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Cystic Fibrosis |
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Lipid
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Frequently
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Newsletter "The
Essential News on Fats" | Crohn's/IBD | key differences with other groups |
If you are interested in referring patients with Cystic Fibrosis for nutritional evaluation, please contact us. We analyze very small amounts of blood (plasma) to assess EFA abnormalities.
· CF is a genetic disease affecting approximately 30,000 children and adults in the United States. The disease causes poor absorption of key nutrients. The resulting imbalance of nutrients affects the function of many cells in the body. One consequence is poor function of the cell pumps that regulate the balance of sodium (Na) and chloride (Cl). Cells in the lung and pancreas are particularly affected. Cl does not move properly because the protein product of the CF gene is defective -- and makes a faulty channel for the Cl to leave the cell. Abnormal cell membrane composition makes the problem worse.
· CF occurs in approximately one of every 3,000 live Caucasian births. There are about 1,000 new cases of CF diagnosed each year. According to the CF Foundation's National Patient Registry, 1/2 of all individuals with CF live to the age of 32; however, 1/2 do not. One in 31 Americans (one in 28 Caucasians) — more than 10 million people — is an unknowing, symptomless carrier of the defective gene. A individual must inherit a defective copy of the CF gene — one from each parent — to have cystic fibrosis. Each time two carriers conceive a child, there is a 25 percent chance that the child will have CF; a 50 percent chance that the child will be a carrier; and a 25 percent chance that the child will be a non-carrier.
· The defect in CF causes the body to produce an abnormally thick, sticky mucus within cells lining organs such as the lungs and pancreas. This abnormal mucus clogs the lungs and contributes to life-threatening infections. The thick CF mucus also obstructs the pancreas, preventing enzymes from reaching the intestines to help break down and digest food.
· CF has many symptoms. The nature and extent of the symptoms depends on the extent of nutritional abnormalities. The most common are: very salty-tasting skin; persistent coughing, wheezing or pneumonia; excessive appetite but poor weight gain; and bulky stools. A common test to diagnose CF measures the amount of salt in the sweat. A high level of salt indicates that a person has CF.
· The treatment of CF depends upon the stage of the disease and which organs are involved. Chest physical therapy is used to dislodge the thick mucus from the lungs (there is a special way to do it, requires expert training). Antibiotics are also used to treat lung infections and are administered intravenously, via pills, and/or medicated vapors which are inhaled to open up clogged airways. Whenever possible, the antibiotic must match the infection.
Treatment
The defective CF gene was discovered in 1989. However, all the functions of the gene are not yet known. In early 1993 the first experimental gene therapy treatment was given to a patient with CF. Researchers modified a common cold virus to act as a delivery vehicle — carrying the genes to the CF cells in the airways. For more information on CF gene therapy, see Gene Therapy and CF. This treatment is not yet practical or fully effective. Many cells may be defective and it is not possible to change all the defective cells in the body. Gene therapy can produce eventually some cells that are fairly normal, but we are very far from being able to correct all the defective cells. Thus, we must still use nutrition and other therapies to prevent the complications of CF.
Cystic Fibrosis (CF) causes malabsorption and EFA deficiency. EFAs are needed to create new cells in the intestine and to protect the body from toxic chemicals. The nutritional problems pertaining to EFA abnormalities in cystic fibrosis (CF) are similar to those in Crohn’s disease.
"The basic defect in cystic fibrosis increases the metabolism of EFAs and thereby gradually gives rise to EFA deficiency, which is a well documented finding in most cases with this disease." EFA abnormalities and their metabolic products, i.e., different eicosanoids, and EFA deficiency "...cause gastrointestinal symptoms, and the sequence of this development will mirror the natural history of the disease"(Strandvik B. Relation between EFA metabolism and gastrointestinal symptoms in CF. Acta Paediatr. Scand. Suppl., 1989; 363:58-65).
Often, a decrease in total fat (and probably EFA abnormalities) is the first detectable sign of the deterioration characteristic of cystic fibrosis(Tomezsko, JL, Scanlin, TF, Stallings VA. Body composition of children with CF with mild clinical manifestations compared with normal children. Am J. Clin. Nutr. 1994; 59:123-8). There is evidence that, in CF, there is an impairment in the conversion of EFA precursors to their derivatives, as well as biochemical evidence of EFA deficiency (Lloyd-Still HD, Johnson SB, Holman RT. EFA status in CF and the effects of safflower oil supplementation. Am. J. Clin.Nutr. 1981; 34:1-7).
It is recommended "...that close monitoring of plasma EFAs be carried out in CF, because of the high incidence of EFA deficiency despite efforts to improve and liberalize fat intake"(Lepage G, Levy E, Ronco N, Smith L, Galeano N, Roy CC. Direct transesterification of plasma fatty acids for the diagnosis of EFAD in CF. J. Lipid Res. 1989; 30:1483-1490). These authors recommend analyzing plasma for the detection of EFA abnormalities, and cite Siguel’s research to describe their findings. The authors suggest that correction of EFA abnormalities will assist with easier "...control of chest infections, marginally better respiratory function, and perhaps extended survival." These results, together with those of numerous other published articles, provide compelling evidence that the treatment of CF prior to 1994 has ignored effects of EFA abnormalities on CF.
EFA abnormalities and EFA deficiencies are
highly common in CF and probably affect most or all patients. These
deficiencies are highly complex and vary from one patient to another.
Individualized diagnosis and treatment is necessary.
EFA abnormalities contribute to impaired
function of all organs, including lung function and gastrointestinal disease,
and are likely to be a major factor in premature death.
EFA abnormalities and deficiencies can be
corrected with appropriate oral or intravenous supplements.
Correction of EFA abnormalities provides
significant improvement to patients with CF.
Correction of EFA abnormalities may require large amounts of oil and could take years unless intravenous lipids are used. Intravenous lipids may be required because of fat malabsorption. These issues also occur in Crohn’s disease.
Vitamin E is an antioxidant and may have a role in the protection of lung tissue against oxidative damage in cystic fibrosis. Tissue vitamin E levels are low in patients with cystic fibrosis who do not receive supplements, but can be normalized in most children with 100 mg of vitamin E per day(Peters SA; Kelly FJ. Vitamin E supplementation in CF. J Pediatr Gastroenterol Nutr 1996 May;22(4):341-5). To check for vitamin E levels, it is preferable to measure erythrocyte (red cells) vitamin E concentrations rather than plasma concentrations.
Dr. Siguel’s book “Essential Fatty Acids in Health and Disease” (see elsewhere at essentialfats.com) contains detailed descriptions of how to diagnose essential fat abnormalities and how to treat them in CF.
Case study: Cystic
Fibrosis and Crohn's disease with EFA Deficiency
A 35 year old woman with Crohn's disease for over 5 years, partial intestinal resection. She has elevated 20:3w9 /20:4w6, and significantly decreased levels of EFAs and derivatives. Both the percent and the absolute quantities of EFAs are decreased, a condition we call Absolute EFA Insufficiency. The purpose of therapy is to achieve normal results as measured by the fatty acid test EFA-SRä. Because EFAs are essential for the intestine to repair itself and make more cells, correcting EFA abnormalities will minimize complications of the disease and increase bowel healing.
Treatment: Oral soybean oil supplements (15-30 ml/day) plus 200 I.U. Vit. E/day, plus cholestyramine to minimize diarrhea. (Large vitamin E doses are needed due to malabsorption.)
Results: A repeat of the fatty acid profile after three months found that EFA levels increased significantly and that derivatives were formed. Although there was a marked increase in the percent of PUFAs, due to the severe extent of the deficiency, the patient was still very deficient. We estimated that it would take many years to correct the deficiency using only oral supplements.
The patient was then hospitalized for one week to receive a "loading" dose of EFAs with intravenous lipids and extra supplements of trace minerals, vitamins, and other minerals. Now at home, she continues on a diet which includes a mixture of regular foods and EFA oral supplements.
Repeated analyses have shown significant normalization of the fatty acid profile EFA-SRŌ: The w3s have returned to normal but w6s are still deficient. Her oral dose of oils was then changed to 1/2 safflower and 1/2 soybean mixture, to increase the w6/w3 ratio.
To interested patients
with Cystic Fibrosis and physicians:
Research has found fatty acid abnormalities, mostly EFA deficiencies, in patients with Cystic Fibrosis (CF). The deficiencies are caused by a combination of factors, including the typical American Diet (which is low in EFAs) and pancreatic insufficiency with malabsorption (caused by CF). Abnormalities of EFAs lead to suboptimal cell and tissue function, one consequence of which is increased water evaporation from the skin (the skin cells cannot retain water properly; this is a common consequence of EFA deficiency).
In a study of 163 CF patients, Dr. LePage found a substantial number with biochemical evidence of EFA deficiency. Dr. LePage stated that "easier control of chest infections, marginally better respiratory function, and perhaps extended survival following supplementary nutrition programs may in part be due to correction of EFA deficiencies..." He recommends that "the nutritional intake of calories be maximized in order to correct EFA deficiency, especially since AA and eicosanoids are important regulators of chloride transport, currently thought to be the basic defect associated with CF"(LePage, G et al. Direct transesterification of plasma fatty acids for the diagnosis of EFA deficiency in CF. J. Lipid Research, 1989; 30:1483-1490). He cites other studies on CF and EFAs and also cites Dr. Siguel’s methods and research findings.
Strandvik found that EFA deficiency is a major factor in the gastrointestinal symptoms in CF(Strandvik B. Relation between EFA Metabolism and Gastrointestinal Symptoms in CF. Acta Paediatr. Scand. Suppl 1989; 363:58-65). Correction of EFA abnormalities has no known side effects and may improve the condition of patients with CF.
The following comments are from Dr. Siguel
Based on my clinical experience and research, it is my opinion that an assessment of fatty acid abnormalities and EFA status provides useful and practical information in the evaluation and monitoring of patients likely to suffer from fatty acid abnormalities. For the past several years, I have been evaluating fatty acid profiles in TPN patients and patients with chronic intestinal disorders, obesity, neurological disease, cystic fibrosis, and other conditions (for a brief description of our results, see Siguel EN, Lerman RH. Trans fatty acid patterns in patients with angiographically documented coronary artery disease. Am. J. Cardiology 1993; 71:916-920; and Siguel EN, Lerman RH. Fatty acid patterns in patients with angiographically documented CAD. Metabolism, Aug 1994).
I found that significant abnormalities of fatty acid metabolism in many
patients have been overlooked by traditional methods of laboratory testing. As
many of my patients have difficulties in absorbing or tolerating lipids
enterally, and some cannot tolerate lipids parenterally, I find that fatty acid
analysis allows me to determine the smallest quantity of fatty acids necessary
to maintain EFA status and adequate overall nutrition.
Resources
The information in this page was derived from facts available from the US Government, The Cystic Fibrosis Foundation, research by Dr. Siguel and other sources.
Cystic Fibrosis
Foundation
6931 Arlington Road
Bethesda, MD 20814
E-Mail info@cff.org
List of resources: vmsb.csd.mu.edu/~5418lukasr/cystic.html
Portions of this section have
been excerpted from the book "EFAs in Health and
Disease" (how to order, table of contents, references, notes,
excerpts).
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© 1998 Edward Siguel. All rights reserved |
modified 1/15/00 |