Book Notes for From Fatigued to Fantastic!
Chapter 2: More Information On Energy Nutrients That Fire Up Your Mitochondrial Energy Furnaces!
In this section:
• The Consequences of Mitochondrial Dysfunction
• Improving Mitochondrial Function
• Aspartates and Malic Acid
• Thiamine Pyrophosphate (TPP)
• L-Carnitine and Acetyl-L-Carnitine
• Coenzyme Q10, Iron, Sulfur, and Copper: The Electron Transport System
• Treating Mitochondrial Dysfunction Summarized
• Important Points
Although the premier nutrient for enhancing energy production is D-ribose (Corvalen1 scoop or 5000 mg 3x day for 3 weeks then 2x day), other nutrients can also be helpful. These include:
* CoEnzyme Q10
* Mg-K aspartate
Let’s look at these in more depth.
Besides the fact that fatigue in itself suggests low energy production, a large number of clinical findings common in CFIDS/FMS can be explained by mitochondrial furnace malfunction. For example, if the mitochondrial furnaces are working poorly, this would affect the brain, and could account for that common CFIDS/FMS symptom known as brain fog. In addition, mitochondrial dysfunction can cause decreases in levels of neurotransmitters in the brain, specifically low dopamine and acetylcholine, and possibly low serotonin. Particularly severe changes in the hypothalamus have been seen in mitochondrial dysfunction syndromes. This could account for the hypothalamic suppression characteristic of CFIDS/FMS.1
In the liver, you would see a decreased ability to eliminate toxins and medications. This could contribute to sensitivities to both medications and environmental factors. In the muscles, mitochondrial dysfunction would lead to low energy production and accumulation of excessive amounts of lactic acid during exercise. Lactic acid is the compound that causes your muscles to ache after exercise, so this can cause achiness and may cause postexertional fatigue.
The kidneys also could be affected. Specifically, there might be a defect in the filtration and detoxification process. CFIDS/FMS researcher Dr. R. Paul St. Amand, postulates that fibromyalgia is caused by a genetic defect in phosphate excretion by the kidneys. It is conceivable that poor kidney function resulting from mitochondrial dysfunction may also be involved.
Mitochondrial dysfunction would also cause digestion to suffer. This could be related to the bowel problems that plague so many people with chronic fatigue and fibromyalgia. Finally, in the immune system, you would expect to see poor white blood cell function and therefore a decreased ability to fight infection. Thus, mitochondrial dysfunction might well be the root cause of—or at least a contributing factor to—the hypothalamic, immune, neurotransmitter, nutritional, detoxification, sleep and other disorders seen in CFIDS/FMS. (For a visual representation of the interrelationships between all these factors, see Figure 8.1, The CFIDS/FMS Cycle.)
If mitochondrial dysfunction is an underlying or contributing cause to CFIDS/FMS, the next question is whether anything can be done to make those cellular energy furnaces work better. Fortunately, there are a number of natural treatments available to do just that. Let us now look at some of the treatments that can improve mitochondrial energy production.
Aspartates and malic acid are compounds that are needed to “rescue” part of the Krebs cycle when levels of the nutrient thiamine pyrophosphate (TPP) are low. (More about TPP later in this chapter.) The Krebs cycle is series of chemical reactions that take place in the body’s cells and allow glucose to be used for the production of energy. It is also sometimes referred to as tricarboxylic acid (TCA) cycle.
As dietary supplements, aspartates and malic acid have at least three excellent qualities: They are very effective; they are safe and nontoxic, even for those with chemical sensitivities; and they are cheap! Although the other supplements I will discuss in this chapter are also safe and usually have no side effects, they can be expensive.
Aspartates are compounds based on the amino acid aspartic acid. Many studies show aspartates to be helpful for various fatigue syndromes. Over 3,000 patients have been studied, with many in placebo-controlled trials.2 To achieve the desired effect, the potassium and magnesium needed to be chemically attached to the aspartate. Studies using each component separately or in various combinations did not show the desired effect.3
When the proper type of aspartate was used, about 70 to 85 percent of patients improved, compared with to 25 percent of patients given a placebo.4 Results often begin in ten days. The usual dose is 1 gram (1,000 milligrams) twice a day (or 500 milligrams four times day) after meals. You can stop taking the supplement after twelve weeks. If fatigue recurs, you should resume the aspartate for six- to eight-week periods as needed.
As noted above, a true aspartate needs to be subjected to a process that creates a solid bond between the aspartate and the potassium and magnesium. This makes sense, because aspartate plays a role in transporting potassium and magnesium across cell membranes—the boundary between the insides and outsides of cells. There is evidence to suggest that cell membranes may malfunction in CFIDS. If magnesium and potassium are not properly bound to aspartate, it is more difficult for the aspartate to carry them into the cell, and, perhaps, into the mitochondria.5 If a company says a product is fully reacted, it’s probably the real thing. If it says “aspartate complex,” it may not be as effective. General Nutrition Centers has a product containing 250 milligrams each of magnesium aspartate and potassium aspartate—that is, a total of 500 milligrams of aspartates in the same tablet—that has the proper ratios to suggest it is chemically reacted.
The combination of magnesium and malic acid is also critical. Malic acid is a compound that occurs naturally in foods, in fruits in general and in especially high levels in apples. (Remember the old saying: An apple a day keeps the doctor away.) When levels of malic acid and the other compounds discussed in this article are low, the body often has to shift to a very inefficient (anaerobic) means of generating energy. This contributes to the abnormal buildup of lactic acid (noted above) that occurs after exertion in CFIDS/FMS.6 This causes muscle pain, achiness, and fatigue.
Malic acid is critical both during healthy (aerobic) and inefficient (anaerobic) muscle metabolism. Interestingly, malic acid can be converted to aspartate as well. My favorite tablet forms of magnesium with malic acid is Fibrocare, made by a company called To Your Health. Each tablet contains 75 milligrams of magnesium glycinate, which is better tolerated than most magnesium preparations; 25 milligrams of vitamin B6, which increases magnesium cell membrane transfer and utilization; 300 milligrams of malic acid; 25 milligrams of vitamin B1 (thiamine); 50 milligrams of vitamin C; and 2H milligrams of manganese. I recommend taking two tablets two to three times a day for eight months, and then decreasing to two tablets a day. Take less if diarrhea is a problem. An even better recommended source of magnesium and malic acid is the From Fatigued To Fantastic Energy Revitalization System powder formula.
Thiamine pyrophosphate is the activated form of vitamin B1 (thiamine). It is essential for many steps in the process of energy production. For example, it is needed to get carbohydrates to burn efficiently. It is also needed to clear out excess lactic acid, which makes muscles ache. I suspect that TPP is another key player in mitochondrial dysfunction. Dr. Jean Eisenger and his associates in Toulon, France, have done brilliant research in this area. He has found significant impairment of thiamine (vitamin B1) function in FMS. Thiamine must be converted to its activated form (TPP) to do its job.
A compound called adenosine triphosphate (ATP) is the “currency” used by the mitochondria in the cells of living things to generate energy. Anything that depletes ATP (for example, infections, toxic exposures to the liver, chronic muscle shortening from any cause, and, possibly, brain ATP loss) may prevent the formation of TPP, which in turn further diminishes ATP production. This can effectively shut down the functioning of those mitochondria, resulting in a Catch-22—energy is like the body’s money and, as the old saying goes, It takes money (energy) to make money (energy)!
The good news is that Dr. Eisenger has found that several treatments can help. First, receiving 50 milligrams of TPP by intramuscular injection three times a week for six weeks decreased pain in over 76 percent of FMS patients he studied.7 This is not yet readily available in the United States, but it can be imported for personal use from Lab ISI in Italy, which sells it under the trade name CoCarboxylase (see Appendix J: Resources). I would use the 100-milligram vials (about two dollars each wholesale) three times a week. These shots do cause a sore bottom.
Taking 25 to 100 milligrams of vitamin B6 (pyridoxine) and 300 to 450 milligrams of magnesium is helpful. Vitamin B6 is critical to thiamine function. However, if magnesium is not added, thiamine can aggravate magnesium deficiency.8
Phosphocreatine (and, I suspect, creatine) also helps if you need a quick burst of energy. I will discuss creatine below. Finally, using the other treatments suggested in this chapter to promote ATP production will likely result in the body making its own TPP. Therefore we no longer use TPP.
Low levels of the carnitine compound acylcarnitine in the blood or muscles of people with CFIDS/FMS have been found by two different research centers.9 Carnitine plays many roles in the body. It has the critical function of preventing the mitochondria from being shut down when the system backs up. It does this by keeping a substance called acetyl coenzyme A from building up and shutting down the TCA cycle and the electron transport system, the cell’s effective energy burning systems. (More about the electron transport system later in this chapter.) Also, without sufficient carnitine, the body cannot burn fat (and, in fact, makes excess fat), resulting in large weight gains.
L-Carnitine is a naturally occurring form of carnitine that is only found in animal flesh. Beef is high in carnitine. Carnitine can also be synthesized in the body. This process requires adequate amounts of the amino acid lysine, which is low in rice-based vegetarian diets (which also have no carnitine).10 I suspect that the real reason many CFIDS patients who take lysine to prevent herpes outbreaks see their symptoms improve may be that this increases the body’s carnitine production.
In my experience, and that of other clinicians, taking supplemental L-carnitine has not been very helpful, and D-L-carnitine can actually worsen symptoms.11 Taking 500 to 1,000 milligrams of acetyl-L-carnitine milligrams three times a day, however, can be very helpful. It has no side effects except for its cost, usually $1.50 or more for 1,000 milligrams. Adding 500 to 1,000 milligrams of L-lysine, which is cheaper, can decrease the amount of acetyl-L-carnitine you need to take by helping your body to make its own carnitine. The body also requires vitamin C (I recommend 200 milligrams a day) and B-complex vitamins to make carnitine.12 I suspect that most people can lower their dose of acetyl-L-carnitine after eight to twelve weeks—for example, to 500 milligrams a day—or even stop it. Any brand is fine as long as it is pure acetyl-L-carnitine.
Nicotinamide adenine dinucleotide plus high-energy hydrogen (NADH), also known as coenzyme 1, is necessary to carry the energy made by burning carbohydrates, proteins, and fats from the TCA cycle to the electron transport system in the mitochondria, so that it can be converted into ATP energy “dollars.” NADH’s ability to be turned into energy depends on the proper functioning of various enzymes and other compounds.
In people with CFIDS/FMS, the body has difficulty producing NADH. Because NADH has many other functions, a lack of it is disastrous for the body. One major function of NADH is in stimulating the production of the important neurotransmitters dopamine, norepinephrine, and serotonin. These neurotransmitters appear to be low in people with CFIDS/FMS; low NADH may contribute to these deficiencies. Serotonin is important for sleep and emotional balance. Norepinephrine is responsible for alertness, concentration, and mental activity. Dopamine is also responsible for a sense of well-being and for energizing the body. It stimulates strength, coordination, cognition (mental functioning), mood, sex drive, and the secretion of growth hormone, which is also low in people with CFIDS/FMS. In addition, serotonin needs NADH and ATP to get into the cells where it does its job. NADH stimulates the enzyme tyrosine hydroxylase (TH), which is the key enzyme for the production of dopamine. Taking supplemental NADH can stimulate the production of dopamine and norepinephrine by up to 40 percent.
In addition to the functions mentioned above, dopamine lowers levels of prolactin, a hormone that is often elevated in people with CFIDS/FMS. It also lowers appetite.13 Work being done by Dr. Dan Malone of the University of Wisconsin, using medications that raise dopamine and/or serotonin, suggests that dopamine plays a very important role in CFIDS/FMS and, like serotonin, appears to be low in people with this disorder.14
Indeed, NADH has been found to improve depression in a study of 205 depressed patients, with 93 percent of the patients showing a beneficial clinical effect.15 Because of NADH’s effect on dopamine levels, it is also very helpful in treating Parkinson’s disease and may help restless leg syndrome.16
The Georgetown University Medical School did a placebo-controlled study of NADH treatment of CFIDS under the direction of Dr. Joseph A. Bellanti, who is the director of Georgetown’s International Center for Interdisciplinary Studies of Immunology, and Dr. Harry Preuss. Dr. Bellanti proposed that NADH works by replenishing depleted cellular stores of ATP, thus improving the fatigue and cognitive dysfunction. In their study, patients were given 10 milligrams of NADH a day for one month. In that time, thirty-one of the CFIDS patients showed at least 10 percent improvement. Outside the study, they continued the NADH for a second month, and found that 80 percent of CFIDS/FMS patients felt somewhat improved after two months. (Because of this, you should not try NADH unless you are willing to give it at least a two-month trial.) Increasing the dose to 20 milligrams each morning sometimes increased the effect. Dr. Preuss feels that NADH is a safe natural compound. Georgetown researchers are also studying NADH in the treatment of Alzheimer’s disease and hope to begin studies on the drug’s use for treating depression and obesity. NADH certainly seems to be a promising new treatment for CFIDS/FMS.
Unfortunately, NADH is very sensitive to stomach acid. I use only NADH that is made by the company that produced it for the Georgetown study—the Menuco Corporation. Their brand name for NADH is Enada. I recommend a dosage of 10 milligrams daily. It is critical that NADH be taken first thing in the morning on an empty stomach, one-half hour before taking any food or supplements, except for thyroid hormone. The reason for this is that anything that is in the stomach could stimulate the production of stomach acid, which makes it harder for NADH to survive and also binds the NADH in the stomach, preventing its absorption. Since NADH costs about $1.80 for a 10-milligram daily dose, it is important that it be taken under optimum conditions. If it doesn’t help after two months, you can stop taking it or try increasing the dosage to 20 milligrams a day for six weeks.
Sometimes, after two to three months, the dose can be reduced to 5 milligrams a day, and after four to five months, it may be possible to stop taking it altogether, especially if NADH is taken as part of the complete program described below. Hopefully, this will jump-start the mitochondrial furnaces so that they can function on their own without any further aid. Overall, about 25 percent of my CFIDS/FMS patients have found that NADH helps enough for them to want to stay on it.
Although I have spoken about ATP being the body’s main energy source, the body does not store much ATP—it makes it as it needs it. During the initial stages of exercise, the body’s main energy source—the main thing it uses to create ATP—is a compound known as phosphocreatine. This maintains ATP levels while the body gears up to burn food to make ATP, a process called glycolysis.17
Creatine is also important for brain function.18 As noted earlier in this chapter, the muscles of people with CFIDS/FMS make more lactic acid during exercise than do those of healthy people. Creatine acts as a buffer to reduce lactic acid buildup and allow sluggish mitochondria to kick in.19 Otherwise, low creatine will prevent you from getting up to peak exercise—even if this means simply walking across the room—or will result in aggravated next-day muscle pain. Its main effect is to supply the initial burst of energy for an activity. This may increase endurance and enhance your ability to exercise without fatigue or achiness.20
Creatine is a naturally occurring protein that, like carnitine, is found in animal muscle (for example, in meat, fish, and poultry). Because of this, supplemental creatine is even more helpful for vegetarians.21 Cooking tends to destroy creatine. The body can also make creatine from the amino acids arginine, glycine, and methionine.
Supplemental creatine may be taken with a small amount of sweets to enhance its absorption. It should be taken on an empty stomach with a lot of water and a bit of honey.22 It can be taken in the form of creatine monohydrate, at a dosage of 5 grams (5,000 milligrams) four times a day for five days (the so-called loading dose), and then 2 grams (2,000 milligrams) a day (the maintenance dose). Alternatively, you can begin with and stay on 3 grams (3,000 milligrams) a day. The loading dose is more effective, however.23 Another form of supplemental creatine, phosphocreatine, is available overseas, but this form may not get across cell membranes as well as creatine.
Coenzyme Q10, iron, sulfur, and copper are critical for the electron transport system (ETS) to do its job of harvesting over 75 percent of the ATP energy from food. Since most cellular functions are dependent on an adequate supply of ATP, the health of the entire body is therefore dependent on an adequate supply of coenzyme Q10, iron, sulfur, and copper.
A great deal has been written on coenzyme Q10 and CFIDS/FMS. I will simply note that studies have demonstrated it can do the following:
* Enhance immune function.24
* Assist weight loss when dieting.25
* Improve exercise tolerance in sedentary people.26
In addition, coenzyme Q10 may decrease allergies.27 I recommend taking 100 to 200 milligrams of coenzyme Q10 a day. Take it with some kind of oil (butter, olive oil, salad dressing, vitamin E, or an oil supplement). This may significantly enhance its absorption.
Iron, sulfur, and copper are also critical to ETS function. Iron deficiency is easy to test for and treat. Ferritin levels should be kept over 40 and iron percent saturation over 22 percent. Adequate amounts of copper (1 to 3 milligrams a day) are present in the multivitamins I recommend, as are the B vitamins. Sulfur is harder to come by. A good form of supplemental sulfur is methylsulfonylmethane (MSM). Early experience suggests taking MSM may be very helpful for some people with chemical sensitivities, allergies, muscle and joint pain, and poor wound healing. I recommend taking four to six 500-milligram tablets twice a day, with meals, for six to eight weeks, then as needed.
To sum up, following is my recipe for treating mitochondrial dysfunction and jump-starting your body’s energy production. The supplements are listed in order of priority, in case cost is an issue (some of them can be expensive).
1. Take a good multivitamin daily.
2. Take two magnesium/malic acid two tablets three times a day (less if it causes diarrhea) for eight months, then cut back to two tablets a day.
3. Take 100 to 200 milligrams of coenzyme Q10 daily.
4. Take 2,000 to 3,000 milligrams of magnesium-potassium aspartate a day for three months, then stop. Be sure to take a brand that is fully reacted, such as the General Nutrition Centers brand.
5. Get vitamin B12 shots, especially if your B12 level is under 540 picograms per milliliter (pg/mL) of blood. I recommend getting 3,000 micrograms intramuscularly one to three times a week for ten to twenty shots. If injections are not available, take 1,000 to 5,000 micrograms a day in tablet form.
6. Get injections of thiamine pyrophosphate (TPP, available as CoCarboxylase). I recommend getting 100 milligrams intramuscularly three times a week for four to six weeks. This is not yet available in the United States, but individuals (perhaps with their doctors’ help) can import it for personal use from Lab ISI in Italy (see Appendix J: Resources).
7. Take 500 to 1,000 milligrams of acetyl-L-carnitine three times a day for three months. Then take 500 to 1,000 milligrams a day as needed or discontinue it. Add 1,000 milligrams of L-lysine three times a day for three months to help the body make its own carnitine. Then you can reduce the lysine to 1,000 milligrams a day.
8. Take two 5-milligram tablets of nicotinamide adenine dinucleotide plus high-energy hydrogen (NADH) each morning for six to twelve weeks. It must be the Enada brand. It also must be taken first thing in the morning on an empty stomach—at least one-half hour before any food, medications, or supplements.
9. Take 5 grams (5,000 milligrams) of powdered creatine monohydrate four times a day for five days, then cut back to 2 grams (2,000 milligrams) a day. Mix it with water, and, if you tolerate it well, add 1 teaspoon of honey or sugar to the glass to help absorption. Get one that is assayed as 99+ percent pure.
10. Get injections of adenosine monophosphate (AMP). I recommend 100 milligrams given intramuscularly three times a week. Alternatively, you can take 50 milligrams of My-B-Tabs (AMP) from LeGere Pharmaceuticals dissolved under the tongue three times a day. Give AMP six to twelve weeks to have an effect. It is most likely to help if you have a lot of flu- or mono-like symptoms. The tablets help only infrequently, however.
11. Take four to six 500-milligram tablets of methylsulfonylmethane (MSM) twice a day for six to eight weeks, then as needed—for example, one to three tablets two times a day.
12. If your ferritin test is under 40 or your percent saturation is under 22 percent, take an iron supplement. I prefer the prescription product Chromagen-FA, although there are many other good forms. Take the iron on an empty stomach. Do not take it within six hours of taking any hormones.
Although the treatments listed above work best if used together, you can probably get a good effect, even if the TPP, NADH, AMP, and MSM are left out. Except for the multivitamin and magnesium/malic acid, which should be taken forever, the above supplements can all be stopped after eight to twelve weeks. They can also be used safely, though, for long periods of time if needed, though you probably will not need the full dose.
1. The mitochondria are the energy furnaces in your cells that burn food for energy. Many studies and findings suggest that these furnaces are functioning inefficiently in CFIDS/FMS.
2. Due to mitochondrial dysfunction, a person with CFIDS/FMS can lose over 75 percent of the energy in carbohydrates because they are shunted into the inefficient burning system. As a result, the body cannot burn fat and makes more fat. The furnace is turned down and the body becomes unable to make the “tools” the furnace needs to work well—a vicious cycle that occurs throughout the body, affecting the brain (fatigue, brain fog), liver (chemical and other sensitivities), bowel (malabsorption of nutrients) and muscles (pain and postexertional fatigue).
3. Begin with the Energy Revitalization System vitamin powder and B complex (1/2 to 1 scoop a day plus 1 capsule) plus D-Ribose (Corvalen) 1 scoop 3 x day for 3 weeks then 2 x day
4. A number of other substances that are available in supplement form appear to be low, and, especially when used together for eight to twelve weeks, may get one’s energy furnaces up and running. These include magnesium-potassium aspartate, acetyl-L-carnitine, NADH, and coenzyme Q10.
Footnotes for section 2
1. P.O. Behan, “Post-Viral Fatigue Syndrome Research,” in The Clinical and Scientific Basis of Myalgic Encephalitis and Chronic Fatigue Syndrome, ed. Byron Hyde, Jay Goldstein, and Paul Levine (Ottawa, Ontario, Canada: Nightingale Research Foundation, 1992), p. 238.
2. J.T. Hicks, “Treatment of Fatigue: A Double Blind Study,” Clinical Medicine, January 1964; pp. 85–90. D.L. Shaw, et al., “Management of Fatigue,” American Journal of Medical Science, June 1962, pp. 758–769. C.A. Kruse, “Treatment of Fatigue with Aspartic Acid Salts,” Northwest Medicine, June 1961, pp. 597–603. A. Gaby, “Potassium-Magnesium Aspartate,” Nutrition and Healing, October 1995, pp. 3–11.
3. J.T. Hicks, op. cit.
4. D.L. Shaw, et al., op. cit. J.T. Hicks, op. cit.
5. A. Gaby, op. cit.
6. Byron Hyde, Jay Goldstein, and Paul Levine, eds., The Clinical and Scientific Basis of Myalgic Encephalitis and Chronic Fatigue Syndrome (Ottawa, ON: Nightingale Research Foundation, 1992).
7. J. Eisenger, L.M.M. Medicine du-sud-est 25 (7/8) (April 1989): 12371. J. Eisenger, “Transketolase Stimulation in Fibromyalgia,” Journal of the American College of Nutrition 9 (1) (1990): 56–57.
8. J. Eisenger, “Transketolase Stimulation in Fibromyalgia,” op. cit.
9. A.V. Plioplys and S. Plioplys, “Amantadine and L-Carnitine Treatment of Chronic Fatigue Syndrome,” Neuropsychobiology 35 (1) (1997): 16–23. H. Kuratsune, K. Yamaguti, M. Takahashi, et al., “Acylcarnitine Deficiency in Chronic Fatigue Syndrome,” Clinical Infectious Disease 18 (3 Supplement 1) (January 1994): S62–S67.
10. V. Tanphaichitr and P. Leelahagul, “Carnitine Metabolism and Human Carnitine Deficiency,” review article, Nutrition 9 (3) (May-June 1993): 246–252.
11. R.E. Keith, “Symptoms of Carnitine Like Deficiency in a Trained Runner Taking DL-Carnitine Supplements,” letter, Journal of the American Medical Association 255 (9) (7 March 1986): 1137.
12. H.E.F. Davies, et al., “Ascorbic Acid and Carnitine in Man,” Nutrition Reports International 36 (1987): 941.
13. J.G.D. Birkmayer, “NADH: The Energizing Coenzyme,” pamphlet (New York, NY: Menuco Corporation, 1996). J.G.D. Birkmayer, interview, Clinical Pearl News 7 (1) (January 1997): 1–2. J.G.D. Birkmayer, “Coenzyme Nicotinamide Adenine Dinucleotide: New Therapeutic Approach for Improving Dementia of Alzheimer’s Type.” Annals of Clinical and Laboratory Science 26 (1) (January-February 1996): 1–9.
14. Daniel Malone, N. Wei, and P. Hitzig, “Treatment of 76 Patients with Primary FMS with Combined Dopaminergic and Serotonergic Drugs,” abstract submitted to the Annual Scientific Meeting of the American College of Rheumatology, 1996.
15. J.G.D. Birkmayer, “The Coenzyme Nicotinamide Adenine Dinucleotide as a Biological Antidepressive Agent,” New Trends in Clinical Neuropharmacology; 5 (1991): 19–25.
16. J.G.D. Birkmayer, C. Vreko, D. Volc, et al., “Nicotinamide Adenine Dinucleotide (NADH)—A New Therapeutic Approach to Parkinson’s Disease. Comparison of Oral and Parenteral Application,” Acta Neurologica Scandinavica 146 (Supplement) (1993): 32–35.
17. Wayne M. Becker, Jane B. Reece, Martin F. Poenie, et al., The World of The Cell, 3rd Edition (San Francisco, CA: Benjamin Cummings, 1996).
18. J.D. Loike, D.L. Zalutsky, E. Kaback, et al., “Extracellular Creatine Regulates Creatine Transport in Rat and Human Muscle Cells,” Proceeds of the National Academy of Sciences USA 85 (3) (February 1988): 807–811.
19. P.L. Greenhaff, A. Casey, A.H. Short, et al., “Influence of Oral Creatine Supplementation on Muscle Torque During Repeated Bouts of Maximal Exercise in Man,” Clinical Science; 84 (5) (May 1993): 565–571. Glenn Caldwell, personal communication, 8 March 1996.
20. P.L. Greenhaff, “Creatine and its Application as an Ergogenic Aid,” International Journal of Sports Nutrition 5 (Supplement) (1995): 100–110.
21. M. Harris, et al., “Alterations in Leg Extension Power of Meat Eating and Non-Meat Eating (Vegetarian) Females with Creatine Supplementation,” updated, poster presentation, Proceedings of Experimental Biology, Federation of American Societies for Experimental Biology, Anaheim, CA, 24–28 April 1994.
22. Laurie Gould, personal communication, 21 April 1997. Glenn Caldwell, personal communication, 8 March 1996. Ray Sahelian, Creatine: Nature’s Muscle Builder (Garden City Park, NY: Avery Publishing Group, 1997), p. 104.
23. P.L. Greenhaff, “Creatine and its Application as an Ergogenic Aid,” op. cit.
24. K. Folkers, S. Shizukuishi, K. Takemura, et al., “Increase in Levels of IgG in Serum of Patients Treated with Coenzyme Q10,” Research Communications in Chemical Pathology and Pharmacology 38 (2) (1982): 335–338. K. Folkers, P. Langsjoen, Y. Nara, et al., “Biochemical Deficiencies of Coenzyme Q10 in HIV Infection and Exploratory Treatment,” Biochemical and Biophysical Research Communications 153 (2) (1988): 888–896. K. Lockwood, S. Moesgaadr, T. Hanoike, et al., “Apparent Partial Remission of Breast Cancer in “High Risk” Patients Supplemented with Nutritional Antioxidants, Essential Fatty Acids and Coenzyme Q10,” Molecular Aspects of Medicine 15 (Supplement) (1994): S231–S240. K. Lockwood, S. Moesgaard, T. Yamamoto, et al., “Progress on Therapy of Breast Cancer with Coenzyme Q10 and the Regression of Metastases,” Biochemical and Biophysical Research Communications 212 (1) (6 July 1995): 172–177. P. Mayer, H. Hamberger, and J. Drew, “Differential Effects of Ubiquinone Q7 and Ubiquinone Analogs on Macrophage Activation and Experimental Infections in Granulocytopenic Mice,” Infection 8 (1980): 256–261. E. Bliznakov, A. Casey, and E. Premuzic, “Coenzymes Q: Stimulants of Phagocytic Activity in Rats and Immune Response in Mice,” Experientia 26 (1970): 953–954.
25. L. Van Gaal, I.D. de Leeuw, S. Vadhanavikit, et al., “Exploratory Study of Coenzyme Q10 in Obesity,” in K. Folkers and Y. Yamamura, eds., Biomedical and Clinical Aspects of Coenzyme Q, Vol. 4 (New York, NY: Elsevier Publishers, 1984), pp. 235–373.
26. A. Gaby, “The Role of Coenzyme Q10 in Clinical Medicine. Part I,” Alternative Medicine Review 1 (1) (1996): 11–17.
27. Y. Ishihara, Y. Uchida, S. Kitamura, et al., “Effect of Coenzyme Q10, a Quinone Derivative, on Guinea Pig Lung and Tracheal Tissue,” Arzneimittelforschung 35 (1985): 929–933.