever, trauma, asthma, lupus, infectious mononucleosis (“mono”) or duodenal ulcer) under stable conditions for a month, received either the standard dose of fully-reacted magnesium and potassium aspartates or placebo tablets for a month, and then crossed over to the other treatment.

While they were taking the supplement, 21 (65%) of these individuals reported relief of their fatigue, while 9 were deemed “questionable” (since they reported relief with magnesium and potassium aspartates, but also seemed to feel better while taking the placebo); only two reported no response. During the placebo period, only three people reported relief of their fatigue, with 25 experiencing no response to the dummy treatment.

Out of curiosity, these same researchers tried giving the aspartate mixture to 46 healthy, unfatigued persons, with no hint as to the results to be expected beyond assuring them of the safety of the supplement. Only four people reported feeling better while taking the supplement, clearly, there was some direct need for the supplement in fatigued individuals.

Finally, the same team used rheotome measurements to test the neuromuscular excitability of healthy persons with no fatigue, fatigued persons with no organic disease, and the same fatigued persons after they had taken magnesium and potassium aspartates. Compared to the control group, fatigued persons showed significant evidence of neuromuscular fatigue, as demonstrated by hyperexcitability of both nerve and muscle. Interestingly, after taking the supplements, the hyperexcitability of the muscles was significantly normalized by fully-reacted magnesium and potassium aspartates – yet the hyperexcitability of the nerves was not affected. The correlation between normalization of the patients’ muscular excitability and his or her subjective experience of relief was 88%. Tests on fatigued individuals with stable, debilitating disease (including cancer, hyperthyroidism, and arthritis) led to similar results.

In her blinded trial, Dr. Palma Formica reported that 87% of her fatigued patients using magnesium and potassium aspartates supplements experienced relief, which she characterized as “startling”: patients taking fully-reacted magnesium and potassium aspartates “had become alert, cheerful, animated and energetic and walked with a lively step. They stated that sleep refreshed them as it had not done for months … Morning exhaustion had completely subsided”.

The Burial

“Spartase” was a listed “drug” for fatigue in the United States in 1961. The company had big plans for it: not only was there a potentially huge market for fully-reacted magnesium and potassium aspartates in desperately fatigued people, but according to Dr. Jonathan V. Wright they also were pursuing evidence that it was also an effective treatment for erectile dysfunction. But instead, the FDA banned this magnesium and potassium aspartates supplement from the pharmaceutical market in 1970. No new evidence had been advanced to suggest that it was unsafe or ineffective. So what happened?

Following amendments to the Food, Drug, and Cosmetics Act of 1962, the FDA commissioned a panel of psychopharmacologists to review all of the drugs that had been introduced between 1938 and 1962. There were serious problems with this process, as outlined in a recent article in the Drug Discovery sister-journal of the prestigious science publication Nature by Dr. Edward Shorter, who is Hannah Chair in the History of Medicine at the University of Toronto and a Jason A. Hannah Medalist. The experts consulted were academics and asylum researchers with minimal clinical experience with the drugs they were reviewing, at a time when 70% of psychiatric drugs were prescribed by GPs and internists. And when the experts disagreed about a drug’s efficacy, even one ‘nay’ on a panel would bump a treatment from being classified “effective” to “probably effective,” even if all the other panelists thought it to be a good therapy.

And then, FDA forced the withdrawal of all of those “probably effective” drugs, unless the companies holding their licenses were ready to initiate a new round of large controlled trials immediately, within months of the panel’s reports. This wasn’t just unreasonable – it was impossibile: in 1970, the National Association of Science writers was told that there literally were “just not enough clinical investigators in this country to carry out all the studies that will be demanded” to fulfill FDA requirements. In the ensuing purge, over 48% of all of the psychiatric drugs on the market were forced off the market – including the previously-registered fully-reacted magnesium and potassium aspartate supplement.

A Rebirth – with Complications

After the Dietary Supplements Health and Education Act (DSHEA) increased Americans’ access to supplements in 1994, various ‘magnesium-potassium aspartate’ supplements appeared on the market, although they continued to be unavailable legally in Canada. Unfortunately, true, fully-reacted magnesium and potassium aspartates are both expensive and bulky, because the aspartic acid chelate takes up a lot of room; as a result, you need four capsules or tablets a day to get 1000 milligrams of each compound a day – the dose established by clinical trials.

To make their pills more competitive, most supplement companies sell “compromise” products. Some companies sell low-potency products, or just tell their customers take less capsules than is needed to get the effective dose. But most companies just don’t put the real thing into their pills: instead, they use so-called magnesium and potassium aspartate “blends,” which contain magnesium and potassium aspartates “cut” with higher-density (but less bioavailable and less effective) magnesium and potassium forms (such as oxides, carbonates, or chlorides). Using these diluted raw materials, companies can pretend that there is more magnesium and potassium aspartate in their pills than there really is, ironically making an inferior product look unusually “high-potency.”

But today, true, fully-reacted magnesium and potassium aspartate supplements are available from responsible suppliers. While it can be hard for consumers to tell a real product from a bogus one, one way to distinguish authentic magnesium and potassium aspartates from “blends” is to look at the claimed elemental content. The real thing assays at 7.5% elemental magnesium and 22.5% potassium by mass (or about 19 and 55 milligrams per 250 mg of the respective chelate ingredients). This means more capsules – and more people experiencing the full benefits of taking the authentic supplement.

Fatigue steals lives. By giving your cells the nutrients they need, in their best, bioactive forms, you can replenish their strength and claim yours back.

References
Hicks JT. Treatment of fatigue in general practice: a double blind study. Clin Med. 1964 Jan; 71(1): 85-90.
Formica PE. The housewife syndrome. Treatment with the potassium and magnesium salts of aspartic acid. Curr Ther Res Clin Exp. 1962 Mar; 4: 98-106.
Shaw DL, Chesney MA, Agersborg HP. Management of fatigue: a physiologic approach. Am J Med Sci. 1962 Jun; 243: 758-69.
Nagle FJ, Balke B, Ganslen RV, Davis AW. The mitigation of physical fatigue with “Spartase”. FAA Office of Aviation Medicine Reports. Rep Civ Aeromed Res Inst US. 1963 Jul;26:1-10.

[hardasnails1973]

@Sean R 3823 wrote:

http://curezone.com/forums/fm.asp?i=1869088#i

The term “chronic fatigue syndrome” is a recent one, but there’s no reason to believe that it’s a new disease. Clinicians recognized the soul-draining exhaustion, poor stamina, flu-like symptoms, unrefreshing sleep, and problems with concentration and short-term memory that characterize the disorder as early as the times of Queen Victoria, when it was termed neurasthenia. The disorder achieved greater recognition the 1950s, although under the dismissive term “housewife syndrome,” and researchers began to look for its biological basis.

The Hunt

Dr. Henri Laborit, a researcher with the French navy who went on to make many fundamental discoveries in psychiatric pharmacology, hypothesized that the exhaustion of body and brain associated with chronic fatigue might be the result of a failure of cellular bioenergetics. Accordingly, he began looking for a treatment by testing a variety of compounds already known, in his day, to be metabolites in the body’s energy cycles, looking for natural molecules that could restore neuromuscle function to exhausted laboratory animals.

Laborit screened a wide range of substances involved in various ways with energy production at the cellular level, including glutamate, glutamine, isotonic ion mixtures, and assorted sugars, vitamins, and amino acids and their mineral salts – and found that fully-reacted magnesium and potassium aspartates most consistently offset metabolic exhaustion in his models.

These compounds exert a range of important influences on the energy-producing tricarboxylic acid (TCA) cycle in the mitochondrial matrix. Aspartic acid is a critical energy-carrying TCA intermediate produced from oxaloacetate, as well as being an excitatory neurotransmitter in the central nervous system. Magnesium plays a critical role in the production and stabilization of ATP: it activates almost all the enzymes of glycolytic and the tricarboxylic acid cycle, and forms a complex with ATP, without which it is quickly broken down into the low-energy adenosine diphosphate (ADP) and inorganic phosphate and cannot fuel cell metabolism and transport. And while widely underappreciated, potassium is an essential electrolyte involved in both electrical and cellular functions in the body, which assists in the regulation of the body’s acid-base balance and is needed for the proper functioning of nerve cells, being essential for the transmission of neurochemical messages along the axon. Potassium deficiency results in symptoms very similar to aspects of chronic fatigue, featuring muscular weakness, depression, fatigue, and malaise. Furthermore, magnesium and potassium are known to cooperate in the body: magnesium enhances the cellular transport of potassium.

The Trials

Laborit’s work was picked up by the pharmaceutical giant Wyeth, who moved the energizing combination through further animal experiments and ultimately into multiple uncontrolled and ultimately double-blind studies involving over 3 000 patients under the trade name “Spartase.” Consistently across these trials, 65 to 91% of chronic fatigue sufferers taking fully-reacted magnesium and potassium aspartates (500 mg of each, twice daily) experienced clear-cut alleviation of their symptoms. Victims typically began to notice the effects within a week: improvements were usually noted within five days, and rarely took more than 10 days to set in.

In one double-blind clinical trial involving 145 patients, 85% of those given potassium and magnesium aspartates reported an increase in strength or physical activity, versus to only 9% of patients taking the placebo. This study included patients whose fatigue had no obvious physical cause, along with patients with fatigue associated with anxiety neuroses, gastrointestinal disturbances, menopause, the postpartum period, and a previous influenza infection.

A second placebo-controlled study involved 84 women and 16 men who had been suffering with fatigue symptoms unrelated to depression for more than two years. Participants in the trial took either the aspartate mixture or dummy pills for periods of either two or 4-6 weeks. Over the course of 4-10 days, people taking the supplement began to awaken from their fatigue, with 87% of the fully-reacted magnesium and potassium aspartate supplementers experiencing relief.

Researchers associated with the company, in collaboration with the Homestead Air Force Base in Florida and the University of Tennessee College of Medicine, performed an additional series of studies. One of these studies was a placebo-controlled clinical trial, in which 32 patients who had some organic disease (including 24 people with arthritis, with the remainder made up of persons with headache, depression, rheumatic fever, trauma, asthma, lupus, infectious mononucleosis (“mono”) or duodenal ulcer) under stable conditions for a month, received either the standard dose of fully-reacted magnesium and potassium aspartates or placebo tablets for a month, and then crossed over to the other treatment.

While they were taking the supplement, 21 (65%) of these individuals reported relief of their fatigue, while 9 were deemed “questionable” (since they reported relief with magnesium and potassium aspartates, but also seemed to feel better while taking the placebo); only two reported no response. During the placebo period, only three people reported relief of their fatigue, with 25 experiencing no response to the dummy treatment.

Out of curiosity, these same researchers tried giving the aspartate mixture to 46 healthy, unfatigued persons, with no hint as to the results to be expected beyond assuring them of the safety of the supplement. Only four people reported feeling better while taking the supplement, clearly, there was some direct need for the supplement in fatigued individuals.

Finally, the same team used rheotome measurements to test the neuromuscular excitability of healthy persons with no fatigue, fatigued persons with no organic disease, and the same fatigued persons after they had taken magnesium and potassium aspartates. Compared to the control group, fatigued persons showed significant evidence of neuromuscular fatigue, as demonstrated by hyperexcitability of both nerve and muscle. Interestingly, after taking the supplements, the hyperexcitability of the muscles was significantly normalized by fully-reacted magnesium and potassium aspartates – yet the hyperexcitability of the nerves was not affected. The correlation between normalization of the patients’ muscular excitability and his or her subjective experience of relief was 88%. Tests on fatigued individuals with stable, debilitating disease (including cancer, hyperthyroidism, and arthritis) led to similar results.

In her blinded trial, Dr. Palma Formica reported that 87% of her fatigued patients using magnesium and potassium aspartates supplements experienced relief, which she characterized as “startling”: patients taking fully-reacted magnesium and potassium aspartates “had become alert, cheerful, animated and energetic and walked with a lively step. They stated that sleep refreshed them as it had not done for months … Morning exhaustion had completely subsided”.

The Burial

“Spartase” was a listed “drug” for fatigue in the United States in 1961. The company had big plans for it: not only was there a potentially huge market for fully-reacted magnesium and potassium aspartates in desperately fatigued people, but according to Dr. Jonathan V. Wright they also were pursuing evidence that it was also an effective treatment for erectile dysfunction. But instead, the FDA banned this magnesium and potassium aspartates supplement from the pharmaceutical market in 1970. No new evidence had been advanced to suggest that it was unsafe or ineffective. So what happened?

Following amendments to the Food, Drug, and Cosmetics Act of 1962, the FDA commissioned a panel of psychopharmacologists to review all of the drugs that had been introduced between 1938 and 1962. There were serious problems with this process, as outlined in a recent article in the Drug Discovery sister-journal of the prestigious science publication Nature by Dr. Edward Shorter, who is Hannah Chair in the History of Medicine at the University of Toronto and a Jason A. Hannah Medalist. The experts consulted were academics and asylum researchers with minimal clinical experience with the drugs they were reviewing, at a time when 70% of psychiatric drugs were prescribed by GPs and internists. And when the experts disagreed about a drug’s efficacy, even one ‘nay’ on a panel would bump a treatment from being classified “effective” to “probably effective,” even if all the other panelists thought it to be a good therapy.

And then, FDA forced the withdrawal of all of those “probably effective” drugs, unless the companies holding their licenses were ready to initiate a new round of large controlled trials immediately, within months of the panel’s reports. This wasn’t just unreasonable – it was impossibile: in 1970, the National Association of Science writers was told that there literally were “just not enough clinical investigators in this country to carry out all the studies that will be demanded” to fulfill FDA requirements. In the ensuing purge, over 48% of all of the psychiatric drugs on the market were forced off the market – including the previously-registered fully-reacted magnesium and potassium aspartate supplement.

A Rebirth – with Complications

After the Dietary Supplements Health and Education Act (DSHEA) increased Americans’ access to supplements in 1994, various ‘magnesium-potassium aspartate’ supplements appeared on the market, although they continued to be unavailable legally in Canada. Unfortunately, true, fully-reacted magnesium and potassium aspartates are both expensive and bulky, because the aspartic acid chelate takes up a lot of room; as a result, you need four capsules or tablets a day to get 1000 milligrams of each compound a day – the dose established by clinical trials.

To make their pills more competitive, most supplement companies sell “compromise” products. Some companies sell low-potency products, or just tell their customers take less capsules than is needed to get the effective dose. But most companies just don’t put the real thing into their pills: instead, they use so-called magnesium and potassium aspartate “blends,” which contain magnesium and potassium aspartates “cut” with higher-density (but less bioavailable and less effective) magnesium and potassium forms (such as oxides, carbonates, or chlorides). Using these diluted raw materials, companies can pretend that there is more magnesium and potassium aspartate in their pills than there really is, ironically making an inferior product look unusually “high-potency.”

But today, true, fully-reacted magnesium and potassium aspartate supplements are available from responsible suppliers. While it can be hard for consumers to tell a real product from a bogus one, one way to distinguish authentic magnesium and potassium aspartates from “blends” is to look at the claimed elemental content. The real thing assays at 7.5% elemental magnesium and 22.5% potassium by mass (or about 19 and 55 milligrams per 250 mg of the respective chelate ingredients). This means more capsules – and more people experiencing the full benefits of taking the authentic supplement.

Fatigue steals lives. By giving your cells the nutrients they need, in their best, bioactive forms, you can replenish their strength and claim yours back.

References
Hicks JT. Treatment of fatigue in general practice: a double blind study. Clin Med. 1964 Jan; 71(1): 85-90.
Formica PE. The housewife syndrome. Treatment with the potassium and magnesium salts of aspartic acid. Curr Ther Res Clin Exp. 1962 Mar; 4: 98-106.
Shaw DL, Chesney MA, Agersborg HP. Management of fatigue: a physiologic approach. Am J Med Sci. 1962 Jun; 243: 758-69.
Nagle FJ, Balke B, Ganslen RV, Davis AW. The mitigation of physical fatigue with “Spartase”. FAA Office of Aviation Medicine Reports. Rep Civ Aeromed Res Inst US. 1963 Jul;26:1-10.

You need to find out why your magnesium are low. Are you toxic, have anxiety issues, or have adrenal imbalances which can cause refractory magnesium deficiency because you waste it at a fast rate. Look for cause not effect relationship.

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