Abstract:
A method for reducing certain effects associated with a negative calorie balance in a human includes the step of administering conjugated linoleic acid to a human in an amount effective to reduce at least one of the effects.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     Not applicable. 
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     Not applicable. 
     BACKGROUND OF THE INVENTION 
     The percentage of persons whose health is jeopardized by too much weight is increasing. Evidence suggests that body weight is multifactorial in origin, reflecting inherited, environmental, cultural, socioeconomic, and psychological conditions. Increasing evidence suggests that being overweight is not a simple problem of will power, as is sometimes implied, but is a complex disorder of appetite regulation and energy metabolism. Many persons have a chronic tendency for becoming overweight that needs lifelong attention. Strategies employed to lose weight include caloric restriction, exercise, behavior modification, drugs, or combinations thereof, with or without medial supervision. Some attempts may be successful in the short term, but often the weight lost is regained.. Efforts to lose weight voluntarily encompass a continuum of individuals including those of normal or low weight who wish to lose weight for cultural, social, or psychological reasons to severely overweight persons who suffer resulting adverse medical consequences. 
     The success of a weight loss program is highly variable. Psychological factors play a role both in the maintenance of weight and in the success of any weight loss program. Participants can reduce baseline depression and anxiety associated with a desire to reduce weight, but only if they successfully lose weight. Little is known about the emotional impact of lesser degrees of success or of failure, but it is assumed that improved self-esteem is instrumental in the overall success of the program. There is also increasing evidence that mildly to moderately overweight women who are dieting may be at risk for binge-eating without vomiting and purging. 
     An individual&#39;s response to a weight loss strategy is unpredictable. Success rates can be expected to vary according to initial weight, the length of the treatment period, the magnitude of weight loss desired, and the motivation for wanting to lose weight. The effectiveness of unsupervised efforts to lose weight is difficult to judge because of limited data on strategies, compliance, and follow-up. Surveys indicate that many overweight people have tried to lose weight on multiple occasions; because many of these persons presumably are using these unsupervised strategies, their long-term success rates may be low. 
     In general, successful programs are those based on realistic goals that involve a negative calorie balance (caloric deficit) leading to a slow, steady weight loss. Success requires a regimen that can be adhered to long enough to reach the goal. Developing new weight reduction practices that could lead to a lifetime of weight control is also important. Other attributes of successful programs involve preparing the person to deal with high-risk emotional and social situations, self-monitor progress, solve problems, reduce stress, and maintain continual professional contact. Barriers to success include lack of feelings of self-efficacy, failure to lose weight early, premature termination of diet modifications or exercise or both, and lack of social and professional support. Serious underlying social or psychological problems such as depression also can be barriers to success. 
     It would be useful to have a treatment that would attenuate the negative psychological and physical aspects of a weight control regimen. 
     BRIEF SUMMARY OF THE INVENTION 
     The present invention is summarized in that a method for reducing at least one adverse effect of a negative calorie balance in a human includes the steps of administering to the human an amount of conjugated linoleic acid (CLA) effective to reduce at least one negative effect selected from the group consisting of a skin rash, a gastrointestinal problem, a negative mood effect, and a cognitive or central nervous system (CNS) side effect. 
     It is an object of the present invention to decrease one or more adverse effects of a negative calorie balance in a human. 
     It is another object of the invention to facilitate weight loss in a human for whom the adverse effects of weight reduction brought about by negative calorie balance pose a significant impediment to successful weight reduction. 
     It is an advantage of the present invention that the method for reducing adverse effects is effective without regard to the means by which a negative calorie balance is achieved. 
     Other objects, advantages, and features of the invention will become apparent upon consideration of the following detailed description. 
     BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
     Not applicable. 
     DETAILED DESCRIPTION OF THE INVENTION 
     A human can be subjected to a negative calorie balance in any of a number of ways. In its most basic form, the term “negative calorie balance” refers to a situation in which a human burns more calories than he or she takes in. A human can take in calories by, e.g., oral ingestion, by gastrointestinal feeding, or by intravenous delivery. Humans can achieve a negative calorie balance by, e.g., reducing food intake, either with or without pharmaceutical assistance, or by increasing calorie-burning activity. 
     As will become apparent from the working example, reductions in adverse effects were observed in a double-blind controlled study of subjects who received either conjugated linoleic acid (CLA) or a vegetable oil placebo. Subjects were asked to self-report any physiological changes noted during the course of treatment. As the data below demonstrate, CLA is shown to have a statistically significant effect on certain conditions, broadly characterized as reduced skin rash, gastrointestinal problems, reduced negative mood, and reduced cognitive/CNS side effects. 
     CLA can contain various isomers of conjugated linoleic acid (the structures of which are known to the art) or can be a preparation of a single isomer. Distinct isomers can have distinct effects on various body systems (see U.S. Pat. No. 6,020,378, incorporated herein by reference as if set forth herein in its entirety). Other recent issued US patents relating to use of CLA include U.S. Pat. Nos. 5,919,451; 5,914,346; and 5,855,917, each of which is incorporated herein by reference as if set forth herein in its entirety. The particular effects of individual isomers on the adverse effects of a weight loss regimen are not well characterized. CLA administered in the method can contain about 1% to 99% trans-10, cis-12 CLA and approximately 99% to 1% cis-9, trans-10 CLA. CLA can be administered as a dietary supplement or in food, as free fatty acids, or as active esters (e.g., triglycerides, diglycerides, or monoglycerides), as active salts thereof, or in any other biologically active form. The CLA can be administered by any route that results in delivery of biologically active material to the recipient, including, but not limited to, oral, intravenous or intramuscular administration. The CLA can be formulated with a carrier to form a composition for administration in the method. An effective CLA-containing composition for oral administration is Tonalin-90, which is a mixture of about 90% CLA isomers (approximately 43.5% trans-10, cis-12 CLA, 42% cis-9, trans-11 CLA, 2% trans-trans CLA isomers, and 1.5% other CLA isomers). On oral administration, an effective amount of CLA is between about 1 and 10 grams per day, preferably 2 to 5 grams per day, although greater or lesser amounts may also be effective. The effective amount can also depend upon the CLA isomer ratio in the administered composition. 
    
    
     EXAMPLE 
     Human subjects were placed on a weight loss regimen of reduced calorie intake and increased exercise. The regimen was such that each subject achieved a negative calorie balance. Eighty-two subjects were in the study when it began and eighty remained in the study when the treatments were randomized. All subjects received a placebo for two weeks. After this stage, 71 subjects remained in the study. Using a double-blind protocol, thirty-five of the subjects then remaining in the study were administered Tonalin-90 CLA and thirty-six were administered a vegetable oil placebo. Subjects were asked to take one pill with each meal (3 grams of Tonalin-90 per day, for a total dose of about 2.7 grams of CLA per day). 
     Visits occurred at 2 week intervals. Subjects were asked about physiological changes or symptoms in a self-reporting questionnaire-style format. For each symptom, subjects were asked to report whether they experienced or did not experience the symptom. Tables 1-6 report the data from the double-blind protocol. The data presented in the (+) and (−) columns indicates the number of subjects in the test and control groups that reported or did not report the indicated symptom at some time during the study. The calculations columns report the CHI-square ranges for each variable. The p-value reported from the CHI-squared analysis of the data report the statistical significance of each observation. A p-value of less than 0.05 is considered statistically significant; a p-value of between 0.05 and 0.1 indicates a trend. In this study, effects having a p-value of less than 0.1 are considered to be meaningful and of interest by the inventors. Table 7 summarizes positive effects of CLA having a p-value of less than 0.1. 
     The present invention is not intended to be limited to the preceding embodiments or to the working example, but rather encompasses all modifications and variations that fall within the scope of the appended claims. 
     
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 CHI-SQUARED ANALYSIS: GI side effects-CLA vs Placebo 
               
             
          
           
               
                   
                 (+) 
                 (−) 
                 calculations: 
               
               
                   
                   
               
             
          
           
               
                   
                 Abdominal Pain 
                   
                   
                   
                   
               
               
                   
                 CLA 
                 7 
                 28 
                  8.380 
                 26.620 
               
               
                   
                 PLACEBO 
                 10 
                 26 
                  8.620 
                 27.380 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.443 
               
               
                   
                 Constipation 
               
               
                   
                 CLA 
                 2 
                 33 
                  3.451 
                 31.549 
               
               
                   
                 PLACEBO 
                 5 
                 31 
                  3.549 
                 32.451 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.248 
               
               
                   
                 Diarrhea 
               
               
                   
                 CLA 
                 8 
                 27 
                 12.324 
                 22.676 
               
               
                   
                 PLACEBO 
                 17 
                 19 
                 12.676 
                 23.324 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.032 
               
               
                   
                 Dry Mouth 
               
               
                   
                 CLA 
                 4 
                 31 
                  4.930 
                 30.070 
               
               
                   
                 PLACEBO 
                 6 
                 30 
                  5.070 
                 30.930 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.526 
               
               
                   
                 Gall Bladder Prob 
               
               
                   
                 CLA 
                 1 
                 34 
                  0.493 
                 34.507 
               
               
                   
                 PLACEBO 
                 0 
                 36 
                  0.507 
                 34.493 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.307 
               
               
                   
                 Nausea/Vomiting 
               
               
                   
                 CLA 
                 8 
                 27 
                 11.338 
                 23.662 
               
               
                   
                 PLACEBO 
                 15 
                 21 
                 11.662 
                 24.338 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.090 
               
               
                   
                 Heartburn 
               
               
                   
                 CLA 
                 6 
                 29 
                  6.901 
                 28.099 
               
               
                   
                 PLACEBO 
                 8 
                 28 
                  7.099 
                 28.901 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.591 
               
               
                   
                 Total GI Symptoms 
               
               
                   
                 CLA 
                 36 
                 209 
                 47.817 
                 197.183 
               
               
                   
                 PLACEBO 
                 61 
                 191 
                 49.183 
                 202.817 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.007 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 CHI-SQUARED ANALYSIS: Negative Mood side 
               
               
                 effects-CLA vs Placebo 
               
             
          
           
               
                   
                 (+) 
                 (−) 
                 calculations: 
               
               
                   
                   
               
             
          
           
               
                 Lower Sex Drive 
                   
                   
                   
                   
               
               
                 CLA 
                 0 
                 35 
                  0.493 
                 34.507 
               
               
                 PLACEBO 
                 1 
                 35 
                  0.507 
                 35.493 
               
               
                   
                   
                   
                 p-val = 
                 0.321 
               
               
                 Anxiety 
               
               
                 CLA 
                 4 
                 31 
                  5.423 
                 29.577 
               
               
                 PLACEBO 
                 7 
                 29 
                  5.577 
                 30.423 
               
               
                   
                   
                   
                 p-val = 
                 0.351 
               
               
                 Depression 
               
               
                 CLA 
                 3 
                 32 
                  5.915 
                 29.085 
               
               
                 PLACEBO 
                 9 
                 27 
                  6.085 
                 29.915 
               
               
                   
                   
                   
                 p-val = 
                 0.065 
               
               
                 Irritability/Anger 
               
               
                 CLA 
                 5 
                 30 
                  6.408 
                 28.592 
               
               
                 PLACEBO 
                 8 
                 28 
                  6.592 
                 29.408 
               
               
                   
                   
                   
                 p-val = 
                 0.387 
               
               
                 Nervousness 
               
               
                 CLA 
                 3 
                 32 
                  1.972 
                 33.028 
               
               
                 PLACEBO 
                 1 
                 35 
                  2.028 
                 33.972 
               
               
                   
                   
                   
                 p-val = 
                 0.290 
               
               
                 Binge Eating 
               
               
                 CLA 
                 1 
                 34 
                  2.958 
                 32.042 
               
               
                 PLACEBO 
                 5 
                 31 
                  3.042 
                 32.958 
               
               
                   
                   
                   
                 p-val = 
                 0.095 
               
               
                 Total Neg Mood Symptoms 
               
               
                 CLA 
                 16 
                 194 
                 23.169 
                 186.831 
               
               
                 PLACEBO 
                 31 
                 185 
                 23.831 
                 192.169 
               
               
                   
                   
                   
                 p-val = 
                 0.027 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 CHI-SQUARED ANALYSIS: CV side effects-CLA vs. Placebo 
               
             
          
           
               
                   
                 (+) 
                 (−) 
                 calculations: 
               
               
                   
                   
               
             
          
           
               
                   
                 Abnormal Heartbeat 
                   
                   
                   
                   
               
               
                   
                 CLA 
                 1 
                 34 
                 2.465 
                 32.535 
               
               
                   
                 PLACEBO 
                 4 
                 32 
                 2.535 
                 33.465 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.174 
               
               
                   
                 Chest Pain 
               
               
                   
                 CLA 
                 2 
                 33 
                 1.479 
                 33.521 
               
               
                   
                 PLACEBO 
                 1 
                 35 
                 1.521 
                 34.479 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.539 
               
               
                   
                 Short of Breath 
               
               
                   
                 CLA 
                 5 
                 30 
                 4.437 
                 30.563 
               
               
                   
                 PLACEBO 
                 4 
                 32 
                 4.563 
                 31.437 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.688 
               
               
                   
                 Total CV Symptoms 
               
               
                   
                 CLA 
                 8 
                 97 
                 8.380 
                 96.620 
               
               
                   
                 PLACEBO 
                 9 
                 99 
                 8.620 
                 99.380 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.847 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 CH-SQUARED ANALYSIS: Positive Mood side effects-CLA vs. Placebo 
               
             
          
           
               
                   
                 (+) 
                 (−) 
                 calculations: 
               
               
                   
                   
               
             
          
           
               
                   
                 Higher Sex Drive 
                   
                   
                   
                   
               
               
                   
                 CLA 
                 1 
                 34 
                 0.493 
                 34.507 
               
               
                   
                 PLACEBO 
                 0 
                 36 
                 0.507 
                 35.493 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.307 
               
               
                   
                 Elevated Mood 
               
               
                   
                 CLA 
                 2 
                 33 
                 2.465 
                 32.535 
               
               
                   
                 PLACEBO 
                 3 
                 33 
                 2.535 
                 33.465 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.666 
               
               
                   
                 Total Pos Mood Symptoms 
               
               
                   
                 CLA 
                 3 
                 67 
                 2.958 
                 67.042 
               
               
                   
                 PLACEBO 
                 3 
                 69 
                 3.042 
                 68.958 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.972 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 CHI-SQUARED ANALYSIS: Cognitive and CNS side 
               
               
                 effects-CLA vs. Placebo 
               
             
          
           
               
                   
                 (+) 
                 (−) 
                 calculations: 
               
               
                   
                   
               
             
          
           
               
                 Altered Sense Time 
                   
                   
                   
                   
               
               
                 CLA 
                 1 
                 34 
                  0.986 
                 34.014 
               
               
                 PLACEBO 
                 1 
                 35 
                  1.014 
                 34.986 
               
               
                   
                   
                   
                 p-val = 
                 0.984 
               
               
                 Loss Concentration 
               
               
                 CLA 
                 2 
                 33 
                  3.451 
                 31.549 
               
               
                 PLACEBO 
                 5 
                 31 
                  3.539 
                 32.451 
               
               
                   
                   
                   
                 p-val = 
                 0.248 
               
               
                 Blurred Vision 
               
               
                 CLA 
                 2 
                 33 
                  2.958 
                 32.042 
               
               
                 PLACEBO 
                 4 
                 32 
                  3.042 
                 32.958 
               
               
                   
                   
                   
                 p-val = 
                 0.414 
               
               
                 Dizziness 
               
               
                 CLA 
                 3 
                 32 
                  6.901 
                 28.099 
               
               
                 PLACEBO 
                 11 
                 25 
                  7.099 
                 28.901 
               
               
                   
                   
                   
                 p-val = 
                 0.020 
               
               
                 Headache 
               
               
                 CLA 
                 17 
                 18 
                 16.761 
                 18.239 
               
               
                 PLACEBO 
                 17 
                 19 
                 17.239 
                 18.761 
               
               
                   
                   
                   
                 p-val = 
                 0.909 
               
               
                 Memory Loss 
               
               
                 CLA 
                 2 
                 33 
                  1.972 
                 33.028 
               
               
                 PLACEBO 
                 2 
                 34 
                  2.028 
                 33.972 
               
               
                   
                   
                   
                 p-val = 
                 0.977 
               
               
                 Tremor 
               
               
                 CLA 
                 1 
                 34 
                  0.493 
                 34.507 
               
               
                 PLACEBO 
                 0 
                 36 
                  0.507 
                 35.493 
               
               
                   
                   
                   
                 p-val = 
                 0.307 
               
               
                 Drowsiness 
               
               
                 CLA 
                 2 
                 33 
                  3.451 
                 31.549 
               
               
                 PLACEBO 
                 5 
                 31 
                  3.549 
                 32.451 
               
               
                   
                   
                   
                 p-val = 
                 0.248 
               
               
                 Fatigue 
               
               
                 CLA 
                 9 
                 26 
                 12.324 
                 22.676 
               
               
                 PLACEBO 
                 16 
                 20 
                 12.676 
                 23.324 
               
               
                   
                   
                   
                 p-val = 
                 0.099 
               
               
                 Total Cognitive and CNS Symptoms 
               
               
                 CLA 
                 39 
                 276 
                 49.296 
                 265.704 
               
               
                 PLACEBO 
                 61 
                 263 
                 50.704 
                 273.296 
               
               
                   
                   
                   
                 p-val = 
                 0.025 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 CHI-SQUARED ANALYSIS: Misc. side effects-CLA v. Placebo 
               
             
          
           
               
                   
                 (+) 
                 (−) 
                 calculations: 
               
               
                   
                   
               
             
          
           
               
                   
                 Abnormal menses 
                   
                   
                   
                   
               
               
                   
                 CLA 
                 5 
                 30 
                  5.423 
                 29.577 
               
               
                   
                 PLACEBO 
                 6 
                 30 
                  5.577 
                 30.423 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.782 
               
               
                   
                 Bruising 
               
               
                   
                 CLA 
                 1 
                 34 
                  2.465 
                 32.535 
               
               
                   
                 PLACEBO 
                 4 
                 32 
                  2.535 
                 33.465 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.174 
               
               
                   
                 Hair Loss 
               
               
                   
                 CLA 
                 1 
                 34 
                  0.986 
                 34.014 
               
               
                   
                 PLACEBO 
                 1 
                 35 
                  1.014 
                 34.986 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.984 
               
               
                   
                 Leg Cramps 
               
               
                   
                 CLA 
                 4 
                 31 
                  3.451 
                 31.549 
               
               
                   
                 PLACEBO 
                 3 
                 33 
                  3.549 
                 32.451 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.662 
               
               
                   
                 Skin Rash 
               
               
                   
                 CLA 
                 0 
                 35 
                  1.479 
                 33.521 
               
               
                   
                 PLACEBO 
                 3 
                 33 
                  1.521 
                 34.479 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.081 
               
               
                   
                 Sweating 
               
               
                   
                 CLA 
                 4 
                 31 
                  4.930 
                 30.070 
               
               
                   
                 PLACEBO 
                 6 
                 30 
                  5.070 
                 30.930 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.526 
               
               
                   
                 Total Misc Symptoms 
               
               
                   
                 CLA 
                 15 
                 195 
                 18.732 
                 191.268 
               
               
                   
                 PLACEBO 
                 23 
                 193 
                 19.268 
                 196.732 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.204 
               
               
                   
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 SUMMARY OF SIDE EFFECTS REDUCED WITH CLA (P &lt; 0.1) 
               
             
          
           
               
                   
                 (+) 
                 (−) 
                 calculations: 
               
               
                   
                   
               
             
          
           
               
                   
                 Skin Rash 
                   
                   
                   
                   
               
               
                   
                 CLA 
                 0 
                 35 
                  1.479 
                 33.521 
               
               
                   
                 PLACEBO 
                 3 
                 33 
                  1.521 
                 34.479 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.081 
               
               
                   
                 Diarrhea 
               
               
                   
                 CLA 
                 8 
                 27 
                 12.324 
                 22.676 
               
               
                   
                 PLACEBO 
                 17 
                 19 
                 12.676 
                 23.324 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.032 
               
               
                   
                 Nausea/Vomiting 
               
               
                   
                 CLA 
                 8 
                 27 
                 11.338 
                 23.662 
               
               
                   
                 PLACEBO 
                 15 
                 21 
                 11.662 
                 24.338 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.090 
               
               
                   
                 Depression 
               
               
                   
                 CLA 
                 3 
                 32 
                  5.915 
                 29.085 
               
               
                   
                 PLACEBO 
                 9 
                 27 
                  6.085 
                 29.915 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.065 
               
               
                   
                 Binge Eating 
               
               
                   
                 CLA 
                 1 
                 34 
                  2.958 
                 32.042 
               
               
                   
                 PLACEBO 
                 5 
                 31 
                  3.042 
                 32.958 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.095 
               
               
                   
                 Dizziness 
               
               
                   
                 CLA 
                 3 
                 32 
                  6.901 
                 28.099 
               
               
                   
                 PLACEBO 
                 11 
                 25 
                  7.099 
                 28.901 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.020 
               
               
                   
                 Fatigue 
               
               
                   
                 CLA 
                 9 
                 26 
                 12.324 
                 22.676 
               
               
                   
                 PLACEBO 
                 16 
                 20 
                 12.676 
                 23.324 
               
               
                   
                   
                   
                   
                 p-val = 
                 0.099