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Oleic Acid: A Novel Nutrient-Based Treatment for Improving Absorption
Gregg W. Van Citters, MS and Henry C. Lin, MD
Weaning from total parenteral nutrition (TPN) is the ultimate, although often elusive, goal for both clinicians and patients. A major obstacle for patients with short bowel syndrome (SBS) to overcome is chronic diarrhea with massive loss of water and nutrients. Some strategies clinicians have tried to wean SBS patients off TPN include: enteral feedings along with dietary counseling; growth hormone, glutamine or GLP-2, to promote gut adaptation and absorption; surgical procedures to lengthen bowel or slow transit time; anti-diarrheal drugs to slow transit time; and intestinal transplantation. This article explores a new, nutrient-based treatment that slows intestinal transit time and thus provides more time for patients to digest and absorb nutrients taken orally. While significant positive results have been achieved using this therapy, it is still in the early stages of research and development.
TPN can dramatically improve the outcome of a wide variety of diseases, and if transition to enteral nutrition (EN) is not possible, may be necessary for survival. Unfortunately, long-term use of TPN is associated with the risks of sepsis, altered metabolism, bone disease and liver dysfunction or failure.
Most of these complications can be avoided by enteral delivery of nutrients, therefore an important therapeutic goal is to wean the patient from dependence on TPN whenever possible. The small intestine, the site of digestion and absorption of food and drugs, is capable of adapting to severe insults such as extensive surgical resection. However, this adaptive process is slow, and successful adaptation may take months or years so prolonged TPN support may be required before EN can be fully tolerated.
Factors Affecting Nutrient Absorption
Length and Type of Remaining Bowel
The site and extent of intestinal resection are important factors in determining whether the small intestine will adapt sufficiently to support oral or enteral feedings. Loss of the lower or distal portion of the small intestine (the ileum) may allow adaptation, but leave the patient with chronic fat, fat soluble vitamins (vitamin A, D, E and K) and divalent cations (calcium, magnesium, zinc and copper) malabsorption. Loss of the upper portion of the small intestine (the jejunum) may add to the devastating effect. A massive intestinal resection may lead to lifetime dependence on TPN due to inadequate length of gut available for nutrient assimilation. The length of the small intestine and the presence of the ileocecal valve, have long been viewed as the critical factors for successful adaptation.
Digestion and absorption of a meal can take several hours, depending on the nutrient composition of the meal. Since digestion and absorption are time-demanding events, the movement of a meal through the digestive tract must be tightly controlled to ensure adequate time for assimilation. Motility of the small intestine determines the duration of time that the contents of a meal is in contact with the digestive enzymes and absorptive mucosal layer of the small intestine. Gastrointestinal motility is normally controlled by transit control mechanisms located in the digestive tract which act to ensure adequate digestion and absorption of the meal. In a normal healthy bowel, this takes place in the proximal and distal small intestine and is known as the “jejunal brake” and the “ileal brake,” respectively. These controls are activated when the end-products of nutrient digestion are available to the nutrient sensors of the small intestine. Fatty acid, an end product of fat digestion, is a very potent trigger of these transit control mechanisms (see Figure 1a). For example, when a person with an intact, healthy digestive tract consumes a fatty meal (e.g., a pizza), the end products of fat digestion from that meal trigger the transit control mechanisms of the small intestine to slow down the movement of the meal in order to optimize digestion and absorption of the meal’s nutrients. This feedback also contributes to the feeling of fullness after such a meal.
While diarrhea may be caused by a variety of factors (unabsorbed fats, bile acids, etc.), the effects of the accelerated transit of a meal through the gastrointestinal tract are poorly appreciated. Inflammation or resection of the small intestine can drastically alter gastrointestinal motility and transit, causing diarrhea (watery stool) and steatorrhea (fatty stool). In this setting intestinal transit may become uncontrolled and rapid. A meal is then poorly digested and absorbed, simply because it moves too quickly through the digestive system; there is insufficient contact with the digestive enzymes and absorptive surface (Figure 1b). The result of this rapid gastrointestinal transit is protein and calorie malnutrition as well as insufficient absorption of water, minerals, and micronutrients such as vitamins. The time available for digestion and absorption then becomes the determining factor in the patient’s ability to maintain nutritional status without TPN. Thus, in a patient with chronic diarrhea due to short bowel syndrome, a strategy based on providing more time rather than more bowel may be effective in reducing dependence on, or weaning from, TPN.
Slowing GI Transit
Building on this idea we postulated there may be a way to slow transit time by stimulating the ‘jejunal brake’ in the proximal (or upper) small intestine in patients with short bowel syndrome. The strategy was to manage diarrhea caused by accelerated transit of nutrients through the digestive tract by triggering the patient’s natural transit control mechanisms with a small amount of fatty acid before they consumed a meal. Recently we described this novel approach in Digestive Diseases and Sciences (Lin et al. “Slowing of Gastrointestinal Transit by Oleic Acid: A Preliminary Report of a Novel, Nutrient Based Treatment in Humans,” Dig. Dis. Sci. 2001;46:223-229).
We found when we administered 1.6 ml and 3.2 ml oleic acid mixed with 50 ml Ensure enteral formula (Ross Laboratories) to patients with chronic diarrhea 15 minutes before a meal, gastrointestinal transit was slowed significantly, with the higher dose producing a greater slowing effect. This increased the time available for completing digestion and absorption of the meal. As a result of having more time for nutrient assimilation, nutrition improved and the amount of diarrhea decreased (Figure 1c).
Transit time in normal, healthy participants averaged about 102.4 minutes. Transit times in patients was shorter at 29.3 minutes with a 0 ml dose, but almost doubled (57.2 minutes) with a 1.6 ml dose and close to tripled (83.3 minutes) with the 3.2 ml dose. Frequency of bowel movements decreased from an average 6.9/24 hrs. to 5.4/24 hrs., as did stool volume which decreased from 1829.0 to 1322.5. ml/24 hrs.. with treatment.
To better illustrate the effects of oleic acid therapy, following are some highlights of the clinical response of two patients. The first patient was a 57-year-old woman with a history of subtotal gastrectomy and gastrojejunostomy for peptic ulcer and gastric cancer. Her symptoms — nausea, cramping, pain, light-headedness, bloating, and explosive diarrhea — were consistent with severe dumping syndrome and occurred after every meal. These symptoms persisted despite aggressive medical therapy, including the use of tincture of opium and anticholinergics. Her transit times with 0, 1.6, and 3.2 ml oleic acid were 16, 99, and 109 min., respectively. On oleic acid, she had only rare episodes of dumping symptoms (about once per month). Her weight increased from 118 to 130 lbs., and bowel movements decreased from four to five liquid, to two to three formed bowel movements per day. This patient took oleic acid for over five years without loss of efficacy.
The second patient was a 34-year-old man with a 30-year history of Crohn’s disease. Five intestinal resections resulted in a remainder of ~100 cm of small intestine and descending colon. He weighed 93 lbs. at presentation and had severe difficulties with oral intake. He was given a central line and expected to be on TPN indefinitely. He had more than 20 bowel movements per day and experienced pain, bloating and nausea with each meal. His transit times with 0, 1.6, and 3.2 ml oleic acid were 8, 16 and 133 minutes, respectively. After the patient began taking oleic acid three times a day, his stool volume decreased during the first 24 hr period from 3400 ml to 1400 ml. Over the course of two months, he gained 30 lbs. without TPN and was able to enjoy an unrestricted diet without symptoms. This patient continues to take oleic acid and has reported no adverse effects in five years of daily use.
In addition to slowing transit time, participants in the study reported other positive benefits of the oleic acid therapy. First, the beneficial effect of the treatment was immediate. There was a dramatic reduction in symptoms and diarrhea after the first dose of oleic acid. Second, the therapy was effective, yet had none of the side effects of established anti-diarrheal drugs such as constipation from opiates. Third, the approach improved their nutrition. Two of the patients studied had severe short bowel syndrome and without this novel approach would have required TPN to maintain their nutritional status. This suggests that oleic acid therapy may be useful in weaning short bowel patients from, or preventing their dependence on, TPN.
In conclusion, the significant factors affecting a patient’s ability to maintain their nutritional status without TPN include quantity and quality of remaining bowel and duration of intestinal transit time. Using an experimental, non-invasive approach that involves administering oleic acid before meals, we were able to slow intestinal transit time and thereby increase nutrient and calorie absorption. The success of this trial suggests that oleic acid therapy may help patients wean from, or avoid dependence on, TPN. This approach is particularly advantageous when it is not possible to increase the length of small intestine or improve its assimilation capacity.
Parts of this article were excerpted with permission from Kluwer Academic Publishers, publishers of Digestive Diseases and Sciences.
Obtaining pure, food grade oleic acid, like that used in the research study, is difficult and expensive. In addition, it is important to know that taking oleic acid straight does not work, since there are significant dispersion, formulation and delivery issues to overcome for patients/physicians wishing to replicate the study protocol. One must also address a number of confounding factors that would neutralize the effects of oleic acid, such as exposure to tobacco and the concurrent use of certain medications that contain an anticholinergic agent such as lomotil. Finally, as an experimental therapy, physicians and patients are best served when this treatment is used under the sanction of an informed, consent-based protocol that is approved by an institutional research board, says Dr. Lin.
For all of these reasons, Dr. Lin believes that this therapy, while promising, may present a number of practical challenges to patients and their physicians. An alternative, and perhaps less frustrating option would be to enroll in one of Dr. Lin’s studies at Cedars-Sinai Medical Center in Los Angeles, CA. Patients/physicians interested in participating should call Tess Constantino, RN, at (310) 423-6143.