Lipid replacement therapy with a glycophospholipid formulation, NADH, and CoQ1O significantly reduces fatigue and improves mood and cognition in intractable fatiguing illnesses and chronic Lyme disease.
(Care and treatment)
Lyme disease (Patient outcomes)
Chronic fatigue syndrome (Care and treatment)
Chronic fatigue syndrome (Patient outcomes)
Lipids (Health aspects)
Mood (Psychology) (Management)
Nicolson, Garth L.
|Publication:||Name: Townsend Letter Publisher: The Townsend Letter Group Audience: General; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 The Townsend Letter Group ISSN: 1940-5464|
|Issue:||Date: June, 2012 Source Volume: 347|
|Topic:||Event Code: 200 Management dynamics Computer Subject: Company business management|
|Geographic:||Geographic Scope: United States Geographic Code: 1USA United States|
Chronic fatigue is the most common complaint of patients seeking
general medical care. (1), (2) It occurs naturally during aging, and it
is also an important symptom in many chronic diseases. (1-3) In the last
few years, natural supplements have been used to reduce fatigue in
patients with chronic fatigue and other chronic medical conditions with
fatigue; however, few of these natural supplements are considered
effective: (3), (4) One approach that has proved effective in reducing
fatigue in aging and chronic illnesses is lipid replacement therapy
(LRT), or the natural replacement of damaged, mainly oxidized, membrane
lipids in mitochondria and other cellular. (3), (5)
Fatigue has been described as a multidimensional sensation, and clinical studies have determined the extent of fatigue in aging and various medical conditions (neurological, respiratory, coronary, musculoskeletal, metabolic, auto-immune and gastrointestinal diseases, cancer, infections). (3), (5-7) Most patients consider fatigue to be a loss of overall energy and inability to perform even simple tasks without exertion. At the cellular level, fatigue is related to energy systems found primarily in the mitochondria and specifically in the inner mitochondrial membrane electron transport system. (8) Damage to mitochondrial membranes occurs in various diseases, mainly by oxidation, and this can result in loss of mitochondrial inner membrane potential and impairment in the ability of mitochondria to produce high-energy molecules. (3), (6), (9)
In fatiguing illnesses, such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), patients have intractable fatigue for at least six months and show increased susceptibility to oxidative stress and peroxidation of membrane lipids. (10), (11) To some degree, this excess oxidative stress can be reduced with antioxidant supplements, but these antioxidants cannot repair the oxidative damage to cell. (12), (13)
Lipid Replacement Therapy
Recent clinical trials have shown the effectiveness of LRT plus antioxidants in the treatment of certain clinical disorders and conditions, such as chronic fatigue. (3), (5), (14-16) LRT results in the actual replacement of damaged cellular phospholipids with undamaged (unoxidized) lipids to ensure proper function of cellular and organelle membranes. Combined with antioxidant supplements, LTR has proved to be an effective method to prevent oxidative damage to cellular activities and functions and for use in the treatment of various clinical conditions. (5-7)
LRT can repair mitochondrial membranes, increase function, and decrease fatigue in various chronic conditions, including aging, chronic fatigue syndrome, fibromyalgia syndrome, and obesity (Table 1). When mitochondrial function was followed in parallel with fatigue in a crossover clinical trial, there was a close correspondence between loss of fatigue and gains in mitochondrial function. (15)
LRT with Glycophospholipids, CoQ10, and NADH
Recently we tested the results of using an oral formulation of glycophospholipids (polyunsaturated phosphatidylcholine, phosphatidylglyerol, phosphatidylserine, phosphatidylinositol, and other membrane phospholipids), CoQ10 plus microencapsulated NADH and other nutrients (Table 2) on suppression of intractable fatigue during a two-month trial. (18) The 58 participants in this study had moderate to severe intractable fatigue (30 females, 51.8 [+ or -] 1.7 years, and 28 males, 58.5 [+ or -] 2.1 years, respectively). They were long-term chronic-illness patients (30 CFS/ME; 17 chronic Lyme disease; 16 other fatiguing illnesses, including fibromyalgia syndrome and Gulf War illness; 4 autoimmune disease, including rheumatoid arthritis; 2 cancer; and 2 diabetes) who had tried unsuccessfully many drugs and supplements (average > 35) to reduce their fatigue. The participants had been fatigued an average of > 17 years and had been to an average of over 15 practitioners without resolution of their fatigue. (18)
Participants took the suggested daily test supplement dose (5 capsules in the morning and 5 at night) for 8 weeks.18 Fatigue was scored using the Piper Fatigue Scale (PFS). (19), (20) The PFS is a validated instrument that measures four dimensions of subjective fatigue: behavioral/severity, affective/meaning, sensory, and cognitive/mood. These were used to calculate the four subscale/dimensional scores and the total fatigue scores). (19), (20) The standardized alpha (Cronbach's alpha) coefficient of reliability was at least 0.960 for any of the subscale data, and the standard alpha for the entire scale was 0.979, indicating excellent reliability and internal consistency. The study participants took the PFS survey at days 0, 7, 30, and 60. (18)
The initial PFS mean total fatigue score [+ or -] SD was 7.51 [+ or -] 0.29, and after 8 weeks of supplementation this improved to 5.21 [+ or -] 0.28, or a 30.7% reduction in fatigue in these patients with intractable chronic fatigue. The mean decrease in fatigue scores was significant by t-test (p < 0.0001) and Wilcoxon signed-rank (p < 0.0001) analyses. The PFS fatigue scores can be further dissected into subcategories (Table 3, p. 60). All of these subcategories showed significant reductions by the end of the 8-week trial (p < 0.0001), indicating that there were significant improvements in all subcategories of fatigue. For example, there was a 30.7% reduction (p < 0.0001) in severity/behavior of fatigue, indicating that there was a significant reduction in the intensity of fatigue, and a significant increase in the ability to complete tasks, socialize, and engage in sexual and other activities. Also, there was a 28.0% improvement (p < 0.0001) in mood and cognitive ability, such as the ability to concentrate, remember, and think clearly (Table 3). (18)
Analysis of Fatigue Data
To see if the trends in fatigue reduction over time during the trial were consistent, occurred with a high degree of confidence, and could predict further reductions in fatigue, we conducted regression analyses of the data. The regression analysis of overall fatigue and in each of the subcategories of fatigue (behavior/ severity, affective meaning, sensory, and cognitive/mood) indicated significant and consistent downward trends in the fatigue data, suggesting that further reductions in fatigue would have been likely if the trial had been continued. The regression R2 values for the various subgroups were: behavior/severity, 0.956; affective meaning, 0.960; sensory, 0.950; and cognitive/mood, 0.980. Regression analysis of the overall fatigue yielded a [R.sup.2] = 0.960. This indicates a high level of confidence and reproducibility in the downward trends in all fatigue data. (18)
We also examined the data to see if there was a difference in response to the test supplement that depended on fatigue severity. As expected from previously trials that used NT Factor alone, the most severely fatigued subjects showed the greatest reductions in fatigue scores. (14), (15) For example, subjects with initial overall fatigue scores above 8 in the PFS scale showed greater reductions in fatigue scores on day 60 (35.3% improvement in overall fatigue) than subjects with lower scores (initial PFS score 4-8, 25% improvement) by day 60. Examination of scores from patients with CFS/ME, Lyme disease, or other diagnosis categories did not reveal major differences in overall fatigue or its reduction by the test supplement. For example, in the CFS/ME, Lyme disease, and other fatiguing illness groups, total fatigue was reduced on day 60 by 29.6%, 26% and 34.6%, respectively. (18)
Effects of CoQ10 and NADH Alone
Prior studies reported that microencapsulated NADH atone had a positive effect on fatigue. Analysis of those studies, however, indicated that a subset of patients responded or the response was for a limited time. In a study on CFS/ME patients 8 of 26 (30.7%) responded to microencapsulated NADH compared with 2 of 26 (8%) on placebo (p < 0.05). (21) However, these results were not considered significant by others. (22) Santaella et al. compared the effectiveness of 24 months of oral NADH versus psychological/ nutritional therapy for 31 CFS/ME and found that NADH only reduced fatigue in the first trimester of the trial. (23) After the first trimester, symptom scores were similar in NADH and psychological/nutritional arms of the trial. In another study, oral NADH was given for two months to CFS/ME patients and showed a decrease in anxiety and maximum heart rate after a stress test, but little difference in the functional impact of fatigue, quality of life, sleep quality, exercise capacity, or functional reserve between the test and placebo groups. (24)
CoQ10 is an important cellular antioxidant and an essential electron carrier in the mitochondrial respiratory chain as well as a molecule involved in gene regulation. (25) CoQ10 has been used as a dietary supplement in a variety of chronic illnesses and age-related conditions. (25), (26) CoQ1 0 was used here to improve energy transduction and combat oxidative stress. (26)
Chronic fatigue is related to loss of mitochondrial function. (15), (27) The patients here are considered as having intractable fatigue, yet they responded quite well to the combination supplement containing NT Factor, CoQ10, and NADH. (18) Regression analysis indicated that the data were consistent with a high degree of confidence and also suggested that the peak benefits on fatigue were yet to be realized. The supplement was safe, and only two participants experienced minor symptoms that resolved after the supplement was discontinued and could not be directly attributed to the test supplement. The clinical trial here demonstrated that the test supplement was effective and safe for long-term chronic illness patients, such as those with CFS/ME, fibromyalgia syndrome, chronic Lyme disease, Gulf War illness, and other chronic conditions.
Fatigue is the most common complaint of chronic illness patients. A combination oral supplement containing a mixture of phosphoglycolipids, CoQ10, and microencapsulated NADH significantly (p < 0.001) reduced intractable fatigue in a group (n = 58) of patients with chronic fatigue syndrome, fibromyalgia syndrome, Gulf War illness, chronic Lyme disease, and other conditions. These patients had been symptomatic for an average of over 17 years, had been seen by multiple practitioners (> 15), and had used many other supplements and drugs (> 35) without apparent reductions in their fatigue. Analysis of subcategories of fatigue indicated significant improvements in the ability to complete tasks and activities as well as in mood and cognitive abilities. Regression analysis of the data indicated that reductions in fatigue were gradual and consistent, and occurred with a high degree of confidence ([R.sup.2] = 0.960). The combination supplement was a safe and effective method to significantly reduce fatigue in patients with intractable chronic fatigue. (28)
Correspondence should be addressed to: Garth L. Nicolson; PhD; Department of Molecular Pathology, Institute for Molecular Medicine, Huntington Beach, California 92647; email@example.com
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(16.) Ellithorpe RA, Settineri R, Jacques B, Nicolson GL. Lipid Replacement Therapy functional food with NT Factor for reducing weight, girth, body mass, appetite, cravings for foods and fatigue while improving blood lipid profiles. Funct Food Health Dis. 2012; 2(1):11-24.
(17.) Nicolson GL, Ellithorpe RR, Ayson-Mitchell C, Jacques B, Settineri R. Lipid Replacement Therapy with a glycophospholipid-antioxidant-vitamin formulation significantly reduces fatigue within one week. J Am Nutraceutical Assoc. 2010; 13(1):11-15.
(18.) Nicolson GL, Settineri R, Ellithorpe E. Lipid Replacement Therapy with a glycophospholipid formulation with NADH and CoQ10 significantly reduces fatigue in intractable chronic fatiguing illnesses and chronic Lyme disease. Intern J Clin Med. 2012; in press.
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(28.) The authors have no conflicts of interest or ownership in any products or companies discussed in this contribution. This study was supported in part by a grant from Researched Nutritionals Inc.
Professor Garth L. Nicolson is the president, chief scientific officer, and research professor at the Institute for Molecular Medicine in Huntington Beach, CA. He is also a conjoint professor at the University of Newcastle (Australia). He was formally the David Bruton Jr. Chair in Cancer Research and professor and chairman of the Department of Tumor Biology at the University of Texas M. D. Anderson Cancer Center in Houston, and he was professor of internal medicine and professor of pathology and laboratory medicine at the University of Texas Medical School at Houston. He was also professor of comparative pathology at Texas A & M University. Professor Nicolson has published over 600 medical and scientific papers, including editing 19 books, and he has served on the editorial boards of 30 medical and scientific journals and was a senior editor of four of these. Professor Nicolson has won many awards, such as the Burroughs Wellcome Medal of the Royal Society of Medicine (UK), Stephen Paget Award of the Metastasis Research Society, the US National Cancer Institute Outstanding Investigator Award, and the Innovative Medicine Award of Canada. He is also a colonel (honorary) of the US Army Special Forces and a US Navy SEAL (honorary) for his work on armed forces and veterans' illnesses.
Robert Settineri, MS, is the president and research director for Sierra Productions Research (Irvine, CA) and responsible for coordinating clinical and preclinical research. He has over 30 scientific publications on viral immunology, nutritional science, and related fields, as well as produced and directed educational medical films which garnered 25 international awards. Robert has been previously involved in biomedical pharmaceutical research for 17 years where he helped develop immunomodulating compounds that have led to international drug registrations and distribution in 80 countries. He also currently serves as senior vice president and a member of the board of directors for the Journal of the American Nutraceutical Association. Robert is senior inventor of US Patent: Natural Membrane Phospholipid Supplements for Cellular Repair for the Treatment of a Variety of Acute and Chronic Illnesses, Fatiguing Illnesses & Mitochondrial Disorders.
Dr. Rita Ellithorpe received her medical degree in 1982 from the Chicago Medical School/University of Health Science in North Chicago, IL. From there she completed her internship in family practice at Womack Army Hospital, Fort Bragg, NC in 1983. At Fort Knox, KY, she served as an emergency room staff physician, general medical officer, and flight surgeon as chief of the Aviation Clinic 1983-1990. Dr. Ellithorpe is a graduate and guest faculty member of Capitol University of Integrative Medicine (Washington, DC) since January 2001. She is a diplomat of the Board of Anti-Aging Medicine as well as the founder and medical director of Tustin (CA) Longevity Center. A national speaker on the topics of oxidative stress and anti-aging, she also has published her research in several peer-reviewed journals. A staff physician and director of women's studies at Whitaker Wellness Medical Clinic in Newport Beach, CA, she went on to help in the development of natural medicinal therapies at Great Smokies Medical Center in Asheville, NC. Dr. Ellithorpe holds a second doctorate in integrative medicine focusing on health at the cellular level.
Table 1: Effects of Dietary LRT Supplementation on Fatigue Scores (a) Subjects/patients n Av. Time Piper Fatigue Reference age on Scale (PFS) LRT fatigue reduction (%) Chronic fatigue 34 50.3 8 wks 40.5 ** Ellithorpe (b) et al. (14) Aging, chronic 20 68.9 12wks 35.5 * Agadjanyan fatigue (c) et al. (15) Chronic fatigue 15 44.8 8 wks 43.1 * Nicolson syndrome (and/or and fibromyalgia Ellithorpe syndrome) (b) (5) Obesity, fatigue 35 42 8 wks 24 * Ellithorpe (d) et al. (16) Aging, fatigue 67 57.3 1 wk 36.8 * Nicolson et (e) al. (17) (a) Modified from Nicoison and Settineri (b) Propax with NT Factor (c) NT Factor (d) Healthy Curb with NT Factor (e) Advanced Physician's Formula with NT Factor ** p < 0.0001, * p < 0.001 compared to without LRT
Table 2: Test Supplement (ATP Fuel with NT Factor, NADH, and CoQ10) (a) Component Amount % Per Daily Serving Value (b) Vitamin E (as alpha-D-tocopherol) 20 IU 67 Krebs Energy Foundation 35 mg * NADH, Coenzyme Q10 Mitochondria Pro Regulator 260 mg * Calcium (as calcium pyruvate, calcium ascorbate dicalcium phosphate), phosphate/sulfate/pyruvate; Phosphorus (as dicalcium phosphate); Magnesium (as ma nesium oxide) Krebs Cycle Glucose Absorb 180 mg * Alpha-ketoglutaric acid, L-tyrosine RN Fatty Acid Metabolizer 160 mg * L-carnitine, L-tartrate, pantethine NT Factor (c) Maximum Potency 2,000 mg * (a) ATP Fuel is a registered trademark of Researched Nutritionals Inc., Los Olivos, CA (b) Daily values are based on a 2000 calorie per day diet * Daily values not established (c) NT Factor is a nutrient complex containing membrane polyunsaturated phosphoilpids extracted from soy lipids and purified using proprietary processes, Bifido and Lactobacillus bacteria with supportive essential growth media. and phytonutrients for optimal absorption and performance, by Nutritional Therapeutics Inc., Commack, NY.
Table 3: Results From Overall Fatigue and Subcategories of the Piper Fatigue Scale Category Mean Fatigue Level [+ or -] Percent-test P Day 0 SD Day 60 Reduction Overall Fatigue 7.51 [+ or -] 5.21 [+ or -] 30.7 <0.0001 0.29 0.28 Behavior/Severity 7.43 [+ or -] 5.15 [+ or -] 30.7 <0.0001 (a) 0.26 0.12 Affective/Meaning 8.36 [+ or -] 5.90 [+ or -] 29.4 <0.0001 (b) 0.14 0.16 Sensory (c) 7.75 [+ or -] 5.49 [+ or -] 29.2 <0.0001 0.22 0.17 Cognitive/Mood 6.40 [+ or -] 4.61 [+ or -] 28.0 <0.0001 (d) 0.24 0.21 (a) Behavior/Severity subcategory deals with completing tasks, socializing, engaging in sexual activity and other activities. and intensity or degree of degree of fatigue. (b) Affective/Meaning subcategory detemines whether fatigue/tiredness is pleasant/unpleasant, patient is agreeable/disagreeable, protective/destructive, or feels normal/abnormal. (c) Sensory subcategory determines whether patient is strong/weak, awake/sleepy, refreshed/tried, or energetic/unenergetic. (d) Cognitive/Mood subcategory assesses whether patient feels relaxed/tense, exhilarated/depressed, able/unable to concentrate, remember, and think clearly.
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